SAMJ Vol 104, No 5 (2014) by HMPG

MAY 2014

VOL. 104 NO. 5

Fracking and health Odyssean and imported malaria

332 335, 344, 347

INH prophylaxis â&#x20AC;&#x201C; the pros

339

A visual prostate symptom instrument

353

Oral and oropharyngeal HPV

358

Do HR practices drive doctors from the public health sector?

368

CME: Breast cancer

376-384

CPD

MAY 2014

Effective in 2014, the CPD programme for the SAMJ will be administered by Medical Practice Consulting: CPD questionnaires must be completed online at www.mpconsulting.co.za

True (A) or false (B): Health and fracking: Should the medical profession be concerned? 1. Because there is little scientific evidence on the health impacts of fracking, it cannot be concluded that there are no potential harms to health. 2. It has been calculated that up to 29 million litres of water may be needed for a single well, of which up to 250 000 litres may consist of chemicals. Odyssean malaria outbreaks 3. Air traffic from endemic malaria areas in and around SA is the source of most of the malaria-bearing mosquitoes. 4. A key question to put to a patient with fever and thromocytopenia is: do you live in close proximity to a national highway, airport, train station, bus depot, taxi rank or other public transport node? The burden of imported malaria in Cape Town 5. Only a small area – in the north-eastern part of KwaZulu-Natal, and in Mpumalanga and Limpopo provinces – in South Africa (SA) is malaria endemic. 6. Plasmodium ovale is the predominant parasite in ‘imported’ cases of malaria.

10. HPV-related OSCC is paradoxically rare in HIV-infected indivi duals because the natural history of HPV infection is altered when both viral infections coexist. The challenges of managing breast cancer in the developing world 11. Fewer than 11 African countries have access to oral morphine. 12. A recent pilot study of a cancer awareness programme in Sudan suggests that breast self-examination may be useful in low-income countries. Down-staging of breast cancer in the pre-screening era 13. Women in sub-Saharan Africa have among the lowest incidences of breast cancer worldwide. 14. In this study there was no significant correlation between stage and age, with the exception of the very old, who present with more advanced disease. Side-effects of systemic therapy for the management of breast cancer 15. Anthracyclines are the main chemotherapy drugs responsible for cardiotoxicity.

Evaluation of the visual prostate symptom score 7. Possible causes of bladder outflow obstruction in men include urethral stricture, benign prostatic hyperplasia, prostate cancer, prostatitis, bladder stones and bladder neck stenosis.

The management of breast cancer-related lymphoedema 16. Any person who has had surgery and/or radiotherapy for breast cancer is at risk of developing lymphoedema, typically within 3 years of diagnosis and treatment. 17. Manual lymph drainage alone is sufficient to manage chronic lymphoedema.

Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men 8. It has been shown that oral human papillomavirus (HPV) infection, and specifically HPV type 16 infection, causes an up to 50-fold increase in HPV-positive oropharyngeal squamous cell carcinoma (OSCC). 9. HPV-associated OSCC may originate in the soft palate, tongue base, pharyngeal walls or tonsils.

An approach to the management of locally advanced breast can cer: Part 1 18. Inflammatory breast cancer is characterised by erythema and dermal oedema and progresses slowly. 19. Core needle breast biopsy causes minimal tumour disruption and can evaluate prognostic and predictive tumour markers. 20. The standard adjuvant hormonal therapy in pre-menopausal women with ER-positive disease is tamoxifen alone for 5 years.

CPD questions include articles from CME. The full versions of each article can be found on the SAMJ website (http://www.samj.org.za)

A maximum of 3 CEUs will be awarded per correctly completed test.

INSTRUCTIONS 1. Read the journal. All the answers will be found there. 2. Go to www.mpconsulting.co.za to answer the questions. Accreditation number: MDB001/007/01/2014 (Clinical)

May 2014, Vol. 104, No. 5

MAY 2014

GUEST EDITORIAL

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Pink ribbons for breast cancer awareness – a perspective J Edge

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EDITOR’S CHOICE

VOL. 104 NO. 5

EDITOR Janet Seggie, BSc (Hons), MD (Birm), FRCP (Lond), FCP (SA) EDITOR EMERITUS Daniel J Ncayiyana, MD (Groningen), FACOG MD (Hon), FCM (Hon)

CORRESPONDENCE 323

Well-trained generalists can help improve surgical capacity at district hospitals B Mash, response from D L Clarke, C Aldous

323

Parents’ perceptions of HIV counselling and testing in schools: Study methodology deeply flawed S Goldstein, response from R Gwandure, E Ross, A Dhai, J Gardner

324

Rapid, minimally invasive adult voluntary male circumcision with the Unicerc, a novel disposable device V Mutabazi, response from P S Millard

325

‘It would have been better if I had HIV instead of diabetes’ M J A Reid, B Tsima

325 Call for closure of Folateng private wards in public hospitals in southern Gauteng K R L Huddle, T Parbhoo, D Blumsohn, C Menezes, A Peter, M Patel, M Mashabane, J M L Tsitsi, M Tikly, R Shires, R Ally, M R Essop, M Wong, C Ickinger, N Govind, S Bhana, N Mohamed 326

A new horizon for the medical device sector in South Africa D B Mueller, M Govender, D Basu

IZINDABA 327 329

Lowering private investor risk to build a healthier country Population-based health funding under attack

330

OBITUARY/HULDEBLYK Dirk Johannes Jacobus van Velden

331

BOOK REVIEW Breast Care: A Health Professional’s Guide to Diagnosis and Management of Common Breast Conditions

FORUM

332

MEDICINE AND THE ENVIRONMENT Health and fracking: Should the medical profession be concerned? R Mash, J Minnaar, B Mash

335

CLINICAL PRACTICE Odyssean malaria outbreaks in Gauteng Province, South Africa, 2007 - 2013 J Frean, B Brooke, J Thomas, L Blumberg

REVIEW 339 Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control G J Churchyard, R E Chaisson, G Maartens, H Getahun

EDITORIALS 344

Diagnosis and treatment of imported and odyssean malaria S K Dlamini

345

AGREE to disagree – critical appraisal and the publication of practice guidelines R Wiseman, K Cohen, A Gray, K Jamaloodien, T Kredo, J Miot, A Parrish, B Taylor, M Blockman, for the South African Medical Journal Editorial Sub-Committee for Guideline Review

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May 2014, Vol. 104, No. 5

CONSULTING EDITOR JP de V van Niekerk, MD, FRCR DEPUTY EDITOR Bridget Farham, BSc (Hons), PhD, MB ChB EDITORIAL SYSTEMS MANAGER Melissa Raemaekers, BSc (Hons), PhD SCIENTIFIC EDITOR Ingrid Nye, BSc TECHNICAL EDITORS Paula van der Bijl, BA, HDipLib Emma Buchanan, BA NEWS EDITOR Chris Bateman | Email: chrisb@hmpg.co.za HEAD OF PUBLISHING Robert Arendse PRODUCTION ASSISTANT Neesha Hassan ART DIRECTOR Brent Meder DTP & DESIGN Anelia du Plessis | Carl Sampson ONLINE MANAGER Gertrude Fani DISTRIBUTION MANAGER Edward Macdonald | Tel. 021-681-7085 HEAD OF SALES AND MARKETING Diane Smith | Tel. 012-481-2069 Email: dianes@samedical.org PROFESSIONAL ADVERTISING Bronlyne Granger | Tel. 021-681-7000 E-mail: bronlyne.granger@hmpg.co.za HMPG BOARD OF DIRECTORS Prof. M G Veller (Chair), Prof. M Lukhele, Dr M Mbokota, Prof. A A Stulting, Dr M R Abbas, Dr G Wolvaardt ASSOCIATE EDITORS Q Abdool Karim, A Dhai, N Khumalo R C Pattinson, A Rothberg, A A Stulting, J Surka, B Taylor, M Blockman ISSN 0256-9574 Publisher website: www.hmpg.co.za SAMA website: www.samedical.org Journal website: www.samj.org.za

1ST generic 1,5 mg sustained release formulation

DynaIndapamide A4 April.indd 1

2014/04/04 1:32 PM

:32 PM

RESEARCH

CONTENTS LISTED IN Index Medicus (Medline) Excerpta Medica (EMBASE) Web of Knowledge Biological Abstracts (BIOSIS) Science Citation Index (SciSearch) Current Contents/Clinical Medicine

347

The burden of imported malaria in Cape Town, South Africa J Opie, R Freeks, L A du Pisani

350

Perceptions of mental illness among Muslim general practitioners in South Africa Z Mohamed-Kaloo, S Laher

353

Evaluation of the visual prostate symptom score in a male population with great language diversity and limited education: A study from Namibia C F Heyns, B A Steenkamp, J Chiswo, G A Stellmacher, H E A Förtsch, A van der Merwe

SAMJ SUBSCRIPTION RATES Local subscriptions R1 144.00 p.a. Foreign subscriptions R2 580.00 p.a. Single copies R95.00

358

Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: A pilot study C L Davidson, K L Richter, M van der Linde, J Coetsee, S C Boy

Members of SAMA receive the SAMJ only on request, as part of their membership beneﬁt.

362

Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa J V Ershova, L J Podewils, L E Bronner, H G Stockwell, S Dlamini, L D Mametja

368

372

Human resource management practices in a medical complex in the Eastern Cape, South Africa: Assessing their impact on the retention of doctors B Longmore, L Ronnie Reliability and accuracy of the South African Triage Scale when used by nurses in the emergency department of Timergara Hospital, Pakistan M K Dalwai, M Twomey, J Maikere, S Said, M Wakeel, J-P Jemmy, P Valles, K Tayler-Smith, L Wallis, R Zachariah

CONTINUING MEDICAL EDUCATION 376

377

380

Subscriptions: Tel. 012-481-2071 E-mail: members@samedical.org The SAMJ is published monthly by the Health and Medical Publishing Group (Pty) Ltd, Co. registration 2004/0220 32/07, a subsidiary of SAMA. 28 Main Road (Cnr Devonshire Hill Road), Rondebosch, 7700 Tel. 021-681-7200. E-mail: publishing@hmpg.co.za Website: www.hmpg.co.za Please submit all letters and articles for publication online at www.samj.org.za © Copyright: Health and Medical Publishing Group (Pty) Ltd, a subsidiary of SAMA

GUEST EDITORIAL Breast cancer J Edge REVIEW The challenges of managing breast cancer in the developing world – a perspective from sub-Saharan Africa J Edge, I Buccimazza, H Cubasch, E Panieri ARTICLES Down-staging of breast cancer in the pre-screening era: Experiences from Chris Hani Baragwanath Academic Hospital, Soweto, South Africa N Murugan, C Dickens, P Pisa, V McCormack, M Joﬀe, J Jacobson, H Cubasch

381

Side-eﬀects of systemic therapy for the management of breast cancer A Gudgeon

382

The management of breast cancer-related lymphoedema C M Marco, R Pillay, C Schoonheim

383

Stigma, survivorship and solutions: Addressing the challenges of living with breast cancer in low-resource areas M Mutebi, J Edge

384

An approach to the management of locally advanced breast cancer: Part 1 P Govender

Use of editorial material is subject to Creative Commons Attribution – Noncommercial Works License 3.0. http://creativecommons. org/licenses/by-nc/3.0

Plagiarism is defined as the use of another’s work, words or ideas without attribution or permission, and representation of them as one’s own original work. Manuscripts containing plagiarism will not be considered for publication in the SAMJ. For more information on our plagiarism policy, please visit http://www.samj.org.za/index. php/samj/about/editorialPolicies Printed by Creda Communications

An approach to the management of locally advanced breast cancer: Part 2* K Hill ABC – Advocates for Breast Cancer* A Steyn, J du Plessis, S Meyer *Available online only.

PROFESSIONAL ADVERTISING CPD QUESTIONS

Windmill at night in Merweville, the Karoo, South Africa. Photo and text: Eric Nathan Email: eric@ericnathan.com

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May 2014, Vol. 104, No. 5

FIRST PUBLISHED IN 1884

Pink ribbons for breast cancer awareness – a perspective The pink ribbon has become synonymous with breast cancer awareness. Where did the pink ribbon originate? What does breast cancer awareness mean, and can it be used to improve the health of the majority of women in South Africa? The first ribbon to be linked to a cause was yellow. In 1979, Penney Lainegen, the wife of an Iranian hostage, tied a yellow ribbon round a tree to make people aware of the plight of the hostages. Eleven years later, in 1991, a group of artists came together to design a symbol that would remind the world of the plight of AIDS victims. They designed the red ribbon. Red was chosen as a colour of passion: anger and love. The designers believed that it was important to remain anonymous as individuals and to keep the copyright free so that no organisation or individual could profit from the symbol, and that the red ribbon should be used as a consciousness-raising symbol and not as a commercial tool.[1] In 1990, the Susan G Kommen Foundation (one of the largest breast cancer organisations in the USA) gave out pink visors to participants in their events. At about the same time Susan Haley, an individual working at grassroots level, was making peach-coloured ribbons attached to a card on which she wrote ‘The National Cancer Institute’s annual budget is 1.8 billion US dollars, and only 5 percent goes to cancer prevention. Help us wake up our legislators and America by wearing this ribbon.’ There are two origins of the pink ribbon. The first is that in 1992, Alexandra Peney, editor of Self magazine, was trying to market an edition highlighting breast cancer awareness. She liaised with Evelyn Lauder, vice-president of Estée Lauder, and together they agreed to attach a pink ribbon to all cosmetic products. The second is that the Susan G Kommen Foundation approached Susan Haley to suggest that they work in collaboration with Haley’s peach ribbon campaign. When Haley refused, the Foundation adopted the pink ribbon as their symbol.[2] Cause-related marketing is the term used to describe a not-forprofit organisation benefiting from a for-profit company’s marketing. The presence of a symbol on a product vouches for the fact that some money will be donated to a cause. The pink ribbon is an example par excellence. Breast cancer is a perfect disease for companies to use because it is blameless in that the main risk factors are being female, growing older and having a positive family history, none of which can be modified by the individual with the cancer. For companies it is a safe cause to link with and, through the cause, to link with women and their impressive purchasing power. It is also an inexpensive form of advertising (hence the term marketing). All too often, however, only a minute proportion of the money raised ends up going to the cause. For example, in 2002 American Express agreed to donate one cent every time their card was used in October. In reality, a card had to be used one hundred times during the 30-day period to donate $1![3] Another flaw is that the amount

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donated is usually capped, so that, for example, New Balance has agreed to donate money to the Susan G Kommen Foundation but will cease to donate further once the agreed capped amount has been raised. Also, New Balance donate money from sales of their caps, T-shirts and socks, but not from sales of their pink trainers, which are ‘just for awareness’.[2] Should the source of the income matter? The presence of pink ribbons on Kentucky Fried Chicken, sweets and fattening products is surely counterintuitive if, for breast cancer survivors, reducing their body mass index is an important factor in decreasing their risk of cancer recurrence. It is impossible to estimate how much the pink ribbon is worth. It bears noting, however, that the Susan G Kommen Foundation alone raised over $420 million in 2012.[4] The vast majority of the funds raised from the pink ribbon campaigns go to ‘breast cancer awareness’. What does breast cancer awareness mean, and what should we be doing in southern Africa? The Wikipedia definition (interestingly, the only definition I could find) is ‘an effort to raise awareness and reduce the stigma of breast cancer through education on symptoms and treatment. … will lead to earlier detection of breast cancer, which is associated with higher long-term survival rates, and that money raised for breast cancer will produce a reliable, permanent cure.’[5] Women in low-income countries are all too often diagnosed late in the course of disease with advanced breast cancer and frequently cannot access the standard of care needed for treatment. There are many similar problems facing women in South Africa, although it is classified as a middle-income country. These are featured in this month’s CME. The stigma attached to the diagnosis, cost involved in medical treatment, complex referral pathways and inefficiencies in the system are just a few of the challenges. It does not help that breast cancer awareness campaigns are largely confined to middle-class suburbs and tailored to the needs of more affluent citizens. We must know where South Africa’s ‘pink rand’ is going, and whether or not it could be spent more appropriately. Jenny Edge

Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa jennyedge1234@me.com 1. https://www.visualaids.org/projects/detail/the-red-ribbon-project (accessed 6 April 2014). 2. http://thinkbeforeyoupink.org (accessed 6 April 2014). 3. King S. Pink Ribbons, Inc.: Breast Cancer and the Politics of Philanthropy. Minneapolis: University of Minnesota Press, 2008. 4. http://ww5.komen.org/AboutUs/FinancialInformation.html (accessed 6 April 2014). 5. http://en.wikipedia.org/wiki/Breast_cancer_awareness (accessed 6 April 2014).

S Afr Med J 2014;104(5):321. DOI:10.7196/SAMJ.8300

May 2014, Vol. 104, No. 5

EDITOR’S CHOICE

CME: Breast cancer

This month’s CME deals with the topic of breast cancer, a common cancer that consequently receives a lot of publicity. In women who have easy access to screening and medical care, and are aware of the significance of changes in the breast, this cancer presents early and can often be managed very successfully. However, for the majority of our population – and indeed elsewhere in Africa and the developing world – the situation is very different. The cancer presents late, has often already spread, is difficult to manage and has a low cure rate. Jenny Edge and her team concentrate on this aspect of breast cancer. Articles take in the situation in a population of women presenting to Baragwanath Hospital in Soweto, for whom distance to the clinic was a factor in late presentation, as well as management of locally advanced disease, side-effects of systemic therapy, and management of a common post-treatment complication, lymphoedema. These articles should be particularly useful for those who work in the public sector and in private practice in less affluent areas.

Isoniazid prophylaxis – the pros

The March SAMJ carried an article from the Desmond Tutu Institute offering the view that isoniazid prophylaxis against tuberculosis (TB) was inadvisable.[1] In this edition we present the opinion from the Aurum Institute[2] that it may substantially improve TB control, particularly for populations at high risk. As we reported in Izindaba,[3] picking up on the mining indaba recently held in Cape Town, the moment a TB carrier (i.e. dormant) becomes HIV-positive and the immune system is progressively compromised, the risk of developing active TB increases. The prevalence of undiagnosed disease is the driving force of TB transmission at a population level and has changed little at goldmines, based on two surveys a decade apart. The first Aurum Institute survey in 2000, including some 2 000 miners, revealed that 2.5% of them had undiagnosed active TB. The second probe in 2011 (this time of 13 000 miners), done as part of Churchyard’s latest research and recently published in the New England Journal of Medicine, uncovered a similar prevalence (2.3%). I learned (at a recent talk by National Minister of Health Motsoaledi) that 46% of coalminers in the coal/power station belt are HIV-positive. Our continued supply of coal/electricity therefore depends on more than whether the coal is wet or not.

To frack or not to frack?

South Africa (SA) is about to embark on exploratory high-volume hydraulic fracturing (fracking) to extract the huge reserves of natural gas contained in shale rock. Mash et al.[4] summarise the health concerns and discuss them in the SA context. Hundreds of chemicals are used during the drilling and fracking phases, but access to information on them has been limited owing to protection under proprietary legislation. Table 1 in the article shows some of the known chemicals and the purposes for which they are used, while Fig. 1 presents data on 353 of the known chemicals and the percentage of these associated with a variety of potentially adverse effects on health, 77 of which (Table 2) are associated with ≥10 potential adverse health effects.

‘The Revenge of Geography’[5]

Two papers[6-7] are ‘must reads’. Only a small area in SA is malaria endemic – in the north-eastern part of KwaZulu-Natal, and in Mpumalanga and Limpopo provinces. All cases of malaria in other parts of the country are imported, either from malaria-endemic regions of SA or from further afield. Many foreign migrants come from malaria-endemic areas and present to SA healthcare services after arrival. A survey (‘The burden of imported

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malaria in Cape Town’[5]) over 4 years of 118 patients in whom malaria was diagnosed at the National Health Laboratory Service referral laboratory at Groote Schuur Hospital, serving Western Cape clinics and regional hospitals, revealed that 48% (n=57) of patients originated from Somalia, 8.5% (n=10) from SA, 30% from other countries in Africa, and 15.5% (n=18) from countries outside Africa – mostly Bangladesh (n=15; 13%). Of the SA patients, all had travelled to malaria-endemic areas apart from one patient who acquired malaria via a transfusion of platelet concentrate received while an inpatient at GSH. These patients, typically migrants, often have severe falciparum malaria and risk being mismanaged owing to incorrect antimalarial treatment and several re-admissions due to treatment failure from lack of appropriate treatment with Coartem. Then there is the issue of odyssean malaria, i.e. malaria transmitted by translocated infected mosquitoes. Cases are inevitable in SA, given the volume of road, rail and air traffic from malaria risk areas into Gauteng and other non-endemic provinces. Road traffic from endemic areas in and around SA is the source of most of the malariabearing mosquitoes. Odyssean malaria cases are easily missed, with a consequent dangerous delay in diagnosis; the fever is incorrectly ascribed to some other infection. Reporting on outbreaks in Gauteng from 2007 to 2013, Frean et al.[7] warn that malaria should always be kept in mind as a cause of unexplained fever and thrombocytopenia, even in the absence of a travel history. A key question to all such patients is: do you live in close proximity to a national highway, airport, train station, bus depot, taxi rank or other public transport node?

The visual prostate symptom score

Heyns et al.[8] from Stellenbosch University and Windhoek Central Hospital, Namibia, have developed and evaluated a visual prostate symptom score using pictograms to rapidly assess the degree of bladder outflow obstruction for men whose language is not English, or who have had limited schooling or are illiterate.

Oral and oropharyngeal HPV in a sample of SA men[9]

Oral human papillomavirus (HPV) infection, and specifically HPV type 16 infection, causes up to a 50-fold increase in HPV-positive oropharyngeal squamous cell carcinoma (OSCC). The tumour may originate in the soft palate, tongue base, pharyngeal walls or tonsils. These head and neck cancers are, in their turn, related to sexual behaviour, particularly the lifetime number of oral sex partners. HIV-infected individuals have been reported to have up to a six-fold increased risk for HPV-related OSCC. It is thought that HIV and HPV function as a combined risk factor, as HIV-positive individuals have more frequent HPV infections. JS 1. Wood R, Bekker L-G. Isoniazid preventive therapy for tuberculosis in South Africa: An assessment of the local evidence base. S Afr Med J 2014;104(3):174-177. [http://dx.doi.org/10.7196/SAMJ.7968] 2. Churchyard GJ, Chaisson RE, Maartens G, Getahun H. Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control. S Afr Med J 2014;104(5):339-343. [http://dx.doi.org/10.7196/SAMJ.8290] 3. Bateman C. Annually, 1% of gold miners die – 4% sent home sick. S Afr Med J 2014;104(3):160-162. [http://dx.doi.org/10.7196/SAMJ.7998] 4. Mash R, Minnaar J, Mash B. Health and fracking: Should the medical profession be concerned? S Afr Med J 2014;104(5):332-335. [http://dx.doi.org/10.7196/SAMJ.7860] 5. Kaplan RD. The Revenge of Geography. New York: Random House Trade Paperbacks, 2013. 6. Opie J, Freeks R, du Pisani LA. The burden of imported malaria in Cape Town. S Afr Med J 2014;104(5):347-349. [http://dx.doi.org/10.7196/SAMJ.7904] 7. Frean J, Brooke B, Thomas J, Blumberg L. Odyssean malaria outbreaks in Gauteng Province, South Africa, 2007 - 2013. S Afr Med J 2014;104(5):335-338. [http://dx.doi.org/10.7196/SAMJ.7684] 8. Heyns CF, Steenkamp BA, Chiswo J, Stellmacher GA, Förtsch HEA, Van der Merwe A. Evaluation of the visual prostate symptom score in a male population with great language diversity and limited education: A study from Namibia. S Afr Med J 2014;104(5):353-357. [http://dx.doi.org/10.7196/SAMJ.7917] 9. Davidson CL, Richter KL, Van der Linde M, Coetsee J, Boy SC. Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: A pilot study. S Afr Med J 2014;104(5):358361. [http://dx.doi.org/10.7196/SAMJ.7542]

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CORRESPONDENCE

Well-trained generalists can help improve surgical capacity at district hospitals

To the Editor: The evaluation of the surgical outreach programme to district hospitals in Sisonke Health District (SHD), KwaZulu-Natal, South Africa (SA), recently published in the SAMJ demonstrates an admirable commitment to improving district health services.[1] While the authors documented a large number of flying hours and kilometres travelled and 2 160 operations performed over a 6-month period in the four district hospitals, it is difficult to determine what the impact of the surgical outreach was on the number and range of operations performed. They state that ‘surgical outreach is proposed as a strategy to increase the surgical output of district hospitals. Although our programme has succeeded in delivering point-of-care need it has been less successful in building operative capacity.’ Solutions such as enhanced training programmes in district hospitals v. bypassing district hospitals and offering surgical services only at regional centres are offered. However, emergency surgery, such as caesarean sections, cannot be centralised in this way without a negative impact on maternal and other mortality. The authors show no awareness of the potential contribution of well-trained generalists such as family physicians and clinical associates to increasing access to comprehensive services in the district.[2] Family physicians are expert generalists trained in the same model of a 4-year MMed degree programme as other specialists. This new specialty was approved in 2007 and started graduating family physicians in 2011. They are specifically trained to work as generalists in the district, including the district hospital.[3] The list of surgical skills that are part of their training programme incorporates all the emergency and common obstetric, surgical and orthopaedic procedures appropriate to the district hospital.[4] This list is about to be revised 5 years after a national consensus was agreed. In some provinces, such as the Western Cape, the goal is to place at least one such family physician at each district hospital, where they will increase the surgical output and improve operative capacity.[5] The new mid-level doctor, known as the associate clinician, has also been specifically trained to work at the district hospital, and these graduates are now entering the system. Part of the solution to improving surgical as well as other services at district hospitals may therefore lie in an approach that combines the placement of full-time family physicians and associate clinicians at district hospitals with periodic outreach from surgical specialists, who should also enhance the training of these new cadres of health workers. Bob Mash

Department of Family Medicine and Primary Care, Faculty of Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa rm@sun.ac.za 1. Clarke DL, Aldous C. Surgical outreach in rural South Africa: Are we managing to impart surgical skills? S Afr Med J 2014;104(1):57-60. [http://dx.doi.org/10.7196/SAMJ.7252] 2. Howe AC, Mash RJ, Hugo JFM. Developing generalism in the South African context. S Afr Med J 2013;103(12):899-900. [http://dx.doi.org/10.7196/SAMJ.7509] 3. Couper I, Mash B, Smith S, Schweitzer B. Outcomes for family medicine postgraduate training in South Africa. S Afr Fam Pract 2012;54(6):501-506. 4. Couper ID, Mash B. Obtaining consensus on core clinical skills for family medicine training. S Afr Fam Pract 2008;50(6):41. 5. Mash B. Reflections on the development of family medicine in the Western Cape: A 15-year review. S Afr Fam Pract 2011;53(6):557-562.

Clarke and Aldous respond: The problem of ensuring delivery of adequate surgical care in the rural districts of SA is a complex one, and the solutions will not be simple. We have undertaken quite an extensive review of the quality of trauma and acute surgical care in SHD and have identified a number of deficits.[1-3] It seems likely that this situation may

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exist in other rural health districts as well. Addressing these deficits will require a multifaceted approach, and the well-trained competent generalist will be central to any such quality improvement programmes. The idea of formalising a training programme that can produce these competent generalists is a good one, and needs to be encouraged and supported. D L Clarke

Pietermaritzburg Metropolitan Trauma Service and Department of Surgery, Nelson Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa damianclar@gmail.com

C Aldous

School of Clinical Medicine, Nelson Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 1. Clarke DL, Aldous C, Thomson SR. The implications of the patterns of error associated with acute trauma care in rural hospitals in South Africa for quality improvement programs and trauma education. Injury 2014;45(1):285-288. [http://dx.doi.org/10.1016/j.injury.2013.04.011] 2. Clarke DL, Kong VY, Handley J, Aldous C. A concept paper: Using the outcomes of common surgical conditions as quality metrics to benchmark district surgical services in South Africa as part of a systemic quality improvement programme. S Afr J Surg 2013;51(3):84-86. [http://dx.doi.org/10.7196/SAJS.1476] 3. Kong VY, Van der Linde S, Handley J, Aldous C, Clarke DL. Quantifying the disparity in outcome between urban and rural patients with acute appendicitis in South Africa. S Afr Med J 2013;103(10):742745. [http://dx.doi.org/10.7196/SAMJ.7109]

S Afr Med J 2014;104(5):323. DOI:10.7196/SAMJ.7897

Parents’ perceptions of HIV counselling and testing in schools: Study methodology deeply flawed

To the Editor: I am responding to the article by Gwandure et al.[1] that appeared in the January SAMJ. The article claims to explore parents’ views on the HIV counselling and testing campaign to be conducted in high schools, within an interpretative qualitative paradigm. This is an interesting and important topic. However, the methodology of the study is deeply flawed and unfortunately gives qualitative research a bad name. While the authors’ sampling for a qualitative study was acceptable, it is unclear what their ‘snowballing’ means. Since there are so many parents of children in high school (and it is not a sensitive issue to be such a parent), it is unclear why snowballing was necessary; in fact, it creates an unnecessary clustering of possibly like-minded people. This, however, is not my main objection (nor is their description of ‘black’ people as one ethnic group). My main problem with the methodology is that all the data that are presented are quantitative. If this was a quantitative study, then of course the sample of 20 and the sampling process would be woefully inadequate. Presenting the numbers in this context has no meaning and is irrelevant. Had this study been a quantitative one with an adequate sample, it might have had some validity. However, it fails on both qualitative and quantative fronts. The writers present almost no qualitative data and do not contextualise these data in any way. The reader does not know whether the respondent who said something was a woman or a man, and we do not even know how the interviews were conducted, in what language, where and by whom, or how the data were captured and analysed. Qualitative methodology is a well-documented science. In the health sphere it is used in order to see the social world from the perspective of the actor (in this case the parents), and to understand behaviour in the context of meaning systems used by a particular group (in this case parents in Kathlehong). It aims to be fluid and flexible and encourages discovering novel and unanticipated findings. ‘The validity, meaningfulness and insights generated from qualitative enquiry have more to do with the information richness of the cases selected and the observational/analytical capabilities of the researcher than with the sample size.’[2]

May 2014, Vol. 104, No. 5

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RED MEAT AND CANCER More than 13% of all deaths globally are related to cancer1 It is estimated that about 70% and rising of all cancer deaths occur in industrialised countries with the incidence rising1 The burden of cancer is increasing in developing countries as more people live to older ages while adopting western lifestyles, such as smoking, higher consumption of saturated fat and energy dense foods, and reduced physical activity2

Red meat and cancer A critical review of thousands of epidemiologic studies found the totality of the available scientific evidence not supportive of an independent association between red meat or processed meat and cancer5

South African statistics3 1 in 6 men have a lifetime risk of developing cancer - including prostate cancer (1 in 23), lung cancer (1 in 69), esophageal cancer (1 in 82) or colorectal cancer (1 in 97) 1 in 8 women have a lifetime risk of developing cancer - including breast cancer (1 in 29), cancer of the cervix (1 in 35) or colorectal cancer (1 in 162) Cancer is considered a largely preventable disease. Studies consistently show changes in patterns of cancer development as populations shift, and projections indicate that rates of cancer are liable to increase as countries progress towards westernised diets. However, cancer remains a disease of genes which are vulnerable to mutation, particularly over the increasing human lifespan.4 Normally various inherent and environmental factors act together or in sequence to initiate or promote carcinogenesis, and it should be remembered that no single study can prove that a single factor is a cause of, or is protective against, any specific type of cancer. The most common risk factors for the development of cancer Ranking Risk Factor 1 Growing older 2 Tobacco 3 Sunlight 4 Ionizing radiation 5 Certain chemicals and other substances 6 Some viruses and bacteria 7 Certain hormones 8 Family history of cancer 9 Alcohol 10 Poor diet, lack of physical activity, or being overweight A balanced diet builds upon the foundation of healthful foods from a variety of food groups, including whole grains, fruit, vegetables, dairy products and lean meats. In order to promote a healthy cancer-fighting diet, emphasis should be placed on a varied diet rich in vegetables, fruit and other fibre rich foods in combination with a moderate intake of lean red meat. Caution should be placed on Westernised lifestyle habits such as the consumption of refined sugars, processed foods, alcohol and smoking. REFERENCES 1. WHO. 2012. Cancer. Fact sheet No 297. Accessed August 2012. Available online at http://www.who. int/mediacentre/factsheets/fs297/en/. 2. American Cancer Society. 2007. Global Cancer Facts & Figures. Accessed August 2012. Available online at http://www.cansa.org.za/cause_data/images/1056/Research_-_Global_Facts_&_ Figures_2007.pdf. 3. NHLS. 2012. Chairpersons Report. National Cancer Registry. Available aonline at http://www. nioh.ac.za/?page=chairpersons_report&id=67. 4. WCRF/AICR (World Cancer Research Fund / America Institute for Cancer Research). 2007. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington, DC. 5. Alexander et al. 2010. Red Meat and Processed Meat Consumption and Cancer. A Technical Summary of the Epidemiological Evidence. Health Sciences Practice, Exponent, Inc.

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Expert opinion: Dr Carl Albrecht, Head of Research at the Cancer Association of South Africa (CANSA) and the first Cancer Research Advocate in South Africa helping to translate cancer research results into policy, said: â&#x20AC;&#x153;CANSAâ&#x20AC;&#x2122;s main message concerning diet and cancer avoidance is: >

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Our dietary vigilance must continue to involve the most crucial aspect of the entire eating exercise, namely our cooking methods, especially of red meat cooked over an open fire. Although this extremely popular pastime may kindle Neolithic nostalgia it is a dangerous exercise because pyrolysis products of meat, such as PHAs, have been linked to prostate, colorectal and pancreatic cancers in epidemiological studies.

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CORRESPONDENCE

In my view the SAMJ should have rejected the article on methodological grounds. Susan Goldstein

Programme Director, Soul City Institute, Johannesburg, South Africa; Honorary Lecturer, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa suegold@soulcity.org.za 1. Gwandure R, Ross E, Dhai A, Gardner J. Parents’ perceptions of HIV counselling and testing in schools: Ethical, legal and social implications. S Afr Med J 2014;104(1):40-42. [http://dx.doi. org/10.7196/SAMJ.6645] 2. Paton MQ. Qualitative Research and Evaluation Methods. 3rd ed. Thousand. Oaks, CA: Sage Publications, 2002.

Gwandure et al. respond: Thematic content analysis is an acceptable method of qualitative research and involves quantifying the number of persons who articulated the various themes. The original study yielded rich qualitative responses from participants which exemplified these themes. However, the restriction on word count precluded inclusion of direct verbatim quotes illustrating these themes in the article. Snowball sampling is also an acceptable sampling method in qualitative research. The article was based on a much larger research report. Much of what concerns Dr Goldstein is probably a result of what was lost in the process of summarising the research because of the word count limitations of the SAMJ. Dr Goldstein is welcome to read the full report. It is available at the Wits Institutional Repository environment on DSpace (http:// wiredspace.wits.ac.za/handle/10539/45). R Gwandure E Ross A Dhai J Gardner

Steve Biko Centre for Bioethics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa eleanor.ross@wits.ac.za

S Afr Med J 2014;104(5):323-324. DOI:10.7196/SAMJ.8001

Rapid, minimally invasive adult voluntary male circumcision with the Unicirc, a novel disposable device

To the Editor: I congratulate Millard et al.[1] on their publication. My co-workers and I have studied the PrePex male circumcision device in three clinical trials,[2-4] and I would like to share our opinions. The Unicirc is intended to be used exclusively with glue. We therefore consider that any suturing that is necessary with the device should be defined as an adverse event and should have been documented as such, as in the authors’ previous reported study.[5] We have some concerns about the safety of using cyanoacrylate glue in adult circumcisions. According to recommendations, adhesives such as DermaBond (2-octyl cyanoacrylate)[6] are contraindicated for skin that may be regularly exposed to body fluids, as the foreskin is, and should also not be used in high skin tension areas (knuckles, elbows and knees) unless they are immobilised; erections cannot be immobilised, so the use of this type of glue on the penis poses risks. Millard et al.’s[1] report of healing time lacks a definition of complete healing. Moreover, in their previous report[5] they stated that ‘there was no independent, objective measure of wound healing outcomes’. Their conclusion that ‘The cost of expendable materials was similar using the two techniques’ is puzzling, as in the same article[5]

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they report the following costs of expendables for the two arms: surgical = $15; Unicirc + glue = $4 + $5 + $20 = $29. Regarding the reported procedure time, we could not work out whether the waiting time for the local anaesthetic to numb the foreskin was included. Millard et al.[1] report that removal of the PrePex is unpleasant. What scientific research was performed to back up this statement? We have data on acceptability from questionnaires and have reported satisfaction rates as high as 92 - 100% with regard to men’s experience during the removal procedure.[4] In respect of the report of odour, we have recently determined that any odour is directly related to the patient’s personal foreskin hygiene and not to the device or the necrotic foreskin (article under review). Vincent Mutabazi

Director, Research Grants Unit, Rwanda Medical Research Centre, Ministry of Health, Kigali, Rwanda mutabazivincent@yahoo.com 1. Millard PS, Wilson HR, Goldstuck ND, Anaso C. Rapid, minimally invasive adult voluntary male circumcision: A randomized trial of Unicirc, a novel disposable device. S Afr Med J 2014;104(1):52-57. [http://dx.doi.org/10.7196/SAMJ.7357] 2. Bitega JP, Ngeruka ML, Hategekimana T, et al. Safety and efficacy of the PrePex device for rapid scale up of male circumcision for HIV prevention in resource-limited settings. J Acquir Immune Defic Syndr 2011;58(5):e127-e134. [http://dx.doi.org/10.1097/QAI.0b013e3182354e65] 3. Mutabazi V, Kaplan SA, Rwamasirabo E, et al. HIV prevention: Male circumcision comparison between a nonsurgical device and a surgical technique in resource-limited settings: A prospective, randomized, no masked trial. J Acquir Immune Defic Syndr 2012;61(1):49-55. [http://dx.doi. org/10.1097/QAI.0b013e3182631d69] 4. Mutabazi V, Kaplan SA, Rwamasirabo E, et al. One arm, open label, prospective, cohort field study to assess the safety and efficacy of the PrePex device for scale up of non-surgical circumcision when performed by nurses in resource limited settings for HIV prevention. J Acquir Immune Defic Syndr 2013;63(3):315-322. [http://dx.doi.org/10.1097/QAI.0b013e31828e6412] 5. Millard PS, Wilson HR, Veldkamp PJ, Sitoe N. Rapid, minimally invasive adult voluntary male circumcision: A randomised trial. S Afr Med J 2013;103(10):736-742. [http://dx.doi.org/10.7196/ SAMJ.6856] 6. Dermabond. Topical skin adhesive. http://www.accessdata.fda.gov/cdrh_docs/pdf/P960052c.pdf (accessed 24 March 2014).

Dr Millard responds: We appreciate Dr Mutabazi’s thoughtful comments and agree that the need for intra-operative suturing in 17% of the volunteers undergoing the Unicirc procedure was an adverse event. We subsequently added extensions to the thumb screws to increase the compressive force of the device, and our poststudy case series of 50 volunteers (Table 6 of our paper) required no intra-operative suturing. There is a video of the revised instrument in operation (http://www.youtube.com/user/unicircglobal). We cannot take credit for the game-changing use of cyanoacrylate tissue adhesive in circumcision. Numerous previous studies have shown that it is safe and effective in boys[1] and men.[2] Other researchers have not found adhesive failure to be a problem, and we had two partial wound separations (>2 cm in length, none requiring treatment) in 100 Unicirc procedures in our study,[3] and none in 50 procedures in our post-study case series. We did have a higher level of adhesive failure in our earlier Gomco adhesive study in Mozambique,[4] which we attributed to men finding it difficult to keep themselves dry during the rainy season; clearly further research is needed on this important issue in less developed settings. Our two studies were modelled on the World Health Organization’s Framework for Clinical Evaluation of Devices for Adult Male Circumcision.[5] Rather than repeat study definitions in the Unicirc paper, we referred to Table 1 of our previous paper, which defined a healed wound as ‘completely epithelialised; no superficial ulcerations or granulation tissue present’. We defined the duration of the procedure as ‘time from first clamp on foreskin until dressing placed’.[4] With regard to cost of expendable materials, a disposable pack for surgical circumcision (including sutures) costs $15; the much simpler pack for the Unicirc costs $5, and adhesive costs $4 in South Africa.

May 2014, Vol. 104, No. 5

CORRESPONDENCE

Comparison of the total cost therefore depends on the market price of the Unicirc instrument, which has not yet been determined. Reduced personnel costs because of the speed of the procedure and the fact that no subsequent intervention is needed for device removal will result in large cost-savings with the Unicirc method. We appreciate Dr Mutabazi’s groundbreaking research on the PrePex device. Delayed healing by secondary intention is a critical drawback common to all necrotising plastic ring devices like the Prepex, and we have a profound obligation to the millions of men who are receiving this lifesaving intervention to quantify the pros and cons of each technique. We therefore invite Dr Mutabazi to join us in conducting a comparative study of Prepex v. Unicirc circumcision. Peter S Millard

M J A Reid

Graduate Program in Public Health, University of New England, Portland, Maine, USA pmillard@mac.com

Botswana UPenn Partnership, Botswana; Perelman School of Medicine, University of Pennsylvania, USA; School of Medicine, University of Botswana michael.j.a.reid@gmail.com

1. Lane V, Vajda P, Subramaniam R. Paediatric sutureless circumcision: A systematic literature review. Pediatr Surg Int 2010;26(2):141-144. [http://dx.doi.org/10.1007/s00383-009-2475-y] 2. D’Arcy FT, Jaffry SQ. A review of 100 consecutive sutureless child and adult circumcisions. Ir J Med Sci 2011;180(1):51-53. [http://dx.doi.org/10.1007/s11845-010-0545-8] 3. Millard PS, Wilson HR, Goldstuck ND, Anaso C. Rapid, minimally invasive adult voluntary male circumcision: A randomised trial of Unicirc, a novel disposable device. S Afr Med J 2014;104(1):52-57. [http://dx.doi.org/10.7196/SAMJ.7357] 4. Millard PS, Wilson HR, Veldkamp PJ, Sitoe N. Rapid, minimally invasive adult voluntary male circumcision: A randomised trial. S Afr Med J 2013;103(10):736-742. [http://dx.doi.org/10.7196/ SAMJ.6856] 5. World Health Organization. Framework for Clinical Evaluation of Devices for Adult Male Circumcision. Geneva: WHO, 2011.

S Afr Med J 2014;104(5):324-325. DOI:10.7196/SAMJ.7993

‘It would have been better if I had HIV instead of diabetes’

To the Editor: ‘Go ka bo go ne go le botoka go nna le HIV gona le bolwetse jwa sukiri’ (‘It would have been better if I had HIV instead of diabetes’). This flippant comment was overheard in a diabetes clinic waiting room in southern Botswana earlier this year. Although a new diagnosis of diabetes does not carry the stigma of a new HIV diagnosis, for many patients it nonetheless feels like a life sentence. While there are no local data to support the suggestion that type 2 diabetes mellitus (T2DM) confers a worse prognosis than HIV, patients with T2DM in Botswana face at least as many obstacles to high-quality care as do patients with HIV. A network of HIV counselling and testing facilities means that access to free, anonymous, same-day HIV testing is available throughout Botswana.[1] Despite an estimated prevalence of approximately 11%,[2] screening for diabetes is not routinised and most diagnoses are made when patients present late in the course of their disease. While 97% of Batswana adults have been tested for HIV in the past 12 months,[3] more than 80% of patients with T2DM are unaware that they have it.[2] Notably, there are also stark contrasts in the competence of clinicians to manage these diseases. The Ministry of Health has had considerable success in building capacity to deliver HIV care across the country.[4] Many nurses and doctors are now capable of initiating and managing patients on antiretrovirals. In contrast, many healthcare providers lack confidence in managing patients with advancing diabetes, especially those on insulin therapy. That only two oral medications (metformin and glibenclamide) and three insulin formulations (Actrapid, Actraphane and Protophane) are available on the national formulary also illustrates how T2DM remains underprioritised at a policy level. Disparities in how disease-specific complications are managed are also striking. While most HIV-infected patients are screened for

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renal dysfunction and hepatitis before ART initiation and regularly thereafter, screening for DM complications occurs far less frequently. Furthermore, the diagnostic infrastructure to screen for diabetic nephropathy and retinopathy is largely unavailable outside Gaborone. The rapid increase in the incidence of diabetes in Botswana is cause for alarm,[5] as is the marked lack of clinical capacity to manage patients who develop this complex, chronic condition. Botswana has had significant success in responding to the HIV epidemic: in excess of 90% of eligible individuals are now on antiretrovirals. Lessons learnt from this success – leveraging HIV screening strategies and capacity building initiatives – are necessary to improve outcomes for patients living with T2DM in Botswana.

B Tsima

School of Medicine, University of Botswana 1. Creek TL, Alwano MG, Molosiwa RR, et al. Botswana’s Tebelopele voluntary HIV counseling and testing network: Use and client risk factors for HIV infection, 2000-2004. J Acquir Immune Defic Syndr 2006;43(2):210-218. [http://dx.doi.org/10.1097/01.qai.0000230525.71717.5d] 2. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94(3):311-321. [http://dx.doi.org/10.1016/j. diabres.2011.10.029] 3. National AIDS Coordinating Agency. Preliminary Results Botswana AIDS Impact Survey IV. Gaborone: Statistics Botswana, 2013:25. 4. Bussmann C, Rotz P, Ndwapi N, et al. Strengthening healthcare capacity through a responsive, countryspecific, training standard: The KITSO AIDS training program’s support of Botswana’s national antiretroviral therapy rollout. Open AIDS J 2008;2:10-16. [http://dx.doi.org/10.2174/1874613600802010010] 5. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27(5):1047-1053. [http://dx.doi.org/10.2337/diacare.27.5.1047]

S Afr Med J 2014;104(5):325. DOI:10.7196/SAMJ.8216

Call for closure of Folateng private wards in public hospitals in southern Gauteng

To the Editor: The facilities available in southern Gauteng for severely ill patients with diseases related to internal medicine are currently under severe pressure. Central and regional hospitals in this region have frequently had to close to admissions because their bed occupancies have exceeded 100%. This problem started in 2013 and has become progressively worse. The reasons for this crisis are not difficult to understand: (i) there is a very high burden of illness in the population served by these public hospitals, including communicable (HIV/AIDS, tuberculosis) and non-communicable (cardiac, pulmonary, metabolic, oncological) diseases; (ii) Gauteng is the most populous province of South Africa, with just over 12 million people; and (iii) despite this ever-increasing burden of illness, a decision was taken some years ago to close a number of public health facilities such as Hillbrow and Kempton Park hospitals. In addition, a significant number of public healthcare beds were privatised for use by patients with medical aids – Folateng private wards. It is no wonder that our existing public hospitals are overwhelmed. The Department of Medicine at Chris Hani Baragwanath Academic Hospital in Johannesburg has a bed capacity of 730, with bed occupancy of over 90%. We admit over 100 patients a day, and not infrequently have more patients than available beds. The result is that very sick people are kept waiting on chairs for long periods of time. The nurses, the doctors and the support services are frequently overstretched, resulting in suboptimal service delivery. This is a totally unacceptable situation that needs a strategic solution.

May 2014, Vol. 104, No. 5

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CORRESPONDENCE

We the undersigned, senior consultants in the Department of Medicine at Chris Hani Baragwanath Academic Hospital, are extremely concerned at the lack of available hospital beds for very ill medical patients (level 2 and level 3) who require specialist care. We call on the Gauteng Health Department to do the following to alleviate this serious situation: • Close all Folateng private wards at Charlotte Maxeke Johannesburg Academic Hospital (100 beds), Helen Joseph Hospital (40 beds) and Sebokeng Hospital (36 beds), and re-open them for use by public sector patients. Staffing would not be an issue, because staffing already exists in these wards. The private sector has ample capacity for patients who are members of medical aid schemes. • Consider re-opening hospitals such as Hillbrow, Kempton Park and Lenasia South, since the opening of Jabulani Hospital in Soweto will not have significant impact on its own. We feel that it is our moral and ethical duty to raise this as a matter of extreme urgency, with the intention of providing better and more humane care to our patients. K R L Huddle, T Parbhoo, D Blumsohn, C Menezes, A Peter, M Patel, M Mashabane, J M L Tsitsi, M Tikly, R Shires, R Ally, M R Essop, M Wong, C Ickinger, N Govind, S Bhana, N Mohamed Department of Medicine, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa kenneth.huddle@wits.ac.za

Debjani B Mueller

Moreshnee Govender

Department of Community Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; CMeRC Health Technology Assessment Unit, Johannesburg, South Africa

Debashis Basu

Department of Community Health, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; CMeRC Health Technology Assessment Unit, Johannesburg, South Africa 1. World Health Organization. Baseline country survey on medical devices. 2001. http://www.who.int/ medical_devices/countries/en/ (accessed 30 September 2013). 2. Department of Health. Medicines and Related Substances Act, 1965 (Act No. 101 of 1965): Regulations relating to medical devices (No. R586 dated 22 July 2011). Pretoria: Government Printers, 2011. 3. Industrial Development Corporation. Request for proposal to conduct research to guide the development of strategy for the medical devices sector of South Africa. T61/09/13. 2013. http://www.idc.co.za/tenders/ T61-09-13_Research%20for%20the%20Medical%20Devices%20Sector%20of%20South%20Africas_ Bid%20Document_10%20September%202013%20(1).pdf (accessed 30 September 2013). 4. European Union. The dialogue facility. 2013. http://www.dialoguefacility.org/SA%20EU%20 brochure%202013HR.pdf (accessed 30 September 2013).

S Afr Med J 2014;104(5):326. DOI:10.7196/SAMJ.7611

May 2014, Vol. 104, No. 5

SAM

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To the Editor: Access to high-quality, safe and appropriate priority medical devices is becoming the bedrock of delivery of effective and efficient healthcare across the world. The use of medical devices impacts on the continuum of care under the universal health coverage strategy. However, the decision-making process relating to commissioning, maintenance and decommissioning of medical devices, often taken without evidence, results in poor service delivery, particularly in developing countries. The World Health Organization baseline country survey[1] provides a global reference on health technologies, and particularly on the availability of specific medical devices, policies, guidelines, standards and services. It is necessary to develop country-specific case studies to elaborate on these reports and to share road maps from the progress made in different countries. A qualitative analysis of the various processes currently undertaken in South Africa (SA) reveals that medical devices and the medical diagnostic sector are estimated to be worth US$2.5 - US$3 billion. Although the SA pharmaceutical sector is subject to comprehensive

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* m a m

Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Center for Research on Health Economics, Social and Health Care Management (CREMS), University Carlo Cattaneo (LIUC), Castellanza Varese, Italy; CMeRC Health Technology Assessment Unit, Johannesburg, South Africa debjani.mueller@wits.ac.za

S Afr Med J 2014;104(5):325-326. DOI:10.7196/SAMJ.8178

A new horizon for the medical device sector in South Africa

regulation, current knowledge of the medical device sector is deficient. It is noted that the absence of a regulatory system combined with a ‘multi-channel’ system of procurement of medical devices (between the public and private systems as well as within the public system across different provinces) contribute to this problem. Only a few medical devices (such as radiological equipment) are subject to mandatory quality standards, resulting in importation of sub-standard products. Lack of skilled manpower and an integrated approach to management of medical devices, as well as the absence of a regulatory environment, are major challenges. A South African health product regulatory authority is currently being established to address the gap.[2] A detailed study is being planned to document the current regulation and legislation, market funding and financing.[3] In addition, another project is exploring the possibility of setting up a South African health regulatory training institute to address the shortage of skills in regulation.[4] A multi-disciplinary team of practitioners (consisting of engineers, clinicians and health economists) will be required to lead decision making in health systems. Training in health technology assessment could contribute to their expertise in the interdisciplinary work of medical device management. SA is currently in the process of introducing National Health Insu rance to improve provision of universal health coverage. Effective and efficient use of medical devices would assist in this process.

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Lowering private investor risk to build a healthier country A slew of highly innovative, private local and international, socially conscious companies are starting to improve health care outcomes in southern Africa – with some garnering investor returns of between 8% and 10% on debt funds and up to 35% in equity returns. This emerged in a panel discussion entitled ‘Investing for impact’ during the Inclusive Healthcare Innovation Summit organised late last month by the University of Cape Town’s Graduate School of Business (GSB), based at the Mother City’s Foreshore. On the panel were several pioneering social financiers whose forte is unlocking and sourcing funding while minimising risk to enable projects that provide financial and social returns across a wide spectrum. These are specialists in ‘bang-for-buck’ social impact through new financing instruments that identify the interests of each party and align them to achieve outcomes that all can commit to. The global trailblazer in social impact bonds (SIBs), the UK-based Social Finance, has now begun a feasibility study on boosting local job creation with the GSB’s Bertha Centre for Social Innovation and Entrepreneurships and Genesis Analytics, funded by the South African National Treasury and the Flanders Development Agency. The research coalition is also looking at education and health as potential areas for SIBs. With donors cutting back funding since the global financial meltdown 6 years ago, governments, especially in developing countries, are looking for new ways to pay for services provided traditionally by nongovernmental organisations. Jane Newman, the International Director of Social Finance, told the Cape Town seminar that in the UK preliminary data suggest that the first SIB is contributing to a relative decline in re-offending among former prisoners. There are 14 SIBs currently commissioned in the UK. Other areas of exploration for SIBs include early identification and self-management of diabetes, and social clubs and programmes for elderly people to mitigate the burden of mental health disorders and accidents/ emergencies. ‘We’re a financial intermediary – our philanthropic-leaning founders’ challenge to us was, “can you bring a

Jane Newman, International Director of the UKbased Social Finance. Picture: Chris Bateman.

financial lens to tackle social issues, and use that to raise broader capital?” We don’t divert money already available in any sector, but rather look at modest investment costs in prevention to generate savings and social benefit down the line – for which it’s much easier to make a case,’ she stressed.

Comprehensive ‘blue-collar’ healthcare at a fraction of ‘usual’ premiums

A local company that has gained traction since pioneering affordable low-income-based health insurance 6 years ago, is CareCross Health, whose off-shoot OCSACare, provides ‘full-spectrum, unlimited primary care’ for blue-collar workers at just R214/month (contributed by employers). Their scheme’s target members are people earning less than R5 000/month. OCSACare has now built up a network of 1 400 contracted private GPs, and a similar number of dentists, optometrists, radiologists and pathologists to provide a ‘one-man, one-doctor’ service that directly reduces health-related or dysfunctional (read overburdened) State-clinic related absenteeism. According to Statistics South Africa, absent workers cost South Africa more than R12 billion/year – with a third of public sector workers absent for health reasons, compared with just over 9% in the private sector. Drawing from among the more than 80% of South Africans unable to afford the traditional higher-end medical aid premiums (often ten times the premium, though two or

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three have followed the CareCross example), OCSACare today covers 25 000 members – and throws in company education and treatment programmes to tackle the two most common chronic conditions: hypertension and diabetes. The preventive focus includes regular reports to management on illness in the workplace, which allows companies to track and address the most common health complaints. OCSACare’s CEO, Annie Radmanovic, cites the Constitution to remind people that the onus for providing quality healthcare lies not only with government. ‘We’ve been able to prove that bringing affordable private healthcare to all in South Africa is possible,’ she says. CareCross MD, Dr Reinder Nauta, says that remunerating GPs through risk-share models, e.g capitation, ensures an appropriate level of medical care at an affordable price point. This form of remuneration will also underpin the fee models proposed by the National Health Insurance.

Wyer emphasised that it was ‘all about de-risking investments; the less risk, the less return – but a safer, more palatable investment’. CareCross wasn’t the only company looking at innovating fee models. Dr Brian Ruff, General Manager of Discovery Health, noted on several occasions at the summit that the current fee-for-service model was unsustainable. Nauta quipped that CareCross is ‘a not-for-loss company,’ intimating that companies who make money in healthcare are often frowned upon, but without profit there is no sustainability.

Access to cheaper medicines now on the horizon

Managing the Cadiz sub-Saharan Investment Support Fund (Cadiz ASSIST) is former US Agency for International Development (USAID) and World Bank facilitator, Terry Wyer, now Senior Mana ger, Global Partnerships and Impact Invest ment at Cadiz Asset Management, the Investment Manager of the Southern African Regional Programme on Access to

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IZINDABA

Medicines (SARPAM), Africa Medicines Impact Investment Fund (AMIIF). His team recently completed a Department for International Development-funded market assessment on medicine access for low-income communities in South Africa, Lesotho, Namibia and Botswana. They are also in a USAID partnership to finance and develop a product using grant funding and private sector capital (in this case mainly South African pension fund capital) to reduce risk on high-impact investments in South Africa. Their overall goal with AMIIF and their international partnerships is to ‘catalyse’ private sector investment into the health space. ‘Large capital inflows means traction and large-scale social impact,’ says Wyer. His company provides investment and technical assistance; in the process looking at the financial health of the prospective partner business, their marketing plan, creditscoring models and other needs, but, most importantly, their social impact. ‘So far we’ve not had a single default on these high impact projects. We’re actively looking for investors and viable businesses,’ he adds. Heavyweight partners include the US government, Standard Bank, UKaid, Greater Capital, African Management Services Company (AMSCO), Re-action! Consulting, ETM Analytics, Axis (administration), Grant Thornton and BLC Legal Counsel. Carlijn Nouwen is a partner in Dalberg’s Johannesburg office (Dalberg being a strategic advisory firm working to raise living standards in developing countries and address global challenges). She has extensive expertise in solutions that facilitate bank loans to the health sector – something virtually unheard of prior to the advent of innovative low-risk social impact financing. One of the most all-embracing instruments that Nouwen presented is HUGinsure, the first-ever insurance entity dedicated to social impact projects. HUGinsure is a joint venture between D Capital (Dalberg’s impact investment arm) and Hollard Insurance, currently piloting its first products. Unlike a guarantee, HUGinsure provides a way to unpack, manage and spread risks. Says Nouwen, ‘The banks’ major concern is how quickly they’ll get their money back. We insure very specific risk related to the loans, in partnership with major insurance players [Hollard Insurance, Lloyd’s of London].’

Terry Wyer, SARPAM Investment Manager. Picture: Chris Bateman.

What benefits does HUGinsure bring? Among other things, emergency relief organisations will no longer need to use such huge dormant disaster-relief funds to be ready to jump in the next humanitarian crisis. A HUGinsure policy will act as a ‘comfort wrapper’ for banks to give organisations such as Save the Children a credit facility in case disaster strikes. Hundreds of millions of rands ‘sitting doing nothing’ can be freed up to work for social good. Dalberg has worked extensively on advance purchase agreement mechanisms, which enable projects that might otherwise never gain traction and secure predictability. Where this involves farmers, they can rest easy that they’ll sell at a fixed price. In Mozambique, D Capital has designed a development impact bond to fight malaria in partnership with private sector players and the government of Mozambique. The first issuance of the bond is expected later this year.

‘De-risking’ makes it possible – and palatable

Asked what the typical range of returns was for investors, Wyer said it depended on the type of organisation and where on the social and financial returns spectrum they were aiming. ‘For example, mines get uptime for their workers via malaria interventions and this is all they need with regards to return

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expectations, but South African investors are usually looking for 8 - 10% on debt funds as well as social returns and in equity we’re looking at 25 - 35% return expectations from even some of the so-called development institutions. As you go north into Southern Africa you can expect larger returns but still get tremendous social impact.’ Wyer emphasised that it was ‘all about de-risking investments; the less risk, the less return – but a safer, more palatable investment for organisations making these investments.’ Nouwen told seminar delegates that impact investors in malaria control received a 5 - 10% return on their investment, ‘if we’re successful.’ Newman, quizzed on her experience of social issue areas that did not lend themselves to the mechanism, said it was ‘about speed of return on investment and depth of the social issue – you’ve seen the graph with the peak of expectation, trough of desperation and the platform of productivity – we’re hoping we’re some way towards the last.’ She said confounding factors included lack of good or accessible data, explaining, ‘with prisoners, police computers make access easy, but with drugs and alcohol it’s more difficult.’

‘Our philanthropic-leaning founders’ challenge to us was, “can you bring a financial lens to tackle social issues, and use that to raise broader capital?”’ In closing the session, the Bertha Centre’s Director, Dr François Bonnici, remarked on the growth of the social finance sector, saying ‘As this panel has demonstrated, we are seeing the emergence of financial instruments designed specifically for social enterprises and organisations that are creating impact in their communities, these instruments are creating investment opportunities for impact-oriented investors and partnership opportunities for governments and corporations. We see this space continuing to grow exponentially in size and significance.’ Chris Bateman chrisb@hmpg.co.za S Afr Med J 2014;104(5):327-328. DOI:10.7196/SAMJ.8085

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Population-based health funding under attack A ‘static, outdated and inflexible’ population-based funding formula for public health is putting huge pressure on well-run and wellequipped hospitals in the Western Cape, KwaZulu-Natal and Gauteng as people from other provinces migrate there in their tens of thousands to seek a better life. The frustrated heads of health in these top-performing three provinces would much prefer a formula that recognises ‘bang for buck’ results, and for ‘funding to follow functionality and service delivery’. The opposition-led Western Cape is taking legal advice on what it calls a ‘constitutionally unjustified, inefficient, unfair and unacceptable’ formula. The dysfunctional ‘bottom three’ (of nine) provincial health departments, Limpopo, Mpumalanga and the Eastern Cape, are notorious for misspending or outright misappropriating hundred million-rand chunks of their budgets annually, and the National Treasury has regularly intervened to manage their financial health. From bitter experience, many of their patients know that they are likely to get quicker and better help in neighbouring provinces.

Patients go where the services are

Meanwhile, the under-funded ‘topperforming three’ provincial health departments continue to render more efficient services while dealing with an everincreasing inflow of patients that fills most of their hospitals to overflowing – hostages to the national 2011 Census-based health funding formula. (A census is conducted once a decade, but National Treasury updates this annually with a mid-year population estimate by Statistics South Africa (SSA).) SSA estimates that in the five years from 2006 to 2011, some 264 449 people migrated away from the Eastern Cape, while Limpopo’s outward migration stood at 227 919. During the same period the Western Cape and Gauteng experienced a net inflow of migrants of 307 411 and 1 046 641, respectively. No geography prizes for working out that the former came mostly from the Eastern Cape and the latter mainly from Limpopo and Mpumalanga.

Western Cape Health MEC, Theuns Botha. Picture: Chris Bateman.

Western Cape Health MEC Theuns Botha says that an analysis of service pressures at health facilities across his province shows a 28% population increase – which he’s prepared to service, freedom of movement being a constitutional right – but that the national government has a ‘commensurate and constitutional obligation’ to compensate provinces for services rendered. ‘The more we improve our services, the more patients we attract,’ he adds, citing the irony of having seen few visible results in spite of several ‘ground-breaking initiatives’ to reduce waiting times. All Cape Metro acute hospitals were well above the minimum optimal efficiency occupation level of 85%, with the largest and busiest referral hospital, Tygerberg, 87% full, meaning that corridor beds, trolleys in wards and ambulance diversions were the norm. The busiest hospital, the newly commissioned Khayelitsha District Hospital, was 131% full, followed by Westfleur Hospital (107%), Eerste River Hospital (103%), Helderberg Hospital (101%) and Victoria Hospital (99%). The average projected patient occupancy rate for all 13 Cape Metro hospitals for 2013/2014 was 91%. In spite of a large district hospital being built in Khayelitsha, the Peninsula’s most populous township, calculations showed that the unmet patient need there now stood at 1 000 - 1 300 additional admissions per year.

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W Cape hospitals bursting at the seams

Botha said that Tygerberg Hospital saw 20% of the province’s annual patient load of 80 000 and required R267 million per year to run and maintain. However, the province could only afford to allocate R83 million, meaning that the hospital ran on a R192 million annual shortfall. He emphasised that seeking legal advice on the constitutionality of the current Devolution of Revenue Act was not a threat. ‘We need to get the arguments and legal issues sorted out to promote our opinion and change the budget allocation formula. It may require a change in legislation – it will definitely require policy deviation. Perhaps as importantly, there is simply no way a National Health Insurance scheme will fly without this budgetary reform. They used to talk about unfunded mandates – well, this falls within that category,’ Botha added. His examples of ‘ground-breaking’ Western Cape healthcare innovations include decentralised deliveries of prescription medication to nonprimary healthcare sites for collection (with SMS notification), which should lead to a reduction of 30% in the patient load at clinics and day hospitals. So far 50 000 primary healthcare patients are said to be benefiting from this system, which puts medicines closer to their homes, with a targeted patient base of 150 000. Over 100 new healthcare facilities have opened over the

IZINDABA

past four and a half years, while a cell-phonebased patient complaints mechanism means that any complaint is dealt with inside two hours, vastly improving healthcare worker accountability and service quality monitoring. An increasingly efficient patient transport system helps deliver 3 500 rural patients to Cape Metro hospitals monthly, using a widely advertised booking system, while local authorities have helped erect new allweather shelters at specific pick-up points across the province. Botha said a multilateral service agreement between the provincial health department and the four universities that provide expert clinical services meant avoiding the debilitating disputes that made headlines in the Free State, Gauteng and Eastern Cape academic health complexes last year. An ambitious ‘wellness’ programme was now firmly entrenched, as was a private sector foundation aimed at generating further income through innovative public/ private ventures.

Relentless patient pressure blunts most initiatives – Botha

However, the relentless growth in patient pressure has blunted many initiatives. At Tygerberg Hospital, in spite of 30 theatres

being operational daily, long waiting lists for emergency as well as surgical procedures remain. Patients with open fractures wait for up to 72 hours, while waiting times for elective procedures like removal of an enlarged prostate now stretch to a year. Spinal surgery candidates generally wait 48 weeks, and cancer surgery waits stand at between 6 and 16 weeks (there were 280 patients in three cancer groups waiting at the time of writing). Patients requiring knee and hip replacements can wait eight years. Botha said that R6 billion had been set aside to expand and revamp the hospital. Tygerberg Hospital’s three main feeder hospitals had increased maternity referrals by 100 deliveries per month between January 2011 and January 2014 – with 46% of these women requiring caesarean sections, indicating the complexity and urgency of the cases. Over 30% of babies were of low birth weight, requiring further inpatient care. The overall patient-day-equivalent load on Tygerberg had increased by 18%. Just under a third (30%) of all patients requiring dialysis managed to get onto the programme, while there had been a 69% increase in patients needing emergency medical services. Izindaba sources in National Treasury defended the funding formula, claiming

that money went ‘where people get services’, but conceded that responding to migratory patterns was a challenge. There are three main sources of healthcare funding, the largest the equitable grant, followed by the national tertiary services grant, plus the infrastructure health facility revitalisation grant. The overall funding formula is based on each province’s disease burden, its uninsured population and adjusted census data – with actual use of hospitals and clinics measured and factored in. For the first time in the 2013/2014 national budget process, performance-based measurements were used in the health facility revitalisation grant – but the impact is obviously yet to be felt. One national treasury source said that any cost-pressured head of department would like more money, but ‘the other side of the story’ lay in the views of the less-resourced provinces, which faced ‘very real pressures’. ‘You can’t ignore these people and those who depend on their services, but clearly performance needs to be improved,’ he added.

Dirk Johannes Jacobus van Velden (1932 - 2013)

in Somerset West. When his father was called to Montagu he continued his schooling at Jan van Riebeeck High School in Cape Town, matriculating in 1949. With the help of a substantial donation from friends in Richmond, Dirk was able to enrol as a medical student at the University of Cape Town, graduating there in 1955. He met his future wife Ria while on holiday with friends in Stilbaai, and they married on 6 July 1957. After completing his internship under the tutelage of Dr Francie van Zyl at Groote Schuur Hospital, Dirk became the first intern in obstetrics and gynaecology in Professor Jannie de Villiers’ unit at Karl Bremer Hospital. Appointments in Sutherland, Touw’s River and Franschoek followed before he and Ria left for Mkar in Nigeria,

Chris Bateman chrisb@hmpg.co.za S Afr Med J 2014;104(5):329-330. DOI:10.7196/SAMJ.8172

OBITUARY Dirk van Velden was born on 11 October 1932, as one of the six children of Dominee and Mrs Anthonie van Velden of Richmond in the Karoo. He was in good health when he passed away peacefully in his sleep on 1 December 2013 in Altena, Strand, Western Cape. Dirk was an outstanding tutor and mentor and was loved and respected by his colleagues, friends and students alike. To celebrate his achievements, we present a short résumé of his remarkable career. Dirk spent his early childhood years in Richmond before his father was called to lead the congregation in Somerset West, Western Cape, in 1936. His primary school and some of his high school years were spent

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where he formed part of a team that worked at a mission hospital. After a few months there Ria developed a low-grade fever while pregnant, and they decided to cut short their planned 6-month stay. On returning to South Africa, Dirk bought into a practice in Ceres where he worked until a desire to return to academia resulted in his obtaining a post as registrar in obstetrics and gynaecology, once again in the unit of Professor De Villiers. A year later he applied for and was successful in obtaining a post in the Department of Anatomical Pathology, a career move that would change the course of his professional life. He graduated with distinction as a clinical pathologist in 1967, and then undertook a fellowship as a research scientist at the Roswell Cancer Memorial Institute in Buffalo, New York, USA, where he spent a year with his young family. On his return to South Africa, Dirk was invited to apply for and obtained the post of Professor and Head of the Department of Anatomical Pathology in the newly established

Faculty of Medicine in Bloemfontein. There he planned and commissioned an anatomical pathology laboratory with service and academic functions. Various trips overseas followed and helped to ensure maintenance of the highest professional standards in the department. After eight years in academia, Dirk accepted an opportunity to join a private practice in Bloemfontein with part-time involvement in the Department of Anatomical Pathology. His last professional appointment completed a circle that had begun in Cape Town many years previously: he was appointed Professor in the Department of Anatomical Pathology in the Faculty of Medicine at Stellenbosch University, where his main responsibility was running the surgical pathology service as well as the teaching and training of personnel, registrars and students. At the end of 1998, Dirk and Ria retired to Glentana, where they spent ten very happy years before temporarily retiring to Oude Westhof retirement village in Bellville and finally settling in Strand.

Dirk leaves a rich legacy that will live on in his wife, children, grandchildren, colleagues and many others, with whom he enjoyed a wonderful relationship. He will be remembered for his love of and kindness to his fellow-man, for his honesty, integrity and keen sense of humour, for his jovial nature, and for his unshakeable belief in his Creator. Ave atque vale! Peter Wranz Part-time Senior Consultant; previous Head of the Department of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa eswranz@worldonline.co.za Johann Schneider Professor and Head of the Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa

BOOK REVIEW Breast Care: A Health Professionalâ&#x20AC;&#x2122;s Guide to Diagnosis and Management of Common Breast Conditions By Jenny Edge and Dave Woods. Cape Town: Getup Electric Book Works, 2014. ISBN (paperback) 978-1-920218-76-8; ISBN (PDF ebook) 978-1-920218-77-5 (Download at http://www.scribd.com/ doc/215289803/Breast-Care-Free-OnlineEdition). This practical book on the management of breast cancer is part of the Bettercare series of books, aimed at addressing the need for continuing education of healthcare workers. The book was inspired by the Breast Course for Nurses, run by Dr Jenny Edge, a general surgeon with a particular interest in breast surgery, at the Christiaan Barnard Hospital in Cape Town, South Africa. Her co-author, Professor David Woods, is the founder of the Bettercare series and is a retired neonatologist living in Cape Town.

The book is essentially a series of courses on different aspects of common breast conditions, with learning objectives clearly stated at the beginning of each chapter, along with multiplechoice questions for each chapter at the end of the book. Theoretical knowledge is presented in a question-and-answer format to encourage active participation in the learning process, leading the reader step by step through definitions, causes, diagnoses, prevention, dangers and management of a particular problem. Each chapter closes with a few case studies, allowing the reader to consolidate and apply what they have learnt. The case studies are drawn from common presentation at clinics and hospitals. The more practical aspects of management are covered in certain chapters that contain skills workshops and readers are encouraged to practise these, preferably in groups. The skills workshops are often illustrated with line drawings, list essential equipment and offer step-by-step instructions on how to perform each task. There is a final examination that consists of a 75-question multiple-choice exam, managed

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by the Perinatal Education Programme, and participants need to achieve at least 80% to successfully complete the course, for which they receive a certificate. Although Bettercare courses are not yet accredited for nurses, South African doctors can use them to earn CPD points. The course starts with the normal breast, including some changes in the breast that may be worrying, carrying on to clinical examination and special investigations. Benign breast changes are covered first, followed by breast cancer and its treatment. Side-effects of treatment are comprehensively covered, as is palliative care. Although the book is aimed at nurses, its content will be useful for anyone likely to encounter breast problems at any level of practice and should also appeal to undergraduates wanting to improve their knowledge of this very common area of womenâ&#x20AC;&#x2122;s health. Bridget Farham Deputy editor, SAMJ ugqirha@iafrica.com

FORUM

MEDICINE AND THE ENVIRONMENT

Health and fracking: Should the medical profession be concerned? R Mash, J Minnaar, B Mash Rev. Dr Rachel Mash is the environmental co-ordinator of the Anglican Church of Southern Africa. She holds a PhD in Family Medicine from Stellenbosch University, South Africa. Jolynn Minnaar is a journalist and director of Unearthed – an independent, international 18-month investigation into shale gas extraction and the fracking process. Prof. Bob Mash is the Head of Family Medicine and Primary Care, Stellenbosch University, South Africa, and chairs the faculty committee on sustainable development. Corresponding author: R Mash (rmash@mweb.co.za)

The use of natural gas that is obtained from high-volume hydraulic fracturing (fracking) may reduce carbon emissions relative to the use of coal and have substantial economic benefits for South Africa. However, concerns have been raised regarding the health and environmental impacts. The drilling and fracking processes use hundreds of chemicals as well as silica sand. Additional elements are either released from or formed in the shale during drilling. These substances can enter the environment in various ways: through failures in the well casing; via alternative underground pathways; as wastewater, spills and leaks on the wellpad; through transportation accidents; and as air pollution. Although many of these chemicals and elements have known adverse health effects, there is little evidence available on the health impacts of fracking. These health concerns have not yet been fully addressed in policy making, and the authors recommend that the voice of health professionals should be part of the public debate on fracking and that a full health impact assessment be required before companies are given the go-ahead to drill. S Afr Med J 2014;104(5):332-335. DOI:10.7196/SAMJ.7860

South Africa (SA) is about to embark on exploratory high-volume hydraulic fracturing (fracking) to extract the huge reserves of natural gas contained in shale rock.[1] There has been much controversy around this decision as, on the one hand, this could reduce our carbon footprint (natural gas releases 58% less carbon dioxide than coal) and could have significant economic benefits for the country; while, on the other hand, there are concerns about the environmental and health impacts.[2] Some countries, such as France and Bulgaria, have banned fracking, while others such as the UK believe that it can be performed safely if regulations are strictly enforced.[3] The USA has been one of the leaders in fracking, which has transformed their reliance on imported fossil fuels, although some states, such as New York, are calling for a comprehensive health assessment before giving permission.[4] Although fracking has been taking place for a decade in the US, there is surprisingly little scientific evidence on the health impacts. It cannot be concluded that an absence of evidence of harm implies that no harm may result.[5] This article attempts to summarise the health concerns and discuss them within the SA context.

The current situation

Permission has been granted to initiate exploratory fracking in an area of >200 000 km2 in SA, which will affect the Karoo, parts of the Free State, Northern and Eastern Cape, and a portion of KwaZuluNatal. If the gas deposits are found to be financially viable, thousands of wells could potentially be drilled in these areas.[6]

Additives used in the drilling and fracking process

Hundreds of chemicals are used during the drilling and fracking phases, but access to information on the chemical constituents has

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been limited due to protection under proprietary legislation. Table 1 shows some of the known chemicals and the purposes for which they are used. Fig. 1 presents data on 353 of the known chemicals and the percentage of these associated with a variety of potentially adverse effects on health;[7] 77 of them (Table 2) are associated with ≥10 potential adverse health effects.[7] Silica sand is used to keep open the network of tiny spaces in the shale created by fracking, which allow the gas to be released. Each well requires up to 2 000 tons of sand for the fracking process. The US National Institute for Occupational Safety and Health reported that 92/116 air samples obtained from fracking sites in five states exceeded the recommended safe levels for silica.[2] Exposure of workers to silica over several years may result in silicosis, an irreversible lung disease associated with an increased susceptibility to tuberculosis.

Elements accessed during drilling and fracking

In addition to the chemicals used during drilling and fracking, elements inherent in the shale layer are also accessed and brought to the surface during gas extraction. Some are known or suspected carcinogens, endocrine disruptors or substances otherwise toxic to humans. Heavy metals such as arsenic, mercury, chromium, barium and lead, and naturally occurring radioactive matter (NORM) such as uranium and strontium, have been identified.[8] According to the US Centers for Disease Control, such toxic exposure can result in ‘anemia, cataracts, cancer and increased mortality’.[9] The potential health risks in the long term need to be considered, as many diseases such as cancer appear after years of exposure.[5]

Risks of exposure

In SA, water is a scarce resource with 98% of available water already allocated.[10] Yet, it has been calculated that up to 29 million

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Alternative underground pathways

Most geologists report that the chemicals that remain in the shale bed are effectively sealed off from the groundwater by the depth of drilling and layers of impervious rock. However, some

scientists who have studied the unique geology of the Karoo, with its widespread intrusion of dolerite dykes and sills, have expressed concern that there exists the possibility of contaminants reaching the groundwater system.[14]

Wastewater

While water does remain in the shale, ~30 60% of the fluid returns to the surface once the well has been fracked. This flowback is laced with the injected chemicals and elements derived from the shale. These ‘produced’ fluids can contain heavy metals, salts and NORM from below ground. The chemicals used in fracking vary in toxicity; some are known or suspected carcinogens, endocrine disruptors or additives otherwise toxic to humans, including benzene, ethylene glycol, methanol, lead, boric acid and γ-emitting isotopes.[3]

Other

Endocrine disruption

Mutagenic

Cancer

Cardiovascular and blood

Kidney

Immune

Brain and nervous system

Gastrointestinal and liver

100 90 80 70 60 50 40 30 20 10 0 Respiratory

The cement and steel casing around the wellhead, where the borehole meets the surface, needs to be constructed so that no chemicals exit the well – whether during drilling or fracking, when producing gas, or after the well has been declared exhausted and has been abandoned. Current well design and capping technology uses steel that may rust and concrete that can crack. The majority of cases of groundwater contamination have been caused by inadequate cementing or casing.[3] These failures may represent migratory pathways for chemicals to reach surrounding water aquifers. Assertions regarding the flammability of drinking water have been made in the mass media and a study has indicated that drinking water wells within a 1 km radius of a drilling site have a 17 times increased concentration of methane.[2] Methane can leak as a result of improperly constructed wells, poor gas capture or, less commonly, hydraulic fractures.[3] Although methane is not toxic to humans and small amounts can normally be present in drinking water, it is flammable and could build up to explosive levels.[11]

Skin, eye and sensory organs

The well casing

One further study also pointed to the danger of workers being exposed to radon, which is a risk factor for lung cancer. The radon present in shale may mix with the methane as it escapes. The concentrations examined in Marcellus shale were up to 70 times the average from other natural gas wells throughout the USA.[12] It should also be noted that fracking increases the risk of local earth tremors, which have the potential to disrupt the well casing; one such incident was reported in the UK where, during exploratory fracking, the well casings were deformed by the tremor.[13]

Chemicals associated with health effects, %

litres of water may be needed for a single well, of which up to 250 000 litres may consist of chemicals.[3] There are several ways in which these chemicals might enter the environment: through a failure in the well casing; via alternative underground pathways; as wastewater, spills and leaks on the wellpad; through transportation accidents; and by polluting the air.

Fig. 1. Possible health effects of the 353 chemicals used in natural gas operations.

Table 1. Types of chemicals and additives used in the fracking process Additive type

Description/purpose

Examples of chemicals

Proppant

‘Props’ open fractures to allow gas to flow freely

Silica sand, zirconium oxide, ceramic beads

Acid

To dissolve clay to allow the gas to flow

Hydrochloric acid (3 - 28%)

Breaker

Reduces the viscosity of the fluid to release the proppant into the fractures

Peroxydisulphates

Bactericide/biocide

Inhibits growth of organisms that could contaminate methane

Glutaraldehyde: 2-bromo-2-nitro-1,2-propanediol

Buffer

Adjusts and controls the pH

Sodium or potassium carbonate

Clay stabiliser

Prevents swelling of clay which might block pores

Tetramethyl ammonium chloride

Corrosion inhibitor

Reduces rust formation on well casings

Methanol, ammonium bisulphate

Crosslinker

Increases the viscosity of the fluid so that it can carry more proppants

Potassium hydroxide, borate salts

Friction reducer

Allows fluids to be injected at optimum rates

Sodium acrylate-acrylamide copolymer, polyacrylamide

Gelling agent

Increases viscosity of fluid

Guar gum, petroleum distillate

Iron control

Prevents precipitation of carbonates, which could plug off the formation

Ammonium chloride, ethylene glycol, polyacrylate

Solvent

Used to control the wettability of contact surfaces

Aromatic hydrocarbons

Surfactant

Reduces fluid surface tension thereby aiding fluid recovery

Methanol, isopropanol, ethoxylated alcohol

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Table 2. Natural gas drilling and hydraulic fracturing chemicals with ≥10 adverse health effects (2-BE) Ethylene glycol monobutyl ether

Ethanol (acetylenic alcohol)

Naphthalene

2,2',2"-Nitrilotriethanol

Ethyl mercaptan

Natural gas condensates

2-Ethylhexanol

Ethylbenzene

Nickel sulphate

5-Chloro-2-methyl-4-isothiazolin-3-one

Ethylene glycol

Paraformaldehyde

Acetic acid

Ethylene glycol monobutyl ether (2-BE)

Petroleum distillate/naptha

Acrolein

Ethylene oxide

Phosphonium, tetrakis(hydroxymethyl)-sulphate

Acrylamide (2-propenamide)

Ferrous sulphate

Propane-1,2-diol

Acrylic acid

Formaldehyde

Sodium bicarbonate

Ammonia

Formic acid

Sodium bromate

Ammonium chloride

Fuel oil #2

Sodium chlorite (chlorous acid, sodium salt)

Ammonium nitrate

Glutaraldehyde

Sodium hypochlorite

Aniline

Glyoxal

Sodium nitrate

Benzyl chloride

Hydrodesulphurised kerosene

Sodium nitrite

Boric acid

Hydrogen sulphide

Sodium sulphite

Cadmium

Iron

Styrene

Calcium hypochlorite

Isobutyl alcohol (2-methyl-1-propanol)

Sulphur dioxide

Chlorine

Isopropanol (propan-2-ol)

Sulphuric acid

Chlorine dioxide

Kerosene

Dibromoacetonitrile 1

Light naphthenic distillates, hydrotreated

Tetrahydro-3,5-dimethyl-2H-1,3,5-thiadiazine-2thione (Dazomet)

Diesel 2

Mercaptoacetic acid

Titanium dioxide

Diethanolamine

Methanol

Tributyl phosphate

Diethylenetriamine

Methylene bis(thiocyanate)

Triethylene glycol

Dimethyl formamide

Monoethanolamine

Urea

Epidian

Naphtha, petroleum medium aliphatic

Xylene

Accidental spills

It is estimated that each well will require transportation of freshwater, chemicals and wastewater by at least 1 500 trucks or tankers.[6] Given the number of trucks, inexperienced drivers and poor state of many roads, there is a very real possibility of accidents, blowouts or spills. Spills are also common on the wellpad where substantial amounts of diesel and the fracking additives are handled and can potentially contaminate local water sources.[3]

Air pollution

Toxic compounds mix with the escaping methane and the nitrogen oxides from the exhaust of diesel trucks to produce ground-level ozone. Ozone combines with particulate matter <2.5 µm and produces smog thereby creating air pollution, which can spread up to 200 km from the production area. A combination of evaporation from the toxic waste ponds, venting and flaring of escaping methane gas from the wells, and the exhaust from trucks and industrial equipment further impairs air quality and contributes to the smog. Dust pollution also arises from the large-scale transportation of water and chemicals on gravel roads.[15] Up to 37% of the chemicals used in the processes are volatile, with the ability to become airborne with subsequent inhalation, ingestion or absorption through the skin. [8] The US Environmental Protection Agency reports that chronic inhalation may result in headaches, insomnia, gastric disturbances, conjunctivitis, visual disturbances and blindness.[11] Although the

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impact of individual wells on air quality may be low, the cumulative impact of a number of wellpads may be significant.[3]

Risk management

While fracking is undoubtedly associated with many potential health problems, some would argue that these risks can be contained with sufficient regulation.[3] Oil, gas and energy companies, however, do not have a good track record when it comes to avoiding pollution on the African continent. Under SA law, hazardous waste management is a provincial responsibility. The majority of fracking is likely to take place in the Eastern Cape, an under-resourced province with poor administration.[6] In SA, there is a concern that regulations will be less strictly adhered to than in well-resourced settings.

Conclusion

Fracking may indeed have substantial benefits for the SA economy. However, the environmental and health impacts may not be insignificant and these have yet to be considered in sufficient depth. To reduce possible negative public health impacts, a precautionary approach should be adopted and provision made for monitoring and adaptation.[2] The voice of the health profession should be part of the debate and a full health impact assessment required before companies are given the go-ahead to drill. Without strictly enforced regulations in place, it would be irresponsible to allow an industry on this scale to be launched.

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1. Department of Mineral Resources. Mineral and Petroleum Resources Development Act, 2002 (Act No. 28 of 2002). Proposed Technical Regulations for Petroleum Exploration and Exploitation. Government Gazette, 15 October 2013. https://db3sqepoi5n3s.cloudfront.net/files/131015technicalregulationforpe troleum.pdf (accessed 27 February 2014). 2. American Public Health Association. The Environmental and Occupational Health Impacts of HighVolume Hydraulic Fracturing of Unconventional Gas Reserves. Policy No. 20125, 30 October 2012. http://www.apha.org/advocacy/policy/policysearch/default.htm?id=1439 (accessed 27 February 2014). 3. Public Health England. Review of the Potential Public Health Impacts of Exposure to Chemical and Radioactive Pollutants as a Result of Shale Gas Extraction. London: PHE, 2013. http://www.hpa.org. uk/webc/HPAwebFile/HPAweb_C/1317140158707 (accessed 27 February 2014). 4. Concerned Health Professionals of New York. Call for a comprehensive health impact assessment. http://concernedhealthny.org/call-for-a-comprehensive-health-impact-assessment/ (accessed 27 February 2014). 5. Finkel M, Hays J. The implications of unconventional drilling for natural gas: A global public health concern. Public Health 2013;127(10):889-893. [http://dx.doi.org/10.1016/j.puhe.2013.07.005] 6. Fig D. Hydraulic fracturing in South Africa: Correcting the democratic deficits. In: Daniel J, Naidoo P, Pillay P, Southall R, eds. New South Africa Review 3. Johannesburg: Wits University Press, 2013:173-194. 7. Colborn T, Kwiatkowski C, Schultz K, Bachran M. Natural gas operations from a public health perspective. Hum Ecol Risk Assess 2011;17(5):1039-1056. [http://dx.doi.org/10.1080/10807039.2011.605662] 8. Lauver, L. Environmental Health Advocacy: An overview of natural gas drilling in Northeast Pennsylvania and implications for pediatric nursing. J Pediatr Nurs 2012;27(4):383-389. [http://dx.doi. org/10.1016/j.pedn.2011.07.012]

9. Agency for Toxic Substances & Diseases Registry; Centres for Disease Control. Toxicological Profile for Radium. http://www.atsdr.cdc.gov/ToxProfiles/tp.asp?id=791&tid=154#bookmark06 (accessed 27 February 2014). 10. Department of Water Affairs and Forestry. National Water Resource Strategy. Pretoria: DWA, 2004. http://www.dwaf.gov.za/Documents/Policies/NWRS/Default.htm (accessed 27 February 2014). 11. Sumi L. Environmental Concerns and Regulatory Initiatives Related to Hydraulic Fracturing in Shale Gas Formations: Potential Implications for North American Gas Supply. Ottawa: Council of Canadians, 2010. http://www.ontarioenergyboard.ca/OEB/_Documents/EB-2010-0199/Report_ Sumi_CoC.pdf (accessed 27 February 2014). 12. Resnikoff M. Radon in Natural Gas from Marcellus Shale. 10 January 2012. http://www.newyorkwater. org/pdf/Marcellus_Radon_copy.pdf (accessed 27 February 2014). 13. Torjesen I. Fracking poses little risk to public health, but evidence is limited. BMJ 2013;347:f6626. [http://dx.doi.org/10.1136/bmj.f6626] 14. Van Tonder G, de Lange F, Steyl G, Vermeulen D. Potential Impacts of Fracking on Groundwater in the Karoo Basin of South Africa. Bloemfontein: Institute for Groundwater Studies. http://gwd.org. za/sites/gwd.org.za/files/04_G%20vTonder_Potential%20%20Impacts%20of%20Fracking%20on%20 Groundwater.pdf (accessed 27 February 2014). 15. The Endocrine Disruption Exchange. Chemicals in Natural Gas Operations. http://endocrinedisruption. org/chemicals-in-natural-gas-operations/introduction (accessed 27 February 2014).

Accepted 31 January 2014.

CLINICAL PRACTICE

Odyssean malaria outbreaks in Gauteng Province, South Africa, 2007 - 2013 J Frean, B Brooke, J Thomas, L Blumberg John Frean, Lucille Blumberg and Juno Thomas are medical microbiologists in divisions of the National Institute for Communicable Diseases, Johannesburg, South Africa, dealing with malaria diagnosis, surveillance and outbreak response, respectively. Basil Brooke is an NICD entomologist with special expertise in malaria vector mosquitoes and mechanisms of insecticide resistance. Professors Frean and Blumberg and Dr Brooke are also affiliated to the Wits Research Institute for Malaria, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. Corresponding author: J Frean (johnf@nicd.ac.za) Background. Odyssean malaria refers to malaria transmitted by translocated mosquitoes and is a diagnosis of exclusion, as the probability of finding the responsible vector is miniscule. We believe that road traffic from endemic areas in and around South Africa is the source of most of the infected mosquitoes. Because of the unexpected nature of the disease, diagnosis is often delayed and severe and complicated malaria is common. Objectives. To describe outbreaks of odyssean malaria during the period 2007 through 2013 in Gauteng Province, South Africa, and to educate healthcare workers about this form of malaria. Methods. Site visits, environmental hygiene inspections, patient interviews, and entomological investigations for adult mosquitoes and larvae in potential breeding sites were done in each identified outbreak. Results. Over the period, 14 laboratory-proven and 7 probable cases of odyssean malaria were investigated. There were 2 deaths (9.5% case fatality rate, approximately 10 times higher than the national fatality rate for malaria). We describe two recent clusters of cases in detail, and emphasise the importance of clinician awareness of this rare but frequently severe form of malaria. Conclusion. Odyssean malaria cases are inevitable in South Africa, given the volume of road, rail and air traffic from malaria risk areas into Gauteng and other non-endemic provinces. It is likely that many cases are missed, owing to the rare and sporadic nature of the condition. Malaria should always be kept in mind as a cause of unexplained fever and thrombocytopenia, even in the absence of a travel history. S Afr Med J 2014;104(5):335-338. DOI:10.7196/SAMJ.7684

The acquisition of malaria outside endemic areas is inherently unexpected, which delays diagnosis and treatment, and is therefore disproportionately associated with severe illness or a fatal outcome. The recognition in the 1970s in Europe of such cases of ‘airport malaria’ (and its subsidiaries suitcase, baggage or luggage

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malaria) led to the awareness that aircraft are not the only vehicles that can transport vector mosquitoes out of their normal habitats, and the entities of harbour, container, and minibus (or taxi rank) malaria were described.[1,2] To unify this plethora of essentially equivalent descriptions, the term ‘odyssean malaria’ was coined.[3] Odysseus was the legendary Greek hero who, on his way home from the

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Trojan wars, wandered the Mediterranean region, experiencing many adventures and narrow escapes. Similarly, a lost mosquito might have many dangerous encounters as she navigates a suitcase, aircraft cabin, cargo hold or taxi, escaping being deliberately swatted, accidentally squashed, eaten by a predator, or succumbing to heat or cold on her way to her next blood meal, far from her natural home. Between 1996 and 2004, we accumulated 46 cases of odyssean malaria in Gauteng Province, South Africa (SA) (Table 1).[1] These patients are clearly at risk of substantially higher mortality compared with the national malaria case fatality rate, and given SA’s position at the southernmost extent of malaria transmission on the continent, attract intense local media interest and speculation about spread of malaria to this (non-endemic) province. No odyssean malaria cases were noted in 2005 and 2006 (although we believe that several cases are missed every year), but we have investigated cases in nearly every malaria season since then, including two outbreaks in the 2012 - 2013 season. We discuss the clinical and public health aspects of this frequently severe form of malaria.

were interviewed and detailed clinical and travel histories obtained. Adult mosquitoes, when present, were caught inside houses and other buildings around the patients’ dwellings. Mosquito larvae were collected from surface water bodies and containers, if such breeding sites were found. Standard entomological techniques were used to identify mosquitoes to species level.

Results

Eight outbreaks were investigated during the study period, yielding 14 laboratory-proven and 7 probable cases of odyssean malaria. There were 2 deaths (9.5% case fatality rate, approximately 10 times greater than the current national case fatality rate for malaria, and nearly 20 times the national target of 0.5%) (Table 2). The most recent outbreaks are described in detail.

Outbreak 1

A couple living on a smallholding in Donkerhoek/Mooiplaats, on the eastern outskirts of Pretoria, Gauteng Province, experienced Table 1. Odyssean malaria in Gauteng Province, South Africa, 1996 - 2004[1]

Methods

Case definition

A case of odyssean malaria is one in which there is no travel history, and the possibility of mechanical transmission (by blood transfusion, injection or needlestick injury) is excluded. Malaria is a notifiable medical condition. Most cases came to our attention through local health authorities in the course of their investigations of notifications, when we were requested to help with clinical, epidemiological and entomological aspects.

Case investigations

Clinical details were obtained from doctors caring for the patients. Outbreaks were investigated in conjunction with local health officials, including environmental health officers. Site visits were undertaken and, where possible, surviving patients and their families

Total number of cases identified

Time to diagnosis after onset, median (range)

6 days (1 - 11 days)

Most frequent initial clinical diagnoses

Influenza, viral hepatitis, septicaemia

Proportion of patients with thrombocytopenia

80%

Malaria species involved

All Plasmodium falciparum

Case fatality rate

13%

National malaria case fatality rate (1999 - 2005)

0.6 - 1%

Table 2. Odyssean malaria cases, Gauteng Province, 2007 - 2013 Year

Cases

Outcome

Species

Location of outbreak

Putative source/s of mosquito

2007

Survived

P. ovale

Johannesburg, Gauteng Province

Patient’s car had gone on loan to LP and returned recently

2009

2 (siblings)

Survived

P. falciparum

Heidelberg, Gauteng Province

Near road and railway to MP; Mozambican neighbour

2010

2 (siblings)

Survived

P. falciparum

Soweto, Gauteng Province Possibly LP, via neighbour who had visited there recently

3 (father and siblings)

2 survived 1 fatal

P. falciparum P. falciparum presumed†

Soweto, Gauteng Province Not known; residence 1 km away from above cluster

3 (unrelated)

Survived

P. falciparum presumed†

Soshanguve, Gauteng Province

Not known

3 (unrelated)

Survived

P. falciparum presumed†

Pretoria East, Gauteng Province

Mozambican and Zimbabwean labourers living nearby

Dec. 2012*

3 (2 spouses, 1 unrelated)

2 survived 1 fatal

P. falciparum

Donkerhoek, Gauteng Province

Near highway toll plaza; Mozambican labourers living nearby; tyre importer nearby

Jan. 2013*

4 (2 father and 4 survived son; 2 unrelated)

P. falciparum

Kempton Park, Gauteng Province

Wife and mother of cases 1 and 2 had returned from LP recently; case 3 worked at a police station with illegal immigrants; father of case 4 recently returned from Angola

Jan. 2012

LP = Limpopo Province; MP = Mpumalanga Province. *Outbreaks described in detail in this article. †

Reported as malaria cases by local health authorities, but confirmatory laboratory reports were not available.

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onset of influenza-like symptoms on 22 December 2012. The husband (46 years old) developed chest pain, for which he was admitted to a tertiary hospital. His wife (34 years old) collapsed at home the following day and was hospitalised. Despite the absence of a travel history, Plasmodium falciparum antigen tests and blood smears were requested in both cases by the attending clinicians. P. falciparum antigen tests were positive in both cases, with parasitaemia counts of 2% and <1% reported for the wife and husband, respectively. Both had complications requiring intensive care, but recovered. A 46-year-old woman living on the neighbouring plot in Donkerhoek/Mooiplaats became ill on 25 December 2012 while on a vacation trip along the Orange River in southern Namibia, a non-transmission area for malaria. Her symptoms worsened and she was taken to a healthcare facility in the Northern Cape Province on 1 January 2013, where she was treated for ‘exhaustion’. On returning home, she was admitted to hospital on 4 January 2013, critically ill. Investigations were done for malaria; the P. falciparum antigen test was positive, and a parasitaemia of 23% noted. Unfortunately, this patient had numerous malaria-related complications and died 3 days later.

Outbreak 2

On 17 January 2013, 3 cases of laboratory-confirmed malaria were reported at a private hospital in Kempton Park (a suburb of Ekurhuleni Municipality, east of Johannesburg, Gauteng Province), as follows. A 30-year-old woman was admitted on 13 January 2013 and subsequently diagnosed with cerebral malaria (P. falciparum antigen-positive, 33.4% parasitaemia). Her only recent travel had been to Rustenburg, North West Province (a non-malaria-endemic area) for 2 days over Christmas. An unrelated 41-year-old man was admitted on 16 January 2013 and diagnosed with malaria (positive P. falciparum antigen test, 0.8% parasitaemia); he subsequently required intensive care. His 12-year-old son was admitted on 17 January 2012, with uncomplicated malaria (P. falciparum antigen test positive, 3.5% parasitaemia). The father and son lived in the same house in a Kempton Park suburb, a few blocks from the home of the first case. A 12-year-old boy with haemophilia (factor VIII-deficient), living within walking distance of the other 3 cases, developed fever on 14 January 2013, initially thought to be associated with intraarticular injections administered the day before. He was subsequently admitted to a Johannesburg hospital on 30 January 2013 with uncomplicated P. falciparum malaria. Despite the delayed diagnosis, he responded well to treatment and was subsequently discharged. There was no clinical or epidemiological evidence that the malaria infection was related to the haemophilia therapy.

Entomological investigations

None of the adult or larval mosquitoes collected were malaria vectors, and no anopheline mosquito breeding sites were found (Fig. 1). In the first cluster, the two affected houses were close together (approximately 300 m separation, on adjacent plots) and the same infected mosquito/es could have infected all the patients. Mozambican labourers were resident on one of the properties, and a national highway toll plaza and a tyre warehouse that allegedly imported tyres from Zambia were both a few hundred metres away, and therefore could plausibly have been the source of the mosquito or mosquitoes. The highway in question is a main route to Mpumalanga Province and Mozambique, both malaria transmission areas. In the second cluster, an international airport and major highway were less than 5 km away, but rather too far for mosquito dispersal. Other possible sources for infected mosquitoes were identified (Table 2), but as is usual in odyssean malaria outbreaks, these are speculative.

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Discussion

Clinical aspects of odyssean malaria

The importance of odyssean malaria is related to the frequently delayed or missed diagnosis of the cause of illness in affected patients, with associated high rates of complications and mortality. Absence of a history of travel to a malaria-endemic area is almost always responsible for the delayed diagnosis. In some cases, the diagnosis is only made at autopsy.[2] The risk of a tragic outcome can, however, be reduced if clinicians in non-endemic areas are alerted to the existence of this form of malaria transmission, and educated accordingly. Malaria parasites should routinely be sought in one or more successive blood films of any febrile patient in whom a diagnosis is not readily apparent, especially if the platelet count is low. Unexplained jaundice, depressed consciousness or coma, and apparent ‘sepsis’ that is unresponsive to antibiotics are common clinical presentations in these cases. Clinicians should specifically request malaria examinations and should not assume that these will automatically be done when a full blood count is requested. Since thrombocytopenia is a very common, although not invariable, finding in patients with both uncomplicated and severe malaria, its unexplained presence in a febrile patient should alert the physician to the possibility of malaria. Quantitative parasite counts should always be requested, as these give an indication of the severity of illness and are useful in monitoring the response to treatment. The presence of falciparum gametocytes on blood films indicates the presence of malaria infection of at least 10 days’ duration (but frequently 3 weeks or longer), and hence the possibility of missed or delayed infection. Point-of-care (rapid diagnostic) malaria tests should be more widely utilised when routine laboratory diagnosis is delayed or not available, such as in primary health clinics (provided users are appropriately trained). Inexperience in recognising and managing clinically severe malaria contributes to mortality,[4] and patients should be managed at the highest level of care available. The apparent decrease in odyssean malaria during the period under review, compared with the previous series (Table 1), is probably largely due to SA’s sustained success in controlling malaria since 2000,[5] but odyssean malaria will remain a risk in the nonendemic provinces until malaria is eliminated in the region.

Epidemiological aspects of odyssean malaria

In SA active malaria transmission is restricted to regions bordering on Mozambique, Zimbabwe and, to a much lesser extent, Botswana.[6] Road transport from malarious areas is undoubtedly more important than air transport as a source of translocated mosquito vectors. Gauteng Province is the economic hub of SA. It is a non-transmission area for malaria because of its altitude and climate, although it carries about 20% of the country’s malaria burden in the form of imported cases.[7] Any malaria-infective mosquitoes in Gauteng Province must therefore have been transported from a malaria-affected region. Within Gauteng Province, the Johannesburg-Pretoria metropole is the destination of a large volume of road passenger and freight traffic from neighbouring countries, mainly Mozambique and Zimbabwe, as well as from the malaria risk regions within SA. In southern Africa, Anopheles arabiensis and A. funestus are the principal vectors of malaria,[8] and are most likely to be responsible for the odyssean malaria cases recorded in Gauteng. Escaping from a vehicle, a travelling mosquito is likely to seek a nearby indoor resting site, especially if it is a malaria vector species that prefers to bite humans. Depending on its physiological state, it is then likely to acquire one or several blood meals from the household occupants after dusk. In general, a malaria vector mosquito is not likely to fly further

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than 1.5 km[9] or to survive longer than approximately 1 month, during which period she is potentially able to infect several people in a short space of time, even in a single night.[10,11]

Investigation of odyssean malaria outbreaks

Assuming it has been established that the infected person/s have no recent travel history to a malaria-affected region, and mechanical transmission has been excluded, the following questions are pertinent from an outbreak investigation aspect: (i) Do they live in close proximity to a national highway, airport, train station, bus depot, taxi rank or other public transport node? (ii) Have any of their neighbours, or other persons living in close proximity, travelled to a malariaaffected region during the past 2 - 3 weeks? (iii) Did they notice the unusual presence of any mosquitoes or mosquito bites on their person during the past 2 - 3 weeks? and (iv) Do they use insecticides in the home? During entomological investigations in households where odyssean malaria has occurred, places to search for culprit mosquitoes are indoors in dark crevices, under furniture, and in or behind hanging clothing. Because the time lag from receiving a malaria-infective bite to onset of the first symptoms is usually at least 10 days to 2 weeks, the chances of finding the culprit Anopheles female are very small indeed. Bodies of standing water (large or small, natural or artificial) near dwellings where malaria infections have been acquired should be investigated for the presence of anopheline mosquito larvae (Fig. 1), as there is always a chance that localised breeding is temporarily taking place if the weather is suitable, and there is potential for propagated outbreaks if gametocyte carriers are present in the local community. Two additional unrelated incidents of odyssean malaria occurred in January 2014 in communities on the southern edge of Johannesburg. Both patients survived, although diagnosis and therapy was delayed in one patient, who developed severe and complicated malaria and required intensive care. For details visit http://www.nicd.ac.za/assets/ files/Malaria(2).pdf. Acknowledgements. We thank all the communicable disease control coordinators, environmental health officers, healthcare workers, local health authorities, and staff and students of the Vector Control Reference Laboratory and Outbreak Response Unit, National Institute for Communicable Diseases, who assisted in the outbreak investigations.

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Fig. 1. Odyssean malaria, outbreak 1. Hunting mosquitoes in a discarded tyre, a potential breeding and resting site (by kind permission of Professor Lizette Koekemoer, National Institute for Communicable Diseases).

1. Frean JA, Blumberg L. Odyssean and non-mosquito-transmitted forms of malaria. In: SchlagenhaufLawlor P, ed. Travelers’ Malaria. Hamilton, Ontario: BC Decker Inc., 2008. 2. Isaäcson M. Airport malaria: A review. Bull World Health Organ 1989;67(6):737-743. 3. Isaäcson M, Frean JA. African malaria vectors in European aircraft [Letter 2: Odyssean malaria]. Lancet 2001;357(9251):235. [http://dx.doi.org/10.1016%2FS0140-6736%2805%2971340-4] 4. Mehta U, Durrheim DN, Blumberg L, et al. Malaria deaths as sentinel events to monitor healthcare delivery and antimalarial drug safety. Trop Med Int Health 2007;12(5):617-628. [http://dx.doi. org/10.1111/j.1365-3156.2007.01823.x] 5. Maharaj R, Raman J, Morris N, et al. Epidemiology of malaria in South Africa: From control to elimination. S Afr Med J 2013;103(10):779-783. [http://dx.doi.org/10.7196/SAMJ.7441] 6. Sinka ME, Bangs MJ, Manguin S, et al. A global map of dominant malaria vectors. Parasit Vectors 2012;5(1):69. [http://dx.doi.org/10.1186%2F1756-3305-5-69] 7. National Department of Health. Malaria Elimination Strategic Plan 2012-2018. Pretoria: NDoH, 2012. 8. Sinka ME, Bangs MJ, Manguin S, et al. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: Occurrence data, distribution maps and bionomic précis. Parasit Vectors 2010;3(1):117. [http://dx.doi.org/10.1186%2F1756-3305-3-117] 9. De Meillon B. The Anophelini of the Ethiopian Geographical Region. Johannesburg: South African Institute for Medical Research, 1947:120-122. 10. Gillies MT, Coetzee M. A Supplement to the Anophelinae of Africa South of the Sahara. Johannesburg: South African Institute for Medical Research, 1987:79-81. 11. Beier JC. Frequent blood-feeding and restrictive sugar-feeding behavior enhance the malaria vector potential of Anopheles gambiae s.l. and An. funestus (Diptera: Culicidae) in western Kenya. J Med Entomol 1996;33(4):613-618.

Accepted 21 November 2013.

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REVIEW

Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control G J Churchyard, R E Chaisson, G Maartens, H Getahun Gavin Churchyard is Chief Executive Officer: Aurum Institute, Johannesburg, South Africa, and an Honorary Professor in the School of Public Health, University of the Witwatersrand, Johannesburg, South Africa. Richard Chaisson is Director: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Gary Maartens is Professor and Chair of the Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa. Haileyesus Getahun is Coordinator, TB/HIV and Community Engagement, Global TB Programme, World Health Organization, Geneva, Switzerland. Corresponding author: G J Churchyard (gchurchyard@auruminstitute.org)

Tuberculosis (TB) remains a global health problem, and South Africa (SA) has one of the world’s worst TB epidemics. The World Health Organization (WHO) estimated in 1999 that one-third of the world’s population was latently infected with TB. In SA up to 88% of HIVuninfected young adults (31 - 35 years) are latently infected with TB. In the most recent meta-analysis, 6 - 12 months of isoniazid preventive therapy (IPT) was associated with a lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 0.85), with the greatest benefit among individuals with a positive tuberculin skin test (TST) (RR 0.38; 95% CI 0.25 - 0.57). A clinical trial of IPT given with antiretroviral therapy (ART) for 12 months reduced TB incidence by 37% compared with ART alone (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94). The effect of IPT is limited in high-burden countries. IPT for 36 months v. 6 months reduced TB incidence among HIVpositive, TST-positive participants by 74% (HR 0.26; 95% CI 0.09 - 0.80). A study of more than 24 000 goldminers confirmed that IPT is safe, with only 0.5% experiencing adverse events. A meta-analysis of studies of IPT since 1951 did not show an increased risk of developing resistance. Alternative TB preventive therapy regimens, including high-dose isoniazid and rifapentine given weekly for 3 months, have been shown to have similar efficacy to IPT. Mathematical modelling suggests that scaling up continuous IPT targeted to HIV-positive persons, when used in combination with other treatment and prevention strategies, may substantially improve TB control. S Afr Med J 2014;104(5):339-343. DOI:10.7196/SAMJ.8290

Burden of tuberculosis (TB) disease

TB remains a global health problem with an estimated burden of disease in 2012 of 8.6 million new cases, 13% co-infected with HIV, and an estimated 1.3 million TB deaths.[1] South Africa (SA) has one of the world’s worst TB epidemics, with the highest TB incidence among the 22 highest TB burden countries in the world, estimated at 933/ 100 000 population in 2012, the third-largest absolute number of cases and the largest number of HIV-associated TB cases.[1] Approximately 65% of TB patients in SA are HIV-infected.[1]

Burden of latent TB infection (LTBI)

The World Health Organization (WHO) estimated in 1999 that onethird of the world’s population is latently infected with Mycobacterium tuberculosis.[2] The greatest burden of LTBI is in South-East Asia (46%), the Western Pacific region (32%), Africa (31%) and the Eastern Mediterranean region (27%).[3] Sub-Saharan Africa, however, has the largest number of persons with LTBI who are co-infected with HIV. In high-transmission settings such as SA, up to 88% of HIV-uninfected young adults (31 - 35 years) are latently infected with TB, and 89% of SA goldminers are TB-infected.[4-7] These data suggest that the burden of LTBI in SA is enormous. The prevalence of tuberculin skin test (TST) positivity among people co-infected with HIV is estimated to be 22.8% overall and highest among those

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with CD4+ counts ≥500 cells/µl (37.4%).[8] This is explained by the compromised ability of HIV-infected persons to react to the skin test because of cutaneous anergy associated with immunosuppression.

Risk of TB disease

LTBI occurs when individuals infected with M. tuberculosis harbour the organism in a latent state, characterised by slowed or intermittent metabolism and replication below the level necessary to produce clinical illness.[9] The lifetime risk of reactivation of latent infection in healthy HIV-uninfected individuals is 10%, with 5% developing TB during the first 2 - 5 years after infection. The risk is greatly increased in the context of immunosuppression, most notably due to HIV infection.[3] The WHO estimates that in countries with a generalised HIV epidemic, HIV-infected persons have a 20 - 37-fold greater risk of developing TB than HIV-uninfected persons. Although antiretroviral treatment (ART) reduces the risk of TB by approximately twothirds,[10-12] TB remains a common cause of morbidity[13,14] and a leading cause of early mortality in individuals on ART.[15]

Purpose of this article

The purpose of this article is to present the evidence to support isoniazid preventive therapy (IPT) use, particularly continuous IPT (cIPT), in HIV-positive people as part of a combination of TB prevention strategies to reduce individual risk of TB and to contribute to TB control. Alternative TB preventive therapy regimens for

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persons living with HIV and preventive therapy for HIV-uninfected persons at high risk of TB are also discussed. The paper focuses exclusively on TB preventive therapy for adults.

IPT in HIV infection

History of IPT in SA The IPT guidelines for TST-positive people living with HIV were initially incorporated into the SA ART guidelines in 2005. Uptake of IPT was poor after introduction of these guidelines, largely due to TST creating a programmatic barrier to implementation and concerns of generating isoniazid resistance.[16] In 2010, in line with the WHO recommendations, SA revised its national IPT guidelines and removed TST as a requirement to initiate IPT, to facilitate programmatic implementation of IPT. The uptake of IPT increased dramatically and more than 375 000 South Africans living with HIV were started on IPT in 2011 and 2012, respectively, making the IPT programme one of the largest in the world. Despite this, uptake of IPT among people living with HIV in care, including pregnant women, remains poor. The SA IPT guidelines were re-issued in 2013 and recommend at least 36 months of IPT for TST-positive HIV-infected persons, including people on ART; 6 months of IPT for those whose TST status is unknown, regardless of whether they are on ART or not; and 12 months of IPT for persons on ART if their TST is negative.[17] People living with HIV who are not on and do not require ART, and who have a negative TST, do not need IPT.

Screening for TB

Screening for active TB disease is required before commencing IPT to minimise the risk of developing drug resistance by inadvertently treating active TB with an inadequate regimen. An individual participant metaanalysis showed that a symptom screen of a cough (any duration), night sweats, loss of weight and fever was able to identify HIV-positive people with a very low probability of having undiagnosed active TB disease.[18] Chest radiography combined with symptom screening increased the sensitivity of TB screening, particularly among SA goldminers.[18-20] On the basis of these results, the WHO recommends that TB disease among people living with HIV be excluded before starting IPT, using a symptom screen of current cough, night sweats, fever and weight loss.[21] In HIV clinics that routinely screen their patients at every clinic visit, the WHO TB symptom screen performs less well, particularly among patients on ART.[22] In settings with a high prevalence of undiagnosed TB disease, some experts recommend excluding TB by doing a sputum culture or, in sick hospitalised patients, using a lateral flow assay for mycobacterial lipoarabinomannan on urine combined with Xpert MTB/RIF on sputum or urine.[22-24] TB screening before starting IPT may detect TB cases earlier, thereby reducing transmission and TB-associated mortality.

IPT, taken for 12 months with ART, decreased TB incidence by 37% (hazard ratio (HR) 0.63; 95% CI 0.41 - 0.94) overall compared with ART alone.[32,33] The effectiveness of IPT was similar when assessed by interferon-gamma release assay and TST status.[33] The results of this study underpin the current SA guidelines for IPT with ART.

cIPT

Recent evidence from studies conducted in high-transmission settings suggests that cIPT may be beneficial. Among HIV-infected participants in Botswana who received 36 v. 6 months of IPT, TB incidence was reduced by 43% overall (HR 0.57; 95% CI 0.33 - 0.99); among TST-positive participants TB incidence was reduced by 74% (HR 0.26; 95% CI 0.09 - 0.80), whereas TST-negative participants received no benefit (HR 0.75; 95% CI 0.38 - 1.46).[31] In the per protocol analysis, there were no incident cases of TB among TSTpositive persons who took 36 months of IPT. Among TST-positive, HIV-infected SA adults, incidence rates of TB or death were similar between participants who received cIPT or 6 months of IPT in the intention-to-treat analysis (2.7 v. 3.6/100 person-years, incidence rate ratio (IRR) 0.75; 95% CI 0.38 - 1.38).[34] In the per protocol analysis, the incidence of TB or death was reduced by 58% in the cIPT study arm, compared with the 6 months of IPT arm.

Durability of IPT

In the pre-HIV era, IPT was associated with a durable reduction in TB incidence in mental institutions and Alaskan villages.[35-38] In the HIV pre-ART era, 6 months of IPT in high-transmission settings was durable for up to 18 months.[39,40] In the ART era, IPT has limited durability in high TB transmission settings.[40,41] In the Botswana trial of 6 v. 36 months of IPT, among persons who took 6 months of IPT the risk of TB increased approximately 200 days after stopping IPT,[31] while among persons who took 36 months of IPT, TB incidence increased by 90% after stopping IPT.[42] Among SA goldminers, the incidence of TB in the intention-to-treat analysis was reduced by 58% during the intended 9-month IPT period. TB incidence increased rapidly following cessation of IPT and was similar to that observed for those who did not start IPT in the post-treatment period.[43]

Safety of IPT

In the most recent meta-analysis of people with HIV, 6 or 12 months of IPT was associated with a 32% lower incidence of active TB than placebo (relative risk (RR) 0.68; 95% confidence interval (CI) 0.54 0.85).[25] This benefit was greatest among individuals with a positive TST (RR 0.38; 95% CI 0.25 - 0.57).[25] IPT was also effective when implemented in a routine HIV care programme for SA goldminers, prior to ART availability.[26] IPT, given for 6 - 12 months after TB treatment, is effective in reducing the risk of recurrent TB disease and is recommended by the WHO.[21,27]

The safety of IPT was recently confirmed in more than 23 500 SA goldminers. With clinical monitoring during the 9 months of IPT, the risk of isoniazid-associated adverse events, including clinical hepatitis, was low (0.5%), even among older patients and those on ART.[44] In the individually randomised trial of IPT with ART v. placebo with ART, participants on IPT were 2.13 times (95% CI 0.97 - 4.67) more likely to discontinue the study medication due to grade 3 adverse events or raised liver enzymes.[32] Among HIV-positive adults in Botswana, the risk of severe adverse events and death was similar in the 6-month and cIPT groups; however, the risk of death among persons with a negative TST was increased, although none of the deaths were attributed to isoniazid.[31] Among HIV-infected South Africans taking cIPT (v. 6 months of IPT), serious adverse reactions were more common (18.4 v. 15.4/100 person-years) as was permanent discontinuation of treatment (36.5% v. 1.9%).[34] Grade 3 or 4 elevation of aspartate or alanine aminotransferase during the treatment phase was much more common with cIPT than with 6 months of IPT (28.0% v. 5.5%; p<0.001).[34]

IPT with ART

Isoniazid resistance

Efficacy of 6 - 12 months of IPT

IPT combined with ART reduced the risk of TB disease by 80 - 97% and death by up to 50% in HIV-infected persons.[28-31] A recent individually randomised, pragmatic, controlled trial demonstrated that

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Theoretically, if active TB is missed and the bacterial load is large enough, treatment with monotherapy or an inadequate regimen has the potential to generate drug resistance. A systematic review of

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studies of IPT conducted between 1951 and 2005 concluded that IPT was not associated with an increased risk of isoniazid resistance and that isoniazid resistance is much more likely to result from inadequate treatment of active disease.[45] The studies of cIPT in Botswana and SA did not show an increased risk of isoniazid resistance.[31,34] Among 126 goldminers with TB after starting IPT, the prevalence of isoniazid resistance and treatment outcomes were similar to those in TB cases without previous exposure to IPT.[46] The impact of wide-scale uptake of preventive therapy on generating drug resistance is unknown. Mathematical modelling suggests that the emergence of isoniazid resistance with IPT use may be reduced by delivering IPT to those who will benefit the most and by improved case finding and prompt treatment of those with drug-resistant TB disease.[47,48]

Population-level effect of IPT

In the pre-HIV era, community-wide IPT was evaluated in Alaska, Greenland and Tunisia, all of which had epidemic TB. In Alaska, IPT was given to households for 1 year, which reduced the risk of TB by 69%.[35] As the intervention was so successful, 12 months of IPT was given to both placebo and IPT groups 5 years later, and the population-level effect has been durable for more than 3 decades.[36] In Greenland and Tunisia, the effect of community-wide IPT was modest (31% and 26% reduction in TB incidence, respectively), largely owing to an inadequate dose of isoniazid and/or poor adherence to IPT in both of the trials.[49,50] The Thibela TB study[51] evaluated the effectiveness of community-wide IPT in addition to standard of care, compared with standard of care alone, among SA goldminers. The intervention, which is unprecedented in the history of TB control, included mass screening for TB using chest radiography and symptoms, simultaneously linked to treatment for active disease or latent infection. Despite reducing the individual risk of TB by 58% while participants took the 9-month course of IPT, the effect waned soon after stopping IPT and there was no measurable reduction in TB incidence or prevalence at a population level after the intervention was completed.[43] Mathematical modelling suggested that even if the intervention was optimally implemented, a 20% reduction in TB incidence at a population level was the most that could be expected.[51] The modelling also suggested that cIPT would have a profound impact on TB incidence at a population level.[51]

TB after IPT: Possible mechanisms

TB that occurs after IPT may be due to reactivation of inadequately treated TB or reinfection with a new strain of TB. Isoniazid impairs mycobacterial wall synthesis and is a potent bactericidal drug that results in a rapid decline in actively multiplying mycobacteria. A recent study showed that isoniazid rapidly killed actively dividing M. smegmatus. However, a few cells continued to divide in the presence of isoniazid owing to dynamic persistence associated with stochastic pulsing of catalase-peroxidase (KatG), which activates isoniazid.[52] When isoniazid was withdrawn, the surviving cells underwent exponential growth again and were susceptible to isoniazid when it was reintroduced, suggesting that they had not developed resistance to the drug. It is likely that a similar phenomenon occurs when M. tuberculosis is treated with isoniazid. In support of this hypothesis, mathematical modelling of the Thibela TB intervention was not able to mirror the observed data unless the model assumed that IPT does not cure LTBI. If the model is correct and IPT does not cure LTBI, reactivation of inadequately treated LTBI after stopping treatment may in part explain the lack of durable benefit. In high-transmission settings, reinfection with a new strain of TB has been shown to be an important cause of recurrent TB disease after successful completion

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of treatment in HIV-infected and HIV-uninfected TB patients.[53,54] In settings with a high annual risk of infection such as SA (estimated at 4.7% per year), it is likely that reinfection will contribute to the limited durability of IPT. In high-burden settings, both reactivation of inadequately treated LTBI and reinfection are likely to limit the durability of IPT. Regardless of the mechanism of TB after IPT, cIPT will reduce the risk of TB in persons living with HIV.[31,42]

Alternative TB preventive therapy regimens

Efficacy of alternative preventive therapy regimens

Alternative TB preventive therapy regimens have also been evaluated in people living with HIV. A meta-analysis of TB preventive therapy regimens found rifampicin-containing regimens (rifampicin and pyrazinamide; isoniazid and rifampicin; isoniazid, rifampicin and pyrazinamide) not to be more effective than IPT alone.[25] In the pre-ART era, however, the rifampicin-based regimens were shown to have a more durable effect than isoniazid alone.[40,41] A novel regimen of intermittent high-dose isoniazid and rifapentine given weekly for 3 months has recently been evaluated in low and high TB burden settings. Rifapentine is a rifamycin with a long half-life and greater potency against M. tuberculosis than rifampicin. In mouse models of LTBI, rifapentine had a greater sterilising effect than isoniazid,[55] and weekly high-dose rifapentine and isoniazid for 3 months (3HP) had greater efficacy than isoniazid alone.[56] The TB Trials Consortium Study 26[57] compared 3 months of high-dose once-weekly isoniazid (900 mg) and rifapentine (900 mg) (3HP) with 9 months of daily isoniazid (300 mg) (9H) in a non-inferiority study design.The study was conducted in low to medium TB and HIV burden settings (USA, Canada, Brazil and Spain). Eligible participants aged 2 years and above were enrolled into the study, regardless of HIV status. The study showed that 3HP was non-inferior to 9H in the modified intention-to-treat and per protocol analysis, and there was a trend towards superiority in reducing TB incidence (9H: 16/100 person-years; 3HP: 7/100). The 3HP study arm had a higher treatment completion rate than the 9H arm (82% v. 69%).[57] As few HIV-infected persons were enrolled into Study 26 (2.6% HIV-infected), an ancillary study was conducted to evaluate safety, tolerability and efficacy of 3HP in HIV-infected adults. Among 399 HIV-infected persons (193 9H, 206 3HP), 3HP was non-inferior to 9H, with cumulative TB incidences in the 3HP v. the 9H arm of 1.01 and 3.69/100 person-years, respectively.[58,59] 3HP compared with 9H in HIV-infected persons was tolerable and had higher completion rates (88% v. 64%).[58,59] The 3HP regimen was also compared with 6 months of IPT (6H) in HIV-infected, ART-naive (at enrolment), TST-positive SA adults. In the intention-to-treat analysis, the incidence rates of active TB or death in the 3HP and 6H arms were similar (3.1 v. 3.6/100 personyears, respectively, crude IRR 0.87 (95% CI 0.54 - 1.39)).[34] Based on the results of TB Trials Consortium Study 26, the US Centers for Disease Control (CDC) issued recommendations for the use of the 3HP regimen for the treatment of LTBI.[47] The CDC is currently evaluating self-administered, as opposed to directly observed, 3HP.

Safety of alternative preventive therapy regimens

Rifampicin-based regimens (rifampicin and pyrazinamide; isoniazid and rifampicin; isoniazid, rifampicin and pyrazinamide), compared with IPT, in people with HIV are associated with a greater rate of treatment discontinuation due to adverse effects.[25] In Study 26 participants, the vast majority of whom were HIV-uninfected, there was reduced drug-related hepatotoxicity in the 3HP study arm

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compared with the 9H arm (0.4% v. 2.7%), but rates of permanent discontinuation due to an adverse event were higher (4.9% v. 3.7%).[57] In the follow-on trial to Study 26 among HIV-infected persons taking 3HP v. 9H, the rates of drug discontinuation due to adverse drug reactions were similar (3.4% v. 4.2%).[58,59] Among HIV-infected, TSTpositive adult South Africans taking 3HP v. 6 months of IPT, grade 3 or 4 hepatotoxicity (elevated alanine or aspartame aminotransferase) occurred less commonly in the 3HP study arm (1.5% v. 5.5%, respectively), and the rates of permanent discontinuation of the study drug were similar (1.8% v. 1.9%, respectively).[34]

TB preventive therapy for HIVuninfected persons at high risk of TB

TB preventive therapy is recommended for HIV-uninfected persons who are receiving chemotherapy or anti-tumour necrosis factor (TNF) therapy and are at increased risk of developing TB. The South African Rheumatism and Arthritis Association recommends a regimen of either isoniazid or rifampicin for 3 months or IPT for 6 - 9 months for TST-positive persons prior to starting anti-TNF drugs. Silicosis is an occupational lung disease that results from chronic silica dust exposure and is associated with an approximately threefold greater risk of TB than in silica-exposed workers who do not have silicosis. The National Department of Health has included recommendations for HIV-uninfected persons with silicosis in the 2013 IPT guidelines: 36 months of IPT if TST-positive; 6 months IPT if TST unknown; no IPT if TST-negative. For people living with HIV and silicosis, the IPT guidelines for people living with HIV should be followed.

Combination TB prevention: The role of IPT

The WHO recommends IPT for people living with HIV as part of a combination of TB prevention strategies that include infection control to reduce exposure to TB, intensified case finding to detect cases earlier, and ART to reduce vulnerability to TB, in addition to reducing the numbers lost to follow-up prior to starting TB treatment and reducing the time to starting TB treatment.[21,60-62] However, implementation of these strategies has been poor. Mathematical modelling has suggested that high coverage of IPT, particularly if it is given continuously and in combination with other treatment and prevention strategies, will contribute to TB control and accelerate progress towards elimination of the disease.[51,63,64]

Conclusion

IPT is safe, does not generate isoniazid resistance, and reduces the risk of TB among persons living with HIV, particularly if given continuously to those with evidence of TB infection. Continuous IPT should be used in combination with other TB treatment and prevention strategies to contribute to TB control. Alternative TB preventive therapy regimens may be considered for certain patients at high risk of TB. 1. World Health Organization. Global Tuberculosis Report 2013. WHO/HTM/TB/2013.11. Geneva: WHO, 2012. 2. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: Estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA 1999;282(7):677-686. [http://dx.doi.org/10.1001/jama.282.7.677] 3. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: Global trends and interactions with the HIV epidemic. Arch Intern Med 2003;163(9):1009-1021. [http://dx.doi.org/10.1001/archinte.163.9.1009] 4. Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb) 2004;84(1-2):29-44. [http://dx.doi.org/10.1016/j.tube.2003.08.003] 5. Young DB, Gideon HP, Wilkinson RJ. Eliminating latent tuberculosis. Trends Microbiol 2009;17(5):183-188. [http://dx.doi.org/10.1016/j.tim.2009.02.005] 6. Wood R, Liang H, Wu H, et al. Changing prevalence of tuberculosis infection with increasing age in highburden townships in South Africa. Int J Tuberc Lung Dis 2010;14(4):406-412. 7. Hanifa Y, Grant AD, Lewis J, Corbett EL, Fielding K, Churchyard G. Prevalence of latent tuberculosis infection among gold miners in South Africa. Int J Tuberc Lung Dis 2009;Jan13(1):39-46.

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44. Grant AD, Mngadi KT, van Halsema CL, Luttig MM, Fielding KL, Churchyard GJ. Adverse events with isoniazid preventive therapy: Experience from a large trial. AIDS 2010;24(Suppl 5):S29-S36. [http://dx.doi. org/10.1097/01.aids.0000391019.10661.66] 45. Balcells ME, Thomas SL, Godfrey-Faussett P, Grant AD. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis 2006;12(5):744-751. [http://dx.doi.org/10.3201/eid1205.050681] 46. van Halsema CL, Fielding KL, Chihota VN, et al. Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AIDS 2010;24(7):1051-1055. [http:// dx.doi.org/10.1097/QAD.0b013e32833849df] 47. Mills HL, Cohen T, Colijn C. Response to comment on ‘Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: A model-based analysis’. Sci Transl Med 2013;5(204):204lr4. 48. Mills HL, Cohen T, Colijn C. Community-wide isoniazid preventive therapy drives drug-resistant tuberculosis: A model-based analysis. Sci Transl Med 2013;5(180):180ra49. 49. Horwitz O, Payne PG, Wilbek E. Epidemiological basis of tuberculosis eradication. 4. The isoniazid trial in Greenland. Bull World Health Organ 1966;35(4):509-526. 50. Nyboe J, Farah AR, Christensen OW. Report on tuberculosis chemotherapy pilot project (Tunisia 9). WHO/ TB/Technical Information/10. 22 April 1963. 51. Chihota VN, Popane F, Churchyard GJ, et al. Community-wide isoniazid preventive therapy among gold miners in South Africa: The Thibela TB study. South African TB Conference 2012, 12-15 June 2012, Durban, South Africa. http://www.auruminstitute.org/thibela-TB/Thibela-SA-TB-conf-12-06-12.pdf (accessed 11 April 2014). 52. Wakamoto Y, Dhar N, Chait R, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science 2013;339(6115):91-95. [http://dx.doi.org/10.1126/science.1229858] 53. Verver S, Warren RM, Beyers N, et al. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med 2005;171(12):1430-1435. [http://dx.doi.org/10.1164/ rccm.200409-1200OC] 54. Charalambous S, Grant AD, Moloi V, et al. Contribution of reinfection to recurrent tuberculosis in South African gold miners. Int J Tuberc Lung Dis 2008;12(8):942-948. 55. Miyazaki E, Chaisson RE, Bishai WR. Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis. Antimicrob Agents Chemother 1999;43(9):2126-2130.

56. Chapuis L, Ji B, Truffot-Pernot C, O’Brien RJ, Raviglione MC, Grosset JH. Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice. Am J Respir Crit Care Med 1994;150(5 Part 1):13551362. [http://dx.doi.org/10.1164/ajrccm.150.5.7952564] 57. Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011;365(23):2155-2166. [http://dx.doi.org/10.1056/NEJMoa1104875] 58. Sterling TR, Person AK. TB Trials Consortium Study 26.AIDS Clinical Trials Group 5259. Tolerability among HIV-infected persons of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. The PREVENT TB Study. 19th International AIDS Conference, 22-27 July 2012, Washington, DC, USA. Abstract MOAB0302. 59. Sterling T, Benson C, Scott N, et al. Three months of weekly rifapentine+INH for M. tuberculosis infection in HIV-infected persons. Conference on Retroviruses and Opportunistic Infections, 3-6 March 2014, Boston, MA, USA. Abstract 817. 60. World Health Organization. The Stop TB Strategy: Building on and enhancing DOTS to meet the TB-related Millenium Development Goals. http://whqlibdoc who int/hq/2006/WHO_HTM_STB_2006 368_eng pdf (accessed 24 March 2014). 61. World Health Organization. WHO policy on collaborative TB/HIV activities: Guidelines for national programmes and other stakeholders. http://www who int/tb/publications/2012/tb_hiv_ policy_9789241503006/en/index html (accessed 24 March 2014). 62. Suthar AB, Lawn SD, Del Amo J, et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: A systematic review and meta-analysis. PLoS Med 2012;9(7):e1001270. [http://dx.doi.org/10.1371/journal. pmed.1001270] 63. Dye C, Glaziou P, Floyd K, Raviglione M. Prospects for tuberculosis elimination. Annu Rev Public Health 2013;34(7):271-286. [http://dx.doi.org/10.1146/annurev-publhealth-031912-114431] 64. Abu-Raddad LJ, Sabatelli L, Achterberg JT, et al. Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics. Proc Natl Acad Sci U S A 2009;106(33):13980-13985. [http://dx.doi. org/10.1073/pnas.0901720106]

Accepted 6 April 2014.

This month in the SAMJ ... Jenny Edge,*,† guest editor for CME this month, is a general surgeon with a particular interest in the management of breast diseases. She completed her undergraduate training at University College Hospital, London, also undertaking an intercalated BSc in Anthropology and graduating BSc, MBBS. She went on to pursue an FRCS and MMed (Surg), undertaking her surgical training at Stellenbosch University. She worked in the UK and New Zealand before joining her husband in South Africa. She now works at the Christiaan Barnard Memorial Hospital and is an honorary lecturer at the University of Cape Town. * Edge J. Pink ribbons for breast cancer awareness – a perspective. S Afr Med J 2014;104(5):321. [http://dx.doi.org/10.7196/SAMJ.8300] †

Edge J. Breast Cancer. S Afr Med J 2014;104(5):376. [http://dx.doi.org/10.7196/SAMJ.8262]

Gavin Churchyard* is a specialist physician and founder and Chief Executive Officer of the Aurum Institute, an independent, not-for-profit, proudly South African public benefit organisation that focuses on tuberculosis and HIV service delivery, management and research. He is an honorary professor at the School of Public Health, University of the Witwatersrand, Johannesburg, and at the Faculty of Epidemiology and Population Health, Department of Infectious Diseases, London School of Hygiene and Tropical Medicine. Prof. Churchyard is Chair of the World Health Organization (WHO) Task Force for the Development of New Policies for the Treatment of TB and a member of the WHO Strategic Technical Advisory Group for TB. He is Vice-Chair of the NIH/DAIDS-funded AIDS Clinical Trials Group (ACTG) Network and the Transformative Science Group for TB, and Chair of the ACTG Host Directed Therapy for TB Working Group. * Churchyard GJ, Chaisson RE, Maartens G, Getahun H. Tuberculosis preventive therapy: An underutilised strategy to reduce individual risk of TB and contribute to TB control. S Afr Med J 2014;104(5):339-343. [http://dx.doi.org/10.7196/SAMJ.8290]

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EDITORIAL

Diagnosis and treatment of imported and odyssean malaria Malaria has long been regarded as a major public health burden in South Africa (SA), affecting vast regions of the country. However, SA is now one of eight countries in Africa that is close to malaria elimination.[1,2] This was documented in a supplement to the October 2013 SAMJ. Even though SA is on the threshold of malaria elimination, many countries in Africa continue to experience high morbidity and mortality related to the disease. Malaria may also be encountered in parts of SA not known to have malaria, in ways not typical of how it is usually transmitted or acquired. In this issue of SAMJ two articles[3,4] discuss two forms of malaria seen in nonendemic areas, imported malaria and odyssean malaria. Imported malaria is defined as malaria presenting in a country other than that in which it was acquired, while odyssean malaria is malaria acquired in a non-malarious area from the bite of an imported mosquito.[5] The former is often a well-recognised form of the disease, but the latter is not common and therefore not as easy to recognise. Runway malaria is an example of imported malaria, while examples of odyssean malaria include airport malaria, baggage malaria, luggage malaria, suitcase malaria, container malaria, port malaria, taxi rank malaria and minibus malaria.[5] These terms are based on the various modes of passive transport experienced by infected mosquitoes. Imported malaria and odyssean malaria are important because of the high incidence of complications and mortality often associated with them.[5] Global travel has become easier, and humans are able to cover vast distances in a short period. In a recent publication in Science, Abel and Sander[6] quantify global international migration flows. They estimate that the largest movements occur between southern and western Asia, from Latin to North America, and within Africa.[6] The report clearly shows that there is a huge circulation of migrants among sub-Saharan African countries. This migration dwarfs the number leaving Africa, and receives no media attention.[6] SA is one of the countries in sub-Saharan Africa that is a common destination for migrants. The Western Cape and Gauteng provinces are regions of SA that are malaria non-endemic.[2] They are also popular destinations for some migrant communities. In their retrospective observational study, Opie et al.[3] describe a number of imported cases of malaria at Groote Schuur Hospital (GSH), Cape Town. In this study a high rate of malaria was seen in Somali and Bangladeshi migrants over a 4-year period. Plasmodium falciparum was the most common malarial species identified. A mortality rate of <1% was found in this study, which is in keeping with the national target rate. Opie et al. postulate that the low mortality rate may be due to the semi-immunity of the majority of the patients, who came from malaria-endemic areas. Another possibility not mentioned in the article could be that GSH has a dedicated infectious disease department that advises on the management of all cases of malaria admitted to the hospital. It must be noted that not all folders were found and analysed, a common limitation of retrospective reviews that has the potential to underestimate the true mortality.

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The increased influx of migrants from malaria-endemic countries has a significant impact on imported malaria cases.[7] The number of migrants who return to their home countries to visit friends and relatives (VFRs) has also increased. Often VFRs do not consider themselves at risk of acquiring malaria and therefore may not seek pre-travel advice on malaria prophylaxis. A common misconception among VFRs is that they have lifelong immunity to malaria.[7] Frean et al.[4] describe outbreaks of odyssean malaria over a 6-year period. They demonstrate a high complication rate and mortality due to delayed or missed diagnoses. They emphasise that malaria should always be remembered as a cause of unexplained fever and thrombocytopenia, even in the absence of a travel history. The treatment for uncomplicated P. falciparum malaria that is currently recommended in all endemic and non-endemic provinces of SA is artemether-lumefantrine.[8] Primaquine is used for radical cure of P. vivax and P. ovale infections.[8] Severe malaria is a medical emergency that requires high-level hospital care, so when a severe case is diagnosed at a primary healthcare facility or by a private general practitioner, emergency transfer to hospital is the norm in endemic and non-endemic provinces.[8] Intravenous artesunate is the parenteral antimalarial currently recommended by the World Health Organization for the treatment of severe malaria in children and adults.[9] It is not yet registered for use in SA, but there is limited availability through a special access programme for compassionate use on a named-patient basis.[8] Patterns of migration in Africa demonstrate that the largest movement of people occurs in sub-Saharan Africa. SA in particular is a common destination for many migrant populations. Imported and odyssean malaria should be remembered as a cause of unexplained fever and thrombocytopenia. Key to reducing the complications and mortality related to malaria is early recognition and treatment. S K Dlamini Division of Infectious Diseases and HIV Medicine, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa sk.dlamini@uct.ac.za 1. Coetzee M, Kruger P, Hunt RH, Durrheim DN, Urbach J, Hansford CF. Malaria in South Africa: 110 years of learning to control the disease. S Afr Med J 2013;103(10 Part 2):770-778. [http://dx.doi. org/10.7196/SAMJ.7446] 2. Maharaj R, Morris N, Seocharan I, et al. The feasibility of malaria elimination in South Africa. Malar J 2012;11:423-433. [http://dx.doi.org/10.1186/1475-2875-11-423] 3. Opie J, Freeks R, du Pisani LA. The burden of imported malaria in Cape Town. S Afr Med J 2014;104(5):347-349. [http://dx.doi.org/10.7196/SAMJ.7904] 4. Frean J, Brooke B, Thomas J, Blumberg L. Odyssean malaria outbreaks in Gauteng province, South Africa, 2007 - 2013. S Afr Med J 2014;104(5):335-338. [http://dx.doi.org/10.7196/SAMJ.7784] 5. Isa채cson M, Frean JA. African malaria vectors in European aircraft. Lancet 2001;357(9251):235. [http://dx.doi.org/10.1016/s0140-6736(05)71340-4] 6. Abel GJ, Sander N. Quantifying global international migration flows. Science 2014;343(6178):15201522. [http://dx.doi.org/10.1126/science.1248676] 7. Pavli A, Maltezou HC. Malaria and travellers visiting friends and relatives. Travel Med Infect Dis 2010;8(3):161-168. [http://dx.doi.org/10.1016/j.tmaid.2010.01.003] 8. Upke IS, Moonasar D, Raman J, Barnes KI, Baker L, Blumberg L. Case management of malaria: Treatment and chemoprophylaxis. S Afr Med J 2013;103(10 Part 2):793-798. [http://dx.doi. org/10.7196/SAMJ.7443] 9. World Health Organization. Guidelines for the Treatment of Malaria. 2nd ed. Geneva: WHO, 2011.

S Afr Med J 2014;104(5):344. DOI:10.7196/SAMJ.8306

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AGREE to disagree: Critical appraisal and the publication of practice guidelines Faced by an explosion in available evidence for multiple new treatments, busy clinicians value guidelines that are clear, reliable, unbiased and locally applicable. Finding them can be difficult, however. The science of guideline development has moved rapidly in the past decade, resulting in a more robust and systematic process. However, just as the language of evidence-based medicine can be subverted to sound convincing while hiding errors and biases, so too guidelines may look convincing but lack many of the elements needed to ensure quality of care. In particular, the pharmaceutical and health technology industries are intensely aware of the marketing potential offered by widely disseminated and ostensibly neutral documents that ultimately influence medical practice. A few examples illustrate the potential challenges. The recently published JNC8 guidelines on hypertension management[1] followed a very robust process,[2] and yet ended with some of the authors taking a dissenting view,[3] which at the least raised concerns about the credibility of the guideline. The European Society of Cardiology guideline on perioperative beta-blockade was the subject of potential conflict of interest concerns when the guideline chairperson was investigated for scientific misconduct related to the DECREASE family of trials.[4] At the time it was estimated that 10 000 iatrogenic deaths could have been prevented annually by refraining from following this guideline.[5] A 2009 review of cardiology guidelines[6] found that of 7 000 recommendations only 11% were based on randomised controlled trial (RCT) evidence, and a 2011 study of infectious disease guidelines[7] reported a similar finding, with only 14% of 4 000 recommendations having RCT backing. These observations were further corroborated in a recent systematic analysis in which the validity of guidelines published by interventional medical societies was investigated. It was established that most associated guidelines failed to grade the evidence, and when graded, lower-quality evidence was used. Furthermore, most guidelines failed to disclose conflicts of interests.[8] The US Institute of Medicine has defined clinical practice guidelines as ‘statements that include recommendations intended to optimise patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options’.[9] They are important in influencing public health policy, promoting distributive justice and advocating better healthcare delivery for those in need.[10,11] The increased frequency with which clinical treatment guidelines/recommendations are being published in South Africa (SA) is of great significance in a resource-poor country, accentuating the need to ensure their validity. Consequently, heightened responsibility is called for in terms of applying due process throughout the development and publication of all guidelines.

Evidence collection and synthesis

The application of the evidence-based medicine philosophy, while not infallible, is central to the promotion of a fair and equitable distribution of resources. Sackett et al.[12] define evidence-based medicine as ‘the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.’ By individual clinical expertise, they refer to the proficiency and judgement that individual clinicians acquire through clinical experience and clinical practice.[12] While it is accepted that ‘expert opinion’ falls low down on the hierarchy of

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sources of clinical evidence, if principles of evidence-based medicine are to be applied in the true spirit of their intention, then the need for consensus opinion is fundamental.[13] It is in this context that clinical guidelines and recommendations contribute profoundly towards the process of decision making and resource allocation.

Making recommendations

Priority setting is challenging in any health system. Irrespective of our sector of practice, financial resources are finite and there are competing interests in terms of resource allocation. The demand for health services exceeds available resources, and in order to meet the health needs of a community, allocation of health services and associated financial resources must be prioritised.[14] As Chinnock et al. state,[15] wherever healthcare is provided, it is essential to know which interventions work, which do not, and which are likely to be harmful. This is especially important in situations where health problems are severe and scarcity of resources makes it vital that they are not wasted. In a 2011 position paper regarding the effective and efficient conservation and distribution of healthcare resources, the American College of Physicians[16] noted the requirement for a transparent and publically acceptable process for making resource allocation decisions with a focus on medical efficacy, clinical effectiveness and need, with consideration for cost, based on the best available medical evidence. It is important to emphasise that rationing in this context is not about the denial of care, but rather about choosing clinically effective alternatives based on peer-reviewed medical evidence to provide clinically appropriate and cost-effective care that maximises value.[16] Recommendations therefore need to integrate evidence, concepts of best practice and resource constraints in order to set practice directions and provide tools to audit the care delivered. This process is seldom easy, and it is useful for practitioners to understand the strength of the recommendation in order to decide how best to apply it in their practice.

Clinical guidelines and the SAMJ

The SAMJ (and its HMPG ‘siblings’) has recognised the important role that guidelines play in setting standards of clinical practice as well as the imperative of following transparent due process in their development and publication. To this end, it has sought to establish a formalised peer-review process. In fulfilling this obligation, we introduce the readership to the AGREE II instrument as an objective appraisal mechanism against which prospective clinical guidelines will be assessed before their publication. This internationally developed and validated quality assessment tool is available in the public domain (at www.agreetrust. org) and can be applied generically to assess the quality of guidelines across all disease areas and at any stage of the healthcare continuum, whether it be screening, diagnosis or treatment.[17] It can also be used to inform guideline development processes and provides guidance on the type of information that should be reported in a guideline. The purpose of the AGREE II tool is to provide a framework (from Brouwers et al.[17]) to: (i) assess the quality of guidelines; (ii) provide a methodological strategy for the development of guidelines; and (iii) inform what information ought to be reported in guidelines, and how it should be reported. AGREE II outlines six unique domains of guideline quality:[17] Domain 1. Scope and purpose ‘is concerned with the overall aim of the guideline, the specific health questions, and the target patient population’.

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EDITORIAL

Domain 2. Stakeholder involvement ‘focuses on the extent to which the guideline was developed by the appropriate stakeholders and represents the views of its intended users’. Domain 3. Rigour of development ‘relates to the process used to gather and synthesise the evidence, the methods to formulate the recommendations, and to update them’. It ensures an explicit link between the recommendation and the supporting evidence and facilitates an assessment of whether health benefits, adverse effects and risks were considered in formulating the recommendations. Domain 4. Clarity of presentation ‘deals with the language, structure, and format of the guideline’. Domain 5. Applicability ‘pertains to the likely barriers and facilitators to implementation, strategies to improve uptake, and resource implications of applying the guideline’. Domain 6. Editorial independence ‘is concerned with the formulation of recommendations not being unduly biased by competing interests’. Any potential conflict of interest must be reported and appropriately managed. An editorial sub-committee under the leadership of Prof. Marc Blockman has been appointed by the SAMJ to undertake this responsibility. This represents an important step in ensuring the rigour and validity of future guidelines available in SA.

Conclusion

A quality guideline is one in which there is confidence that the potential biases of guideline development have been addressed adequately, one which is deemed to be externally valid via a peerreview process, and one which is locally applicable and feasible. [18] The introduction of this tool, as a critical appraisal mechanism, is an important advance in the use of evidence-based medicine principles (in its true sense) in the development and publication of practice guidelines in SA. Through ensuring the application of sufficient rigour in the development process, there is a firm belief that a clinician’s ability to make informed clinical decisions will be enhanced, ultimately leading to improved patient care through discouraging the use of ineffective and wasteful interventions. This, in turn, will result in more efficient resource utilisation, will elevate the level of trust in the guideline itself, and is likely to impact on the ability and willingness to implement such a guideline in practice. Declarations of interest. MB is a member of the National Essential Medicines List Committee and is chair of the Tertiary/Quaternary Essential Medicines List Committee. He is also a member of the Western Cape Provincial Pharmacy and Therapeutics Committee and its executive committee, a member of the Medicines Control Council (MCC) and its central clinical committee, and chair of the MCC’s pharmacovigilance committee. MB also consults for various private sector drug and therapeutics committees, including those for Liberty Health and Metropolitan Health Risk Management. KC is a member of the Western Cape Provincial Pharmacy and Therapeutics Committee and its executive committee. AG is a member of the National Essential Medicines List Committee, the KwaZulu-Natal Provincial Pharmacy and Therapeutics Committee and the World Health Organization Expert Panel on Drug Policies and Management. KJ is a senior pharmaceutical policy specialist in the Essential Medicines Programme at the National Department of Health. TK has received funding from the South African Medical Research Council for the South African Guideline Excellence (SAGE) Project to explore guideline development and implementation in the South African primary healthcare context. JM is a member of the Gauteng Provincial Pharmacy and Therapeutics Committee and consults on health economics and health technology assessment to Discovery Health. AP is a member of the National Essential Medicines List Committee, a member of the Tertiary/Quaternary Essential Medicines List Committee, and chair of the Adult Essential Medicines Committee. He is also chair of the Eastern Cape

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Provincial Pharmacy and Therapeutics Committee. BT oversees the process of health technology assessment, including medicines evaluation, for medical schemes contracted to Medscheme. RW is responsible for medicine policy development at Liberty Health Holdings.

Roger Wiseman Liberty Health Holdings, Cape Town, South Africa roger.wiseman@vmed.co.za Karen Cohen Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa Andy Gray Division of Pharmacology, Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, Durban, South Africa Khadija Jamaloodien National Department of Health, South Africa Tamara Kredo South African Cochrane Centre, South African Medical Research Council, Cape Town, South Africa Jacqui Miot Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Andy Parrish Department of Internal Medicine, Walter Sisulu University, Mthatha, and Cecilia Makiwane Hospital, East London, Eastern Cape, South Africa Bettina Taylor Medscheme Health Policy Unit, Cape Town, South Africa Marc Blockman Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, South Africa For the South African Medical Journal Editorial Sub-Committee for Guideline Review 1. James PA, Oparil S, Carter BL, et al. Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):507-520. [http://dx.doi.org/10.1001/jama.2013.284427] 2. Sox HC. Assessing the trustworthiness of the guideline for the management of high blood pressure in adults. JAMA 2014;311(5):472-474. [http://dx.doi.org/10.1001/jama.2013.284429] 3. Wright JT, Fine LJ, Lackland DT, et al. Evidence supporting a systolic blood pressure goal of less than 150 mm Hg in patients aged 60 years or older: The minority view. Ann Intern Med 2014;160(7):499-503. [http://dx.doi. org/10.7326/M13-2981] 4. Hawkes N. Use of β blockers during surgery may have caused 10 000 deaths in the UK. BMJ 2013;347:f4914. [http://dx.doi.org/10.1136/bmj.f4914] 5. Bouri S, ShunShin MJ, Cole GD, et al. Heart 2014;100(6):456-464. [http://dx.doi.org/10.1136/ heartjnl-2013-304262] 6. Tricoci P, Allen JM, Kramer JM, et al. Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA 2009;301(8):831-841. [http://dx.doi.org/10.1001/jama.2009.205] 7. Lee DH, Vielemeyer O. Analysis of overall level of evidence behind Infectious Diseases Society of America practice guidelines. Arch Intern Med 2011;171(1):18-22. [http://dx.doi.org/10.1001/archinternmed.2010.482] 8. Feuerstein JD, Akbari M, Gifford AE, et al. Systematic analysis underlying the quality of the scientific evidence and conflicts of interest in interventional medicine subspecialty guidelines. Mayo Clin Proc 2014;89(1):16-24. [http://dx.doi.org/10.1016/j.mayocp.2013.09.013] 9. Institute of Medicine; Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E, eds. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press, 2011. http://www.iom.edu/ Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust/Standards.aspx (accessed 3 April 2014). 10. Qaseem A, Forland F, Macbeth F, Ollenschläger G, Phillips S, van der Wees P, for the Board of Trustees of the Guidelines International Network. Guidelines International Network: Toward international standards for clinical practice guidelines. Ann Intern Med 2012;156(7):525-531. [http://dx.doi.org/10.7326/0003-4819-1567-201204030-00009] 11. Woolf SH, Grol R, Hutchison A, et al. Potential benefits, limitations, and harms of clinical guidelines. BMJ 1999;318(7182):527-530. [http://dx.doi.org/10.1136/bmj.318.7182.527] 12. Sackett DL, Rosenberg WMC, Gray JA, et al. Evidence based medicine: What it is and what it isn’t. BMJ 1996;312(7023):71-72. [http://dx.doi.org/10.1136/bmj.312.7023.71] 13. Evans D. Hierarchy of evidence: A framework for ranking evidence evaluating healthcare interventions. J Clin Nurs 2003;12(1):77-84. [http://dx.doi.org/10.1046/j.1365-2702.2003.00662.x] 14. Gibson JL, Martin DK, Singer PA. Evidence, economics and ethics: Resource allocation in health services organizations. Healthc Q 2005;8(2):50-59. [http://dx.doi.org/10.12927/hcq..17099] 15. Chinnock P, Siegfried N, Clarke M. Is evidence-based medicine relevant to the developing world? PLoS Med 2005;2(5):e107. [http://dx.doi.org/10.1371/journal.pmed.0020107] 16. American College of Physicians. How Can Our Nation Conserve and Distribute Health Care Resources Effectively and Efficiently? Philadelphia: American College of Physicians, 2011. http://www.acponline.org/ advocacy/current_policy_papers/assets/health_care_resources.pdf (accessed 13 March 2014). 17. Brouwers M, Kho ME, Browman GP, et al., on behalf of the AGREE Next Steps Consortium. AGREE II: Advancing guideline development, reporting and evaluation in healthcare. Can Med Assoc J 2010;182:E839-E842. [http://dx.doi.org/10.1503/cmaj.090449] 18. AGREE Collaboration. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: The AGREE project. Qual Saf Health Care 2003;12(1):18-23.

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RESEARCH

The burden of imported malaria in Cape Town, South Africa J Opie, MB ChB, MRCP (UK), FRCPA (Haem); R Freeks, MB ChB; L A du Pisani, MB ChB, FCPath (SA) (Haem) Division of Haematology, Faculty of Health Sciences, University of Cape Town and C17 Clinical Pathology Laboratory, National Health Laboratory Service and Groote Schuur Hospital, Cape Town, South Africa Corresponding author: J Opie (jessica.opie@uct.ac.za) Background. The Western Cape Province of South Africa (SA) is not malaria endemic; however, a considerable number of patients present with malaria to our healthcare services. Objectives. To establish the frequency of patients presenting with malaria at Groote Schuur Hospital (GSH), Cape Town, SA, and to describe their demographics, clinical outcomes and laboratory findings. Methods. An observational, retrospective, descriptive study was conducted, which included all patients presenting with smear-positive malaria to GSH over a 4-year period between 1 April 2008 and 31 March 2012. Results. During the study period, 134 malaria patients presented to GSH for management; 85% (n=114) were male, median age was 27 years. Of the total smear-positive tests, 96% (n=128) were Plasmodium falciparum, 3% (n=4) P. ovale, and in 1% (n=2) the species was not identified. The number of malaria patients increased markedly, from 6 cases in 2008 to 50 cases in 2012. Of the patients, 48.3% (n=57) were from Somalia, 8.5% (n=10) from SA and 29% (n=30) from other African countries. One SA patient acquired transfusiontransmitted malaria from a pooled platelet product, and the other SA patients had travelled to malaria-endemic areas. The remaining cases were from countries outside of Africa, including 13% (n=15) from Bangladesh. Almost two-thirds (62%; n=72) were admitted to hospital with a median length of stay of 3 days (range 1 - 32). Clinical outcomes were good with only one death and the remaining patients being discharged. Conclusion. Imported malaria is imposing a significant burden on health resources. The costs of medical care for the emergency treatment of foreign nationals needs to be recognised, and adequately budgeted for. S Afr Med J 2014;104(5):347-349. DOI:10.7196/SAMJ.7904

Only a small area within South Africa (SA) is malaria endemic and this is in the north-eastern part of KwaZulu-Natal, and in Mpumalanga and Limpopo provinces.[1] All cases of malaria in other areas of SA are imported, either from malariaendemic parts of SA or from further afield. A large number of migrants travel to SA for economic, political and social reasons. According to the United Nations Refugee Agency, SA was the leading worldwide destination country of new asylum seekers between 2006 and 2011. Between 2008 and 2012, the SA Department of Home Affairs registered 778 600 new asylum applications, with Zimbabweans accounting for more than half of these.[2] However, as only a proportion of migrants to SA are registered as asylum seekers, the true number of migrants is unknown. Many foreign migrants come from malaria-endemic areas and present to SA healthcare services after arrival. Groote Schuur Hospital (GSH) in Cape Town is a tertiary hospital serving the Western Cape Province, with 975 beds and a busy medical casualty department that handles ~40 000 patients/year. The aim of this study was to establish the number of malaria patients presenting to GSH over the 4-year period between 1 April 2008 and 31 March 2012, and to describe their demographics, clinical outcomes and laboratory findings.

Methods

Using the laboratory information system at the National Health Laboratory Service (NHLS) at the GSH haematology laboratory, a database was compiled of all malaria tests performed during the

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4-year study period. A malaria test includes a thick and thin malaria smear (using a Giemsa stain) and an immunochromatographic (ICT) malaria antigen test (BinaxNOW, Alere, USA). However, for our study, only the first smear-positive result was included for analysis as this is the gold standard.[3] The ICT results were therefore not included. Repeat tests for the same patient were also excluded, unless performed >1 month after the initial test, in which case it was regarded as a second event. Only patients with smear-positive malaria who presented to GSH were included for analysis. Using results derived from the laboratory information system, laboratory findings were documented and patient medical records were then reviewed for data on patient demographics and clinical outcomes. The study was approved by the Faculty of Health Sciences Ethics Committee, University of Cape Town.

Results

During the 4-year study period, 1 410 malaria tests were performed at the NHLS GSH haematology laboratory; 333 tests were smearpositive and 1 077 -negative. Since GSH NHLS is a referral laboratory serving a wide region, including clinics and regional hospitals, only 134 of the total positive tests involved patients attending GSH. Of these, 85% (n=114) were male. The median age of patients was 27 years (range 2 - 59). Plasmodium falciparum was identified on the smear in 96% (n=128) of cases, P. ovale in 3% (n=4) of cases, and in two cases identification of the Plasmodium sp. was inconclusive due to a very low parasitaemia with only a single ring form identified. The median haemoglobin concentration on presentation was 11.9 g/dl (range 1.3 - 17.7), the median platelet count was 75 × 109/l (range 13

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- 275), and the median total white cell count was 6.06 × 109/l (range 1.4 - 34) (Table 1). A total of 118 medical folders were retrieved; 48.3% (n=57) of patients originated from Somalia, 8.5% (n=10) from SA, 29% (n=30) from other countries in Africa, and 15.5% (n=18) came from countries outside Africa – mostly Bangladesh (n=15; 13%) (Fig. 1). Of the SA patients, all had

travelled to malaria-endemic areas apart from one patient who acquired malaria via a transfusion of platelet concentrate received while an inpatient at GSH. During the first year of study, six patients with malaria presented to GSH. This increased sharply to 24 cases in the second year and 54 and 50 cases in the third and fourth years, respectively (Fig. 2). Of the total, 38.5%

Table 1. Haematology and parasitology results On presentation, median (range) Haemoglobin (g/dl)

11.9 (1.3 - 17.7)

Platelet count (× 109/l)

75 (13 - 275)

White cell count (× 109/l)

6.06 (1.4 - 34)

Species identified by microscopy, n (%) (N=134) Plasmodium falciparum

128 (96)

Plasmodium ovale

4 (3)

Inconclusive*

2 (1)

*In each of these cases a single ring form was seen; therefore the parasitaemia was too low to conclusively identify the Plasmodium sp.

10%

Somalia Bangladesh Malawi South Africa Mozambique

48%

Democratic Republic of the Congo

8.5%

Other countries in Africa Other countries outside Africa

8.5%

Not recorded in notes

13%

Fig 1. Distribution of malaria patients by country of origin.

Table 2. Demographics and clinical outcomes Malaria patients (male), % (N=134)

Age (years), median (range)

27 (2 - 59)

Clinical outcomes, n (%)* Admitted to ward

72 (62)

Liver dysfunction

44 (38)

Renal dysfunction

13 (11)

Cerebral malaria

6 (5)

Outpatient management

45 (38)

Deaths

1 (<1)

Duration of admission (days), median (range)

3 (1 - 32)

*A total of 118 medical folders were retrieved. One patient refused admission.

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(n=45) were managed as outpatients and 62% (n=72) were admitted to hospital wards. One patient refused admission. One death occurred in a patient with P. falciparum complicated by cerebral malaria. The remainder were discharged. The median hospital stay was 3 days (range 1 - 32). Of the total patients for whom folders were found, 38% (n=44) had liver dysfunction, 11% (n=13) had renal dysfunction, and 5% (n=6) had documented cerebral malaria (Table 2).

Discussion

Our study findings demonstrate a marked increase in patients presenting with malaria to GSH during the 4-year study period between 2008 and 2012. This is in contrast to malaria-endemic regions of SA where cases of malaria are showing a downward trend. [1] Of the study patients, 91.5% came from countries outside SA, which is in keeping with the pattern of increasing migration into this country and into the Western Cape Province. The findings are similar to those of a recent study on children with sickle cell disease presenting to Red Cross War Memorial Children’s Hospital, Cape Town, which demonstrated an increase in new patients over a 10-year period and found that 93% of the patients originated from African countries outside SA.[4] These findings should therefore be regarded as an indicator of the increased migrant population presenting to SA healthcare services across all fields of medicine. The commonest country of origin of malaria patients in our study group was Somalia (48% of patients). A significant proportion came from Bangladesh (13%), having travelled via other countries in Africa. Two-thirds of patients required hospital admission, the mean length of admission being 3 days. One SA patient acquired transfusion-transmitted malaria from a pooled platelet product. Transfusiontransmitted malaria is an exceedingly rare occurrence. Since 1985, the Western Province Blood Transfusion Service has confirmed three cases of transfusion-associated malaria, two from red cell concentrates and one from pooled platelets. The transfusion donors of these three cases were found to have very low levels of parasitaemia, to have previously lived in malaria-endemic areas and to be clinically asymptomatic. The clinical outcomes in this study group were good with only one death (<1% of all patients). This low mortality is a likely reflection of the semi-immunity of the majority of our patients who came from malaria-endemic areas.[5] This is in contrast

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This may be regarded as an indicator of the changing demographics of patients presenting to the SA healthcare services, including to the general medical, surgical and obstetric sectors. This growing trend is imposing a significant burden on healthcare services, which are already under strain. This issue needs to be addressed in a constructive manner. We recommend that a formal budget allocation be made by the Department of Health for emergency healthcare of foreign migrants.

Cases, n

Acknowledgement. The authors thank Dr Gregory Bellairs and the staff of the Western Province Blood Transfusion Service who investigated the case of transfusion-transmitted malaria.

0 2008 - 2009

2009 - 2010

2010 - 2011

2011 - 2012

Fig. 2. Frequency of malaria at Groote Schuur Hospital over the 4-year study period (N=134).

to non-malaria immune patients who are known to have a higher mortality if contracting malaria following travel to an endemic area.[6] Rapid testing for malaria species using ICT rapid diagnostic tests that detect parasite antigen using a dipstick format are now widely available. ICT tests are particularly useful in remote areas where microscopy is unavailable or where laboratory personnel are inexperienced in the interpretation of smear findings. ICT tests are also quick and easy to perform at the point of care, however, they have drawbacks particularly in terms of sensitivity. The BinaxNOW ICT test used at GSH NHLS is known to have a high sensitivity for the diagnosis of P. falciparum, but is less sensitive for non-P. falciparum malaria.[7] Thin and thick smear blood film preparations therefore remain the ‘gold standard’ for malaria diagnosis and a first thin and/or thick smear-positive test was used to determine inclusion in this study.

P. falciparum, the commonest malaria species in Africa and also the commonest species causing death in Africa, was the species identified in the vast majority of cases. [8] Most patients were mildly anaemic with a median haemoglobin of 11.9 g/dl (reference range for males 13 - 17), and had moderate thrombocytopenia with a median platelet count of 75 × 109/l (reference range for males 137 - 373). The mechanism for thrombocytopenia in malaria is not yet elucidated fully, but a component of malarial antigen-associated platelet immune destruction has been demonstrated to occur in some cases.[9] The median white cell count was low-normal at 6.06 × 109/l (reference range 4 - 10), reflecting that malaria does not typically evoke an inflammatory response with an associated neutrophil leucocytosis. The tertiary healthcare services in Cape Town are seeing increased numbers of patients with imported malaria who have originated from countries outside SA.

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References 1. Maharaj R, Raman J, Morris N, et al. Epidemiology of malaria in South Africa: From control to elimination. S Afr Med J 2013;103(10 Suppl 2):779-783 [http://dx.doi.org/10.7196/SAMJ.7441] 2. United Nations High Commissioner for Refugees. Displacement: The New 21st Century Challenge – UNHCR Global Trends 2012. Geneva: UNHCR, 2012. http://unhcr.org/ globaltrendsjune2013/ (accessed 5 March 2014). 3. Frean J, Poonsamy B, Shandukani B, Moonasar D, Raman J. Case management of malaria: Diagnosis. S Afr Med J 2013;103(10 Suppl 2):789-793 [http://dx.doi.org/10.7196/SAMJ.7442] 4. Wonkam A, Ponde C, Nicholson N, Fieggen K, Ramessar R, Davidson A. The burden of sickle cell disease in Cape Town. S Afr Med J 2012;102(9):752-754 [http://dx.doi.org/10.7196/ SAMJ.5886] 5. Pistone T, Diallo A, Mechain M, Receveur M-C, Malvy D. Epidemiology of imported malaria give support to the hypothesis of ‘long-term’ semi-immunity to malaria in sub-Saharan African migrants living in France. Travel Med Infect Dis 2014;12(1):4853. [http://dx.doi.org/10.1016/j.tmaid.2013.08.006] 6. Checkley A, Smith A, Smith V, et al. Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: An observational study. BMJ 2012;344:e2116. [http:// dx.doi.org/10.1136/bmj.e2116] 7. Farcas G, Zhong K, Lovegrove F, et al. Evaluation of the Binax NOW ICT test versus polymerase chain reaction and microscopy for the detection of malaria in returned travellers. Am J Trop Med Hyg 2003;69(6):589-592. 8. World Health Organisation. World Malaria Report 2012. Geneva: WHO, 2012:59. http://www.who.int/malaria/ publications/world_malaria_report_2012/en/index.html (accessed 18 December 2013). 9. Kelton J, Keystone J, Moore J, et al. Immune-mediated thrombocytopenia of malaria. J Clin Invest 1983;71(4):832-836.

Accepted 13 January 2014.

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Perceptions of mental illness among Muslim general practitioners in South Africa Z Mohamed-Kaloo, MA (Clinical Psychology); S Laher, PhD Department of Psychology, School of Human and Community Development, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: S Laher (sumaya.laher@wits.ac.za) Background. Mental health literacy on the part of medical practitioners is an important component of mental healthcare. General practitioners (GPs) are typically the first doctors consulted by a person who is ill. Exploration of their perceptions regarding mental illness, aetiological issues and treatment is important. Objective. To investigate perceptions of mental illness in a sample of 10 South African Muslim GPs (five male, five female) in the Lenasia area (Johannesburg, South Africa). Methods. Using a qualitative approach, semi-structured interviews were conducted with each GP. The questionnaire encompassed 37 questions relating to the context in which the GPs practised, perceptions of mental illness, understanding of religion and culture, and treatment of mental illness (including aspects of spiritual illness). Thematic content analysis was used to analyse the data. Results. Six dominant themes were identified, namely GPs’ understanding of mental illness and its causation; stigma, secrecy and somatisation; the beneficial effects of religion in mental illnesses; perceptions of spiritual illnesses; collaboration with traditional healers; and collaboration with psychiatrists and psychologists. Conclusion. Greater awareness regarding the stigmatisation of mental illness is needed. Furthermore, it is important that healthcare professionals have an understanding of religious and cultural taxonomies of illness and the use of traditional healing as a mode of treatment. Participants identified a need for increased collaboration between healthcare professionals, including traditional healers. S Afr Med J 2014;104(5):350-352. DOI:10.7196/SAMJ.7863

Local and international research consistently empha sises the importance of mental health literacy on the part of healthcare professionals and community members. Mental health literacy extends beyond the biopsychosocial sphere and calls for a greater awareness of religious and cultural values that can influence healthcare professionals and their patients. General practitioners (GPs) are often the first point of entry when people seek medical treatment, and their perceptions of mental illness, aetiological issues and treatment are important. An examination of current research in the South African (SA) context indicates that research has focused on the prevalence of mental illness generally and across different groups.[1] It has also focused on assessing the role of traditional healers and traditional healing in relation to more conventional care.[2] Issues of mental health literacy[3] and explanatory models of mental illness[4] have been addressed. This research has mainly been quantitative. Qualitative studies have examined perceptions of mental illness in samples of traditional healers, volunteer counsellors, community members, psychologists and psychiatrists, but not among GPs.[5,6] The GP, often the family physician and the community doctor, is typically the first professional from whom a person who is ill seeks treatment and healthcare advice. According to Ng,[7] culture can often influence mental illness in terms of perception, conception, experience of symptoms, classification, treatment, recognition, labelling and the course of mental illness. This is particularly the case in the SA context, where supernatural, religious, magical and moralistic approaches to mental illness exist.[5-7] Spiritual punishment or sorcery is often identified as a cause of illness.[5,7] It is therefore essential that GPs’ perceptions of mental illness be explored, as they deal with patients from various cultures and religions and are well positioned to inform research on mental illness in SA.

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Objective

We sought to investigate perceptions of mental illness among SA Muslim GPs, and to do this qualitatively to provide a richer descrip tion of their experiences.

Methods Participants

A non-probability, convenience sample of ten Muslim general practitioners (five male and five female) in private practice in the Lenasia area of Johannesburg were interviewed. Participants were selected from Lenasia because it has the largest Muslim community in Gauteng Province. Members of the community provided the names of GPs who were most frequently consulted. GPs who were well established in the community were therefore selected for possible interview, and the first few who were interviewed provided referrals to other GPs practising in the area, permitting ‘snowballing sampling’ to obtain additional participants. GPs were contacted telephonically, and the first five females and five males who agreed to participate in the study were interviewed. A balanced sample in terms of patient gender was obtained because female patients generally visit female practitioners and male patients visit male practitioners. The sample consisted of both recently graduated and experienced doctors, with time in practice ranging from 1.5 to 40 years (mean 19.6).

Instruments

Semi-structured interviews approximately 45 minutes in length were conducted with each participant. The interview schedule was developed by consulting the relevant literature as well as four interview schedules from previous studies,[6,8-10] and consisted of 37 questions covering contextual issues, GPs’ perceptions of mental illness, understanding of religion and culture, questions on the treatment of mental illness and questions on spiritual illness.

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Procedure

Ethics clearance was obtained from the Human Research Ethics Committee (HREC Non-Medical) of the University of the Witwatersrand, Johannesburg (protocol no. MCLIN/11/004 IH). Participants were contacted telephonically and were informed regarding the nature and purpose of the study. The interviews were conducted with those participants who consented to be interviewed, at a place and time convenient to the participant. All interviews were audio-recorded and then transcribed.

Data analysis

Thematic content analysis as described by Braun and Clarke[11] was used to analyse the data. Thematic content analysis aims to determine themes or patterns in data and involves reading and transcribing of the data, generation of initial codes, assembling codes into potential themes, generating a thematic map, and defining and naming themes. Transcripts were analysed using the ATLAS TI program.

Results and discussion

Six dominant themes were identified in the analysis. The first theme centred around GPs’ understanding of mental illness and its causation. The second theme considered issues of stigma, secrecy and somatisation. The third theme focused on the beneficial effects of religion in the treatment of mental illnesses, while the fourth centred around GPs’ perceptions of spiritual illnesses. Collaboration with traditional healers and collaboration with psychiatrists and psychologists were the final two themes identified. These themes are presented and discussed.

GPs’ understanding of mental illness and its cause

Sixty per cent (n=6) of the participants understood mental illness as any condition that affects one’s daily functioning and mental wellbeing. Thirty per cent (n=3) provided an intellectual understanding of mental illness based on their medical exposure and training and therefore defined it in terms of specific disorders (i.e. depression, anxiety, bipolar disorder, schizophrenia, etc.). Generally, participants’ understanding of mental illness was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classification. This understanding of mental illness corresponded with participants’ belief that in addition to organic causes, stress and lifestyle had a major influence on the development of mental conditions, most notably anxiety, depression and stress disorders. Participants elaborated on the above, stating that family issues have a serious impact on patients’ well-being in the Lenasia community (reflecting financial pressures on married couples, both of whom often need to work, limited family time, marital conflicts, or changes in marital status such as divorce or death of a spouse). This concurs with Chiu et al.’s[8] finding that Canadian Asian women reported becoming mentally ill due to their extremely stressful lifestyles when they were expected to work, take care of children and do household chores. Marital conflict and relationships with in-laws were exacerbating factors. The typical busy Western lifestyle in Canada resulted in lack of family time and absence of social support from neighbours and friends, in contrast to lifestyles in India, where the community often gave support.[8] These results concur with studies in the SA context, where psychosocial factors, notably stress, have been identified as a major cause of mental disorders.[3,9]

Stigma, secrecy and somatisation

Most participants acknowledged that mental illness is often stigmatised in the Lenasia community. All mentioned that their

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patients tended to keep mental illness a secret from their families as well as from the community at large. Patients were even reluctant to disclose their mental status to their GP, and concealing mental illness was common in the Indian Muslim community. Participants also mentioned the embarrassment faced by families when a member has a mental condition. Mental illness is therefore often disguised as a medical illness (e.g. diabetes or hypertension), which is more acceptable because it carries less stigma. Participants also stated that patients often present with pain-related complaints such as headaches, backaches or abdominal pain; however, these symptoms are not due to a medical condition but caused by underlying emotional distress. According to Greenwood et al.,[10] Asian patients may not be referred for psychiatric care because they are prone to somatise psychological problems and consequently mental illnesses are not identified and diagnosed. These findings concur with reports by Chiu et al.[8] and Jacob et al.[12] that the tendency to hide illness often resulted in GPs failing to detect mental illness, and many patients either being undiagnosed or misdiagnosed. Jacob et al.[12] also found that doctors often believe that mental illness is managed within the family in Asian communities. A similar tendency was revealed in the current study, with a few of our participants mentioning that in the Indian Muslim population, people tend to rely on their extended families for support. Together with the above factors, fear of stigmatisation may prevent people from seeking help.[3] Participants in the current study supported this, and indicated that members of the Lenasia community also lack information about mental illness, which in turn contributes to stigmatisation. This concurs with the finding of Hugo et al.[3] that misinformation about mental illness led to stigmatisation of mental illness in the Cape Town community. Given the high prevalence of stigmatisation and lack of knowledge about mental illness, the participants in our study felt that campaigns to increase awareness were needed in Lenasia. Similarly, Mavundla et al.[13] and Sorsdahl and Stein[9] have recommended that educational programmes are needed to inform communities about the causes of mental illness, coping methods and the importance of counselling and medication, as well as cultural conceptualisations of mental illness.

Beneficial effects of religion on mental illness

Some participants (n=5) in the current study reported that the Muslim community’s religious beliefs, the teachings that Islam prescribes and their faith in the will of God makes it easier for Muslims to deal with issues. They felt that such faith reduces the prevalence of mental illnesses such as depression and substance abuse. Islam also assists by prohibiting (ab)use of alcohol and substances. Participants also acknowledged the potential benefit of religious practices such as dua (supplication), zikr (meditation) and salaah (ritual prayer, the second pillar of Islam). According to Carter and Rashidi,[14] meditation and prayers have been used to promote and enhance emotional experiences as well as to establish a connection with God. A few participants (n=2) were of the opinion that patients may find it easier to relate to their GP and disclose their problems if disclosing to a GP from the same culture as themselves. Cinnirella and Loewenthal[15] found that patients preferred GPs who were of the same religion, because they could recommend prayers that would assist in treating the ailment.

GPs’ beliefs regarding spiritual illness: Understanding aetiology and treatment

The majority of the participants in this study (n=8) acknowledged that spiritual illness exists, and patients often discussed experiences

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of such illnesses with their GPs. Spiritual illness was understood by the participants to mean symptoms that were beyond medical classification and therefore supernatural, such as jadoo (witchcraft), nazr (‘evil eye’) and jinn (spirits). Four participants mentioned that spiritual illness is common in the black African population, and that spiritual illness and traditional healing form part of SA culture. Recent studies have found that members of the black SA community often attribute mental health problems to cultural causes, such as witchcraft or the ancestors, rather than genetic or biological causes.[2,5,13] Previous studies, locally and internationally, have also acknowledged the existence of a belief in witchcraft, the ‘evil eye’ and spirit possession in the Indian and/or Muslim populations, and the consequent belief that mental illness is a cause of such spiritual afflictions.[5,6,14]

Collaboration with traditional healers

Participants reported that in addition to consulting medical professionals, patients regularly consulted traditional healers such as maulanas (Muslim clergy) and sangomas (African traditional healers). It has been documented that a significant proportion of people in SA who suffer from mental health problems consult traditional healers.[2,5] The participants noted that collaboration with and referral to traditional healers are important. According to Sorsdahl et al.,[2] SA has limited psychiatric care facilities and it may therefore be beneficial to work with traditional healers who are knowledgeable about cultural norms. Williams et al.[1] reported that in SA there are four psychiatrists, eight psychiatric nurses, four psychologists and 20 social workers per 100 000 of the population. According to Sohrsdahl et al.,[2] there are at least 200 000 traditional healers (1 per 500 population). Participants in this study also indicated that alternative forms of healthcare can be more accessible to patients than Western modes of treatment, as they are often cheaper. This is supported by the findings of Sorsdahl et al.[2]

Collaboration with psychologists and psychiatrists

All the participants agreed that they would refer patients to a psychiatrist if the need arose. However, they emphasised that patients were often reluctant to see psychiatrists and psychologists, preferring to be treated by their GP. Furthermore, three participants very rarely referred patients to psychiatrists, preferring psychologists because patients ‘just needed a space to talk’. This is in agreement with previous findings in the SA context,[2,9] which have indicated that people prefer to receive counselling rather than medication, particularly for mental illnesses such as depression. The participants also mentioned that in the Indian Muslim community there may be stigma associated with seeing a psychologist or psychiatrist, as doing so is equated with madness, added to which are cultural expectations that emotional difficulties should be handled without professional help. A further factor preventing patients from seeking help is concern over confidentiality.

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Study limitations

The findings of this study are based on a convenience sample of Muslim GPs from a specific area, Lenasia. The transferability of the results is therefore limited. The sample size was also small. However, the study allowed for an initial in-depth exploration of perceptions of mental illness. Similar studies with bigger and more representative samples will be useful in further research.

Conclusion

The participants stressed the importance of community awareness regarding mental illness in the form of educational interventions aimed at enhancing knowledge on the part of both GPs and the general public, with the intention of diminishing stigma. It is clear that cultural and religious taxonomies of illness need further exploration, especially as they pertain to spiritual illnesses. There is a need for greater collaboration between healthcare professionals, including traditional healers. Opportunities for the above should be made available through various continuing professional development activities or via conferences. The Health Professions Council of South Africa could play an important role in initiating such activities. There is also a need for further qualitative research to provide a richer understanding of the role of culture and religion in the understanding, aetiology and treatment of mental disorders, which can then inform training and intervention in the SA context. References 1. Williams DR, Herman A, Stein DJ, et al. Twelve-month mental disorders in South Africa: Prevalence, service use and demographic correlates in the population-based South African Stress and Health Study. Psychol Med 2008;38(2):211-220. [http://dx.doi.org/10.1017/S0033291707001420] 2. Sorsdahl K, Stein DJ, Grimsrud A, et al. Traditional healers in the treatment of common mental disorders in South Africa. J Nerv Ment Dis 2009;197(6):434-441. [http://dx.doi.org/10.1097/ NMD.0b013e3181a61dbc] 3. Hugo CJ, Boshoff DEL, Traut A, Zungu-Dirwayi N, Stein DJ. Community attitudes toward and knowledge of mental illness in South Africa. Soc Psychiatry Psychiatr Epidemiol 2003;38(12):715-719. [http://dx.doi.org/10.1007/s00127-003-0695-3] 4. Petersen I, Lund C. Mental health service delivery in South Africa from 2000 to 2010: One step forward, one step back. S Afr Med J 2011;101(10):751-757. 5. Ally Y, Laher S. South African Muslim faith healers perceptions of mental illness: Understanding, aetiology and treatment. J Relig Health 2008;47(1):45-56. [http://dx.doi.org/10.1007/s10943-007-9133-2] 6. Bulbulia T, Laher S. Perceptions of mental illness among South African Muslim psychiatrists. South African Journal of Psychiatry 2013;19(2):52-54. 7. Ng C. The stigma of mental illness in Asian cultures. Aust N Z J Psychiatry 1997;31(3):382-392. [http:// dx.doi.org/10.3109/00048679709073848] 8. Chiu L, Ganesan S, Clark N, Morrow M. Spirituality and treatment choices by South and East Asian women with serious mental illness. Transcult Psychiatry 2005;42(4):630-656. [http://dx.doi. org/10.1177/1363461505058920] 9. Sorsdahl K, Stein DJ. Knowledge of and stigma associated with mental disorders in a South African community sample. J Nerv Ment Dis 2010;198(10):742-747. [http://dx.doi.org/10.1097/ NMD.0b013e3181f4b2d7] 10. Greenwood N, Hussain F, Burns T, Raphael F. Asian in-patient and carer views of mental health care: Asian views of mental health care. J Ment Health 2000;9(4):397-408. [http://dx.doi.org/10.1080/jmh.9.4.397.408] 11. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol 2006;3(2):77-101. [http:// dx.doi.org/10.1191/1478088706qp063oa] 12. Jacob KS, Bhugra D, Lloyd KR, Hannah AH. Common mental disorders, explanatory models and consultation behaviour among Indian women living in the UK. J R Soc Med 1998;91(2):66-71. 13. Mavundla TR, Toth F, Mphelane ML. Caregiver experience in mental illness: A perspective from a rural community in South Africa. Int J Ment Health Nurs 2009;18(5):357-367. [http://dx.doi. org/10.1111/j.1447-0349.2009.00624.x] 14. Carter DJ, Rashidi A. Theoretical model of psychotherapy: Eastern Asian-Islamic women with mental illness. Health Care Women Int 2003;24(5):399-413. [http://dx.doi.org/10.1080/07399330390212180] 15. Cinnirella M, Loewenthal K. Religious and ethnic group influences on beliefs about mental illness: A qualitative interview study. Br J Med Psychol 1999;72(4):505-524. [http://dx.doi. org/10.1348/000711299160202]

Accepted 20 January 2014.

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RESEARCH

Evaluation of the visual prostate symptom score in a male population with great language diversity and limited education: A study from Namibia C F Heyns,1 MB ChB, MMed (Urol) PhD, FCSSA (Urol); B A Steenkamp,1 BSc, MB ChB; J Chiswo,2 MB ChB; G A Stellmacher,2 MB ChB, MMed (Urol); H E A Förtsch,2 MB ChB, MMed (Urol), FCSSA (Urol); A van der Merwe,1 MB ChB, MMed (Urol) FCUrol (SA) 1 2

Department of Urology, Faculty of Health Sciences, Stellenbosch University and Tygerberg Hospital, Tygerberg, Cape Town, South Africa Department of Urology, Windhoek Central Hospital, Namibia

Corresponding author: C F Heyns (cfh2@sun.ac.za) Background. A visual prostate symptom score (VPSS) using pictograms was developed to assess the force of the urinary stream, urinary frequency, nocturia and quality of life (QoL). Objective. To compare the VPSS with the international prostate symptom score (IPSS) and maximum (Qmax) and average (Qave) urinary flow rates in men from diverse language groups with limited schooling. Methods. Men with lower urinary tract symptoms admitted to the urology ward at Windhoek Central Hospital, Namibia, were evaluated. Patients who were unable to complete the questionnaires alone were assisted by a doctor or nurse. Local ethics committee approval was obtained. Statistical analysis was performed using Student’s t-test and Spearman’s rank correlation test. Results. One hundred men (mean age 56.3 years, range 20.1 - 95.4) were evaluated over a period of one year. All the men understood one or more of 15 languages, and 30 were illiterate; 32 had <5 years of schooling, 34 had 5 - 9 years and 34 had >9 years. The VPSS took significantly less time to complete than the IPSS. There were statistically significant correlations between the total VPSS and IPSS scores, between the four VPSS questions and the corresponding IPSS questions, and between Qmax and Qave and the VPSS total and VPSS questions on the force of the urinary stream and QoL. Conclusion. The VPSS pictograms depicting the force of the urinary stream and QoL correlated significantly with Qmax and Qave, indicating that they can be used as single-item questions to rapidly assess bladder outflow obstruction in men with limited education. S Afr Med J 2014;104(5):353-357. DOI:10.7196/SAMJ.7917

The international prostate symptom score (IPSS) (Fig. 1) is used widely to assess lower urinary tract symptoms (LUTS) in men before and after treatment.[1] The IPSS is relatively complicated, especially for patients with low education levels, and elderly patients with visual impairment may find it difficult to read the small print.[2-4] Illiteracy is a major problem with administration of the IPSS in developing countries.[5] Translating the IPSS into various languages requires extensive validation studies and constant surveillance to ensure consistency.[6] A drawback of the IPSS is that it does not evaluate all lower urinary tract symptoms, such as incontinence, pain or macroscopic haematuria. More comprehensive questionnaires have been developed, such as the Core LUTS Score with 10 questions, and the EpiLUTS tool evaluating 18 symptoms.[7,8] While providing more information, these require a high level of patient education, are timeconsuming to administer and analyse, and may not be useful for clinical application. Some authors have proposed using fewer questions that may be more useful in clinical practice. A previous study has indicated that an abbreviated form of the IPSS consisting of three or four questions only may be used to assess patients more rapidly.[3] It has also been suggested that the IPSS quality of life (QoL) question alone is as useful as the more complicated Benign Prostatic Hypertrophy Impact Index (BPH-II).[9]

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Others have proposed the use of single-item questionnaires, which have the advantages of speed and ease of administration and interpretation, but the disadvantage that a single question cannot quantify the variety of symptoms present, their intensity, duration and frequency, or the distress they cause.[1] A recent study indicated that patients’ perceptions of the severity of and changes in their symptoms can be captured with single-item questions that are simple, valid and easily administered.[10] We developed a visual prostate symptom score (VPSS) that uses pictograms to assess the force of the urinary stream, daytime urinary frequency, nocturia and QoL.[11-13] At the time we were unaware that Peeling[14] had described a pictogram representing the force of the urinary stream in 1989, and that in 2006 Ushijima et al.[15] had described a visual analogue scale for the IPSS, consisting of facial pictograms with expressions ranging from a broad smile (delighted) to a tearful face (distressed).

Objective

To compare the IPSS and VPSS with urinary flow rate measurements in men with LUTS who were illiterate or had very limited schooling, and who spoke a diversity of languages.

Methods

Men with LUTS admitted to the urology ward at Windhoek Central Hospital, Namibia, were evaluated with the IPSS (Fig. 1) and the VPSS (Fig. 2). Maximum (Qmax) and average (Qave) urinary flow

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rates were measured using a Dantec Urodyn flowmeter. The original version of the VPSS[11,12] was modified in a subsequent study.[13] The pictogram of the force of the urinary stream (question 3 in the original version) was moved to become question A, because the pictogram of urination made it easier for the patient to understand the pictograms of frequency and nocturia (questions 2 and 3 in the original, and questions B and C in the modified VPSS).[11-13] The following demographic data were collected: the patient’s age, his mother’s language, his home language, which languages he was able to understand, speak and read or write, years of schooling, occupation and monthly income. The patient was requested to fill in the IPSS and VPSS, with assistance if necessary from a physician and/or a nurse able to speak the patient’s home language. The time taken to fill in the IPSS and the VPSS was recorded using a stopwatch. The following clinical data were collected: findings on digital rectal examination, urine dipstick analysis, Qmax and Qave, voided volume (VV), serum creatinine, serum prostate-specific antigen, findings on cystoscopy, treatment given and histological results. Patients were requested to return for follow-up at 3 and 6 months after treatment. The study protocol was approved by the Ministry of Health and Social Services of Namibia. Statistical analysis was performed with Student’s t-test (paired or unpaired, as appropriate) for parametric data, Spearman’s rank test for correlations and Fisher’s exact test for contingency tables, using GraphPad InStat software.

Results

During the period February 2012 - February 2013, a total of 100 new patients were evaluated; 39 returned for follow-up, with a total of 155 visits (some patients had more than one follow-up visit). The distance between the patient’s home and the hospital was <100 km in 44 cases, 100 - 500 km in 32, 500 - 1 000 km in 22 and >1 000 km in

Fig. 1. International prostate symptom score.[1]

two. Overall, 25 patients had never attended school. The number of years at school was <5 years in 32 cases, 5 - 9 years in 34 and >9 years in 34. Overall, 30 patients were not able to read or write. Table 1 shows the mother languages of the patients, and the languages they spoke at home and were able to understand, speak and read or write. The number of languages understood by the patients was one in 21% of cases, two in 35%, three in 23%, four in 16% and five in 5%. Table 2 shows the number of languages understood by the patients in the five most common language groups. On admission to hospital, 19 men had an indwelling suprapubic catheter and 14 an indwelling transurethral catheter. The mean duration of catheterisation was 3.7 months (range 0.1 - 41.3). For these men, the symptom scores for the month before catheterisation were obtained; uroflowmetry could not be undertaken. The final diagnosis was urethral stricture in 61 men, benign prostatic hyperplasia (BPH) in 32, no abnormality on cystoscopy in five, prostate cancer in three, prostatitis in three, bladder stones in two and bladder neck stenosis in one (some patients had more than one diagnosis). The surgical treatment involved direct-vision internal urethrotomy in 60 cases, transurethral resection of the prostate in 17, open prostatectomy in six, bladder neck incision in one and urethroplasty in one. Both the IPSS and VPSS were filled in without assistance by only 18 of patients at the first visit, 82 requiring assistance. At follow-up the IPSS and VPSS were filled in without assistance by 7/55 (12.7%) and 8/55 (14.5%) of patients. For all visits, the mean time taken to complete the IPSS and VPSS was 278 seconds (range 80 - 690) and 124 seconds (30 - 556), respectively (p<0.0001). Comparing the first with follow-up visits, the mean time taken to complete the IPSS was 306 seconds (80 690) v. 227 seconds (80 - 572), and the mean time taken to complete the VPSS was 173 seconds (30 - 556) v. 100 seconds (30 - 270) (p<0.001). Table 3 compares the groups of men with schooling <5 v. >9 years.

Fig. 2. Visual prostate symptom score consisting of pictograms to evaluate (A) force of the urinary stream, (B) daytime frequency, (C) nocturia, and (D) quality of life.

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Table 1. Languages of the study group (N=100) Motherâ&#x20AC;&#x2122;s language* n

Home language n

Able to understand n

Able to speak n

Able to read/write n

Oshiwambo

Otjiherero

Afrikaans

Damara

Nama

Himba

Nyemba

Portuguese

Rukwangali

1 3

Shilozi

Dhemba

English

Mbukushu

Sifwe

German

*Some subjects had a mother who spoke more than one language.

Table 2. Number of languages understood by members of the study group with the most common mother languages Languages understood (N), n (%) Motherâ&#x20AC;&#x2122;s language

Oshiwambo (N=27)

6 (22.2)

9 (33.3)

8 (29.6)

3 (11.1)

1 (3.7)

Otjiherero (N=23)

11 (47.8)

6 (26.1)

5 (21.7)

1 (4.3)

Afrikaans (N=15)

10 (66.7)

4 (26.7)

1 (6.7)

Damara (N=11)

4 (36.4)

5 (45.5)

2 (18.2)

Nama (N=9)

6 (66.7)

2 (22.2)

1 (11.1)

Table 4 shows the correlations between the various VPSS and IPSS questions, Qmax and Qave in the study group as a whole, and Qmax and Qave in patients with VV >150 ml and <150 ml. Comparing the groups with VV >150 ml and <150 ml, there were significant correlations between the total VPSS and total IPSS (0.934 v. 0.741, respectively) and between the VPSS and IPSS questions related to the force of the stream (0.775 v. 0.541) and QoL (0.902 v. 0.692). In the group with VV >150 ml there were significant correlations between Qmax and the IPSS and VPSS questions on the force of the urinary stream (-0.365 v. -0.456) and QoL (-0.284 v. -0.223). In the group with VV <150 ml there were even stronger correlations between Qmax and the IPSS and VPSS questions on the force of the stream (-0.434 v. -0.425) and QoL (-0.501 v. -0.387). The same was true for correlations of Qave with the IPSS and VPSS questions about the force of the urinary stream and QoL.

Discussion

In a previous study of 96 men with LUTS referred to a urology outpatient clinic, Van der Walt et al.[11] found that a greater proportion of patients with <7 v. >10 years of schooling could complete the VPSS without assistance compared with the IPSS (68% v. 13% and 92% v. 76%, respectively). There were statistically significant correlations between the total VPSS and IPSS scores, and between the total VPSS, Qmax and Qave. In

Table 3. Comparison of patient groups with <5 v. >9 years of schooling Whole group (N=100)

Schooling <5 years (N=32)

Schooling >9 years (N=34)

p-value

Age (years), mean (range)

56.3 (20.1 - 95.4)

71 (38.8 - 95.4)

43.2 (20.1 - 87.5)

<0.0001

Able to read and write, %

100

<0.0001

Income per month (Namibian $), mean (range)

3 205 (0 - 30 000)

1 732 (0 - 30 000)

5 926 (0 - 25 000)

<0.0001

IPSS completed without assistance, %

<0.0001

VPSS completed without assistance, %

<0.0001

Time to complete IPSS (seconds), mean (range)

278 (80 - 690)

324 (148 - 690)

294 (80 - 630)

0.366

Time to complete VPSS (seconds), mean (range)

124 (30 - 556)

178 (58 - 556)

107 (30 - 330)

0.003

VPSS total v. IPSS total

r=0.863 p<0.0001

r=0.775 p<0.0001

r=0.673 p<0.0001

VPSS QA (force of stream) v. IPSS Q5 (weak stream)

r=0.657 p<0.0001

r=0.589 p=0.0007

r=0.295 p=0.09

VPSS QB (frequency) v. IPSS Q2 (frequency)

r=0.522 p<0.0001

r=0.379 p=0.036

r=0.451 p=0.008

VPSS QC (nocturia) v. IPSS Q7 ( nocturia)

r=0.898 p<0.0001

r=0.844 p<0.0001

r=0.851 p<0.0001

VPSS QD (QoL) v. IPSS QoL

r=0.806 p<0.0001

r=0.635 p=0.0001

r=0.387 p=0.024

Correlations

IPSS = international prostate symptom score; VPSS = visual prostate symptom score; Q = question; QoL = quality of life.

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Table 4. Correlations between the visual prostate symptom score, international prostate symptom score and maximum and average urinary flow rates All follow-up visits (N=155) Spearman’s rank correlation

Coefficient (r)

p-value

VV >150 ml (N=57) Coefficient (r)

p-value

VV <150 ml (N=44) Coefficient (r)

p-value

VPSS v. IPSS Total

0.863

<0.0001

0.934

<0.0001

0.741

<0.0001

PSS QA (force of stream) v. IPSS V Q5 (weak stream)

0.657

<0.0001

0.775

<0.0001

0.541

0.0002

PSS QB (frequency) v. IPSS V Q2 (frequency)

0.522

<0.0001

0.525

<0.0001

0.552

0.0001

PSS QC (nocturia) v. IPSS V Q7 (nocturia)

0.896

<0.0001

0.913

<0.0001

0.907

<0.0001

VPSS QD (QoL) v. IPSS QoL

0.806

<0.001

0.902

<0.0001

0.692

<0.001

Total

-0.409

<0.0001

-0.284

0.038

-0.371

0.022

Qmax v. IPSS Q2 (frequency)

-0.159

0.121

-0.007

0.962

-0.275

0.095

Qmax v. IPSS Q5 (weak stream)

-0.458

<0.0001

-0.365

0.007

-0.434

0.006

Qmax v. IPSS Q7 (nocturia)

-0.082

0.427

0.142

0.304

-0.186

0.263

Qmax v. IPSS QoL

-0.489

<0.0001

-0.284

0.038

-0.501

0.001

Total

-0.340

0.0007

-0.174

0.208

-0.362

0.026

Qmax v. VPSS QA (force of stream)

-0.522

<0.0001

-0.456

0.0005

-0.425

0.008

Qmax v. VPSS QB (frequency)

-0.109

0.109

-0.005

0.973

-0.246

0.136

Qmax v. VPSS QC (nocturia)

-0.072

0.488

-0.152

0.272

-0.125

0.455

Qmax v. VPSS QD (QoL)

-0.368

0.0002

-0.223

0.105

-0.350

0.031

Total

-0.479

<0.0001

-0.441

0.0006

-0.337

0.025

Qave v. IPSS Q2 (frequency)

-0.227

0.020

-0.095

0.481

-0.307

0.043

Qave v. IPSS Q5 (weak stream)

-0.481

<0.0001

-0.507

<0.0001

-0.289

0.057

Qave v. IPSS Q7 (nocturia)

-0.194

0.047

0.016

0.097

-0.287

0.059

Qave v. IPSS QoL

-0.549

<0.0001

-0.437

0.0007

-0.447

0.002

Total

-0.425

<0.0001

-0.334

0.011

-0.371

0.013

Qave v. VPSS QA (force of stream)

-0.522

<0.000

-0.572

<0.0001

-0.413

0.005

Qave v. VPSS QB (frequency)

-0.165

0.109

-0.077

0.570

-0.222

0.147

Qave v. VPSS QC (nocturia)

-0.072

0.488

0.022

0.869

-0.193

0.209

Qave v. VPSS QD (QoL)

-0.440

<0.0001

-0.379

0.004

-0.333

0.027

Qmax v. IPSS

Qmax v. VPSS

Qave v. IPSS

Qave v. VPSS

VPSS = visual prostate symptom score; IPSS = international prostate symptom score; VV = voided volume; Q = question; QoL = quality of life; Qmax = maximum urinary flow rate; Qave = average urinary flow rate.

a further analysis of the uroflowmetry data, Heyns et al.[12] found that the VPSS question on the subject’s assessment of his urinary stream showed a significant negative correlation with Qmax (r=-0.37, p=0.002) and Qave (r=-0.31, p=0.011), whereas the IPSS question on the subject’s urinary stream did not correlate significantly with Qmax or Qave. In a study of 100 men followed up after a diagnosis of urethral stricture, Wessels and Heyns[13] found that the VPSS correlated significantly with the IPSS, Qmax and urethral diameter and took significantly less time to complete than the IPSS. In the current study, the mean patient age (56.3 years) was considerably lower than in other studies of men with LUTS (64 70 years).[5,9,11] This is explained by the fact that the underlying pathology was urethral stricture in 61%, with BPH in only 32% of the study cohort. The majority of the patients (66%) had <10 years of schooling, 25% had never attended school and 30% were illiterate. The patients

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with <5 years of schooling were significantly older than those with >9 years of schooling (mean age 71 v. 43.2 years) (Table 3), indicating that the older men grew up in a time when access to school education was less readily available. The study patients all spoke one or more of 15 languages, so it is not surprising that 82% overall, and 100% in the group with <5 years of schooling, required assistance to complete the IPSS and VPSS. The time taken to complete the VPSS was significantly less than that for the IPSS for the group as a whole (124 v. 278 seconds) and also in the groups with <5 years of schooling (178 v. 324 seconds) v. >9 years of schooling (107 v. 294 seconds), confirming that the VPSS takes less time to complete than the IPSS, especially in men with limited education.[11] The mean time to complete both the IPSS and VPSS was shorter at follow-up (173 and 100 seconds) than at the first visit (306 and 227 seconds), indicating that patients learn how to answer the questions more quickly.

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The group with lower schooling (<5 years v. >9 years) showed stronger correlations between the total VPSS and total IPSS, between VPSS question A and IPSS question 5 (force of the urinary stream), and between the VPSS and IPSS QoL questions (Table 3). This indicates that the correlations between the VPSS and IPSS scores may be even better in men with very limited schooling than in those with a higher level of schooling. Although it is generally accepted that Qmax and Qave are only reliable if the VV is >150 ml, in a study of 1 271 men Reynard et al.[16] found that low-volume uroflowmetry can provide useful diagnostic information and the data from such voids should therefore not be discarded. In their study, those voiding <150 ml had a 72% likelihood of bladder outlet obstruction, while in those voiding >150 ml the likelihood was 56%.[16] Comparing the groups with VV >150 ml v. <150 ml in the current study, there were significant correlations between the total VPSS and total IPSS and between the VPSS and IPSS questions related to the force of the stream and QoL (Table 4). In the group with VV >150 ml there were significant correlations between Qmax and the IPSS and VPSS questions on the force of the urinary stream and QoL. In the group with VV <150 ml there were even stronger correlations between Qmax and the IPSS and VPSS questions on the force of the stream and QoL. The same was true for correlations of Qave with the IPSS and VPSS questions about the force of the urinary stream and QoL (Table 4).

Conclusion

The VPSS takes significantly less time to complete than the IPSS, especially in men with limited schooling. The VPSS correlates significantly with the IPSS with regard to total score, the questions about the force of the urinary stream, and overall QoL. Since the VPSS pictograms correlate significantly with the corresponding IPSS questions and Qmax and Qave, they can be used as single-item questions to rapidly assess the degree of bladder outflow obstruction in men who are illiterate or have limited education.

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Source of funding. South African Urological Association. References 1. Griffith JW. Self-report measurement of lower urinary tract symptoms: A commentary on the literature since 2011. Curr Urol Rep 2012;13(6):420-426. [http://dx.doi.org/10.1007/s11934-012-0286-5] 2. Cam K. BPH: How useful is a visual prostate symptom score for patients? Nat Rev Urol 2011;8(10):536537. [http://dx.doi.org/10.1038/nrurol.2011.137] 3. Cam K, Senel F, Akman Y, Erol A. The efficacy of an abbreviated model of the International Prostate Symptom Score in evaluating benign prostatic hyperplasia. BJU Int 2003;91(3):186-189. [http://dx.doi. org/10.1046/j.1464-410X.2003.04055.x] 4. Oztürk MÎ, Koca O, Keleş MO, Güneş M, Kaya C, Karaman MÎ. International prostate symptom score: Really appreciated by all patients or not? Urol J 2011;8(3):227-230. 5. Ogwuche EI, Dakum NK, Amu CO, Dung ED, Udeh E, Ramyil VM. Problems with administration of international prostate symptom score in a developing community. Ann Afr Med 2013;12(3):171-173. [http://dx.doi.org/10.4103/1596-3519.117628] 6. Kim JH, Doo SW, Yang WJ, Song YS. Homogeneity among the Korean international prostate symptom score questionnaires used in real practice. Korean J Urol 2013;54(4):249-251. [http://dx.doi. org/10.4111/kju.2013.54.4.249] 7. Fujimura T, Kume H, Nishimatsu H, et al. Assessment of lower urinary tract symptoms in men by international prostate symptom score and core lower urinary tract symptom score. BJU Int 2012;109(10):1512-1516. [http://dx.doi.org/10.1111/j.1464-410X.2011.10445.x] 8. Coyne KS, Barsdorf AI, Thompson C, et al. Moving towards a comprehensive assessment of lower urinary tract symptoms (LUTS). Neurourol Urodyn 2012;31(4):448-454. [http://dx.doi.org/10.1002/ nau.21202] 9. O’Leary MP, Wei JT, Roehrborn CG, Miner M; BPH Registry and Patient Survey Steering Committee. Correlation of the International Prostate Symptom Score bother question with the Benign Prostatic Hyperplasia Impact Index in a clinical practice setting. BJU Int 2008;101(12):1531-1535. [http:// dx.doi.org/10.1111/j.1464-410X.2008.07574.x] 10. Viktrup L, Hayes RP, Wang P, Shen W. Construct validation of patient global impression of severity (PGI-S) and improvement (PGI-I) questionnaires in the treatment of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. BMC Urol 2012;12(1):30. [http://dx.doi. org/10.1186/1471-2490-12-30] 11. Van der Walt CL, Heyns CF, Groeneveld AE, Edlin RS, van Vuuren SP. Prospective comparison of a new visual prostate symptom score versus the international prostate symptom score in men with lower urinary tract symptoms. Urology 2011;78(1):17-20. [http://dx.doi.org/10.1016/j. urology.2011.01.065] 12. Heyns CF, Van der Walt CL, Groeneveld AE. Correlation between a new visual prostate symptom score (VPSS) and uroflowmetry parameters in men with lower urinary tract symptoms. S Afr Med J 2012;102(4):237-240. 13. Wessels SG, Heyns CF. Prospective evaluation of a new visual prostate symptom score, the international prostate symptom score, and uroflowmetry in men with urethral stricture disease. Urology 2014;83(1):220-224. [http://dx.doi.org/10.1016/j.urology.2013.08.058] 14. Peeling WB. Diagnostic assessment of benign prostatic hyperplasia. Prostate Suppl 1989;2:51-68. 15. Ushijima S, Ukimura O, Okihara K, Mizutani Y, Kawauchi A, Miki T. Visual analog scale questionnaire to assess quality of life specific to each symptom of the International Prostate Symptom Score. J Urol 2006;176(2):665-671. [http://dx.doi.org/10.1016/j.juro.2006.03.031] 16. Reynard JM, Yang Q, Donovan JL, et al. The ICS-‘BPH’ Study: Uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. Br J Urol 1998;82(5):619-623. [http://dx.doi.org/10.1046/ j.1464-410X.1998.00813.x]

Accepted 18 February 2014.

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Prevalence of oral and oropharyngeal human papillomavirus in a sample of South African men: A pilot study C L Davidson,1 BChD; K L Richter,2 MMed (Path) (Virology); M van der Linde,3 PhD; J Coetsee,3 MCom (Statistics); S C Boy,1 PhD Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, South Africa Department of Medical Virology, School of Medicine, Faculty of Health Sciences, University of Pretoria, and National Health Laboratory Service, Tshwane Academic Division, Pretoria, South Africa 3 Department of Statistics, Faculty of Natural and Agricultural Sciences, University of Pretoria, South Africa 1 2

Corresponding author: C L Davidson (christy.davidson@up.ac.za) Background. Human papillomavirus (HPV) infection is well known to be associated with head and neck cancers (HNCs). HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners, but the epidemiology of oral and oropharyngeal HPV in South African men has not yet been studied. Objectives. To determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa (SA). Methods. Male factory workers were recruited. Oral rinse and gargle samples were tested for 37 HPV types using the Linear Array HPV Genotyping Test (Roche Molecular Systems). A questionnaire was used to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional. Results. The HPV prevalence was 5.6% among men (N=125) aged 17 - 64 years. High-risk HPV (hrHPV) types 16 and 68 were found in two men. Oral sex seemed to be an uncommon practice in the majority of respondents, but the two respondents with hrHPV did practise oral sex. There was a statistically significant association between HPV infection and an increased number of sexual partners (p=0.027), but not between HPV and substance use, HIV status or clinical mucosal pathology. Conclusion. The prevalence of oral and oropharyngeal HPV was lower than reported in other countries. An association between oral HPV and having multiple sexual partners was found. A larger nationwide study would give a more representative view of the burden of oral and oropharyngeal HPV infection in SA. S Afr Med J 2014;104(5):358-361. DOI:10.7196/SAMJ.7542

Oropharyngeal squamous cell carcinoma (OSCC) may originate in the soft palate, tongue base, pharyngeal walls or tonsils. The association of high-risk human papillomavirus (hrHPV) types with increased risk for a subset of OSCC has been established by many studies.[1-5] It has been shown that oral human papillomavirus (HPV) infection, and specifically HPV type 16 infection, causes an up to 50-fold increase in HPV-positive OSCC.[6] The pathogenic association of OSCC with HPV was therefore recently accepted by the International Agency for Research on Cancer.[7] Head and neck cancer (HNC), of which OSCC is a subset, is the sixth most common cancer in the world. In South Africa (SA) there has been a proven increase in OSCC since 1995, and 90% of these cancers were associated with HPV 16.[8] Males were affected more frequently than females.[8] Gillison et al.[9] recently published the first population-based study that concurrently examined the epidemiology of oral HPV infection among males and females and showed an almost three-fold higher HPV prevalence in males; the HPV 16 prevalence was five-fold higher in males than in females. The aims of this pilot study were to determine the oral and oropharyngeal HPV strain prevalence in a selected male population in Pretoria, SA, as well as the association of HPV with sexual practices and substance use.

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Methods

Participant selection

Male participants were voluntarily recruited from an industrial factory in Pretoria in 2012. Written informed consent was obtained from each participant for HPV testing and answering the questionnaire. Separate consent was obtained for voluntary HIV testing. Refusal of HIV testing did not serve as a criterion for exclusion from the study, but refusal of HPV testing did. Approval for the study was obtained from the Ethics Committee of the Faculty of Health Sciences, University of Pretoria (no. 101/2012).

Clinical examination and saliva sample collection

Participants underwent a thorough oral and oropharyngeal clinical examination by a senior dentist/oral pathologist. All dental and other soft-tissue abnormalities were noted and photographed. Oral rinse samples were collected by means of a 20-second oral rinse and gargle with 5 ml phosphate-buffered saline (PBS) (Sigma Life Sciences, USA) given to the patient in a 40 ml sterile collection cup (Lasec, SA). Participants alternately swished and gargled and then expectorated the saliva into the cup. All samples were numbered consecutively and stored on ice until sample preparation.

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Questionnaire

The questionnaire comprised specifically formulated questions pertaining to past and present sexual histories, substance and alcohol use and any medical conditions. The numbers of the questionnaires corresponded with the oral rinse samples, and their content was treated as confidential.

Voluntary HIV counselling and testing

Participants who opted for HIV testing received pre-test counselling from the occupational health practitioner (OHP) of the company. A rapid point-of-care HIV screening test (U test HIV/AIDS, Humor Diagnostica, SA) that detects HIV-1 and HIV-2 antibodies was then performed according to the manufacturer’s instructions. Confirmatory follow-up testing and continued care were conducted by the same OHP.

Molecular laboratory techniques

Specimen preparation Saliva samples were prepared for HPV genotyping within 24 hours of collection. The samples were washed three times with sterile PBS and the cell pellets were stored at -70°C until subsequent DNA extraction. DNA extraction DNA extraction from the cell pellets was performed using the DNA Isolation Kit (Roche Molecular Systems, USA) on the MagNA Pure automated extraction system. HPV DNA amplification and genotyping HPV DNA amplification and genotyping was done using the Linear Array HPV Genotyping Test (Roche Molecular Systems). The pool of primers in the kit are designed to amplify HPV DNA from 15 high-risk genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82), 3 probable high-risk genotypes (26, 53 and 66) and 19 low/undetermined risk types (6, 11, 40, 42, 54, 55, 61, 62, 64, 67, 69, 70, 71, 72, 81, 83, 84, IS39 and CP6108).[10] The β-globin gene was amplified concurrently for each sample and served as internal control for cellular adequacy, extraction efficiency and amplification.

Statistical analysis

The relationship between the prevalence of HPV and the prevalence of the variables substance use, alcohol use, sexual history, HIV and oral lesions was investigated using the chi-square test for independence or, where appropriate, Fisher’s exact test. The Kruskal-Wallis test was used to analyse whether or not any of the variables

Table 1. Summary of human papillomavirus status and results for the variables investigated in all the participants HPV+ (N=7) n (%)

HPV- (N=118) n (%)

Total (N=125) n (%)

Age (years)

p-value† 1.000

≤40

2 (28.6)

36 (30.5)

38 (30.4)

>40

5 (71.4)

82 (69.5)

87 (69.6)

Yes

4 (57.1)

54 (45.8)

58 (46.4)

3 (42.9)

64 (54.2)

67 (53.6)

Smoking

0.703

Alcohol

0.343

Yes

7 (100.0)

93 (78.8)

100 (80.0)

25 (21.2)

25 (20.0)

Lifetime sexual partners

0.027

0-5

1 (14.3)

19/117* (16.2)

20/124 (16.1)

5 - 20

2 (28.6)

79/117* (67.5)

81/124 (65.3)

>20

4 (57.1)

19/117* (16.2)

23/124 (18.5)

Sexual partners in the past 6 months

1.000

None

0 (0)

3/117 (2.6)

3/124 (2.4)

1-3

7 (100)

104/117 (88.9)

111/124 (89.5)

0 (0)

10/117 (8.5)

10/124 (8.1)

Yes

3 (42.9)

48 (40.7)

51 (40.8)

4 (57.1)

70 (59.3)

74 (59.2)

Practise oral sex

0.525

Lifetime oral sex partners

0.592

19/48 (39.6)

19/51 (37.3)

1/3 (33.3)

16/48 (33.3)

17/51 (33.3)

2/3 (66.7)

17/48 (35.4)

19/51 (37.3)

Oral sex partners in the past 6 months

0.518

None

4 (57.1)

83 (70.3)

87 (69.6)

2 (28.6)

26 (22.0)

28 (22.4)

1 (14.3)

9 (7.6)

10 (8.0)

Positive

5 (4.2)

5 (4.0)

Negative

4 (57.1)

81 (68.6)

85 (68.0)

Declined testing

3 (42.9)

32 (27.1)

35 (28.0)

HIV

0.563

Clinical lesions

0.592

With

18 (15.3)

18 (14.4)

Without

7 (100.0)

100 (84.7)

107 (85.6)

HPV+ = HPV-positive; HPV- = HPV-negative. *One questionnaire was not completed. † Fisher’s exact test.

investigated had any significant influence on the HPV status of the participants.

Results

Oral rinse specimens were collected from 128 males between the ages of 17 and 64 years

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(median 50). The participants originated from all over SA. Three participants who did not complete questionnaires were excluded from the study. Only 7/125 participants (5.6%) tested positive for HPV. One participant was co-infected with HPV types 71 and 72. Two

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Table 2. Summary of human papillomavirus-positive results for all the variables investigated HPV type/s

Age (years)

Smoking

Alcohol

Sex

Oral sex

HIV status

Oral lesions

16 (hr)

Yes

Yes (m)

Yes

Declined testing

Yes

Yes (m)

Declined testing

Yes

Yes (m)

Negative

68 (hr)

Yes

Negative

Yes

Yes (m)

Declined testing

71, 72

Yes

Yes (m)

Negative

Yes

Yes (m)

Yes

Negative

HPV = human papillomavirus; hr = high-risk HPV type; m = multiple sexual partners.

participants tested positive for hrHPV types, namely HPV 16 and HPV 68, respectively. Table 1 summarises the findings for all the variables investigated. The quantity and frequency of the different substances used were not investigated. An overall score was calculated, which only reflected whether a respondent used or did not use any of the substances listed in the questionnaire. All participants were sexually active, 90/125 (72.0%) of them reporting having had their first sexual encounter between 15 and 20 years of age. The association between HPV and the number of sexual partners was statistically significant (p=0.027). In the subgroup of 90 men (72.0%) who volunteered for HIV testing, only five (5.5%) tested positive. Unfortunately only 4/7 HPVpositive participants (57.1%) opted for HIV testing; one of these was found to have an hrHPV type. All the HPV-positive participants who tested for HIV were negative. Only 18 of the 125 participants (14.4%) were found to have oral mucosal lesions on clinical examination. The lesions encountered included white lesions, red lesions, ulcerative lesions and Candida albicans infection. None of the HPV-positive participants had clinically visible mucosal pathology. Table 2 summarises the findings for the variables investigated in the HPV-positive participants.

Discussion

The natural history of oral and oropharyngeal HPV infection in men is unknown. A recent study found the prevalence of oral HPV in men in the USA to be around 10%.[9] This pilot study among a group of SA men had an unexpectedly low HPV prevalence of only 5.6%. This could be attributed to the small sample size, or to the observation that oral sex did not seem to be a common practice among the group of men studied. A much larger nation-wide analysis with interinstitutional collaboration will be necessary to confirm whether this figure is in fact truly representative of oral and oropharyngeal HPV in SA men. Known risk factors for oral and oropharyngeal HPV infection currently include lifetime number of sexual partners,[6,9,11] number of oral sex partners,[1,12] substance use[9,12-14] and infection with HIV.[15-18] Sexual contact, either genital or oral, remains the primary mode of HPV transmission, and it is well documented that having multiple partners increases the prevalence of oral and genital HPV.[6,9,19,20] A study in KwaZulu-Natal, SA, reported male undergraduate students to have had a median of four sexual partners in the previous year.[11] In many African cultures it is acceptable for men to have multiple partners and engage in sex outside the primary relationship.[21,22] A statistically significant association between the number of sexual partners and the presence of oral HPV was seen in this study (p=0.027), with 4/7 HPV-positive participants having had >20 sexual

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partners and 2/7 having had between five and 20 partners. The numbers of sexual partners of the HPV-positive participants in the past 6 months ranged from one to three. Tobacco use is an accepted cause of HNCs, but it is not considered a strong risk factor for HPV-associated oropharyngeal cancers.[1,6] We found no statistically significant association between smoking and the presence of HPV (p=0.703), although the only participant with HPV 16 in our study was a current cigarette smoker. An increased oral HPV prevalence has been shown to be associated with current and previous smoking, but the exact pathogenic mechanisms are unknown.[12,13] Alcohol has the ability to modify mucosal tissue, allowing easier entry of the virus, and is also known to modify the host immune response, thereby increasing susceptibility to HPV infection.[14,23] In our study we found no statistical association between alcohol use and HPV (p=0.343), although all the HPV-positive participants were current alcohol users. The HIV pandemic and attempts to prevent spread of the virus have increasingly highlighted sexual practices other than penetrative sex. Oral sex has increased to a marked extent, especially among teenagers, as a result of the false perception that sexually transmitted diseases such as HIV infection cannot be passed on in this manner.[12,24] Studies on oral sex practices in the USA have shown that 19.6 - 78% of young adults had engaged in oral sex in their lifetime.[25] Gillison et al.,[9] in line with other studies, found oral sex performed on women to be one possible explanation for the increased prevalence of oropharyngeal HPV in males, who in their study on average had more partners than the females. Sexual behaviour studies in SA are few, and those that do exist are not specific in their data regarding genital versus oral sexual practices and the gender differences that exist. However, it was later discovered through the male fieldworker that most men in our study interpreted oral sex to mean contact of the female’s oral mucosa with the man’s genital mucosa rather than the other way around. This could explain the low prevalence of oral HPV. Only 51 of all participants (40.8%) and 3/7 HPV-positive participants (42.9%) answered ‘yes’ to the question whether they had practised oral sex. Considering the participants’ understanding of the definition of oral sex, one should be cautious in interpreting these figures. Of note was that both the individuals with hrHPV types said that they had had oral sex with more than one partner. Oral HPV infection is considered to be bimodal in age distribution, with a high prevalence in younger men (30 - 34 years of age) and in later years (60 - 64).[9] The participants who were HPV-positive in this study were between 29 and 64 years of age, and those with hrHPV were between 50 and 60 years of age. It has been speculated that the higher HPV prevalence at older ages could be due to increased duration of infections at older ages, rather than an increased

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acquisition of new HPV infections.[26] In our study, however, all the participants who were positive for HPV had had between one and three sexual partners in the past 6 months, suggesting that their HPV infections could have been newly acquired. HIV-infected individuals have been reported to have an up to six-fold increased risk for HPV-related OSCC.[27] It is thought that HIV and HPV function as a combined risk factor, as HIV-positive individuals have more frequent HPV infections, but the natural history of these infections may be altered when they co-exist.[15] In SA, the total estimated number of adults aged 15 - 49 years living with HIV in 2013 was 5.26 million, giving an HIV prevalence of 10%.[28] The HIV prevalence in this study was only 5.5%. Only four of the HPV-positive participants (n=7) volunteered to test for HIV, and all were negative. One of the participants who was found to have hrHPV 16, which is associated with OSCC, declined HIV testing. A much larger nationwide study with an HIV prevalence more representative of that for the country as a whole will be needed to determine the role of HIV infection in the natural history of oral and oropharyngeal HPV infection. The 18 participants who presented with oral mucosal lesions were all negative for HPV. All patients with dental or mucosal pathology were referred to peripheral dental clinics or the Oral Medicine Clinic of the Oral and Dental Hospital, Pretoria, for surgical biopsies and clinical follow-up.

Study strength

Ours is the first study of this nature to investigate the oral and oropharyngeal HPV prevalence in SA men. Although the sample size was small, we did find a statistical association between HPV and the number of lifetime sexual partners.

Study limitations

The greatest limitation of this study is the small sample size, which was restricted owing to funding. Another limitation is the fact that not all the participants opted to test for HIV, which may also have an influence on the conclusions. Because this was a pilot study some of the conclusions made, including the role of HIV, will need to be verified by a larger, nationwide study.

Conclusion

In contrast to the prevalence of genital HPV in SA females and the role of the virus in the pathogenesis of cervical carcinoma, little is known about the prevalence of HPV in the oropharyngeal mucosa of SA men, who are known to acquire HPV-related OSCC more frequently than women. The prevalence of oral and oropharyngeal HPV in this study is lower than reported in other countries. Even though the number of participants was low, a statistically significant association was shown between oral and oropharyngeal HPV and having multiple sexual partners. Oral sex, although not practised by the majority of participants, was practised by those identified with hrHPV types. The high number of deaths from HPV-related cervical carcinoma and the increase in HPV-related OSCC, especially in males, makes it urgently necessary to investigate the prevalence of oral and oropharyngeal HPV in the larger SA population. Specific reference to the roles of sexual practices and HIV in the natural history of HPV is essential. Deeper investigations into the nature of sexual practices among South Africans are needed, and the diversity of the SA population will have to be considered in any future study of this nature.

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Acknowledgements. We thank Dental Warehouse for the generous donation of the materials used for the oral rinse and gargle collection, the Dental Research Education and Development Trust of the South African Dental Association for funding, Professor A Ligthelm, Dean of the School of Dentistry, Faculty of Health Sciences, University of Pretoria, and Professor M Pepper, Director of the Institute for Cellular and Molecular Medicine at the University. We also thank Matron Ella Khumalo and Mr S Mafiri for their valuable assistance with the sampling and Sister Marina Jordaan for all her assistance with and organisation of the study. References 1. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007;356(19):1944-1956. [http://dx.doi.org/10.1056/NEJMoa065497] 2. Gillison M. Human papillomavirus-related diseases: Oropharynx cancers and potential implications for adolescent HPV vaccination. J Adolesc Health 2008;43(4 Suppl):S52-S60. [http://dx.doi.org/10.1016/j. jadohealth.2008.07.002] 3. Andrews E, Seaman WT, Webster-Cyriaque J. Oropharyngeal carcinoma in non-smokers and non-drinkers: A role for HPV. Oral Oncol 2009;45(6):486-491. [http://dx.doi.org/10.1016/j.oraloncology.2008.07.008] 4. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: A systematic review. Cancer Epidemiol Biomarkers Prev 2005;14(2):467-475. [http:// dx.doi.org/10.1158/1055-9965.EPI-04-0551] 5. Pannone G, Santoro A, Papagerakis S, Lo Muzio L, De Rosa G, Bufo P. The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: An overview. Infect Agent Cancer 2011;6:4. [http:// dx.doi.org/10.1186/1750-9378-6-4] 6. Gillison ML, D’Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 2008;100(6):407-420. [http://dx.doi.org/10.1093/jnci/djn025] 7. International Agency for Research on Cancer. Human papillomaviruses: IARC monographs working group on the evaluation of carcinogenic risks to humans. 2007. http://www.monographs.iarc.fr/ENG/Monographs/ vol90 (accessed 22 August 2013). 8. WHO/ICO Information Centre on HPV and Cervical Cancer. Human papillomavirus and related cancers in South Africa. Summary report 2010. http://www.who.int/hpvcentre (accessed 22 August 2013). 9. Gillison ML, Broutian T, Pickard RKL, et al. Prevalence of oral HPV infection in the United States, 2009-2010. JAMA 2012;307(7):693-703. [http://dx.doi.org/10.1001/jama.2012.101] 10. Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348(6):518-527. [http://dx.doi.org/10.1056/NEJMoa021641] 11. Hoque ME. Sexual practices among male undergraduate students in KwaZulu-Natal, South Africa. Southern African Journal of Epidemiology and Infection 2011;26(3):157-160. [http://dx.doi.org/10.4102/phcfm. v3i1.281] 12. D’Souza G, Agrawal Y, Halpern J, Bodison S, Gillison ML. Oral sexual behaviours associated with prevalent oral human papillomavirus infection. J Infect Dis 2009;199(9):1263-1269. [http://dx.doi.org/10.1086/597755] 13. Kreimer AR, Villa A, Nyitray AG, et al. The epidemiology of oral HPV infection among a multinational sample of healthy men. Cancer Epidemiol Biomarkers Prev 2011;20(1):172-182. [http://dx.doi.org/10.1158/10559965.EPI-10-0682] 14. Smith EM, Ritchie JM, Summersgill KF, et al. Human papillomavirus in oral exfoliated cells and risk of head and neck cancer. J Natl Cancer Inst 2004;96(6):449-455. [http://dx.doi.org/10.1093/jnci/djh233] 15. Steinau M, Reddy D, Sumbry A, et al. Oral sampling and human papillomavirus genotyping in HIV-infected patients. J Oral Pathol Med 2012;41(4):288-291. [http://dx.doi.org/10.1111/j.1600-0714.2011.01093.x] 16. Beachler DC, Weber KM, Margolick JB, et al. Risk factors for oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiol Biomarkers Prev 2012;21(1):122-133. [http://dx.doi.org/10.1158/1055-9965.EPI-11-0734] 17. Marais D, Passmore J-AS, Denny L, Sampson C, Allan B, Williamson A-L. Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa. J Med Virol 2008;80(6):953-959. [http://dx.doi.org/10.1002/jmv.21166] 18. Fakhry C, D’Souza G, Sugar E, et al. Relationship between prevalent oral and cervical human papillomavirus infections in human immunodeficiency virus-positive and -negative women. J Clin Microbiol 2006;44(12):4479-4485. [http://dx.doi.org/10.1128/JCM.01321-06] 19. Schwartz S, Daling J, Doody D, et al. Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection. J Natl Cancer Inst 1998;90(21):1626-1636. [http://dx.doi.org/10.1093/ jnci/90.21.1626] 20. Hernandez BY, Wilkens LR, Zhu X, et al. Transmission of human papillomavirus in heterosexual couples. Emerg Infect Dis 2008;14(6):888-894. [http://dx.doi.org/10.3210/eid1406.0706162] 21. Ackermann L, Klerk G. Social factors that make South African women vulnerable to HIV infection. Health Care Women Int 2002;23(2):163-172. [http://dx.doi.org/10.1080/073993302753429031] 22. Jewkes R, Morrell R. Gender and sexuality: Emerging perspectives from the heterosexual epidemic in South Africa and implications for HIV risk and prevention. J Int AIDS Soc 2010;13(6):1-11. [http://dx.doi. org/10.1186/1758-2652-13-6] 23. Molina P, McClain C, Valla D, Guidot D, Diehl A, Lang C. Molecular pathology and clinical aspects of alcoholinduced tissue injury. Alcohol Clin Exp Res 2002;26(1):120-128. [http://dx.doi.org/10.1111/j.1530-0277.2002. tb02440.x] 24. Cherie A, Berhane Y. Oral and anal sex practices among high school youth in Addis Ababa, Ethiopia. BMC Public Health 2012;12:5. [http://dx.doi.org/10.1186/1471-2458-12-5] 25. Ompad DC, Strathdee SA, Celentano DD, et al. Predictors of early initiation of vaginal and oral sex among urban young adults in Baltimore, Maryland. Arch Sex Behav 2006;35(1):53-65. [http://dx.doi.org/10.1007/ s10508-006-8994-x] 26. Kreimer AR, Pierce Campbell CM, Lin HY, et al. Incidence and clearance of oral human papillomavirus infection in men: The HIM cohort study. Lancet 2013;382(9895):877-887. [http://dx.doi.org/10.1016/S01406736(13)60809-0] 27. Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 2008;123(1):187-194. [http://dx.doi.org/10.1002/ijc.23487] 28. Statistics South Africa. Mid-year population estimates 2013. http://www.statssa.gov.za/publications/P0302/ P03022013.pdf (accessed 22 August 2013).

Accepted 22 November 2013.

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Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa J V Ershova,1,2 PhD, MS, MPH; L J Podewils,1 MS, PhD; L E Bronner,1 MPH; H G Stockwell,2 ScD; S Dlamini,3 MPH, MA; L D Mametja,3 MPH Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA College of Public Health, University of South Florida, Tampa, Florida, USA 3 Tuberculosis Control and Management, National Department of Health, Pretoria, South Africa 1 2

Corresponding author: J V Ershova (jhe3@cdc.gov) Background. Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. Objectives. To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. Methods. We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. Results. Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). Conclusion. Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes. S Afr Med J 2014;104(5):362-368. DOI:10.7196/SAMJ.7655

According to the World Health Organization (WHO), South Africa (SA) was one of five countries with the highest TB incidence in 2011, estimated at 500 000 new TB cases and approximately 25 000 deaths.[1] In 2009 the South African National Tuberculosis Programme (NTP) released new national tuberculosis management guidelines for healthcare personnel and managers.[2] The guidelines include treatment strategies suggested by the WHO and recommend that all patients receive directly observed therapy (DOT) for the entire treatment course. However, despite NTP efforts to improve access to treatment and treatment adherence among TB patients, the proportion with successful treatment outcomes remains low (79% v. target of 86% cured or completed treatment) and mortality rates remain high (49/100 000).[1] Patients in whom treatment fails or who do not complete treatment are at risk for acquisition of drug-resistant TB, additional morbidity, and mortality. A patientâ&#x20AC;&#x2122;s ability to adhere to TB treatment is a complex, dynamic phenomenon with a wide range of factors impacting on treatmenttaking behaviour. Non-adherence to assigned treatment has been cited as the major barrier to TB control worldwide.[3-8] Although DOT has been well documented to improve patient adherence to TB treatment and optimise treatment outcomes,[4-6] studies have reported that DOT coverage remains low in many parts of the world, including SA.[3-6] A study conducted in the North West Province of SA found that the proportion of TB patients receiving DOT was as low as 56.8%, with coverage lowest among TB retreatment patients,[5]

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while another in KwaZulu-Natal reported that only 43 of 70 priority facilities (61%) had a DOT programme.[6] Furthermore, although countries have implemented the WHOrecommended directly observed, short-course (DOTS) strategy[7] that includes DOT along with four other components, individual healthcare workers (HCWs) may not be aware of or fully informed about the strategy, may not be willing to implement it, or may not have the resources to implement it. Studies have reported that not all HCWs have been exposed to the national TB treatment guidelines, and many are not prescribing recommended regimens.[8-10] A 2012 systematic review that included 31 studies from 14 countries cited wide variation in HCW knowledge of treatment regimens (8 - 100%) and treatment duration (5 - 99%).[11] According to another recent review, inappropriate treatment regimens were often prescribed to patients (in 67% of 37 studies included in the review), with the proportion of patients on inappropriate treatment regimens ranging between 0.4% and 100%.[12] In SA, while several studies evaluating DOT have been conducted,[5-6] the effect on treatment outcomes of failing to adhere to guidelines for standard treatment regimens and DOT has not been investigated previously. Knowledge of the impact of non-adherence to standard regimens and DOT on treatment outcomes will allow programmes and clinicians to recognise practices essential to treat and manage patients with TB effectively. We aimed to describe treatment management practices in three SA provinces, including assignment of treatment regimen and DOT

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coverage for TB patients; evaluate treatment regimen practices and DOT coverage in the context of national TB treatment guidelines; and assess the impact of failing to adhere to standard treatment regimens and DOT on TB treatment outcomes.

Methods

We conducted a secondary analysis of data collected as part of a parent project aimed at evaluating the TB surveillance and electronic tuberculosis registry (ETR) in SA.[13] The parent project included 1 339 patients diagnosed with TB in the first quarter of 2009 in Gauteng, KwaZulu-Natal and Mpumalanga provinces. Information on key TB variables was abstracted onto standardised forms from multiple data sources, including the patient treatment card, the paper TB register at the health facility, and the ETR[14] at the sub-district (initial), district, provincial and national levels. Owing to missing information in the ETR at these district, provincial and national levels, the current analysis was restricted to the three initial data sources: patient treatment card, TB register and initial ETR. We used the following decision rules to resolve discrepant information from the multiple data sources: (i) if there was information in all 3 data sources, we accepted the variable value reflected in 2 of 3 sources; (ii) if 3 or 2 data sources had a value available but all had different values, the value in the TB register was used; and (iii) if only 1 data source had information available, we took the value from this source. Our analysis included all TB patients in the parent project for whom information was available on TB treatment regimen, DOT coverage, and treatment outcome in at least one data source. All cases with missing information on TB treatment regimen, DOT coverage or treatment outcome and those who moved or transferred out during the current treatment episode were excluded. Treatment regimens were categorised as appropriate or inappropriate based on national guidelines.[2] The guidelines include WHO-recommended treatment strategies for new patients (regimen 1), retreatment patients (regimen 2) and children (regimen 3).[2] Adults and children aged 8 years and older with no history of a previous TB episode who were prescribed standard therapy (regimen 1) were considered to be on appropriate therapy; all other regimens for these patients were classified as inappropriate. Regimen 2 was considered appropriate for retreatment patients, and regimen 3 was considered to be appropriate for children younger than 8 years of age; other regimens prescribed for these patient

groups were considered inappropriate. DOT adherence was categorised as full for those who received DOT during the entire course of TB treatment (100% of doses through DOT), partial for patients receiving DOT during either the intensive or the continuation phase, and no DOT for patients who were not provided any DOT during treatment. Death, treatment failure and default were considered poor TB treatment outcomes; cure and treatment completion were considered successful outcomes. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to measure the effect of adherence to standard treatment regimens and DOT on treatment outcomes. Univariate associations were further examined to identify potential confounders and effect modifiers. A multivariate log-binomial regression model was developed to identify independent predictors of poor treatment outcome among TB patients. Variables with an established biological plausibility based on previous research or that were significant based on a cut-off of p≤0.05 were retained in the final model.

Ethical considerations

Since data collection was a part of routine TB control efforts, individual patient consent or parental assent was not required. All data were safeguarded to protect patient confidentiality and no individual patient identifiers were retained in the study database. Participation of the US Centers for Disease Control and Prevention (CDC) and the South African National Department of Health in this project did not meet the definition of engagement in research on human subjects because the investigators did not interact with study subjects or have access to patient identifiable data, so separate institutional review board approval was not required. A formal written waiver for the need for ethics approval was issued by the CDC/DTBE associate director of science.

Results

Of 1 339 patients in the parent project, 598 (44.7%) were excluded owing to missing information on final treatment outcome (n=130), DOT coverage (n=213) or both

Records collected in the database 1 339 (100%)

382 (28.5%) excluded – missing treatment outcome

Records with treatment outcome available 957 (71.5%)

213 (15.9%) excluded – missing DOT

Records with treatment outcome and DOT available 744 (55.6%)

3 (0.2%) excluded – missing treatment regimen

Records with treatment outcome, DOT and treatment regimen 741 (55.3%)

Fig. 1. Selection of patient population (DOT = directly observed therapy).

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Table 1. Sociodemographic and clinical characteristics of the patient population

Characteristics

All collected cases (N=1 339) n (%)

Analytic cohort (N=741) n (%)

Excluded cases (N=598) n (%)

Gender

p-value* 0.98

Male

720 (53.8)

399 (53.9)

321 (53.8)

Female

617 (46.2)

341 (46.1)

276 (46.2)

120 (9.0)

74 (10.0)

46 (7.7)

≥8

1 216 (91.0)

667 (90.0)

549 (92.3)

Mean

Urban

480 (35.9)

332 (44.8)

148 (24.8)

Rural

859 (64.1)

409 (55.2)

450 (75.3)

Positive

735 (75.0)

444 (72.6)

291 (79.1)

Negative

245 (25.0)

168 (27.4)

77 (20.9)

Age (years)

0.15

Population type

0.03 <0.0001

HIV status

0.02

Site of disease

0.1

Pulmonary

1 048 (81.4)

608 (82.8)

440 (79.4)

Extrapulmonary

240 (18.6)

126 (17.2)

114 (20.6)

New patient

1 071 (85.5)

635 (87.7)

436 (82.6)

Retreat after default

37 (2.9)

16 (2.2)

20 (3.8)

Other previously treated

145 (11.6)

73 (10.1)

72 (13.6)

Relapse

99 (7.9)

55 (7.6)

44 (8.3)

Retreat after failure

18 (1.4)

6 (0.8)

12 (2.3)

Other

28 (2.3)

12 (1.7)

16 (3.0)

Full DOT

465 (53.2)

443 (59.8)

22 (16.5)

Partial DOT

Patient category

0.03

DOT

N/A 384 (43.9)

274 (37.0)

110 (82.7)

Intensive phase only

364 (41.6)

256 (34.6)

108 (81.2)

Continuation phase only

20 (2.3)

18 (2.4)

2 (1.5)

25 (2.9)

24 (3.2)

1 (0.8)

1: 2RHEZ/4RH

1 006 (75.7)

571 (77.0)

435 (72.7)

2: 2RHZES/1RHEZ/5RHE

195 (14.7)

88 (11.9)

107 (17.9)

3: 2RHZ/4RH

125 (9.4)

79 (10.7)

46 (7.7)

4: INH chemoprophylaxis

2 (0.1)

2 (0.3)

0 (0)

5: Other chemoprophylaxis

1 (0.1)

0 (0)

No DOT Treatment regimen

N/A

Inappropriate treatment

N/A

Yes

53 (4.0)

35 (4.7)

18 (3.0)

1 207 (90.6)

697 (94.1)

516 (86.3)

Unknown

79 (5.4)

9(1.2)

64 (10.7)

Treatment outcome

N/A

Favourable

771 (59.4)

617 (83.3)

154 (27.7)

Cured

388 (29.9)

329 (44.4)

59 (10.6)

Treatment completed

383 (29.5)

288 (38.9)

95 (17.1)

Continued...

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Table 1 (continued). Sociodemographic and clinical characteristics of the patient population

Characteristics Poor

All collected cases (N=1Â 339) n (%)

Analytic cohort (N=741) n (%)

Excluded cases (N=598) n (%)

186 (14.4)

124 (16.7)

62 (11.2)

Treatment defaulted

111 (8.6)

66 (8.9)

45 (8.1)

Treatment failure

8 (0.6)

6 (0.8)

2 (0.4)

Died

67 (5.2)

52 (7.0)

15 (2.7)

Transferred out

111 (8.6)

0 (0)

111 (20.0)

Moved out

228 (17.6)

0 (0)

228 (41.1)

p-value*

DOT = directly observed therapy; R = rifampicin; H = isoniazid; E = ethambutol; Z = pyrazinamide; S = streptomycin; 2RHEZ /4RH = the intensive phase is 2RHEZ, 2 months in total, treatment with rifampicin, isoniazid, ethambutol and pyrazinamide in fixed-dose combinations given 7 days a week; the continuation phase is 4RH, 4 months, treatment with rifampicin and isoniazid in fixed-dose combinations given 7 days a week; 2RHZES /1RHEZ /5RHE = the intensive phase is 2RHZES/1RHEZ, 3 months in total â&#x20AC;&#x201C; for the first 2 months rifampicin, isoniazid, ethambutol and pyrazinamide in fixed-dose combinations and streptomycin injections given 7 days a week, in the 3rd month only rifampicin, isoniazid, ethambutol and pyrazinamide in fixed-dose combinations given 7 days a week; the continuation phase is 5RHE, 5 months, treatment with rifampicin, isoniazid and ethambutol in fixed-dose combinations given 7 days a week; 2RHZ /4RH = the intensive phase is 2RHZ, treatment with rifampicin, isoniazid and pyrazinamide in fixed-dose combinations given 7 days a week for 2 months; the continuation phase is 4RH, 4 months, treatment with rifampicin and isoniazid in fixed-dose combinations given 7 days a week; wINH chemoprophylaxis = prophylactic treatment with isoniazid; N/A = not applicable. *Comparison of analytic cohort and excluded cases.

Table 2. Distribution of TB management practices and treatment outcomes by patient and population type (N=741)* New patients (N=635) n (%)

Retreated patients (N=89) n (%)

Rural (N=332) n (%)

Urban (N=409) n (%)

Yes

24 (3.8)

8 (9.0)

17 (5.2)

18 (4.5)

611 (96.2)

81 (91.0)

311 (94.8)

386 (95.5)

Full DOT

384 (60.5)

51 (57.3)

205 (61.7)

238 (58.2)

Partial DOT

230 (36.2)

36 (40.5)

125 (37.7)

149 (36.4)

No DOT

21 (3.3)

2 (2.3)

2 (0.6)

22 (5.4)

Cured

283 (44.6)

40 (44.9)

139 (41.9)

190 (46.4)

Treatment completed

250 (39.4)

28 (31.5)

129 (38.9)

159 (38.9)

Treatment defaulted

52 (8.2)

13 (14.6)

45 (13.6)

21 (5.1)

Treatment failure

4 (0.6)

2 (2.3)

2 (0.6)

4 (1.0)

Died

46 (7.2)

6 (6.7)

17 (5.1)

35 (8.6)

Characteristics Inappropriate treatment

DOT

Treatment outcome

DOT = directly observed therapy. *Missing information: of 741 patients, 17 had missing information on previous treatment and 9 had missing information on appropriateness of treatment.

(n=252), or treatment regimen (n=3) (Fig. 1). Compared with the patients with complete data (analytic cohort, n=741), patients with a missing outcome had a different distribution of DOT categories: a lower proportion of full DOT but a higher proportion of partial DOT (Table 1). Additionally, the 213 patients with missing DOT data had worse outcomes than the 741 patients in the analytic cohort. The analytic cohort included cases who were younger on average than excluded cases (mean age 33 v. 35â&#x20AC;&#x201A; years among excluded cases; p=0.03) and were less likely to be HIV-infected (72.6% v. 79.1%, p=0.02) and to live in rural settings (55.2% v. 75.3%; p<0.0001) (Table 1). There was no significant difference in gender distribution (approximately half were male: 53.9%; p=0.9) or site of disease (82.8% pulmonary v. 79.4% pulmonary disease; p=0.1). Most patients in the analytic cohort (635, 87.7%) were new cases, although 89 (12.3%) were previously treated, including 55 (7.6%) relapses and 22 (3.0%) retreated after failure or default. Seventeen patients had missing information on previous treatment. Approximately three-quarters of patients (571, 77.0%) received treatment regimen 1, 88 (11.9%) received regimen 2, and 79 (10.7%)

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received regimen 3. Thirty-five patients (4.8%), including 8 children (22.9%), were considered to have received an inappropriate regimen for TB treatment according to national guidelines. We were not able to assess appropriateness of treatment among 9 adult patients owing to missing information on patient category. Almost all patients (96.8%) received DOT during treatment: 443 (59.8%) received DOT during the entire treatment course, and 274 (37.0%) received DOT during either the intensive or continuation phase, including 256 (34.6%) receiving DOT during the intensive phase only (Table 1). Of the 635 new cases, 24 (3.8%) received inappropriate treatment regimens; 384 (60.5%) received DOT during the entire course of TB treatment, 230 (36.2%) received partial DOT during the intensive or continuation phase, and 21 (3.3%) did not receive DOT during treatment (Table 2). Among 89 retreated patients, 8 (9.0%) received inappropriate treatment regimens; 51 (57.3%) received DOT during the entire course of TB treatment, 36 (40.5%) received partial DOT, and 2 (2.3%) did not receive DOT during treatment (Table 2). Among the 741 patients, 124 (16.7%) had a poor treatment outcome, including 66 (8.9%) who defaulted, 6 (0.8%) in whom

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Table 3. Association between sociodemographic, clinical and treatment factors and poor treatment outcome (N=741)* Poor outcome (N=124) n (%)

Favourable outcome (N=617) n (%)

95% CI

p-value

Male

75 (18.8)

324 (81.2)

1.3

0.96 - 1.86

0.09

Female

48 (14.1)

293 (85.9)

Reference

0.37 - 1.33

0.2

0.95 - 1.81

0.09

0.98 - 2.44

0.06

0.90 - 1.10

0.9

Characteristics Gender

Age (years) <8

9 (12.2)

65 (87.8)

0.7

≥8

115 (17.2)

552 (82.8)

Reference

Rural

64 (19.3)

268 (80.7)

1.3

Urban

60 (14.7)

349 (85.3)

Reference

Positive

82 (18.5)

362 (81.5)

1.6

Negative

20 (11.9)

148 (88.1)

Reference

Population type

HIV status

Site of disease Pulmonary

102 (16.8)

506 (83.2)

Reference

Extrapulmonary

22 (17.5)

104 (82.5)

0.91

102 (16.1)

533 (83.9)

Reference

Patient category New patient Retreat after default

8 (50.0)

3.1

1.85 - 5.24

<0.0001

Other previously treated

13 (17.8)

60 (82.2)

1.1

0.66 - 1.87

0.7

0.37 - 1.93

0.7

Inappropriate treatment Yes

5 (14.3)

30 (85.7)

0.9

118 (16.9)

579 (82.1)

Reference

Full DOT

43 (9.7)

401 (90.3)

Reference

Partial DOT

78 (28.3)

198 (71.7)

2.9

2.06 - 4.10

<0.0001

76 (29.5)

182 (70.5)

3.1

2.16 - 4.28

<0.0001

DOT

Intensive phase only Continuation phase only No DOT

2 (11.1)

16 (88.9)

1.2

0.30 - 4.37

0.8

3 (12.5)

4 (87.5)

1.3

0.43 - 3.86

0.7

RR = risk ratio; CI = confidence interval; DOT = directly observed therapy. * Missing information: of 741 patients, 17 had missing information on previous treatment and 9 had missing information on appropriateness of treatment.

treatment failed, and 52 (7.0%) who died. Paradoxically, the proportion of patients with a poor outcome was lower among patients who received inappropriate treatment (5/35, 14.3%) compared with those on appropriate treatment (118/697, 17.0%). Patients receiving partial DOT during treatment and those who did not receive DOT had higher proportions of poor outcomes (78/256, 28.3% and 3/7, 12.5%, respectively) than patients who received DOT during the entire course of the treatment (43/444, 9.7%) (Table 3). In univariate analysis, predictors of poor treatment outcome were receiving partial DOT (RR 2.9, 95% CI 2.1 - 4.1; p<0.001) and having defaulted during a previous TB treatment episode (RR 3.1, 95% CI 1.9 - 5.2; p=0.001) (Table 3). Patients who received DOT during the intensive phase had an increased risk of a poor outcome compared with patients who received DOT during the entire course of treatment (RR 3.1, 95% CI 2.2 - 4.3; p<0.001). There was no significant association between inappropriate regimen and treatment outcome. Stratified analysis did not reveal any effect modification of these associations by sociodemographic, clinical or treatment practice indicators.

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In a multivariate regression model, having received DOT during only the intensive phase of treatment (adjusted risk ratio (aRR) 3.1, 95% CI 2.2 - 4.3) and a history of previous TB treatment default (aRR 2.3, 95% CI 1.1 - 4.8) were independently associated with a poor outcome after adjusting for age, gender, HIV status and population type (Table 4).

Discussion

This evaluation provides a detailed description of TB treatment management practices in three provinces of SA, including assignment of treatment regimen and DOT coverage, and their impact on treatment outcomes. Our findings demonstrate that incomplete DOT, specifically receiving DOT during the intensive phase only, is independently associated with poor treatment outcome. Our results are consistent with previous research and programme evaluation findings on TB management practices citing standardised DOT coverage as essential to TB control.[3-6] A study evaluating DOT in KwaZulu-Natal demonstrated that the facilities with high DOT coverage had significantly better cure rates than those with low DOT

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Table 4. Independent* predictors of poor treatment outcome in the population analysed (N=741) Poor outcome n (%)

Favourable outcome n (%)

aRR

Full DOT

43 (9.7)

400 (90.3)

Reference

Intensive phase DOT

76 (29.7)

180 (70.3)

Continuation phase DOT

2 (11.1)

16 (88.9)

No DOT

3 (12.5)

New patient

Characteristics

95% CI

p-value

3.1

2.16 - 4.27

<0.0001

1.2

0.31 - 4.44

0.8

4 (87.5)

1.4

0.48 - 4.15

0.5

102 (16.1)

533 (83.9)

Reference

Retreat after default

8 (50.0)

2.3

1.14 - 4.77

0.02

Other previously treated

13 (17.8)

60 (82.2)

0.9

0.54 - 1.51

0.7

DOT

Patient category

aRR = adjusted risk ratio; CI = confidence interval; DOT = directly observed therapy. *Multivariate binomial regression adjusted for age, gender, HIV status and population type.

coverage (p=0.045).[6] A Nigerian study reported that implementing DOT in hospitals led to a significant increase in the number of patients completing treatment and a significant reduction in mortality among TB patients.[4] DOT helps to ensure that patients adhere to and complete TB treatment regimens. A study in Zambia established that 29.8% of TB patients stopped taking their TB treatment once they started feeling better.[15] Similarly, researchers in Uganda reported that the continuation phase of TB treatment was significantly associated with non-adherence to TB treatment (odds ratio 6.2; p<0.001).[16] These previous studies support our finding that patients who do not receive DOT during the continuation phase have a threefold increased risk for poor treatment outcome compared with patients who receive DOT throughout the course of treatment. The majority of patients received appropriate treatment regimens, with 96.2% of new and 91.0% of retreatment patients receiving the recommended therapy according to the NTP guidelines. Inappropriate treatment regimens were not, however, associated with poor treatment outcomes. This may be because the regimens classified as inappropriate include some that were ‘stronger’ or ‘longer’ than the standard recommended regimens. We did identify that patients with a history of treatment default are at an increased risk of poor outcome compared with new patients. The increased risk of poor outcome associated with partial DOT and previous default illustrates the importance of adherence to TB treatment in achieving a successful outcome. This study has several limitations. Owing to missing information on TB treatment regimen, DOT coverage and treatment outcome, 598 cases (44.7%) were excluded from analysis. Although the gender distribution was similar between analysed and excluded cases, parameters such as age, population type, HIV status, patient category, DOT use and treatment outcomes were different. However, the purpose of this analysis was to evaluate the status of the existing TB control programme in these locations, not to make inferences regarding the larger population of all TB patients. Representative sampling is therefore less of an issue, and the results reported reflect the actual situation in this sample. Further, the data were obtained retrospectively from medical and surveillance documents recorded as part of programmatic surveillance, not as part of a research study. It is therefore possible that the recording of information may not have been standardised across different health facilities and providers. Also, owing to the presence of multiple sources of information, decision rules were established to resolve discrepant

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values. Unfortunately, there was no mechanism to determine which data source most accurately reflects patient information. While most studies rely on a single source document that may not accurately reflect the true value, this analysis was able to maximise the completeness and reliability of information by utilising several data sources. Because we were not able to assess inappropriate treatment in more detail from a clinical perspective owing to lack of patient information on severity of disease and smear status of paediatric patients, this evaluation may have overestimated the actual number of patients receiving inappropriate treatment. However, we believe this information would have impacted on our results only minimally because few clinical indications would have led to reclassification of regimen appropriateness, as regimen standards are based on general patient groups (new/retreatment; adult/child). Finally, there is a possibility of confounding by other factors that were not available in the current dataset. However, we examined all available sociodemographic, clinical and treatment factors as potential confounders and effect modifiers in the current analyses. In conclusion, our evaluation demonstrated a high level of adherence to NTP treatment and management guidelines in the selected provinces of SA. Receiving DOT during only the intensive phase of treatment and a history of previous TB treatment default were independently associated with poor treatment outcome. The results suggest that health facilities in these provinces may need additional training and resources to ensure that all patients receive DOT throughout the course of treatment. These results underscore the importance of DOT as a critical element in overall TB programme success. Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the University of South Florida and the South African National Department of Health. Author contributions. JVE had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. She substantially contributed to conception and design, acquisition of data, statistical analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. LJP substantially contributed to conception and design, acquisition of data, statistical analysis and interpretation of data, drafting and critical revision of the manuscript for important intellectual content, provided administrative and technical support and supervision, and

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revised and approved the final version to be published. LEB substantially contributed to conception and design, acquisition of data, statistical analysis and interpretation of data, drafting and critical revision of the manuscript for important intellectual content, and revised and approved the final version to be published. HGS substantially contributed to statistical analysis and interpretation of data, drafting and critical revision of the manuscript for important intellectual content, and revised and approved the final version to be published. SD substantially contributed to conception, design, and acquisition of data, provided administrative, technical and material support, and revised and approved the final version to be published. LDM substantially contributed to conception, design, and acquisition of data, provided administrative, technical and material support, and revised and approved the final version to be published. References 1. World Health Organization. Global Tuberculosis Report 2012. Geneva: WHO, 2012. http://www.who. int/tb/publications/global_report/en/ (accessed 30 September 2013). 2. National Department of Health, South Africa. The National Tuberculosis Control Programme. National Tuberculosis Policy Guidelines 2009. http://familymedicine.ukzn.ac.za/Libraries/Guidelines_ Protocols/TB_Guidelines_2009.sflb.ashx (accessed 25 October 2013). 3. Chaulk CP, Moor-Rice K, Rizzo R, Chaisson RE. Eleven years of community-based directly observed therapy for tuberculosis. JAMA 1995;274(12):945-1184. [http://dx.doi.org/10.1001/ jama.1995.03530120037038] 4. Daniel OJ. Pre- and post-directly observed treatment era in the management of TB: A teaching hospital experience. Trop Doct 2006;36(3):163-165. [http://dx.doi.org/10.1258/004947506777978280]

5. Tumbo J, Ogunbanjo G. Evaluation of directly observed treatment for tuberculosis in the Bojanala health district, North West Province of South Africa. African Journal of Primary Health Care & Family Medicine 2011;3(1):191-194. [http://dx.doi.org/10.4102/phcfm.v3i1.191] 6. Ntshanga SP, Rustomjee R, Mabaso ML. Evaluation of directly observed therapy for tuberculosis in KwaZulu-Natal, South Africa. Trans R Soc Trop Med Hyg 2009;103(6):571-574. [http://dx.doi. org/10.1016/j.trstmh.2009.03.021] 7. World Health Organization. DOTS Expansion. Geneva: WHO, 2014. http://www.who.int/tb/dots/en/ (accessed 24 January 2014). 8. Munro SA, Lewin SA, Smith HJ, Engel ME, Fretheim A, Volmink J. Patient adherence to tuberculosis treatment: A systematic review of qualitative research. PLoS Med 2007;4(7):e238. [http://dx.doi. org/10.1371/journal.pmed.0040238] 9. Shimeles E, Aseffa A, Yamuah L, Tilahun H, Engers H. Knowledge and practice of private practitioners in TB control in Addis Ababa. Int J Tuberc Lung Dis 2006;10(10):1172-1127. 10. Harries AD, Gausi F, Salaniponi FM. Prescriptions and dosages of anti-tuberculosis drugs in the National Tuberculosis Control Programme of Malawi. Int J Tuberc Lung Dis 2004;8(6):724-729. 11. Van der Werf MJ, Langendam MW, Huitric E, Manissero D. Knowledge of tuberculosis-treatment prescription of health workers: A systematic review. Eur Respir J 2012;39(5):1248-1255. [http://dx.doi. org/10.1183/09031936.00125611] 12. Langendam MW, van der Werf MJ, Huitric E, Manissero D. Prevalence of inappropriate tuberculosis treatment regimens: A systematic review. Eur Respir J 2012;39(4):1012-1020. [http://dx.doi.org/10.1183/09031936.00125511] 13. The Electronic Tuberculosis Register (ETR). Country implementation. http://www.etrnet.info/ CountryImplementations.aspx (accessed 25 October 2013). 14. Naicker M. The Electronic TB Register (ETR.Net). Presentation at the PEPFAR SA HMIS Workshop, Cape Town, South Africa, 14 May 2008. http://southafrica.usembassy.gov/root/pdfs/pepfar-hmisdocs/national-system-etr.net.pdf (accessed 25 October 2013). 15. Kaona FA, Tuba M, Siziya S, Sikaona L. An assessment of factors contributing to treatment adherence and knowledge of TB transmission among patients on TB treatment. Int J Tuberc Lung Dis 2007;11(1):59-64. [http://dx.doi.org/10.1186/1471-2458-4-68] 16. Amuha MG, Kutyabami P, Kitutu FE, Odoi-Adome R, Kalyango JN. Non-adherence to anti-TB drugs among TB/HIV co-infected patients in Mbarara Hospital Uganda: Prevalence and associated factors. Afr Health Sci 2009;9(suppl 1):S8-15.

Accepted 11 November 2013.

Human resource management practices in a medical complex in the Eastern Cape, South Africa: Assessing their impact on the retention of doctors B Longmore, MB ChB; L Ronnie, PhD Graduate School of Business, University of Cape Town, South Africa Corresponding author: L Ronnie (linda.ronnie@gsb.uct.ac.za) Background. Human resource management (HRM) practices have the potential to influence retention of doctors in the public health sector. Objective. To explore the key human resource (HR) practices affecting doctors in a medical complex in the Eastern Cape, South Africa. Methods. We used an open-ended questionnaire to gather data from 75 doctors in this setting. Results. The most important HR practices were paying salaries on time and accurately, the management of documentation, communication, HR staff showing that they respected and valued the doctors, and reimbursement for conferences and special leave requests. All these practices were judged to be poorly administered. Essential HR characteristics were ranked in the following order: task competence of HR staff, accountability, general HR efficiency, occupation-specific dispensation adjustments and performance management and development system efficiency, and availability of HR staff. All these characteristics were judged to be poor. Conclusion. HRM practices in this Eastern Cape medical complex were inadequate and a source of frustration. This lack of efficiency could lead to further problems with regard to retaining doctors in public sector service. S Afr Med J 2014;104(5):368-371. DOI:10.7196/SAMJ.7751

The Eastern Cape Province of South Africa (SA) is described as having a healthcare crisis. Failure to pay salaries to staff and shortages of medicines and basic medical supplies have been cited as manifestations of what were believed to be far-reaching systemic failures in the financing and management of services in the province.[1] At the

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heart of this crisis lie two key issues, namely poor management and severe staff shortages. It may be obvious that sound human resource management (HRM) of healthcare workers (HCWs) is critical for the functioning of a healthcare system, but the importance of HRM seems to be overlooked in some SA settings. One of the most concerning factors facing healthcare in

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the Eastern Cape is the province’s struggle to retain doctors in the hospital system. Although this retention issue seems to be multifaceted, the role HRM appears to play at an Eastern Cape health institution badly affected by staff shortages is of particular concern. The Eastern Cape medical complex, like many others, has recently experienced severe staffing difficulties. Delayed payment of salaries to critically important healthcare employees was quoted as one of the reasons why doctors and other health professionals abandon their public healthcare posts.[2] This situation exposes the relationship between HRM and retention, and highlights the need to assess and understand it. Although the present Minister of Health has recognised that human resource (HR) capacity is a problem facing the health system in general and has included its improvement in the Department of Health’s 10-point strategy plan,[3] there is a concern that insufficient effort is being channelled to address the issues timeously. As recently as May 2012, the Minister suggested a possible intervention to address the state of affairs in the Eastern Cape,[4] which has 2.97 public doctors per 10 000 people, a ratio among the lowest in the country.[5] This situation appears to have been deteriorating over the past few years, as highlighted in the poor publicity the province has attracted.

Objectives

The purpose of this research was to explore the potential impact of various HRM practices on the retention of public sector doctors in the Eastern Cape. The research has made it possible not only to appreciate the importance of the various practices and their characteristics, but also to understand perceptions of how these practices are being executed in an SA setting that is facing significant retention challenges. We suggest that an improved understanding of the HRM challenges in this public hospital setting may be utilised at a national level to facilitate retention of doctors in the SA public sector as a whole.

Methods

An Eastern Cape hospital complex with staffing difficulties was identified as a setting within which to conduct the study. A mixed-methods approach was adopted that combined both qualitative and quantitative strategies. This facilitated the exploratory and descriptive study to be conducted in the cohort of affected doctors. A three-stage process was followed. The first stage consisted of a review of the literature

and revealed a paucity of studies surrounding HRM practices and their impact on retention of HCWs in the public health sector. Studies on factors underpinning HCW migration[6] and HCW motivation[7,8] were therefore drawn on to begin the research process. A second phase consisting of semi-structured interviews with the hospital complex’s clinical heads of department was then undertaken to shed light on the intended role of the HR department and reveal the potential impact of HR practices from a managerial point of view. With the above information and the findings from the literature, the third and final part of the research, a survey questionnaire, was designed. Following a small pilot study, the survey was administered anonymously to more than 250 doctors in the complex via an electronic platform following an email and SMS request. Responses to the survey were gathered over a 2-week period. During this time, the full doctor complement received reminders via e-mail and SMS to complete the survey. At the time of closing, 93 responses were entered; however, only 75 were complete, giving a 30% response rate from an estimated sample population of 250. The open-ended questionnaire separated HRM into two distinct parts, the first being HR practices and the second HR characteristics. After respondents provided demographic data, they were asked to rank five identified HR practices in order of importance. This was followed by an open question requesting an explanation of the respondents’ highest-ranked practice. The doctors were then asked to rate the performance of the complex’s HR department in the five practices. This template was repeated for the second theme, the five HR characteristics.

Results

Table 1 shows the demographic characteristics of the survey respondents. There were marginally more males than females and the majority of responses came from the age group 25 - 32 years (‘Generation Y’). Medical officers formed the largest group of respondents (31%), closely followed by interns and then community service doctors. Almost 74% of the survey respondents reported that they had worked at the complex for less than 5 years. Generational classification was intention ally used for the age category selection to determine whether there were generational variations in the survey responses. Generation Y, or individuals from 25 to 32 years of age, formed the largest group of respondents (almost 70%). This is interest ing for a number of reasons. If the sample

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population is representative of the whole, a significant portion of the complex’s medical workforce is made up of a generation that is proving difficult to manage. [9] The resounding agreement in the literature regarding this difficulty indicates a growing challenge. Seen as the most high-maintenance group to enter the workforce, Generation Y are multi-taskers who have high expectations of both themselves and their employers.[10] This poses attraction, motivation and retention challenges for the public health sector.

Key HR practices – importance ranking (Table 2)

Most doctors felt that paying them on time and accurately was the most important HR practice. There was much emotion surrounding remuneration inconsistencies and resulting financial insecurity, doctors feeling that it is simply not acceptable to fail to pay salaries on time. Documentation management and communication, both essential HR components, were ranked by responding doctors as second and third, respectively. Like salary errors, documentation loss and failures of communication were detested, and resulted in extreme levels of frustration. Ranking fourth, being respected and valued by HR staff was something that doctors felt was less important than the basic HR functions being undertaken Table 1. Demographic characteristics of respondents Variable

Gender (male)

Age (years) 25 - 32

33 - 50

51 - 66

≥67

Current position Intern

Community service

Medical officer

Registrar

Consultant

Duration of service at the complex (years) <2

≥2 - 5

≥5 - ≤10

>10

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properly. However, one doctor ranked this practice as first, stating, ‘If the staff of HR respected and valued us, then they would pay us on time, keep our documents safe, strive to communicate effectively and place priority on our continued education.’ The last HR practice, reimbursement for ed and special courses/conferences attend leave requests, although playing a critical role in both the doctors’ development and the clinical functioning of the hospital complex, was ranked by doctors as least important. Like value and respect, it was trumped by the importance of timeous salary payment, documentation management and communication.

Respondents’ rating of the complex’s key HR practices (Table 2)

Both the quantitative and qualitative data collected showed that this Eastern Cape health complex failed in all five key HR practices. Accurate payment of salaries, with its critical role in employee security, was mentioned as problematic 45 times in the open responses. Many doctors had been victims of late or inaccurate payment, and numerous others feared non-payment on a monthly basis. Quantitative data revealed a spread of responses describing a practice that is completely unacceptable in the private sector. Document management and communication efforts by the complex HR staff

Table 2. Importance ranking and respondents’ rating of HR practices Respondents’ rating, %

Importance ranking HR practice

Unacceptable

Acceptable

Good

Very good

Monthly salary paid on time

An adequate document collection, filing and storage system

Good communication, e.g. regarding post availability, status of requests made to the department, and the whereabouts of submitted documents

To be respected and valued by HR staff and receive friendly and helpful service

Reimbursement for courses/conferences attended, and processing of special leave requests

HR = human resource.

were rated by 84% of doctors as dismal. Doctors cited numerous cases of repeated document loss, identity fraud and failure of communication. Sixty-four per cent of doctors felt that they were not respected and valued by HR staff. This was corroborated by the qualitative responses in both the interviews and the survey. As mentioned above, the crucial administration regarding continuing education and career development, although ranked least important, received a vote of failure from 57% of responding doctors.

Essential HR characteristics

The second theme of HR characteristics was dominated by doctors ranking task competence of HR staff as the most important factor. It was clear that HR staff did not exhibit competence when dealing with their concerns, causing annoyance and frustration. This characteristic was followed in the importance ranking by accountability, a characteristic that doctors perceived to be a driver of excellence and quality. The third-ranked characteristic that doctors felt it was important for HR staff to exhibit was general process efficiency. Responses emphasised that process effi ciency enables timeous handling of critical activities such as application processing, problem identification and failure resolution. This importance was confirmed by the fourth-ranked characteristic, salary adjustment efficiency relating to the occu pation-specific dispensation (OSD) and the performance management and develop ment system (PMDS). When their salary adjustments were correctly carried out, doctors felt that their concerns in this regard had been adequately attended to by the HR department. Availability of HR staff was the fifth-ranked characteristic. As a result of their substantial clinical load,

Table 3. Importance ranking of HR performance characteristics and respondents’ rating Respondents’ rating, %

Importance ranking

HR performance characteristics

Unacceptable

Acceptable

Good

Very good

Not applicable

Task competence of HR staff

Accountability of HR staff for queries made or documents submitted

General HR process efficiency

OSD salary level adjustments and PMDS efficiency

Availability of HR staff during tea and lunch breaks

HR = human resource; OSD = occupation-specific dispensation; PMDS = performance management and development system.

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doctors struggled to visit the HR department at times other than their tea and lunch breaks, during which HR staff were frequently unavailable.

Rating the complex’s HR performance characteristics (Table 3)

Seventy-seven per cent of doctors rated the task competence of HR staff as unacceptable, making it clear that a deficiency existed in this core function. Many doctors felt that this was the greatest failure of the HR department and believed that the solution to the problems of poor HRM lay in the training of HR staff. This failure impacted on doctors on a daily basis through fundamental remuneration uncertainty, and was noticeably frustrating for them. The second- and third-ranked characteristics, accountability and general process efficiency, were very poorly rated by the responding doctors. Alarmingly, these characteristics were perceived to be unacceptable by 82% and 87% of doctors, respectively. There were many examples of doctors being affected by these failures, corroborated by a comment from a senior doctor: ‘I have examples of doctors who applied to work in my department who, when finally offered a post, had already been working in an alternative post elsewhere for over 6 months.’ OSD and PMDS performance, although lower down on the importance ranking, was rated as unacceptable by 51% of doctors. The responses indicate that this crucial tool for incentivising doctors is now more of a frustration for them. Lastly, the non-availability of HR staff during tea and lunch breaks received a verdict of ‘unacceptable’ from 65% of respondents.

Discussion

All HR practices in the complex studied are in need of substantial improvement. Based on the qualitative responses and the performance ratings, doctors in the complex are clearly frustrated by the poor levels of HRM. This frustration is unfortunately bound to have negative effects on the institution’s capacity to retain medical staff. It is clear that the HRM characteristics identified are all being performed unacceptably poorly, despite their relative rankings of importance. Doctors were overwhelmingly dismayed regarding the performance of HR staff, with virtually all written responses being negative. The findings highlight the fact that the HRM in the hospital complex studied is paying insufficient attention to HR issues. The fundamental failings of the HR department have caused substantial frustration among doctors, providing a significant ‘push factor’ away from service in the state sector and having a direct impact on doctors’ willingness to remain in service at the complex. Only 32% of the respondents were willing to commit to continue working in this environment, while 45% indicated a desire to leave and 23% were undecided. The impact of poor HRM revealed in this study can therefore only perpetuate the staffing problems that plague the institution.

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HRM in the health sector is known to be an enormous challenge,[11] and although many of the problems in this study were attributed to the staff in the HR department, the influence of system inefficiencies cannot be discounted. HR staff in the hospital complex may in fact be hamstrung, with little ability to enhance their productivity and as frustrated as doctors are by their limited capability. An investigation into this aspect of HR may warrant further research, the results of which could potentially significantly enhance our understanding of public health HRM. If HR is going to play an active part in retaining doctors at the complex studied, substantial improvement in all areas is urgently needed. As members of Generation Y come to predominate in the workforce, managing, motivating and, most importantly, retaining these health professionals is set to become increasingly challenging. HRM improvement is therefore critical, not only to alleviate immediate staffing concerns but also to prepare for a diverse generational blend of HCWs.

Conclusion

This study has revealed that unacceptable HRM practices appear to be perpetuating the shortage of doctors and adversely affecting retention of key health personnel. The link between sound HRM and doctor retention is clearly evident, as is the importance of urgently addressing HRM shortcomings. South African public hospitals need to strive to become ‘magnet hospitals’,[11] attracting doctors who want the opportunity to gain clinical experience. However, this will not happen unless the doctors working in these hospitals know that highly trained HR staff members who are passionate about their work are successfully attending to all their administrative concerns. References 1. Kahn T. Red lights flash for Eastern Cape Health. 8 August 2012. http://www.bdlive.co.za/ articles/2012/05/31/red-lights-flash-for-eastern-cape-health;jsessionid=8B0AE735CF274F6E48F517B F0E6DBDAD.present2.bdfm (accessed 1 February 2013). 2. De Waal M. Eastern Cape’s so-called health system: In dire need of resuscitation. 27 June 2012. http:// www.dailymaverick.co.za/article/2012-06-27-eastern-capes-so-called-health-system-in-dire-need-ofresuscitation/#.UoZCq2thiSM (accessed 1 February 2013). 3. National Department of Health. Strategic Plan 2010/11-2012/13. Pretoria: NDoH, 2010. http://www. mm3admin.co.za/documents/docmanager/2D5ED792-878C-4371-9575-8281A96BBB26/00023294. pdf (accessed 8 October 2013). 4. SABC News. E Cape doctor shortage prompts Motsoaledi to intervene. 31 May 2012. http://www.sabc. co.za/news/a/df29a6004b70e6e8906498a9f8f2aadf/E-Cape-doctor-shortage-prompts-Motsoaledi-tointervene-20120531 (accessed 8 October 2013). 5. Human Resources for Health South Africa. HRH Strategy for the Health Sector: 2012/13 – 2016/17. Pretoria: NDoH, 2012. http://www.info.gov.za/view/DownloadFileAction?id=152486 (accessed 8 October 2013). 6. Padarath A, Chamberlain C, McCoy D, et al. Health personnel in southern Africa: Confronting maldistribution and brain drain. Harare: Network for Equity in Southern Africa, 2003. 7. Kotzee T, Couper ID. What interventions do South African qualified doctors think will retain them in rural hospitals of the Limpopo province of South Africa? Rural Remote Health 2003;6(3):581. http:// www.rrh.org.au/publishedarticles/article_print_581.pdf (accessed 8 October 2013). 8. Willis-Shattuck M, Bidwell P, Thomas S, et al. Motivation and retention of health workers in developing countries: A systematic review. BMC Health Serv Res 2008;8(1):247. [http://dx.doi.org/10.1186/14726963-8-247] 9. Cennamo L, Gardner D. Generational differences in work values, outcomes and person-organization values fit. Journal of Managerial Psychology 2008;23(8):891-906. 10. Erickson T. Plugged In: The Generation Y Guide to Thriving at Work. Boston: Harvard Business School Publishing, 2008:1-278. 11. Buchan J. What difference does (‘good’) HRM make? Hum Resour Health 2004;2(1):6. [http://dx.doi. org/10.1186/1478-4491-2-6]

Accepted 22 November 2013.

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Reliability and accuracy of the South African Triage Scale when used by nurses in the emergency department of Timergara Hospital, Pakistan M K Dalwai,1,2 MB ChB; M Twomey,2 BSc, PhD; J Maikere,1 MB ChB, FCS, PhD; S Said,1 BSc (Nursing); M Wakeel,3 MB ChB; J-P Jemmy,4 MB ChB; P Valles,4 MB ChB; K Tayler-Smith,4 L Wallis,2 MB ChB, FCEM, PhD; R Zachariah,4 MB ChB édecins Sans Frontières, Pakistan M Division of Emergency Medicine, Faculty of Health Sciences, University of Cape Town, South Africa 3 Ministry of Health, Islamabad, Pakistan 4 Médecins Sans Frontières, Medical Department (Operational Research), Operational Centre, Brussels, Belgium, MSF-Luxembourg (LuxOR), Luxembourg 1 2

Corresponding author: M K Dalwai (mkdalwai@gmail.com) Background. Triage is one of the core requirements for the provision of effective emergency care and has been shown to reduce patient mortality. However, in low- and middle-income countries this strategy is underused, under-resourced and poorly researched. Objective. To assess the inter- and intra-rater reliability and accuracy of nurse triage ratings when using the South African Triage Scale (SATS) in an emergency department (ED) in Timergara, Pakistan. Methods. Fifteen ED nurses assigned triage ratings to a set of 42 reference vignettes (written case reports of ED patients) under classroom conditions. Inter-rater reliability was assessed by comparing these triage ratings; intra-rater reliability was assessed by asking the nurses to re-triage 10 random vignettes from the original set of 42 vignettes and comparing these duplicate ratings. Accuracy of the nurse ratings was measured against the reference standard. Results. Inter-rater reliability was substantial (intraclass correlation coefficient 0.77; 95% confidence interval (CI) 0.69 - 0.85). The intrarater agreement was also high with 87% exact agreement (95% CI 67 - 100) and 100% agreement allowing for a one-level discrepancy in triage ratings. Overall, the SATS had high specificity (97%) and moderate sensitivity (70%). Across all acuity levels the proportion of overtriage did not exceed the acceptable threshold of 30 - 50%. Under-triage was acceptable for all except emergency cases (66%). Conclusion. ED nurses in Pakistan can reliably use the SATS to assign triage acuity ratings. While the tool is accurate for ‘very urgent’ and ‘routine’ cases, importantly, it may under-triage ‘emergency’ cases requiring immediate attention. Approaches that will improve accuracy and validity are discussed. S Afr Med J 2014;104(5):372-375. DOI:10.7196/SAMJ.7604

With the increase in urbanisation and violent conflicts, together with the growing burden of chronic noncommunicable diseases in many low- and middleincome countries (LMICs), there is an increased burden on emergency healthcare services.[1] In many LMICs, one of the main challenges facing emergency services is the capacity to deal with high patient loads.[2] The process of ‘triage’ is one way of addressing this challenge, since it optimises the allocation and use of existing resources. Triage is the process of sorting critically ill patients who need immediate lifesaving interventions from patients who need medical attention but can safely wait to be seen.[3] Triage aims to determine a patient’s ‘acuity level’ – i.e. how urgently they require medical attention. Triage is recognised as being one of the core requirements for the provision of effective emergency care and has been shown to reduce patient mortality.[4] However, in LMICs this strategy is underused, under-resourced and poorly researched. The South African Triage Scale (SATS) was developed in 2004 for pre- and in-hospital emergency units throughout South Africa (SA).[5] It was specifically designed to be used by nursing assistants and as such was intended to serve as a coping measure to address medical staff shortages and limited resources – challenges that are commonplace in SA, as in other LMICs.[6]

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In 2011, Médecins Sans Frontières (MSF), an international medical humanitarian organisation, implemented the SATS in Timergara Hospital (TH) in the rural district of Lower Dir in the province of Khyber Pakhtunkhwa (KPK), Pakistan. MSF had been working at this hospital alongside the Pakistan Ministry of Health to improve emergency healthcare for the population. Against a backdrop of limited resources, overstretched staff and the absence of a standardised triage system, MSF implemented the SATS with good preliminary results.[7] The SATS has been assessed extensively in SA and implemented in several LMIC settings.[8,9] However, a more formal assessment of the SATS in a LMIC setting outside sub-Saharan Africa has not yet been undertaken. The two most common measures for assessing a triage scale are reliability and validity. Reliability is the extent to which the triage scale yields the same result on repeated assessments of the same patient. Inter-rater reliability determines whether there is variability between different staff rating the same patient, while intra-rater reliability assesses the variability for one member of staff re-triaging the same patient. Validity has been defined as indicating how closely an acuity rating assigned using the triage scale is to the true acuity of that patient.[10] However, limitations exist when trying to validate triage scales in any setting, owing to lack of a gold standard. As

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such, validity has been assessed using surrogate markers such as hospital admission, discharge and resource utilisation.[11] In LMICs, however, the use of these surrogate markers is difficult owing to poor record keeping, varying levels of clinical skills and limited resources. Previous studies in LMICs have instead attempted to assess the validity of a triage scale by comparing the triage ratings assigned by emergency department (ED) staff for a series of simulated cases against those obtained from an expert panel based on the panel’s expert opinion.[12] For the purpose of this study, we will refer to this methodology and use a set of 42 reference vignettes as a reference standard against which accuracy is measured.[13] This study therefore aimed to determine the reliability (inter- and intra-rater) and accuracy of the adult version of the SATS when used by ED nurses in TH, Pakistan.

Methods

Study design

This was a cross-sectional study using a set of 42 reference vignettes (short, written, clinical case reports of ED patients) as a proxy for live ED cases.

Setting

TH is situated in the predominantly rural district of Lower Dir in the KPK province of Pakistan. It is the only district hospital in Lower Dir, serving an estimated population of 1.8 million. The ED has an estimated annual caseload of ~48 000 patients, comprising both adults and children. The caseload is largely made up of medical emergencies (typically respiratory infection, cardiac disease and gastrointestinal illness) and trauma (most often road traffic accidents).

SATS and its use in the TH ED

The SATS uses a physiologically based composite scoring system, the Triage Early Warning Score, together with a list of discriminators, with which to triage patients into one of five colour-coded groups according to their degree of urgency for medical attention. The colour categories are as follows: (i) red, ‘emergency’ (to be seen immediately); (ii) orange, ‘very urgent’ (to be seen within 10 min); (iii) yellow, ‘urgent’ (to be seen within 60 min); (iv) green, ‘routine’ (to be seen within 240 min, i.e. minor injuries/ illness); and (v) black, ‘dead’. The SATS was introduced in the TH ED in June 2011. All ED staff received a 1-hour structured training course, which was carried out by the expatriate ED doctor. It involved explaining patient flow in the ED together with each step of the triage algorithm and the composite physiological score where each vital sign is not seen in isolation but rather as a composite part of an early warning score. Each discriminator was explained using common local ED examples. Using the SATS, triage was routinely undertaken by two triage nurses during each work shift. Once triaged, ‘red’ and ‘orange’ patients were seen by the MSF team (a national doctor, three nurses and an expatriate doctor) in the resuscitation room, while ‘yellow’ and ‘green’ patients were seen by the national casualty medical officers in a room adjacent to the ED. At the time of the study, 23 nurses were on the ED rota and carrying out triage.

Study population

The study included all nurses at TH who fulfilled the following inclusion criteria: (i) those who had received training in the SATS and had at least 1 month’s experience performing patient triage using this tool; and (ii) those who agreed to participate in the study. As the study attempted to recruit all nurses fulfilling the above criteria, it was not necessary to calculate the required sample size.

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Data collection

Under classroom conditions, nurses participating in the study were required to assign one of four priority categories to the set of 42 reference vignettes according to the SATS acuity levels of ‘emergency’, ‘very urgent’, ‘urgent’ and ‘routine’. The vignettes had been collected and validated in a previous study and were based on real ED cases from a secondary hospital in SA.[13] The type and spectrum of patient presentations captured in these vignettes closely mirrored the sort of cases presenting at the TH ED. The vignettes included information on patient gender, age, presenting complaint, mode of arrival to the ED, and vital signs. Some vignettes also included information from additional investigations such as blood glucose test and haemoglobin, as done at the time of triage. For the purpose of this study, the vignettes were translated from English into Urdu, the national language of Pakistan. This was carried out by a professional translator and ratified by a local bilingual doctor to ensure the correct medical terminology.

Reliability

Inter-rater reliability was measured by comparing the different nurse triage ratings for the 42 vignettes, while intra-rater reliability was measured by asking the nurses to re-triage 10 random vignettes from the original set of 42 vignettes and comparing these duplicate ratings.

Accuracy

The accuracy of nurse triage ratings for the 42 vignettes was measured by comparing their ratings with the acuity ratings assigned to the same set of vignettes by an international expert panel. The panel of 18 experts, made up of emergency medicine physicians and emergency nurses from developing and developed countries, were chosen from countries where triage scales were already established and validated or being established and validated. They had already independently reviewed the vignettes used in the current study, and via a modified Delphi technique, obtained consensus on ‘true’ acuity level for each vignette. They assigned an acuity level based on their expert opinion rather than through the application of the SATS. The acuity levels that they assigned had to fall into one of four categories to mirror the SATS categories of ‘emergency’, ‘very urgent’, ‘urgent’ and ‘routine’.

Data analysis

In accordance with the Guidelines for Reporting Reliability and Agreement Studies (GRRAS), inter-rater reliability was assessed using the unweighted, linearly weighted and quadratically weighted κ (QWK) statistic, as well as the intraclass correlation coefficient (ICC).[14] The QWK is commonly used when reporting on reliability studies because it takes into account the degree of disagreement. A weighted κ uses maximum weights at two opposite ends of the scale and is therefore identical to the ICC.[10] Whereas the unweighted and linear weighted κ is not commonly used in triage literature, it has been reported in this case to follow the GRRAS for easy comparisons between other studies.[14] Point estimate values for QWK and ICC were graded using the Landis and Koch classification system as follows: 0.0 - 0.20 – slight agreement; 0.21 - 0.40 – fair agreement; 0.41 - 0.60 – moderate agreement; 0.61 - 0.80 – substantial agreement; and 0.81 - 1.00 – almost perfect agreement.[10] Intra-rater reliability was assessed by calculating the percentage of exact agreement and also the percentage of agreement allowing for one level of discrepancy in the triage ratings. The accuracy of the nurse triage ratings was assessed by calculating the sensitivity, specificity, and associated over-/under-triage relative to the experts’ triage ratings. Over- and under-triage were interpreted using an accepted range for average under-triage of not more than 5 - 10% and an

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associated average over-triage rate of 30 - 50%; these are the ranges considered acceptable by the American College of Surgeons Committee on Trauma.[7] Data were analysed using STATA (version 9.2).[15]

Ethics approval

Ethics approval was obtained from the MSF Ethics Review Board, Geneva, Switzerland, and the Human Research Ethics Committee, University of Cape Town, as well as the Pakistan Bioethics Review Board. Informed consent was obtained from all nurses partici pating in the study.

Results

Characteristics of the study population

Of a total of 23 nurses carrying out triage, 20 met the study inclusion criteria and were invited to participate in the study. Fifteen of these nurses agreed to participate, while five declined due to scheduling conflicts and transport issues. The convenience sample therefore represented 75% of all eligible triage nurses.

Reliability of nurse triage ratings

A total of 780 ratings were obtained for analysis, consisting of 15 nurses assigning ratings for 42 vignettes (n=630) and the same 15 nurses assigning ratings for the 10 duplicate vignettes (n=150). Table 1 summarises the different reliability measures calculated to assess inter- and intra-rater reliability. Inter-rater reliability, as measured by the ICC and QWK, was substantial. Similarly, the level of exact intra-rater agreement among the nurses in our study was almost perfect (87%; 95% confidence interval (CI) 67 - 100), and there was 100% agreement when allowing for a one-level discrepancy in triage ratings.

Accuracy of nurse triage ratings

Table 2 summarises the accuracy of the nurse acuity ratings using the SATS, compared with the expert panel ratings of the vignettes. Overall, the SATS demonstrated a high level of specificity (97%) and a moderate level of sensitivity (70%). Broken down by acuity level, the SATS showed the highest sensitivity (93%) for ‘very urgent’ cases. However, the

Table 1. Different measures calculated to assess inter- and intra-rater reliability of ED nurse triage ratings using the SATS at Timergara Hospital, Pakistan Point estimate (95% CI)

Level of agreement*

0.77 (0.69 - 0.85)

Substantial

Unweighted

0.55 (0.51 - 0.60)

Moderate

Linearly weighted

0.65 (0.61 - 0.71)

Substantial

Quadratically weighted

0.77 (0.69 - 0.84)

Substantial

Exact agreement, % (95% CI)

87 (67 - 100)

Agreement with one SATS category discrepancy, %

100

Reliability measure Inter-rater reliability Intra-class correlation coefficient κ statistic

Intra-rater reliability

ED = emergency department; SATS = South African Triage Scale; CI = confidence interval. *According to the Landis and Koch criteria.[10]

level of sensitivity for ‘emergency’ cases was exceptionally low (34%). Across all acuity levels, over-triage rates did not exceed the acceptable threshold of 30 - 50%. Similarly, for ‘very urgent’, ‘urgent’ and ‘routine’ cases, under-triage rates were below the acceptable threshold (5 - 10%). However, for emergency cases, the rate of under-triage was exceptionally high (66%), although almost all of these mis-triaged cases were only under-triaged by one acuity level, being rated as ‘very urgent’.

Discussion

This is the first study to assess the reliability and accuracy of nurse triage ratings using the SATS in a resource-poor Asian setting.[7] Nurse ratings using this triage scale demonstrated good inter- and intra-rater reliability and acceptable accuracy for ‘very urgent’ and ‘routine’ cases. However, nearly two-thirds of ‘emergency’ cases were under-triaged as ‘very urgent’, which warrants attention. Supported by study findings from Botswana and SA,[6,8] our study demonstrates that after minimal formal training, the SATS can be applied reliably by nursing staff in an ED in Pakistan. However, there are concerns about the accuracy of these ratings. In our study, the degree of accuracy of the nurse triage ratings using the SATS was acceptable for ‘very urgent’ and ‘routine’ cases, but not for ‘urgent’ and ‘emergency’ cases. In particular, a high proportion of emergency cases were under-triaged, which mirrors the findings from a study in SA evaluating the validity of the SATS.[13] The undertriage of ‘emergency’ cases may be reflected inaccurately on account of several study biases which we discuss below. Alternatively, it may be that this is really the case. If so, this could either be because nursing staff are applying the SATS inaccurately, or because the SATS is poorly constructed to accurately identify true emergency cases. We suspect

Table 2. Comparison of TH ED nurse ratings using the SATS with the expert panel’s ratings of the vignettes Expert panel triage category

Nurse ratings, % (N=630) Vignettes, n

Triage ratings, n

Emergency

135

Very urgent

Urgent Routine

SATS performance v. expert panel (reference standard)

Emergency

Very urgent

Urgent

Routine

Sensitivity, % (95% CI)

34*

0.4

34 (30 - 38)

99 (99 - 100)

66 (62 - 70)

255

93*

93 (91 - 95)

97 (95 - 98)

0.4 (0 - 1)

7 (5 - 9)

150

59*

59 (55 - 63)

94 (93 - 96)

35 (33 - 37)

7 (5 - 9)

78*

78 (75 - 81)

97 (96 - 98)

22 (19 - 25)

70 (66 - 74)

97 (92 - 100)

15 (4 - 25)

22 (9 - 34)

Mean

TH = Timergara Hospital; ED = emergency department; SATS = South African Triage Scale; CI = confidence interval. * Nurse ratings matching the expert panel’s rating (reference standard) across each acuity level.

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Specificity, % (95% CI)

Overtriage, % (95% CI)

Undertriage, % (95% CI)

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that staff inaccuracy is not to blame, as regular audits of the SATS in Pakistan together with the findings from a previous study have shown a high level of staff accuracy.[13] If the construct of the SATS itself is responsible for the under-triage of ‘emergency’ cases, this needs further investigation. The clinical implications of under-triage of ‘emergency’ cases in our setting are negligible as almost all of the ‘under-triaged’ emergency cases were rated as ‘very urgent’, and in the context of TH all ‘emergency’ and ‘very urgent’ patients are seen by the same cadre of healthcare workers in the same area and within the same timeframe. Although we do not have data to substantiate this, a 10-minute delay linked to misclassification of ‘emergency’ to ‘very urgent’ cases is unlikely to have clinical implications. Nonetheless, in a setting where there are clear distinctions between the ways in which ‘emergency’ and ‘very urgent’ patients are managed, under-triage in this way needs to be avoided, as it may be associated with poorer outcomes (i.e. a higher risk of mortality, worsening morbidity and additional medical complications). This makes the case for ensuring that any assessment of the SATS is context specific.

Study limitations

A number of study limitations and various methodological issues related to assessing the validity of a triage tool have been brought to our attention by this study. First, while there is no universally accepted time period recommended between assessments for inter- and intra-rater reliability, 2 - 14 days has been suggested.[10] Owing to ED staff time constraints, we conducted the intra-rater assessments immediately after the inter-rater assessment; this may have led to a recall bias in the response ratings. Second, although the vignettes were paper based, in the absence of non-verbal patient cues and contextual information, raters’ triage decisions may have been affected. That said, a previous study comparing the use of paper-based cases with live ED patients as a way of assessing the inter-rater reliability of a triage tool showed an acceptable level of agreement between the two methods.[16] The main benefits of using paper-based vignettes over real ED cases in LMIC settings is that they provide a cost-effective, time-saving, non-invasive and culturally acceptable way of undertaking this type of study. Third, the written vignettes were based on ED cases seen in SA, not in the TH ED in Pakistan. In the study by Twomey et al.,[13] a set of vignettes ratified by a modified Delphi technique are proposed as a set of reference standard vignettes. Using these vignettes in Pakistan was deemed appropriate due to the following: (i) SA and Pakistan are both LMIC settings; (ii) the two settings have similar rates of trauma (66 trauma presentations per 1 000 patients in SA and 41/1 000 in Pakistan);[17,18] and (iii) the reference vignettes depict similar case presentations. However, the epidemiological pattern of disease is different. In future studies like this, it would seem important to develop specific reference vignettes based on ED cases seen in the actual study setting. This would ensure the use of a better reference standard of comparison adapted to the study context. Fourth, when comparing nurse acuity ratings using the SATS to acuity ratings assigned by the expert panel, we cannot be sure whether an identified discrepancy between the two was: (i) because the nursing staff were not applying the SATS accurately; or (ii) because the SATS had poor construct validity – in other words did not measure what it purports to. As indicated earlier, we suspect that staff inaccuracy did not account for many of the observed discrepancies in this study. However, in future studies assessing the

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validity of a triage tool, it would be more appropriate to compare the ratings by several SATS experts (using the SATS) to the expert panel ratings (reference standard). This would help to control for the issue of staff error. Finally, as in other studies, our reference standard was an expert panel that assigned acuity ratings to a series of paper vignettes according to their expert opinion. Almost all of these experts were based in high-income rather than LMIC settings and as such their opinion of ‘true’ patient acuity level may not have fully reflected the reality as in LMIC settings like Pakistan – they may have tended to over-rate patient acuity, especially at the higher end of the triage spectrum. In conjunction with this, it has been reported that nurses tend to under-rate patient acuity when using paper-based vignettes over live cases.[16] In our particular study, these two factors may have contributed to the under-triage of emergency cases that was reported.

Conclusion

Our study shows that the SATS can be used reliably by nurses in an ED in Pakistan. Our results suggest that the SATS is accurate for very urgent and routine cases but, importantly, may ‘under-triage’ ‘emergency’ cases. Although this is unlikely to influence patient outcomes in TH, there may be serious implications in other settings and it therefore merits specific investigation and correction. Acknowledgements. We are grateful to the Pakistani Ministry of Health for their collaboration, and we are particularly grateful to the staﬀ in the field for their hard work. The MSF project in TH, Pakistan, is funded by MSF-Operational Centre Brussels. References 1. Van Rooyen M, Venugopal R, Greenough PG. International humanitarian assistance: Where do emergency physicians belong? Emerg Med Clin North Am 2005;23(1):115-131. [http://dx.doi. org/10.1016/j.emc.2004.09.006] 2. Hodkinson PW, Wallis LA. Emergency medicine in the developing world: A Delphi study. Acad Emerg Med 2010;17(7):765-774. [http://dx.doi.org/10.1111/j.1553-2712.2010.00791.x] 3. Horne S, Vassallo J, Read J, Ball S. UK triage – an improved tool for an evolving threat. Injury 2013;44(1):23-28. [http://dx.doi.org/10.1016/j.injury.2011.10.005] 4. Robison JA, Ahmad ZP, Nosek CA, et al. Decreased pediatric hospital mortality after an intervention to improve emergency care in Lilongwe, Malawi. Pediatrics 2012;130(3):e676-e682. [http://dx.doi. org/10.1542/peds.2012-0026] 5. Emergency Medicine Society of South Africa. The South African Triage Scale (SATS). http://emssa.org. za/sats/ (accessed 11 March 2014). 6. Twomey M, Wallis LA, Thompson ML, Myers JE. The South African Triage Scale (adult version) provides valid acuity ratings when used by doctors and enrolled nursing assistants. African Journal of Emergency Medicine 2012;2(1):3-12. [http://dx.doi.org/10.1016/j.afjem.2011.08.014] 7. Dalwai M, Tayler-Smith K. Implementation of a triage score system in an emergency room in Timergara, Pakistan. Public Health Action 2013;3(1):43-45. [http://dx.doi.org/10.5588/pha.12.0083] 8. Twomey M, Mullan PC, Torrey SB, Wallis L, Kestler A. The Princess Marina Hospital accident and emergency triage scale provides highly reliable triage acuity ratings. Emerg Med J 2012;29(8):650-653. [http://dx.doi.org/10.1136/emermed-2011-200503] 9. Harrison H-L, Raghunath N, Twomey M. Emergency triage, assessment and treatment at a district hospital in Malawi. Emerg Med J 2012;29(11):924-925. [http://dx.doi.org/10.1136/ emermed-2011-200472] 10. Streiner D, Norman G. Health Measurement Scales. A Practical Guide to Their Development and Use. 4th ed. New York: Oxford University Press, 2008. 11. Twomey M, Wallis LA, Myers JE. Limitations in validating emergency department triage scales. Emerg Med J 2007;24(7):477-479. [http://dx.doi.org/10.1136/emj.2007.046383] 12. Olofsson P, Gellerstedt M, Carlström ED. Manchester Triage in Sweden – interrater reliability and accuracy. Int Emerg Nurs 2009;17(3):143-148. [http://dx.doi.org/10.1016/j.ienj.2008.11.008] 13. Twomey M, Wallis L, Myers J. Evaluating the construct of triage acuity against a set of reference vignettes developed via modified Delphi method. Emerg Med J 2013. [http://dx.doi.org/10.1136/ emermed-2013-202352] 14. Kottner J, Audigé L, Brorson S, et al. Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed. J Clin Epidemiol 2011;64(1):96-106. [http://dx.doi.org/10.1016/j. jclinepi.2010.03.002] 15. StataCorp. 2005. Stata Statistical Software: Release 9. College Station, TX: StataCorp LP. 16. Worster A, Sardo A, Eva K, Fernandes CMB, Upadhye S. Triage tool inter-rater reliability: A comparison of live versus paper case scenarios. J Emerg Nurs 2007;33(4):319-323. [http://dx.doi. org/10.1016/j.jen.2006.12.016] 17. Wallis LA, Twomey M. Workload and casemix in Cape Town emergency departments. S Afr Med J 2007;97(12):1276-1280. 18. Nasrullah M, Xiang H. The epidemic of injuries in Pakistan – a neglected problem. J Pak Med Assoc 2008;58(8):420-421.

Accepted 7 January 2014.

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GUEST EDITORIAL

Breast cancer The management of breast cancer requires a multidisciplinary approach in its broadest sense. In keeping with this ethos, the May edition of CME contains articles written by surgeons, oncologists, epidemiologists, nurses, physiotherapists, occupational therapists and patient advocates. Ranked according to GDP (R7 500 per capita),[1,2] South Africa is classed as a middle-income country. Rated internally, however, its healthcare system is best envisaged as a mixture of elements of a highincome (HIC) and a low-income country (LIC). A collaborative article gives an overview of breast cancer in LICs, while a study from Baragwanath Hospital, Soweto, Johannesburg, shows that >60% of women seen have stage 3 or 4 breast cancer at the time of diagnosis. These two articles illustrate the need for an edition of CME primarily devoted to the management of breast cancer in developing countries. There are two articles that describe practical approaches to patients with locally advanced breast cancer. One is by Dr P Govender, an oncologist from Durban, and the other by Sister K Hill, a nurse from Christiaan Barnard Memorial Hospital, Cape Town. Initially, the plan was to combine the articles but they are fully complementary in their approach to the problem; therefore they are published as two separate articles. An article by Dr A Gudgeon discusses the management of the side-effects of systemic treatment. Lymphoedema is a common complication of locally advanced breast cancer, which has received scant attention from the medical profession over the years. A collaborative article written by

lymphoedema therapists has also been included. Dr M Mutebi, a surgeon from Kenya, describes some of the stigmas that are still attached to the diagnosis of breast cancer. Breast cancer features in the political discourse in many countries. Advocacy groups have lobbied to place it high on their governments’ agendas. In South Africa, even though breast cancer is one of the most common causes of cancer mortality in women, it does not receive the recognition or the allocation of resources that it needs. A coalition of interested organisations was launched this year in an effort to redress the situation. Their founding statement in its early form is included. Breast cancer mortality figures in South Africa must be improved, and this will only follow from a truly multidisciplinary approach by all healthcare and other practitioners. This month’s edition of CME aims to highlight some of the important aspects concerning this disease. Jenny Edge Guest editor jennyedge1234@me.com 1. Statistics South Africa. South Africa GDP Growth Rate. http://www.tradingeconomics.com/southafrica/gdp-growth (accessed 23 March 2014). 2. United Nations Industrial Development Organization 2014. The High-Level Conference of MiddleIncome Countries, San José, Costa Rica 12 - 14 June 2013. http://micconference.org/mic/list-of-mics (accessed 23 March 2014).

S Afr Med J 2014;104(5):376. DOI:10.7196/SAMJ.8262

Dyna Gliclazide SR 30 mg. Each modified release tablet contains 30 mg gliclazide. Reg. No.: RSA S3 42/21.2/0249 NAM NS2 12/21.2/0110. For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority.

4) Department of Health website http://www.doh.gov.za - Accessed on 01/04/2014.

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REVIEW

The challenges of managing breast cancer in the developing world â&#x20AC;&#x201C; a perspective from sub-Saharan Africa J Edge,1 MBBS, BSc, FRCS, MMed (Surg); I Buccimazza,2 MB ChB, FCS (SA), FACS; H Cubasch,3 MB ChB, FCS (SA); E Panieri,4 MB ChB, FCS (SA) Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa Department of Surgery, Nelson Mandela School of Medicine, Durban, South Africa 3 Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Department of Surgery, Faculty of Health Sciences, University of Cape Town, South Africa 1 2

Corresponding author: J Edge (jennyedge1234@me.com)

Communicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer, and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model. S Afr Med J 2014;104(5):377-379. DOI:10.7196/SAMJ.8249

Communicable diseases are the major cause of mortality in lower-income countries. Two-thirds of the worldâ&#x20AC;&#x2122;s HIV population live in sub-Saharan Africa (SSA) and 75% of global deaths due to this disease occur in this region.[1] As a result, both local and international resources have been channelled towards addressing the impact of communicable diseases. However, there is evidence that this pattern of disease burden in low-income countries (LICs) is changing, as HIV is being successfully treated and people are living longer. Cancer predominantly affects the older population. As the life expectancy in LICs increases, the incidence of cancer will increase. The World Health Organization (WHO) has predicted a dramatic rise in the global number of cancer cases in the next 15 years, the majority of which will be in LICs and middle-income countries (MICs). It has been predicted that by 2020 there will be 17 million new cancer cases, and that by 2050 this figure will be 24 million. Of these cases, 70% will be in the developing world.[2] The treatment of cancer is expensive and complex. In the USA, more than US$120 billion per year is spent on cancer care.[3,4] This is in stark contrast to the developing world, where 5% of global cancer funds are spent on 70% of the cancer cases (Table 1).

In LICs, the delivery of healthcare is hampered by many socioeconomic factors such as poor nutrition, sanitation, literacy and transport, and is compounded by the lack of medical personnel, poor infrastructure and health policies.

Table 1. Some discrepancies between LICs and HICs*[5] LIC

HIC

Life expectancy at birth (years)

57.8

82.4

Average GNI per capita (2009, US$)

403

36 953

Total national health expenditure per capita (2009, US$)

4 266

GDP spent on healthcare, %

5.1

11.2

Proportion of healthcare paid by public funding, % 42.0

61.3

Out-of-pocket health expenditure, %

36.3

4) Department of Health website http://www.doh.gov.za - Accessed on 01/04/2014.

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79.2

LICs = low-income countries; HICs = high-income countries; GNI = gross national income; GDP = gross national product. * Figures based on World Bank Health, Nutrition and Population Statistics database.

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The sub-Saharan Africa perspective

According to the WHO, SSA comprises 13% of the world’s population. It also carries 24% of the global disease burden, but has only 1% of the global financial resources to do this. SSA’s demographics show a young population of whom 40% are <15 years of age. The mortality figures mirror this – 80% of all deaths occur in those who are <60 years old. Conversely, in high-income countries (HICs), 80% of deaths occur in those >60 years of age.[6] The cancer patterns seen in SSA are different from those in the developed world. Although the overall cancer incidence is lower than in developed countries, relatively more malignancies are seen in children and young people. The commonest malignancies in women are cervical and breast cancer. There is a lack of medical personnel in SSA. The WHO recommends that ideally the physician:population ratio should be 50:100 000, while in Africa it is only 18:100 000. More than 100 medical schools in SSA were surveyed; half of these reported losing 6 - 8% of their staff in the past 5 years.[7] While the management of cancer requires specialist knowledge, there is a paucity of all types of specialists in SSA. In addition, there RSA: 100 000 739

are discrepancies within the SSA region, with South Africa (SA) faring better than its neighbours. In this regard, it should be noted that SA is essentially an MIC, but due to the gross disparities in socioeconomic class it is effectively both an HIC and a LIC. For example, in Uganda there are 10 specialist anaesthetists[8] compared with 800 in SA (I Buccimazza – unpublished data, 2008) (Fig. 1). Not only are specialist resources scarce, but support services and essential medications are also lacking. Half of those who die from HIV need active pain management during the last 3 months of their life, while 80% of those who die from cancer need pain medication. Yet, access to oral morphine is available in fewer than 11 African countries.[1]

Breast cancer in South Africa

The precise incidence of breast cancer in SA is unknown. There is no reliable national data registry, and the information available is gleaned from individual units in the larger healthcare centres. It is known that in state healthcare facilities, a significant number of patients present with clinically advanced disease. Treatment options are Uganda: 100 000

736

189

172

134

75 20 General

Orthopaedic

6 Neuro

3 Cardiothoracic

Paediatric

3 Plastic

Fig. 1. Comparison of the number of surgical specialists in South Africa (RSA) and Uganda.

further compounded by a high incidence of HIV disease. In a survey, the stage, HIV status and type of breast cancer in 1 200 women who presented to Chris Hani Baragwanath Academic Hospital were documented. Of those tested, 19.7% were HIV-positive, over half presented with locally advanced or metastatic cancer (stage 3 or 4) and 1.5% presented with ductal carcinoma in situ (DCIS). In a screened UK population, nearly 20% of women were diagnosed with DCIS.[9,10] The management guidelines formulated in HICs are unaffordable, unobtainable and inappropriate for the management of breast cancer in LICs. Sambo et al.[11] have summarised the challenges in cancer management in SSA as follows: • Absence of cancer prevention, control policy, strategies and programmes. Most experts agree that mammographic screening is unaffordable and breast examination is generally not a good screening modality. However, studies have not tested this premise in countries where most tumours are clinically obvious or advanced at presentation. A Sudanese pilot study by Abuidris et al.[12] showed the potentially beneficial effects of a cancer awareness programme using trained nonmedical volunteers, and suggests that clinical breast examination may be useful in low-resource settings.[13] There is no national breast cancer policy in place, and regional programmes are in their infancy. A greater emphasis needs to be placed on competent diagnostic units to fast track patients with breast cancer to the appropriate centre of care. • Insufficient recent and comprehensive data for cancer and death registration. For any country to plan a comprehensive health policy, a national register of disease incidence must be kept. • The heavy economic and psychosocial burden of cancer. • Inadequate or no information about cancer, insufficient numbers of skilled

4) Department of Health website http://www.doh.gov.za - Accessed on 01/04/2014.

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•

• • •

healthcare personnel, and scarce local, effective, and sustainable research. A number of initiatives are aimed at retaining medical personnel in their country of origin. The Medical Education Partnership Initiative (MEPI) 2010 provides funds to foreign institutions in SSA countries that receive US President’s Emergency Plan for AIDS Relief (US PEPFAR) support to develop or expand models of medical education. The aim is to improve the quality and quantity of graduates, retain specialists and improve research.[14] The African Organisation for Training and Research in Cancer (AORTIC) held a workshop in Durban to discuss ways of retaining specialists in their country of training.[15] The high cost of immunisation against human papillomavirus and other infections that cause cancer. In SA, the state has recently started a national human papillomavirus immunisation campaign. Unavailability of secondary prevention for cancer amenable to this intervention. Unaffordability of treatment resources and neglect of palliative care. Oral morphine must be made available for use in palliative care. Absence of collaboration or co-ordination of interventions with regard to stakeholders and donors to combat cancer. It is imperative that interested stakeholders unite and work towards a common goal.

Conclusion

The incidence of breast cancer will increase significantly in all LICs. SA and its neighbouring countries will be significantly affected. It is

therefore imperative that healthcare resources, policies and planning focus on this in a co-ordinated and rational way.

References

1. O’Brien M, Mwangi-Powell F, Adewole I, et al. Improving access to analgesic drugs for patients with cancer in sub-Saharan Africa. Lancet Oncol 2013;14:e176-182. [http://dx.doi.org/10.1016/S1470-2045(12)70343-1] 2. Lingwood RJ, Boyle P, Milburn A, et al. The challenges of cancer control in Africa. Nat Rev Cancer 2008;8:398403. [http://dx.doi.org/10.1038/nrc2372] 3. National Cancer Institute. Cancer research funding. http://www.cancer.gov/cancertopics/factsheet/NCI/ research-funding (accessed 30 June 2012). 4. National Cancer Institute. Cancer, Changing the Conversation: The Nation’s Investment in Cancer Research. An Annual Plan and Budget Proposal for Fiscal Year 2012. Bethesda, MD: National Cancer Institute, 2011. http://www.cancerscreening.nhs.uk/breastscreen/publications/baso2010-2011.pdf (accessed 9 March 2014). 5. Anderson BO, Cazap E, El Saghir NS, et al. Optimisation of breast cancer control in low-resource and middleresource countries: Executive summary of the Breast Health Global Initiative Consensus, 2010. Lancet Oncol 2011;12:387-398. [http://dx.doi.org/10.1016/S1470-2045(11)70031-6] 6. World Bank. World development indicators 2012. http://data.worldbank.org/data-catalog/worlddevelopment-indicators/wdi-2012 (accessed 9 March 2014). 7. African Progress Panel. Maternal health: Investing in the lifeline of healthy societies and economies. African Progress Panel Policy Brief, September 2010. http://www.who.int/pmnch/topics/maternal/app_maternal_ health_english.pdf (accessed 9 March 2014). 8. Ozgediz D, Kijjambu S, Galukande M, et al. Africa’s neglected surgical workforce crisis. Lancet 2008;371:627628. [http://dx.doi.org/10.1016/S0140-6736(08)60279-2] 9. Cubasch H, Joffe M, Hanisch R, et al. Breast cancer characteristics and HIV among 1,092 women in Soweto, South Africa. Breast Cancer Res Treat 2013;140(1):177-186. [http://dx.doi.org/10.1007/s10549-013-2606-y] 10. McCormack VA, Joffe M, Van den Berg E, et al. Breast cancer receptor status and stage at diagnosis in over 1,200 consecutive public hospital patients in Soweto, South Africa: A case series. Breast Cancer Research 2013,15:R84. [http://dx.doi.org/10.1186/bcr3478] 11. Sambo LG, Dangou JM, Adebamowo C, et al. Cancer in Africa: A preventable public health crisis. J Afr Cancer 2012;4:127-136. 12. Abuidris DO, Elsheikh A, Ali M, et al. Breast-cancer screening with trained volunteers in a rural area of Sudan: A pilot study: Lancet Oncol 2013;14:363-370. [http://dx.doi.org/10.1016/S1470-2045(12)70583-1] 13. Panieri E. Breast-cancer awareness in low-income countries (Editorial). Lancet Oncol 2013;14:274-275. [http:// dx.doi.org/10.1016/S1470-2045(13)70020-2] 14. Collins FS, Glass RE, Whitescarver J, et al. Developing health workforce capacity in Africa. Science 2010;330:1324-1325. [http://dx.doi.org/10.1126/science.1199930] 15. Morhason-Bello IO, Odedina F, Rebbeck TR, et al. Cancer Control in Africa 1. Challenges and opportunities in cancer control in Africa: A perspective from the African Organisation for Research and Training in Cancer. Lancet Oncol 2013;14:e142-151. [http://dx.doi.org/10.1016/S1470-2045(12)70482-5]

4) Department of Health website http://www.doh.gov.za - Accessed on 01/04/2014.

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ARTICLE SUMMARY

Down-staging of breast cancer in the pre-screening era: Experiences from Chris Hani Baragwanath Academic Hospital, Soweto, South Africa N Murugan,1 MB ChB, FCS (SA); C Dickens,2 PhD; P Pisa,3 PhD; V McCormack,2 PhD; M Joffe,1 PhD; J Jacobson,4 MBA, PhD; H Cubasch1 MB ChB, FCS (SA) Breast Unit, Department of Surgery, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France 3 MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA 1 2

Corresponding author: N Murugan (nivs6ster@gmail.com)

In a survey of the stage of breast cancer seen at first diagnosis, the main determinant of late-stage presentation was found to be travel distance – a factor more apparent in elderly patients. A consecutive series of women with newly diagnosed breast cancer seen at Chris Hani Baragwanath Academic Hospital (CHBAH), Soweto, South Africa, were studied. Electronic patient records were retrospectively reviewed. Data were extracted for: (i) stage and year at diagnosis; (ii) travel distance (estimated straightline distance from GPS-coded residential address to CHBAH); (iii) receptor subtypes; and (iv) age of patient. Generalised linear models were applied to estimate risk ratios for late- v. early-stage disease. The study included patients (N=1 071) with a mean age of 55 years; 90% were black Africans. Of the study participants who lived >20 km from the hospital, 61.8% presented with late-stage disease compared with 50.2% who lived ≤20 km from the hospital. Most (74%) patients >70 years of age who lived >20 km away presented with advanced breast cancer. In younger patients, age showed no clear association with stage of breast cancer at presentation. The literature shows that the incidence and mortality rates of breast cancer in Africa have risen rapidly in recent years. Women in sub-Saharan Africa have some of the lowest incidence rates of breast cancer worldwide; however, the disproportionately high mortality rate reflects poor survival in these developing countries. An advanced stage of disease at first diagnosis contributes significantly to poor survival rates. Predictive factors may include a lack of early detection programmes, poor healthcare infrastructure, and suboptimal availability of and adherence to timely treatment.

Stage at diagnosis, particularly in developing countries, is a strong predictor for breast cancer survival, and understanding the determinants of delays in diagnosis is essential for controlling this increasing burden. The current study provides evidence for the potential down-staging of breast cancer in a peri-urban setting in South Africa in the absence of population-wide mammographic screening. The observed decline in late-stage breast cancer over a 5-year period suggests that down-staging was observed in the absence of screening, probably due to improved access and heightened awareness. Increased travel distance is also likely to affect the postdiagnosis experience of a breast cancer patient as it may influence treatment access and compliance. Repeated cycles of chemotherapy, radiotherapy and post-surgical follow-up visits invariably have a significant financial impact on patients, and travel-associated barriers may intensify as the patient becomes weaker. Another notable finding of our study was that 66.6% of patients were diagnosed with oestrogen and/or progesterone receptor-positive tumours, with only 21.5% of cancers being triple-negative. The predominance of these luminal A and B tumours, which have a better prognosis, and the strong down-staging trend observed over the study period, suggest that late stage at diagnosis in similar settings is increasingly driven by non-biological determinants rather than by an aggressive, rapidly growing tumour.

S Afr Med J 2014;104(5):380. DOI:10.7196/SAMJ.8243

4) Department of Health website http://www.doh.gov.za - Accessed on 01/04/2014.

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Side-effects of systemic therapy for the management of breast cancer A Gudgeon, MB ChB Oncology Unit, Life Vincent Pallotti Hospital, Cape Town, South Africa Corresponding author: A Gudgeon (anneg@iafrica.com)

Systemic treatment for breast cancer is given as neoadjuvent therapy to reduce tumour bulk before surgery, and as adjuvant therapy after surgery to control micrometastatic disease, reduce tumour bulk and improve quality of life in metastatic disease. Systemic therapy is divided into endocrine therapy, chemotherapy and biological response modifier therapy. Before embarking on any systemic therapy, patients should be counselled, as all therapies will cause a higher rate of anxiety and depression, and loss of libido, which for many is a major problem. In pre-menopausal patients, fertility issues should be discussed as the agents used can cause a decrease in or, in some cases, loss of fertility. The decision to administer systemic therapy should be made by a multidisciplinary team consisting of oncologists, radiotherapists, surgeons, nurses and social workers. Any adjuvant agent can be administered in metastatic therapy, but the aim of treatment here is to reduce tumour-related side-effects. As it is not the objective to replace the latter by treatment-related side-effects, metastatic disease is treated with single-agent sequential drugs, while adjuvant therapy employs drug combinations aimed at eliminating micrometastatic disease and reducing drug resistance. The downside of combination therapy is an increase in sideeffects. Many new drugs are being used for cancer management

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and the alleviation of side-effects. One of the major advances in the management of nausea associated with chemotherapy is the improvement in anti-emetic medication.

Common side-effects

Common side-effects include myelosuppression, nausea and vomiting (now well controlled with anti-emetics), alopecia (usually temporary), tiredness, neurotoxicity, hypersensitivity reactions, and cardiotoxicity. Mucositis, oral ulcers, dry itchy eyes and bladder sensitivity with chemical cystitis may occur with varying frequency. Most of the drugs have some or all of these side-effects, which are very rarely problematic. All the side-effects, except for alopecia, are manageable and reduced or eliminated by premedication and dose scheduling according to body surface area. It is important to discuss all side-effects with the patient before treatment so that they are fully informed. The management of breast cancer has become more personalised, and a multidisciplinary team caring for the patient should decide on the systemic regimens used. Most side-effects resulting from chemotherapy can be managed. In future, more targeted therapies will be used. S Afr Med J 2014;104(5):381. DOI:10.7196/SAMJ.8250

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The management of breast cancer-related lymphoedema C M Marco,1 RN, MPhil MCH, Certified Lymphoedema Therapist (Norton School of Lymphatic Therapy, USA); R Pillay,2 BSc OT, Certified Lymphoedema Therapist (Norton School of Lymphatic Therapy, USA); C Schoonheim,3 BSc PT, Certified Lymphoedema Therapist (Norton School of Lymphatic Therapy, USA) Private Practice, Claremont, South Africa Department of Occupational Therapy, Groote Schuur Hospital, Cape Town, South Africa 3 Private Practice, Hout Bay, South Africa 1 2

Corresponding author: C M Marco (cmarco@telkomsa.net)

Lymphoedema is a chronic debilitating condition characterised by an accumulation of protein-rich fluid in interstitial spaces due to insufficient functioning of the lymphatic system. The condition may be referred to as primary (congenital malformation) or secondary (damage to the lymphatic system) lymphoedema. Lymphoedema is currently incurable, but can be alleviated with appropriate treatment. However, if ignored, it can progress and become difficult to manage. Breast cancer-related lymphoedema (BCRL) is a secondary form of lymphoedema and a major complication of post-breast cancer surgery and radiotherapy. It occurs when the network of lymphatic vessels and lymph nodes is damaged by disease, surgery or radiotherapy. The lymph, a protein-rich fluid, then accumulates in the tissue spaces, which is clinically manifested by swelling of the upper limb on the affected side. Sometimes the chest and breast areas may also be affected. If BCRL is not detected and treated in its early stages, the condition becomes chronic and debilitating with severe physical, psychosocial and economic implications on the breast cancer survivorâ&#x20AC;&#x2122;s quality of life. The physiological factors include recurrent infections, limited movement of the limb due to pain, numbness and tenderness. The psychosocial factors include social isolation, anxiety, depression, and poor self- or body image. The economic factors include loss of employment and increased medical costs.

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All breast cancer survivors are at risk of developing BCRL despite new surgical techniques. The lifetime risk of BCRL ranges from 33% to 44%. In addition, if lymphoedema is left untreated, it may result in recurrent cellulitis in the limb and generalised systemic infection. Currently there is no cure for BCRL, but there are international best practice guidelines to prevent or reduce its severity. These recommended best practice guidelines, referred to as combined decongestive therapy (CDT), include gentle massaging known as manual lymph drainage, use of multilayered compression bandaging to the affected limb, exercise and skin care. CDT facilitates functioning of the impaired lymphatic system and the eventual reduction of lymph volume in the affected upper limb. Lymphoedema is a chronic condition that requires compliance and self-management. Therefore, those living with the condition must be educated in basic management of the condition and in identifying severe symptoms such as cellulitis in order to seek professional medical treatment. South Africa lacks official guidelines and protocols on the management of lymphoedema. There are few lymphoedema specialists in the country and most of them are in the private sector.

S Afr Med J 2014;104(5):382. DOI:10.7196/SAMJ.8251

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ARTICLE SUMMARY

Stigma, survivorship and solutions: Addressing the challenges of living with breast cancer in low-resource areas M Mutebi,1 MB ChB, MMed (Surg); J Edge,2 MBBS, BSc, FRCS, MMed (Surg) Surgical Oncology Fellow, Department of Endocrine and Surgical Oncology, Groote Schuur Hospital, Cape Town, South Africa, Aga Khan University Hospital, Nairobi, Kenya, and Research Advocacy, African Organisation for Research and Treatment in Cancer (AORTIC), Cape Town, South Africa 2 Netcare Christiaan Barnard Memorial Hospital, Cape Town, South Africa 1

Corresponding author: M Mutebi (mcmutebi@yahoo.com)

Breast cancer in developing nations is characterised by late diagnosis. The causes are multifactorial and many are addressed in other articles in this edition of CME. Breast cancer is also seen in younger women. The late-presentation trend is slowly changing in some areas, and an increasing number of women are presenting earlier. These patients, if managed appropriately, have a more favourable prognosis. As a result, developing nations must now begin to consider the concerns of breast cancer survivorship. In developed countries, there are a number of organisations that support breast cancer survivors. In this article, we highlight some of the psychosocial aspects of living with breast cancer in low-resource areas.

Age at presentation

It has been demonstrated that the overall mean age at which African women present with breast cancer is 35 - 45 years, 10 - 15 years earlier than their Caucasian counterparts. A 3-year retrospective review of 374 breast cancer patients in Kenya showed a median age of 44 years at presentation; only 26 of 250 patients (10.4%) had early breast cancer. In another review, 72.8% presented with advanced breast cancer (Manchester stage III and IV disease). In South Africa, no national data exist. Individual breast centres are increasingly reporting their experience with early presentation.

Stigma

Stigma refers to the attachment of negative connotations to a diagnosis. The Livestrong Foundation Report determined that stigma is an important part of cancer diagnosis. Studies in African American women show that fatalism, stigma and privacy are some of the key factors influencing non-attendance in regions where national screening programmes exist, and especially in low-resource environments where facilities do not exist. Fedaloc CME island.pdf

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Patients in low-resource settings face unique challenges in having to cope with breast cancer. They have to deal not only with the emotional impact of a cancer diagnosis, but also with the additional constraints of poverty, lack of access to care and dependence on their partners for financial support.

Survivorship

The American College of Surgeons classifies survivorship as â&#x2030;Ľ5 years since the initial diagnosis of cancer. Little has been written on survivorship in low- and middle-income countries owing to the frequent lack of national cancer registries and poor patient follow-up. Survivorship in developing countries constitutes a newly emerging concept. With the transition to survivorship, there are new concerns along the Ferrell domains, all of which may warrant interpretation in a regional context. Breast cancer survivors encounter unique challenges in the face of socioeconomic constraints and in the absence of an established survivor support system.

Solutions

Regardless of the patientâ&#x20AC;&#x2122;s environment, a comprehensive care plan should be developed for cancer survivors. We need to optimise ways to ameliorate the overall suffering and remove the stigma of breast cancer. Practical strategies in low-resource environments include the development of an effective cancer navigation system, as well as increasing breast cancer awareness, promoting cancer advocacy and strengthening the survivorship base by providing positive role models who have survived cancer.

S Afr Med J 2014;104(5):383. DOI:10.7196/SAMJ.8253

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CONTINUING MEDICAL EDUCATION

ARTICLE SUMMARY

An approach to the management of locally advanced breast cancer: Part 1 P Govender, MB ChB, FC Rad Onc (SA), MMed, Certification in Medical Oncology European Society for Medical Oncology (ESMO) Department of Radiotherapy and Oncology, University of KwaZulu-Natal, Durban, South Africa Corresponding author: P Govender (govenderp10@ukzn.ac.za)

Locally advanced breast cancer (LABC) comprises a heterogeneous group of diseases. It incorporates a subset of stage IIB (T3N0) disease, stage III disease and inflammatory breast cancer. In the developed world, 7% of breast cancer patients have stage III disease at diagnosis. However, in developing countries LABC constitutes about 30 - 60% of all cases, most probably attributable to a lack of education and poor socioeconomic status.

Initial patient evaluation

A detailed history of the presenting symptoms, previous breast pathology, risk factors for breast cancer, medical and surgical comorbidities and, in the pre-menopausal female, aspects surrounding family planning and fertility, are important. This should be followed by a complete clinical examination and blood tests, including a full blood count, a liver function test and alkaline phosphatase levels. Core needle breast biopsy is the standard diagnostic procedure as it results in minimal tumour perturbation while offering important diagnostic information. It also provides information on tumour biomarkers, tumour grade and the Ki67 proliferation marker. In our practice, patients with LABC undergo an initial isotope bone scan to exclude bone metastases and an abdominal ultrasound scan to exclude liver metastases.

Neoadjuvant chemotherapy Rationale

Neoadjuvant chemotherapy refers to chemotherapy prior to surgery and is the current standard of care for LABC. Benefits include eradication of occult distant micrometastases and down-staging of an inoperable tumour to an operable one.

Regimens

These are historically anthracycline-based regimens and cyclo- phosphamide with or without fluoropyrimidines, e.g. 5-deoxyfluoro uridine. Second-generation trials focused on the addition of taxanes (paclitaxel or docetaxel), either in combination or sequentially with Fedaloc CME island.pdf 1 2014/04/02 3:36 PM anthracycline-based regimens.

Neoadjuvant hormonal therapy

Neoadjuvant hormonal therapy is an effective therapeutic modality for down-sizing primary tumours and rendering them operable, as well as increasing conversion rates from mastectomy to breast conservation surgery in post-menopausal, HR-positive breast cancer patients.

HER2-directed therapies

Approximately 20% of breast cancers overexpress the epidermal growth factor receptor HER2-neu, providing a prognostic and predictive marker for improving pCR rates.

Adjuvant radiotherapy

Radiotherapy can usually start within 2 - 4 weeks of surgery. Patients receiving chemotherapy can usually begin radiotherapy 3 weeks after the last cycle of chemotherapy.

Adjuvant hormonal therapy Pre-menopausal females

The standard adjuvant hormonal therapy in pre-menopausal women with ER-positive disease is tamoxifen alone for 5 years, but benefit has also been shown with ovarian function suppression (OFS) using luteinizing hormone-releasing agonists, specifically in the absence of chemotherapy. Nonetheless, the use of OFS added to chemotherapy, tamoxifen or a combination of both is not routinely recommended.

Post-menopausal females

The aromatase inhibitors (AIs), anastrozole, letrozole and exemes tane, have been widely investigated in the adjuvant setting. These drugs may be used as up-front therapy for 5 years, ‘switch’ strategy of initial tamoxifen for 2 - 3 years, followed by an AI for 2 - 3 years, the reverse sequence, or as an extended treatment after 5 years of tamoxifen, especially in node-positive patients.

S Afr Med J 2014;104(5):384. DOI:10.7196/SAMJ.8245

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