Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

James A Church; Sandra Rukobo; Margaret Govha; Ethan K Gough; Bernard Chasekwa; Benjamin Lee; Marya P Carmolli; Gordana Panic; Natasa Giallourou; Robert Ntozini; Kuda Mutasa; Monica M McNeal; Florence D. Majo; Naume V. Tavengwa; Jonathan R. Swann; Lawrence H Moulton; Beth D Kirkpatrick; Jean H Humphrey; Andrew J Prendergast

EClinicalMedicine (Nov 2021)

Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

James A Church,
Sandra Rukobo,
Margaret Govha,
Ethan K Gough,
Bernard Chasekwa,
Benjamin Lee,
Marya P Carmolli,
Gordana Panic,
Natasa Giallourou,
Robert Ntozini,
Kuda Mutasa,
Monica M McNeal,
Florence D. Majo,
Naume V. Tavengwa,
Jonathan R. Swann,
Lawrence H Moulton,
Beth D Kirkpatrick,
Jean H Humphrey,
Andrew J Prendergast

Affiliations

James A Church: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK; Corresponding authors at: Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
Sandra Rukobo: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Margaret Govha: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Ethan K Gough: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Bernard Chasekwa: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Benjamin Lee: Departments of Pediatrics, Vaccine Testing Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Marya P Carmolli: Departments of Microbiology and Molecular Genetics, Vaccine Testing Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Gordana Panic: Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Natasa Giallourou: Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Robert Ntozini: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Kuda Mutasa: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Monica M McNeal: Department of Pediatrics, University of Cincinnati College of Medicine, Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Florence D. Majo: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Naume V. Tavengwa: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
Jonathan R. Swann: Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Lawrence H Moulton: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Beth D Kirkpatrick: Departments of Microbiology and Molecular Genetics, Vaccine Testing Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Jean H Humphrey: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Andrew J Prendergast: Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe; Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Corresponding authors at: Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.

Journal volume & issue: Vol. 41
p. 101173

Abstract

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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.

Published in EClinicalMedicine

ISSN: 2589-5370 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General)
Website: https://www.thelancet.com/journals/eclinm/home

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