Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

Abstract

Background: Oral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.

Methods: In urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.

Results: Campylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (-0.08 change in log titer per tenfold increase in quantity; P=0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64-0.96; P=0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05-1.71; P=0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.

Conclusion: In this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses. ClinicalTrials.gov Identifier: NCT01375647.

Keywords: Enteric infections; Oral polio vaccine; PCR; Rotavirus vaccine; Vaccine efficacy; Vaccine immunogenicity.

Supplementary Fig. 1

Association between EV burden and Rotarix efficacy. Density plots of fecal EV (A) and Sabin strain poliovirus (B) quantity at 10 weeks in children with (blue, n = 45) and without (red, n = 232) rotavirus-positive diarrhea between weeks 18 and 52. For each color, the area under the curve for any range of pathogen quantities represents the probability that the pathogen quantity falls in that range.

Fig. 1

Prevalence of enteric infections detected by quantitative PCR in week 6 (n = 339) and 10 (n = 159) pre-vaccination stool specimens. Pre-vaccination stool specimens were collected at the time points indicated and assayed for enteropathogens by TAC. All tested helminths and M. tuberculosis were exceedingly rare (0–3%) and are not shown. All infections were tested by TAC except OPV; OPV prevalence is overlaid on enterovirus prevalence with light blue for week 6 and light red for week 10).

Fig. 2

Association between EV quantity and serum neutralizing antibody titers to serotype P1, P2, and P3. Enterovirus-negative samples are jittered on the x-axis.