Enteropathogen-specific pathways linking moderate-to-severe diarrhea to linear growth faltering in sub-Saharan African children: a decomposition analysis of the GEMS study

BACKGROUND: Associations exist between moderate-to-severe diarrhea (MSD) and growth faltering in children; however, the underlying mechanisms are not well-understood. We evaluated the extent to which seven enteropathogens explain the association between MSD and linear growth faltering in children from sub-Saharan Africa. METHODS: We conducted a pathway decomposition analysis using data from 20,695 children from the Global Enteric Multicenter Study (GEMS), with 8,382 MSD cases and 12,313 controls. Seven pathogens were assessed as possible explanatory variables for the MSD-growth association. RESULTS: Two pathogens significantly explained the MSD-growth association: ETEC (27.0%, p<0.001) and Cryptosporidium (42.8%, p<0.001). Shigella (71.7%, p=0.063) and Adenovirus (80.5%, p=0.067) showed potential but imprecise effects. Rotavirus did not explain linear growth (28.2%, p=0.243) but strongly explained weight-related outcomes (WAZ: 119.1%; WHZ: 79.7%). CONCLUSION: The MSD-growth association was explained by ETEC and Cryptosporidium. Rotavirus explained weight-related outcomes but not linear growth. Growth benefits associated with rotavirus vaccination may operate through prevention of acute wasting rather than stunting.