Gates Foundation: Building bridges between laboratory innovation and public health intervention

A simple credo fuels most of the charitable activities of the Bill & Melinda Gates Foundation: All lives have equal value.

This credo manifests itself in the form of vast sums of money contributed to research and public health efforts, primarily in developing countries.

Funding from the Foundation is channeled to high-profile causes such as malaria control, HIV/AIDS prevention and efforts to eradicate lesser-known diseases, such as lymphatic filariasis.

Although much of the organization’s focus is placed on infectious diseases in sub-Saharan Africa, its presence can be felt throughout the world, including recently in Haiti, where the Foundation provided grants for relief organizations assisting with earthquake response.

“I applaud the Gates Foundation,” Theodore C. Eickhoff, MD, professor of medicine at the University of Colorado, Denver, and an Infectious Diseases in Children editorial board member, said in an interview. “They have the biggest pot of money in the world and I am delighted that they are using it to do what they are doing.”

Grants for research conducted by institutions in the developed world and partnerships with organizations that are involved in hands-on activities in the developing world guide the Foundation’s approach. A large portion of the funding goes toward the development and delivery of vaccines to prevent and eradicate infectious diseases. Underlying all of this is a belief that technological innovation is a pathway toward improved global health outcomes, according to several medical experts interviewed by Infectious Diseases in Children.

Walter Orenstein, MD, deputy director for vaccine delivery of the global health program at the Bill & Melinda Gates Foundation, and member of the Infectious Diseases in Children editorial board, said the Foundation tries to have a “catalytic” effect on efforts in which it becomes involved.

“We are not in there for prolonged sustained interventions,” Orenstein said. “The aim is to stimulate buyer commitment in the programs and encourage local governments to contribute more resources to public health.”

“The fact that the (Gates Foundation) has local governments in the affected regions working toward self-sustaining programs is a unique approach to foundation-type work. This sets them apart from other similar organizations,” Eickhoff said.

Malaria

Christian Loucq, MD, director of the PATH Malaria Vaccine Initiative, which receives much of its funding from the Gates Foundation, said that the Foundation helps his organization serve as a “bridge between the laboratory and development.”

“Malaria kills a lot of children aged younger than 5 years in sub-Saharan Africa,” Loucq said. “There is no market to justify the development of a vaccine. If there is no public or not-for-profit organization that comes into the picture to share risks, developments will never take place. These children will not get treated.”

The preventive and curative tools currently available to fight malaria are insufficient. PATH and the Foundation have focused on innovative vaccine strategies, including support for phase-3 trials of the RTS,S vaccine, a pre-erythrocytic vaccine, transmission-blocking vaccines and tools to develop a vaccine against Plasmodium vivax.

“No single initiative has the power to be 100% effective,” Loucq said. “However, there is a consensus that a vaccine coming off of the new initiatives may allow us to finish the job.”

The RTS,S vaccine is the most advanced candidate, and Loucq said the development of the product would not have been possible without the Gates Foundation.

“We received our first grant from them in 1999,” he said. “Who would have thought that 10 years down the road, we would have a vaccine in phase-3 trials? This is quite simply an excellent result.”

Effective artemisinin-based combination therapies are too expensive for many individuals in the developing world to afford, so patients often resort to artemisinin monotherapies or counterfeit medications that increase the likelihood of resistance, according to information on the Gates Foundation Web site.

Primarily through the Medicines for Malaria Venture, the Foundation is assisting in reducing the cost of artemisinin through financing and subsidies, developing non-artemisin-based therapies, monitoring resistance trends and improving diagnostics.

The Foundation is also investigating efforts that would increase the availability and use of long-lasting insecticide-treated bed nets and indoor residual spraying. Of particular concern is the development of insecticide resistance.

In collaboration with WHO and UNICEF, strategies such as intermittent preventive treatment of children and approaches to reducing the burden of malaria among pregnant women are also being explored.

HIV/AIDS

The Foundation’s approach to HIV/AIDS is similar to its approach to malaria interventions. Chiefly, the Foundation supports existing, proven interventions, including male circumcision, needle exchange programs for injection drug users, youth behavior change, counseling and testing initiatives.

The long-term goal is to develop preventive microbicides and an effective vaccine, but recent setbacks indicate that such developments may be many years away. In the meantime, the Foundation is supporting HIV/AIDS programs throughout the world with programs such as Avahan in India and the African Comprehensive HIV and AIDS Partnership in Botswana.

Through programs such as the Male Circumcision Partnership, governments in Swaziland and Zambia have been encouraged to take an active role in promoting voluntary circumcision among nearly 650,000 men. Through collaboration with the government of Botswana, preliminary data indicate that prevention of mother-to-child transmission of HIV may have been reduced by as much as 90%, according to findings published on the Gates Foundation Web site. These findings also indicate that antiretroviral therapy coverage may be more than 90% in Botswana.

“[U.S. President’s Emergency Plan for AIDS Relief] has had great success, but it is not enough,” Eickhoff said. “The fight against HIV/AIDS in the developing world needs the kind of money that only the Gates Foundation can provide.”

Tuberculosis

Partnerships between the Foundation and organizations such as the Areas Global TB Vaccine Foundation, the Global Alliance for TB Drug Development (TB Alliance) and the TB Drug Accelerator program may facilitate the WHO target to reduce the prevalence of and deaths attributable to TB by 50% by 2015 and eliminate TB as a public health threat by 2050.

A combination of innovative vaccines, improved diagnostics and more diverse treatment options is supported by the Foundation. Of particular interest is the use of isoniazid preventive therapy, which the Foundation is supporting via the Consortium to Respond Effectively to the AIDS/TB Epidemic.

“TB is one area where technology is really helpful, particularly with regard to diagnostics,” Eickhoff said. “This is a disease that almost demands a technological approach.”

As for progress, two Gates-funded vaccine candidates, MVA85A/AREAS-485 and AREAS-402/Crucell Ad35, are in phase-2b trials; two moxifloxacin-containing drugs are in phase-3 trials; and the Foundation for Innovative New Diagnostics has a cross-section of assays, microscopes and visual reading molecular platforms in development.

Polio

Orenstein said that the Gates Foundation has made substantial investments to help achieve polio eradication. These investments range from support for vaccine purchase, delivery of vaccine in mass campaigns, improved detection of cases of polio to efforts to develop vaccines that will be critical to sustaining polio eradication.

“Industrialized nations might have little interest in developing vaccines because there is little market for them in the industrialized world,” Orenstein said. Bill Gates visited Nigeria last year to meet with political and religious leaders.

“His presence drove the point home that polio is a serious concern,” Orenstein said. “The result was that polio-related initiatives were prioritized and more resources went to public health.”

A partnership with the Global Polio Eradication Initiative forms the backbone of the Gates Foundation strategy to eradicate the disease.

Administration of the oral polio vaccine to children aged younger than 5 years is key to interrupting ongoing circulation. Stringent surveillance activities are also necessary to account for cases of acute flaccid paralysis.

The Foundation supports the development of real-time polymerase chain reaction assays, laboratory assays and environmental systems for conducting surveillance of trends in poliovirus. Additionally, the global fund was responsible for delivering 1 billion doses of the oral polio vaccine in India in 2008 and 222 million doses among children in 22 high-risk countries during the last 10 days of May 2009.

Other infectious diseases

The relationship between the Gates Foundation and the Carter Center has been well-documented in the media and the medical community. Infectious Diseases in Children spoke with Donald R. Hopkins, MD, MPH, vice president of health programs at the Carter Center, about eradication efforts being conducted by the two organizations.

“Seven years ago, we scanned the horizon looking for other diseases that could be candidates for eradication or at least for better control,” Hopkins said. “These included Guinea worm disease, polio, lymphatic filariasis, mumps, rubella, cysticercosis and measles.”

Although the Carter Center has received much attention for the largely successful battle against Guinea worm disease, Hopkins outlined several lower-profile fights on which the two organizations are collaborating. For example, in Nigeria, the use of bed nets to reduce lymphatic filariasis is being investigated, and in Central and South America, interventions to eradicate onchocerciasis by 2012 are under way.

“The Gates Foundation is outcome-oriented and influential,” Hopkins said. “At the Carter Center, we know our strengths and our limitations, and this makes for a good collaboration.”

The Gates Foundation has identified a broad portfolio of infectious diseases that they have grouped into the categories of “other” or “neglected,” not necessarily because they are any less important, but because they disproportionately affect the poorest populations in the developing world. That list of diseases includes:

• Cysticercosis
• Dengue fever
• Guinea worm disease
• Hookworm and other soil-transmitted helminths (ascariasis and trichuriasis)
• Human African trypanosomiasis
• Japanese encephalitis
• Lymphatic filariasis
• Onchocerciasis
• Schistosomiasis
• Trachoma
• Visceral leishmaniasis

The Bill & Melinda Gates Foundation has supported the Global Alliance to Eliminate Lymphatic Filariasis in delivering nearly 2 billion units of Mectizan (Merck) and albendazole (GlaxoSmithKline) to children in 83 countries; the Schistosomiasis Control Initiative has overseen the delivery of approximately 40 million treatments of praziquantel; and the Global Network for Neglected Tropical Diseases has spearheaded a campaign to deworm approximately 1.9 million children in Tanzania.

“At the Carter Center, we are manic about two things: changes at the grassroots level and measuring results,” Hopkins said. “From what I have observed, Bill and Melinda Gates are intelligent people who ask probing questions and understand these diseases. The result is measurable public health outcomes in the diseases they have identified.”

Concerns

Despite the Foundation’s well-documented successes, the organization is not immune to criticism.

David McCoy, DrPH, of the Centre for International Health and Development, recently published an article in The Lancet in which he called on the Gates Foundation to have better transparency and accountability for its donations.

“While the Foundation has the legal right to decide how it should use its money, it has a social duty to be accountable and responsible to the range of other actors involved within the health sector,” McCoy told Infectious Diseases in Children. “It must act as a responsible actor within the health sector. This is a duty for all of us, but one that is especially pertinent to the Gates Foundation because of its huge power and influence.”

McCoy said he is concerned about the technological and clinical approaches employed by the Foundation, and that the emphasis on the role of markets and private actors may have limitations as an approach to public health.

“The mentality that was developed in Microsoft and which is embedded more generally in the business sector is the overwhelming frame of reference [for the Gates Foundation],” he said. “The problem is that there is little appreciation about what makes health and health care so different from other services and commodities.

“I take it at face value that Bill and Melinda Gates genuinely want to put their fortune to good use and that there is therefore a need to treat this with respect,” McCoy said. “However, they need to force themselves to be more self-critical and to be much more thoughtful and careful about how they use their money and wield their influence.”

Orenstein said because of the active role the founder has taken in understanding the science behind the interventions, he considers Bill Gates a “scientific colleague.”

“Bill Gates does not dictate. He listens and discusses,” Loucq said. “I am impressed by his knowledge of science. The result is that the Foundation is involved primarily in data-driven interventions.”

Hopkins said there are concerns that the Foundation focuses on disease-based, vertical programs rather than integrated interventions.

“This is a criticism we at the Carter Center often hear,” he said. “My response is that I put myself in the place of someone in a village that is being torn apart by one of these diseases. The thing that I have heard most from people in that position is simply, ‘thank God someone is doing something.’”

Hopkins said there is a lot of talk about focusing more on primary health care, but this does not necessarily translate into action or outcomes.

“Donors talk about primary health care but give their money to vertical programs,” he said. “The perception is that it is easier to measure progress in a fight against a specific disease than it is to measure progress in general health. Personally, I do not believe this to be true, but that is the perception among donors. So therefore, I will ask: Who is helping these countries develop primary care facilities?” (see sidebar)

Annual statement

The Foundation recently published its second annual statement, which provides a comprehensive look at what has been accomplished and what can be expected in the future.

“In 2008, for the first time, fewer than 9 million children under age 5 died,” Bill Gates wrote in the annual statement. He attributed this reduction to what he called “the miracle of vaccines.”

Beyond the broad category of neonatal mortality, pneumonia and diarrhea-related diseases cause the most significant death rates among children. He highlighted the work of the Global Alliance for Vaccines and Immunization (GAVI) in delivering rotavirus and pneumococcal vaccines to poor, endemic areas. “Rotavirus vaccine could save 225,000 to 325,000 lives per year and pneumococcal vaccine could save 265,000 to 400,000 lives per year,” Gates wrote.

The current structure allows GAVI to purchase pneumococcal vaccines for $3.50 per dose. Participating countries will co-pay a portion of the cost. GAVI also handles the interventions that focus on increasing HiB vaccination coverage.

The Global Enterics Multicenter Study and the Malnutrition-Enteric Disease Network are two organizations that are investigating the epidemiology and pathophysiology of enteric diseases. Exploration of biomarkers to enhance diagnostics and novel approaches such as zinc taken with oral rehydration therapy are approaches that Foundation officials said may reduce the incidence of diarrheal and enteric diseases.

In the end, the Gates Foundation strategy comes back to innovation.

“I am optimistic that innovations will allow us to avoid bleak outcomes,” Gates wrote. “Melinda and I see our foundation’s key role as investing in innovations that would not otherwise be funded.” – by Rob Volansky

What are some of the most important contributions the Gates Foundation has made to public health?

For more information:

• Visit the Bill & Melinda Gates Foundation Website.
• McCoy D et al. Lancet. 2009;373:1645-1653.