Cases of MSD were identified in SHCs (hospital, urgent care facilities, and community clinics) to capture those illnesses that are most severe and that collectively constitute a significant cost in healthcare services, and thus would be targeted for prevention by vaccines and other interventions (Figure 1). GEMS staff were situated in the intake area at each SHC to complete a registration log documenting each visit made by a child 0–59 months old belonging to the DSS. The GEMS registrar was given access to the DSS database to verify that a child belonged to the DSS, and to record each enrolled child's unique DSS number as a means for determining, at a later date, who was enrolled into GEMS more than once. Each visit was assigned a unique screening identification number, and the registrar recorded the date and time the child entered the SHC; the child's age, sex, and village/neighborhood; whether the child had diarrhea; and whether the child was hospitalized. The GEMS registrar referred all children from the DSS who were aged 0–59 months and had diarrhea to a GEMS clinician. The clinician informed the parent/primary caretaker about the study, determined the child's eligibility (Table 2), and obtained informed consent. If an eligible child was not enrolled, the reasons for nonenrollment were documented (eg, refusal, missed opportunity, stool sample inadequate or not obtained, 14-day quota filled, or child died before enrollment).

Inclusion Criteria for Cases

1. Child is 0–59 mo of age
2. Child belongs to the demographic surveillance system population at the site
3. Child is not currently enrolled as a case (meaning previously enrolled and pending 60-day visit)a
4. Child meets case definition of diarrhea (≥3 abnormally loose stools in the previous 24 h)
5. Diarrhea episode is:  • Acute (onset within 7 d of study enrollment) and  • Represents a new episode (onset after ≥7 diarrhea-free days) [23 (link), 24 (link)]
6. Diarrhea is moderate-to-severe, meaning that the child met at least 1 of the following criteria: • Sunken eyes, confirmed by parent/primary caretaker as more than normal • Loss of skin turgor (determined by abdominal skin pinch (slow return [≤2 s] or very slow return [>2 s]) • Intravenous rehydration administered or prescribed • Dysentery (visible blood in a loose stool) • Hospitalized with diarrhea or dysentery

a A child was eligible to be enrolled as a case irrespective of whether he or she had been included as a case or as a control previously; whereas cases were eligible for reenrollment only after the 60-day follow-up visit had been completed, controls could be enrolled as a case at any time they met the criteria.

Flow diagram illustrating major study activities. Abbreviations: DSS, demographic surveillance system; SHC, sentinel health center; HUAS, Health Care Utilization and Attitudes Survey.

Each site aimed to enroll approximately 220 MSD patients per year into each of 3 age strata: 0–11 months, 12–23 months, and 24–59 months, totaling 1980 cases over 3 years. To ensure even sampling throughout the year, the target was to enroll approximately 8–9 cases per age stratum (25–26 cases overall) per fortnight. This strategy prevented the strata from being filled prematurely in seasons with high volume and respected the capacity limitations of the clinical and microbiology personnel, but because all DSS children with MSD were recorded, temporal increases in the case load of MSD and of specific diarrheal pathogens could be measured. Analyses for events that might have seasonal variation will take into account the sampling fraction of MSD for each period.