Enteric Infections Gut Inflammation and Response to Oral Poliovirus Vaccine

Abstract

The studies reported here evaluated the role of enteropathogens in affecting the immunogenicity of the oral vaccines using molecular and immunological methods. We also evaluated the association of gut inflammation and biomarkers of environmental enteropathy with enteropathogen presence and OPV response. The following are the major findings of these studies: A real-time PCR based molecular assay (enteropathogen TAC assay) for enteropathogen detection was optimised and performed on fecal samples. The assay enabled us to detect multiple enteropathogens and showed good sensitivity and specificity compared to conventional assays. It detected more enteropathogens compared to all the conventional assays put together. There was ubiquitous presence of enteropathogens in the guts of asymptomatic infants at different ages and from different locations in the country. Among the most common enteropathogens were bacterial enteropathogens like EAEC and EPEC and enteric viruses like NPEV. The enteropathogen burden was considerably higher among 6-11 month old infants compared to younger infants at 6 weeks age from similar settings. Levels of biomarkers of gut inflammation like fecal calprotectin and MPO were significantly elevated in samples with multiple enteropathogens, especially bacterial enteropathogens. A 3-day prophylactic dose of azithromycin in asymptomatic infants aged 6-11 months significantly decreased bacterial enteropathogen types and load. Presence of enteric viruses, especially NPEV, at the time of immunization were significantly associated with mOPV3 non-response. Other enteropathogens found in significantly higher proportion of PV3 seronegative infants were Giardia spp. A course of azithromycin did not improve the seroconversion rates to mOPV3 in infants aged 6-11 months despite significantly decreasing the load and prevalence of bacterial enteropathogens. Elevated levels of gut inflammatory biomarkers and putative biomarkers of environmental enteropathy did not show significant association with lack of response to mOPV3 vaccine.