Enteropathogens and Rotavirus Vaccine Immunogenicity in a Cluster Randomized Trial of Improved Water, Sanitation and Hygiene in Rural Zimbabwe

James A Church, Elizabeth T Rogawski McQuade, Kuda Mutasa, Mami Taniuchi, Sandra Rukobo, Margaret Govha, Benjamin Lee, Marya P Carmolli, Bernard Chasekwa, Robert Ntozini, Monica M McNeal, Lawrence H Moulton, Beth D Kirkpatrick, Jie Liu, Eric R Houpt, Jean H Humphrey, James A Platts-Mills, Andrew J Prendergast, James A Church, Elizabeth T Rogawski McQuade, Kuda Mutasa, Mami Taniuchi, Sandra Rukobo, Margaret Govha, Benjamin Lee, Marya P Carmolli, Bernard Chasekwa, Robert Ntozini, Monica M McNeal, Lawrence H Moulton, Beth D Kirkpatrick, Jie Liu, Eric R Houpt, Jean H Humphrey, James A Platts-Mills, Andrew J Prendergast

Abstract

Background: Oral rotavirus vaccines (RVVs) are less efficacious in low-income versus high-income settings, plausibly due to more enteropathogen exposure through poor water, sanitation and hygiene (WASH). We explored associations between enteropathogens and RVV immunogenicity and evaluated the effect of improved WASH on enteropathogen carriage.

Methods: We detected stool enteropathogens using quantitative molecular methods and measured anti-rotavirus immunoglobulin A by enzyme-linked immunosorbent assay in infants enrolled to a cluster randomized 2 × 2 factorial trial of improved WASH and improved infant feeding in Zimbabwe (NCT01824940). We used multivariable regression to explore associations between enteropathogens and RVV seroconversion, seropositivity and geometric mean titer. We evaluated effects of improved WASH on enteropathogen prevalence using linear and binomial regression models with generalized estimating equations.

Results: Among 224 infants with enteropathogen and immunogenicity data, 107 (47.8%) had ≥1 pathogen and 39 (17.4%) had ≥2 pathogens detected at median age 41 days (interquartile range: 35-54). RVV seroconversion was low (23.7%). After adjusting for Sabin-poliovirus quantity, pan-enterovirus quantity was positively associated with RVV seroconversion (relative risk 1.61 per 10-fold increase in pan-enterovirus; 95% confidence interval: 1.35-1.91); in the same model, Sabin quantity was negatively associated with RVV seroconversion (relative risk: 0.76; 95% confidence interval: 0.60-0.96). There were otherwise no meaningful associations between individual or total pathogens (bacteria, viruses, parasites or all pathogens) and any measure of RVV immunogenicity. Enteropathogen detection did not differ between randomized WASH and non-WASH groups.

Conclusions: Enteropathogen infections were common around the time of rotavirus vaccination in rural Zimbabwean infants but did not explain poor RVV immunogenicity and were not reduced by a package of household-level WASH interventions.

Conflict of interest statement

J.A.C. (Grant 201293/Z/16/Z) and A.J.P. (Grant 108065/Z/15/Z) are supported by the Wellcome Trust. E.T.R.M. is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Grant K01AI130326). The other authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Associations between (A) individual pathogens and (B) grouped pathogens (grouped pathogen exposures do not include Sabin viruses and rotavirus) and oral rotavirus vaccine immunogenicity. Effect sizes and 95% confidence intervals shown are for the adjusted analysis. aEPEC indicates atypical enteropathogenic Escherichia coli; EAEC, enteroaggregative E. coli; NPEV, non-polio enterovirus.

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