Journal of Infectious Diseases 2021

Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The Global Enteric Multicenter Study.

Nasrin D, Blackwelder WC, Sommerfelt H, Wu Y, Farag TH, Panchalingam S, Biswas K, Saha D, Hossain MJ, Sow SO, Breiman RF, Sur D, Faruque ASG, Zaidi AKM, Sanogo D, Tamboura B, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Omore R, Ochieng JB, Oundo JO, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Mandomando I, Nhampossa T, Bassat Q, Roose A, O'Reilly CE, Mintz ED, Ramakrishnan U, Powell H, Liang Y, Nataro JP, Levine MM, Kotloff KL
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.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.Among 8,077 MSD cases analyzed, the proportion with stunting (HAZ<-1) increased from 59% at enrollment to 65% at follow-up (p<.0001). Pathogens significantly associated with linear growth decline were Cryptosporidium (p<0.001), 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<0.001) and Cryptosporidium (p=0.03) among toddlers (12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (p=0.02).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.© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.