The incidence, aetiology, and adverse clinical consequences of less severe diarrhoeal episodes among infants and children residing in low-income and middle-income countries: a 12-month case-control study as a follow-on to the Global Enteric Multicenter Study (GEMS)

Abstract

Summary Background Diarrheal diseases remain a leading cause of illness and death among children younger than 5 years in low-income and middle-income countries. The Global Enteric Multicenter Study (GEMS) has described the incidence, aetiology, and sequelae of medically attended moderate-to-severe diarrhoea (MSD) among children aged 0–59 months residing in censused populations in sub-Saharan Africa and south Asia, where most child deaths occur. To further characterise this disease burden and guide interventions, we extended this study to include children with episodes of less-severe diarrhoea (LSD) seeking care at health centres serving six GEMS sites. Methods We report a 1-year, multisite, age-stratified, matched case-control study following on to the GEMS study. Six sites (Bamako, Mali; Manhiça, Mozambique; Basse, The Gambia; Mirzapur, Bangladesh; Kolkata, India; and Bin Qasim Town, Karachi, Pakistan) participated in this study. Children aged 0–59 months at each site who sought care at a sentinel hospital or health centre during a 12-month period were screened for diarrhoea. New (onset after ≥7 diarrhoea-free days) and acute (onset within the previous 7 days) episodes of diarrhoea in children who had sunken eyes, whose skin lost turgor, who received intravenous hydration, who had dysentery, or who were hospitalised were eligible for inclusion as MSD. The remaining new and acute diarrhoea episodes among children who sought care at the same health centres were considered LSD. We aimed to enrol the first eight or nine eligible children with MSD and LSD at each site during each fortnight in three age strata: infants (aged 0–11 months), toddlers (aged 12–23 months), and young children (aged 24–59 months). For each included case of MSD or LSD, we enrolled one to three community control children without diarrhoea during the previous 7 days. From patients and controls we collected clinical and epidemiological data, anthropometric measurements, and faecal samples to identify enteropathogens at enrolment, and we performed a follow-up home visit about 60 days later to ascertain vital status, clinical outcome, and interval growth. Primary outcomes were to characterise, for MSD and LSD, the pathogen-specific attributable risk and population-based incidence values, and to assess the frequency of adverse clinical consequences associated with these two diarrhoeal syndromes. Findings From Oct 31, 2011, to Nov 14, 2012, we recruited 2368 children with MSD, 3174 with LSD, and one to three randomly selected community control children without diarrhoea matched to cases with MSD (n=3597) or LSD (n=4236). Weighted adjusted population attributable fractions showed that most attributable cases of MSD and LSD were due to rotavirus, Cryptosporidium spp, enterotoxigenic Escherichia coli encoding heat-stable toxin (with or without genes encoding heat-labile enterotoxin), and Shigella ...

Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: Evidence from the Global Enteric Multicenter Study

“…Sentinel hospitals and health centers (including both primary care and referral facilities) were selected which provided care to the largest number of children with diarrhea in each study region, and which offered appropriate infrastructure for computerized data management, secure freezer storage, at least intermittent internet access, the ability to ship specimens abroad, and laboratory capacity to perform coprocultures, antigen-detection tests, and nucleic acid-based assays. The design, procedures, and primary outcomes of GEMS have been reported previously [14][15][16]18]. Briefly, all children seeking care at sentinel hospitals and health centers were screened for diarrhea, defined as �3 loose stools in the preceding 24 hours; cases were considered eligible if newly-onset (within the preceding 7 days) and acute (preceded by �7 diarrhea-free days) illness was reported.…”

“…The Global Enteric Multicenter Study (GEMS) [14][15][16][17] was undertaken before rotavirus vaccine implementation in seven LMICs across sub-Saharan Africa and South Asia to determine the burden and etiology of diarrhea among children under five years old in these settings.…”

Postbiotics against Pathogens Commonly Involved in Pediatric Infectious Diseases

“…Infection with pathogenic strains of E. coli is one of the most common etiological agents of moderate-to-severe diarrhea in low-income countries and is considered a significant public health problem [ 84 , 85 ]. Accumulated evidence from in vitro studies supports the use of postbiotics for the protection against infectious diseases.…”

Enterotoxigenic Escherichia coli Heat-Stable Toxin Increases the Rate of Zinc Release from Metallothionein and Is a Zinc- and Iron-Binding Peptide

“…ETECs are classified as LT only, ST only, or LT and ST double positive. ETECs producing any combination of these toxins can cause secretory diarrhea in humans (3); however, ST-producing ETECs are one of the top four pathogens in children aged 0 to 60 months with moderate to severe diarrhea (MSD) (4,5) and one of the top two pathogens in children aged 0 to 60 months with less severe diarrhea (LSD) (6). Despite progress, there are currently no licensed ETEC vaccines.…”