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 eliminate the gap in mortality from enteric and diarrheal diseases between developed and developing countries and to significantly reduce impaired development associated with these diseases in children under age 5.

The Challenge

At A Glance

Enteric and diarrheal diseases kill nearly 1 million children under age 5 each year, primarily in the developing world.

These diseases can also cause malnutrition, which can lead to stunted growth and impaired cognitive development as well as other long-term health problems.

Vaccines are a cost-effective way to protect infants from infection by specific pathogens and, together with other interventions such as oral rehydration therapy and micronutrient supplements, to prevent deaths from enteric diseases.

We use a combination of approaches to protect children from infection, including improved water quality, sanitation, and hygiene and exclusive breastfeeding in the first six months of life.

Our Enteric and Diarrheal Diseases strategy, updated in 2012, 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 nearly 1 million children under age 5 each year. For those who survive these illnesses—which are transmitted through the fecal-oral route and include rotavirus, cholera, and typhoid—repeated episodes of severe diarrhea in the early years of life can lead to serious, lifelong health problems.
 
Diseases from enteric infections can lead to malnutrition, 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 number and complexity 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 due to high cost, limited availability, and poor marketing.

The Opportunity

In the developed world, advances in clean water and safe sanitation, the availability of antibiotics, adequate nutrition, and widespread use of vaccines have contributed to a dramatic drop in deaths due to diarrheal diseases. These same approaches and tools can be used to prevent and treat these diseases in children who live in poorer countries.

A woman collects water in rural Mozambique.

Safe and effective vaccines exist for rotavirus, cholera, and typhoid. WHO has recommended that rotavirus vaccine be included in all national immunization plans. The GAVI Alliance, a public-private partnership that funds vaccines for children in the poorest countries, plans to expand use of the rotavirus vaccine to about 40 countries by 2015, which could save 2.46 million lives by 2030. New vaccines are in development that could increase supplies and expand the rotavirus vaccine market in the next several years. The cholera vaccine Shanchol was licensed in India and prequalified by WHO in 2011. Multiple typhoid vaccines are in development, as are a combined typhoid and paratyphoid vaccine and vaccines against enterotoxigenic E. coli (ETEC) and Shigella.

Low-cost interventions are available to help prevent infection and death from acute diarrhea in young children, including oral rehydration solution (ORS), Vitamin A and zinc supplements, exclusive breastfeeding in the first six months of life, improved personal and household hygiene, and access to safe water and better sanitation.

Our Strategy

A health worker holds a newborn at the Ujiarpur Primary Health Centre in the Indian state of Bihar.

Because enteric and diarrheal diseases are caused by multiple pathogens—and vaccines exist for only a limited number of these—we use a combination of approaches to protect children from infection. Improved water, sanitation, and hygiene and exclusive breastfeeding in the first six months of life can help protect children against most enteric diseases, and vaccines are a cost-effective way to prevent severe illness and death. Quick treatment of infected children is essential, using proven therapeutics including ORS and zinc.

We support research into the underlying factors that contribute to intestinal disease and damage, which in turn can lead to malnutrition, impaired development, and death. We also work to better understand 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. Our strategy also calls for working with international children’s health organizations to ensure that countries, donors, and partners focus sufficient resources and coordinate efforts to address enteric and diarrheal diseases.

Areas of Focus

Rotavirus

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.

Therapeutics

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.

Typhoid

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

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.

Environmental Enteric Dysfunction (Gut Dysfunction)

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

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.

Monitoring and Surveillance

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.

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