Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants
Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants
Background: oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED.
Methods: we measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED.
Findings: among 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups.
Interpretation: we found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions.
Africa, Enteropathy, Environmental enteric dysfunction, Infants, Oral vaccine, Rotavirus
Church, James A
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Rukobo, Sandra
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Govha, Margaret
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Gough, Ethan K
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Chasekwa, Bernard
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Lee, Benjamin
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Carmolli, Marya P
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Panic, Gordana
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Giallourou, Natasa
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Ntozini, Robert
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Mutasa, Kuda
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McNeal, Monica M
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Majo, Florence D
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Tavengwa, Naume V
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Swann, Jonathan R
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Moulton, Lawrence H
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Kirkpatrick, Beth D
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Humphrey, Jean H
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Prendergast, Andrew J
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15 November 2021
Church, James A
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Rukobo, Sandra
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Govha, Margaret
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Gough, Ethan K
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Chasekwa, Bernard
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Lee, Benjamin
791c9c18-0abb-493a-8837-22d558d51b10
Carmolli, Marya P
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Panic, Gordana
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Giallourou, Natasa
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Ntozini, Robert
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Mutasa, Kuda
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McNeal, Monica M
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Majo, Florence D
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Tavengwa, Naume V
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Swann, Jonathan R
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Moulton, Lawrence H
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Kirkpatrick, Beth D
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Humphrey, Jean H
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Prendergast, Andrew J
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Church, James A, Rukobo, Sandra, Govha, Margaret, Gough, Ethan K, Chasekwa, Bernard, Lee, Benjamin, Carmolli, Marya P, Panic, Gordana, Giallourou, Natasa, Ntozini, Robert, Mutasa, Kuda, McNeal, Monica M, Majo, Florence D, Tavengwa, Naume V, Swann, Jonathan R, Moulton, Lawrence H, Kirkpatrick, Beth D, Humphrey, Jean H and Prendergast, Andrew J
(2021)
Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants.
EClinicalMedicine, 41, [101173].
(doi:10.1016/j.eclinm.2021.101173).
Abstract
Background: oral rotavirus vaccines (RVV) are poorly immunogenic in low-income countries. Environmental enteric dysfunction (EED) resulting from poor water, sanitation and hygiene (WASH) may contribute. We therefore tested associations between EED and RVV immunogenicity, and evaluated the effect of improved WASH on EED.
Methods: we measured nine biomarkers of EED among Zimbabwean infants born to mothers enrolled in a cluster-randomised 2 × 2 factorial trial of improved WASH and improved feeding between November 2012 and March 2015 (NCT01824940). We used multivariable regression to determine associations between EED biomarkers and RVV seroconversion, seropositivity and geometric mean titer. Log-binomial regression was used to evaluate the effect of improved WASH on EED.
Findings: among 303 infants with EED biomarkers and immunogenicity data, plasma intestinal fatty-acid binding protein and stool myeloperoxidase were positively associated with RVV seroconversion; adjusted RR 1.63 (95%CI 1.04, 2.57) and 1.29 (95%CI 1.01, 1.65), respectively. There were no other associations between RVV immunogenicity and either individual biomarkers or EED domains (intestinal permeability, intestinal damage, intestinal inflammation and microbial translocation). EED biomarkers did not differ between randomised WASH and non-WASH groups.
Interpretation: we found no evidence that EED was associated with poor RVV immunogenicity. Contrary to our hypothesis, there was weak evidence that EED was associated with increased seroconversion. EED biomarkers were not affected by a package of household-level WASH interventions.
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Accepted/In Press date: 11 October 2021
Published date: 15 November 2021
Additional Information:
Funding Information:
This work was supported by the Wellcome Trust. The SHINE trial was funded by the Bill & Melinda Gates Foundation; UK Department for International Development (UK Aid); Swiss Agency for Development and Cooperation and US National Institutes of Health.
Funding Information:
This work was supported by the Wellcome Trust [203,905/Z/16/Z to JAC and 093,768/Z/10/Z and 108,065/Z/15/Z to AJP]. The SHINE trial was funded by the Bill & Melinda Gates Foundation [OPP1021542 and OPP113707]; UK Department for International Development (UK Aid); Swiss Agency for Development and Cooperation and US National Institutes of Health [2R01HD060338-06]. The study funders approved the trial design, but were not involved in data collection, analysis, interpretation, or manuscript preparation.
Funding Information:
We thank the mothers and babies who participated in the SHINE trial, and the SHINE Trial Team, members of whom are listed in https://doi.org/10.1093/cid/civ844. We gratefully acknowledge the leadership and staff of the Ministry of Health and Child Care in Chirumanzu and Shurugwi districts and Midlands Province (especially environmental health, nursing, and nutrition) for their roles in operationalisation of the study procedures. We acknowledge the Ministry of Local Government officials in each district who supported and facilitated field operations. We are particularly indebted to Mrs. Phillipa Rambanepasi and her team for proficiently managing finances and to Mrs. Virginia Sauramba for managing compliance issues. We thank Professor Bill Petri for the generous donation of REG?1? ELISA kits.
Publisher Copyright:
© 2021 The Authors
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
Keywords:
Africa, Enteropathy, Environmental enteric dysfunction, Infants, Oral vaccine, Rotavirus
Identifiers
Local EPrints ID: 453950
URI: http://eprints.soton.ac.uk/id/eprint/453950
ISSN: 2589-5370
PURE UUID: b8336386-afae-49a8-bcf1-5a0d96760f09
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Date deposited: 26 Jan 2022 17:47
Last modified: 06 Jun 2024 02:08
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Contributors
Author:
James A Church
Author:
Sandra Rukobo
Author:
Margaret Govha
Author:
Ethan K Gough
Author:
Bernard Chasekwa
Author:
Benjamin Lee
Author:
Marya P Carmolli
Author:
Gordana Panic
Author:
Natasa Giallourou
Author:
Robert Ntozini
Author:
Kuda Mutasa
Author:
Monica M McNeal
Author:
Florence D Majo
Author:
Naume V Tavengwa
Author:
Lawrence H Moulton
Author:
Beth D Kirkpatrick
Author:
Jean H Humphrey
Author:
Andrew J Prendergast
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