13. Otros

Lee, G., McCormick, B., Seidman, J., Kosek, M., Haque, R., Olortegui, M., Lima, A., Bhutta, Z., Kang, G., Samie, A., Amour, C., Mason, C., Ahmed, T., Yori, P., Oliveira, D., Alam, D., Babji, S., Bessong, P., Mduma, E., Shrestha, S., Ambikapathi, R., Lang, D., Gottlieb, M., Guerrant, R., Caulfield, L.; For The Mal-Ed Network Investigators.

Am J Trop Med Hyg. 2017 Jul;97(1)

Abstract

The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

Rogawski, E., Guerrant, R., Havt, A., Lima, I., Medeiros, P., Seidman, J., McCormick, B., Babji, S., Hariraju, D., Bodhidatta, L., Shrestha, J., Anania, J., Maro, A., Samie, A., Yori, P., Qureshi, S., Mahfuz, M., Bessong, P., Kosek, M., Ahmed, T., Bhutta, Z., Lang, D., Gottlieb, M., Houpt, E., Lima, A.; MAL-ED Network Investigators

PLoS Negl Trop Dis. 2017 Jul 24;11(7)

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.

Fandiño-Del-Rio, M., Goodman, D., Kephart, J., Miele, C., Williams, K., Moazzami, M., Fung, E., Koehler, K., Davila-Roman, V., Lee, K., Nangia, S., Harvey, S., Steenland, K., Gonzales, G., Checkley, W.; Cardiopulmonary outcomes and Household Air Pollution trial (CHAP) Trial Investigators.

Trials. 2017 Nov 3;18(1)

Abstract

BACKGROUND:

Biomass fuel smoke is a leading risk factor for the burden of disease worldwide. International campaigns are promoting the widespread adoption of liquefied petroleum gas (LPG) in resource-limited settings. However, it is unclear if the introduction and use of LPG stoves, in settings where biomass fuels are used daily, reduces pollution concentration exposure, improves health outcomes, or how cultural and social barriers influence the exclusive adoption of LPG stoves.

METHODS:

We will conduct a randomized controlled, field intervention trial of LPG stoves and fuel distribution in rural Puno, Peru, in which we will enroll 180 female participants aged 25-64 years and follow them for 2 years. After enrollment, we will collect information on sociodemographic characteristics, household characteristics, and cooking practices. During the first year of the study, LPG stoves and fuel tanks will be delivered to the homes of 90 intervention participants. During the second year, participants in the intervention arm will keep their LPG stoves, but the gas supply will stop. Control participants will receive LPG stoves and vouchers to obtain free fuel from distributors at the beginning of the second year, but gas will not be delivered. Starting at baseline, we will collect longitudinal measurements of respiratory symptoms, pulmonary function, blood pressure, endothelial function, carotid artery intima-media thickness, 24-h dietary recalls, exhaled carbon monoxide, quality-of-life indicators, and stove-use behaviors. Environmental exposure assessments will occur six times over the 2-year follow-up period, consisting of 48-h personal exposure and kitchen concentration measurements of fine particulate matter and carbon monoxide, and 48-h kitchen concentrations of nitrogen dioxide for a subset of 100 participants.

DISCUSSION:

Findings from this study will allow us to better understand behavioral patterns, environmental exposures, and cardiovascular and pulmonary outcomes resulting from the adoption of LPG stoves. If this trial indicates that LPG stoves are a feasible and effective way to reduce household air pollution and improve health, it will provide important information to support widespread adoption of LPG fuel as a strategy to reduce the global burden of disease.

TRIAL REGISTRATION:

ClinicalTrials.gov, ID: NCT02994680 , Cardiopulmonary Outcomes and Household Air Pollution (CHAP) Trial. Registered on 28 November 2016.

KEYWORDS:

Behavior change; Biomass fuel; Cardiopulmonary outcomes; Cookstove; Exclusive adoption; Household air pollution; Indoor air pollution; LPG; Personal exposure

McCormick, B., Lee, G., Seidman, J., Haque, R., Mondal, D., Quetz, J., Lima, A., Babji, S., Kang, G., Shrestha, S., Mason, C., Qureshi, S., Bhutta, Z., Paredes, M., Peñataro P., Samie, A., Bessong, P., Amour, C., Mduma, E., Patil, c., Guerrant, R., Lang, D., Gottlieb, M., Caulfield, L., and Kosek, M., for the MAL-ED Network

Am J Trop Med Hyg. 2017 Feb 8; 96(2)

Abstract

Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child’s life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0–24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.

Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child’s life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0–24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.

McCloskey, M., Tarazona-Meza, C., Jones-Smith, J., Miele, C., Gilman, R., Bernabe-Ortiz, A., Miranda, A., and Checkley, W.

International Journal of Behavioral Nutrition and Physical Activity 2017 14:90

https://doi.org/10.1186/s12966-017-0545-4

Abstract

Background

Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru.

Methods

We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers.

Results

Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03).

Conclusions

Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.

Keywords

Nutrition transition, 24-h recall, Urbanization, Overweight, Low- and middle income countries, Chronic diseases.

Kosek M.; MAL-ED Network Investigators.

EBioMedicine. 2017 Apr;18:109-117

Abstract

BACKGROUND:

Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries.

METHODS:

Non-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0-2years of age.

FINDINGS:

Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated.

INTERPRETATION:

The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation.

FUNDING:

Bill & Melinda Gates Foundation.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Child growth; Child health; Enteropathogen; Enteropathy; Stunting; Undernutrition