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 - Yori, Pablo P.
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 - Haque, Rashidul
AU - Kang, Gagandeep
AU - Kosek, Margaret N.
AU - Houpt, Eric R.
AU - Richard, Stephanie A.
N1 - Publisher Copyright:
© 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2018/12
Y1 - 2018/12
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.
UR - http://www.scopus.com/inward/record.url?scp=85056344833&partnerID=8YFLogxK
U2 - 10.1016/S2214-109X(18)30351-6
DO - 10.1016/S2214-109X(18)30351-6
M3 - Article
C2 - 30287125
AN - SCOPUS:85056344833
SN - 2214-109X
VL - 6
SP - e1319-e1328
JO - The Lancet Global Health
JF - The Lancet Global Health
IS - 12
ER -