Bill & Melinda Gates foundation

Ghana’s first lady, Ernestina Naadu Mills, vaccinates a six-week-old child against rotavirus at a ceremony in Accra.

Rotavirus is the most common cause of diarrheal hospitalizations and deaths in young children under age 5. Existing rotavirus vaccines have been shown to dramatically reduce the number of hospitalizations and deaths; WHO recommends its use in all countries, particularly ones in which diarrhea is a major cause of childhood deaths.

Rotavirus vaccines were introduced in the United States and many Latin American countries in 2006, and in 2012 they finally reached children in several developing countries. Many more countries have approved introduction of the vaccine in the next two to three years. We work closely with the GAVI Alliance and national governments to subsidize the cost of rotavirus vaccines, support their introduction where they are most needed, and expand routine immunization of young children against an array of diseases. Our long-term goal is to see the rotavirus vaccine introduced in at least 50 lower- and middle-income countries.

We also work with PATH and vaccine manufacturers in emerging economies such as India, Brazil, Indonesia, and China to invest in new rotavirus vaccines that will diversify the market, increase vaccine supply, and decrease costs.

Most non-dysentery childhood diarrhea deaths can be prevented with proper administration of simple interventions such as ORS and zinc, but they are not widely used. To increase the availability and use of ORS and zinc, we work with partners in India, Nigeria, and Burkina Faso. Our decision to focus on these countries is based on their burden of childhood illness, their readiness to innovate, and strong partner organizations. For example, in Uttar Pradesh, India, we support the Clinton Health Access Initiative and other partners who conduct marketing campaigns to promote the use of ORS and zinc as treatments for diarrhea.

We support research to understand the key barriers to wider use, and we work with manufacturers and distributors to make ORS and zinc products more attractive to consumers—by improving flavors and repackaging products, for example.

We also invest in the development of products that control diarrhea symptoms while also treating dehydration. Because ORS rehydrates the child’s body but does not initially decrease stool output or offer immediate relief of symptoms, caregivers often reject this approach in favor of other, less effective, remedies. We support efforts by PATH to discover and develop novel therapeutics that reduce excess water loss and relieve diarrhea symptoms and will lead to increased use of ORS and zinc.

A vaccine is needed to control typhoid and paratyphoid, which together kill up to 250,000 people a year, mostly children. An effective and affordable vaccine is the best short-term solution to control enteric fever in countries with poor access to clean water, sanitation, and hygiene as well as high rates of antibiotic resistance.

We work with the International Vaccine Institute, Shantha Biotechnics, the Sabin Vaccine Institute, and others to develop a conjugate vaccine that should have a longer duration than the current vaccine and can be used in children under age 2. Better diagnostic tools and data are also needed to understand the true impact of these diseases.

ETEC and Shigella are ubiquitous bacterial pathogens in most regions of the world, particularly in developing countries, where they are a constant risk to both children and adults. ETEC and Shigella kill an estimated 200,000 children under age 5 every year. Even a single episode of Shigella will cause severe damage to the gastrointestinal system.

Our key partner in the development of new ETEC and Shigella vaccines is the PATH Enteric Vaccine Initiative. To increase the chances that a vaccine will reach the market quickly, we support work on a portfolio of vaccine candidates that offer different approaches. The most advanced ETEC and Shigella vaccine candidates are still about a decade away from use in the field.

We are working to understand how environmental and other factors contribute to intestinal disease and damage, which in turn lead to poor nutritional absorption in children. In poor communities, this cycle begins in infancy and persists through childhood, with consequences that frequently include stunted growth, impaired cognitive development, reduced immune response to infection, and death.

We are in the early stages of researching the causal relationship between altered gut function and malnutrition and poor development. Our key investments in this area include support for the Malnutrition and Enteric Diseases (MAL-ED) Consortium, an international project that studies populations with high rates of malnutrition and enteric infections. MAL-ED studies will provide important data to inform development and testing of new approaches to preventing and treating these diseases.

Cholera kills as many as 130,000 people a year and occurs in epidemic and endemic settings. At least 51 countries in Sub-Saharan Africa and Asia have endemic cholera. Several recent epidemics, including those in Zimbabwe, Haiti, Guinea, and Sierra Leone, have severely strained the already under-resourced health systems of those countries.

A hand-washing station and chlorine dispenser that are part of a cholera-prevention study in Bangladesh.

A huge step forward in 2012 was a WHO report that called for the creation of a global oral cholera vaccine (OCV) stockpile and outlined criteria for deploying the vaccine along with other proven interventions such as clean water and improved sanitation. We support the establishment of a stockpile of 2 million doses of OCV. Stable vaccine demand will expand supply, lead to more competitive pricing, and spur demand in countries with a high burden of cholera.

We also support development of evidence-based policy guidelines for OCV use in outbreak settings as well as better data collection to build a case for use of cholera vaccines in endemic areas. We are investing in the development of a low-cost, single-dose cholera vaccine for use in epidemics and for outbreak control. To expand supply, at least one additional manufacturer of low-cost, killed whole-cell cholera vaccine must be prequalified by WHO.

We have made significant investments in the Global Enterics Multi-Center Study (GEMS) to provide better data on the causes and consequences of diarrheal diseases in young children in Africa and Asia. To further our understanding of the major diarrheal pathogens and to measure the impact of interventions, we support development of advanced diagnostic tools and expanded evaluation efforts.

At the regional and country level, we work with existing surveillance networks, such as GEMS, the African Cholera Surveillance Network (Africhol), and the Typhoid Surveillance in sub-Saharan Africa Program (TSAP) to monitor for specific pathogens, including rotavirus, cholera, typhoid, and paratyphoid. As we learn more about the etiology and burden of enteric and diarrheal diseases in these countries, we will expand our initiatives to include surveillance of additional pathogens (such as Cryptosporidium) and to build laboratory capacity in developing countries.