What We Do

Enteric and Diarrheal Diseases

Strategy Overview

Print

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. We also focus on understanding how children can grow and thrive, even in the poorest environments. That’s why we also aim to prevent and reverse growth stunting as mediated by environmental enteric dysfunction in children under 5.

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 also support the delivery of oral rehydration solution and zinc, which can treat and 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 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. Globally, 159 million children are stunted, which means they face diminished opportunities and productivity over the course of their lifetime.

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 and cholera. 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. 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. Also under development are several vaccine candidates for important diarrheal microbes, enterotoxigenic E. coli (ETEC) and Shigella, and 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.

Gut health is a rapidly growing area of research, which is helping us better understand how to support healthy physical and neurocognitive development. Research on the gut microbiome, immune system, and gut barrier present promising opportunities to test and develop new interventions to prevent and reverse stunting.

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. We also invest in research to improve case management and delivery of appropriate treatment to children with diarrhea in high-burden countries. And we are exploring new ways to prevent and reverse growth stunting. 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 enteric and diarrheal disease: Shigella, ETEC, 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 China, 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. By the end of 2015, more than 3.3 million doses had been shipped to 10 countries, and the number of requests have increased every year. In addition, the Gavi board approved a US$115 million investment for oral cholera vaccine use in epidemic and endemic settings from 2014 to 2018.

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

Our key partner in the development of new ETEC and Shigella vaccines, the PATH Enteric Vaccine Initiative (EVI), is working on a portfolio of vaccine candidates, with the ultimate goal of advancing a portfolio of vaccine candidates against both pathogens.

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 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. This vaccine is currently under review for WHO prequalification. We are also exploring bivalent vaccines that target both typhoid and paratyphoid. Important additional areas of work include improving surveillance systems to accurately measure the disease burden, and developing an intervention toolkit that incorporates both vaccine and water and sanitation interventions against typhoid.

Treatment Innovations and Delivery

Oral rehydration solution 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, for children with moderate to severe diarrhea, the risk of death increased by eight-and-a-half times in the two months following the diarrheal episode.

Our treatment strategy focuses on ensuring the availability of existing treatments in the highest-burden countries. We invest in research to improve diarrheal treatment and case management. We are also investing in better understanding and addressing under-nutrition as a risk factor for death among children hospitalized with diarrhea. We collaborate with partners to use these research findings to advocate for policy changes and increased funding to expand the availability of key treatment commodities and delivery systems related to child health.

Gut Health

We are focused on understanding the relationship between gut dysfunction and stunting in order to develop new diagnostics, therapies, and nutritional solutions. To this end, we invest in the Malnutrition and Enteric Diseases (MAL-ED) Consortium, a multinational, multidisciplinary study that aims to clarify the complex relationships between nutrition, gut infection, gut physiology, immune function, and growth in the first years of life.

Through another investment, we are addressing a major obstacle in the field by developing a less invasive way of imaging and sampling the small intestine using a capsule with a microscopic camera and biopsy technology.

We also are taking an initial step into therapeutic trials that address stunting by treating underlying gut dysfunction. One strategy aims to use therapeutic foods directed at the gut microbes. Locally sourced foods are being evaluated to see which combinations most effectively grow the good gut bacteria and inhibit the bad bacteria. Our hope is that this will promote healthy growth and development.

All of these efforts are part of the foundation’s broader Healthy Birth, Growth, and Development Initiative, which takes a holistic approach to understanding physical and neurocognitive development, from conception to adolescence.

Evidence Generation for Enteric Diseases

Epidemiology and Burden. 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 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.

Cryptosporidium. We also support research on Cryptosporidium, which was found to be a significant cause of moderate to severe diarrhea in the GEMS study in South Asia and Africa. Our approach is twofold: First, we are investing in research to better understand the epidemiology and health consequences of the Cryptosporidium parasite. Second, we are pursuing drug development by supporting preclinical tools and models and screening existing compound libraries for potential drugs against Cryptosporidium.

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).

Visit Our Blog