VIDA Case Control

Related studies

GEMS1 Case Control Study
VIDA HUCS Gambia Mali Survey
VIDA HUCS Kenya Survey

Background: Despite considerable progress in reducing diarrhea-related mortality over the past two decades, diarrheal diseases remain the second leading cause of post-neonatal death during the first 5 years of life in developing countries. As further declines are made possible by expanding interventions that target the principal causes of severe disease, the availability of accurate, up-to-date assessments at the country level are essential to guide strategic planning and resource allocation.

During the next few years, rotavirus vaccines are expected to be introduced into routine infant immunization programs across low-income countries, and marked reductions in child deaths and hospitalizations from rotavirus diarrhea are anticipated. However, the impact of vaccine introduction on the epidemiology of diarrheal diseases will likely extend beyond changes in rotavirus-associated morbidity and mortality alone; shifts in the predominant pathogens and adverse outcomes associated with moderate-to-severe diarrhea (MSD) are also expected.

Objectives:

To assess the impact of rotavirus vaccine introduction on the:

Etiology of MSD, by comparing the number and proportion of MSD cases with specific pathogens before rotavirus vaccine introduction (i.e., during GEMS) and in the study period, as well as comparing adjusted pathogen-specific incidence and attributable fraction
Adverse clinical consequences of MSD, measured as the linear growth attainment and mortality during a 2-3 month follow-up period after study enrollment
Overall incidence of MSD
As an exploratory objective, diarrhea- associated under-5 mortality in the DSS population measured using verbal autopsy

To provide a well-characterized library of stool samples for analysis by TaqMan®, a highly sensitive, quantitative molecular assay to more precisely define the pathogen-specific diarrheal disease burden

To determine the effectiveness of a full course of rotavirus vaccine using a case-control study design with two separate control populations: rotavirus test-negative cases with MSD, and matched community controls. Additional information that can be gleaned from the case-control study includes:

Effectiveness of a partial course of rotavirus vaccine
Duration of protection
Presence of protection in children too young to receive vaccine (herd immunity)
Potential risk factors for vaccine failure, including nutritional status, concomitant infection with enteropathogens that may modulate the immune system or the expression of diarrheal symptoms, such as Giardia, soil helminths, and H. pylori

To test whether genetic mutations in histo-blood group antigens FUT2 (secretor) and FUT3 (Lewis) are associated with an increased risk of moderate-to-severe rotavirus diarrhea, among vaccinated children

Methodology:

Geographic Location/Study Sites: This study was conducted in three GEMS sites in sub-Saharan Africa- Bamako, Mali; Basse, The Gambia, and Siaya County, Kenya- that share the observation in GEMS that rotavirus is the most important pathogen in during the first 2 years of life. All three countries recently introduced rotavirus vaccine but vary with respect to the vaccine introduced. Mali and The Gambia are using RotaTeq while Kenya introduced Rotarix. The sites all have moderate-to-high under 5 mortality rates, but differ with respect to setting (urban vs. rural), disease burden (rotavirus incidence and MSD-associated mortality rates), co-morbidities that could affect vaccine take (HIV and malaria transmission, malnutrition), and health indicators that might reflect healthcare quality and utilization.

Dates of Data Collection: 2015- 2018

Study Design: Case-Control study

Eligibility Criteria:

Cases: Cases with a new episode (onset after at least 7 diarrhea-free days) of acute diarrhea (≥3 loose stools in 24 hours lasting fewer than 7 days) seeking care at sentinel health care centers at each site were evaluated for MSD. Diarrhea cases with one of the following criteria were considered to be MSD: 1) sunken eyes, 2) loss of skin turgor, 3) intravenous hydration prescribed, 4) hospitalization recommended, or 5) dysentery. MSD cases were enrolled in 3 age strata: 0-11, 12-23, and 24-59 months.

Controls: One to three matched diarrhea-free controls were identified through the Demographic Surveillance System at each site and enrolled at their homes. Controls were matched by residence (same or nearby village or community), sex, age group, and time (enrolled within 14 days of case enrollment).

Data Collection: Data was collected at enrollment and at a 60-day follow-up visit.

Enrollment visit: Demographic factors including child's age, household size and composition, cooking fuel, access to improved water and sanitation, household possessions, household construction, parental educational attainment, breastfeeding, anthropometric measurements, vaccination information. A single, fresh, whole stool specimen was collected from both cases and controls at enrollment. A saliva sample was collected from eligible VIDA cases and their matched controls. Diarrheal history, physical examination, and visit outcome data was collected only for cases.
60-day follow-up visit: Standardized questionnaire to ascertain the vital status and health of the child- child's axillary temperature, anthropometric measurements; standardized observations about water and sanitation facilities.

Study Documentation:

Case report forms:

CRF 02 Registration for cases
CRF 03G Eligibility for cases
CRF 03M Eligibility for cases
CRF04A Enrollment cases history
CRF04B Enrollment cases medical
CRF05 60 day follow up cases and controls
CRF06 Control eligibility
CRF07 Control enrollment
CRF09 Memory aid score sheet
CRF11 Stool collection
CRF15 Stool accession
CRF16 Stool culture
CRF17 E. coli PCR
CRF18 Protozoan and viral immunoassays
CRF19 RT-PCR for viruses

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.

Acknowledgements: We wish to express our deep gratitude to the families who participated in these studies, the clinical and field staff for their exceptional hard work and dedication, and to the physicians, administration, and health officials at every site who generously provided facilities and support for the conduct of the study. We are grateful to Catherine Johnson at the Emmes Company, LLC for expert data management and reporting. Special thanks go to Carl Kirkwood, Duncan Steele, and Anita Zaidi at the Bill & Melinda Gates Foundation for helpful oversight, Kathy Neuzil for thoughtful suggestions, and to the following members of our International Scientific Advisory Committee for providing insightful comments and guidance: Janet Wittes (Chair), George Armah, John Clemens, Christopher Duggan, Stephane Helleringer, Ali Mokdad, James Nataro, and Halvor Sommerfelt. This supplement is sponsored by the Center for Vaccine Development and Global Health (CVD) at the University of Maryland School of Medicine, Baltimore (UMB).

Financial Support: The VIDA study was funded by the Bill & Melinda Gates Foundation.

Ethics Statement: Approval was granted by the ethics committees at each institution: University of Maryland School of Medicine, Baltimore, MD, USA; Medical Research Council Unit, The Gambia at the London School of Hygiene & Tropical Medicine, Banjul, The Gambia; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya; Centre pour le Développement des Vaccins du Mali (CVD-Mali), Bamako, Mali.

Last Updated: October 17, 2022The Vaccine Impact on Diarrhea in Africa (VIDA) is a prospective, case control study to assess the causes and burden of diarrhea in children under five and determine the effectiveness of rotavirus vaccine at three sites in sub-Saharan Africa. Each site recruited moderate-to-severe diarrheal cases enrolled in three age strata from Sentinel Health Centres within the demographic surveillance system (DSS). One to three diarrhea-free controls were enrolled within two weeks of the case and were matched on age, gender, and residential area. Participants were assessed at enrollment and at a 60-day follow-up visit.