Asian Journal of
Paediatric PRACTICE Volume 14, Number 3
Dr. KK Aggarwal
Dr. Swati Y. Bhave Editor
With Best Compliments From
Asian Journal of
Paediatric Practice An IJCP Group Publication
Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor
From the Desk of Editor
Dr Deepak Chopra Chief Editorial Advisor
Dr KK Aggarwal CMD, Publisher and Group Editor-in-Chief Dr Veena Aggarwal Joint MD and Group Executive Editor Anand Gopal Bhatnagar Editorial Anchor AJPP Speciality Board Chief Editor Dr Swati Y Bhave
Dr Swati Y Bhave............................................................5
From the desk of group editor-in-chief Fever Myth..............................................................6 KK Aggarwal
Editorial Board International (Group) Dr Adenike Grange (Lagos Nigeria) Dr Alberto Bissot (Panama) Dr Anagha (New Zealand) Dr Andreas Constantopoulos (Greece) Dr Dilip Patel (USA) Dr Donald E Greydanus (USA) Dr Ellis D Avner (USA) Dr Giorgio Tamburlini (Italy) Dr Helen Pratt (USA) Dr James Tumwne (Kampala, Uganda) Dr Jesson Unni (Kerala) Prof. Jose Boix Ochoa (Barcelona) Dr Manuel Katz (Israel) Dr Manuel Moya (Spain) Dr MC Rahimy (West Africa) Dr Murat Yurdakok (Turkey) Dr Najwa Khuri-Bulos (Jordan) Dr Sergio Augusto Cabral (Brazil) Dr Shiv Aggarwal (Florida) Dr VB Sanghi (Michigan) Dr Yoshikatsu Eto (Japan) Dr Zulfiqar Bhutta (Pakistan) Dr Zulfi Bhutta (Pakistan) Anand S Vasudev (New Delhi)
IJCP Editorial Board Dr Alka Kriplani Asian Journal of Obs & Gynae Practice Dr VP Sood Asian Journal of Ear, Nose and Throat Dr Praveen Chandra Asian Journal of Clinical Cardiology Dr Swati Y Bhave Asian Journal of Paediatric Practice Dr Vijay Viswanathan The Asian Journal of Diabetology Dr KMK Masthan Indian Journal of Multidisciplinary Dentistry Dr M Paul Anand, Dr SK Parashar Cardiology Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramchandran, Dr Smith A Sethi Diabetology Dr Ajay Kumar Gastroenterology Dr Koushik Lahiri Dermatology Dr Georgi Abraham Nephrology Dr Sidharth Kumar Das Rheumatology Dr V Nagarajan Neurology Dr Thankam Verma, Dr Kamala Selvaraj Obs and Gyne
Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions
original study Assessment of Antioxidant Enzymes . and Trace Elements Status in Children . Suffering from Severe PEM in Western . Madhya Pradesh.....................................................7 Ravinder K Arora, Neelesh Arya, P Sarkar, NM Shrivastava, Nadeem Khan
case report Addisonâ€™s Disease Presenting Initially as Bronchial Asthma in a Child................................11 T Sathish Kumar, Sam Ebenazar, J Julius Xavier Scott
drug therapy Role of Leukotriene Antagonists in . the Management of Allergic Rhinitis . and Asthma...........................................................13 Aru Handa
research article Chronic Pain Associated with the . Chikungunya Fever: Long Lasting . Burden of an Acute Illness...................................18 Daniel Ciampi de Andrade, Sylvain Jean, Pierre Clavelou, Radhouane Dallel, Didier Bouhassira
Asian Journal of
Paediatric Practice Contents
Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Pvt. Ltd. and Published at E - 219, Greater Kailash, Part - 1, New Delhi - 110 048 E-mail: firstname.lastname@example.org Printed at SR Offset Printers, Chennai E-mail: email@example.com © Copyright 2011 IJCP Publications Pvt. Ltd All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Pvt. Ltd. No part of this publication may be published in any form what-soever without the prior written permission of the publisher.
short report Dengue Fever (DF) in Pakistan...........................25 Fridous Jahan
Photo quiz Acute Foot Rash in a Healthy Child . During Travel........................................................30
Cover Photograph by Jeevan Vamsi
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Algorithm for the Management of a Previously Health Infant 0-90 days of Age with Fever . without Source, ≥100.4°F....................................32
practice guidelines AAP Reports on Diagnosis and Prevention . of Iron Deficiency Anemia....................................33
emedinews section From the eMedinewS............................................34
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From the Desk of Editor
Dear Readers Protein energy malnutrition is the leading cause of death among children below five years of age, especially in the developing world. Depleted antioxidant protection may be a contributing factor to the pathophysiology of protein energy malnutrition (PEM) and replenishment of these elements in its management is important. The article by Dr Ravinder K Arora et al ‘Assessment of Antioxidant Enzymes and Trace Elements Status in children Suffering from Severe PEM in Western Madhya Pradesh’ has investigated the role of antioxidant enzymes and trace elements as protective agent and their deficiencies associated with manifestation of PEM.
Dr Swati Y Bhave* Chief Editor
There is an interesting case report ‘Addison’s Disease Presenting Initially as Bronchial Asthma in a Child’ by T Sathish Kumar and co-authors, which alerts clinicians that asthma may be an uncommon presenting sign of Addison’s disease and in the presence of hyperpigmentation in a child with wheezing Addison’s disease should be entertained as a possible association. There are also other articles that deal with management of allergic rhinitis and asthma as well as Chikungunya and Dengue fever, the disease conditions that been much in the news in our country as the cause of recent outbreaks. This journal also contains our regular features like Photo Quiz, Clinical Algorithm and Practice Guidelines and eMedinewS Section. The success of a journal depends directly on the number of quality articles submitted for review. Accordingly, I would like to request your participation by submitting quality manuscripts for review and also encouraging your colleagues to do the same. I appreciate your support as we strive to make our journal the most informative on Pediatric topics. Happy Reading...
Dr Swati Y Bhave
*Executive Director AACCI, Association of Adolescent and Child Care in India Senior Visiting Consultant, Indraprastha Apollo Hospitals, New Delhi IPA Coordinator of Development (International Pediatric Association) VIMHANS, New Delhi Address for correspondence IJCP Group of Publications E - 219, Greater Kailash, Part - 1 New Delhi - 110 048
Asian Journal of Paediatric Practice, Vol. 14, No. 3
From the Desk of Group Editor-in-Chief
Dr KK Aggarwal
Padma Shri and Dr BC Roy National Awardee Sr Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group Editor-in-chief, eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) firstname.lastname@example.org http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)
here’s no need to normalize the child’s temperature. Parents should focus therapeutic efforts on making the child comfortable, according to a new clinical guidance on talking to parents about fever from the American Academy of Pediatrics. There’s no evidence that fever itself can increase the risk of adverse outcomes like brain damage, wrote Janice E Sullivan, MD, of the University of Louisville, and Henry C Farrar, MD, of the Arkansas Children’s Hospital and colleagues. According to the guidance, which was published in the journal Pediatrics, physicians should help parents understand that fever is not a primary illness; rather, it is a physiologic mechanism that has beneficial effects in fighting infection. It retards the growth and reproduction of bacteria and viruses, enhances neutrophil production and T-lymphocyte proliferation, and aids the body’s acute-phase reaction. Parents should also be instructed that antipyretic use does not prevent febrile seizures. The primary goal in treating fever should solely be to improve the child’s overall comfort level. The best way to do so is with antipyretics such as acetaminophen or ibuprofen. The recommended dose for acetaminophen is 10-15 mg/kg/dose every 4-6 hours, and ibuprofen is recommended in a 10 mg/kg dose. There’s no difference between the two medications in efficacy of reducing the symptoms of fever. There’s some evidence that combining these two products - by giving them in alternate doses - may be beneficial, but researchers warn that this may be associated with more adverse effects. They caution that the regimen may be more confusing for parents to keep track of. Ibuprofen may carry a risk of nephrotoxicity, but more so in children with dehydration or complex medical illnesses. Hepatotoxicity with acetaminophen has been observed in the setting of acute overdose, and hepatitis may present in chronic overdose. Parents should not wake children to provide medication. They should also be cautioned about giving other cough and cold products that contain an antipyretic at the same time, which could result in overdose. Parents should be careful to keep children properly hydrated. n
Asian Journal of Paediatric Practice, Vol. 14, No. 3
Assessment of Antioxidant Enzymes and Trace Elements Status in Children Suffering from Severe PEM in Western Madhya Pradesh Ravinder K Arora*, Neelesh Arya**, P Sarkar*, NM Shrivastava**, Nadeem Khan**
Abstract Severely malnourished children have a high mortality rate. About 60% of children in Madhya Pradesh are suffering from malnutrition. The current study was done to assess the levels of antioxidant enzymes (glutathione peroxidase [GPX], superoxide dismutase [SOD]) and trace elements (zinc, copper, selenium) in protein energy malnutrition (PEM) children. This study was carried out in 100 children suffering from PEM (age 1-3 years) and compared with healthy children, which served as control. All patients and controls were subjected to estimation of serum levels of zinc, copper and selenium and also estimation of enzymatic activity of the RBCs SOD and whole blood GPX with the help of spectrophotometer. There was a significant decrease seen in the level of antioxidant enzymes and trace elements in PEM children as compared with the control group. Hypoproteinemia and anemia in malnourished children were also associated with significant decline in both zinc and copper levels. Serum trace element deficiency leading to depleted antioxidant protection may be a contributing factor to the pathophysiology of protein malnutrition and so replenishment of these elements in the management of this condition is important. Key words: Reactive oxygen species, superoxide dismutase, glutathione peroxidase
rotein energy malnutrition (PEM) previously termed protein calorie malnutrition has assumed the position of being the leading cause of death directly or indirectly among children under five years of age in the developing world in the past 40 years,1 in spite of our wide knowledge and understanding of human nutritional requirements. Kwashiorkor and marasmus are clinical consequences of severe protein energy malnutrition. Kwashiorkor is characterized by hypoalbuminemia and edema.2 In recent years, reactive oxygen species (ROS) have been implicated in the pathogenesis of many diseases conditions.3 Oxidative stress in PEM infants may result from either increased production of free radicals or depletion of the antioxidant defense mechanism.3 Disequilibrium in the balance between oxidants and antioxidants has been reported as a possible etiology of kwashiorkor and can be used as prognostic factor in children with PEM.5 Protein energy malnutrition often co-exists with micronutrient deficiencies.6 More than half of all child
*Dept. of Biochemistry, MGM, Indore (MP) **Dept. of Pharmacology, GMC, Bhopal (MP) Address for correspondence Dr Nadeem Khan Dept. of Pharmacology Gandhi Medical College, Royal Market, Bhopal - 462 001, MP
Asian Journal of Paediatric Practice, Vol. 14, No. 3
deaths are associated with malnutrition. Sixty percent of children in Madhya Pradesh are suffering from malnutrition. Madhya Pradesh is only state wherein malnutrition has risen from 55 to 60%, in the last 10 years.7 The aim of this study was to assess the level of antioxidant enzymes and trace elements in children suffering from PEM, and their correlation, and also to highlight the possible role of these antioxidant enzymes and trace elements as protective agents and the association of their deficiencies with manifestation of PEM. Material and Methods Subjects
This study was carried out in 100 children with severe protein energy malnourished admitted to MY Hospital, Indore (MP). Their age range was from 1 to 3 years. The children were examined for clinical signs of malnutrition, grouped as kwashiorkor, marasmus or marasmic kwashiorkor, using the Wellcome criteria of classification. Hundred children (same age group), with an apparently normal and healthy physique and presenting with no clinical or anthropometric signs or symptoms suggestive of any
Five milliliter of blood was collected from peripheral vein in two different vials: 1 ml of blood was transfer in ethylenediaminetetraacetic acid (EDTA) vial for estimation of super oxide dismutase (SOD), glutathione peroxidase (GPX). Remaining blood was transferred in plain vial for estimation of serum zinc copper and selenium. The blood was centrifuged at 3,000 rpm for 10 minutes. The serum and blood was stored and frozen at (–20°C) until further analysis. Biochemical Analysis Enzymes Analysis
Superoxide dismutase activity was measured by the inhibition of pyrogallol auto-oxidation at 420 nm for three minutes according to the method of Marklund and Marklund.8 The enzyme activity was expressed as U/mg protein, where 1 U is the amount of enzyme required to bring about 50% inhibition of the autooxidation of pyrogallol. GPX activity was assayed by the method of Rotruck et al9 using H2O2 as the substrate. Enzyme activity was expressed as _g of glutathione oxidized/min/mg protein. Trace Elements Analysis
The zinc and copper concentrations in serum were measured by means of an Atomic Absorption Spectrometer (Varian spectra A 250 Plus, Australia), with a deuterium background correction. The zinc and copper concentrations in the samples diluted 1:5 with ultradeionized water and values were expressed in µg/dl. Each measurement was performed twice and averages were taken. Statistical Analysis
Statistical evaluation was carried out with appropriate statistical software. Data obtained from the study groups were compared by Student’s t-test. Correlations
and analysis between variables were made by Pearson’s test; p < 0.05 were considered as statistically significant. All the results were expressed as mean with their standard deviation (mean ± SD). Results In the present study, it was observed that concentration of these trace elements levels were significantly (p < 0.05) decreased in malnourished children when compared with controls (Table 1). The mean GPX, SOD enzyme activities were also significantly (p < 0.05) also decreased in malnourished children as compared to controls (Table 2). A negative correlation of zinc with SOD (r = -0.102 p = 0.311), which was Table 1. Mean Serum Trace Elements in Control and Malnourished Children (Mean ± SD) Control (n = 100)
Marasmus (n = 80)
102.42 ± 7.69
75.25 ± 5.37
62.77 ± 1.53
106.49 ± 8.69
70.10 ± 9.30
64.91 ± 2.37
6.37 ± 0.60
5.09 ± 0.54
4.46 ± 0.29
Kwashiorkor p value (n = 20)
Zn = zinc; Cu = Copper; Se = Selenium
Table 2. Mean Antioxidant Enzymes in Control and Malnourished Children (Mean ± SD) Parameters
Control (n = 100)
Marasmus (n = 80)
Kwashiorkor (n = 20)
Cu - Zn SOD (U/ mg)
1263 ± 3.03
942.21 ± 33.82
895.59 ± 65.53
GPX (g/min/mg protein)
48.66 ± 5.00
30.43 ± 4.33
25.1 ± 4.17
120 100 SOD (U/mg)
form of malnutrition were used as the control group. All subjects were of the same socioeconomic background. The children were selected with the help of consultant pediatricians, the volunteers and study protocol were maintained as per norms of Centre Ethics Committee on Human Research (CECHR) and Mahatma Gandhi Memorial Medical College, Indore (MGM) Ethical Committee.
80 60 40 20 0 0
Zn (µg/dl) Figure 1. Correlation between SOD and Zn.
Asian Journal of Paediatric Practice, Vol. 14, No. 3
100 80 60 40 20 0 0
Cu (ug/dl) Figure 2. Correlation between SOD and Cu.
significant decrease in protein energy malnourished children as compared with the control group and are in agreement with that of Shaaban,10 Ashour11 in which GPX deficiency was explained by either consumption in peroxidation reaction due to oxidative stress or as being due to deficiency of selenium. Zinc deficiency in infants and children can result from inadequate dietary intake, impaired absorption and excessive excretion and as inherited defect in zinc metabolism and some other dietary components may inhibit the bioavailability of zinc.13 Clinical features of severe zinc deficiency in children are growth retardation, delayed sexual and bone maturation, diarrhea, impaired appetite, alopecia. Copper deficiency in infants and children may result from inadequate diet, low birth weight, malabsorption syndrome and repeated bouts of acute diarrhea and decreased of breastfeeding.14
60 40 20 0 0
Se (ug/dl) Figure 3. Correlation between GPX and Se.
not statistically significant. Copper showed positive correlation with SOD (r = 0.134, p = 0.184) which was not statistically significant. Also no significant correlation was seen between Selenium and GPX (r = 0.107 p = 0.287) (Figs. 1-3). Discussion In the present study the status of both trace elements and antioxidants were examined in children suffering from PEM and compared them with normal healthy children (controls). The results of the present study shows that SOD level was significantly decreased in all malnourished children as compared to controls and similar findings have been reported by Shaaban,10 where SOD deficiency in PEM was explained by either consumption in dissimulating reactions where ROS are removed by SOD, or as being secondary to deficient levels of copper or zinc both known to be integral parts of copper-zinc SOD. Ashour11 reported an increased in SOD, where as Squali Houssaini12 found no changes in it which is in contrast with our findings. SOD levels were also decreased in children suffering from thalassemia, low birth infants, diabetes mellitus, etc. Mean whole blood GPX showed Asian Journal of Paediatric Practice, Vol. 14, No. 3
Selenium levels have found to be significantly low in malnourished children as compared with the controls; our studies are in agreement with the previous studies done by Samir Mohammed et al.15 Selenium is an essential trace elements for humans and animals and plays an important role in antioxidant defenses, thyroid-hormone metabolism and redox control of enzymes and proteins. Deficiency of selenium in malnourished children can be due to restricted protein intake, unsupported parenteral nutrition, malabsorption.16 Selenium deficiency has been associated with two diseases; a cardiomyopathy known as Keshan disease17 and an endemic osteoarticular disorder known as Kashin-Beck disease.18 It seems that relation is not simple, and other factors also play an important role in protein energy malnutrition. There are multinutrient deficiencies including calories, vitamins and minerals. It could be that some minerals affect the metabolism of others and also some vitamins cannot be probably metabolized if certain vitamins or minerals are not present in sufficient quantities. This may involve intravenous fluids to treat dehydration and blood transfusion to treat anemia. Of utmost importance is the nutritional support, which may require initial parental nutrition and slowly advance to oral feedings. Conclusion Children with PEM are potentially susceptible to high oxidative stress and the harmful effect of free
original study radicals had to edema and many other serious diseases. Disturbances of this system in malnourished children may result from a dietary insufficiency of nutrient antioxidants, protein and minerals. It is therefore advisable to include antioxidant nutrients, protein and trace metals supplements to the therapies used for the management of PEM. Suggested Reading 1. Ibukun-Olu Alade. Public Health Nutrition. 2nd edition, Tosco Press, Nigeria 2001:107-13, 33-8. 2. Khalil IF. Disorders of malnutrition. In: Community Medicine. 2nd edition, EI Frass Printer 1995:267-70. 3. Sive AA, Subotzky EF, Malan H, Dempster WS, Heese HD. Red blood cell antioxidant enzyme concentration in Kwashiorkor and marasmus. Ann Trop Pediatr 1993;13(1):33-8. 4. Albrecht R, Pelissiar MA. L hypotheses radicalaire du kwashiorkor cahiers de Nutrition et de dietetiqye 1994;29:12-5. 5. Fantone JC, Ward PA. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol 1982;107(3): 395‑418. 6. Gracey M. Diarrhea and malnutrition: a challenge to pediatricians. J Pediatr Gastroentrol Nutr 1996; 22(1):6-16. 7. Kumar K. Why malnutrition deaths continue to happen in Madhya Pradesh? http://www.Countercurrents.org 27 July, 2008. 8. Miller JK, Brzeinska-Slebodzinska E, Madsen FC. Oxidative stress, antioxidants, and animal function J Dairy Sci 1993;76(9):2812-23. 9. Bhor VM, Raghuram N, Sivakami S. Oxidative damage and altered antioxidant enzyme activities in the small
intestine of streptozotocin-induced diabetic rats. Int J Biochem Cell Biol 2004;36(1):89-97. 10. Kumar AP, Rajagopal G. Lipid peroxidation in erythrocytes of patients with type 2 diabetes mellitus. Indian J Clin Biochem 2003;18(1):71‑4. 11. Shaaban SY, Nassar MF, Ibrahim SA, Mamoud SE. Impact of nutritional rehabilitation of enzymatic antioxidant levels in protein energy malnutrition. East Mediterr Health J 2002;8(2-3):290-7. 12. Ashour MN, Salem SI, EI-Gadban HM, Elwan NM, Basu TK. Antioxidant status in children with proteinenergy malnutrition (PEM) living in Cairo Egypt. Eur J Clin Nutr 1999;53(8):669-73. 13. Houssaini FZ, Iraqi MR, Arnaud J, Richard MJ, Favier A. Trace elements and protein calorie malnutrition in Fes area (Morocco). Biomed Pharamcother 1997;51(8):349-51. 14. Lonnedral B. Dietary factors influencing zinc absorption. J Nutr 2000;130(55 Suppl):1378S-83S. 15. Castillo-Duran C, Uauy R. Copper deficiency impairs growth of infants recovering from malnutrition. Am J Clin Nutr 1988;47(4):710-4. 16. Mohammed S, Abou EL Hassan. Assessment of the relation between trace elements and antioxidant status in children with protein energy malnutrition. Int J Pediatr Neonatol 2004;4(1):1-12. 17. Beck MA, Lavender OA, Handy J. Selenium deficiency and viral infection. J Nutr 2003;133 (Suppl 1):1463S‑7S. 18. Moreno-Rayes R, Suetens C, Matheiu F, Begaux F, Zhu D, Rivera Mt, et al. Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med 1998;339(16):1112-20. 19. Seims WG, Sommerburg O, Grune T. Erythrocyte free radical and energy metabolism. Clin Nephrol 2000;53 (1 Suppl):S9-S17.
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Addison’s Disease Presenting Initially as Bronchial Asthma in a Child T Sathish Kumar*, Sam Ebenazar**, J Julius Xavier Scott†
Abstract A case of a 2-year-old boy who was admitted as bronchial asthma and eventually diagnosed to have Addison’s disease is presented here. Addison’s disease presenting initially as bronchial asthma is a rare occurrence. We report this case to alert physicians caring for children with asthma that, in the presence of hyperpigmentation in a child with wheezing, Addison’s disease should be entertained as a possible association. Key words: Bronchial asthma, Addison’s disease
Case Report A 2-year-old boy presented to us with acute exacerbation of wheezing. He reportedly had recurrent episodes of wheezing since two months of age. He is the third child born to consanguineous parents. His birth weight was 2.5 kg. He was noticed to have dark complexion since infancy but this was not taken notice of as significant by his parents. His development was normal and he was adequately immunized for age. He was hospitalized thrice in the past for wheezing and needed treatment with intravenous fluids, oxygen, antibiotics, bronchodilators and steroids. He never had any recurrent episodes of vomiting or symptoms of shock. On Examination
On examination, his weight was 11 kg and height was 81 cm. His blood pressure was 90/70 mmHg. He had generalized hyperpigmentation. Rest of the systemic examination was within normal limits. Investigation
Investigations revealed: Hemoglobin - 11 gm%, total leukocyte count - 11,600/mm3, differential count *Reader **Registrar, Christian Medical College, Vellore, Tamil Nadu † Associate Professor, Dept. of Pediatrics Sri Ramachandra Medical College, Porur, Tamil Nadu Address for correspondence Dr J Julius Xavier Scott Associate Professor, Dept. of Pediatrics Consultant, Pediatric Hematology and Oncology, Sri Ramachandra Medical College Hospital, Porur, Tamil Nadu E-mail: email@example.com
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(N 68%, L 25%, BF 4%, E 3%). Serum sodium was 143 mmol/l, potassium was 3.6 mmol/l and creatinine was 0.4 mg%. His random blood sugar was 129 mg%. His chest radiograph was normal and Mantoux test was negative at 48 hours. Initially he was diagnosed and managed as bronchial asthma, but in view of generalized hyperpigmentation, Addison’s disease was considered as a possibility and he was evaluated for this. Serum cortisol at 8 a.m. and 11 p.m. were <1 µg%. His serum 17 hydroxyprogesterone was <5 ng/ml, dehydroepiandrosterone sulfate was 10.4 µg%, plasma renin activity was 0.5 ng/ml/hour. His serum cortisol showed no rise after administering intravenous synacthen 250 µg, with 30 and 60 minutes values remaining <1 µg%. He was started on oral hydrocortisone 10 mg thrice-daily for a week, and then tapered to 10 mg in morning and 5 mg in evening. With steroid replacement therapy, his pigmentation lessened and he had no further recurrence of asthmatic attacks. He is doing well on follow-up. Discussion Addison’s disease with initial presentation as bronchial asthma had rarely been reported in children.1 Green et al and Harris et al reported that there was a possible relationship between Addison’s disease and asthma.2,3 In most of these cases both these symptoms appeared together but in a few cases, clinical features of Addison’s disease were absent.4 In a retrospective survey of 481 patients with Addison’s disease, 27 were described as having allergic disease.5 In our case, the parents noticed Cont’d on page 24... 11
Role of Leukotriene Antagonists in the Management of Allergic Rhinitis and Asthma Aru Handa
Abstract It is now recently recognized that asthma and allergic rhinitis (AR) are linked. Most guidelines now recommend that asthmatic patients should be routinely evaluated on how their AR affects asthma. Cysteinyl leukotrienes are the key drivers of symptoms in both asthma and the early and late phase AR response. This response is not blocked by steroids or antihistamines. Montelukast is an oral leukotriene receptor antagonist (LTRA) that has now proven to be efficacious in the treatment of both asthma and AR and it is the only drug therapy approved to treat both conditions in a single formulation. This article explains the role of leukotriene antagonists alone and in combination therapy in these conditions. Key words: Allergic rhinitis, asthma, leukotriene receptor antagonist, montelukast
eukotriene modifiers are one of the most recent class of medications, which are approved for use in the treatment of asthma and allergic rhinitis (AR), ever since the introduction of inhaled corticosteroids (ICS) in 1972 for these conditions. Leukotriene receptor antagonists (LTRAs) are effective in both AR and asthma patients and they provide a very good option for those patients who are not compliant with topical drugs.1 Therapeutic strategies which use LTRAs are really an advancement in therapy for large numbers of patients with asthma and co-existing AR. A montelukast-induced reduction in airway eosinophilia has been recently reported in the sputum of patients with asthma. This therapy can increase patient compliance and improve the quality-of-life of these patients.2 LTRAs have shown beneficial effects also in challenge models such as allergen and exercise- induced asthma in patients with wheeze and decreased lung function, and also in mild chronic asthma.3 Role of Mediators in AR and Asthma Cysteinyl leukotrienes are found to be 5,000 times more potent than histamine in causing nasal congestion. Both histamine and cysteinyl leukotrienes are noted to be elevated in the nasal secretions of patients with AR. Histamine induces the typical responses of AR (e.g., itching and sneezing).2 The inflammation of the lower airways is characterized by an Co-ordinator and Senior Consultant Dept. of ENT Moolchand Medcity, New Delhi
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excess of CD4+ T-lymphocytes, eosinophil accumulation and activation, a slight increase in mucosal mast cells, thickening of the basement membrane, and fragility of the airway epithelium. The inflammatory cells within the airways produce various mediators that directly affect the bronchial smooth muscle, vasculature and mucussecreting cells of the airway and signal to other cells to attract and activate them. The most important mediators causing contraction of the bronchial smooth muscle are the cysteinyl leukotrienes; they may have significant effects such as edema formation, mucus secretion and induction of bronchial hyperresponsiveness.3 Role of Leukotriene Receptor Antagonists in Asthma Leukotrienes are synthesized from arachidonic acid, which is liberated by immunological or nonimmunological stimulation of various inflammatory cells. Arachidonic acid can be metabolized either by the cyclo-oxygenase system to form prostaglandins and thromboxanes or by the 5-lipoxygenase enzyme system to form leukotrienes. Cysteinyl leukotrienes have different types of receptors. The cysteinyl leukotrienesâ€‘1 receptor, which is present on airway smooth muscle, is blocked by most of the leukotriene antagonists. LTC4, D4 and E4 bind to this receptor. The cysteinyl leukotrienes have biological actions which is implicated in cases of asthma. They are very potent constrictors of bronchial smooth muscle in vitro and, when inhaled by healthy or asthmatic patients, they cause bronchoconstriction at doses 100 or 1,000 times less 13
Drug Therapy than histamine. Now there is a good evidence for the production of leukotrienes both in models of asthma and in clinical asthma. Allergen challenge studies of atopic asthmatic patients found that, there is an increase in leukotriene levels in bronchoalveolar lavage fluid and a rise in urinary levels of LTE4, greatest during the early asthmatic response. Recently in asthmatic patients, leukotrienes have been found in lavage fluid and in acute severe asthma leukotriene levels in the blood have been reported to be increased.3 The potent LTRAs can block upto 70-80% of early responses to inhaled allergen and nearly 50% of the late asthmatic responses. Drugs which antagonize leukotriene receptors or inhibit leukotriene synthesis have now been shown to be effective in clinical models of asthma for antigen- and exercise-induced bronchoconstriction, and in clinical trials they have improved the control of asthma. Nearly 2-5% of adult asthmatic patients are found to be sensitive to aspirin. In these patients, leukotriene antagonists improve basal airway function and can block the effects of aspirin. So, leukotriene antagonists can also be beneficial in this group of patients, whose asthma is difficult to treat.3 Among the latest LTRAs, montelukast is now widely used in clinical otolaryngology practice.3 Montelukast was approved by the FDA in 1998. The safety and effectiveness of montelukast has been demonstrated in children as young as six months of age. Role of Leukotriene Receptor Antagonists in AR LTRAs are found to be as effective as antihistamines in AR patients and they are noted to be very effective, when used as they can improve symptoms and qualityof-life in patients with seasonal AR. A study compared the clinical efficacy of LTRAs with antihistamines, nasal corticosteroids in patients with AR and nasal polyposis. This study showed that LTRAs reduced mean daily rhinitis symptom scores 5% (95% confidence interval [CI]: 3-7%) more than the placebo.4 Another multicenter, double-blind trial in patients with spring seasonal AR, randomly assigned to oncedaily montelukast (10 mg), loratadine (10 mg) or placebo demonstrated that both the day-time and night-time nasal symptom scores were significantly (p < 0.001) reduced with montelukast and loratadine 14
compared with placebo.5 The quality-of-life was also improved with montelukast and loratadine versus placebo (p < 0.005). In an another study, after two weeks of treatment, peripheral blood eosinophil counts were found to be significantly (p â‰¤ 0.001) decreased with montelukast but not with loratadine or placebo.6 The effects of an LTRA and antihistamine oral combination (montelukast plus cetirizine) were compared with mometasone, an intranasal steroid. The study showed that the combination of montelukast plus cetirizine produced significant (p < 0.05) improvements compared with placebo in the indices like peak nasal expiratory flow rate, nasal oral index, nasal symptoms, nasal itching, nasal blockage and daily activity score.7 This study found that there were no significant differences between mometasone and montelukast plus cetirizine. Efficacy of Montelukast in AR and Asthma Montelukast 10 mg is a safe and effective treatment for patients of both asthma and AR. Many studies have confirmed the effectiveness of montelukast 10 mg orally in adults with both asthma and AR. A phase IV study was done to investigate the efficacy and safety of montelukast 10 mg in adults with both asthma and AR in a real-life setting.8 This study found that after treatment with 10 mg montelukast, 86.5% of patients reported a strong or marked improvement in day-time asthma symptoms and 88.5% reported improvement in night-time symptoms and a high proportion of patients had a strong or marked improvement in all symptoms of AR [i.e., sneezing/itching (84%), rhinorrhea (81.7%), nasal congestion (79.3%)]. The study also found that the use of asthma and rhinitis medication was also reduced and 92.3% patients intended to continue montelukast therapy. This study concluded that montelukast is well-tolerated for both AR and asthma patients. Banasiak NC et al also reported that leukotriene modifiers are a useful alternative medication for use in children with mild persistent asthma, especially those who are unable to comply with inhaled steroids.9 They are also considered to be an additional medication for the step-up approach, or combination therapy, for moderate and severe persistent asthma not controlled with ICS alone. Asian Journal of Paediatric Practice, Vol. 14, No. 3
Drug Therapy Montelukast has a protective effect against both lower and upper airway responses during exposure to high levels of cat allergen. A study determined the benefit of montelukast 10 mg, for patients with concomitant asthma and AR seen by protection against both lower and upper airway responses to cat allergen challenge.10 Montelukast provided significant (p ≤ 0.001) protection against allergen challenge in the lower airway co-primary endpoint of area under the curve during challenge (AUC0-60 min) for percentage decrease in forced expiratory volume in 1 second (FEV1): Mean of 10.5%/hour and 14.7%/hour for montelukast and placebo, respectively. The overall nasal symptoms score (NSS) during recovery showed statistically significant (p = 0.048) protection by montelukast. The analyses of simultaneous lower and upper airway responses showed that more patients taking montelukast (43%) versus placebo (26%) were protected from both asthma and rhinitis (p = 0.02), with an odds ratio of 2.24 (95% CI, 1.16-4.32) in favor of montelukast. Concept of Allergic Rhinobronchitis Management The ‘One Airway Survey’ elucidates the fact that treating both AR and asthma effectively is a great concern of respondents. Nearly 75% patients in this survey responded that they found it difficult to treat both conditions effectively at the same time. Eighty-five percent patients expressed concerns on using too many medications to treat the two conditions. Nearly two-thirds (65%) reported that they preferred to use oral medication rather than nasal sprays.2 The general view of respiratory allergy has changed now. The link between rhinitis and asthma has been seen not only through clinical observations and epidemiological studies, but also through immunological observations and therapeutic outcomes. The airway allergy is now considered not a disease of a specific organ, but rather a disorder of the whole respiratory tract. These observations lead to the understanding of concept of ‘allergic rhinobronchitis (ARB)’.11 The common comorbidities and shared pathophysiologies of asthma and AR have led to the concept of ‘one airway, one disease’ and the need for a common therapeutic approach. The Allergic Rhinitis and its Impact on Asthma (ARIA) workshop group in collaboration with Asian Journal of Paediatric Practice, Vol. 14, No. 3
the World Health Organization (WHO) now advocates that patients with persistent AR should be evaluated for asthma, and that patients with asthma should be evaluated for rhinitis. Functional relationships between the two diseases demonstrate that co-morbid AR significantly worsens asthma. A strategy combining the treatment of both upper and lower airway disease in terms of efficacy and safety is optimal. The LTRAs now provide a rational approach to such ‘one airway’ disease management.11 Montelukast has been found to give significant relief from symptoms of seasonal AR, also simultaneously giving a benefit for asthma, in patients with ARB. A study evaluated montelukast 10 mg daily as treatment for AR in patients with symptomatic AR and active asthma in allergy season.12 This study found that montelukast reduced the daily rhinitis symptoms score: Difference between montelukast and placebo in mean change from baseline was –0.12 (95%, CI –0.18, –0.06; p ≤ 0.001). The day-time nasal symptoms (–0.14 [–0.21, –0.07; p ≤ 0.001]) and night-time symptoms (–0.10 [–0.16, –0.04; p ≤ 0.001]) were also improved and montelukast provided benefit in the global evaluations of asthma by patient and by physician: Mean differences were –0.24 (–0.41, –0.06; p = 0.008) and –0.17 (–0.33, –0.01; p = 0.037). The needed β-agonist use (puffs/day) was reduced significantly with use of montelukast (p ≤ 0.005). Role of Montelukast as Add-on Therapy in AR and Asthma A combined strategy can be used to treat upper and lower airway diseases, with treatment tailored according to various parameters like disease severity, comorbidities, treatment availability and affordability, etc. for achieving an optimal efficacy in treatment. Montelukast add-on therapy is now considered effective for managing asthma and AR symptoms in patients who were previously uncontrolled with ICS or long-acting b2-agonist (LABA)/ICS treatment. A study evaluated the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent AR who remain uncontrolled while receiving ICS monotherapy or ICS/LABA therapy in a community practice setting. This study found that at the eight week assessment, 229 patients (76.1%) achieved asthma control and 164 15
Drug Therapy patients (54.7%) achieved well-controlled asthma. A statistically and clinically significant reduction in the overall Mini Rhinitis Quality-of-Life Questionnaire score was achieved with a decrease from 2.57 ± 1.20 to 1.12 ± 1.00 (–1.45 ± 1.35; p < 0.001) and patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when it was compared with baseline treatment.13 In another study, once-daily inhaled plus intranasal budesonide and once-daily montelukast showed comparable efficacy on lower airway and budesonide was found to have significant efficacy on upper airway inflammatory markers.14 This study found that there were no significant differences between the placebos for any measurement. For adenosine monophosphate PC20, geometric mean fold differences (95% CI for difference) were 6.4 (2.2-18.6) for placebo versus budesonide, 2.9 (1.0-8.4) for placebo versus montelukast and 2.1 (1.1-4.5) for budesonide versus montelukast. For exhaled nitric oxide (ppb) there was significant (p < 0.05) suppression with both montelukast (10.9) and budesonide (10.1) compared with placebo (18.8). For nasal nitric oxide and nasal peak flow there were only significant differences with budesonide compared with placebo. Both the treatments reduced total seasonal AR symptoms.
This study concluded that in asthmatic patients with AR, a combined treatment approach of including montelukast and budesonide can provide significantly greater efficacy in reducing airflow obstruction as compared to just doubling the dose of budesonide. The results of the COMPACT trial support the recommendation by ARIA group which suggested that a single approach for treating the airway inflammation common to both diseases is beneficial for the large percentage of asthmatic patients who also suffer from AR. Montelukast can provide additional asthma control in patients who are benefiting from, but incompletely controlled on inhaled beclomethasone. A study was done to see whether montelukast provides additional
COMPACT Trial Recent studies have demonstrated that montelukast is effective in treating day-time and night-time AR symptoms in asthmatic patients. A study was done to see whether asthmatic patients with co-morbid AR respond different from those patients without co-morbid AR in terms of asthma control. The Clinical Outcomes with Montelukast as a Partner Agent to Corticosteroid Therapy (COMPACT) study was done as a randomized double-blind trial in 889 asthmatic adults whose asthma symptoms persisted despite use of ICS.15 The trial demonstrated that montelukast added to budesonide (MNT + BD) was as efficacious as double the dose of budesonide (dBD) in improving morning peak expiratory flow (AM PEF) in adult asthmatics. In this study, there was a 9.2% increase in AM PEF from baseline in the MNT + BD group compared with a 6% increase in the dBD group. The least square mean difference [(MNT + BD) − dBD] was 14.2 l/min (p = 0.028). 16
Take Away Messages Airway allergy is considered not a disease confined to nose or bronchi, but is now considered as a disorder of the whole respiratory tract, called as ‘allergic rhinobronchitis (ARB)’. ARIA group and WHO suggest a single approach for treating the airway inflammation common to both diseases. A strategy combining the treatment of both upper and lower airway disease in terms of efficacy and safety is optimal. Leukotrienes are a group of naturally occurring chemicals in the body that promote inflammation in asthma and seasonal AR. Most important mediators causing contraction of the bronchial smooth muscle are the cysteinyl leukotrienes. Leukotriene receptor antagonists (LTRAs) are considered effective, safe and beneficial in both AR and asthma patients. The LTRAs now provide a rational approach to ‘one airway’ disease management. Montelukast (a LTRA) provides significant relief from symptoms of seasonal AR, simultaneously giving a benefit for asthma, in patients with both AR and asthma as a monotherapy. The COMPACT trial highlights the benefit of montelukast with steroids as a combination therapy, in both asthma and AR patients.
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Drug Therapy clinical benefit to the effect of ICS.16 This study found that montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV1, day-time asthma symptom scores and nocturnal awakenings. In their study results, blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control and blind removal of beclomethasone in the presence of montelukast resulted in less asthma control. References 1. Pawankar R. Allergic rhinitis and asthma: the link, the new ARIA classification and global approaches to treatment. Curr Opin Allergy Clin Immunol 2004; 4(1):1-4. 2. Oneairway Survey by Wirthlin Worldwide Survey done in four Asian countries: Taiwan, Korea, Hong Kong and Singapore, with sponsorship from an unrestricted educational grant from Merck Sharp and Dohme; 2003. 3. Barnes N. Leukotriene receptor antagonists: clinical effects. J Royal Soc Med 1997;90(4):200-4. 4. Wilson AM, Oâ€™Baryne MA, Parmeshwaran K. Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis. Am J Med 2004;116(5):338-44. 5. Meltzer EO, Malmstrom K, Lu S, Prenner BM, Wei LX, Weinstein SF, et al. Concomitant montelukast and loratadine as treatment for seasonal allergic rhinitis: a randomized, placebo-controlled clinical trial. J Allergy Clin Immunol 2000;105(5):917-22.
2001;31(1):61-8. 8. Virchow JC, Bachert C. Efficacy and safety of montelukast in adults with asthma and allergic rhinitis. Respir Med 2006;100(11):1952-9. 9. Banasiak NC, Oliver NM. Leukotrienes: leukotriene modifiers. Pediatr Nurs 2005;31(1):33-8. 10. Perry TT, Corren J, Philip G, Kim EH, ConoverWalker MK, Malice MP, et al. Protective effect of montelukast on lower and upper respiratory tract responses to short-term cat allergen exposure. Ann Allergy Asthma Immunol 2004;93(5):431-8. 11. Pawankar R. Allergic rhinitis and asthma: from the link to emerging therapies. Indian J Chest Dis Allied Sci 2003;45(3):179-89. 12. Philip G, Nayak AS, Berger WE, Leynadier F, Vrijens F, Dass SB, et al. The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Curr Med Res and Opin 2004;20(10):1549-58. 13. Keith PK, Koch C, Djandji M, Bouchard J, Psaradellis E, Sampalis JS, et al. Montelukast as add-on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial). Can Respir J 2009; 16(Suppl A):17A-31A. 14. Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clin Exp Allergy 2001;31(4):616-24.
6. Pawankar R. Exploring the role of leukotriene receptor antagonists in the management of allergic rhinitis and co-morbid asthma. Clin Exp Allergy Rev 2003;3(2): 74-80.
15. Price DB, Swern A, Tozzi CA, Philip G, Polos P. Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial. Allergy 2006;61(6):737-42.
7. Wilson AM, Orr LC, Sims EJ, Lipworth BJ. Effects of monotherapy with intra-nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis. Clin Exp Allergy
16. Laviolette M, Malmstrom K, lu S, Chervinsky P, Pujet JC, Peszek I, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. Am J Respir Crit Care Med 1999;160(6):1862-8.
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Chronic Pain Associated with the Chikungunya Fever: Long Lasting Burden of an Acute Illness Daniel Ciampi de Andrade, Sylvain Jean, Pierre Clavelou, Radhouane Dallel, Didier Bouhassira
Abstract Background: Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control. Methods: We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL). Results: The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ) (15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05). Conclusions: There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment. Key words: Chikungunya fever, autochthonous, neurotropism, nociceptive
hikungunya fever is a viral disease caused by the arthropod-borne Chikungunya virus, from the Togaviridae family. It is transmitted to humans by the Aedes ssp mosquitoes. The virus was first isolated in 1953, in Uganda, during an epidemic in the province of Newala in Tanganyika (now Tanzania).1 Its name derives from the Makonde language, meaning, “he, who walks bent up”. The infection gives rise to an unusual clinical finding during its clinical course: pain, which is virtually universal and is the major symptom of the disease. Since the recognition of the first case of CHIKV infection, both sporadic and major epidemics have been reported in Africa, India, South-East Asia and Western Pacific.1,2 Epidemics of unprecedented magnitude occurred in 2005-2006 in the islands of the South-West Indian Ocean. In particular, there was a major outbreak of CHIKV in Réunion Island, Citation: de Andrade et al.: Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness. BMC Infectious Diseases 2010, 10:31.
a French overseas département (French administrative unit), with 266,000 people infected, constituting 34% of the island’s total population.3 Interest in this viral infection has grown in recent years. Competent vectors (i.e. Aedes mosquitoes) are widely distributed throughout the world; thus many countries not initially hit by previous epidemics present a potential risk of outbreaks.4 Autochthonous cases were recently reported in northern Italy5 and imported cases in travelers returning from affected areas have been reported in several European countries and in the United States of America.6-8 The clinical course of the acute phase of infection has been well characterized during previous epidemics in African countries, the Indian subcontinent and Southeast Asia.1 It involves an incubation period lasting between two to six days, followed by the abrupt onset of fever associated with intense diffuse muscle and joint pain. Headache, photophobia, nausea, vomiting, Asian Journal of Paediatric Practice, Vol. 14, No. 3
research Article diarrhea and a maculopapular or morbilliform skin rash may accompany these symptoms. Treatment is mainly symptomatic, with remission observed in most patients some days after the infection. Some studies have reported cases in which arthralgia persists after resolution of the acute infection, thus leading to chronic pain.9,10 Despite these initial studies, a broader characterization of chronic pain related to Chikungunya infection is still needed. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. The neurotropism of CHIK virus, reflected in the neurological complications,11 is compatible with this notion. Given that neuropathic pain syndromes require specific treatment, including antiepileptics and antidepressants,12 the potential neuropathic component of this disease should be a major factor affecting the symptomatic management of such cases. We carried out a study at the end of the major twowave outbreak lasting 17 months in Réunion Island. The aims of this study were to assess and characterize pain, particularly chronic pain in patients attending general practices who have confirmed serologic infection by the CHIKV and to evaluate the impact of this pain on quality of life (QoL). Methods This study was approved by our institutions ethics review board in compliance to the Helsinki declaration. It was carried out from June to July 2006 in 13 general practices located throughout Réunion Island. All subjects received written information on the study and gave written informed consent prior to participation. All patients spontaneously seeking medical attention were directly asked whether they were on pain. Patients were included if they presented with any type of pain and previous serologic confirmation of CHIKV infection based on CHIKV IgG and IgM detected by direct ELISA and ELISA following immunocapture, respectively, as originally established at the Centre National de Référence pour les Arbovirus (Pasteur Institute, Lyon, France).13 The enrollment period for the study lasted five consecutive working days, and each patient was seen only once. Patients presenting with signs of severe disease such as meningismus, Asian Journal of Paediatric Practice, Vol. 14, No. 3
intense headaches or hemodynamic instability were headed to the nearest hospital and were not included in the study. We excluded patients presenting with pain clearly related to any other etiologies (i.e. rheumatologic, muscular, neurological - i.e: migraines), or those presenting with diabetes, psychiatric illness or a history of drug abuse, including alcohol, since all these conditions may be associated to specific painful syndromes and thus might constitute confounders to our analysis. The assessment included a structured interview and specific questionnaires to characterize the painful syndrome and its impact on QoL.14 The study was approved by our institution’s review board and all patients signed a written informed consent. The intensity, location and effect of pain on quality of life were assessed with the Brief Pain Inventory (BPI).14 In this largely used questionnaire, three numerical rating scales each ranging from 0 (no pain) to 10 (maximal pain) were used to assess minimal, maximal and average pain intensity over the previous week. Then patients were asked to report all sites of pain on a diagram of the body and to specify the location of the most intense pain. The BPI also includes a series of numerical rating scales (equally ranging from 0 to 10) to assess the extent that pain interferes with general activity, mood, walking, sleep, work, relationship with others and life enjoyment (from 0: does not interfere, to 10: complete interference). The short-form McGill Pain Questionnaire (SF-MPQ)15 was used to measure the sensory and affective dimensions of pain. This tool has been widely used in pain studies. It comprises 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe. Three pain scores are derived from the sum of the intensity rank values of the words chosen for sensory, affective and total descriptors. The DN4-interview questionnaire, includes seven pain descriptors that must be answered “yes” or “no” based on their presence or absence, respectively, in a given painful body location.16 Since this questionnaire is aimed at differentiating neuropathic pain from other pain syndromes (ie.: nociceptive pain) all its descriptors must be directed to the same painful phenomenon at a time (ie.: the same body region). Quite frequently, patients are asked to answer the questionnaire 19
research Article according to the site of the “most troublesome pain”. So patients with diffuse pain, but presenting a body region where pain is more intense can easily respond to the questionnaire. This method has been shown to present a high sensibility and specificity in diverse pain trials.12 However, it is recommended that it should not be administered to patients who have a similar intensity of pain in multiple locations. The duration of pain was also assessed and chronic pain was defined as daily pain for more than three months.17 In addition, patients were asked to provide details of current pain treatment (eg.: analgesic drugs prescribed so far) and their efficacy: low = < 30% pain reduction, moderate = 30-70% pain reduction and good = > 70% pain reduction. Pain relief after analgesics was considered a >30% pain reduction from baseline.12 Statistical Analysis Quantitative variables were expressed as means and standard deviations (SD). Qualitative variables expressed as proportions and percentages. We used analyses of variance (ANOVA), with Fisher’s PLSD test, to compare pain intensity and duration and questionnaire scores between patients with or without chronic pain and between patients with or without neuropathic characteristics. Multiple regression was used to analyze the association between the effect of pain on QoL (i.e. mean interference score) and clinical characteristics (i.e. age, pain intensity and duration, DN4 questionnaire score, SF-McGill sensory and affective scores). The Chi2 test was used to compare proportions. P < 0.05 was considered significant in all instances. Results Pain Characteristics
One hundred and six consecutive painful patients (79 women) were included in this study (47.3 ± 11.9 years). All reported pain at multiple sites. All patients reported pain in at least one joint (Table 1). Besides joint pain, some patients also reported nonarticular pain, especially on the lower limbs. The mean intensity of pain measured by the BPI was 5.8 ± 2.1, with minimum and maximum pain intensity of 3.6 ± 2.1 and 8.3 ± 1.9, respectively. 20
Table 1. Description of the Patients and Percentages of Patients Reporting Pain at Different Locations Clinical and demographic data Mean age ± SD (range)
47.33 ± 11.9 (19-73)
Sex (women/men) (%)
Mean duration of pain (days ± SD) (range)
89.1 ± 55.5 (1-318)
Mean pain intensity ± SD (range) Pain locations Head/neck Thorax/abdomen Back Upper limbs Lower limbs
5.8 ± 2.1 (1-10) % 26 14 49 95 98
Location of joint pain Shoulder Elbow Hand/wrist Hip Knee Ankle/foot
54 48 77 9 72 81
The mean duration of pain was 89 ± 2 days. Seventeen patients (16%) had suffered pain for less than one month, 33 patients (31%) between one and three months and 56 (53%) patients suffered chronic pain (mean: 128 ± 41 days, range: 95-318 days). Pain had neuropathic characteristics (NC) in 20 patients (18.9%) of patients. Pain with NC was located mostly in the upper (37%) or lower (48%) limbs and more rarely in the back (7%) or head/neck (7%). About half (53%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the SF-MPQ (15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. Impact on Quality of Life
The mean pain interference score calculated from the BPI was significantly higher in patients with chronic pain than in patients without (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without NC (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05). Multiple regression analysis showed that the interference of pain with quality of life was significantly Asian Journal of Paediatric Practice, Vol. 14, No. 3
research Article Table 3. Pain Treatment used for CHIKF-related Pain and Number (%) of Patients under Treatment
Main analgesic treatment
En joy life
Sl ee p
W or Re k lat .o the rs
W alk ing
Ge ne ra la cti vit y
10 9 8 7 6 5 4 3 2 1 0
Figure 1. Comparison of BPI items related to the impact (“interference”) of pain on quality of life, between patients with pain with or without neuropathic characteristics. Abbreviations: Relat. others: relationship with others. *p < 0.05; **p < 0.01; ***p < 0.001.
associated with average pain intensity, the DN-4 score and SF-MPQ affective score, but not with age or duration of pain (Table 2). The items altered the most were working, mood and sleep (Figure 1). Symptomatic Treatment
Eighty-eight (83%) patients had received analgesic treatment for their pain. The most frequently used drugs included: corticoids (40%), non-steroid anti-inflammatory drugs (NSAID) (22%) and acetaminophen (8%) (Table 3). Twenty-five (24%) patients reported poor pain relief, 53 patients (50%) reported moderate pain relief and 28 (26%) good pain relief with their symptomatic treatment. The percentage of pain relief was significantly lower (p < 0.01) in patients with NC (39 ± 24%) than in patients without NC (56 ± 27%).
N = 106 (%)
Non-steroidal anti-inflammatory drugs
Acetaminophen + opioid
Discussion Our data from a sample of painful patients attending general practices presenting with pain and serologically confirmed infection by the CHIKV after the last major CHIKV outbreak in Réunion Island showed that about half (51%) of these patients suffered from chronic pain. Consistent with previous reports, all of our patients presented with arthralgia. Joint involvement has been increasingly recognized in CHIKV infections and its relationship with certain predisposing genetic profiles, such as HLA B27, has been proposed.18-20 However, we identified a subgroup of patients whose most troublesome pain was not located in the joints and had neuropathic characteristics (NC) (ie.:, burning pain, cold pain, electric-shocks like pain, tingling, pins and needles, numbness, itching). The presence of NC, related with specific pain mechanisms, was associated with a significantly poorer quality of life and lower efficacy of treatment.
Table 2. Results of the Multiple Regression Analysis Showing the Association between Alteration of Mean Pain Interference Score and Mean Pain Intensity, SF-McGill Affective and Sensory Scores and DN4 Questionnaire Score Coefficient
Mean pain intensity
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research Article The association between chronic pain and CHIKV has been assessed in only a few studies.9,10 The largest retrospective study from RĂŠunion Island suggested that up to 63% of hospitalized patients are affected by chronic joint pain caused or aggravated by CHIKV infection.10 Previous studies focused on chronic arthralgia and it was suggested that a rheumatoid syndrome could be responsible for chronic pain in these patients. Consistent with this, Brighton and co-workers9 found high antibody titers against CHIKV in the synovial fluid of patients with persistent joint pain and rigidity (5.6% of patients studied). In our study, although chronic arthralgia was ubiquitously present, patients also reported pain in other locations. The mechanisms of nonarticular chronic pain associated with CHIKV infection are still poorly understood and remains elusive. Autopsy studies in other neuroinfectious syndromes, such as zoster radiculopathy, have shown that even years after the viral reactivation axonal atrophy and loss of myelin in peripheral nerves may still be detected. Also, some major pathological changes, such as dorsal horn atrophy were present only in those patients presenting chronic pain after the viral reactivation (postherpetic neuralgia).21,22 This argues for the fact that an active pathological process may take place after the acute infection, being associated with long term pain symptomatology. About one out of five of our patients reported pain with NC, suggesting that other mechanisms were also involved. Neuropathic pain syndromes are caused by a lesion or dysfunction of the nervous system and their mechanisms are not completely understood. However, it is well established that neuropathic pain syndromes do not depend directly on inflammatory processes, but involve specific peripheral and central changes in nociceptive processes.12,16 The fact that our patients did not present with obvious peripheral or central neurological findings may indicate that NC reflected a dysfunction of the nervous system, rather than a neurological lesion induced by the CHIKV. Further clinical and experimental studies will be needed to identify the putative (peripheral and/or central) neurological lesion or dysfunction in these patients. 22
Nevertheless, this subgroup of patients deserves particular attention. Indeed, the presence of NC was associated with a less favorable outcome, in terms of a greater impact on quality of life and lower efficacy of treatment. In particular, the poorer outcome of treatment may be explained by the fact that neuropathic pain syndromes, which do not respond to conventional analgesics, respond better to antiepileptics and tricyclic antidepressants,12 which were used in only a minority of our patients. Whether our findings could be extrapolated to CHIKV infections in other geographic areas remains uncertain, since a series of findings suggest that CHIKV infection during the RĂŠunion outbreak was particularly aggressive. Thus, more cases with severe neurological complications, such as meningoencephalitis, requiring intensive-care units, and the first cases of vertical maternal fetal transmission were reported during this outbreak.1-4,23,24 New viral mutations, not detected during previous epidemics, were detected during this outbreak and may thus be related to the more aggressive clinical progression of the infection.1 Nevertheless, CHIKV strains isolated during RĂŠunion Island epidemics show 99.61% homology to strains isolated in India.25 It is plausible that such an aggressive infection profile will affect other regions during future outbreaks.26 Also, we found a greater proportion of women with pain symptoms, which has also been found in large epidemiological studies.27 Although a female predisposition to present pain after CHIKV infection cannot be ruled out, it could also be related to differences in access to primary care between men and women. Other studies are needed to address this question. Another limitation is that our study was based on the evaluation of patients in a primary care setting. Although this allowed a broad assessment of the study population, more severe cases, treated in secondary and tertiary centers, may have been missed. We also only evaluated patients with painful syndromes seeking medical attention and therefore could not estimate the actual prevalence of chronic pain in CHIKV infections. Future prospective studies including long-term follow-up are warranted to estimate the prevalence of chronic pain related to CHIKV infections. Asian Journal of Paediatric Practice, Vol. 14, No. 3
research Article Conclusions This study suggests that chronic pain is a frequent long-term complication of CHIKV and that the presence of neuropathic features is associated with a more severe condition. Thus, although its mechanisms remain to be determined, improved characterization of pain, including the identification of neuropathic features with an easy-to-use clinical tool, could help to significantly improve treatment outcome. Acknowledgements The authors thank the investigators from La Réunion Island who participated in patients’ recruitment: Dr C Charlette Limbe (Le Port), Dr S Journeaux (Sainte-Marie), Dr D Oudard (Plateau Caillou), Dr E Sery (La Bretagne), Dr C Leveque (Saint-Denis), Dr N Jankowski (Sainte-Clotilde), Dr E Martin-Champetier (Sainte-Clotilde), Dr C Touraine (Le Tampon), Dr H Quercy and Dr F Ravel (Le Guillaume St Paul), Dr J Khoury (Saint-Gilles les Hauts), Dr C Kowalczyk (Champ Borne), Dr JP Moreau (Saint-Benoit), Dr C Chabas (Saint Denis), Dr R Ebode (St Leu).
7. Tilston N, Skelly C, Weinstein P: Pan-European Chikungunya surveillance: designing risk stratified surveillance zones. Int J Health Geogr 2009, 8:61. 8. Lanciotti RS, Kosoy OL, Laven JJ, Panella AJ, Velez JO, Lambert AJ, Campbell GL: Chikungunya virus in US travelers returning from India, 2006. Emerg Infect Dis 2007, 13:764-7. 9. Brighton SW, Prozesky OW, de la Harpe AL: Chikungunya virus infection: a retrospective study of 107 cases. S Afr Med J 1983, 63:313-5. 10. Borgherini G, Poubeau P, Jossaume A, Gouix A, Cotte L, Michault A, Arvin-Berod C, Paganin F: Persistent arthralgia associated with Chikungunya virus: a study of 88 adult patients on reunion island. Clin Infect Dis 2008, 47:469-75. 11. Rampal, Sharda M, Meena H: Neurological complications in Chikungunya fever. J Assoc Physician India 2007, 55:765‑9. 12. Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko T, Sampaio C, Sindrup S, Wiffen P, EFNS Task Force: EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol 2006, 13:1153-69.
1. Pialoux G, Gaüzère BA, Jauréguiberry S, Strobel M: Chikungunya, an epidemic arbovirosis. Lancet Infect Dis 2007, 7:319-27.
13. Grivard P, Le Roux K, Laurent P, Fianu A, Perrau J, Gigan J, Hoarau G, Grondin N, Staikowsky F, Favier F, Michault A: Molecular and serological diagnosis of Chikungunya virus infection. Pathol Biol (Paris) 2007, 55:490-4.
2. Chevillon C, Briant L, Renaud F, Devaux C: The Chikungunya threat: an ecological and evolutionary perspective. Trends Microbiol 2008, 16:80-8.
14. Cleeland CS, Ryan KM: Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994, 23:129-38.
3. Gérardin P, Guernier V, Perrau J, Fianu A, Le Roux K, Grivard P, Michault A, de Lamballerie X, Flahault A, Favier F: Estimating Chikungunya prevalence in La Réunion Island outbreak by serosurveys: two methods for two critical times of the epidemic. BMC Infect Dis 2008, 28(8):99.
15. Melzack R: The McGill Pain questionnaire: major properties and scoring methods. Pain 1975, 1:277-99.
4. Charrel RN, de Lamballerie X, Raoult D: Chikungunya outbreaks - the globalization of vector-borne diseases. N Engl J Med 2007, 356:769-71. 5. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, Cordioli P, Fortuna C, Boros S, Magurano F, Silvi G, Angelini P, Dottori M, Ciufolini MG, Majori GC, Cassone A: CHIKV Study Group: Infection with Chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007, 370:1840-6. 6. Taubitz W, Cramer JP, Kapaun A, Pfeffer M, Drosten C, Dobler G, Burchard GD, Löscher T: Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis 2007, 45:1-4. Asian Journal of Paediatric Practice, Vol. 14, No. 3
16. Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lantéri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E: Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005, 114:29‑36. 17. Merskey H, Bogduk N, editors: Classification of Chronic Pain. IASP Press, Seattle 1994. 18. Bouquillard E, Combe B: A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint Bone Spine 2009. 19. Mathieu A, Paladini F, Vacca A, Cauli A, Fiorillo MT, Sorrentino R: The interplay between the geographic distribution of HLA-B27 alleles and their role in infectious and autoimmune diseases: a unifying hypothesis. Autoimmun Rev 2009, 8:420-5.
research Article 20. Hamdulay SS, Glynne SJ, Keat A: When is arthritis reactive? Postgrad Med J 2006, 82:446-53. 21. Watson CP, Watt VR, Chipman M, Birkett N, Evans RJ: The prognosis with postherpetic neuralgia. Pain 1991, 46:195-9. 22. Watson CP, Deck JH, Morshead C, Kooy Van der D, Evans RJ: Post-herpetic neuralgia: further post-mortem studies of cases with and without pain. Pain 1991, 44:105-17. 23. Economopoulou A, Dominguez M, Helynck B, Sissoko D, Wichmann O, Quenel P, Germonneau P, Quatresous I: Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion. Epidemiol Infect 2009, 137:534-41. 24. Lemant J, Boisson V, Winer A, Thibault L, André, Tixier F, Lemercier M, Antok E, Cresta MP, Grivard P, Besnard M, Rollot O, Favier F, Huerre M,
Campinos JL, Michault A: Serious acute chikungunya virus infection requiring intensive care during the Reunion Island outbreak in 2005-2006. Crit Care Med 2008, 36:2536‑41. 25. Arankalle VA, Shrivastava S, Cherian S, Gunjikar RS, Walimbe AM, Jadhav SM, Sudeep AB, Mishra AC: Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic. J Gen Virol 2007, 88:1967-76. 26. Lalitha P, Rathinam S, Banushree K, Maheshkumar S, Vijayakumar R, Sathe P: Ocular involvement associated with an epidemic outbreak of Chikungunya virus infection. Am J Ophthalmol 2007, 144:552-6. 27. Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C: Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008, 136:380-7.
...Cont’d from page 11 that the child’s wheezing attacks and skin pigmentation developed simultaneously but yet it was not taken as significant and evaluated in the previous admissions.
hyperpigmentation in a child with wheezing, Addison’s disease should be entertained as a possible association.
Glucocorticoids are involved in modulation of b-adrenoreceptor density and responsiveness.6 In the steroid deficient state, b-adrenergic receptors of bronchi decrease in number or lose responsiveness to catecholamines presenting clinically with wheeze. A favorable response in asthma to steroid therapy will also support this fact. Asthma may be an uncommon presenting sign of Addison’s disease because a child developing adrenal failure needs to be just on the threshold of bronchoconstriction for the latter to occur before other features of Addison’s disease. We report this case to alert physicians caring for children with asthma that, in the presence of
1. Saraclar Y, Türktas I, Adalioğlu G, Tuncer A. Bronchial asthma with Addison’s disease. Respiration 1993; 60(4):241-2.
2. Green M, Lim KH. Bronchial asthma with Addison’s disease. Lancet 1971;1:1159-62. 3. Harris PW, Collins JV. Bronchial asthma with Addison’s disease. Lancet 1971;26:1349-50. 4. Sanerkin NG, El-Shaboury AH. Chronic adrenalitis with bronchial asthma. Lancet 1965;2(7410):468-70. 5. Carryer HM, Sherrick DW, Gastineau CF. Occurrence of allergic disease in patients with adrenal cortical hypofunction. J Am Med Assoc 1960;172:1356-60. 6. Reinhardt D. Adrenoreceptors and the lung: their role in health and disease. Eur J Pediatr 1989;148(4):286-93.
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Dengue Fever (DF) in Pakistan Fridous Jahan
Abstract Dengue is a widespread mosquito-borne infection in human beings, which in recent years has become a major international public health concern. Symptomatic dengue virus infections can present with a wide range of clinical manifestations, from a mild febrile illness to a life-threatening shock syndrome. Both viral and host factors are thought to contribute to the manifestations of disease in each infected. It is important to understand its burden on health care, morbidity and mortality. Early diagnosis and suspicion of DF in primary care might reduce the complications if handled properly. We must understand the depth of the problem in terms of its transmission, clinical presentation, diagnosis, management and prevention. Key words: Dengue hemorrhagic fever, epidemics, thrombocytopenia
he World Health Organization (WHO) declares dengue and dengue hemorrhagic fever to be endemic in South Asia. WHO currently estimates there may be 50 million dengue infections worldwide every year. In 2007 alone, there were more than 890,000 reported cases of dengue in the Americas, of which 26,000 cases were Dengue Hemorrhagic Fever (DHF).1 The disease is now endemic in more than 100 countries in Africa, Americas, the Eastern Mediterranean, South-east Asia and the Western Pacific. South-east Asia and the Western Pacific are the most seriously affected. Pakistan is at high risk of being hit by large epidemics because of many over crowded cities, unsafe drinking water, inadequate sanitation, large number of refugees and low vaccination coverage. These conditions promote the spread of infectious diseases and consequently every year a large number of epidemics/outbreaks occur in different parts of the country, which result in increased morbidity and mortality. Epidemiology Global Burden
Dengue virus infection is increasingly recognized as one of the worldâ€™s emerging infectious diseases. About
Citation: Jahan: Dengue fever (DF) in Pakistan. Asia Pacific Family Medicine 2011,10:1.
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50-100 million cases of dengue fever and 500,000 cases of Dengue Hemorrhagic Fever (DHF), resulting in around 24,000 deaths, are reported annually.1 A pandemic of dengue began in Southeast Asia after World War II and has spread around the globe since then. In the 1980s, DHF began a second expansion into Asia when Sri Lanka, India, and the Maldive Islands had their first major DHF epidemics. Local Prevalence
Pakistan first reported an epidemic of dengue fever in 1994. The epidemics in Sri Lanka and India were associated with multiple dengue virus serotypes, but DEN-3 was predominant and was genetically distinct from DEN-3 viruses previously isolated from infected persons in those countries. In Asian countries where DHF is endemic, the epidemics have become progressively larger in the last 15 years. In 2005, dengue is the most important mosquito-borne viral disease affecting humans.2 Dengue virus is now endemic in Pakistan, circulating throughout the year with a peak incidence in the post monsoon period. Recent flood in Pakistan made the situation worse. Dengue Surveillance Cell Sind province of Pakistan reports 1,809 suspected Dengue out of which 881 confirmed till 11th October 2010 with 5 deaths while 16 confirmed cases reported in Islamabad without any mortality. 25
short report Till now 563 confirmed cases were reported at our institution since January 2010. Reported cases are usually complicated or with hemorrhagic manifestation. In primary health care the usual presentation is mild to moderate fever treated as suspected dengue fever. Researchers have identified that co-circulation of DEN-2 and DEN-3 was responsible for the 2006 outbreak in Karachi. Primary and secondary cases were seen in both groups. Cases with DHF showed marginal association with DEN-2. Introduction of a new serotype (DEN-3) and or a genotypic shift of endemic serotype (DEN-2) are the probable factors for the recent outbreak of DHF in this region.3 Transmission Aedes Aegypti mosquito, which generally acquires the virus while feeding on the blood of an infected person and transmit the disease to another non-infected person. It is primarily a daytime feeder lives around human habitation. This mosquito rests indoors, in closets and other dark places. Outside, it rests where it is cool and shaded. The female mosquito lays her eggs in water containers in and around homes, schools and other areas in towns or villages. These eggs become adults in about 10 days. Dengue mosquitoes also breed in stored, exposed, water collection systems. The favored breeding places are: barrels, drums, jars, pots, buckets, flower vases, plant saucers, tanks, discarded bottles/tins, tyres, or water coolers, and other places where rainwater collects or stored. Dengue infection is caused by any of 4 different serotypes of the virus (DEN-1, DEN-2, DEN-3, and DEN-4). After an incubation period of 2-8 days after an infective mosquito bite, the disease usually begins with sudden onset of fever and headache. Clinical Features WHO Case Definition
Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death. The clinical features of dengue fever vary according to the age of the patient. Infants and young children may have a non-specific febrile illness with rash. Older children and adults may have either a mild febrile syndrome or the classical incapacitating disease 26
with abrupt onset and high fever, severe headache, pain behind the eyes, muscle and joint pains, and rash.4 Common presentations in our clinical practice, high grade fever typically accompanied by any of the following: chilliness, retro-orbicular pain, photophobia, backache, severe muscle ache (one synonym of dengue is “break-bone fever”), and joint ache, nausea, vomiting, abdominal pain. High fever may be sustained over 5-6 days. Other signs and symptoms include a generalized maculopapular rash, lymph node enlargement, hepatosplenomegaly, a positive tourniquet test, petechiae, and other hemorrhagic manifestations, such as epistaxis and gastrointestinal bleeding. In some cases it started as common cold and flu like symptoms. In general, convalescence occurs spontaneously and abruptly, but it might be prolonged, sometimes taking several weeks, and may be accompanied by pronounced asthenia and depression. In DHF characteristically, the overall vascular system is damaged, vascular instability, decreased vascular integrity and platelet dysfunction resulting in bleeding from different sites.5 Clinical presentation may vary from undifferentiated fever, classic dengue fever (DF), Dengue hemorrhagic fever (DHF) to Dengue shock syndrome (DSS). The risk of severe disease is much higher in sequential rather than primary dengue infection.6 Necessary Criteria for DHF:
Fever, or recent history of acute fever Hemorrhagic manifestations Low platelet count (100,000/mm3 or less) Objective evidence of “leaky capillaries:” n elevated hematocrit (20% or more over baseline) n low albumin n pleural or other effusions
Grade 1 DHF: Fever and non-specific constitutional symptoms, Positive tourniquet test is only hemorrhagic manifestation. Thrombocytopenia and rise in hematocrit level (more than 20%). Grade 2 DHF: Grade 1 manifestations + spontaneous bleeding, circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or Asian Journal of Paediatric Practice, Vol. 14, No. 3
short report less) or hypotension with the presence of cold clammy skin and restlessness, Capillary relief time more than two seconds. Thrombocytopenia and rise in hematocrit level (more than 20%). Grade 3 DHF/DSS: Signs of circulatory failure (rapid/ weak pulse, narrow pulse pressure, hypotension, cold/ clammy skin). Grade 4 DHF/DSS: Profound shock (undetectable pulse and BP), abdominal pain - intense and sustained, persistent vomiting, abrupt change from fever to hypothermia, with sweating and prostration, restlessness or somnolence. Laboratory Tests Usually clinical suspicion for Dengue fever is sufficient for supportive treatment. Complete blood picture may show high hematocrit, leukopenia and thrombocytopenia. Other laboratory tests include serum albumin, chest X-ray if required. A normal blood count does not rule out DF however platelet <50,000 and leukocyte count <3 might be a sign of bad prognosis. Diagnosis of dengue fever or its complications is established by culture of the virus itself, by detection of viral DNA with use of PCR, or by serological methods. Although detection of specific IgM indicates fresh infection, a significant increase in IgG titer in paired serum samples is also sufficient for diagnosing dengue fever. Currently employed methods include capture ELISAs, immunofluorescence tests, and hemagglutination assays. Low white cell count, low platelet count, abnormal liver function test, IgM ELISA test for serologic diagnosis, IgM detectable 5, 6 days after the onset of illness, IgG: day 14 of illness in primary and day 2 in secondary infections.7
infections locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission) and virus strain (genotype).8 Epidemic potential is dependent on viremia level, infectivity and virus serotype, DHF risk is greatest for DEN2, followed by DEN-3, DEN-4 and DEN-1.9 Antibody-dependent enhancement is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production. Infected monocytes release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS.10 There are other febrile illness prevalent in Pakistan like other viral infections, Malaria, Enteric fever and Congo hemorrhagic fever which can cause leukopenia and thrombocytopenia worth considering during the investigation and relevant investigations are done according to the clinical presentation.11,12 Dengue IgM is a costly investigation not freely available although it confirms the diagnosis but never changes the management. Management
There is no specific treatment available; the management is entirely supportive like keeping body temperature below 39°C, give the patient paracetamol (not more than four times in 24 hours. Avoid Aspirin or Brufen/Ponston. Advice to drink large amounts of fluids (water, soups, milk and juices) along with the patient’s normal diet. The patient should rest. Complete blood picture should be done if fever is continuous for three days. Oral rehydration salt (ORS) should be started even if there is no significant clinical dehydration as patient can go in rapid deterioration if dehydration commences. Primary care physician can start intravenous fluid according to the patients need, it is life saving if administered on proper time.13
Studies has shown that median age of dengue patients has decreased now and younger patients may be more susceptible in the recent outbreak. Total and differential leukocyte counts and platelet count may help identify patients at risk of hemorrhage. Severity of disease depends on virus strain, pre-existing anti-dengue antibody previous infection maternal antibodies in infants, host genetics, age, secondary
Clinical manifestation of impending hemorrhage are, abdominal pain - intense and sustained, persistent vomiting, abrupt change from fever to hypothermia, with sweating and prostration, restlessness or somnolence. Thrombocytopenia <50,000, WBC <3.0, evidence of “leaky capillaries:” high hematocrit (>20% normal), low albumin, pleural or other effusions needs urgent referral for hospitalization.
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short report Health Education and Prevention Primary care professionals have the potential and ability to provide comprehensive care for most patients, given adequate training, resources, and, when needed, specialist advice. General practitioners and community nurses can play a major role in health education and hygiene.14 Effectiveness of Family Physiciansâ€™ use of specific communication skills in enhancing the care of the physical, mental and emotional health of both patients and their families is essential. Our health educational system needs to be updated regularly, the information regarding Dengue Fever to be made more generally available, the popular sources of information like newspapers and television should be used to disseminate information on a large scale.15 Dengue mosquitoes bite during the daytime. Protection from the bite by wearing full-sleeve clothes and long dresses to cover the limbs, use of repellents, mosquito coils and electric vapour mats during the daytime. Insecticide treated nets (ITNs) are available to protect young children, pregnant women, old people, in addition to others who may rest during the day. Curtains (cloth or bamboo) can also be treated with insecticide and hung at windows or doorways, to repel or kill mosquitoes. Drainage of water from desert/ window air coolers when not in use, in addition to tanks, barrels, drums, and buckets. Remove all objects containing water such as plant saucers from the house. All stored water containers should be kept covered at all times. Collect and destroy discarded containers in which water collects, such as bottles, plastic bags, tins, tyres, etc. Vector control is implemented using environmental management and chemical methods.16 Proper solid waste disposal and improved water storage practices, including covering containers to prevent access by egg laying female mosquitoes, are encouraged through community-based programs.17 The application of appropriate insecticides to larval habitats, particularly those used by the households, such as water storage vessels can prevent mosquito breeding for several weeks therefore these insecticides must be used periodically.18 Recent outbreaks have shown significant mortality and morbidity in Pakistan. The best health outcome 28
depends upon accurate diagnosis and appropriate treatment. A patient centered communication provides a more complete clinical picture which leads to improvement in health outcomes such as symptom resolution, reduced psychological distress, improvement of health and functional status, relief from pain and anxiety control. Conclusion Family Physicians have a vital and active role to play in providing care, support and identifying the signs of impending hemorrhage which is a serious consequence of Dengue Fever and needs referral to tertiary care for intravenous fluid replacement, platelet transfusion along with supportive care. Family practice also has opportunity for research-based evidence on Dengue fever; more interventional research is required in community to eradicate this problem. On-going public awareness campaigns need to be strengthened and vigorous campaigns need to be initiated at all levels. Family doctors in primary health care setting have an opportunity to not only give the best possible supportive care to their patients but also educate them regarding the spread of Dengue fever and vector control. References 1. Dengue Fever World Health Organization Fact Sheet No.117.2009 [http://www.who.int/mediacentre/ factsheets/fs117/en/]. 2. Khan E, Kisat M, Khan N, Nasir A, Ayub S, Hasan R: Demographic and clinical features of dengue fever in Pakistan from 2003-2007: a retrospective cross-sectional study. PLoS One 2010, 5(9):e12505. 3. Jawad KA, Masood S, Tassawar H, Inam B, Waheeduz ZT: Outbreak of Dengue Hemorrhagic Fever in Karachi. Pak Armed Forces Med J 2001, 51(2):94-8. 4. Naseem S, Farheen A, Muhammad A, Fauzia R: Dengue fever outbreak in Karachi, 2005âˆ’A clinical experience. Infect Dis J 2005, 14(4):115-7,5. Gibbons RV, Vaughn DW. Dengue: an escalating problem. BMJ 2002, 324:1563-6. 5. Guzman MG, Kouri G: Dengue: an update. Lancet Infect Dis 2002, 2:33-42. 6. Almas A, Parkash O, Akhter J: Clinical factors associated with mortality in dengue infection at a tertiary care center. Southeast Asian J Trop Med Public Health 2010, 41(2):333-40. Asian Journal of Paediatric Practice, Vol. 14, No. 3
short report 7. Butt N, Abbassi A, Munir SM, Ahmad SM, Sheikh QH: Haematological and biochemical indicators for the early diagnosis of dengue viral infection. J Coll Physicians Surg Pak 2008, 18(5):282-5. 8. Khan E, Hasan R, Mehraj V, Nasir A, Siddiqui J, Hewson R: Co-circulations of two genotypes of dengue virus in 2006 outbreak of dengue hemorrhagic fever in Karachi, Pakistan. J Clin Virol 2008, 43(2):176-9. 9. Humayoun MA, Waseem T, Jawa AA, Hashmi MS, Akram J: Multiple dengue serotypes and high frequency of dengue hemorrhagic fever at two tertiary care hospitals in Lahore during the 2008 dengue virus outbreak in Punjab, Pakistan. Int J Infect Dis 2010, 14(S3):e54-9. 10. Jamil B, Hasan R, Zafar A, Bewley K, Chamberlain J, Mioulet V, Rowlands M, Hewson R: Dengue virus serotype 3, Karachi, Pakistan. Emerg Infect Dis 2007, 13(1):182-3. 11. Ali N, Nadeem A, Anwar M, Tariq WU, Chotani RA: Dengue fever in malaria endemic areas. J Coll Physicians Surg Pak 2006, 16(5):340-2. 12. Wasay M, Channa R, Jumani M, Zafar A: Changing patterns and outcome of Dengue infection; report from a tertiary care hospital in Pakistan. J Pak Med Assoc 2008, 58(9):488-9. 13. Muhammad A, Adel MK, Eman HL, Shahid B, Adnaan YA, Sawsan AU: Characteristics of Dengue Fever in a
large public hospital, Jeddah, Saudi Arabia. J Ayub Med Coll Abottabad 2006, 18(2):9-13. 14. Syed M, Saleem T, Syeda UR, Habib M, Zahid R, Bashir A, Rabbani M, Khalid M, Iqbal A, Rao EZ, Saleem S: Knowledge, attitudes and practices regarding dengue fever among adults of high and low socioeconomic groups. J Pak Med Assoc 2010, 60(3):243-7. 15. Ageep AK, Malik AA, Elkarsani MS: Clinical presentations and laboratory findings in suspected cases of dengue virus. Saudi Med J 2006, 27(11):1711-3. 16. Riaz MM, Mumtaz K, Khan MS, Patel J, Tariq M, Hilal H, Siddiqui SA, Shezad F: Outbreak of dengue fever in Karachi 2006: a clinical perspective. J Pak Med Assoc 2009, 59(6):339-44. 17. Kay BH, Nam VS, Tien TV, Yen NT, Phong TV, Diep VT, Ninh TU, Bektas A, Aaskov JG: Control of aedes vectors of dengue in three provinces of Vietnam by use of Mesocyclops (Copepoda) and communitybased methods validated by entomologic, clinical, and serological surveillance. Am J Trop Med Hyg 2002, 66(1):40-8. 18. Hanh TTT, Hill PS, Kay BH, Quy TM: Development of a Framework for Evaluating the Sustainability of Community-based Dengue Control Projects. Am J Trop Med Hyg 2009, 80(2):312-8.
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Acute Foot Rash in a Healthy Child During Travel
uring a trip to Brazil, a two-year-old girl presented with sudden foot pain while playing in the dirt near a tree. Her mother saw no glass, nails, or insects on the ground where the child was playing. The sole of the child’s left foot initially turned white in a linear pattern. Three hours later, the foot was erythematous with multiple petechiae (Figure 1). Swelling progressed from the sole to the rest of the foot, and then to the ankle with linear streaks. The child could not put weight on the foot. Four hours after the injury, she developed a fever of 103°F (39.4°C) and was difficult to console. Oral and topical antibiotics and acetaminophen were ineffective.
Question Based on the patient’s history and physical examination, which one of the following is the most likely diagnosis? A. Acute dermatitis. B. Cellulitis C. Contusion. D. Foreign body injury. E. Insect bites. Discussion The answer is A: Acute dermatitis from a caterpillar sting. Further investigation found lime green caterpillars feeding on the leaves of the tree near where the child was playing (Figure 2). Caterpillars usually camouflage themselves on tree leaves. The family returned to the United States nine days after the injury, and the mother took the child to their family physician. Physical examination revealed swelling, purulent pockets, and multiple black caterpillar hairs/spines on the bottom of the foot. The physician discontinued the antibiotics and cleaned the area with soapstone (localized debridement). The child was able to walk on the foot after two days, and her fever subsided. Stinging Source: Adapted from Am Fam Physician. 2011;83(2):201-202.
caterpillars have specialized spines that contain poison glands. If the spines penetrate the skin, toxins spread on the surface of the skin, causing dermatitis.1,2 Reactions vary from mild, localized itching to more severe pain, swelling, and inflammation. Occasionally, a systemic response with diarrhea occurs. There have been reports from around the world of reactions from caterpillar stings, including dermatologic, pulmonary, and other systemic reactions.2,3 Removal of the caterpillar spines through debridement is the most effective means to counteract the toxic process and clear the localized reaction. Stings from some species of caterpillars can cause hemorrhagic reactions and arthritis.4,5 Cellulitis Asian Journal of Paediatric Practice, Vol. 14, No. 3
photo quiz Summary Table Condition
A transient but sometimes painful inflammatory reaction of the skin; reactions vary from mild, localized itching to more severe pain, swelling, and inflammation; more severe systemic reactions are rare but possible
Diffuse inflammation of subcutaneous and loose connective tissue caused by bacterial infection; may lead to localized pain, erythema, swelling, and warmth
Mechanical injury resulting in hemorrhage beneath unbroken skin; often associated with blunt trauma; injury may evolve with time
Foreign body injury
Localized trauma causing a wound; traumatic injuries can range from minor to life threatening
Inflammation at the site of punctured skin; usually appears within minutes to a few hours after the bite
is a diffuse inflammation of subcutaneous and loose connective tissue caused by bacterial infection. It can lead to localized pain, erythema, swelling, and warmth. Typical treatment involves appropriate antibiotic therapy.6 Contusions are usually caused by mechanical injury resulting in hemorrhage beneath unbroken skin. They are often associated with blunt trauma, and the injury may evolve over time. Foreign body injuries are associated with localized trauma that causes a wound. Traumatic injuries can range from minor to
Asian Journal of Paediatric Practice, Vol. 14, No. 3
life threatening. A typical reaction to an insect bite is an inflammatory response at the site of the punctured skin. It usually appears within minutes to a few hours after the bite. Insects that commonly bite humans include fleas, mosquitoes, ticks, bedbugs, blackflies, and sand flies.6,7 References 1. Stanton G. Stinging caterpillars out in late summer and‑fall.‑http://ipmnet.umd.edu/landscape/docs/ Stinging Caterpillars-UMD.pdf. Accessed July 5, 2009. 2. Diaz JH. The evolving global epidemiology, syndromic classification, management, and prevention of caterpillar envenoming. Am J Trop Med Hyg 2005;72(3):347-57. 3. Bessin R. Stinging caterpillars. http://www.ca.uky.edu/ entomology/entfacts/ef003.asp. Accessed July 5, 2009. 4. Secretaria de Estado da Saude do Parana. (Lonomia) acidentesII.http://www.saude.pr.gov.br/modules conteudo/conteudo.php?conteudo=389.‑Accessed July 5, 2009. 5. Lima C. Largatas que queimam. January 31, 2008. http://www.olharvital.ufrj.br/2006/index.php?id_edicao =114&codigo=10. Accessed July 5, 2009. 6. Ectoparasite infestations and arthropod and stings: caterpillar stings and dermatitis. In: Kasper DL, Harrison TR, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:2607. 7. Lepidoptera: arthropods and leeches. In: Cecil RL, Goldman L, Ausiello DA, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa.: Saunders; 2004:2128-2129.
Algorithm for the Management of a Previously Health Infant 0-90 Days of Age with Fever without Source, ≥100.4°F Toxic appearing, 28-90 days of age and ‘Low-risk’*
Admit to hospital
Blood culture Urine culture Lumbar puncture Parenteral antibiotics Chest X-ray**
Blood culture Urine culture Lumbar puncture Ceftriaxone 50 mg/kg IM Re-evaluation within 24 hours
Blood culture Urine culture Re-evaluation within 24 hours
*Low-risk criteria for febrile infants. **Chest X-ray if signs of pneumonia: Respiratory distress, abnormal breath sounds, tachypnea, pulse ox <95%
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AAP Reports on Diagnosis and Prevention of Iron Deficiency Anemia
ron is the most common single-nutrient deficiency among children in developing countries and is a common cause of anemia in industrialized nations. Evidence shows that iron deficiency and iron deficiency anemia during infancy and childhood may have longlasting detrimental effects on neurodevelopment that may not be reversible. Approximately 80 percent of the iron in newborn infants is accumulated during the third trimester of pregnancy; therefore, infants born prematurely may be iron deficient. Maternal conditions such as anemia, hypertension with intrauterine growth restriction, or diabetes mellitus can also result in low fetal iron stores. Full-term healthy infants have sufficient iron for at least the first four months of life. Because human milk contains little iron, infants who are breastfed exclusively are at risk of iron deficiency after four months of age and should receive 1 mg of supplemental iron daily per kg of body weight. Supplementation should continue until iron-containing foods are introduced in the diet. Starting at four months of age, infants who are breastfed for more than one-half of their feedings should also receive 1 mg of supplemental iron daily per kg of body weight. In formula-fed infants, iron needs can be met for the first 12 months of life by using formula that contains 12 mg of iron per dL and by introducing ironcontaining foods after four to six months of age. Whole milk should not be given before 12 months of age. Iron intake in infants between six and 12 months of age should be 11 mg per day. Liquid iron supplements are appropriate if iron needs are not being met. Iron intake in children one to three years of age should be 7 mg
per day. Liquid supplements are suitable in those who do not receive this intake. Chewable multivitamins can be used in children three years and older. Iron intake in preterm infants should be at least 2 mg per day through 12 months of age. Preterm infants who are breastfed should receive 2 mg of supplemental iron per kg of body weight each day by one month of age, and supplementation should continue until the infant is weaned to iron-fortified formula or begins to eat foods that supply 2 mg of iron per kg of body weight. Supplementation is not required in infants who have received an iron load from multiple transfusions of packed red blood cells. Universal screening for anemia should be performed at 12 months of age, with measurement of hemoglobin levels and an assessment of risk factors associated with iron deficiency and iron deficiency anemia. Additional screening can be performed in children one to three years of age who have risk factors for iron deficiency or iron deficiency anemia. Further evaluation is required in children with hemoglobin levels less than 11 g per dL (110 g perâ€‘L) at 12 months of age. If the child is at high dietary risk of iron deficiency, testing should be performed because of potential adverse effects on neurodevelopmental outcomes. Additional screening tests should include measurement of serum ferritin and C-reactive protein levels, or measurement of reticulocyte hemoglobin concentration. Children with mild anemia (hemoglobin level of 10 to 11 g per dL [100 to 110 g per L]) who can be monitored closely can be diagnosed by documenting an increase of 1 g per dL in plasma hemoglobin concentration after one month of iron-replacement therapy. n
Source: Adapted from Am Fam Physician. 2011;83(5):624.
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From the eMedinewS Acetaminophen Intake During Pregnancy may Increase Risk for Childhood Asthma
Mothers who use acetaminophen when they are pregnant may be placing their unborn child at risk for asthma, according to a study in the April issue of Clinical and Experimental Allergy.
Children as Young as 11 may Show Signs of Future Cardiovascular Danger According to two studies presented at a cardiology meeting, children as young as 11 show worrisome signs of future cardiovascular danger. In the first study involving 1,104 students, researchers found that 16% of the adolescents had low HDL cholesterol levels 40 mg/dl or less. A second study by the same group of researchers revealed that there were children with poor cardiovascular fitness identified through their heart rate recovery after a threeminute step test. Obesity Update
References 1. Brown KH, Dewey KG, Allen LH. Complementary Feeding of Young Children in Developing Countries: A Review Of Current Scientific Knowledge. WHO/ UNICEF, 1998. 2. Dewey KG. Guiding Principles for Complementary Feeding of the Breastfed Child. PAHO/WHO, 2003. 3. WHO. Complementary Feeding: Family Foods for Breastfed Children. Geneva: World Health Organization, 2000. —Dr Neelam Mohan, Director Pediatric Gastroenterology, Hepatology and Liver Transplantation, Medanta – The Medicity
Infants of Overweight Mothers
Is there any Increased risk of Epilepsy in Children with Febrile Seizures Later in Life?
Even in moderately overweight mothers (BMI 25-30 or 120-150% of ideal body weight), the incidence of perinatal death in the infants was 1.15- to 2.5-fold higher than that in normal-weight women. In obese women (BMI >30 or >150% of ideal body weight), the incidence of perinatal death in infants exceeded that in normal-weight women by 2.5 and 3.4. Maternal complications and preterm deliveries largely contribute to this excessive mortality. Pediatric Update Complimentary Feeding Practices between Six and 24 Months
Diversify the diet to improve quality and micronutrient intake.
Feed meat, poultry or fish daily or as often as possible, if feasible and acceptable. Use fortified foods, such as iodized salt, vitamin Aenriched sugar, iron-enriched flour or other staples, when available. Give vitamin-mineral supplements when animal products and/or fortified foods are not available. Avoid giving drinks with low nutrient value, such as tea, coffee and sugary beverages.
Feed vitamin A-rich fruits and vegetables daily.
Self-limited generalized convulsion lasting <15 minutes is not associated with any long-term effects on brain function or intelligence. If more than a single febrile seizure in a lifetime, caregiver can be informed that the risk of a child developing this condition after a single simple febrile seizures is very low. In the large British birth cohort-study, the background rate of epilepsy was 0.4% by 10 years of age. Children who had a simple febrile seizure had 1% risk. Although this represents a significantly increased relative risk, the overall prevalence remains low. To emphasize this, parents can be told that there is a 99% chance that their child will not have epilepsy. —Dr Neelam Mohan, Director Pediatric Gastroenterology, Hepatology and Liver Transplantation, Medanta – The Medicity
Asian Journal of Paediatric Practice, Vol. 14, No. 3
emedinews section Legal Question of the Day
What is the Procedure if a Child is Brought Dead by a Mob (or Group of Relatives?)
What is Choanal Atresia? How does the Child Present?
If there is a mob (or a group of relatives), immediately divide the doctor’s working team in two parts. One team shall explain to the parents that child is dead yet if you permit we may give some treatment but situation may not change. The second team tackles the mob that wants the child to be treated anyhow. Tell them he is already dead but the team of doctors is doing its best. Declaration of death in a child brought dead by a mob should be essentially preceded by rapid assessment and an attempt to resuscitate after talking to the group as mentioned above. This declares death at terms and conditions desired by medical team rather than swept away by the unruly behavior of the mob. When a child is brought by mob, which is not amenable to explanations, then one should surely inform police for protection and only then declare final death. The situation will be considered all the more serious, if the child is brought dead. Avoid loose talk, which may spark problems and may lead to physical abuse of medical team.
—Dr GM Singh
Choanal atresia is narrowing or complete blockage of one or both posterior ends of nasal passages. It is a congenital problem. Bilateral complete choanal atresia is diagnosed at birth. As small kids are obligate nose breathers, children with bilateral choanal atresia develop respiratory distress and cyanosis which may improve with crying. To confirm, a red rubber catheter is passed through the nose which in case of choanal atresia cannot be passed to the oropharynx. Nasal endoscopy, CT scan or X-ray with radio-opaque dye in the nose will further confirm the diagnosis. Patients with unilateral atresia may present late with unilateral nasal blockage, discharge or difficulty in taking feeds. Choanal atresia needs to be corrected surgically and bilateral choanal atresia is an emergency situation requiring airway management through intubation followed by corrective surgery. Choanal atresia is one of the conditions of CHARGE syndrome, others being -Coloboma of eyes, Heart defects, Retardation of growth, Genital abnormalities and Ear anomalies or deafness. —Dr Aru Handa, Dept Co-coordinator and Senior Consultant, Dept. of ENT Moolchand Medcity
Inspirational Story The Three Frogs
Question: Three frogs sat on a log and one decided to jump off. How many frogs were left on the log? Answer: Three. Explanation: Although almost everyone answers ‘two’, the correct answer is ‘three.’ Just because the frog decided to jump off the log does not necessarily mean that it actually did it. Is there a gap between what you decide to do and what you actually do? Laugh a While The Leave Applications
A leave letter to the headmaster: “As I am studying in this school I am suffering from headache. I request you to leave me today”. An employee applied for half-day leave as follows: “Since I’ve to go to the cremation ground at 10 O’ clock and I may not return, please grant me half-day casual leave”. “As my mother-in-law has expired and I am only one responsible for it, please grant me 10 days leave”.
Asian Journal of Paediatric Practice, Vol. 14, No. 3
Asian Journal of
Paediatric Practice Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Asian Journal of Paediatric Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.
Covering letter – The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. – Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. – Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.
Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures). – The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures. – All pages should be numbered consecutively beginning with the title page. Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.
Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.
Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references.
Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.
– These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described.
Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. – Confidence intervals for the measurements should be provided wherever appropriate.
Asian Journal of Paediatric Practice, Vol. 14, No. 3
Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.
Discussion – This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g. practicality and cost.
References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are:
Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.
Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985. Articles in Books Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.
– The legend must include enough information to permit interpretation of the figure without reference to the text.
– Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. – The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. – Color illustrations will be accepted if they make a contribution to the understanding of the article. – Do not use clips/staples on photographs and artwork. – Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.
Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________ 5. Special requests ____________________________ 6. Suggestions for reviewers (name and postal address) Indian 1.___________ Foreign 1._ ___________ 2.___________ 2._ ___________ 3.___________ 3._ ___________ 4.___________ 4._ ___________ 7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________
Tables – These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.
Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.
Asian Journal of Paediatric Practice, Vol. 14, No. 3
For Editorial Correspondence: Dr KK Aggarwal Group Editor-in-Chief
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