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Your companion on the red-eye from Dulles airport to Geneva is a two inch-thick Yellow Book—478 pages of previous meeting notes, disease eradication plans, reviews of evidence, references, and more related to the meeting of WHO’s Strategic Advisory Group of Experts (SAGE)—including at least seven global policy questions you will need to make a decision about. All this in 30 hours of meetings over three days.
Feeling fuzzy getting off your flight? Grab a double expresso as you are head over to WHO HQ on Avenue Appia. Outcomes of these meetings will inform WHO’s Director-General and lead to new recommendations from WHO for all countries on the best ways to ensure vaccines improve health and save lives for as many people as possible.
Welcome to SAGE!
IVAC's Delegation at SAGE 2017
From October 17-19, three faculty members from the International Vaccine Access Center (IVAC), of the Johns Hopkins Bloomberg School of Public Health (JHSPH), provided technical expertise and leadership at the annual SAGE meeting, an advisory body formed in 1999 to provide guidance on immunizations to the WHO.
IVAC’s delegation included Director of Epidemiology Bill Moss, Director of Science Maria Deloria Knoll, and IVAC Executive Director Kate O’Brien. The meeting, held in the August Room where WHO’s 34-member Executive Board meets, was attended by about 200 people and included presentations from nine Working Groups. SAGE Working Groups delve in to key immunization-related questions of interest to policymakers around the world.
The Executive Board’s elevated screen helps viewers sitting on multiple tiers follow presentations. Maria’s purple sweater helped people locate her in the immense room.
How did IVAC members at SAGE support policy-making for WHO?
Measles and Rubella
Dr. Moss, who also serves as a Professor in the Departments of Epidemiology, International Health, and Molecular Microbiology and Immunology (MMI) at JHSPH, has been a member of SAGE’s Measles and Rubella Working Group since 2011. Dr. Moss presented evidence supporting a recommendation that people living with HIV do not need to be re-vaccinated against measles if they were not infected with HIV at the time of their measles vaccination in young childhood. This policy has implications on the estimated 34.5 million adults living with HIV infection and on the achievement of measles elimination goals.
Rabies
Dr. O’Brien, who is a Professor in both Departments of International Health and Epidemiology at JHSPH, has served as a SAGE member since 2012 and has participated in multiple Working Groups over the past four years. This year Dr. O’Brien chaired the SAGE Working Group on rabies vaccines and rabies immunoglobulins, which are antibodies that recognize and bind to the rabies virus to destroy it. Sidebar… Dr. O’Brien’s analysis of rabies vaccine policy became personally relevant during a holiday in Mexico: a bat flew into her son Jack’s face and sent them on a complicated journey to locate rabies immune globulin and vaccine (fortunately, they found them both and Jack remains healthy!).
Pneumococcal conjugate vaccine
Dr. O’Brien also co-led the Pneumococcal Conjugate Vaccines Working Group (more about this below). During this meeting, Dr. Knoll, who serves as an Associate Scientist in the JHSPH Department of International Health, presented on a review IVAC authored of over 200 studies assessing the effect of both of WHO’s recommended dosing schedules on vaccine-type disease, or the strains of pneumococcus included in the 10- and 13-valent conjugate vaccines.
Recommendations to WHO Director-General
Dr. O’Brien and the other 14 members of SAGE—each representing a different institution and country—considered the evidence and made formal recommendations to WHO. For example, based on the evidence presented, SAGE concluded that both WHO-recommended PCV schedules have a substantial impact on reducing vaccine-type disease. All evidence presented during the meeting is available in the Yellow Book.
How SAGE gathered evidence to optimize the impact of pneumococcal conjugate vaccines
Starting in January, the pneumococcal conjugate vaccines (PCV) working group, led by SAGE members Dr. O’Brien and Dr. Andrew Pollard of the University of Oxford, reviewed extensive evidence on PCV impact. One of the main sources of evidence was the PCV Review of Impact Evidence (PRIME) Systematic Review, an effort co-led by IVAC with partners including the US CDC, WHO, the University College of London, and Agence de Médecine Préventive. Over the past two years, the PRIME group reviewed studies to assess differences in disease, immunogenicity, and carriage impact by PCV schedule and product, as well as evidence of immunogenicity of catch up immunization. This systematic review served as an update to a previous review conducted by IVAC, which compared impact of different schedules in the context of PCV7 use and served as an important evidence base for previous SAGE WHO PCV recommendations.
Among the PRIME review’s findings on PCV schedules:
Immunogenicity: A 3-dose primary series induces a greater immune response compared to a 2-dose primary series. However, in a 3-dose schedule, the third dose is more immunogenic when given as a booster (2+1) for most serotypes. It is important to note that greater immunogenicity may not necessarily mean better protection from disease.
Nasopharyngeal Carriage: Both schedules showed an impact on overall vaccine serotype carriage (product specific vaccine-type).
Invasive Pneumococcal Disease: Both schedules showed impact on overall vaccine-type invasive disease. For serotype 1, the 2+1 schedule showed clear evidence of impact from a substantial body of evidence; for the 3+0 schedule although some impact was seen the data were more limited.
WHO’s recommendations related to dosing schedule, catch up vaccination, and product usage will be published in a PCV Position Paper in 2018. If there are opportunities to improve impact, countries using pneumococcal vaccines may consider update their schedule and product choices.
In the meantime, we’re clearing off our bookshelf space for the next onslaught of documents… SAGE will re-convene April 17-19, 2018 – see you there!
For more information, see the resources below:
By Adam L. Cohen  | The operator of a clean cookstove cooperative in Mulanje, Malawi. Photo by Matt Feldman / IVAC. |
When I moved to South Africa a year and a half ago to work for the U.S. Centers for Disease Control and Prevention on surveillance for pneumonia and influenza, I didn’t realize how much pneumonia affects communities here. Most of the children in the hospital wards where I work are having trouble breathing, hospitalized with pneumonia. Pneumonia is the leading cause of death among children under five in South Africa and worldwide. Mothers want their children with pneumonia to get better, and public health policymakers want to do what they can to make their country as healthy as possible. But how can we help countries do this? There are multiple, proven interventions to prevent and treat pneumonia, but it can be difficult to get these interventions to the people who need them most. At the CDC, we set out to examine the opportunities presented by the delivery of preventive measures, such as childhood immunization, to explore practical approaches for integrating other interventions to treat and control pneumonia in children. Our complete findings are published in the Bulletin of the World Health Organization. With so many existing methods of reducing the burden of childhood pneumonia, there are exciting opportunities to integrate multiple approaches to improving child health. But there are also many challenges. Most children have access to basic immunizations—could we use this to help protect the children of the world against pneumonia? Globally, many routine vaccination programs are strong, which means that huge strides could be made in pneumonia prevention and treatment by integrating interventions like pneumococcal and Hib vaccinations, zinc distribution, and caregiver education with routine immunizations. Neither vaccination nor case management alone is enough to eliminate child pneumonia deaths, owing in part to the large number of bacteria and viruses that cause pneumonia. Other important interventions include caregiver education, referral to health care facilities during routine immunization visits, zinc supplements, HIV testing, and the promotion of health behaviors such as breastfeeding, proper nutrition, hand-washing with soap, and the reduction of indoor air pollution. However, not all interventions are easily distributed, like cleaner burning but bulky cookstoves, and overburdening community heath workers could cause frail health systems to falter or break. There are few of us in the field of public health working to evaluate the integration of multiple interventions. Further, integration of service delivery would require coordination and cooperation across the entire range of donor organizations, NGOs, and governmental ministries. To address these challenges, we must conduct small-scale studies that elucidate best practices and evaluate the impact of integration before scaling up to large national programs. This will help us empty the hospital wards in South Africa and worldwide. Dr. Adam L. Cohen is the Influenza Program Director at Centers for Disease Control and Prevention in Pretoria, South Africa.
By Dr. Hope Johnson  | Children in Phalombe, Malawi. Photo by Matt Feldman / IVAC. |
Understanding the major causes of child mortality is essential to establish health priorities and improve the health of children globally. Over the past decade, WHO and UNICEF’s Child Health Epidemiology Reference Group (CHERG) has strived to meet this need by publishing national, regional, and global estimates of the causes of child mortality. This information has been crucial to the development of child health interventions and long-term child survival strategies. Since CHERG’s first report, estimation methods and the quality and quantity of child mortality data reported by country vital registration systems have drastically improved. This week, a new CHERG report presents for the first time annual disease-specific time trends for causes of child mortality over the past decade. The new data, published in The Lancet, show that child mortality fell by 2 million deaths, from 9.6 million to 7.6 million between 2000 and 2010. According to CHERG, declines in mortality over this period are likely due to improving socioeconomic factors and the successful implementation of child survival interventions in developing countries, particularly those targeting nutrition. But what continues to claim the lives 7.6 million children around the world every year? Infectious diseases are the main culprits–responsible for 64% of all deaths in children under five. And notorious killers, pneumonia and diarrhea, remain important causes and together were responsible for more than 2 million deaths in 2010. Sadly, a striking 40% succumb within the first month of life most often due to complications related to preterm birth. Despite the historical drop in mortality seen between 2000 and 2010, the current rate of mortality reduction is insufficient to achieve the fourth UN Millennium Development Goal (MDG4): reduce the child mortality rate by two-thirds, before 2015. Rapid introduction and scale-up of existing child survival strategies focused on infectious and neonatal causes, particularly in high burden areas of Africa and southeast Asia, is critical for achievement of MDG4. There’s reason to hope, however, with the continued rollout of life saving vaccines for pneumococcal disease and rotavirus by GAVI Alliance and its partners at an unprecedented pace, and at a price low-income countries can afford. But vaccines alone won’t stop pneumonia and diarrhea–other proven interventions such as improved nutrition, appropriate antibiotic treatment, and breastfeeding are also essential elements in this fight. This newest CHERG report provides a valuable picture of the current state of child mortality worldwide. The data will allow policy makers to prioritize introduction and scale-up of effective interventions to reduce child mortality. CHERG’s job, however, is not over: monitoring the evolving causes of child deaths will continue to be a crucial part of global efforts to erase the 7.6 million child deaths that still occur each year. Dr. Hope Johnson is an Epidemiologist at IVAC.
Keywords:
cherg, unicef, who
By David R. Curry  | Villagers line up to be vaccinated against Smallpox at an outdoor clinic, Côte d'Ivoire, 1970s. From the WHO Archives. |
In February, 2012, I participated in the WHO Extraordinary SAGE meeting in Geneva, called to review the Global Vaccine Action Plan (GVAP) being developed by the Decade of Vaccines Collaboration (DoVC). On the flight back to the U.S., I was reflecting on the continuing challenge of identifying and scoping "game changers" in the GVAP to help realize the DoV’s ambitious vision: The vision for the DoV is a world in which all individuals and communities enjoy lives free from vaccine-preventable diseases. Its mission is to extend, by 2020 and beyond, the full benefits of immunization to all people, regardless of where they are born, who they are, or where they live. We need “game changers” because of the scale of the challenge, to be sure. But I was also reflecting on the history of global immunization strategies and that we have faced the same core challenges for generations. Having arrived early for the SAGE meeting, I spent a day in the WHO Archives pursuing the broad question of when the WHO first considered anything like a global immunization strategy, and at least one other reference point for perspective. Two original documents caught my attention. The first was a report from what appears to be the first expert consultation on this theme: the first session of the Expert Committee on Maternal and Child Health, Geneva, January 1949. The session title was Immunization Against Principal Communicable Diseases of Childhood - Plan for an International Program (WHO/MCH/5). The meeting report surveys the then-current knowledge on immunization – informed by WWII – and includes a key recommendation for convening an "international expert conference on immunization procedures as soon as possible. This conference should bring together epidemiologists, paediatricians, heads of child-health services, and experts responsible for the preparation of vaccines in state and other official laboratories and institutes. The conference should discuss the use of the newer techniques for producing the more effective vaccines (e.g. pertussis vaccine) and plans for their widespread application in immunization programs..." The proposed conference was later convened as a result of a resolution adopted at the Second World Health Assembly. But in the meeting report, the assessment of immunization and its challenges in 1949 (as thinking about an international program was just underway) was alarmingly "current": "Where immunization programmes have failed, the main reasons for such failure have been 1) a false sense of security when the incidence of these diseases happened to be low, although the population has not yet been adequately immunized; 2) Lack of adequate health education of the public; 3) Insufficient information among the medical professions as regards new immunization procedures; 4) Reluctance to use auxiliary personnel for mass immunization; 6) Lack of appropriate immunization agents [vaccines]; and 7) Lack of appropriate legislation and funds for immunization programmes." A companion recommendation was the release of a circular letter by WHO to all WHA members surveying "active immunization" programmes, including an inventory of which diseases and what age groups might be involved in either "advocated" or "compulsory" immunization, whether the country's programme was "assisted by an organized public information campaign," and whether the public is "generally eager for immunization, passive, or reluctant..." The second reference point comes from a 1974 Consultation on the WHO Expanded Programme on Immunization held at Geneva (VIR/74.15), obviously very early in the EPI era. The report notes: "...most diseases against which vaccines are available are still uncontrolled in virtually all developing countries. The principal problems are a) lack of trained personnel (and often the idea that only physicians or highly trained nurses should administer vaccines); b) use of complicated immunization schedules appropriate to developed countries but which do not recognize the local epidemiological and administrative realities of the developing world; c) the high cost of equipment and difficulties of maintenance of e.g. transport, refrigeration and jet injectors; d) the cost of many of the vaccines, and e) restrictions on the production of some vaccines because vaccine strains or methods have been patented." Later in the report, two additional factors around "shortcomings in immunization activities" caught my attention: that “cost benefit and cost effectiveness analyses are either not appreciated by health planners and administrators, or have not been undertaken...” and that “illiteracy and poorly developed public information media result in the lack of public understanding of the need for immunization..." Finally, this 20-page analysis concludes with a series of recommendations for the year ahead, asserting: "Immunization must be recognized as an essential and permanent programme for the control of communicable diseases and must be a primordial responsibility of the country concerned. The role of the WHO is to stimulate countries to set up immunization programmes and to assist them in doing so..." These two reference points – from over 60 years ago and almost 40 years ago – are, in a sense, humbling. But they also are a fresh call-to-action. Now is the time to focus our energies and stretch our collective imagination to complete the GVAP with critical game changers, and boldly implement it in the decade-plus ahead. Now is the time for us all to commit our generation to realize the DoV vision. David R. Curry is Executive Director of the Center for Vaccine Ethics and Policy, a joint program of the Penn Center for Bioethics, the Wistar Institute Vaccine Center, the Vaccine Education Center of the Children’s Hospital of Philadelphia.
By Lois Privor-Dumm This is a moment we have been cautiously optimistic about. Was today going to finally be the day? Friday the 13th is not an unlucky day this year – it is the day that India has gone one year without a single new case of poliovirus! Every time I look out the window as I’m driving around India, I witness the all-too-common sight of someone suffering the debilitating effects of the disease. That image is a reminder about how horrible this disease is and that polio’s impact is not just on the individual, but a whole nation. | A man who contracted polio walks on crutches in the village of Kosi, 113 miles from Patna, India. Photo by Altaf Qadri / AP. |
The efforts to stop this disease in India have been dramatic and it has been a roller coaster with significant ups and downs. After 741 new cases in 2009, there were only 42 in 2010 – the country was almost there. And then in 2011, there was just a single new case in 18-month old named Rukhsar from West Bengal. It was a heartbreaking occurrence, but efforts persevered. I am struck by the level of effort committed to this goal: government, civil society and international organizations including WHO, the National Polio Surveillance Project (NPSP) based in Delhi, UNICEF, CDC and Rotary are all laser-focused on making sure that kids even in the hardest to reach places were immunized. The Bill & Melinda Gates Foundation is also instrumental in these efforts. It was no easy feat, as we’ve seen in other polio-endemic countries including Nigeria, Pakistan and Afghanistan. India was considered one of the toughest countries to tackle, making this effort all the more impressive. | | History of Polio Case Numbers in India |
The infrastructure requires an enormous amount of coordination with stakeholders who were not part of the government or its partners. Civil society, including community and religious leaders, NGOs and others all needed to be engaged. The outcome of polio eradication efforts is not just the achievement of interrupting transmission, but the commitment that is gained by those involved in disease prevention efforts. I don’t work directly on polio, but I recognize the benefits of building an understanding of the value of vaccines, creating a system that can handle the supply chain, monitoring and evaluation and constant communication. On a recent GAVI consultation visit to India, I was very happy to hear that the discussion was about how we can leverage the infrastructure created by the polio efforts. It is important that we learn the lessons from polio and leverage the best practices, not only in India, but in other large countries like Nigeria, where stopping Polio is also within reach. One of the biggest lessons is that there are a lot of stakeholders that contribute to a successful vaccine program – it takes a village. The government plays a big role, but it is the community, that will directly determine success. Building an understanding of what can be achieved, and helping to implement the strategies that can lead to that success, are ways that the IVAC team is privileged make contributions. We are all working towards the goal of improved health for people in countries like India and Nigeria. Today’s milestone inspires others to act in ways that can help not only polio eradication efforts, but disease prevention and control efforts more broadly. One year without a new case of polio in India is an important milestone, but as we continue to make great strides around the world, our best years are ahead of us. Lois Privor-Dumm is the Director of Alliances and Information at IVAC.
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