GEMS1 Case Control

Related studies:

GEMS1A Case Control is a follow-on study to the GEMS1 study that included children with less severe diarrhea.
GEMS1 HUAS/HUAS Lite Survey: Three community-based Healthcare Services Utilization and Attitudes Surveys conducted in conjunction with the GEMS1 case control study.
GEMS1A HUAS Lite Survey: Two community-based Healthcare Services Utilization and Attitudes Surveys conducted in conjunction with the GEMS1A case control study.

Background: Globally, diarrheal disease causes one in ten child deaths during the first 5 years of life, resulting in about 800,000 fatalities worldwide annually, most occurring in sub-Saharan Africa and south Asia. Although diarrheal mortality remains unacceptably high, it is decreasing by about 4% per year, whereas disease incidence is declining more modestly. Interventions that target the main causes and focus on the most susceptible children should further accelerate these declines. To guide these efforts, robust data characterising the burden, risk factors, microbiological aetiology, sequelae, and case fatality of most life-threatening and disabling episodes are essential; until now, such data have been scarce in regions with the highest child mortality. The Global Enteric Multicenter Study (GEMS) was created to address these knowledge gaps.

The research consortium involved in the project represents most of the world's major players in vaccine development and the diagnosis and treatment of diarrheal diseases. Institutions and organizations participating in the project included:

Centro de Investigaçao em Saude da Manhiça Manhiça, Mozambique
Medical Research Council, Basse, Gambia
CDC/Kenya Medical Research Institute Research Station, Kisumu, Kenya
Centre pour le Développement des Vaccins du Mali (CVD-Mali), Bamako, Mali
National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India
International Center for Diarrheal Disease Research (ICDDR,B), Mirzapur, Bangladesh
Aga Khan University, Pakistan
Perry Point Veterans Administration Medical Center, Maryland, USA
U.S. Centers for Disease Control and Prevention
The University of Chile
The University of Virginia School of Medicine
The International Vaccine Institute in Seoul, Korea
The Institut Pasteur in Paris, France
The World Health Organization
The Center for International Health at the University of Bergen and the Institute of Public Health, Norway
The University of Goteborg, Sweden
Rollins School of Public Health at Emory University, Atlanta, USA
The Johns Hopkins University Bloomberg School of Public Health, Maryland, USA

Objectives: The major goal of this project was to conduct a multi-center study to quantify the burden and identify the microbiologic etiology of severe diarrheal disease among children 0-59 months of age living in developing countries in two global regions- Africa and Asia. The study was conducted at seven experienced and well-characterized sites using a common research protocol of rigorous epidemiologic and microbiologic design, to address limitations of previous studies and to satisfy contemporary needs for information.

The ultimate goal is to provide data needed to guide development and implementation of enteric vaccines and other public health interventions that can diminish morbidity and mortality from diarrheal diseases.

The following specific objectives were designed to achieve this overriding goal:

To quantify the burden and adverse clinical consequences of severe diarrheal disease and to identify the microbiologic etiology according to age stratum (0-11 months, 12-23 months, 24-59 months) and clinical syndrome at each individual site, in each region, and across all sites.
To characterize the phenotype and/or genotype distribution of major enteric pathogens.
To prepare an evidence-based assessment (based on disease burden, economic analysis, and public perception) of the financial costs, both public and private, of diarrheal disease caused by major indicated pathogens, by country and by region, among children 0-59 months of age, and the public demand for an intervention.
To archive and store the well-characterized clinical specimens and isolated etiologic agents so that they can be accessed in the future for research and technology development.

Methodology:

Study Sites: The GEMS1 study was conducted at seven sites in Africa and Asia (Bangladesh, India, Kenya, Mali, Mozambique, Pakistan, The Gambia), representing developing countries with moderate or high infant mortality rates; rural or urban settings; and high or low HIV and malaria prevalences.

Dates of Data Collection: Dec 1, 2007 to March 3, 2011

Study Design: Prospective, multi-center, case-control study

Eligibility Criteria: Each site recruited up to 880 children with severe diarrhea from hospitals or ambulatory facilities and 880 matched community controls in each of three age strata: 0-11 months, 12-23 months and 24-59 months.

Cases: To be included as a case, the episode had to be new (onset after ≥7 diarrhea-free days), acute (onset within the previous 7 days), and fulfil at least one of the following criteria for moderate-to-severe diarrhea:

Sunken eyes (confirmed by parent or caretaker as more than normal)
Loss of skin turgor (abdominal skin pinch with slow or very slow recoil)
Intravenous hydration administered or prescribed
Dysentery (visible blood in loose stools)
Admission to hospital with diarrhoea or dysentery

Controls: Controls were matched to every individual patient with moderate-to-severe diarrhea by age (±2 months for patients aged 0-11 months and 12-23 months, and ±4 months for patients aged 24-59 months), sex, and residence (same or nearby village or neighbourhood as the patient with diarrhea). Controls were randomly selected from the site's DSS database and enrolled within 14 days of the index case. Potential controls who had diarrhea in the previous 7 days were ineligible.

Data Collection: At enrollment, parents or primary caretakers of patients with moderate-to-severe diarrhoea and controls underwent standardized interviews to solicit demographic, epidemiological, and clinical information. The child's length or height was measured. Medical management and clinical condition upon discharge were documented. Fieldworkers made one follow-up visit to every household of every patient with moderate-to-severe diarrhea or control child about 60 days after enrolment to assess the child's vital status, capture interim medical events, and repeat anthropometric measurements. At enrollment, each case and control provided a stool sample.

Study Documentation:

Case Report Forms (CRFs):

CRF_02 Registration Log for Cases
CRF_03 Eligibility for Cases
CRF_04A Enrollment Questionnaire for Cases (Non-Medical)
CRF_04B Enrollment Questionnaire for Cases (Medical)
CRF_05 60-Day Follow-Up Questionnaire for Cases and Controls
CRF_06 Eligibility for Controls
CRF_06 Eligibility for Controls, Revised
CRF_07 Enrollment Questionnaire for Controls
CRF_09 Memory Aid Score Sheet
CRF_11 Stool Collection
CRF_16 Stool Culture Results
CRF_17 E.coli Polymerase Chain Reaction Results
CRF_17A EPEC Polymerase Chain Reaction Results
CRF_18 Protozoal & Viral Immunoassay Results
CRF_19 RT-PCR for Viruses
All CRFs as PDFs in .zip format

ClinEpiDB Data Integration: Data files were provided to ClinEpiDB as SAS files. Variables were processed and redundant or administrative columns were dropped from presentation on ClinEpiDB.org. All dates were obfuscated per participant through the application of a random number algorithm that shifted dates no more than seven days to comply with the ethical conduct of human subjects research. Most microbiology test results are presented as cleaned analytic variables which were defined for convenience in computer programming for analysis. They are No-Yes variables (No if the putative pathogen was not isolated, Yes if it was isolated). The raw test results are also provided as separate variables. If there are questions about variables, the protocol or how data were collected, please contact [e-mail].

Last updated: May 14, 2021
The Global Enteric Multi-Center Study (GEMS) was a prospective, multi-center, case-control study of acute diarrhea in children 0-59 months of age. Each site recruited cases with severe diarrhea from hospitals or ambulatory facilities and up to three matched community controls per case. Participants were assessed at enrollment and at a 60-day follow-up visit.