The Prevention Debate Is Sometimes Posited As One About Hygiene, Safe Water and Other

Seminar, March 2012

Interview

In the summer of 2011, Seth Berkley moved from New York to Geneva as the new chief executive of the Global Alliance for Vaccines and Immunization (GAVI). For over a decade previously, Berkley had run the International AIDS Vaccine Initiative (IAVI), an institution he had founded. This experience confirmed his status as one of the world’s frontline soldiers in the battle against disease. A polymath and explorer in his spare time, Berkley is a public health specialist of some renown. Trained as a clinical epidemiologist with degrees from Brown and Harvard Universities, Berkley previously worked at the Centre for Disease Control and Prevention, Atlanta, the United States. In 2009, Timemagazine named him as one of the ‘100 most influential people in the world’. In a lengthy interview, Berkley answered Seminar’squestions on the immunization challenge, and his mandate at GAVI to make our planet a safer, healthier place.

The prevention debate is sometimes posited as one about hygiene, safe water and other basics for good health versus immunization. This is, of course, problematic from a public health perspective. How do we present these phenomena as not adversarial but rather as supplementing and complementing each other? What is the role of GAVI in ensuring a comprehensive approach to childhood disease prevention?

Vaccines are a critical tool in combating disease. Their ability to prevent a child from dying or living a debilitated life doesn’t diminish the value of any other preventive tool. To the contrary, I believe they reinforce them. Delivering vaccines in an integrated way with other prevention, treatment and control strategies is undeniably the best formula.

The exciting thing about vaccines is they are a highly cost-effective intervention and can work in places where there are difficulties in fixing the more long-term infrastructure related to the transmission of infection. Immunization programmes have been in place for many years with well-established rules of planning, management and monitoring. The strengthening of routine immunization over the past decade – based on GAVI’s experience in many countries – provides a strong platform to deliver other health interventions such as maternal health services.

Similarly, the introduction of pneumococcal and rotavirus vaccines have the potential to re-energize or strengthen other aspects of pneumonia and diarrhoea control, including safe drinking water and sanitation.

Complementary to the vaccine support we provide, GAVI also contributes to strengthening the capacity of integrated health systems to deliver immunization and support national health strategies. In Afghanistan for instance, GAVI funding has been used to establish health centres and in-service training programmes for health workers.

How do you make a persuasive connection between MDGs and immunization?

GAVI was established in the exact same year as the Millennium Development Goals (MDGs). The Alliance’s creation was part of the new energy and thinking around the MDGs (a perfect example of MDG 8 of global partnerships) and how to tackle the world’s great inequities in innovative ways – in this case, the great inequity in health. The long-term health benefits of immunization accrue to all MDGs, but specifically to MDG 4, and GAVI Alliance partners lead the charge. Vaccines are also one of the most pro- poor and pro-woman interventions in development, thereby affecting MDGs 1 and 3.

Vaccines can have a huge impact. Nearly two million children die of vaccine-preventable diseases each year – this is unacceptable. Pneumonia and severe diarrhoea are the two biggest child killers, responsible for nearly 40 per cent of all children’s deaths in the world each year, yet the main causes of severe pneumonia and diarrhoea are vaccine preventable. Also of great concern is the urgent need to reach the 23 million children worldwide who remain unvaccinated. In front of such a challenge, it is obvious that vaccines are more than ever part of the solution to addressing MDG 4, which is aimed at reducing child mortality by two-thirds by 2015.

Last June, at the GAVI Alliance’s first pledging conference, partners recognized the inadequate progress towards MDG 4 and the substantial unmet demand for vaccines. Thanks to the overwhelmingly positive commitment from donors, the GAVI Alliance is poised to immunize a quarter of a billion children by 2015, and accelerate the introduction of vaccines to prevent more children from dying or suffering from serious diseases. If all pledges materialize, 90 million children will be immunized with pneumococcal vaccines; 50 million with rotavirus; and 230 million with the 5-in-1 pentavalent vaccine against (diphtheria, tetanus, pertussis, hepatitis B and Hib) in the next five years.

We are also keen to expand the range of vaccines available for countries to include in their programmes and are currently considering four vaccines against the human papillomavirus (HPV) cancer, Japanese encephalitis, rubella and typhoid because they address diseases that have the greatest burden in developing countries.

Also on the horizon are promising new vaccines that could have more impact on the lives and health of people in the developing world. I would welcome increased partnership with India to make an even stronger impact on the MDGs. With its scientific capacity and strong vaccine manufacturing base, India has a lot to offer.

GAVI’s donors have given it a commitment of US$ 4.3 billion at the 13 June 2011 conference in London. Does this overwhelm you? Are you worried that the numbers and dollar signs will overtake the actual work that remains to be done, and the children who remain unimmunized? How do you plan to use the money?

The US$ 4.3 billion in additional funds pledged at our first replenishment conference constitutes a vote of confidence on the value of vaccines and the GAVI Alliance. Most importantly, it provides further impetus to build on the tremendous momentum we have created around immunization.

I believe we have two tasks. First, GAVI must ensure pledges announced in London materialize over the next four years, amid global fiscal challenges. Second, GAVI needs to continue to deliver on the promise of immunizing more children with more vaccines – a task that in fact is far bigger than possible through the US$ 7.7 billion available during this five-year period.

If all pledges are received, I can assure you GAVI will capitalize on the unique opportunity to reach higher coverage rates and greater equity access. And country demand for vaccines is increasing: 50 countries have made 74 applications for vaccines and health system strengthening in the current 2011 funding round. This is a record number of applications; nearly twice the highest number ever before received for a funding round.

Twenty per cent of the world’s children remain beyond the ambit of immunization. How are they spread geographically? Does GAVI advocate different strategies for each region or country at this, the last mile, stage? What role does advocacy play here?

Over the past decade, GAVI has contributed to significant increases in immunization coverage among children in poor countries. As a result, many developing countries now have similar immunization rates as richer countries or, in some cases, have even surpassed them. But reaching the last 10-15 per cent of children is very hard. Often they are among the poorest of the poor or are marginalized by society.

GAVI support is flexible as it enables countries to develop and implement specific strategies that extend their immunization coverage to these hard-to-reach children. We also work with civil society organizations or CSOs in reaching the marginalized groups in many countries. In India, for example, GAVI is working with the government and Alliance partners to ensure that our collaboration is most relevant to India’s specific circumstances and challenges. However, GAVI needs to do more and we will refine our knowledge base and tailor strategies to specific countries.

The size of India – one of the largest birth cohorts in the world – combined with the numbers of unimmunized children in the country and the particular public health landscape, requires a very special approach. I am very dedicated to working with my Indian colleagues and feel confident that the partnership between GAVI and India will have a catalytic impact in supporting India’s priorities to improve immunization. Advocacy is very important. The results that the Alliance has achieved over the past decade would not have been possible without the involvement of partners bringing attention to the life-saving impact of vaccines and extending immunization coverage.

In this respect it is important to recognize the partnership that GAVI has with CSOs. For example, at the global level, CSOs are influential in issues such as vaccine pricing; at a country level, they can be instrumental in introducing or extending the use of new or underused vaccines, especially through social mobilization and holding political leaders to account. In other cases, they are a key partner with governments in service delivery, especially to the hard-to-reach populations.

Indian civil society organizations are crucial to building stronger public and political will. Ensuring that they have the support to educate poorer communities about immunization and influence decision making will be critical to further increasing immunization rates in the country.

In many senses, India is a paradox. It manufactures 40 per cent of vaccines used in universal immunization programmes across the world. But a third of all unimmunized children are Indian. As a public health specialist, how do you see this contradiction?

Global immunization rates are at an all-time high of about 80 per cent, but this still means one in every five children remains unvaccinated. There are many reasons to explain this reality, and there are also tangible solutions to further lower the number of unvaccinated children. WHO estimates that if all the vaccines now available against childhood diseases were widely adopted, and if countries could raise vaccine coverage to a global average of 90 per cent, an additional two million deaths a year could be prevented among children under five years old by 2015.

I see this as an opportunity for India to take advantage of. Many experts in the country as well as myself are deeply concerned by the number of children who remain unimmunized worldwide – and in India – and there is no doubt that there is a need for further concerted efforts to ensure all children benefit from necessary immunizations.

Your government’s strong commitment to primary health care has already contributed a great deal to scaling-up immunization coverage throughout the country. India’s significant infrastructure and lessons learnt from the hard work and investment in polio can be leveraged to increase synergies with routine immunization programmes, particularly for the hardest to reach populations. Lessons from Kerala, Tamil Nadu and, more recently, Bihar on how to reach unimmunized children should be taken into account. With a concerted effort there is no doubt that India can reach many more children with immunization.

In the end, it is a question of equity. And GAVI and its partners must also continue to work towards ensuring all children, regardless of where they live, receive the full benefits of immunization, including new and improved vaccines. This means equity between the poor and non-poor nations (wealth equity), between low-and high-coverage districts (geographical equity) and between boys and girls (gender equity). GAVI provides funding to the World Health Organization (WHO) to identify major inequalities in coverage within GAVI-eligible countries and to address these inequalities.

What role does the pentavalent vaccine play in today’s immunization discourse? What can India learn from other countries that have introduced the pentavalent vaccine?

Vaccines in general play an extremely important role in preventing illness and death. Unfortunately, each vaccine added makes the regimen more complex and increases the storage and delivery requirements. Combining vaccines is therefore an incredibly important strategy. As a result, the pentavalent vaccine has been critical to the health of children worldwide. In fact, the introduction of the 5-in-1 pentavalent vaccine (diphtheria, tetanus, pertussis, hepatitis B and Hib) has been used as a trigger for improving immunization coverage or routine immunization in numerous other countries such as Bangladesh, Pakistan and Sri Lanka.

The burden of Hib disease is difficult to directly measure using conventional surveillance, but there is plenty of evidence from a number of studies, including from India, that suggest that Hib is a public health problem worldwide and especially so in countries where pneumonia is a major cause of child death.

GAVI is committed to support India in introducing the Hib vaccine. The fears about the safety of this vaccine are misplaced. Over 160 countries worldwide have used Hib in the pentavalent vaccines, some for over two decades, and found them to be among the safest vaccines available. GAVI has supported the introduction of vaccines containing Hib in over 60 countries beginning in 2000.

There is every reason to believe that the pentavalent vaccine will have the same huge impact on meningitis and pneumonia in India that we have observed in other countries that have introduced it with GAVI support.

One of your achievements at IAVI was synergizing your skills as a scientist and as a public health specialist, working with both Big Pharma and small communities. How do you plan to bring this experience to GAVI? For instance, can the pentavalent model be used for a potential heptavalent or even nonavalent vaccine? How do you convince stakeholders of the imperative to pack more antigens into an ampoule?

One of the critical challenges faced by vaccine developers is due to the very long lead times and high investment costs required to bring a vaccine to market. There needs to be a very strong understanding between scientists and experts who develop products and the public health community. This is to ensure that the products made available are the right ones for developing countries and are made in a way that is suitable for delivery in these countries and at a price that is affordable in the long-term.

With my experience in vaccine development and in developing countries, I can see that GAVI has a critical role in promoting this dialogue and sending out clear signals to manufacturers. Specifically on combination vaccines, the added convenience for countries of having several vaccines delivered in one vial is important as it increases the chances for children to be protected against several deadly diseases. It also reduces the cost to the healthcare system (replacing one vial by another without having to manage separate products) and increases the convenience to the mother and child. However, we also know that the complexity of manufacturing rises with each antigen added.

At GAVI, we are actively looking at developments beyond pentavalent vaccines that include other critical antigens such as polio.

What is the biggest obstacle to genuine universal immunization? Is it finance, capacity and access, or inadequate appreciation of the power of immunization?

The most important barrier is political will. We know that all countries should immunize their children – one of the most cost-effective interventions in the health sector. Of course, reaching the 20 per cent of children who do not receive all the necessary immunizations in their first year of life will require overcoming a number of critical barriers: mainly financing, health systems, local support and knowledge and political will. All must be robust to reach sustainable, universal coverage.

Every country in the world has implemented the Expanded Programme for Immunization (EPI), which is the system by which high quality vaccines are delivered. While the EPI in the poorest counties have made tremendous strides in reaching the neediest populations, more efforts are needed. Expanding the reach of the EPI to the remotest villages and most disadvantaged populations will require investments in the immunization programmes of many countries.

Beyond expanding reach, there is the underlying weakness of health systems such as a lack of health workers and insufficient cold chain capacity. Ethiopia’s recent expansion of a district-level health workforce is a good example of what can be achieved.

But the ability of health systems to deliver services such as immunization is also intrinsically linked to political and financial commitments. In countries most successful in maximizing coverage, the evidence suggests effective political leadership and national ownership of immunization programmes as critical success factors.

While innovative funding mechanisms are essential to help developing countries increase immunization coverage, governments too must step up to the mark by increasing their own spending on vaccines and immunization. We have seen impressive increases since 2000 in national and universal immunization coverage rates, but these need to be continuously sustained and improved to ensure the long-term sustainability of investments made.

Do controversies and debates about vaccines, especially new vaccines, keep you up at night? You are a passionate believer in vaccines but there are several doubting voices out there. How do you react to them?

Vaccines offer the promise of protecting children against a variety of potentially fatal and severe morbidity diseases and they have a high degree of safety. Despite the media attention and strong views from some quarters, vaccines are one of the most cost- effective and safest prevention tools in public health.

The threat posed by false information or persistent rumours about vaccine safety is a barrier to progress. Dealing with such rumours and with adverse events following immunization requires an efficient surveillance and investigation system based upon scientific data. Part of that system must focus on communicating the findings to health workers, health officials, parents, and the general public in a clear manner while addressing fears.

Most commonly, however, communities may simply not recognize the value of vaccines – an intervention that helps healthy people stay healthy. Fifty years ago, all of today’s vaccine-preventable diseases were commonly seen and feared in the community. Thanks to vaccines, today many of these diseases are a distant memory for many of the population. It is also true that value may not be recognized in areas where parents or even politicians lack a basic understanding of how vaccines work. Therefore, treatment – rather than prevention – is emphasised. The result is routine immunization programmes may fail.

To counter misconceptions, well-balanced information and social mobilization campaigns are needed to transform a community’s ‘passive acceptance’ or rejection of immunization into a well-informed demand for ‘the miracle of prevention’ – vaccines.

Further advocacy and communication efforts are needed to address controversies and debate around vaccines. The involvement of different actors including the government of India, civil society, the media, as well as mothers, is crucial. Greater awareness, education and high-level commitment can really make a difference.

Vaccine science is at an interesting and perhaps unprecedented juncture. There is an explosion in vaccine R&D and a number of new vaccines, for a variety of diseases, are on the anvil. Is this an opportunity or will it end up cluttering public and policy debates on which vaccines are ‘necessary’ and which are not?

We do live in exciting times. Never before have we seen so many scientific innovations for vaccines in such a short period of time. To name just two: children can now be protected from the major cause of deadly diarrhoeal disease, and women from cervical cancer. In the coming years, we hope to see a vaccine against malaria and hopefully not too far in the distant future against HIV and TB.

We must use these innovations in vaccine technology as an opportunity to approach things differently, not just by trying to put more vaccines in the system, but by taking a more fundamental look at the way we deliver vaccines in countries and the strength of health systems. If we do this, we will save lives and misery as well as health care expenses.

These new vaccines in the pipeline create opportunities but also imply choices. Countries that apply for GAVI support decide which vaccines they want to introduce while GAVI provides evidence-based information to support their decision making.

Finally, at GAVI do you see India as the vaccine supplier to the world, not only in vaccine manufacture but also in development of new vaccines?

India’s strong vaccine manufacturing capacity is absolutely critical for the world and for the GAVI Alliance. Indian manufacturers can produce vaccines that meet high quality standards, are appropriate to specific country settings, and are offered at reduced prices through a reliable supply over time. Of course, we do need to make sure that the effort is sustainable and we don’t drive prices so low that companies cannot invest in quality assurance and control – factors necessary for a sustainable and healthy vaccine market.

Recently, before I left IAVI and joined GAVI, we signed an exciting new agreement to create a joint AIDS vaccine design and development laboratory. We came to India because of the quality of the science and the possibilities to engage innovative biotechnology companies in applied vaccine development.

Another example of the innovation in vaccinology underway is the meningitis vaccine (menA) – and I am excited at the prospect of seeing Indian manufacturers develop more combination vaccines as well as tackling new diseases that are especially relevant to developing countries.

India’s emergence as a leader in vaccine science is a prime example of how the vaccine landscape has so dramatically changed over the past 20 years. In the 1990s, global pharmaceutical companies were exiting the market as they no longer saw vaccines as sufficiently attractive to justify continued investment. Vaccines today are considered excellent investments in the high-income countries and most of the major companies are engaged in their development. Over the past 10 years, GAVI has been instrumental in creating large and stable markets for the developing world by assuring serious attention to this marketplace.

Today, more than half of GAVI vaccines suppliers are based in emerging countries and a large part of those are in India. Moving forward, Indian manufacturers like other suppliers will need to be sure there is a market for their products. And it will be equally important that all countries express their interest in purchasing these vaccines when they become available.

The approach that Indian manufacturers have taken should be applauded and is perfectly in line with GAVI’s objectives to ensure sustainable supply of affordable vaccines. As I take on my new responsibilities at GAVI, I am excited about the possibilities of increasing our collaboration with India on this front as well as on many others.