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Multicenter Study
. 2017 Jul 24;11(7):e0005798.
doi: 10.1371/journal.pntd.0005798. eCollection 2017 Jul.

Epidemiology of enteroaggregative Escherichia coli infections and associated outcomes in the MAL-ED birth cohort

Elizabeth T Rogawski  1   2 , Richard L Guerrant  2 , Alexandre Havt  3 , Ila F N Lima  3 , Pedro H Q S Medeiros  3 , Jessica C Seidman  4 , Benjamin J J McCormick  4 , Sudhir Babji  5 , Dinesh Hariraju  5 , Ladaporn Bodhidatta  6 , Jasmin Shrestha  7 , Japhat Anania  8 , Athanasia Maro  8 , Amidou Samie  9 , Pablo Peñataro Yori  10 , Shahida Qureshi  11 , Mustafa Mahfuz  12 , Pascal O Bessong  9 , Margaret N Kosek  10   13 , Tahmeed Ahmed  12 , Zulfiqar A Bhutta  11 , Dennis R Lang  14 , Michael Gottlieb  14 , Eric R Houpt  2 , Aldo A M Lima  3 ; MAL-ED Network Investigators
Affiliations
Multicenter Study

Epidemiology of enteroaggregative Escherichia coli infections and associated outcomes in the MAL-ED birth cohort

Elizabeth T Rogawski et al. PLoS Negl Trop Dis. .

Abstract

Background: Enteroaggregative E. coli (EAEC) have been associated with mildly inflammatory diarrhea in outbreaks and in travelers and have been increasingly recognized as enteric pathogens in young children with and without overt diarrhea. We examined the risk factors for EAEC infections and their associations with environmental enteropathy biomarkers and growth outcomes over the first two years of life in eight low-resource settings of the MAL-ED study.

Methods: EAEC infections were detected by PCR gene probes for aatA and aaiC virulence traits in 27,094 non-diarrheal surveillance stools and 7,692 diarrheal stools from 2,092 children in the MAL-ED birth cohort. We identified risk factors for EAEC and estimated the associations of EAEC with diarrhea, enteropathy biomarker concentrations, and both short-term (one to three months) and long-term (to two years of age) growth.

Results: Overall, 9,581 samples (27.5%) were positive for EAEC, and almost all children had at least one detection (94.8%) by two years of age. Exclusive breastfeeding, higher enrollment weight, and macrolide use within the preceding 15 days were protective. Although not associated with diarrhea, EAEC infections were weakly associated with biomarkers of intestinal inflammation and more strongly with reduced length at two years of age (LAZ difference associated with high frequency of EAEC detections: -0.30, 95% CI: -0.44, -0.16).

Conclusions: Asymptomatic EAEC infections were common early in life and were associated with linear growth shortfalls. Associations with intestinal inflammation were small in magnitude, but suggest a pathway for the growth impact. Increasing the duration of exclusive breastfeeding may help prevent these potentially inflammatory infections and reduce the long-term impact of early exposure to EAEC.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Incidence of EAEC.
Cumulative incidence of first EAEC detection in A) surveillance and diarrheal stools at all sites and B) surveillance stools by site among 2,092 children with at least one stool sample in the MAL-ED birth cohort. BGD–Dhaka, Bangladesh; BRF–Fortaleza, Brazil; INV–Vellore, India; NEB–Bhaktapur, Nepal; PEL–Loreto, Peru; PKN–Naushahro Feroze, Pakistan; SAV–Venda, South Africa; TZH–Haydom, Tanzania.
Fig 2
Fig 2. Short-term growth.
Adjusted site-specific associations between EAEC detection in monthly surveillance stools and A) weight-for-age z-score (WAZ) velocity and B) length-for-age z-score (LAZ) velocity over the subsequent month among 2,050 children in the MAL-ED cohort with at least one surveillance stool and at least one month of complete anthropometric measurements and testing for EAEC and Campylobacter.
Fig 3
Fig 3. Long-term growth.
Adjusted site-specific association between EAEC detection in monthly surveillance stools and A: weight-for-age z-score (WAZ) and B: length-for-age z-score (LAZ) at two years of age among 1,727 children in the MAL-ED cohort who had anthropometric measurements at two years. Estimates are the z-score difference associated with a high frequency of EAEC detection compared to a low frequency of EAEC detection. Definitions for high and low frequency are based on the 10th and 90th percentiles of stool positivity in the cohort. Low: ≤11% of surveillance stools positive for EAEC; high: ≥50% of surveillance stools positive for EAEC.
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