Search

BackgroundMetabolic syndrome is a cluster of risk factors for cardiovascular disease thought to afflict over a billion people worldwide and is increasingly being identified in younger age groups and socio-economically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may lead to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood.Methods217 subjects previously enrolled in a birth cohort in Amazonian Peru were followed up annually from ages 2 to 5 years. Blood samples collected in later childhood were analyzed for a panel of 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, and other analytes. These were matched to extant early-life markers of enteropathy ascertained between birth and 2 years of age. Multivariate and multivariable regression models were fitted to test for associations adjusting for confounders.ResultsFecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose and mannitol) measured from birth to 2 years of age were independently associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also strongly, directly associated with later levels of the anti-inflammatory adipocytokine omentin-1. Cumulative enteric protozoa exposure before 2 years of age showed stronger associations with later cardiometabolic markers than enteric viruses and bacteria and overall diarrheal episodes.ConclusionEarly-life markers of enteric infection and enteropathy were associated with numerous changes in adipokine, apolipoprotein and cytokine profiles later in childhood consistent with those of an adverse cardiometabolic disease risk profile in this Peruvian birth cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy, may predict disruptions to cytokine and adipocytokine production in later childhood that are precursors to metabolic syndrome in adulthood. Chronic enteric infections, such as by protozoan pathogens, may be more important drivers of these changes than symptomatic diarrhea or growth faltering.FundingBill & Melinda Gates Foundation OPP1066146 and OPP1152146.

Diarrheal disease remains a major cause of childhood mortality and morbidity causing poor health and economic outcomes. In low-resource settings, young children are exposed to numerous risk factors for enteric pathogen transmission within their dwellings, though the relative importance of different transmission pathways varies by pathogen species. The objective of this analysis was to model associations between five household-level risk factors&mdash, water, sanitation, flooring, caregiver education, and crowding&mdash, and infection status for endemic enteric pathogens in children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000 stool samples were tested for 16 specific enteropathogens using qPCR. Risk ratios for pathogen- and taxon-specific infection status were modeled using generalized linear models along with hazard ratios for all-cause diarrhea in proportional hazard models, with the five household-level variables as primary exposures adjusting for covariates. Improved drinking water sources conferred a 17% reduction in diarrhea risk, however, the direction of its association with particular pathogens was inconsistent. Improved sanitation was associated with a 9% reduction in diarrhea risk with protective effects across pathogen species and taxa of around 10&ndash, 20% risk reduction. A 9% reduction in diarrhea risk was observed in subjects with covered floors, which were also associated with decreases in risk for zoonotic enteropathogens. Caregiver education and household crowding showed more modest, inconclusive results. Combining data from diverse sites, this analysis quantified associations between five household-level exposures on risk of specific enteric infections, effects which differed by pathogen species but were broadly consistent with hypothesized transmission mechanisms. Such estimates may be used within expanded water, sanitation, and hygiene (WASH) programs to target interventions to the particular pathogen profiles of individual communities and prioritize resources.

Undernourished children are metabolically immature relative to those growing normally across 3 diverse epidemiologic contexts., Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growth-constrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker’s association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects’ length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker’s adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score–a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies., Author summary Childhood undernutrition is widespread throughout the world and has severe, long-lasting health impacts. Substances measured in blood, urine and stool could be used as biomarkers to identify children undergoing growth failure before these impacts occur. However, it is not yet known which of the many markers that can be identified are accurate and clinically useful predictors of poor growth in infants and children. This study used a large number of candidate biomarkers of immune activation, metabolism and hormones and applied statistical methods to narrow them down from 110 different substances, to the 36 best predictors of growth in 258 Peruvian infants. It also estimated how large the effect of each of these markers was on height two months later. The biomarker with the largest effect was transferrin, a glycoprotein that can be measured in blood samples. 15-month old children with elevated transferrin were around two thirds of a centimeter taller on average at 17 months than those with low levels. Transferrin and other proteins, glycoproteins, hormones and antibodies that this study identified, can be measured easily and affordably in standard laboratories making them feasible to be used broadly as prognostic markers as part of child health and nutrition programs in under-resourced settings.

Background: Environmental enteropathy (EE) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EE reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker's association with linear growth in infancy and early childhood. Methods: 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects' length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker's adjusted effect on growth. Findings: Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score - a coefficient value of 0.76 (0.48, 1.05) for each log2 increase in plasma transferrin concentration relative to the sample mean. Other biomarkers with large effect size estimates included 4-hydroxyproline, tumor necrosis factor receptor 2, beta-2-microglobulin, proline, serum amyloid P-component and adiponectin. The selected subset explained up to 26.0% of the variability in LAZ-score. Interpretation: Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EE. There is a need to systematically express the strength of association of biomarkers with linear growth or other select outcomes to compare results across studies. Funding: Bill & Melinda Gates Foundation. Declaration of Interest: The authors report no conflicts of interest. The information has not previously been presented in any meetings. Ethical Approval: Ethical approval for MAL-ED was given by the Johns Hopkins Institutional Review Board as well as the Ethics Committee of Asociacion Benefica PRISMA, and the Regional Health Department of Loreto.

Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites&mdash, Loreto, Peru&mdash, were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic E. coli (ST-ETEC) was identified (RR = 1.73 [1.10, 2.71]) along with a decreased risk of enteric adenovirus (RR = 0.36 [0.23, 0.58]). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 [2.70, 10.40]) and sapovirus (RR = 2.47 [1.79, 3.41]) were observed, in addition to increases in transmission of Shigella spp. (RR = 2.86 [1.81, 4.52]) and Campylobacter spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P[4]) strain of the virus. Policy-makers should target interventions towards these pathogens&mdash, including vaccines as they become available&mdash, in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.

We present an example of a tool for quantifying the burden, the population in need of intervention and resources need to contribute for the control of soil-transmitted helminth (STH) infection at multiple administrative levels for the region of Latin America and the Caribbean (LAC). The tool relies on published STH prevalence data along with data on the distribution of several STH transmission determinants for 12,273 sub-national administrative units in 22 LAC countries taken from national censuses. Data on these determinants was aggregated into a single risk index based on a conceptual framework and the statistical significance of the association between this index and the STH prevalence indicators was tested using simple linear regression. The coefficient and constant from the output of this regression was then put into a regression formula that was applied to the risk index values for all of the administrative units in order to model the estimated prevalence of each STH species. We then combine these estimates with population data, treatment thresholds and unit cost data to calculate total control costs. The model predicts an annual cost for the procurement of preventive chemotherapy of around US$ 1.7 million and a total cost of US$ 47 million for implementing a comprehensive STH control programme targeting an estimated 78.7 million school-aged children according to the WHO guidelines throughout the entirety of the countries included in the study. Considerable savings to this cost could potentially be made by embedding STH control interventions within existing health programmes and systems. A study of this scope is prone to many limitations which restrict the interpretation of the results and the uses to which its findings may be put. We discuss several of these limitations.

The Inter-American Development Bank (IDB) (http://www.iadb.org/en/inter-american-developmentbank,2837.html) is the regional, multilateral development bank for Latin America and the Caribbean (LAC). The largest source of external development financing for the region, the IDB support efforts by LAC countries to reduce poverty and inequality with the aim of bringing about development in a sustainable, climate-friendly way. Of the IDB’s 48 member states, 26 are borrowing countries which own majority shares in the institution. In 2010, the IDB approved an unprecedented 170 projects and US$ 570 million in grant financing. The IDB’s Social Protection and Health (SPH) division falls under the social sector and has a total of 56 staff working in the fields of health and social protection with the majority based in country offices of the borrowing countries themselves. The SPH division’s priorities in social protection are: (i) early childhood development (ECD), with focus on infants up to 3 years of age; (ii) youth at risk (in coordination with other business units); and (iii) poverty alleviation programmes.