Abstract
Given the challenges in accurately identifying unexposed controls in case-control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within 'control' children (0-59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea ('MSD pathogens') in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and 'any' (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case-control studies examining diarrhoea.
Highlights
Over 1.7 billion children are affected each year by diarrhoea [1], an important – yet complex – health condition
Of the 2534 controls in the Global Enteric Multicenter Study (GEMS) Kenya site with follow-up during the acceptable window, 2384 (94%) had a completed memory aid for diarrhoea recall; we excluded from further analysis the 150 (6%) who did not (Table S1a)
At least one moderate-to-severe diarrhoea (MSD) enteric pathogen was detected in 460 stool specimens collected from controls at enrolment (19%); detection rates decreased by age group (Table 1)
Summary
Over 1.7 billion children are affected each year by diarrhoea [1], an important – yet complex – health condition. Even the most detailed studies fail to identify the aetiologic agent in all cases, but clinical and laboratory data exist to estimate pathogen-specific disease burdens. Diarrhoea can be caused by various infectious agents – bacteria, viruses, protozoa and soil-transmitted helminths – that differ in their relative contribution to diarrhoeal morbidity and mortality [3,4,5]. These organisms vary in their incubation period, the probability with which symptoms occur following exposure, and the duration during which the organism is excreted in faeces after symptoms resolve [6]. During epidemiologic studies of diarrhoeal diseases, these variations make it difficult to accurately identify unexposed controls and to identify the precise cause of acute symptoms when multiple pathogens are identified in stool testing
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