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Vaccines and Immunization at CrossRoads Revolutionizing AIDS Vaccine Design In Nepal, A New Battle Starts Against TB

Issue 08

Fall 2010 $4.95 U.S.

Vaccine Redux www.globalhealthmagazine.com —


Ben-Gurion University of the Negev - Faculty of Health Sciences

The Medical School for International Health in collaboration with Columbia University Medical Center

Interested in a career in global health? The Medical School for International Health is the only four-year, North-American style medical school that incorporates global health coursework into all four years of the required M.D. curriculum.

I did my undergraduate work at the McGill University in Montreal, but I chose the MSIH because it gave me the unique opportunity to study population health and cross-cultural medicine as part of my M.D. degree, and gave me clinical experience in areas like refugee health and humanitarian emergencies. Classes are taught in English. The campus in Beer-Sheva, Israel is the perfect location for hands-on experience with diverse populations. I took my clinical electives in India and at Columbia University Medical Center and placed in a competitive U.S. residency program in Pediatrics. Where will you be in four years?

Now accepting applications for admission to the entering class of Fall 2011. Applications are reviewed on a rolling basis. 212-305-9587 admissions bgcu-md@columbia.edu www.cumc.columbia.edu/dept/bgcu-md


Page 1 —

issue 08

contents —

In this issue:

06 Vaccines at CrossRoads

09 Dengue – An Escalating Threat

COVER STORY: vaccine redux

12 Tragedy Brings Faces and Names to TB

17 New Approaches to Immunization Logistics

14 Building Bridges, Dismantling Walls: Revolutionizing AIDS Vaccine Design 20 Resisting vaccines 22 In Ancient Culture, New Battle Starts Against TB

screenshots —

04 Age of First Use: IDUs in Eastern Europe 05 Russia: Abandonment of Infants by HIV+ mothers 05 Comparison of HIV Prevalence among MSM and Adults of Reproductive Age

www.globalhealthmagazine.com


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Issue 08

Global Health

letter

from the editor

Executive Editor

Annmarie Christensen Managing Editor

Tina Flores

Web

Winnie Mutch Liza Nanni Graphic Design

Shawn Braley E-mail:

Vaccines revisited

magazine@globalhealth.org Global Health Council

We know they are an effective intervention. We know that investing in immunizations pays long-term dividends in the form of a reduced disease burden and economic advantages of a healthier population. But as Dr. Adel Mahmoud adeptly expresses in his article, we are at a crossroads. While modern technologies have advanced the development and distribution of vaccines, so too have infectious diseases evolved, like a tricky Darwinian dance. Diseases like dengue, as Hosbach and Feldman say, are cropping up in Northern climates. But what will it take to get ahead? It will entail more than commitment and resources – although certainly they are essential to this process. Perhaps it is time to take greater risks. Invest in new ideas, new people, new countries. Beth Waters, to whom this issue is dedicated, took a risk when, at the age of nine, she became a “polio pioneer.” Whether it be unlocking the key to the HIV virus in IAVI’s New York City laboratory; or finding a way to deliver time-honored immunizations better and more efficiently as PATH does; or reaching out in communities where there is resistance to the idea of vaccinations. We need to continue to find ways to advance the progress of vaccines by putting intelligent hypotheses to work. Everything we know now about vaccines started as a humble idea brought to fruition. The naissance of modern vaccination was, for all intents and purposes, in a milking shed. Not a laboratory. Smallpox was ferried to the New World, quite literally, by orphans. Not refrigerated containers. Necessity is the mother of invention, as the old adage says. Sometimes, the greater the need, the more acceptable – or understandable – the risk. So in the race of survival of the fittest, who is winning?

The Editors ISSUE 08 fall 2010

Board of Directors

Joel Lamstein, SM, chair William Foege, MD, MPH, chair-emeritus Valerie Nkamgang Bemo, MD, MPH Alvaro Bermejo, MD, MPH George F. Brown, MD, MPH Rev. Dr. Joan Brown Campbell Christopher Elias, MD, MPH Elizabeth Furst Frank, MBA Julio Frenk, MD, PhD Michele Galen, MS, JD Gretchen Howard, MBA Hon. Jim Kolbe, MBA Patricia McGrath Reeta Roy Jeffrey L. Sturchio, PhD, President and CEO Global Health is published by the Global Health Council, a 501(c)(3) nonprofit membership organization that is funded through membership dues and grants from foundations, corporations, government agencies and private individuals. The opinions expressed in Global Health do not necessarily reflect the views of the Global Health Council, its funders or members. Learn more about the Council at www.globalhealth.org


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In Memory of Beth Waters 2006

Reflections on a Lifetime Dedicated to Public Health Advocacy

issue 08

online exclusives —

Beth Waters was a communications professional committed to advancing the cause of vaccine development and delivery. Among her many achievements, she helped to create a model for improving access to HIV treatment that has been applied to scale up treatment for other diseases.

C

go to www.globalhealthmagazine.com for further reading

A reporter in the early years of her career, Beth was a senior managing director of Ogilvy Public Relations before co-founding Cooney/Waters Group, a health-care public relations and public affairs company in New York City. Beth was indefatigable in her work on vaccine advocacy, traveling the world to lend her intensity and expertise to her clients, governmental committees and non-governmental organizations; and promoting immunization against polio, HIV/ AIDS, avian influenza and meningococcal disease. Beth was a wise counselor, a creative problem-solver, and a relentless optimist.

C Hot Escapes

Molly McHugh escapes on a safari in Tanzania

She was a founding member of the advisory board of the Vaccine Education Center of the Children’s Hospital of Philadelphia and a member of the HIV Vaccine Communications Steering Group of the National Institute of Allergy and Infectious Disease. Beth Waters often said that her first job in immunization advocacy was as a child of nine. She was a “polio pioneer” – one of the children who participated in the U.S. clinical trials of the vaccine that would mark the beginning of the end of the scourge of the disease that crippled or killed children and young adults throughout the 20th century. An unrelenting crusader for the prevention of infectious diseases, her involvement with global polio eradication continued right through the last decade of her life. Indeed, much of her 30 years in communications and public affairs centered on advocacy for vaccines to protect against diseases in both industrialized countries and the developing world. 

C Field

Notes

International Relief & Development battles infectious diseases and the elements in postflood Pakistan

Every aspect of immunization intrigued her, from the intricacies of production and supply to the involvement of communities in clinical trials of candidate vaccines for mass immunization programs. Indefatigable in her efforts, she traveled the world to lend her intensity and expertise in international scientific forums and at the grassroots level, working with her client sanofi pasteur, governmental committees and nongovernmental organizations. “Beth’s work exemplifies the power of communications in bringing together people and groups to advance the prevention and treatment of infectious diseases, most notably HIV/ AIDS,” said Wayne Pisano, chairman and CEO of international vaccines company sanofi pasteur. “It was impossible to slow her down. She fought for disease prevention with an energy and enthusiasm that was often as contagious as any of the microbes she battled.” www.globalhealthmagazine.com

Corporate sponsorship provided by sanofi pasteur.


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Global health statistics

screenshots —

Age of first use: IDUs IN EASTERN EUROPE aged 15-24 years 100% 90% 80% 70% Injected before 15 years

60%

Injected before 18 years

50% 40% 30% 20% 10% 0%

Albania

moldovia

Romania

Serbia

(mean age 15.6 yrs)

(mean age 17.5 yrs)

(mean age 16 yrs)

(mean age 18.7 yrs)

ISSUE 08 fall 2010

Source: Blame and Banishment: The Underground HIV epidemic affecting children in Eastern Europe and Central Asia. Unicef, 2010


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Russia: Abandonment of Infants by HIV+ mothers per 1,000 live births, russian federation, 2008 160 140 120 HIV (-) women

100 80 60

HIV (+) women

40 20

far eastern

sibirsky

uralsky

privolzhsky

south

north-west

Russian federation

central

0

Source: Blame and Banishment: The Underground HIV epidemic affecting children in Eastern Europe and Central Asia. Unicef, 2010

Comparison of HIV Prevalence among MSM and Adults of Reproductive Age prevalence rate %

pepfar countries

guatemala

0

2.5

5

7.5

10

12.5

15

17.5

20

22.5

25

27.5

30

32.5

+ + + + + + + + + + + + + + + + + + + + + +

jamaica

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

cote d’ivoire

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

zambia

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

malawi

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + ++ + + ++ + + + + + +

vietnam

+ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

china ukraine

35

prevalence

+ + + + + + + + + + + + + + + + + + + + + + + +++ + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +

MSM and the Global HIV/AIDS Epidemic: Assessing PEPFAR and Looking Forward. amFAR, 2010

aggregate msm

population (15+ years old)

Click on the source at C www.globalhealthmagazine.com.


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by Adel Mahmoud MD, PhD

Global Perspective:

Vaccines and Immunization at Crossroads

Vaccines and immunization were voted as the top public health achievements of the 20th Century in a 1999 survey of workers in the field. The reasons are obvious to many who live in developed countries where vaccinepreventable diseases have decreased dramatically. But in spite of its remarkable success in stemming infectious diseases, the overall status of vaccination is spotty. In fact, the total global effort is inadequate to address the multifaceted threats of infectious diseases. Furthermore, vaccine discovery, development and deployment for the needs of the developing world are lagging. The crucial question is, why? A better understanding of the nature and evolution of human-microbe interplay is a necessary first step. Microorganisms are cohabitants of this earth, as microbiologist Joshua Lederberg argued for more than two decades. The war metaphor – we vs. them – has failed not only because of development of resistance but more importantly because prevention and control need comprehensive, multifaceted approaches. Antibiotics and other entities that were once tools in the arsenal are being met with resistance. Nevertheless, prevention and control of infectious diseases have been accomplished in many parts of the world where vaccines played a central role.

ISSUE 08 fall 2010

Current Status of Vaccines Most of the vaccines used today to protect human populations are made of the whole organism – either modified by attenuation or killed to induce protection with little or no side effects. Similarly, we use extracts of whole organisms in the induction of protection. However, these old technologies are, for the most part, exhausted and new avenues need to be explored. In only a few cases have we actually succeeded in defining the protective components of an infectious agent and managed to clone and express these components in vitro. The products are remarkably successful vaccines such as those for Hepatitis B and Human papillomavirus. Our progress on this front has been slow and fraught with many hurdles – reflecting the magnitude and complexity of the task. In spite of the gains in our knowledge of monoclonal antibodies, immunology, gene sequences, etc., the road to discovery and paving the way for vaccines against the major global infections such as HIV, malaria and TB has been challenging, to say the least. Vaccine Development and Manufacturing Another reason undermining vaccine availability and deployment is the relatively limited global base for these endeavors. Until recently, vaccine development

Adel Mahmoud MD, PhD is a professor in the Department of Molecular Biology and at the Woodrow Wilson School of Public and International Affairs at Princeton University.


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This is not the time for observing, analyzing or prescribing. It is time for a concerted effort.

and manufacturing has been limited to a few global pharmaceutical companies. This concentration of human talent and industrial capital resulted in inadequate supplies of the most-needed vaccines for global use. A recent example of this was the threat of pandemic flu. The supply of vaccine was immensely inadequate and many developing countries were left struggling to secure a fraction of what they needed from the limited global supply. The restricted global development and manufacturing capacity also results in a diminished interest to scale-up or invest in new vaccine efforts. Indeed, with the complex clinical and regulatory environment, investment in new facilities has been slow and inadequate to meet global needs. The situation is rapidly changing because of an evolving global market for vaccines. Over the past decade, entry of vaccine companies in middle-income countries in the development and manufacturing of sorely-needed supplies of standard vaccines – especially those for childhood immunization programs – is a welcome development. The impact of these manufacturers has been tremendous. For example, more than 50 percent of vaccines procured for GAVI Alliance programs are now supplied by middle-income country vaccine producers. Their entry may have been accelerated by market size growth and future prospects, but it also reflects the expanding base of vaccine manufacturing in these countries. What is also more encouraging is that manufacturers in middle income countries are gradually moving from the production of traditional vaccine products to the development of new vaccines, combination products and others. It is a matter of time until they become fully fledged vaccine development and manufacturing powerhouses capable of playing major roles in the global marketplace. These countries also have the

added advantage of a lower cost structure which allows them a competitive market position. The global interests of big pharmaceutical concerns have changed course as well. Over the past decade, most, if not all, the major global pharmaceutical companies have entered the market either through acquisitions and mergers with existing vaccine companies, or alliances with biotechnology organizations. Today, all largest pharmaceutical companies are heavily invested in vaccine discovery and development. The rationale is complex and probably reflects the recent market appeal as well as the growth curve of global vaccine utilization; the scientific challenge of discovery for some of the major infectious diseases; as well as exploring the potential for vaccines to target cancer and other conditions. Finally, the slowing of drug discovery and development in general has encouraged many big pharmaceutical companies to extend their pipeline into vaccines and biologicals as a companion strategy for growth. It remains unclear whether this expanded repertoire of the pharmaceutical industry in developed countries will take into consideration the total global needs for vaccines or will remain focused on large, economically rewarding markets. The Global Reach of Vaccines The global map of vaccine use and deployment is uneven at best. The global efforts championed by the World Health Organization, UNICEF and organizations such as GAVI Alliance have contributed significantly, but the reach of the vaccine umbrella is still inadequate. A uniform, sustained, high coverage of EPI vaccines has not been achieved. While this situation is multi-faceted, the gaps in immunization rates are staggering. Vaccine use and coverage is inadequate in most developing

C click on the source at www.globalhealthmagazine.com


Page 8

countries and is under attack in several developed countries.

of vaccine discovery will necessitate the best, brightest and most innovative of our intellectual and scientific talents.

In addition, it is difficult to introduce new vaccines to the developing world while maintaining the rate of inoculation with traditional immunizations when there is a financial shortfall. Furthermore, the global vaccination agenda is now facing several new vaccines that were introduced late in the previous decade or early during the turn of the century. These include pneumo conjugate, rotavirus and human papilloma virus vaccines, as well as new opportunities with cholera and typhoid vaccines. One also has to realize that the challenge of introducing new vaccines is no longer limited to the developing world. Societal, cultural and economic forces are shaping vaccine introductions in developed countries as well. What happened with the introduction of human papilloma virus vaccine in the USA compared to the UK and other European countries is a recent example of the challenges. Moreover, the multiple negative and antivaccine sentiments further compromise the reach of the vaccine umbrella in the developed world. Equally distressing is the challenge of TB, malaria, HIV, lower respiratory tract infections and diarrheal diseases. While the scientific efforts for discovery have been remarkable, the attempts have been uniformly unsuccessful. The time is now to take a step back, reexamine our knowledge base, our approaches and invite a new generation of talent and sciences to target one of the biggest challenges facing humanity. Now is the Time for Action The overall assessment of where global vaccines and immunization are positioned in a comprehensive effort to prevent and control infectious diseases is distressing and is at a crossroads. However, this is not the time for observing, analyzing or prescribing. It is the time for a concerted effort on multiple fronts. First: an expanded investment in understanding molecular organization of microbes; what regulates their interaction with humans; and a more quantitative appreciation of the relevant immunologic responses. These are the three fronts that are in need of an aggressive scientific effort in order to discover and develop new vaccines. This is a tall order but the easy tasks have already been accomplished. The next phase

ISSUE 08 fall 2010

Second: National leaders in developing countries need to articulate a vision and a strategic approach to the infectious diseases that are devastating their people. This vision has to be based on solid scientific information on the burden of illness and impact of these diseases within the general framework of public health priorities. An investment portfolio of material and human resources needs to be allocated and a clear cut plan for prevention and control of infectious disease needs to be implemented. Leaders of developing countries need to cease their dependence on foreign aid and assistance unless it fits into their national priorities. It is impossible to imagine that change in the developing world – whether it relates to disease control, or for that matter, any of its developmental prospects – will come from outside its borders. Generations of dependency on foreign aid and outside support resulted in few achievements and multiple instances of lack of progress, corruption and disappointment of those who give aid and for those who received it. Third: Global activism and advocacy for the appropriate and well conceived prevention and control plan is not a neocolonial approach. The developed world has a lot to offer in helping the developing countries tackle these challenges. By championing a comprehensive approach to prevention and control of infectious disease, the developed world is serving the total global need. We should not shy away from articulating comprehensive and coordinated approaches and insisting on the front seat role for national leadership and the people of the developing world. Fourth: Prevention and control of infectious disease is a multifaceted and complex process which involves more than delivering the “magic bullet.” Infectious disease prevalence, endemicity, is not only due to the interaction of microorganisms with susceptible human hosts. Rather it involves social, cultural and economic forces as well. Prevention and control of infectious disease on a global scale is necessary for the ENTIRE world, not just a segment of the population. The task therefore, has to be scientifically-based, comprehensive and involves ALL segments of the global community. GH —

C Visit www.globalhealthmagazine.com to learn more about the history of vaccines.


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by Philip Hosbach and Stuart Feldman —

The U.S. Centers for Disease Control and Prevention reported May, 2010, 28 cases of dengue fever acquired by people who lived in or had visited Key West, FL. This news on dengue raised the eyebrows of public health experts. The Key West cases were the first dengue infections reported in the continental United States, outside the Texas-Mexico border, in 65 years. There is no effective treatment against dengue and vector control has proven ineffective. While dengue fever is still primarily a tropical disease that occurs in cycles in South Asia and Central and South America, the Key West outbreak is a loud wake-up call to the rapid growth and geographic spread of dengue over the past three decades and the need for a preventative vaccine. Jon Hrusa/EPA

Dengue might be mistaken for a rare disease, given its tropical origins and exotic-sounding name. In fact, dengue is considered by the World Health Organization (WHO) to be the most common vector-borne viral disease in the world. An estimated 2.5 billion people

Philip Hosbach is vice president of Immunization Policy and Government Relations at sanofi pasteur. Stuart Feldman is director of Public Policy and Government Relations at sanofi pasteur.

Photo courtesy of CDC.

An Escalating Global Threat and the Need for a Vaccine – more than one-third of the world’s population – live in areas that put them at risk for dengue. Of those, an estimated 50 to 100 million people get dengue every year. The disease is characterized by high fever; severe pain in the joints, muscles and behind the eyes; and rash. Dengue is often called break-bone fever due to the pain associated with the disease. An estimated 2 million people each year develop a more serious and potentially life-threatening form of the disease, dengue hemorrhagic fever (DHF), which can cause enlargement of the liver, sudden rise in body temperature, and circulatory failure that can lead to shock, coma and death. There are four closely-related serotypes of the dengue virus. Infection with one type confers lifelong immunity to that type, but not to the other types. Along with other factors, some studies suggest people who are

www.globalhealthmagazine.com


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In the 1950s, just nine countries reported outbreaks of dengue to the WHO. Today, more than 100 countries in Africa, the Americas, the Eastern Mediterranean, and the Western Pacific are considered endemic regions. infected with one subtype, and then become infected with another subtype, may be more likely to come down with DHF, which can be fatal in up to 10 to 15 percent of cases. In recent decades, the dengue virus has dramatically increased its range. Large scale urbanization, travel and climate change are factors contributing to the spread of the disease. Increased international travel and migration have also played a critical role in the spread of the virus. In the 1950s, just nine countries reported outbreaks of dengue to the WHO. Today, more than 100 countries in Africa, the Americas, the Eastern Mediterranean, and the Western Pacific are considered endemic regions. Southeast Asia and the Western Pacific are considered to be most seriously affected, while epidemics are spiking in South and Central America. More than 890,000 cases of dengue were reported in the Americas in 2007 alone. Puerto Rico had more than 6,300 suspected dengue cases in the first seven months of 2010. It’s been more than 200 years since dengue was first described in medical literature. Since then, many outbreaks have plagued the Americas. By the 1950s -1960s, the disease was finally brought under control through improved public health, piped water, modern housing with screened windows and air conditioners, and pesticides to eradicate mosquitoes. But in the 1970s, when these efforts waned, dengue began making a dramatic comeback. By 1989, the Caribbean countries, followed closely by Central America and Mexico experienced more than 1 million reported cases of dengue. By 2007, dengue’s spread soared to more than 4.7 million reported cases – more than two-thirds occurring in Brazil, Paraguay, Argentina, Chile and Uruguay. During the 1980-1989 to 2000-2007 time periods, the incidence rate rose more than 15-fold in these countries with the rate in the Andean sub-region (Bolivia, Columbia, Ecuador, Peru and Venezuela) increasing more than seven-fold.

ISSUE 08 fall 2010

While mosquito control is a necessary step in thwarting the spread of dengue, it is not enough. Unlike malaria, simple technologies like bed nets will not do the job. That is because the Ades aegypti mosquito, which transmits dengue, bites during the day; the Anopheles mosquito, which transmits malaria, bites at night. On the other hand, more aggressive approaches, like mosquito eradication with insecticides, are expensive to implement and often do not work. Vaccines are urgently needed as a sustainable prevention measure to interrupt dengue’s growing geographic spread and to reduce the mounting number of hospitalizations and deaths affecting children and adults in endemic regions. Dengue vaccine development has been recognized as a priority by the WHO through the creation of the Dengue Vaccine Development Guidelines for use by researchers. For the scientific community, these initiatives have helped illuminate the many challenges and complexities associated with developing a tetravalent dengue vaccine, mainly a satisfactory safety profile (particularly in children living in endemic areas) as well as an ability to protect against all four subtypes of the dengue virus. During the past decade, considerable progress has been made by vaccine manufacturers and researchers. Currently, several vaccines are in various stages of advanced development with encouraging preliminary data. An immune response was generated against all four subtypes of the dengue virus in a recent study among American adults using sanofi pasteur’s candidate vaccine. A large-scale clinical study using the sanofi pasteur vaccine candidate to assess efficacy in children has begun in Thailand with other Phase 3 trials scheduled to begin by year’s end. If the sanofi pasteur trials are successful, dengue vaccine could be available as early as 2015-2016, providing a much needed public health intervention for this growing, worldwide threat. The availability of a vaccine that clinical trials have shown to be safe and effective would be a significant scientific triumph. To turn a vaccine into a true victory against dengue will require a good deal more work on the part of the international global health community and the governments of endemic countries. Establishing incidence and prevalence by region and by country will be essential for making decisions about how and where to focus immunization efforts. No less pressing is the issue of how to finance the purchase of the large number of doses needed to have an impact in preventing a disease that affects a vast geography. Some global health experts worry that too few studies have been conducted to determine the true burden of the disease in terms of morbidity and mortality or its


Page 11 —

A young girl beside a cartel sponsoring the fight against dengue in Iquitos, Belen district, Peru. Photo by Marco Simola, courtesy of Photoshare

economic impact in heavily affected countries. Disease surveillance is adequate in a few countries, inconsistent in many others, and virtually non-existent in the rest. It is believed that cases of dengue are under-detected, as reporting varies widely and laboratory confirmation is often lacking. According to a 2009 joint report by The United Nations Children’s Fund (UNICEF) and WHO, entitled State of the World’s Vaccines and Immunization, effective disease surveillance provides vital intelligence needed to guide public health policy and the design and execution of immunization programs. For a disease like dengue, where estimates of the number of doses required for initial immunization of just the youngest part of the vaccine-eligible population are significant, improved surveillance is crucial. As the vaccine comes into wide use, monitoring and case-based surveillance, supported by laboratory confirmation, will be necessary to fully understand the vaccine’s impact on targeted populations. Dengue is a top priority in affected countries, many of which are eager to introduce dengue vaccines once a safe and effective vaccine is licensed. However, several issues still need to be addressed. Appropriate vaccination strategies need to be considered by country or region, as well as vaccine introduction, catch-up campaigns, and innovative financing mechanisms to purchase a dengue vaccine. This could include

financial support from multilateral and bilateral donors, international development banks, private philanthropy, national governments of affected nations, and publicprivate partnerships. Despite obstacles, new innovations have emerged to address the issue of vaccine purchase. In recent years, Advanced Market Commitments, which provide vaccine manufacturers with incentive to invest in vaccine development and increased manufacturing capacity, have been piloted for the introduction of pneumococcal vaccine. The International Finance Facility for Immunization is another creative approach, where grants to support immunization activities are funded through the sale of bonds backed by financial commitments from seven donor nations. Dengue is no longer an isolated tropical disease. Experts project that half the world’s population may be at risk for dengue by 2085 – a 50 percent increase from the current threat level. It is only through a consistent and coordinated approach by the global health community that we can enhance our understanding of dengue fever and fully realize the potential benefits of this urgently needed vaccine. For the first time in recent history, we are on the precipice of having a potential innovative vaccine to combat dengue. The global community needs to mobilize quickly to seize this unique opportunity. GH —

C click on the source at www.globalhealthmagazine.com


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Tragedy Brings Faces and Names to TB “Quieres cafe, mi amor? Would you like some coffee, my love?” Romel Lacson would ask this question to his wife Dr. Claudia Lacson every morning. He even asked it while she lay dying from TB meningitis in an Atlanta, GA hospital in 2004. He prayed for her to hear his voice and wake-up so they could continue their life filled with love and promise. Yet the complications from TB were too great. Claudia, along with her prematurely born daughter Emma, died in the summer of 2004. Romel knew that Claudia’s story and the stories of millions of people affected by TB needed to be shared and used in a way that would help prevent the root causes of TB. Their stories and perspectives, often reflecting stigma, isolation, poverty, as well as hope and family support, were missing from the global TB conversation. Guided by Claudia’s deep compassion for caring and advocating for others, Romel founded TB Photovoice in 2005. Using a method called photovoice, persons affected by TB document their own health realities by taking photographs of the people, places and systems that both positively and negatively affect their TB care and treatment. Through this process, participants share their local knowledge and photographs with each other in small groups. They identify themes associated with TB and craft recommendations toward improved TB diagnosis, effective and compassionate person-centered treatment, and ultimate TB elimination. TB Photovoice participants act as recorders, and potential catalysts for social action and change in their own communities. TB Photovoice has assisted projects in Mexico, South Africa, Thailand, Philippines, Brazil and the United States. Photovoice has been a transformative experience for participants in eight locations across Mexico and one in El Paso Texas-Ciudad Juarez border region. As a collective, they have expressed their journey through the fear of loss of a loved one, to the relief of healing. TB Photovoice reminds us that there is a human face to TB. There are faces like Claudia’s and those whose words and photos are represented here. Their voices will help to change policies that impact the root causes of TB if they are given the opportunity. GH

Nostalgia, Longing Aun la recuerdo: su linda voz, cabello negro y largo, esos 2 chongos que me hacia… fue una gran persona, siempre se preocupo por darme lo mejor y cuidar que nada me lastimara… un día se enfermo de tuberculosis, las cosas cambiaron, ella no volvió a ser la misma… siempre trato e salir adelante por mi pero no lo logro… ya nunca la volví a ver. Papi dice que desde el cielo me cuidara pero aquí le voy a necesitar. I still remember her. Her lovely voice, her long black hair and the two pig tails she made for me. She was a great person, always carrying me and watching over me. She got sick one day with tuberculosis and things changed. She was never the same. She always tried to give me her best but she couldn’t. I didn’t see her again. Dad says that she is in heaven and she is looking after me, but I need her here with me. J. David

ISSUE 08 fall 2010

In Mexico, TB Photovoice partners with Project Concern International, Solucion TB Project, The Allliance of Border Collaboratives, Programa de Investigacion en Migracion y Salud (PIMSA), and other TB organizations and community organizations. Visit www.tbphotovoice.org


Page 13 —

Libertad Freedom

Quemar esta mascarilla fue muy importante para mi. La use por varios meses y fue muy doloroso. Mis compañeros no sabían como era mi rostro y mi sonrisa. Cuando la queme, fue como quitarme el stigma. Me sentí libre. Burning this mask was very important to me. I wore it for several months and it was very painful. My peers didn’t know what my face and smile looked like. When I burned the mask, it was like getting rid of the stigma, I felt free. Rachel

Mi obligación y responsabilidad My Duty and Responsibility

Text

Tomar los medicamentos no es fácil, saben feos, y me incomodan mucho el estómago. Cuando me los tomo, no me gusta que nadie me hable. Tiene que pasar un tiempo antes de que yo me sienta mejor. Se que es mi obligación y responsabilidad, ¿pero hasta cuando los voy a dejar de tomar? Taking medications is not easy. They taste bad and they make my stomach upset. After I take them, I don’t like anyone to talk to me. It takes a while before I feel better. I know it is my obligation and responsibility, but how much longer must I take them? -Photovoice Project Participant

C Link to the sources on www.globalhealthmagazine.com

The border areas have been struggling with TB, a disease that knows no political boundary. The Mexico-U.S. border states reported a tuberculosis incidence rate higher than the national average, with rates of 7.9 in U.S. border states and 26.3 in Mexican border states.


Page 14

By Seth Berkley

Photo courtesy of IAVI

Building Bridges, Dismantling Walls

How Global Collaboration and Cross-Sectoral Cooperation are Revolutionizing AIDS Vaccine Design The development of a vaccine to prevent HIV infection is one of the most daunting scientific challenges of our time. Yet, for all its complexity, this field of research seeks to answer a relatively simple question: how do you get the immune system to detect and disable HIV before it has a chance to insert itself into the human genome and establish an intractable infection? Most vaccines against viruses, such as those that prevent measles and polio, do so by teaching the immune system’s B cells to generate neutralizing antibodies – exquisitely targeted protein missiles that bind to invading pathogens and tag them for destruction. HIV, however, is no ordinary adversary. It has evolved multiple strategies to flummox the immune response. Not least among these is a nearly unparalleled mutability that has vexed vaccine designers for the better part of three decades. Any vaccine devised to seriously curb the AIDS ISSUE 08 fall 2010

pandemic will, at a minimum, have to protect against those HIV subtypes that predominate in developing countries, where some 90 percent of new infections occur. It should also thwart multiple variants of those viruses. This poses extraordinary scientific and logistical challenges. But it also has significant implications for the policies that guide and shape AIDS vaccine research and development. First, it requires that candidate HIV vaccines be tested in developing countries, which entails the establishment of the requisite human resources and technical capacity in such places. Second, in light of the unique scientific challenges of AIDS vaccine development, funders and policy-makers need to find ways to encourage innovation and the application of hitherto untapped technologies to solve the toughest problems in the field. Finally, global efforts to develop AIDS vaccines would benefit from greater participation from the private sector. The market disincentives Dr. Seth Berkley is president, CEO and founder of the International AIDS Vaccine Initiative.


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and risks – most prominently high failure rates and opportunity costs – inherent to HIV vaccine development have traditionally discouraged industrial participation. But appropriate incentives and funding policies could do much to change that. This is especially true today. Following the failure of two AIDS vaccine candidates over the past decade, some commentators had begun to suspect that AIDS vaccine researchers might be tilting at windmills. But significant breakthroughs in the past year have countered such doubts. Late last year, a clinical trial in Thailand demonstrated – for the first time ever in humans – that a vaccine can prevent HIV infection (though this particular vaccine candidate provided only modest protection). A few weeks prior to that, researchers at the International AIDS Vaccine Initiative (IAVI) and in the Neutralizing Antibody Consortium (NAC) it oversees reported in the journal Science that a highly collaborative effort involving some 1,800 HIV-positive volunteers in eleven countries on four continents had resulted in the isolation, from a single African volunteer, of a pair of novel antibodies capable of neutralizing a wide spectrum of HIV variants. The two broadly neutralizing antibodies (bNAbs) – PG9 and PG16 – were found to be exceptionally potent neutralizers of HIV. This discovery was closely followed by the isolation of equally potent bNAbs by the Vaccine Research Center (VRC) of the U.S. National Institutes of Health, and several others from IAVI’s antibody project. Why should these findings matter? In short, because they clear a path to solving one of the most pressing problems of AIDS vaccine development – the elicitation of sufficiently potent antibodies against many of the subtypes of HIV in circulation. Most of the experimental AIDS vaccines that have been put into clinical trials in recent years have been devised to primarily harness cell-mediated immunity (CMI). This is the branch of the immune response that depends on the recruitment of specialized soldiers known as T lymphocytes to detect and destroy cells already infected by HIV. But most researchers believe that an effective vaccine will also need to activate a neutralizing antibody response. In this view, the ideal vaccine would first deploy antibodies to prevent HIV from infiltrating cells, and would then mobilize the CMI response to mop up any viruses that slip past that biologic barrier. One of the major difficulties with this strategy has been in designing immunogens – the active ingredients of vaccines – that can teach B cells to produce broadly and potently neutralizing antibodies.

Where the samples came from

Blood samples from 11 locations were sent to IAVI’s Human Immunology Laboratory in London

Researchers have long known that some HIV positive people produce just such antibodies. And animal experiments suggest that these bNAbs, if elicited by a vaccine, would block HIV from establishing an infection in the first place. This is why researchers had exhaustively studied four particularly versatile – though not especially potent – bNAbs that were isolated more than a decade ago. But it was clear that more such antibodies were sorely needed to inform vaccine design. Antibodies attach with exquisite precision to unique folds and surfaces on large molecules. These shapes are known as epitopes. The careful study of purified bNAbs, and the epitopes they target, is the first step to devising strategies to elicit similar antibodies via vaccination. One approach to the neutralizing antibody problem – known as reverse vaccinology, the driving objective of the NAC – is to study these shapes in atomic detail, recreate them in the lab (or at least find similar structures) and use the synthetic epitopes as immunogens. Of course, the more such antibodies researchers have to scrutinize, the more likely they are to find an epitope that can be replicated to make a broadly effective vaccine. NAC researchers have found that the newly discovered bNAbs, PG9 and PG16, have several potentially valuable traits. They latch on to a relatively unchanging patch on its endlessly mutable spike – a roughly toadstool-shaped scrum of proteins on its surface that HIV uses to invade its target cells. This epitope may prove an Achilles heel

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on HIV, given that it appears to be relatively accessible compared to the target sites of previously isolated bNAbs. This means scientists might have an easier time devising immunogens to elicit similar antibodies. Finally, the antibodies are notable for their potency. This is of great practical significance because candidate HIV vaccines have historically failed to elicit vigorous antibody responses, and the more potent an antibody the less of it is needed to block infection. Beyond the elegance of the science, IAVI’s antibody project provides a lesson in how well-conceived policies can drive the development of drugs and vaccines that may have questionable market prospects but are of critical significance to global health. For one thing, it confirms the value of cultivating biomedical research capacity in developing countries and working in partnership with local scientists and institutions to conduct vaccine trials and HIV research. A network of clinical research centers IAVI supports in five southern African countries played an indispensible role in the antibody project. The network, along with a halfdozen other research centers worldwide, provided the NAC with well-characterized cohorts of HIV positive volunteers who could be studied for the project. And it allowed IAVI to cast a wide net in the antibody hunt: there’s no guarantee that a single, small cohort of volunteers would have yielded even a single antibody of interest. The IAVI-supported clinical trials network continues to contribute to the antibody project, especially through cohorts participating in Protocol C, an IAVI study of HIV positive volunteers that tracks how the virus and the immune response to it evolve from the earliest phases of infection. Thanks in part to their access to these cohorts, IAVI researchers recently received a major grant from the NIH to explore why it is that only some HIV-positive people make potent bNAbs. The antibody project also illustrates how practices that promote partnerships with the private sector can advance science in the public interest. The detection and isolation of bNAbs were accomplished through close collaboration between IAVI and affiliated scientists and researchers at two biotech companies – Monogram Biosciences in San Francisco, and Theraclone Sciences in Seattle. The former adapted its existing screening technology to evaluate hundreds of blood serum samples for their ability to neutralize a panel of HIV variants selected by IAVI researchers. Theraclone, one of four laboratories charged with isolating antibodies from IAVI’s blood samples, was

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the first to succeed, successfully isolating PG9 and PG16. It was the recipient of a grant from the Innovation Fund, which IAVI supports in partnership with the Bill & Melinda Gates Foundation to underwrite the novel application of existing technologies to AIDS vaccine development. Until it became involved in the antibody project, the company had applied its technology primarily to discover drugs for autoimmune disorders. By participating in the project, it got to showcase the versatility and power of its technology, which is just the sort of thing a start-up needs to generate new streams of revenue. In fact, Theraclone’s success with PG9 and PG16 helped it win new business from a Japanese drug company. IAVI continues to work with Theraclone and Monogram to isolate new bNAbs from several other serum samples collected in the antibody project, and has engaged other biotechs in vaccine design through the Innovation Fund. Other policy approaches that might draw more private sector participation in AIDS vaccine development include the fashioning of better incentives, advance market commitments and even public sector support to lessen the financial risk of tackling such a formidable problem. Finally, policies that support long-term rather than project-by-project financing for research would benefit AIDS vaccine design. The NAC, for example, funds labs that have a long track record of success and a demonstrated ability to innovate. This not only gives researchers the time they need to pursue the painstaking business of designing vaccines. It also frees them to adapt their strategies to respond to advances in the swiftly evolving fields of HIV pathogenesis and immunology. It is noteworthy that the NAC and the VRC, which takes a similar approach to funding, have both made several significant contributions to AIDS vaccine design. By providing a measure of financial and professional security, such policies also create a space for young HIV researchers to hone their skills in vaccinerelated research, and ready the best of them for future scientific leadership. Thanks to the recent renaissance in R&D, the outlook for an AIDS vaccine is more promising today than ever. The progress was achieved in laboratories and in clinical testing centers, but was made possible by policies and practices, beyond the domain of pure science, that encourage collaboration, capacity-building, innovation and private-sector engagement. Those practices must be extended and expanded if we are to reach the goal of making an AIDS vaccine a reality. GH —


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by Simona Zipursky, Debra Kristensen and Michel Zaffran

New Approaches To Immunization Logistics

Since the launch of the Expanded Programme on Immunization in the mid-1970s, most developing countries have been using the same standard package of six vaccines – to prevent measles, tetanus, diphtheria, whooping cough (pertussis), tuberculosis (TB) and polio. Over the last decade, however, as the public-health impact of vaccines has become increasingly recognized, funding for new vaccine development has surged.

and are considering pneumococcal and rotavirus vaccines. Uganda and Vietnam have even conducted demonstration projects with the recently licensed human papillomavirus vaccine. Throughout the next decade, countries will have opportunities to introduce many new lifesaving vaccines – in some cases doubling the number of vaccines offered in their programs. This is great news for the children, adolescents, and adults who will receive them, but it places an increasing burden on the systems responsible for their delivery.

Today, most countries have incorporated hepatitis B vaccine into their infant immunization programs. Many have added Haemophilus influenzae type b vaccine

Part of the challenge stems from the differences between the traditional six vaccines and their new counterparts. Traditional vaccines such as measles, diphtheria-tetanus-

Simona Zipursky is an advocacy and policy officer at PATH, Debra Kristensen is the group leader for Vaccine Technologies at PATH, and Michel Zaffran is director of project Optimize and senior adviser for the Department of Immunization, Vaccines and Biologicals at the World Health Organization.

Acknowledgements The authors would like to recognize the contributions of the following individuals for their help in the development of this article: Jan Grevendonk, Heidi Lasher, Joe Little, Kristina Lorenson, and Amy Wales.


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pertussis, and oral polio are now relatively inexpensive, in general costing between US$0.14 and $0.23 per dose. By comparison, new vaccines are priced between $3.50 and $15.00 per dose – even when purchased in large quantities for developing countries. Although prices will likely decrease over time, it is unlikely that they will ever be as low as traditional vaccines due to the complexity required to manufacture them. In part because of their higher cost, new vaccines are packaged differently. Traditional vaccines often come in 10- and 20-dose vials, resulting in high rates of wastage, sometimes up to 60 percent to 70 percent. While this level of wastage may be acceptable for a product that costs $0.10 per dose, the picture changes when this cost is closer to $10.00. As a result, new vaccines are coming to market in one- or two-dose vials or in readyto-use packaging that features a prefilled single-dose vaccine with an attached syringe. Such changes in packaging help to reduce vaccine wastage and increase quality and safety. These changes mean far more space is needed in the cold chain, and the risks to the system are much greater. For example, if a refrigerator full of new vaccines breaks down, or accidentally falls below freezing for a few hours, thousands – instead of hundreds – of dollars worth of temperature-sensitive vaccines could be destroyed. Addressing these challenges requires out-of-the-box thinking vis-á-vis the characteristics and packaging of these new vaccines and the design and management of the systems tasked with delivering them. Harnessing the Power of Mobile Technologies The key to strengthening the supply system is having solid information on its performance. Computerized information systems have the ability to improve the way in which data are collected and managed, as well as the way in which program decisions are made. Yet, until recently, the use of these electronic information systems in low-resource countries has not been feasible because they have required real-time connectivity in the “last mile.” In Albania, all of that is changing. The electronic immunization registry currently being piloted in the Skhodra region works to minimize the amount of paperwork health-care workers need to complete and increases the timeliness of data flow. Capitalizing on expanding cellular networks and the affordability of mobile devices, the system collects data and makes information available at the point of care through the Internet or through mobile phones where Internet access is problematic. In addition to improving the health-care workers’ ability to track individual children,

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ensuring follow-up appointments are not missed, and reducing the administrative burden of reporting, the system also includes vaccine ordering and stock control. Accordingly, the right amount of vaccine arrives at each health center in time to vaccinate the right number of children – thereby reducing the estimation errors associated with vaccine ordering and the need to maintain high buffer stocks. Both Guatemala and Vietnam are planning to implement similar pilot projects. Mobile technologies are also helping to ensure that vaccines are being stored properly, safeguarding their effectiveness. In Sudan and Iran, the national vaccine store is equipped with a short message service (SMS)based temperature monitoring system that automatically alerts staff to potentially damaging variations in the temperature of the vaccine cold room. In a pilot project in Nicaragua, the concept has moved a step further down the supply chain – refrigerators in health-care centers are online and sending temperature-status reports via SMS text messages to cell phones and a central management server. The same system can enable health workers to enter vaccine orders and surveillance reports. In Vietnam several pilot sites at district and national levels are evaluating the benefits of barcode readers – not unlike the scanners used in supermarkets – to scan vaccines in and outside of storage locations. Once a barcode is read, information on the type of vaccine, lot number, and expiry date is transmitted via the mobile network to a logistics management information system improving accuracy, stock tracking, and inventory management. If the usefulness of this approach for immunization programs is validated, the industry will be encouraged to adopt universal barcode standards for all vaccines. Gaining Efficiencies Using Environmentally Conscious Solutions The addition of new, bulkier vaccines to immunization programs around the world has driven the need to search for more economical solutions. Fortunately, many of the new avenues being explored are not only good for system cost and efficiency, they are good for the environment. For example, experts are assessing whether shipping vaccines by sea on special pallets can save costs. If proven to be cost-effective and efficient, shipping by sea may soon be the preferred method because it causes less environmental impact than shipping by air. Work is also under way in Tunisia to demonstrate the ability of health-care centers to be energy generators rather than just energy consumers. In the district of


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The key to strengthening the supply system is having solid information on its performance.

Work is under way to maximize synergies by establishing a single integrated supply chain system for all vaccines and drugs with consolidated transportation and warehouses at the regional and district levels. Also, rather than having health-care workers come to the district to pick up their vaccines, these products will now be bundled with antiretrovirals, TB, and malaria drugs and distributed directly to health-care workers. The “moving warehouse” staff will be able to take inventory and replenish stock as they visit each site and perform basic maintenance on equipment as needed. Optimizing Vaccine Products

Kasserine, a “net-zero energy” approach is being explored. All the energy needs – from refrigeration and lighting to charging an electric vehicle for transporting health commodities and health workers up to the last mile – will be offset by the solar energy produced by recently installed photovoltaic panels. Any excess energy produced will be fed back into the national electricity grid for other uses. Out-of-the-Box Strategies To extend the reach of immunization programs, innovations have also centered on making optimal use of the stability of a given vaccine without compromising safety or requiring expensive new equipment. In East Sepik, a remote district of Papua New Guinea where cold chain conditions are near impossible to maintain, a pilot project has proven the feasibility of community health-care workers delivering a package of postnatal services that includes vitamin A for mothers and the hepatitis B vaccine birth dose to infants. Taking advantage of the heat stability of the vaccine and its vaccine vial monitor (a “smart sticker” that gives a warning sign when the level of heat exposure could negatively affect the vaccine potency), the community health-care workers stored and transported the vaccine at controlled ambient temperatures (without refrigeration) for up to 30 days – increasing birth dose coverage of hepatitis B vaccine from approximately 27 percent to up to 80 percent and 100 percent. In Senegal, vaccines and other drugs (such as antiretrovirals for HIV/AIDS, TB treatments, and other essential medicines) are all initially stored in the same national warehouse. Then, because they each have their own supply chain, they are distributed throughout the country in separate trucks and stored in separate regional and district warehouses. The systems used for ordering products and conducting maintenance on equipment at health-care centers are also separate.

Work is also under way to help ensure that new vaccine products are developed with the programmatic needs of countries in mind. Public-sector stakeholders, including WHO, UNICEF, PATH, United States Centers for Disease Control and Prevention, John Snow Inc., and the GAVI Alliance, among others, are collaborating with national immunization programs and the vaccine industry to develop target product profiles for new vaccines – many of which will help address the immunization logistics challenges that countries are currently facing. Ideally, the vaccine products of the future will be designed in such a way that they will be less voluminous (thereby minimizing shipping and storage costs) and incorporate inherent safety and ease-of-use features so they can be delivered and disposed of more effectively and efficiently by health workers. Sending signals about desirable product attributes to the vaccine manufacturers during the early phases of research and development will result in more suitable, cost-effective vaccine products in the long run. Planning for the Future Improving the health outcomes for the world’s children is a priority in global health. The recent launch of the Decade of Vaccines by the Bill & Melinda Gates Foundation, strongly supported by the WHO Director General, Margaret Chan, in her recent speech to the World Health Assembly, has renewed the world’s attention and commitment to combating vaccinepreventable diseases. It is good news that many countries now have the chance to add new vaccines to their programs, but we need to ensure that the systems tasked with delivering them are able to cope. Innovative solutions exist – and they have been shown to significantly improve vaccine performance and delivery. Yet, there is work to be done. Without fully adequate or reliable vaccine delivery systems, the backbone of immunization, lifesaving interventions will not reach the very people who need them most. GH —

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by Eliza barclay

Resisting Vaccines Whether it is fighting for funding or distribution, providing immunizations continue to be challenging In recent years the contours of the battle against vaccine-preventable diseases have changed dramatically. While immunization rates worldwide are at an all-time high largely because international health institutions are reaching thousands of new children each year, vaccines have also come under fire from parents and critics questioning their safety. Not only are skeptics in countries like the United States and United Kingdom opting out of vaccines, but the anti-vaccine movement has also recently ignited in countries like India and Ukraine.

mortality. Deaths from measles, for example, fell by 74 percent between 2000 and 2007. But according to a 2009 report by UNICEF, the World Bank and the World Health Organization one in five children, or 24 million infants, are not receiving routine vaccinations.

“What has happened globally is that we are becoming more terrified of vaccines than the diseases themselves,” said John Budd, UNICEF’s chief of communication for Central and Eastern Europe and the Commonwealth of Independent States, who has witnessed active anti-vaccine communities in Ukraine, Moldova, Georgia and Romania, derailing vaccination campaigns.

Among the diseases that have eluded eradication is polio. Since 1988, when public health leaders committed to eliminate the disease forever, the number of polio cases has gone down by 99 percent. But the disease remains stubbornly endemic in four countries: Afghanistan, Nigeria, India and Pakistan. The campaign against polio also suffered a setback this year with a major outbreak of polio in Tajikistan, a country certified as polio-free since 2002. According to UNICEF, which procured vaccines and educated people about the disease during the outbreak, there were 26 deaths and 458 confirmed cases of polio in Tajikistan this year.

A sudden outbreak of polio in Tajikistan this year has also raised new questions about the exhaustiveness of routine immunization programs in countries certified as polio-free. All of these new challenges are causing vaccine advocates to reexamine their strategies and look for new ways to sustain high immunization coverage and eradication goals. With the dedication of new funds for research and global immunization drives to beat back and eradicate several vaccine-preventable diseases, vaccines have become more effective and much more widely available. Worldwide, immunizations are at an all-time high and cases of measles, yellow fever, polio, rotavirus, and other vaccine-preventable diseases have fallen dramatically resulting in huge improvements in child

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“Getting to the last 20 percent is the toughest,” said Jeffrey Rowland, spokesman for the GAVI Alliance in Geneva. “We’re talking about weak health systems, and the most remote and poorest people who have the least access to health care.”

Jeff Raikes, the CEO of the Bill & Melinda Gates Foundation, wrote in September that wiping out the disease is still among the foundation’s top priorities, but that there is a funding shortfall. “Right now, there is not enough money past next summer to carry out all of the immunization activities to keep the world on track to eradicate polio,” wrote Raikes. “It’s very clear: This is make-or-break time for polio eradication.” If less than 90 percent of a population has received a vaccine, the community at large can lose its herd immunity to a disease like polio, putting more people at

Eliza Barclay is a freelance journalist based in Washington, D.C. whose work has appeared in The Atlantic and The New York Times.


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risk in an outbreak. While the World Health Organization is still investigating the exact reasons for the polio outbreak in Tajikistan, experts suspect that it occurred because routine vaccination programs in Tajikistan were not as thorough as reported.

the successful campaign to eradicate smallpox. Foege’s home is on the island of Vashon in Puget Sound, which has three times more children who are not fully vaccinated than in the rest of the state, according to county health officials.

The Tajikistan outbreak also caught the eye of many vaccination experts in other polio-free countries who noted that they may be at risk of similar outbreaks because routine immunization rates have declined slightly. Paul Hébert, an epidemiologist at the University of Ottawa, told a writer for the Journal of the American Medical Association that “we seem to have let our guard down” in maintaining high vaccination rates and that the threat of polio in countries like Canada and the United State is “more than theoretical.” Several states in the U.S. have already seen an uptick in measles and pertussis cases in recent years; California, for example, had over 4,000 confirmed, probable or suspected cases of pertussis as of mid-September, the most reported since 1955.

“I am concerned by parents’ refusal of immunizations because of the unintended harm they expose their own children to but also to weakening of the social contract that protects all of us collectively,” said Foege.

Part of the problem is that some parents have been curbing vaccinations for their children or eschewing them altogether. Doubts about the safety of vaccines sprouted in the United Kingdom and United States in 1998 with the publication of an article in The Lancet by Dr. Andrew Wakefield on a possible link between children with developmental problems like autism and the Measles-Mumps-Rubella vaccine. The article ignited an intense debate among parents with autistic children around the question of whether vaccines were responsible for their children’s condition, and many organizations formed to denounce compulsory vaccines. Since the article’s publication – and even after The Lancet retracted it in February 2010 – the anti-vaccine movement has become more vocal and prolific in its generation of Internet-based materials refuting the safety of vaccines. According to a 2004 study published in the journal Pedriatrics, each year 2.1 million American children aged 19 to 35 months are under-vaccinated or receive no vaccinations at all. Not all of these cases are motivated by vaccine safety suspicions, but several health departments around the U.S. report that parents are choosing “philosophical exemptions’’ from normal vaccination requirements. To the scientists and other public health officials who have developed revolutionary vaccines and are still rolling them out around the world to children who lack access to them, these developments are disturbing. Dr. William Foege is a senior fellow with the Bill & Melinda Gates Foundation and an epidemiologist who worked in

Budd of UNICEF says that public health community has struggled to combat the misinformation of the anti-vaccine movement. “We are big institutions, and the anti-vaccine movement is very nimble and passionate,” said Budd “They don’t subscribe to same rigid standards of science, while we have to make sure everything we say is accurate.” But the United States is not the only country where antivaccine advocates have managed to convince parents not to vaccinate their children. In 2008 in Ukraine, UNICEF and WHO decided to launch a campaign to vaccinate 9 million people against measles and rubella between the ages of 16 and 29. But the government decided to move the campaign forward by two weeks, which did not allow health workers enough time to educate the public on the safety and importance of the vaccine. In the interim vocal vaccine critics cast doubt on the campaign. One Ukrainian politician even went so far as to call vaccinations the “medical genocide of Ukrainians.” The campaign was initially postponed but in the face of the firestorm was eventually cancelled within a year. “The consequence is that that cohort of young people remain incredibly vulnerable to measles and rubella,” said Budd. David Wood, a coordinator in the department of immunization, vaccines and biologicals at the World Health Organization, saw a similar backlash to the Human Papilloma Virus in vaccine in India. A pilot project this year was stopped due to local groups’ critiques of the safety of the vaccine. “In a globalized environment, there are advocacy groups in different parts of world who are picking up on the anti-vaccine message through the Internet to help them further their cause,” said Wood. “This is a big issue that we need address, and we have to continue to try to get information about the safety of vaccines into the pubic domain.” GH —

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By john donnelly

In Ancient Culture, New Battle Starts Against TB KATHMANDU, Nepal – The history of fighting tuberculosis has its share of disasters – piecemeal control efforts, resistant strains of TB passed stealthily from cell to cell in prisons, and national programs suddenly running out of money due to political revolutions or even just a change of administrations. And then there was a moment, in the midst of a luncheon at the four-star Bluestar Hotel in Kathmandu on Feb. 23, 1996, when Nepal’s early efforts to seriously battle TB were called out as going nowhere. In the fall of 1995, Nepal had become one of the first countries in Asia to sign onto the World Health Organization’s ambitious efforts to install a DOTS strategy, which called for following a series of unbreakable rules, including that health workers should directly observe a patient swallow TB drugs every day for months. But in that luncheon, a group of international experts presented a report that basically gave Nepal an F. “DOTS is not being implemented properly, and very few patients are being supervised at the treatment centres,” the report read. “No action is taken for patients who are late for treatment. The drug supply system is not functioning properly, and several treatment centres have suffered stock outs of drugs. … The laboratory network is not functioning, because posts for microscopists have not been established.” What would Nepal do? Pretend it didn’t hear, or attack the problem?

Tuberculosis Centre, looking back at that moment 14 years later. “I agreed with them – the pilot programs we had started were really not that good. I said, `OK, give us six months. Let’s see what we can do.”’ Country Director Hits the Road Bam, his chief assistant, Dr. Ian Smith, and several others started to travel frequently to the countryside, insisting that health workers and patients follow the DOTS protocol. “Those who refused,” Bam said, “I removed them.” The Ministry of Health’s strategy – it was backed by a group of about a half-dozen NGO partners who were directing the programs, donors such as the Japanese government, and WHO’s technical advisers – began to produce results. It took many players, often cajoled by the near-maniacal country TB director, but Nepal built its program step by step.

It attacked. “Those experts who came in were right,” said Dr. Dirgh Singh Bam, then the director of the National

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“We put in place a much more robust program of supervision, recording and treatment,” said Smith, who is now an adviser to WHO Director-General Margaret

John Donnelly is a free-lance writer specializing on global health issues. His trip to Nepal was supported in part by the World Health Organization.


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Jeevraj Adhikari, a TB educator in the Kathmandu slum, talks to people about the disease. Photo by Kiran Panday.

Chan. “Dr. Bam was constantly on the road, always out supervising people, meeting with private doctors, trying to motivate them. He was a stickler for information – he made sure people submitted the right information. From then on, there was a different picture. For the next four or five years, we had a period of rapid expansion to reach 100 percent of the country.” TB cure rates, which had hovered around 45 percent before DOTS began, soared to more than 80 percent, and would eventually reach 90 percent in 2009. The country achieved nationwide DOTS coverage in 2001, started to treat multiple-drug resistant TB in 2005, and wrote a new National Strategic Plan in 2010 that outlined strategies and goals for the next five years. The Global Fund to Fight AIDS, TB, and Malaria awarded Nepal a $56 million, five-year grant to help it meet those goals. Nepal, a rarely told story in the expansion of global TB efforts, now is being tested again. The small mountainous country of 27 million people, wedged between India and China, is intensifying its battle against TB strains resistant to drugs, which threaten to torpedo past efforts.

Dr. Kashi Kant Jha, a TB medical specialist who worked with Bam in those early days, now leads the country program. He is confident Nepal’s TB program can meet new difficulties. “If your home is strong and you are earnest, you will get support and get good results,” he said. Long List of New Challenges But Jha said the job wouldn’t be easy. Among the new challenges: health workers need more training; the lack of laboratory facilities in many parts of the country; the high number of MDR- and XDR-TB (extensively drug resistant) cases identified in the last five years; concerns of co-infection with the country’s estimated 60,000 HIV-positive patients; and the lack of a TB hospital in the entire country, which means that even people with infectious drug-resistant TB remained in the community, not in an isolated setting. The National Strategic Plan calls for 125 new microscopy centers in under-served areas; building Nepal’s first chest hospital that would have 150 beds;

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MDR-TB cases now comprise about 3 percent of all new TB cases – which is not high compared to rates approaching a quarter of all cases in some Central Asia cities, but not insignificant either. The country has identified 826 cases in the last five years. Dr. Dirgh Singh Bam, director of the National Tuberculosis Centre. Photo by Kiran Panday.

improve the control program in urban areas; immediately identify and rent 10 hostels for MDR- and XDR-TB patients; and greatly expand an effort to intensify case finding in crowded settings, such as slums, prisons, refugee camps, and factories. As with any TB control effort, all strategies are necessary in order to be successful. But experts here have put particular focus on the last two points – the treatment of drug-resistant TB patients and becoming more aggressive in finding cases. In Pokhara, a city in Nepal’s center that draws tourists for the magnificent views of the snow-peaked Annapurna mountain range, Dr. Prakash Mishra, director of the Regional Tuberculosis Centre who oversees treatment for dozens of TB patients, believes the two strategies go hand in hand. “Where did we get MDR-TB from?” he said. “Either we didn’t do the right thing in the past, or we compromised the treatment somewhere. If we do not find all of these cases, the exposure to people in the community continues.” MDR-TB cases now comprise about 3 percent of all new TB cases – which is not high compared to rates approaching a quarter of all cases in some Central Asia cities, but not insignificant either. The country has identified 826 cases in the last five years.

“We need to now move from a passive system of case finding to an active one,” Mishra said. “We need to let people know that if they cough for a couple of weeks, they should immediately come in and get tested for TB.” ‘I was a TB patient’ Some outreach is under way. One afternoon this fall in a slum along the Manahara River in Kathmandu, health educator Jeevraj Adhikari gathered about 40 women and children in a small room to talk to them about TB. Rain poured outside – so loud on the tin roof that Adhikari couldn’t be heard for more than 15 minutes. He patiently waited it out. He asked what they knew about TB. Answers came from all corners. Still, he warned them: “TB is everywhere, inside your home, outside your home.” He asked if any of them knew someone who had TB. Several hands rose. He called on Devi Kunwar. She said she was a TB patient. All eyes turned to her. “How are you doing?” Adhikari asked. She said she was much better following six months of treatment. “Now, I am cured,” she said. “That is great news,” Adhikari said. GH —

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C

On the BLOG

By John Donnelly —

C Who is in the Driver’s Seat? As world leaders gathered at the United Nations in New York for the Summit on the Millennium Development Goals, one pressing issue was who calls the shots in trying to reach those goals in developing countries.

Read the full blog on www.globalhealthmagazine.com

By alex palacios

By Neda Dowlatshahi

C Doing something about the ‘D’ Word: Diarrhea

C Tuberculosis: The Middle

No one likes to talk about diarrhea – the “D” word as some might euphemistically refer to it. For most of us, it’s an annoying and sickening result of a bug or some bad food that temporarily knocks us out for a few days. Then, as quick as it came, it’s gone and we get on with our lives.

…While we have made strides in treatment, we need more resources to accelerate the research and development of more effective TB drugs. Better drugs promote better adherence and will avert cases of Multiple Drug-Resistant (MDR) TB. According to WHO, in 2007 there were an estimated 500,000 cases of MDR-TB globally. This is harder and more costly to treat: while drug sensitive TB takes six to 12 months to treat, MDRTB takes up to two years. Even more unnerving is the spread of Extensively Drug-Resistant (XDR) TB, which is yet more difficult to treat. By failing to prevent the progression from latent to active TB, not only are we risking more lives but we are losing money.

That isn’t so for everyone. The fact is diarrhea is the second biggest killer of young children in the world – in absolute terms. Nearly 1,400 children die from rotavirus infections every day. That’s more than 500,000 child deaths each year. The vast majority of these deaths are in Africa and Asia. Read the full blog on www.globalhealthmagazine. com

ISSUE 08 fall 2010

In a series of daily question-and-answer pieces with journalist John Donnelly, eight policy and thought leaders in global health discussed the next steps in giving countries what they crave: ownership of their health programs.

Child in the ID family?

Read the full blog on www.globalhealthmagazine. com www.globalhealthmagazine.com


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Issue #8 - Vaccine Redux - Global Health Magazine