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Background: The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. Methods: In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. Results: Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12–2.17), as well as cows (RR, 1.61; 95% CI, 1.16–2.24) and sheep (RR, 1.48; 95% CI, 1.11–1.96) living in the compound, were associated with Shiga toxin–producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15–1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. Conclusions: Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children. We assessed survey-based water, sanitation, and animal factors associated with enteric pathogens in cases of moderate to severe diarrhea and controls. Animals, cows and sheep (cases) and fowl (controls), were associated with bacterial carriage; surface water was associated with bacteria and protozoa in controls. [ABSTRACT FROM AUTHOR]

Background: As part of the Vaccine Impact on Diarrhea in Africa (VIDA) Study, we examined the prevalence, clinical presentation, and seasonality of Cryptosporidium in children to understand its relative burden after the introduction of rotavirus vaccine. Methods: VIDA was a 3-year, age-stratified, matched case-control study of medically attended acute moderate-to-severe diarrhea (MSD) in children aged 0–59 months residing in censused populations at sites in Kenya, Mali, and The Gambia. Clinical and epidemiologic data were collected at enrollment, and a stool sample was tested for enteropathogens by quantitative PCR. An algorithm was created based on the organism's cycle threshold (Ct) and association with MSD to identify the subset of Cryptosporidium PCR-positive (Ct <35) cases most likely to be attributed to MSD. Clinical outcomes were assessed at 2–3 months after enrollment. Results: One thousand one hundred six (22.9%) cases of MSD and 873 controls (18.1%) were PCR positive for Cryptosporidium; 465 cases (42.0%) were considered attributable to Cryptosporidium, mostly among children 6–23 months. Cryptosporidium infections peaked in The Gambia and Mali during the rainy season, while in Kenya they did not have clear seasonality. Compared with cases with watery MSD who had a negative PCR for Cryptosporidium, cases with watery MSD attributed to Cryptosporidium were less frequently dehydrated but appeared more severely ill using a modified Vesikari scale (38.1% vs 27.0%; P < 0.001), likely due to higher rates of hospitalization and intravenous fluid administration, higher prevalence of being wasted or very thin very thin (23.4% vs 14.7%; P < 0.001), and having severe acute malnutrition (midupper arm circumference <115 mm, 7.7% vs 2.5%; P < 0.001). On follow-up, Cryptosporidium-attributed cases had more prolonged and persistent episodes (43.2% vs 32.7%; P <0.001) and linear growth faltering (change in height-for-age z score between enrollment and follow-up: −0.29 vs −0.17; P < 0.001). Conclusions: The burden of Cryptosporidium remains high among young children in sub-Saharan Africa. Its propensity to cause illness and further impact children longer term by compromising nutritional status early in life calls for special attention to enable appropriate management of clinical and nutritional consequences. The burden of Cryptosporidium remains high among young children in sub-Saharan Africa. Its propensity to cause illness and further impact children longer term by compromising nutritional status early in life necessitates appropriate management of clinical and nutritional consequences. [ABSTRACT FROM AUTHOR]

Background: Diarrheal disease is heterogeneous, including watery diarrhea (WD) and dysentery, some cases of which become persistent diarrhea (PD). Changes in risk over time necessitate updated knowledge of these syndromes in sub-Saharan Africa. Methods: The Vaccine Impact on Diarrhea in Africa (VIDA) study was an age-stratified, case-control study of moderate-to-severe diarrhea among children <5 years old in The Gambia, Mali, and Kenya (2015–2018). We analyzed cases with follow-up of about 60 days after enrollment to detect PD (lasting ≥14 days), examined the features of WD and dysentery, and examined determinants for progression to and sequelae from PD. Data were compared with those from the Global Enteric Multicenter Study (GEMS) to detect temporal changes. Etiology was assessed from stool samples using pathogen attributable fractions (AFs), and predictors were assessed using χ2 tests or multivariate regression, where appropriate. Results: Among 4606 children with moderate-to-severe diarrhea, 3895 (84.6%) had WD and 711 (15.4%) had dysentery. PD was more frequent among infants (11.3%) than in children 12–23 months (9.9%) or 24–59 months (7.3%), P =.001 and higher in Kenya (15.5%) than in The Gambia (9.3%) or Mali (4.3%), P <.001; the frequencies were similar among children with WD (9.7%) and those with dysentery (9.4%). Compared to children not treated with antibiotics, those who received antibiotics had a lower frequency of PD overall (7.4% vs 10.1%, P =.01), and particularly among those with WD (6.3% vs 10.0%; P =.01) but not among children with dysentery (8.5% vs 11.0%; P =.27). For those with watery PD, Cryptosporidium and norovirus had the highest AFs among infants (0.16 and 0.12, respectively), while Shigella had the highest AF (0.25) in older children. The odds of PD decreased significantly over time in Mali and Kenya while increasing significantly in The Gambia. Conclusions: The burden of PD endures in sub-Saharan Africa, with nearly 10% of episodes of WD and dysentery becoming persistent. This report updates our knowledge of the risk factors and etiology associated with persistent diarrhea and dysentery. We demonstrate that both persistent and bloody diarrhea remain serious problems with distinct etiology, presentation, and outcomes among sub-Saharan African infants. [ABSTRACT FROM AUTHOR]

Background: Studies conducted before rotavirus vaccine introduction found that moderate-to-severe diarrhea (MSD) in children aged <5 years was associated with stunting at follow-up. It is unknown whether the reduction in rotavirus-associated MSD following vaccine introduction decreased the risk of stunting. Methods: The Global Enteric Multicenter Study (GEMS) and the Vaccine Impact on Diarrhea in Africa (VIDA) study, two comparable matched case-control studies, were conducted during 2007–2011 and 2015–2018, respectively. We analyzed data from 3 African sites where rotavirus vaccine was introduced after GEMS and before starting VIDA. Children with acute MSD (<7 days onset) were enrolled from a health center and children without MSD (diarrhea-free for ≥7 days) were enrolled at home within 14 days of the index MSD case. The odds of being stunted at a follow-up visit 2–3 months after enrollment for an episode of MSD was compared between GEMS and VIDA using mixed-effects logistic regression models controlling for age, sex, study site, and socioeconomic status. Results: We analyzed data from 8808 children from GEMS and 10 579 from VIDA. Among those who were not stunted at enrollment in GEMS, 8.6% with MSD and 6.4% without MSD became stunted during the follow-up period. In VIDA, 8.0% with MSD and 5.5% children without MSD developed stunting. An episode of MSD was associated with higher odds of being stunted at follow-up compared with children without MSD in both studies (adjusted odds ratio [aOR], 1.31; 95% confidence interval [CI]: 1.04–1.64 in GEMS and aOR, 1.30; 95% CI: 1.04–1.61 in VIDA). However, the magnitude of association was not significantly different between GEMS and VIDA (P =.965). Conclusions: The association of MSD with subsequent stunting among children aged <5 years in sub-Saharan Africa did not change after rotavirus vaccine introduction. Focused strategies are needed for prevention of specific diarrheal pathogens that cause childhood stunting. Despite reductions in the attributable burden of rotavirus following vaccine introduction, the association between moderate to severe diarrhea and stunting at a 2–3 month follow-up did not change between studies conducted before and after rotavirus vaccine introduction at 3 sub-Saharan African sites. [ABSTRACT FROM AUTHOR]