The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis

Abstract

Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12,600 analyzable cases and 12,600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467,000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease.

Figure 1.

An infant who presented with diarrheal dehydration consequent to simple gastroenteritis that was not treated promptly or effectively. Loss of turgor of skin over the abdomen is visible as “tenting,” following pinching. Simple gastroenteritis caused by many etiologic agents in young infants in developing countries can lead to dehydration. The fundamental reason is that per kilogram of body weight, the daily water and electrolyte requirements of young infants are substantially greater than those of older children. Thus, abnormal losses from diarrhea, vomiting, and fever, accompanied by inadequate fluid intake and lack of prompt and appropriate replacement (as with glucose/electrolyte oral rehydration solution), can lead to moderate and severe dehydration and death. This photograph was kindly provided by Dr Dipika Sur of the National Institute of Cholera and Enteric Diseases, Kolkata, India.

Figure 2.

Dysentery is diagnosed clinically as the presence of gross blood in diarrheal stools. Dysentery stools can be quite scanty and composed mainly of mucus and blood (shown here). Bacillary dysentery is typically preceded by 18–24 hours of watery diarrhea, accompanied by high fever and toxemia, before the loose stools become scanty and bloody. Dysentery indicates substantial damage to the mucosa of the colon and terminal ileum.

Figure 3.

A Bangladeshi child with cholera is shown who experienced copious purging of rice water stools prior to presenting with severe dehydration. The child, with deeply sunken eyes, is lying on a cholera cot with his watery stools being collected in a bucket for measurement of volume (to guide replacement therapy). After rapid replacement of the child's fluid and electrolyte deficits with intravenous fluids, the health worker is attempting to transition the child to oral rehydration fluids administered by his caretaker, under supervision.