Enteric dysfunction and enteropathogens among hospitalized south Asian and sub-Saharan African children

Enteropathogens and enteric dysfunction (ED) among acutely ill children in low-and-middle income countries (LMICs) may contribute to poor post-discharge outcomes. Enteropathogen prevalence and fecal ED biomarkers (myeloperoxidase, calprotectin, α-1-antitrypsin) from children aged 2–23 months hospitalized at nine LMIC facilities (n = 811) were compared to community children (n = 248). Host and pathogen correlates of ED biomarkers were identified through crude and adjusted linear mixed effect models, and Cox-proportional hazard models assessed ED biomarker associations with mortality in the 30-days following admission and 180-days following discharge. Invasive enteropathogens were more prevalent at admission (69%) than discharge (60% p < 0.001) or among community children (61% p = 0.004). Among the biomarkers, myeloperoxidase was higher at admission (2290 ng/ml interquartile range [IQR]: 868 6052 p = 0.014) and lower at discharge (1380 ng/ml IQR: 611 3193 p < 0.001) compared to community children (2268 ng/ml IQR: 1051 5421) while calprotectin was similar at admission (215 ug/ml IQR: 77 746 p = 0.351) but lower at discharge (170 ug/ml IQR: 68 369 p = 0.007) when compared the community children (252 ug/ml IQR: 124 691). α-1-antitrypsin concentrations were lower at admission (121 mg/l IQR: 49 303 p = 0.049) compared to the community (201 mg/ml IQR: 100 412) but more comparable at discharge (144 mg/ml IQR: 69 275 p = 0.380). Admission myeloperoxidase and calprotectin concentrations were associated with invasive enteropathogens detection (respectively p = 0.003 and p = 0.002) and lower MUAC (respectively p = 0.002 and p = 0.012) while admission α-1-antitrypsin was associated with breastfeeding diarrhea malaria and pneumonia (all p < 0.05). The only ED biomarker associated with mortality after confounder adjustment was fecal calprotectin (hazard ratio: 1.36 95% CI:1.07 1.72 p = 0.011) at discharge. Enteric inflammation biomarker concentrations and enteropathogen prevalence were high at hospital admission but by discharge were lower than among community peers. Interventions to prevent re-colonization with enteropathogens and increased enteric inflammation may improve child health in the post discharge period.