Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The global enteric multicenter study

Abstract

Background: The association between childhood diarrheal disease and linear growth faltering in developing countries is well-described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment.Methods: The Global Enteric Multicenter Study (GEMS) enrolled children seeking healthcare with moderate-to-severe diarrhea (MSD) at seven sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, ~60 days later, to calculate change in length/height for age Z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested by linear mixed effects regression models.Results: Among 8,077 MSD cases analyzed, the proportion with stunting (HAZ\u3c-1) increased from 59% at enrollment to 65% at follow-up (p\u3c.0001). Pathogens significantly associated with linear growth decline were Cryptosporidium (p\u3c0.001), typical enteropathogenic Escherichia coli (p=0.013), and untreated Shigella (p=0.009) among infants (0-11 months), and enterotoxigenic E. coli encoding heat stable toxin (p\u3c0.001) and Cryptosporidium (p=0.03) among toddlers (12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (p=0.02).Conclusion: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella