Non-polio enterovirus association with persistent diarrhea in children as revealed by a follow-up study of an Indian cohort during the first two years of life

We recently reported significant association of non-polio enteroviruses (NPEVs) with acute diarrhea in children. Persistent diarrhea (PD) remains a major cause of morbidity and mortality in infants below two years of age in developing countries. Understanding age-dependent frequency and duration of NPEV infections is important to determine their association with persistent diarrhea and disease burden. Objectives: A cohort of 140 infants was followed for 6 months to 2 years of age to determine the frequency, duration, and association with PD of NPEV infections in comparison with rotavirus and other agents. Study design: Stool samples were collected every 14 days, and diarrheal episodes and their duration were recorded. Enteroviruses were characterized by RT-PCR and VP1 gene sequence analysis, rotavirus by electropherotyping, and other agents by PCR. Results: Of 4545 samples, negative for oral polio vaccine strains, 3907 (85.96%) and 638 (14.04%) were NPEV-negative and NPEV-positive, respectively, representing 403 (8.87%) infection episodes. About 68% of NPEV infections occurred during the first year with every child having at least one episode lasting between four days and four months. Approximately 38% and 22% of total diarrheal episodes were positive for NPEV and RV, respectively. While about 18% of NPEV infection episodes were associated with diarrhea, 6% being persistent, 13% of total diarrheal episodes were persistent involving infections by monotype NPEV strains or sequential infections by multiple strains and other agents. Conclusions: This is the first report revealing NPEVs as the single most frequently and persistently detected viral pathogen in every PD episode.