Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study

The MAL-ED Network Investigators

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Abstract

Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.

Original languageEnglish (US)
Pages (from-to)e1319-e1328
JournalThe Lancet Global Health
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2018

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Shigella
Molecular Pathology
Cohort Studies
Giardia
Campylobacter
Growth
Infection
Asymptomatic Infections
Escherichia coli
Diarrhea
Enterocytozoon
Growth Disorders
Norovirus
Enteropathogenic Escherichia coli
Cryptosporidium
Child Development
Malnutrition
Parasites
Viruses
Bacteria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{1ef9b8615fde4505b8a2bb88464e3ec0,
title = "Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study",
abstract = "Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95{\%} CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95{\%} CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.",
author = "{The MAL-ED Network Investigators} and Rogawski, {Elizabeth T.} and Jie Liu and Platts-Mills, {James A.} and Furqan Kabir and Paphavee Lertsethtakarn and Mery Siguas and Khan, {Shaila S.} and Ira Praharaj and Arinao Murei and Rosemary Nshama and Buliga Mujaga and Alexandre Havt and Maciel, {Irene A.} and Operario, {Darwin J.} and Mami Taniuchi and Jean Gratz and Stroup, {Suzanne E.} and Roberts, {James H.} and Adil Kalam and Fatima Aziz and Shahida Qureshi and Islam, {M. Ohedul} and Pimmada Sakpaisal and Sasikorn Silapong and {Penataro Yori}, Pablo and Revathi Rajendiran and Blossom Benny and Monica McGrath and Seidman, {Jessica C.} and Dennis Lang and Michael Gottlieb and Guerrant, {Richard L.} and Lima, {Aldo A.M.} and Leite, {Jose Paulo} and Amidou Samie and Bessong, {Pascal O.} and Nicola Page and Ladaporn Bodhidatta and Carl Mason and Sanjaya Shrestha and Ireen Kiwelu and Mduma, {Estomih R.} and Iqbal, {Najeeha T.} and Bhutta, {Zulfiqar A.} and Tahmeed Ahmed and Kosek, {Margaret N.} and Robert Black and Laura Caulfield and William Checkley and Kerry Schulze",
year = "2018",
month = "12",
day = "1",
doi = "10.1016/S2214-109X(18)30351-6",
language = "English (US)",
volume = "6",
pages = "e1319--e1328",
journal = "The Lancet Global Health",
issn = "2214-109X",
publisher = "Elsevier BV",
number = "12",

}

TY - JOUR

T1 - Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings

T2 - longitudinal analysis of results from the MAL-ED cohort study

AU - The MAL-ED Network Investigators

AU - Rogawski, Elizabeth T.

AU - Liu, Jie

AU - Platts-Mills, James A.

AU - Kabir, Furqan

AU - Lertsethtakarn, Paphavee

AU - Siguas, Mery

AU - Khan, Shaila S.

AU - Praharaj, Ira

AU - Murei, Arinao

AU - Nshama, Rosemary

AU - Mujaga, Buliga

AU - Havt, Alexandre

AU - Maciel, Irene A.

AU - Operario, Darwin J.

AU - Taniuchi, Mami

AU - Gratz, Jean

AU - Stroup, Suzanne E.

AU - Roberts, James H.

AU - Kalam, Adil

AU - Aziz, Fatima

AU - Qureshi, Shahida

AU - Islam, M. Ohedul

AU - Sakpaisal, Pimmada

AU - Silapong, Sasikorn

AU - Penataro Yori, Pablo

AU - Rajendiran, Revathi

AU - Benny, Blossom

AU - McGrath, Monica

AU - Seidman, Jessica C.

AU - Lang, Dennis

AU - Gottlieb, Michael

AU - Guerrant, Richard L.

AU - Lima, Aldo A.M.

AU - Leite, Jose Paulo

AU - Samie, Amidou

AU - Bessong, Pascal O.

AU - Page, Nicola

AU - Bodhidatta, Ladaporn

AU - Mason, Carl

AU - Shrestha, Sanjaya

AU - Kiwelu, Ireen

AU - Mduma, Estomih R.

AU - Iqbal, Najeeha T.

AU - Bhutta, Zulfiqar A.

AU - Ahmed, Tahmeed

AU - Kosek, Margaret N.

AU - Black, Robert

AU - Caulfield, Laura

AU - Checkley, William

AU - Schulze, Kerry

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.

AB - Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.

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U2 - 10.1016/S2214-109X(18)30351-6

DO - 10.1016/S2214-109X(18)30351-6

M3 - Article

C2 - 30287125

AN - SCOPUS:85056344833

VL - 6

SP - e1319-e1328

JO - The Lancet Global Health

JF - The Lancet Global Health

SN - 2214-109X

IS - 12

ER -