What We Do

Enteric and Diarrheal Diseases

Strategy Overview

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Mothers and infants at the Germana Gale Health Post in Silte, Ethiopia.

our goal:

to end diarrheal disease deaths in children under age 5 in low- and middle-income countries and to significantly reduce the burden of ill health and impaired nutrition due to enteric infections in populations of low- and middle-income countries.

The Challenge

At A Glance

Enteric and diarrheal diseases kill about 550,000 children under age 5 each year, primarily in the developing world.

Enteric pathogens are also associated with growth faltering, which can lead to impaired cognitive development as well as other long-term health problems.

We focus on vaccines as a cost-effective way to protect children from infection by specific pathogens. We also support the delivery of interventions such as oral rehydration therapy and zinc, which can prevent deaths from diarrheal diseases.

We support the goals of the integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD), an effort led by WHO and UNICEF to accelerate disease prevention and control.

Our Enteric and Diarrheal Diseases strategy is led by Anita Zaidi, director, and is part of the foundation’s Global Health Division.

Enteric (gastrointestinal) and diarrheal diseases are a major cause of childhood death in the developing world, killing about 550,000 children under age 5 each year. For those who survive these illnesses, repeated infections by enteric pathogens in the early years of life can lead to serious, lifelong health problems.

Evidence suggests an association between enteric infections and gut dysfunction, which may lead to poor nutrient absorption, weaker immune response to oral vaccines, stunted growth, and impaired cognitive development. This means diminished opportunities and productivity over a lifetime for millions of people.

The impact of these diseases has gone largely unnoticed. UNICEF and the World Health Organization (WHO) achieved some important successes in the 1970s and 1980s through the Diarrheal Diseases Control Program. But there remains a lack of adequate research, funding, and political commitment to address these diseases globally. Key knowledge gaps exist about the mortality and morbidity burden of the pathogens (including viruses, bacteria, and parasites) that cause these diseases and about the environmental factors that increase their incidence.

Some effective interventions and tools are available, but most are not widely used in the developing world.

The Opportunity

Although diarrheal mortality has declined significantly in children under age 5 over the past 20 years, in part because of better access to treatment, half a million children still die each year from diarrheal diseases in developing countries and the incidence of childhood diarrhea in low-income countries has not fallen appreciably. Prevention efforts that focus on vaccines in the short term and improvements in water, sanitation, and hygiene in the long term can significantly reduce both morbidity and mortality from these diseases.

A baby in Sudan receives a dose of rotavirus vaccine. (©PATH/Doune Porter).

Safe and effective vaccines exist for rotavirus and cholera. WHO has recommended that rotavirus vaccine be included in all national immunization plans. By 2015, Gavi, the Vaccine Alliance, and its partners plan to support the introduction of life-saving rotavirus vaccines in more than 30 of the world’s poorest countries. In 2014, a new rotavirus vaccine called ROTAVAC was licensed in India. Other new vaccines that are in development should increase supplies and lower prices via an expanded rotavirus vaccine market in the next several years. The cholera vaccine Shanchol was licensed in India and prequalified by WHO in 2011, and in 2013 a cholera stockpile was established for disbursement of the vaccine for use in epidemic and endemic settings. Several vaccine candidates for enterotoxigenic E. coli (ETEC) and Shigella and a typhoid conjugate vaccine are under development.

Low-cost interventions such as oral rehydration solution (ORS), zinc supplements, and antibiotics for children with dysentery are available to treat children suffering from diarrhea. Other interventions, such as exclusive breastfeeding in the first six months of life, improved personal and household hygiene, and access to safe water and better sanitation, can help protect children from infection in the first place.

Our Strategy

The primary focus of the Bill & Melinda Gates Foundation’s Enteric and Diarrheal Diseases strategy is to advance the development of safe, affordable, and effective vaccines for the leading causes of diarrheal and enteric diseases in low- and middle-income countries. We also invest in research to address improvement in case management and delivery of appropriate treatment to children with diarrhea in high-burden countries, and we support research on the global and regional burden of these diseases to inform decisions on when and how to deploy new interventions and expand the use of existing ones.

Areas of Focus

Enteric Vaccines

Dr. Sushmita Karunashri at work in the Laboratory for Rotavirus Studies at the Christian Medical College (CMC) in Vellore, India, 2013.

Our portfolio focuses heavily on vaccines because we are committed to preventing children from acquiring enteric and diarrheal diseases. Our efforts include investments in vaccines for rotavirus and the leading bacterial causes of enteric and diarrheal disease: ETEC, Shigella, typhoid, and cholera.

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

We work closely with Gavi and national governments to support the introduction and sustainable delivery of rotavirus vaccines (including ROTAVAC) where they are most needed and to ensure adequate supply and appropriate formulations, packaging, and labeling. Our long-term goal is to see rotavirus vaccines introduced in at least 50 low- 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.

ETEC and Shigella. ETEC and Shigella are ubiquitous bacterial pathogens in most regions of the developing world, where they are major causes of moderate-to-severe diarrhea in children under age 5.

Our key partner in the development of new ETEC and Shigella vaccines is the PATH Enteric Vaccine Initiative (EVI). EVI is working on a portfolio of vaccine candidates, with the ultimate goal of a combination vaccine that will be licensed around 2025.

Typhoid. Typhoid kills about 160,000 people each year, with the highest known burden in South Asia. An effective and affordable vaccine is the best short-term solution for controlling typhoid fever in countries with poor access to clean water, sanitation, and hygiene as well as high rates of antibiotic resistance.

We are working with the International Vaccine Institute, the Sabin Vaccine Institute, and vaccine manufacturers to develop a conjugate vaccine that will have a longer duration of protection than the current polysaccharide vaccine and can be used in children under age 2. We are also exploring bivalent vaccine approaches that include paratyphoid vaccine candidates. Better surveillance and diagnostic tools are also needed to understand the true burden of typhoid.

Cholera. Cholera kills as many as 130,000 people each year and occurs in both epidemic and endemic settings. At least 51 countries in Sub-Saharan Africa and Asia have endemic cholera. Several recent epidemics in Zimbabwe, Haiti, Guinea, Sierra Leone, and elsewhere 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.

With our support and the support of other international partners, WHO established a global oral cholera vaccine (OCV) stockpile in 2013—a key milestone for cholera prevention and control. Over the past year, about 1.5 million doses of OCV have been distributed via nine disbursements to the Democratic Republic of the Congo, South Sudan, Guinea, Ethiopia, Haiti, and Nepal. In addition, the Gavi board recently approved a US$115 million investment in OCV for use in epidemic and endemic settings from 2014 to 2018. Stable vaccine demand should expand supply, lead to more competitive pricing, and spur demand in countries with a high burden of cholera.

We invested in the development of Shanchol, an oral cholera vaccine manufactured by Shantha (a Sanofi company) that has been licensed for use and is part of the global stockpile, and we are supporting research on the efficacy of a single dose of Shanchol for use in outbreak settings.

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. 

Treatment Innovations and Delivery

ORS and zinc are effective treatments for acute diarrhea, but use of these essential interventions remains low. In addition, acute diarrhea deaths sometimes occur despite the use of oral rehydration, particularly among younger or malnourished children. The landmark Global Enteric Multicenter Study (GEMS) in seven Sub-Saharan African and South Asian countries showed that children with moderate to severe diarrhea had an 8.5-fold increased risk of death in the two months following the diarrheal episode.

Our treatment strategy focuses on ensuring the availability of existing treatments in the highest-burden countries through advocacy and policy efforts. We also invest in research on improving diarrheal treatment and case management and ways to increase care seeking and use of appropriate therapies. We collaborate with a network of partners to use the research findings to advocate for policy changes related to child health and increased funding to expand the availability of key treatment commodities and delivery systems.

Evidence Generation for Enteric Diseases

We work to generate evidence that can inform our understanding of the burden and impact of enteric diseases and help us evaluate our current work and plan future investment strategies. These efforts include studies to define the burden of diarrheal and enteric disease pathogens and to assess the impact of vaccine introductions on diarrheal diseases. We have made significant investments to provide better data on the causes and consequences of diarrheal diseases in young children in Africa and Asia. In support of these studies, we also invest in the development of advanced diagnostic tools.

We are supporting several surveillance networks, including the African Cholera Surveillance Network (Africhol) and the Typhoid Surveillance in sub-Saharan Africa Program (TSAP) to monitor for specific pathogens. Moving forward, we will work closely to align our surveillance efforts with a larger network of foundation-funded sites through the Sentinel Etiology and Epidemiology (SEED) Network.

Our work also includes support for research on Cryptosporidium, which was found to be a significant cause of moderate to severe diarrhea in the GEMS study in South Asian and African countries. A better understanding of the Cryptosporidium parasite is needed to support the development of appropriate therapeutic and preventive interventions.

We are part of the foundation’s Healthy Birth, Growth, and Development Initiative, which is in the early stages of researching the underlying causes of and potential interventions for environmental enteric dysfunction (EED) and poor growth in children. Poor nutritional absorption in children due to EED can lead to stunted growth, impaired cognitive development, reduced immune response to infection, and death. One of the key foundation investments in this area is the Malnutrition and Enteric Diseases (MAL-ED) Consortium, a multinational and multidisciplinary study that aims to improve scientific understanding of the complex interrelationships among nutrition, enteric infection, gut physiology, immune function, and growth in young children.

Advocacy

We work to ensure that child health is a global priority, with sufficient funding and political will to scale up delivery of vaccines, preventive interventions, and treatments for enteric and diarrheal diseases. Our efforts include supporting the goals of the integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD).

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