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Johns Hopkins Bloomberg School of Public Health


Date: Sep 2012

By Dr. Mathuram Santosham

If you ask a scientist why it’s important to be an advocate, most scientists would probably be puzzled. After all, a scientist’s job is to research and study to find what works, test alternate hypotheses and document findings. Advocating is the job of an activist, they’d likely reply.

And they’d be partly right; advocacy is the job of an activist. But as scientists and medical providers, it is our duty to ensure that the knowledge that we have gained through research and best clinical practices is transferred to appropriate decision makers so that ALL children benefit from these life-saving interventions.

As a doctor, I have seen the grief of parents who have brought their children in for treatment for preventable diseases like pneumonia and diarrhea, only to be told they’ve arrived too late. As a scientist, I have conducted the research and know that vaccines against these diseases are effective and have the potential to prevent millions of unnecessary deaths in the next decade.

Panelists at the ROTA Council session

Panelists at the ROTA Council session "Translating Evidence Into Policy to Fulfill the Promise of Rotavirus Vaccines" at the 10th International Rotavirus Symposium included Kathy Neuzil, PATH; Tony Nelson, Chinese University of Hong Kong; George Armah, University of Ghana; Mathuram Santosham, Johns Hopkins University; and Andy Seale, PATH.

Rotavirus is one of these diseases. Today, rotavirus diarrhea is a leading killer of children in the developing world and the leading cause of hospitalization all over the world. Time and again, research has demonstrated that vaccines can protect children from rotavirus diarrhea or lessen its severity, yet introduction has been slow, especially in low-income countries where children need it the most. Only 41 countries have introduced the vaccine since it became available in 2006, including only a handful of countries in Africa and Asia, where the burden is greatest.

In the past three decades we have made tremendous advances in science that have allowed us to come up with numerous life-saving interventions. One of the most powerful interventions is vaccination. Vaccines have saved millions of lives in the past 50 years and have the potential to save millions more in the next 50 years. However, many children are deprived of life-saving vaccines, in my opinion partially because we have failed to appropriately communicate available knowledge to parents, healthcare providers, program managers and decision makers.

This is why Dr. Ciro de Quadros and I came together to form the ROTA Council, an organization of technical experts committed to providing the evidence policy makers need to accelerate the introduction of rotavirus vaccines in high-burden countries. Last week we hosted our second strategy meeting in Thailand during the 10th International Rotavirus Symposium, where we shared ideas to amplify our efforts. We also hosted an advocacy session during the Symposium to train and empower other scientists gathered from around the world on how to become advocates for rotavirus vaccines.

Last week’s Symposium offered a breadth of insights on the latest research including surveillance and modeling to confirm the burden of rotavirus mortality and morbidity, the ability of vaccines to reduce death and hospitalizations in real-world conditions, and the safety of the vaccines. There are several promising candidate vaccines in the pipeline from developing country manufacturers which, when ready, should improve vaccine availability and reduce cost. Important research also continues on rotavirus pathogenesis, immunity, vaccine performance and correlates of protection.

ROTA Council members gather for an annual strategy meeting in Bangkok.

ROTA Council members gather for an annual strategy meeting in Bangkok.

Going forward, it is vital that we communicate data like we heard last week to the decision makers who must act in order to accelerate vaccine introduction. As scientists, medical practitioners AND advocates, we are in the unique position of being able to make the evidence come to life in ways that other messengers cannot. We are on the frontlines, conducting the research and treating the patients, and therefore we must add to our responsibilities the job of spreading the word so that policymakers are moved to act. We bring a double bank of knowledge that makes our voices incredibly powerful. The time has come for us as scientists to add our voices to the chorus calling for introduction of rotavirus vaccines.

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.  

Next month, Dr. Orin Levine will leave his post as Executive Director of IVAC at Johns Hopkins Bloomberg School of Public Health to join the Bill & Melinda Gates Foundation as Director for Vaccine Delivery in the Global Development Program. Before he leaves, we asked him to reflect on the last 10 years and the changes he has seen in vaccine access and in the organization he helped build.

You started at Johns Hopkins with a single vaccine access project, GAVI’s PneumoADIP. Today, IVAC is a leader in vaccine access research and practice, with projects tackling a wide range of vaccine-preventable diseases across a mix of disciplines. What were your goals for the organization, and did you imagine it becoming anything like what it is today?

When we started PneumoADIP (Pneumococcal Vaccine Accelerated Development and Introduction Plan) we had no idea it would grow so quickly and evolve into what is now IVAC. And I know that because, when I took the job my wife and I had just had our first daughter and I told her, ‘don’t worry it’s just a three year grant, $30 million, a small team of about seven or eight people.’ Now, almost 10 years later, with a team of more than 30 people and the scope and breadth of what we are doing – it was almost unimaginable when we got started.

PneumoADIP was a really remarkable opportunity. One of the things the PneumoADIP team was really focused on was that this was the best chance we had ever had at making a really big difference on accelerating vaccine access. We were very focused on moving the needle, on getting pneumococcal vaccines out faster and more widely than ever before. So that team, that purpose, that mission, really came together all at once in a very special way.

Tell us about the evolution from PneumoADIP to IVAC.


Dr. Orin Levine speaking at the launch of the UK All-Party Parliamentary Group on pneumococcal disease prevention in 2007. (Photo Credit: Amit Lennon)

In retrospect, PneumoADIP occurred at a really exciting time in global health and global vaccine access. GAVI was new, the Bill & Melinda Gates Foundation was new, and people were asking questions about what is possible and raising their ambitions. At the same time all the architecture was also new and small. There was an incredible space for a team based at Johns Hopkins Bloomberg School of Public Health (JHSPH) to play a leading role in the effort to get new vaccines out in collaboration with GAVI and a lot of other players.

The team really embraced that. We were very focused on a handful of core strategic goals. We designed everything to be rigorous and collaborative. Those are qualities that have carried forward into IVAC. We saw a compelling injustice, that pneumococcal vaccines were being used here in the United States and not where they were needed the most. That injustice is what drove people here at IVAC – and still does – to get up and come into work and do what they do.

You often refer to the ‘summer that wasn’t’ in 2008. Can you tell us about that?

The summer of 2008 was pivotal for us at IVAC and one busy summer. At that time, it was apparent that pneumococcal vaccines were going to roll out in GAVI countries and we were ahead of any historical precedent with a new vaccine. They were poised to take off, but they weren’t yet in the countries. There was a feeling here at PneumoADIP, soon to be IVAC, that while we could take some legitimate credit for having built things to the point where the table was set for rollout, it hadn’t quite rolled out, and we were anxious that if we left the scene, for whatever reason, it wouldn't continue the way we had envisioned. So, we were in this moment where the success, the thing we had worked so hard for, was almost there but not quite. We wanted to be part of that next step - the sometimes messy process of getting to implementation.

The PnuemoADIP contract was coming to an end so we knew that to be part of the next phase we had to write a proposal. At the same time, we wanted to keep the team together not knowing what was going to happen. We were pretty busy writing proposals in the summer of 2008. We wrote two really big proposals, one for the follow on from PneumoADIP - AVI - and one for PERCH, the world’s largest pneumonia etiology case-control study in a generation.

We had this attitude that we would be happy working as a team on either grant and then we won both. That was a really big step for us. It helped us feel like we could continue on the pathway that we had started with PneumoADIP, but it also really said to us that people recognize what our team can do. From that time forward, we just continued to diversify our portfolio, building off that same core of teamwork and innovation in solving difficult problems.

So were you able to rest at all that summer? Was sleep on the agenda?

It was, but not much. As with everything at IVAC, it was a team effort pulling those proposals together but, as I always tell people, when you pack a printer for your vacation, it's a pretty bad sign the vacation won’t go how you planned. That was certainly true that summer. I remember it so well. We were packing up the car with towels and boogie boards and there was a box with a laptop and a printer in it.

What are some of the other highlights over the past 10 years?


Dr. Orin Levine in South Africa filming a documentary about pneumococcal disease for BBC in 2004. (Photo Credit: IVAC)

I'll give you a few because there were many, obviously with a team as talented as this one. One of the highlights was the very first strategic retreat of the PneumoADIP team. We got the PneumoADIP award in January of 2003 and by June, had identified, recruited and brought on campus everybody on the team. Together, with Thomas Cherian from WHO, we sat down for two days in Baltimore and built the strategic plan. Basically we mapped out the next few years of PneumoADIP on big sticky notes on the wall. It was really great to see everybody come together around this common vision and suspend disbelief for a couple days. You know it was pretty outrageous to believe in 2003 that we were going to accelerate access to the world’s most expensive vaccine for the world’s poorest countries, and yet they bought it and it has made a big impact.

The first IVAC video documentary we did was another highlight. We really put a face on pneumococcal disease, the problem and what could be done in a way that hadn’t happened before. I remember a few days after it aired on BBC World I got a phone call from a senior executive at a major vaccine manufacturer who said ‘That documentary was incredible. I watched it with my teenage kids and at the end they said to me, dad you need to get that vaccine for those kids in developing countries.’ With that I really came to appreciate the power of making the case with video and other multimedia. The case always starts with evidence, but using that kind of tool was really important.

We had a number of other highlights on the evidence side. It was a major accomplishment when our team built up pneumococcal surveillance in collaboration with WHO in more than 50 countries, then leveraged that data to generate disease burden estimates for the whole world, and then, in order to meet the needs of the $1.5 billion Advance Market Commitment, did the most incredible work on this project called the global serotype project. That's memorable because we had an incredibly tight turnaround. We got the final analysis and then had to summarize and submit back to GAVI and the AMC committee the night before it was due. I remember it was in August because it was Kate O’Brien’s birthday, and we spent her birthday as a team in her kitchen up until 3 a.m. writing that report.

So birthdays and vacations were often spent writing reports?

Definitely not, but I can see how it looks that way. [laughs] We have a team that knows how to celebrate as well as work hard and we shared many great times together. But when the team saw a $1.5 billion opportunity for pneumococcal vaccines, they made the sacrifices too.

Was there an especially memorable achievement for you over the years?

A really memorable moment was being in Rwanda for the launch of the first GAVI-supported pneumococcal vaccine program in 2009. I was there with the CEO of GAVI at the time, Julian Lob-Levyt, and seeing the expression of our work as kids getting vaccinated for the first time was a tremendously


Dr. Orin Levine speaking with a nurse in Rwanda at the launch of the first GAVI-supported pneumococcal vaccine program in 2009. (Photo Credit: Thomas Rippe)

memorable experience. We had an event in Rwanda where kids got vaccinated and then we arranged a conference call back to Baltimore with the whole PneumoADIP team. The GAVI CEO joined me for that call and thanked the team for their work over the years to make this launch possible. Even though I wasn’t in Baltimore, you could feel, even over the phone, the pride that was coming from the team at having made a really big contribution to that achievement.

Wow, it must have been amazing to hear people say we need to fix this problem and then just a few years later see children being vaccinated.

Yes, it was, for the whole team. I think the thing that pulls people to work at IVAC more than anything is the mission. It's a mission-driven group, they are committed to the notion that we can do something about vaccine access. And when we do, it makes a difference in peoples lives and communities. There are lots of organizations that talk about that, and here we have the privilege and benefit to actually deliver on it. That’s one of the things that make IVAC special.

While we are talking about the mission, what do you envision in the future for IVAC?

IVAC is in a terrific position. The number one strength of IVAC is its team. We have incredibly talented people here who are going to carry the mission forward for years to come. You know, I see many opportunities for IVAC in the future. Really the question that IVAC probably will face is, out of so many opportunities, which do they choose to focus on? It’s a good problem to have.

What are the things you value most about the team here at IVAC?

One of the things that make it hardest to leave is the team. There are a few people who have been with me shoulder-to-shoulder from the beginning, like Kate O’Brien, Mathu Santosham and Maria Knoll, and others like Dagna Constenla, Danny Feikin and Lois Privor-Dumm, who have come on board later. What is really remarkable in many ways is that as we grew we retained a core set of ambitions: a sense that we didn't want incremental change, we wanted that big change, and that it was possible; a willingness to question things, not in an arbitrary or personal way, but in a very results-focused way;


Dr. Orin Levine and members of the PERCH Expert Committe at a meeting in Baltimore in 2012. (Photo Credit: IVAC)

and an innovation-centered approach, that idea that if it was easy it would have been done already, so let’s try something a little bit different. Those are some of the things that IVAC is going to carry forward, especially this sense of bringing innovation to difficult problems and the willingness to experiment and fail, which is integral to making a difference.

What’s your vision for vaccine access in general? What changes do you think we will see in the next 5-to-10 years?

It’s an exciting time to be working on vaccine access. There are some really important trends that are going to impact vaccine access in the years to come. From my perspective, one trend is going to be an emphasis on more and more country-driven immunization programs. Countries are going to be less reliant on donors and international agencies and more self-reliant. That's a great opportunity and it requires shifting towards a policy dialogue model. I also think we are moving to a more integrated approach to delivering interventions within health and even between health and other sectors. So you are seeing things like financial services and health connecting. And then the last area that I think is going to be really exciting is improving service delivery. We have improved our vaccine introduction and accelerated that more in the last decade than we have improved coverage or service delivery. We made big gains by narrowing the time-lag in access to new products, but the next big step is going to have to be boosting us to universal coverage in every community.

So what excites you the most about your new position?

I think working at the Bill & Melinda Gates Foundation will be exciting because of their results-based approach to tackling problems. The foundation brings to bear great minds, substantial resources, and a prolonged focus.

And you are moving to Seattle. What are you looking forward to about that? Aside from the rain...

Well, the well-known weather patterns of Seattle are certainly a draw. The city itself is really beautiful and, for me and my family, who really enjoy the outdoors, there is just tremendous opportunity to enjoy the Seattle environment. I think we – me professionally and hopefully my family too – both literally and figuratively, will have new hills to climb that will make us stronger and bring us new rewards.

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.

Why Nigeria?

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”.

Nigeria's Minister of State for Health - Dr. Muhammad Pate

Nigeria's Minister of State for Health, Dr. Muhammad Pate, speaking at Nigeria's National Vaccine Summit.

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. 

Identifying solutions

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.

Health Clinic in Nigeria

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.

Nigeria - Breaking Down Barriers to Immunization Coverage (Infographic)

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.

By Orin Levine and Ciro de Quadros

The world is anxious for a dengue vaccine. It is estimated that 40 percent of the global population is at risk, and in too many countries, dengue fever is common and frequently causes outbreaks. When it hits, the effects on families and communities include pain, economic hardship and fear of whether tomorrow will bring a fatal or serious illness to a household member. 

Today The Lancet released the first ever results from a dengue vaccine trial with enough cases to measure the vaccine’s effectiveness. The trial’s results provide signals rather than definitive answers, and a mixture of both promise and unresolved challenges. To date, these represent the most promising indications that a safe, effective vaccine to prevent dengue is technically feasible. At the same time, the results on protection were inconclusive, somewhat inconsistent with the measured immune responses, and uneven across the four strains included in the vaccine. Fortunately, a much larger trial already underway in 10 different countries is likely to tell us by 2014 if the signals observed in this trial are accurate or not.

This phase 2b randomized, controlled trial, which was conducted in one dengue-affected area of Thailand called Ratchaburi, allowed the investigators to measure the vaccine’s safety and protective effects. The signal on safety was very promising. There were no significant safety concerns identified in this trial. Larger trials with longer follow up of people will be required to further establish the safety of these vaccines but the absence of safety concerns in a group of approximately 4000 participants is encouraging.

The mixed signals come in the area of protective efficacy.  To understand the results you need to remember that dengue is not caused by a single virus, but rather by four different related viruses, known as DENV 1, 2, 3, and 4 and that the vaccine in this trial is designed to protect against all four. This is where the results are mixed and largely inconclusive. On the one hand, there was no overall reduction in dengue cases observed from the use of the vaccine. On the other hand, in sub-analyses of the overall study, there were indications of protective efficacy versus three of the four serotypes (DENV 1, 3, and 4). The disappointing signal was in the fact that no protection was observed versus infections with the DENV 2 virus, which was the most common serotype in this community (and hence, no overall protection was observed when the effects of all 4 were combined). This lack of observed protection vs. DENV 2 was also surprising, given that the vaccine appeared to stimulate good immune responses among those who received it. Deeper analysis of these results are needed to determine what might explain this observation, and more importantly, what might be done to overcome it.

It will be important to see the results of the larger trial and the effectiveness of the vaccine in different epidemiological settings. These results may mirror what we have seen in Thailand, but we could also see stronger results and demonstrably good protection in these larger trials. It’s just impossible at this point to predict. We at the Dengue Vaccine Initiative (DVI) will continue to follow the progress of Sanofi’s vaccine as we work to lay the foundations for the adoption and rollout of a licensed dengue vaccine in the future.

Vaccine research requires focus, creativity, tremendous dedication and multi-disciplinary teams. Success is never guaranteed, and many great ideas for vaccine candidates fail to become successful public health vaccines. For these reasons, the research teams in Thailand and at Sanofi deserve recognition for their tireless efforts to advance the dengue vaccine. We are grateful for the efforts to date, and eager to see what results come out of the next, larger phase 3 trial. In the meantime, the dengue virus better look out. A safe, effective vaccine might be right on its tail and about to overtake it.

Dr. Orin Levine is the Executive Director of the International Vaccine Access Center. Dr. Ciro de Quadros is Executive Vice President of the Sabin Vaccine Institute. Both organizations are members of the Dengue Vaccine Initiative.

Cross-posted at DVI and The Huffington Post.