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Global Enteric Multicenter Study (GEMS)

GEMS Study Pinpoints Main Causes of Childhood Diarrheal Diseases, Suggests Effective Solutions

The Global Enteric Multicenter Study (GEMS) is the largest, most comprehensive study of childhood diarrheal diseases ever conducted in developing country settings. Globally, diarrheal diseases are the second leading cause of death among children under five, despite the existence of effective interventions, such as oral rehydration solutions (ORS) and zinc supplements as general treatments. Many different bacteria, viruses and other pathogens can cause diarrheal disease.

However, it has been difficult to prioritize and target interventions because previous studies cannot be easily compared or combined due to differences and limitations in the methods used. By studying more than 22,000 children (9,439 cases and 13,129 controls) across two continents with consistent methods, GEMS provides important, new data that will help researchers, policymakers, donors and advocates make evidence-based decisions to help to reduce the global burden of diarrheal diseases.

News Release | Fact Sheet | Country Specific-Fact Sheets | Infographic | Clinical Infectious Diseases Supplement

Study Findings

GEMS was a three-year, case-control study conducted at seven sites in Africa and Asia that investigated (1) the cause, (2) the incidence and (3) the impact of moderate-to-severe diarrhea (MSD), which was characterized by severe dehydration, dysentery or hospitalization.

Country-specific results are presented in the accompanying fact sheets.

Key findings across sites published May 2013 in The Lancet include:

1. Cause: Just four pathogens were responsible for the majority of moderate-to-severe diarrhea cases.   To determine the fraction of cases attributable to each pathogen, researchers tested stool samples from children diagnosed with MSD for nearly 40 pathogens and compared them to samples from age- and gender-matched control children.

  • Rotavirus, for which a vaccine already exists, was the leading cause of MSD during infancy (0-11 months of age) across all study sites. (These vaccines are just now being rolled out in developing countries in Asia and Africa.)
  • Cryptosporidium, a pathogen not expected to be a major contributor, was found to be the second leading cause of infant MSD at five sites. Shigella, a type of bacteria that invades intestinal cells, was the first or second leading cause of MSD among children 12-59 months of age at most field sites.
  • Shigella, a type of bacteria, was the first or second leading cause of MSD among toddlers at five sites.
  • Enterotoxigenic E. Coli (specifically ST-ETEC) was a significant pathogen in at least one age group at every site.

2. Incidence: Diarrheal disease has a major impact across settings, especially on infants. GEMS researchers estimated the yearly number of new MSD cases (incidence) for each pathogen in the populations of children age 0-11 months, 12-23 months and 24-59 months residing in the field sites in seven study countries.

  • Overall Burden: GEMS estimated roughly 20 episodes of MSD each year per 100 children under the age of two years. This equates to roughly one episode per five children each year.
  • Burden by Age: Among the age groups investigated, infants showed the highest burden of MSD with approximately 30 cases per 100 children each year. Burden by Country: Specific data for each country are included in supplemental fact sheets.
  • Burden by Country: Specific data for each country is included in supplemental fact sheets.

3. Impact: Moderate-to-severe diarrhea had lasting health repercussions even after the initial, acute phase of diarrheal disease.GEMS conducted 60-day follow-up visits to determine the longer-term impact of diarrheal diseases, which is often not measured since it occurs outside the hospital setting. Researchers compared growth, mortality and other indicators between children with MSD and controls.

  • Mortality Risk:
    • Children presenting with a single episode of MSD had a nearly 8.5-fold increase in risk of death over a two-month follow-up period compared to control children without MSD.
    • Notably, 61% of deaths occurred more than one week after children were diagnosed with MSD, when children may no longer be receiving care.
    • 56% of deaths among cases occurred at home, suggesting that earlier studies that focus ed only on deaths occurring in health centers may underestimate the total burden of MSD.
  • Growth Delays: Children with moderate-to-severe diarrhea grew significantly less in length in the two months following their episode compared to age- and gender-matched controls.

Implications for Diarrheal Disease Control

Although GEMS investigated diarrheal diseases in diverse settings, findings were largely consistent across study sites. This suggests that the key takeaways are broadly applicable for driving research and program implementation strategies in other high-burden areas.

These takeaways include:

  • Expanding access to existing tools to prevent and treat diarrhea – particularly rotavirus vaccines – can save a significant number of lives right now.
  • Changing the way diarrheal disease care is delivered to include longer-term monitoring and nutritional rehabilitation could improve child health and survival. In particular, instituting a follow-up visit after the initial treatment, either in a healthcare setting or at home, could dramatically improve health outcomes.
  • Developing new tools that specifically target the GEMS-identified top diarrheal pathogens – particularly Cryptosporidium, for which few interventions currently exist – is essential.

By building upon GEMS findings and infrastructure, researchers can accelerate progress toward reducing the diarrheal disease burden. GEMS established a well-equipped network of laboratories in high-burden areas that are prepared to conduct future studies or roll out diarrheal interventions, and GEMS researchers will provide open access to their data.

Study Sites


Principal Investigator

Myron M Levine M.D., D.T.P.H
"By filling critical gaps in knowledge, we hope GEMS will help countries across these two highest-burden regions focus their efforts to improve child health."

Lead Author

Karen L Kotloff M.D.
"Because children living in poverty in these regions of the world are already fragile, episodes of diarrhea seem to have a very severe impact on their health and well-being."

GEMS: Designed to Address Knowledge Gaps

  • Size: Largest and most in-depth diarrheal disease study to date in developing countries, with 22,568 children enrolled, divided into three age groups (0-11 mo. (infants); 12-23 mo. (toddlers); 24-59 mo.).
  • Scope: Evaluated nearly 40 pathogens to map  each one’s relative contribution to diarrheal disease.
  • Location: Conducted in Africa (The Gambia, Kenya, Mali, Mozambique) and Asia (Pakistan, India and Bangladesh), regions where more than 80% of under-five deaths occur; sites included a mix of moderate and high infant mortality rates, rural and urban settings, and high and low HIV and malaria burdens.
  • Follow-Up: Involved 60-day follow-up visits with all study children to provide new insight on the longer-term impact of diarrheal disease outside the hospital setting.
  • Duration: Lasted three years, to overcome seasonal and annual variations in diarrheal incidence.