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Lancet Glob Health. 2018 Dec;6(12):e1319-e1328. doi: 10.1016/S2214-109X(18)30351-6. Epub 2018 Oct 1.

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.

Author information

1
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
2
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA.
3
Aga Khan University, Karachi, Pakistan.
4
Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
5
Asociación Benéfica PRISMA, Iquitos, Peru.
6
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
7
Christian Medical College, Vellore, India.
8
University of Venda, Thohoyandou, South Africa.
9
Haydom Global Health Institute, Haydom, Tanzania.
10
Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
11
Federal University of Ceara, Fortaleza, Brazil.
12
Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil.
13
Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
14
Asociación Benéfica PRISMA, Iquitos, Peru; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
15
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
16
Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
17
Foundation for the National Institutes of Health, Bethesda, MD, USA.
18
National Institute for Communicable Diseases, Johannesburg, South Africa.
19
Walter Reed/AFRIMS Research Unit, Nepal, Kathmandu, Nepal; University of Bergen, Bergen, Norway.
20
Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA. Electronic address: erh6k@hscmail.mcc.virginia.edu.

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.

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