A new international study published today in The Lancet provides the clearest picture yet of the impact and most common causes of diarrheal diseases, the second leading killer of young children globally, after pneumonia.
The Global Enteric Multicenter Study (GEMS) is the largest study ever conducted on diarrheal diseases in developing countries, enrolling more than 20,000 children from seven sites across Asia and Africa.
GEMS, coordinated by the University of Maryland School of Medicine’s Center for Vaccine Development, confirmed rotavirus – for which a vaccine already exists – as the leading cause of diarrheal disease among infants and identified other top causes for which additional research is urgently needed. GEMS found that approximately one in five children under the age of two suffer from moderate-to-severe diarrhea (MSD) each year, which increased children’s risk of death 8.5-fold and led to stunted growth over a two-month follow-up period.
“Our ability to reduce the burden of diarrheal diseases has always been limited by a lack of understanding of exactly which pathogens cause the most disease,” said Dr. Jahangir Hossain of the Child Survival Theme at the MRC Unit in The Gambia, and GEMS Principal Investigator at The Gambia trial site. “GEMS data serves as a guide on how to reach our goals for reducing this burden and improving child health.”
Despite many causes, GEMS found that targeting just four pathogens could prevent the majority of MSD cases. Expanding access to vaccines for rotavirus, the leading cause of MSD among infants at every site, could save hundreds of thousands of lives. Likewise, GEMS data suggests that accelerating research on vaccines, treatments and diagnostics for the three other leading pathogens – Shigella, Cryptosporidium and ST-ETEC, a type of E. coli – could have a similar impact. Prior to GEMS, Cryptosporidium was not considered a major cause of diarrheal disease and as a result there is currently little research on this pathogen underway.
“The GEMS findings help set priorities for investments that could greatly reduce the burden of childhood diarrheal diseases,” said Dr. Thomas Brewer, deputy director of the Enteric & Diarrheal Diseases team at the Bill & Melinda Gates Foundation, which funded the study. “Vaccines and treatments available today can save thousands of children right now but targeted research to develop new tools to combat severe diarrhea could save many more lives in the future.”
The GEMS findings also suggest that longer-term monitoring and care of children with diarrheal diseases could reduce mortality and developmental delays. Children with MSD grew significantly less in height in the two months following the diarrheal episode when compared with control children without diarrhea, and were 8.5 times more likely to die over the course of the two-month follow-up period. Notably, 61 percent of deaths occurred more than a week after the initial diarrheal episode, with 56 percent of deaths happening after families had returned home from a healthcare facility.
The GEMS study in The Gambia was conducted in Basse through the Medical Research Council. Similar to other sites, rotavirus was the leading cause of MSD in infants – reinforcing the importance of rotavirus vaccines – and Shigella, Cryptosporidium and ST-ETEC were all major contributors. Unlike at other sites, Norovirus GII was the third leading cause of MSD and the overall burden of MSD was greater among toddlers than infants.Linear growth delays were significant among children ages 1-5 years old in the two months following their MSD episode, and a single episode of MSD increased children’s risk of death sevenfold over the same period. In The Gambia, just a small proportion of children with MSD in the community are routinely receiving oral rehydration solution and zinc, which are known to be effective treatments.
“GEMS strongly indicates that follow-up care after the initial diarrheal episode is critical to protect the health and wellbeing of children,” said Professor George Griffin, Senior Co-Chair of the GEMS International Strategic Advisory Committee and Professor at St. George’s, University of London. “By focusing only on the acute diarrhea that brings children to hospitals, we overlook a significant portion of diarrheal diseases’ burden.”
Expanding access to existing interventions that protect against or treat all diarrheal diseases, including oral rehydration solutions, zinc supplements, clean water and sanitation, can save lives and improve the health of children immediately.
“GEMS is a landmark study for the child health community,” said Professor Fred Binka, Co-Chair of the GEMS International Strategic Advisory Committee and Vice-Chancellor at the University of Health and Allied Sciences, Ghana. “By using consistent methods across countries, GEMS sites generated data that can guide evidence-based decision making at both the local and global levels.”
Release of the GEMS findings follows last month’s announcement by the World Health Organization and UNICEF of the first-ever Integrated Global Action Plan for the Prevention and Control of Pneumonia and Diarrhea (GAPPD). The GEMS findings add to the scientific evidence cited in the GAPPD strategy for effectively controlling pneumonia and diarrhea, which together are the two leading causes of death among young children globally.
GEMS, coordinated by the University of Maryland School of Medicine’s Center for Vaccine Development, was a case-control study conducted at seven diverse, high-burden sites in Asia and Africa: The Gambia, Kenya, Mali, Mozambique, Bangladesh, India and Pakistan. The study enrolled 22,568 children under five years of age, a sample size that is large enough to provide comprehensive data on the causes, incidence and impact of the range of diarrheal diseases affecting children around the world.
GEMS established a network of well-equipped laboratories in the study countries that can be used to accelerate future research on diarrhea and other child health priorities. Investigators have provided open access to their data, which can provide baselines for further studies. Supplemental materials on GEMS methods and sub-studies can be found in Clinical Infectious Diseases (volume 55, supplement 4, and December 2012) and the American Journal of Tropical Medicine and Hygiene. Additional analyses of GEMS data are ongoing.
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