The Integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD) was launched last month. Now this week we’ve learned that a new rotavirus vaccine from India, Bharat Biotech‘s ROTAVAC, looks promising, and The Lancet featured results from the Global Enteric Multi-Center Study or GEMS, which offers a comprehensive look at the causes of diarrhea in children, such as rotavirus. In light of this recent news and its impact on efforts to prevent and treat diarrheal disease, especially rotavirus, we sat down with Mathu Santosham, MD, MPH. Dr. Santosham co-chairs the ROTA Council and also chaired the Data Safety and Monitoring Board for the ROTAVAC trial established to protect the participating infants’ rights and needs during the trial.
Why is all of this recent news important for children?
Mathu Santosham, MD, MPH
We know that pneumonia and diarrhea are the leading killers of children under 5 worldwide, and we know that we need an integrated approach that uses all proven tools to tackle these two illnesses and prevent unnecessary suffering and death. GAPPD is important because it provides a framework, designed to inform global and national programs and policies, for integrating efforts against these two child killers. It sets ambitious but achievable goals including reducing under-five pneumonia and diarrhea deaths to 3 per 1,000 live births and 1 per 1,000 live births, respectively. A big part of the strategy for tackling both illnesses is vaccination.
For diarrhea, we know rotavirus – a pathogen for which there is a vaccine – is the leading cause of severe diarrhea among infants and children. In fact, the active surveillance results announced from the seven sites in GEMS reaffirmed this understanding, and offered important insights that will help better target interventions to the pathogens like rotavirus that are causing the most diarrhea. We also know that rotavirus contributes significantly to child mortality. According to the most recent estimates, more than 450,000 children died from rotavirus diarrhea in 2008. Rotavirus vaccine is critical to protecting children from rotavirus and preventing illness and death.
There are currently two licensed rotavirus vaccines, and they are saving lives and improving health today in the countries where they are in use. Having an additional vaccine from an Indian manufacturer will expand the market, which will offer more options to protect children in India and around the world. If licensed, Bharat has committed to offering the initial frozen formulation at $1 per dose, which will increase market competition for countries and organizations procuring vaccine. Also, it is especially encouraging to see India making so much progress toward a vaccine because nearly one-quarter of rotavirus deaths occur in India.
Why is rotavirus such a large concern?
Rotavirus is highly contagious and can last for long periods of times on hands and surfaces. It is not adequately prevented by proper hygiene or improvements in water and sanitation, like other pathogens that cause diarrhea. So even children in developed countries are susceptible to contracting rotavirus. In fact, nearly every child will be infected at least once by the age of 5. Once infected, a child often experiences symptoms that include fever, vomiting, and diarrhea. In developed countries where access to care is more reliable, children are unlikely to die from this infection, but in developing countries, children are less likely to have quick access to oral rehydration, making them at risk to suffer severe dehydration. This can lead to hospitalization and even death. In addition, children who suffer from malnutrition are more vulnerable to diarrhea, and diarrhea in turn worsens their malnutrition, resulting in a vicious cycle. For these reasons, rotavirus is a concern worldwide, but especially in developing countries.
What can we do about rotavirus?
Rotavirus cannot be treated with antibiotics or other drugs. However, its symptoms can be alleviated by prompt use of oral rehydration therapy (ORT), which includes home available fluids, oral rehydration salts (ORS), and, in cases of severe dehydration, IV fluids. ORT can effectively treat most rotavirus infections, but when the treatment is received too late, rotavirus can be deadly. In India, only about 4 in 10 children receive ORT when they have diarrhea. Vaccination, on the other hand, can actually prevent rotavirus diarrhea from happening in the first place. The two currently licensed vaccines, Rotarix and RotaTeq, have been demonstrated to be safe and effective and have been introduced in more than 45 countries. When combined with ORT, zinc supplementation, breastfeeding, and improvements in nutrition, hygiene, and water quality, vaccines contribute to the comprehensive approach required to effectively prevent severe illness and deaths caused by rotavirus diarrhea.
What is ROTA Council doing about this problem?
Dr. Santosham with other members of the ROTA Council at the International Rotavirus Symposium in Bangkok, September 2012.
The ROTA Council, which I co-chair with Dr. Ciro de Quadros of Sabin Vaccine Institute, is a dedicated team of technical experts with the mission of saving children’s lives by accelerating the introduction of rotavirus vaccines. We work at the global and country level to ensure that policy makers have the latest evidence-based information to inform their decisions about introducing and scaling up rotavirus vaccines as part of broader diarrhea control efforts. At the same time, many of our Council members are on the frontlines of research, conducting the studies needed to demonstrate vaccine efficacy, safety, and impact. We are pleased to see that more than 45 countries have introduced rotavirus vaccines, but many more are still leaving their children unprotected, particularly in Asia, where countries have been slow to introduce the vaccine.
Why should India and other low- and middle-income countries introduce rotavirus vaccine?
Rotavirus diarrhea is a ubiquitous problem that can have some very serious consequences. In India, and other countries where access to care can be quite unequal, prevention becomes even more critical. If left untreated, rotavirus infection can lead to unnecessary illness, hospitalization, and even death, which is not only concerning from a health standpoint, but also takes a very serious toll from a social and economic standpoint. Hospitalization for one child with rotavirus costs nearly the entire amount of an average Indian household’s spending in a month. Diarrhea related healthcare needs are also costly for the country and stretch its already burdened state healthcare system. Beyond direct costs, vaccination could avoid productivity losses and help children grow into healthy, educated, productive adults.
The vaccine has the potential to make a big difference in the lives of families around the developing world. In India alone, we could prevent tens of thousands of deaths, not to mention nearly 300,000 hospitalizations and more than 300,000 doctor visits, which amounts to savings of over US$20 million in medical costs.
Based on your experiences, what is your hope for India and the rotavirus vaccination?
As a medical student in India in the 60s I saw children dying of diarrhea every day. Over the years, we were fortunate enough to develop powerful treatments like ORT, which helped to reduce the number of diarrheal deaths per year from 5 million in 1980 to less than a million now. However, more than 700,000 children continue to die from diarrhea annually because they don’t get the necessary treatment on time. Rotavirus is the leading cause of these diarrheal deaths, and it is a tragedy to see a child die from rotavirus when we have such a powerful weapon to combat this disease. It is my sincere hope that every child in India will soon have access to this life-saving vaccine.
Mathuram Santosham, MD, MPH, is Co-Chair of the ROTA Council and Professor of Pediatrics and International Health at Johns Hopkins University. He also serves as Director of the Center for American Indian Health, Director of the International Center for Maternal and Neonatal Health, and a Senior Advisor at IVAC.
By Dr. Dagna Constenla
Dengue is a painful and debilitating mosquito-borne virus affecting millions of people worldwide every year. Prior to 1970, the disease was endemic in just nine countries. Today it is endemic in more than 100 countries, and WHO estimates that 2.5 billion people are at risk of infection each year.
Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures
As the global burden of dengue grows, so too does the realization of just how little we know about the health and economic toll of the disease. At the same time, the prospect of a licensed vaccine is growing near, and dengue-endemic countries will have to begin to consider whether or not to introduce the vaccine. An important question they must ask when weighing the costs against the benefits of vaccine introduction is, “how much does dengue cost?”
In response to the growing need to answer that question and lay the groundwork for vaccine decision making by endemic countries, the International Vaccine Access Center, as part of its work on the Dengue Vaccine Initiative (DVI), convened an expert panel in March 2012 to discuss and develop a standardized methodology for estimating costs of dengue in the Americas. The resulting guidelines, Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures, published late last month, aim to ensure robust assessment of the economic burden of dengue infections and to make the results of future dengue cost studies more comparable among Latin American countries.
The guidelines highlight the many considerations that need to be taken into account when doing analysis to understand the overall economic burden borne by a community as a result of dengue, from understanding the health care system where the study is being conducted to determining the definition of a dengue outbreak. The expert panel concluded that, while there is no single theoretically correct approach to costing dengue, experts generally adhered to certain principles including:
The adoption of a societal (broad rather than individual) perspective;
The inclusion of all relevant costs and effects (direct medical and non-medical costs of treating a case of dengue, productivity loss of patient and caregiver, etc);
The use of an adequate sample size, and;
The optimal collection and valuation of unit cost data for use in multi-country settings (making sure that data collected from a variety of countries and settings is collected well and able to be compared).
Creation of these guidelines was just one piece of IVAC’s work on dengue. This spring we plan to convene leaders from Latin America to tackle another key challenge in dengue vaccine introduction – financing. We are also tasked, through the DVI, with linking epidemiologic and economic modeling to create a strategic demand forecast for dengue vaccines.
It is important to note that estimation of dengue costs is a new area in which there is little published literature and in which few of the guideline authors had practical experience. Dengue financing is also an area that experts are just now beginning to address. It is our hope that our work will spur further discussion and research that will help position countries to make well-informed decisions about vaccine introduction. We welcome your thoughts on the guidelines and other dengue costing and financing issues here, or via email to firstname.lastname@example.org.
Dagna Constenla, PhD, is the Director of Economics & Finance at IVAC.
By Dr. Kate O'Brien
Being a doctor doesn’t necessarily make being a mom to a sick baby any easier. Like every mother, I’ve spent my share of sleepless nights tending to my kids sick with a cold, or diarrhea, or an earache, but those episodes are just a distant blur for me. Not so the time my son had pneumonia.
It was his first Christmas and we were both really sick with a respiratory illness that I’m sure was the flu. I kept telling myself we would both feel better soon. But we didn’t. In fact, Jack got worse. By evening and into the night, with more rapid breathing and some tugging of his chest with each breath, there was no question we needed to get him medical care. These were signs that something was very wrong.
An x-ray confirmed that Jack had pneumonia. My heart sank. I was supposed to have gotten him vaccinated against the flu weeks earlier, but I put it off. As a pediatrician and vaccinologist, I knew that vaccine could have protected him from pneumonia. As a parent, I should have never have been “too busy” to get him vaccinated. Thankfully with proper treatment, Jack quickly recovered. I knew we were lucky but also knew there were hundreds of thousands of children each year who are not. Read the full blog at Million Moms Challenge.
By Kelly Healy
When I first traveled to India as part of my master of public health program,
Participants at Hib Symposium in Odisha, India in July.
I left feeling inspired to do something to help India’s children and families. Less than a year later, now at The Johns Hopkins University as a new research associate for IVAC, I had the opportunity to return to India as part of a team working to accelerate vaccine introduction to reduce child deaths from pneumonia and diarrhea. While there, I was able to see in real terms the impact efforts by IVAC and its partners have had.
I traveled to Bhubaneswar, a “small” city, if only by Indian standards, with a population of less than 900,000, that is the capital of Odisha. There, on July 9th, technical experts, government officials and other key stakeholders gathered for a one-day Hib Symposium, hosted by the policy unit of the National Institute of Immunology along with the Asian Institute of Public Health and designed to share data and experiences related to Hib disease and available interventions, including vaccines. While lesser known than pneumococcus, Hib or Haemophilus influenzae type b is a leading cause of pneumonia, the top killer of children in India and worldwide. It is also the leading cause of meningitis, which can result in death or serious neurological sequelae.
In 2010, nearly 400,000 deaths of Indian children under five were caused by pneumonia. While Hib vaccines have been proven to reduce cases of pneumonia and have been available for more than a decade, uptake has been slow in India especially in the public sector. However, that seems to be changing now, as more Indian states have expressed interest in adding Hib vaccines to their immunization programs, which would make them available at government clinics that reach the lower income populations who are at greater risk of dying from diseases like pneumonia and meningitis.
Media coverage of Hib Symposium.
Two states, Tamil Nadu and Kerala, have already introduced Hib vaccines (in the form of the pentavalent vaccine, which also protects against diphtheria, pertussis, tetanus and hepatitis B), and six more are slated to do so by the end of 2012. At the symposium, Ministry of Health and Family Welfare officials shared that eight more states have expressed interest. Judging from press coverage of the event, other states may not be far behind. All of this is great news for champions who have been advocating for Hib vaccines for several years, and a sign that Hib vaccine support may have reached a tipping point in India. The current momentum is driven by Indian technical experts and advocates like those who gathered in Bhubaneswar and other stakeholders at the center who recognize the important contribution of the vaccine. Our team at IVAC and its partner Global Health Strategies, Emerging Economies, are proud to offer technical assistance and opportunities to provide insight from other countries’ experiences and enable forums like the Hib Symposium.
However, many pieces of the puzzle still need to fall into place to gain widespread coverage of Hib vaccines among Indian children. In that light, state government representatives from Tamil Nadu and Kerala gave their peers at the symposium helpful insights from their rollouts, in particular highlighting the importance of pre-launch activities including evaluating the cold chain, training staff, establishing monitoring systems for adverse events and sensitizing policymakers and the media. They noted it was especially important to prepare stakeholders for the potential of adverse events following immunizations (AEFIs). One child died in Kerala after receiving the pentavalent vaccine, but thanks to sensitization efforts for government officials and a swift and clear response to the media, the state was able to quickly confirm the death was not caused by the vaccine and avoid derailment of the vaccine rollout. With careful preparation, Kerala and Tamil Nadu were able to carry out smooth launches and vaccinate more than 600,000 children in the two states combined through June.
I am excited to join the team here at IVAC at a time of such promise for India and look forward to seeing more progress in the coming months and years.
Kelly Healy, MPH, is a Research Associate at IVAC.
By Dr. Chizoba Wonodi
Last month, I had the privilege of sharing the findings from a newly released International Vaccine Access Center study – the Landscape Analysis of Routine Immunization in Nigeria (LARI) – with a group of experts at the Center for Global Development (CGD) in Washington, DC. The talk, which focused on overcoming barriers to routine immunization (RI) in Nigeria, was hosted by IVAC’s Executive Director, Dr. Orin Levine.
I didn’t quite expect the level of interest the talk generated. Kudos to CGD’s Amanda Glassman for convening an impressive “sold out crowd” of donors and implementers including veterans and new entrants in the immunization field. The audience gave my colleagues and I plenty to chew on after we presented our findings. Below are some of the key points from the discussion.
Nigeria is an important country in the immunization world. It’s a large country with high child mortality and low immunization coverage rates. Of the 6 million Nigerian children born every year, more than 1 million fail to get fully vaccinated by their first birthday. But despite systemic weaknesses, Nigeria has taken impressive steps to improve vaccine access in recent years. Over the 2000 to 2010 decade, DTP3 coverage increased from 29% to 69%. And in 2012, Nigeria began a three-year rollout of the pentavalent vaccine.
Polio is still a problem for Nigeria. After nearly finishing the job of elimination in 2010, the country slipped, and in the last two years, the virus has made an unnerving comeback. International condemnation of Nigeria over the polio crisis put the government on notice. Everyone wants to know how to crack the polio nut in Nigeria, and raising routine immunization (RI) rates is part of the answer.
“We want to know the bottlenecks and barriers in routine immunization, to help us prioritize our interventions”.
This was the charge that Dr. Muhammad Pate gave to us at the outset of the LARI study. At the time, he was the Executive Director of Nigeria’s National Primary Health Care Development Agency. He’s now Nigeria’s Minister of State for Health.
We anticipated that solutions for routine immunization in Nigeria would need to be local ones. Our role as researchers was to listen, organize, synthesize and disseminate. Over the course of four months in 2011, we spoke to Nigerians working on RI at all levels of government from a sample of seven states and the federal capital territory.
Where are the bottlenecks?
We found that both supply and demand barriers are important impediments to RI performance. In many places, supply is not robust enough to meet existing demand; therefore focusing on addressing supply constraints was a pragmatic first step. Among the plethora of problems identified, three main interlinked barriers emerged: funding constraints, logistical challenges and lack of leadership. Put another way; no money to run programs when needed; inability to deliver vaccines for immunization sessions and lack of cold chain equipment; and political leaders who don’t prioritize RI.
This short list will come as no surprise to most people – they are typical symptoms of weak systems and fledging institutions. And in Nigeria, responsibility for tertiary, secondary and primary health is devolved across the three levels of government – federal, state and local respectively, but the capacity to handle responsibilities varies considerably, and is much lower at lower levels. Primary Health Care, and by extension, immunization services, which is the responsibility of the Local Government Areas (LGAs), bears the brunt of this capacity/responsibility gap.
Interestingly, funding constraints identified resulted more from the failure to expend than failure to budget. There are federal and state budget line items for routine immunization, but the release of such funds is neither guaranteed nor timely. The same thing happens at the LGAs, and to an even greater extent here, provisions are made but funding disbursements are not.
As such, RI programs struggle to conduct basic operational tasks needed to vaccinate children. For example, in the LARI study, program managers and health workers complained about the lack of funds to fuel vehicles or take public transport to collect vaccines from state or LGA cold stores.
With the country’s unreliable power supply, generators are a necessity. Where generators exist, there is often no money to fuel them to maintain the cold chain. Solar fridges and freezers lay fallow due to lack of maintenance. Partners like GAVI, Gates Foundation, WHO, UNICEF, DFID, EU, NORAD and USAID have helped make strides in some areas, but problems still remain.
The federal government plays an important role in procuring and supplying vaccines to states and providing technical oversight, but because of the structure of Nigeria’s government, the federal government does not have authority to drive change at lower levels. Solutions must be implemented at the state and LGA level, because most barriers are occurring in these areas.
The people we spoke to had many ideas for solutions to the problems of Nigeria’s RI system. In selecting solutions, we emphasized the need for in-country stakeholders to consider both impact & feasibility in order to maximize results with limited resources.
A health clinic in Nigeria.
High impact, simple to implement innovations may include:
Mechanisms to make financing more predictable and flexible to reduce barriers at national and sub-national levels. Ebbs in financial flows can be addressed through the use of basket/pooled funds (these have proven successful in some states). Financial guarantees and flexible funding may improve the likelihood that funds designated for RI are spent on RI—in a timely, efficient manner.
The delivery and supply networks also require urgent improvements, which could be implemented using transportation and cold chain maintenance contracts. These contracts could be designed to boost local economies and/or disadvantaged groups. Leadership and ownership at state and local levels are also critical to success. In the absence of the political will to act, holding governments accountable for their responsibilities can drive improvement. But the question is: how do you make political leaders accountable for delivery of immunization services when public awareness of benefits is low and local authorities don’t view immunization as a priority? These are questions for another day.
The Landscape Analysis of Routine Immunization in Nigeria was conducted at the request of Nigerian authorities with support from the Bill & Melinda Gates Foundation and the GAVI Alliance. Chizoba Wonodi, MBBS, MPH, DrPH is Lead of Nigeria Projects at IVAC. Cross-posted at National Vaccine Summit.