Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Collaborators, Affiliations

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

Elizabeth T Rogawski et al. Lancet Glob Health. 2018 Dec.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Associations between diarrhoea and LAZ Analysis includes 37 951 observed child-months among 1469 children in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development cohort study who had molecular testing of stool samples. Per-episode estimates were adjusted for age, site, sex, socioeconomic status, maternal height, LAZ at the beginning of the interval, exclusive breastfeeding, and non-attributable diarrhoea episodes in the same period. 2 year estimates were adjusted for site, sex, socioeconomic status, maternal height, enrolment LAZ, exclusive breastfeeding in the first 6 months, number of antibiotic courses, and number of non-attributable diarrhoea episodes. LAZ=length-for-age Z scores.
Figure 2
Figure 2
Enteropathogen prevalence in non-diarrhoeal stools obtained from 1469 children in the MAL-ED cohort with molecular testing of stool samples MAL-ED=Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development. EAEC=enteroaggregative Escherichia coli. aEPEC=atypical enteropathogenic E coli. LT-ETEC=heat-labile enterotoxigenic E coli. ST-ETEC=heat-stable enterotoxigenic E coli. tEPEC=typical enteropathogenic E coli. STEC=Shiga toxin-producing E coli.
Figure 3
Figure 3
Site-specific effects of enteropathogen infections on height at age 2 years Difference in LAZ at age 2 years between site-specific high and low combined pathogen prevalence in non-diarrhoeal stools among 1469 children in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development cohort. Bacteria include Campylobacter, Shigella, enteroaggregative Escherichia coli, typical enteropathogenic E coli, atypical enteropathogenic E coli, and enterotoxigenic E coli; viruses include norovirus, adenovirus 40/41, astrovirus, and sapovirus; and protozoa include Giardia, Cryptosporidium, and Enterocytozoon bieneusi (the latter is an intracellular parasitic fungus). Estimates were adjusted for site, enrolment LAZ, sex, socioeconomic status, exclusive breastfeeding in the first 6 months, and maternal height. LAZ=length-for-age Z scores.
Figure 4
Figure 4
Effect of specific enteropathogen infections on height attainment at age 2 and 5 years Difference in LAZ according to high and low pathogen prevalence (A) and per one log increase in the mean quantity of pathogen per g of stool (B) in non-diarrhoeal stools. Data were available for 1469 children at 2 years and 1202 children at 5 years in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development cohort. Estimates were adjusted for site, enrolment LAZ, sex, SES, exclusive breastfeeding in the first 6 months, and maternal height. LAZ=length-for-age Z scores. EAEC=enteroaggregative Escherichia coli. tEPEC= typical enteropathogenic E coli. ETEC=enterotoxigenic E coli. aEPEC=atypical enteropathogenic E coli. *Enterocytozoon bieneusi is an intracellular parasitic fungus.
Figure 5
Figure 5
Mean LAZ from birth to age 2 years in the high and low enteropathogen infection burden parametric g-formula conditions The LAZ difference and 95% CI comparing the two conditions at 2 years is overlaid on each graph, for the 13 most prevalent enteropathogens in non-diarrhoeal stools. LAZ=length-for-age Z scores. EAEC=enteroaggregative Escherichia coli. tEPEC=typical enteropathogenic E coli. ETEC=enterotoxigenic E coli. aEPEC=atypical enteropathogenic E coli.

Similar articles

Cited by

References

    1. UNICEF. WHO. The World Bank Group Levels and trends in child malnutrition. Joint child malnutrition estimates. 2017. http://www.who.int/nutgrowthdb/jme_brochoure2017.pdf?ua=1
    1. de Onis M, Blössner M, Borghi E. Prevalence and trends of stunting among pre-school children, 1990-2020. Public Health Nutr. 2012;15:142–148. - PubMed
    1. Olofin I, McDonald CM, Ezzati M. Associations of suboptimal growth with all-cause and cause-specific mortality in children under five years: a pooled analysis of ten prospective studies. PLoS One. 2013;8:e64636. - PMC - PubMed
    1. Victora CG, Adair L, Fall C. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008;371:340–357. - PMC - PubMed
    1. Guerrant RL, DeBoer MD, Moore SR, Scharf RJ, Lima AAM. The impoverished gut—a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. 2013;10:220–229. - PMC - PubMed

Publication types