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

Mami Taniuchi,James A Platts-Mills,Sharmin Begum,Md Jashim Uddin,Shihab U Sobuz,Jie Liu,Beth D Kirkpatrick,E Ross Colgate,Marya P Carmolli,Dorothy M Dickson,Uma Nayak,Rashidul Haque,William A Petri,Eric R Houpt

doi:10.1016/j.vaccine.2016.04.080

Mami Taniuchi, James A Platts-Mills + Show 12 more

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https://doi.org/10.1016/j.vaccine.2016.04.080

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Abstract

BackgroundOral 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. MethodsIn 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. ResultsCampylobacter 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. ConclusionIn 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.

Highlights

The primary oral vaccines in use globally, Oral polio vaccine (OPV) and RV, have poorer efficacy in infants in low-income settings compared to Abbreviations: OPV, oral polio vaccine; RV, rotavirus vaccine; non-polio enterovirus (NPEV), nonpolio enterovirus; EV, enterovirus; PROVIDE, Performance of Rotavirus and Oral Polio Vaccines in Developing Countries; IPV, inactivated poliovirus vaccine; EAEC, enteroaggregative E. coli; EIEC, enteroinvasive E. coli; EPEC, enteropathogenic E. coli; ETEC, enterotoxigenic E. coli; STEC, Shiga-toxin producing E. coli; TaqMan Array Cards (TAC), TaqMan Array Card
Since most individual infections were rare at these early time points, and to avoid spurious associations, we examined the association between those pathogens with at least a 10% prevalence (Campylobacter, EAEC, EV) and OPV immunogenicity using multivariable linear and logistic regression
In the subset of 159 infants tested by TAC at week 6 who received RV per protocol, TAC was performed on week 10 stools, and EV quantity was again associated with reduced rotavirus IgA titer, whereas no other enteric infection exhibited a significant association (Table 3)

Summary

Introduction

The primary oral vaccines in use globally, OPV and RV, have poorer efficacy in infants in low-income settings compared to Abbreviations: OPV, oral polio vaccine; RV, rotavirus vaccine; NPEV, nonpolio enterovirus; EV, enterovirus; PROVIDE, Performance of Rotavirus and Oral Polio Vaccines in Developing Countries; IPV, inactivated poliovirus vaccine; EAEC, enteroaggregative E. coli; EIEC, enteroinvasive E. coli; EPEC, enteropathogenic E. coli; ETEC, enterotoxigenic E. coli; STEC, Shiga-toxin producing E. coli; TAC, TaqMan Array Card.middle- to high-income countries [1,2]. Subsequent studies have implicated several factors, including high maternal antibodies, concurrent breastfeeding, malnutrition, environmental enteropathy, prior or concurrent diarrhea, co-administration of other oral vaccines, or the presence of other enteric infections [5,6,7,8,9,10]. A recent meta-analysis of available studies, did demonstrate reduced odds of OPV seroconversion with concurrent non-polio enterovirus (NPEV) infection at the time of administration, for type 1 OPV [11]. 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 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. Strategies to reduce EV infections may improve oral vaccine responses

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Conclusion