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:

We believe that all children—no matter where they live—should not suffer or die from enteric (gastrointestinal) and diarrheal infections.

Our goals are to end diarrheal disease deaths in children under 5 by 2030 and to eliminate typhoid as a public health problem by 2035.

The Challenge

At A Glance

Each year, enteric (gastrointestinal) and diarrheal infections kill about 500,000 children under 5, primarily in the developing world.

Gut pathogens are also associated with growth faltering and 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 microbes.

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 director Anita Zaidi and is part of the foundation’s Global Health Division.

A major cause of death for children in the developing world, enteric and diarrheal diseases kill about 500,000 children under 5 each year. Children who survive face repeated infections by gut pathogens in the early years of their life, which can lead to serious, lifelong health problems. Evidence suggests an association between repeated gut infections and gut dysfunction, which may lead to poor nutrient absorption, weaker immune response to oral vaccines, stunted growth, and impaired cognitive development.

Typhoid fever and its cousin, paratyphoid A fever, are the main causes of bacterial blood infections in children in Southeast Asia; children in many parts of Sub-Saharan Africa also suffer from typhoid. Typhoid stands out as a neglected disease: Children living in densely populated, poor, urban areas with inadequate water and sanitation infrastructure suffer the highest rates of typhoid and paratyphoid fever. Typhoid fever is becoming an even more dangerous public health problem due to rapid and unregulated urbanization in developing countries, combined with the emergence of multidrug-resistant typhoid.

The impact of these diseases has gone largely unnoticed. There remains a lack of adequate research, funding, and political commitment to address these diseases. As a result, we lack critical information about the pathogens (including viruses, bacteria, and parasites) that cause these diseases and about the environmental factors that increase their occurrence.

There are effective and affordable tools for prevention and treatment available, but most do not reach the poorest.

The Opportunity

Over the past 20 years, there has been a significant decline in the number of children under 5 who have died from diarrhea, in part due to socioeconomic development and better access to treatment. However, too many children still die from infections that are entirely preventable or treatable. 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 suffering and death from these diseases.

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

Safe and effective vaccines exist for rotavirus, cholera, and typhoid. WHO has recommended that all national immunization plans include rotavirus vaccine, and Gavi, the Vaccine Alliance, has supported the introduction of the vaccine for low-income countries since 2009. In 2016, ROTAVAC®, a new rotavirus vaccine manufactured by Bharat Biotech, was introduced in India, where the burden of rotavirus is highest, and in 2018 the vaccine was prequalified by WHO. Other new vaccines in development should increase supplies and improve access over the next several years.

The cholera vaccine Shanchol™, manufactured by Shantha, was licensed in India and approved by WHO in 2011. WHO approved Eubiologics’ oral cholera vaccine, Euvichol®, in 2015. Bharat Biotech’s typhoid conjugate vaccine, Typbar TCV® was approved by WHO in 2018 for use in children and adults. Also under development are vaccine candidates for an important diarrheal microbe, Shigella, and additional typhoid conjugate vaccines to prevent against typhoid fever.

Affordable treatments such as oral rehydration solution, zinc supplements, and antibiotics for children with dysentery are available for children suffering from diarrhea. In addition, exclusive breastfeeding in the first six months of life, improved personal and household hygiene, and access to safe water and better sanitation can help children from getting the infection in the first place.

Our Strategy

Our primary focus is to advance the development of safe, affordable, and effective vaccines for the leading causes of diarrheal and enteric diseases in low- and lower-middle-income countries. Our work in vaccines is complemented and enhanced by interventions that target the underlying biological vulnerability of babies and children, work led by the MNCH Discovery & Tools Team. To inform decisions on when and how to deploy new interventions and expand the use of existing ones, we fund research on the global and regional burden of these diseases.

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 want to prevent children from suffering from enteric and diarrheal diseases. Our efforts include investments in vaccines for rotavirus and the leading bacterial causes of diarrheal and enteric disease: Shigella, cholera, and typhoid.

Rotavirus. Rotavirus is the most common cause of diarrheal hospitalizations and deaths in children under 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 in places where diarrhea is a major cause of death among children.

We work closely with Gavi and national governments to support the introduction and sustainable delivery of rotavirus vaccines where they are most needed and to ensure adequate supply and appropriate formulations, packaging, and labeling.

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

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 outbreaks in Guinea, Haiti, Sierra Leone, Zimbabwe, and elsewhere have severely strained these countries’ under-resourced health systems.

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 stockpile in 2013—a key milestone for cholera prevention and control. Millions of doses have been shipped to >20 countries for outbreak, humanitarian crises and endemic use.

Stable vaccine demand should expand supply, lead to more competitive pricing, and spur additional demand in countries with a high burden of cholera. We also support the development of evidence-based policy guidelines for oral cholera vaccine use in outbreak settings, as well as better data collection to build a case for the use of cholera vaccines in endemic areas.

Shigella. Shigella is a ubiquitous bacterial pathogen in most regions of the developing world, where it is a major cause of moderate to severe diarrhea in children under 5. Unlike rotavirus and cholera, there is no vaccine available against Shigella, but we believe it is possible and are investing in vaccine candidates and enabling tools to accelerate the development process.

Typhoid. Typhoid kills about 160,000 people each year, with the highest known burden in South Asia. The burden of typhoid in Africa is also substantial with several recent outbreaks. 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 and vaccine manufacturers to develop a conjugate vaccine that can be used in children under 2 and that will have a longer duration of protection than the current polysaccharide vaccine. In 2015, Bharat Biotech licensed Typbar TCV®, a new typhoid conjugate vaccine for India, and in January 2018 the vaccine was prequalified by WHO and several hundred thousand doses have now been used, including for outbreak control of a super-resistant typhoid strain in Pakistan. We are also exploring more broadly-protective vaccines that, for example, target both typhoid and paratyphoid. Important additional areas of work include understanding transmission dynamics and improving surveillance systems, including leveraging environmental surveillance, to accurately measure the disease burden.

Evidence Generation for Enteric Diseases

We work to generate evidence that can help enhance our understanding of burden, evaluate the impact of interventions, and plan future investment strategies. These efforts include studies to define the burden of diarrheal and enteric disease pathogens and assess the effects of vaccine introductions.

We are supporting several surveillance networks, including global pediatric diarrheal disease surveillance through WHO, typhoid surveillance in South Asia and Africa, and a larger network of foundation-funded sites through the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Advocacy

We work to ensure that child health is a priority nationally and globally, with sufficient funding and political will to increase the 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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