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

doi:10.1016/j.eclinm.2021.101173

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

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	101173
Journal	EClinicalMedicine
Volume	41
DOIs	https://doi.org/10.1016/j.eclinm.2021.101173
State	Published - Nov 2021

Keywords

Africa
Enteropathy
Environmental enteric dysfunction
Infants
Oral vaccine
Rotavirus

ASJC Scopus subject areas

General Medicine

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10.1016/j.eclinm.2021.101173

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Church, J. A., Rukobo, S., Govha, M., Gough, E. K., Chasekwa, B., Lee, B., Carmolli, M. P., Panic, G., Giallourou, N., Ntozini, R., Mutasa, K., McNeal, M. M., Majo, F. D., Tavengwa, N. V., Swann, J. R., Moulton, L. H., Kirkpatrick, B. D., Humphrey, J. H., & Prendergast, A. J. (2021). Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants. EClinicalMedicine, 41, Article 101173. https://doi.org/10.1016/j.eclinm.2021.101173

Church, JA, Rukobo, S, Govha, M, Gough, EK, Chasekwa, B, Lee, B, Carmolli, MP, Panic, G, Giallourou, N, Ntozini, R, Mutasa, K, McNeal, MM, Majo, FD, Tavengwa, NV, Swann, JR, Moulton, LH, Kirkpatrick, BD, Humphrey, JH & Prendergast, AJ 2021, 'Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants', EClinicalMedicine, vol. 41, 101173. https://doi.org/10.1016/j.eclinm.2021.101173

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

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.",

keywords = "Africa, Enteropathy, Environmental enteric dysfunction, Infants, Oral vaccine, Rotavirus",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = nov,

doi = "10.1016/j.eclinm.2021.101173",

language = "English (US)",

volume = "41",

journal = "EClinicalMedicine",

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T1 - Associations between biomarkers of environmental enteric dysfunction and oral rotavirus vaccine immunogenicity in rural Zimbabwean infants

AU - Church, James A.

AU - Rukobo, Sandra

AU - Govha, Margaret

AU - Gough, Ethan K.

AU - Chasekwa, Bernard

AU - Lee, Benjamin

AU - Carmolli, Marya P.

AU - Panic, Gordana

AU - Giallourou, Natasa

AU - Ntozini, Robert

AU - Mutasa, Kuda

AU - McNeal, Monica M.

AU - Majo, Florence D.

AU - Tavengwa, Naume V.

AU - Swann, Jonathan R.

AU - Moulton, Lawrence H.

AU - Kirkpatrick, Beth D.

AU - Humphrey, Jean H.

AU - Prendergast, Andrew J.

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

KW - Africa

KW - Enteropathy

KW - Environmental enteric dysfunction

KW - Infants

KW - Oral vaccine

KW - Rotavirus

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DO - 10.1016/j.eclinm.2021.101173

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SN - 2589-5370

VL - 41

JO - EClinicalMedicine

JF - EClinicalMedicine

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ER -

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

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