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.