Acquisition and clearance of enteric pathogens in children under 5 years of age in Kigali and Musanze, Rwanda, 2022: A longitudinal cohort study.

Objectives: Reducing diarrhea and stunting due to enteric infections requires an understanding of pathogen acquisition and clearance. This longitudinal study analyzed the dynamics of enteric infections among children in two study sites in Rwanda in 2022.

Methods: Children with diarrhea were enrolled at two study sites (60 at each site; mean age 18.7 [SE=1.11] months, 48% girls), one near the capital Kigali, and one in a northern rural district (Musanze). Rectal swab samples were collected at inclusion and monthly intervals during five months of follow-up, and additionally in case of diarrhea, and were analyzed by real-time PCR for a broad panel of diarrheagenic pathogens.

Results: During follow-up, acquisition of bacteria was very common, corresponding to 1.86 (CI 1.52-2.23) new ETEC-eltB and 1.24 (CI 0.96-1.57) new Shigella/EIEC detections per year per child, and bacterial infections were significantly more common in Musanze (ratio 1.24, P=0.0001), but the acquired infections rarely caused diarrhea. Most viruses (78-100%) and bacteria (47-86%) were cleared before the next sampling time point. Diarrhea was significantly associated with rotavirus (OR 7.24, P<0.0001), despite a high rotavirus vaccination coverage, and with enterotoxigenic Escherichia coli (ETEC) -estA (OR 3.84, P<0.0001), ETEC-eltB (OR1.99, P=0.001), and norovirus genogroup II (OR=2.74, P=0.0004). Detection of Campylobacter at baseline and follow-up correlated (P=0.005), indicating maintained exposure.

Conclusions: New enteric infections were very common, in particular in rural areas, but rarely caused diarrhea and most infections were effectively cleared. The findings show that heavy pathogen exposure rather than persistent infections explain the high prevalence of enteric infections among children in poor countries. Rotavirus remains a significant cause of diarrhea a decade after vaccine introduction, indicating that vaccination mainly protects against severe symptoms and less against infection with no or moderate symptoms.