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1.
Sci Adv ; 6(15): eaay5969, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32284996

RESUMO

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.


Assuntos
Desenvolvimento Infantil , Metabolismo Energético , Fatores Etários , Biomarcadores , Transtornos da Nutrição Infantil/epidemiologia , Transtornos da Nutrição Infantil/metabolismo , Pré-Escolar , Países em Desenvolvimento , Feminino , Humanos , Lactente , Masculino , Desnutrição/epidemiologia , Desnutrição/etiologia , Desnutrição/metabolismo , Metaboloma , Metabolômica/métodos
2.
Epidemiol Infect ; 146(6): 688-697, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29534766

RESUMO

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.


Assuntos
Análise por Conglomerados , Transmissão de Doença Infecciosa , Infecções por Rotavirus/epidemiologia , Estações do Ano , África/epidemiologia , Ásia/epidemiologia , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Prevalência , Infecções por Rotavirus/transmissão , América do Sul/epidemiologia
3.
J Dev Orig Health Dis ; 8(3): 337-348, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28264759

RESUMO

Environmental enteropathy (EE) is a syndrome of altered small intestine structure and function hypothesized to be common among individuals lacking access to improved water and sanitation. There are plausible biological mechanisms, both inflammatory and non-inflammatory, by which EE may alter the cardiometabolic profile. Here, we test the hypothesis that EE is associated with the cardiometabolic profile among young children living in an environment of intense enteropathogen exposure. In total, 156 children participating in the Peruvian cohort of a multicenter study on childhood infectious diseases, growth and development were contacted at 3-5 years of age. The urinary lactulose:mannitol ratio, and plasma antibody to endotoxin core were determined in order to assess intestinal permeability and bacterial translocation. Blood pressure, anthropometry, fasting plasma glucose, insulin, and cholesterol and apolipoprotein profiles were also assessed. Extant cohort data were also used to relate biomarkers of EE during the first 18 months of life to early child cardiometabolic profile. Lower intestinal surface area, as assessed by percent mannitol excretion, was associated with lower apolipoprotein-AI and lower high-density lipoprotein concentrations. Lower intestinal surface area was also associated with greater blood pressure. Inflammation at 7 months of age was associated with higher blood pressure in later childhood. This study supports the potential for a relationship between EE and the cardiometabolic profile.


Assuntos
Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/efeitos adversos , Enteropatias/epidemiologia , Intestino Delgado , Doenças Metabólicas/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Enteropatias/diagnóstico , Enteropatias/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Estudos Longitudinais , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/metabolismo , Peru/epidemiologia , Estudos Prospectivos , Fatores de Risco
4.
BMJ Glob Health ; 1(1): e000066, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28588929

RESUMO

BACKGROUND: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder affecting populations living in conditions of poor sanitation and hygiene. The study tested intestinal barrier function in infants with EED. METHODS: We prospectively studied an advanced high-performance liquid chromatography mass spectrometry assay of urine collected after oral intake of the monosaccharide, L-rhamnose and the disaccharide, lactulose, in 112 children from three continents. FINDINGS: Compared to the US cohort (n=27), the cohorts of children from Peru (n=19) and Zambia (n=85) were older with evidence of growth impairment. The median (range) of age (months) was 8.0 (2.0 to 13.0), 27.0 (15.0 to 29.0) and 21.0 (12.0 to 36.0), respectively. The median (range) of height for age Z score was -0.1 (-1.8 to 2.4), -1.8 (-3.3 to -0.2) and -2.3 (-8.5 to 1.2), respectively. Among children with valid sugar data (n=22 USA, n=19 Peru, n=73 Zambia), there were no significant differences in the median rhamnose urine concentrations between the three groups. The median (range) lactulose concentration (µg/mL) was 6.78 (0.29 to 31.90), 47.60 (4.23 to 379.00) and 75.40 (0.67 to 873.00) in the US, Peruvian and Zambian cohorts, respectively (p<0.001). The lactulose/rhamnose ratio (LRR) was higher in cohorts from Peru (0.75, 0.15, 5.02) and Zambia (2.26, 0.08, 14.48) compared to the US (0.14, 0.06, 1.00) cohort (p<0.001). In a multivariate effect modification model, higher weight-for-age z scores were associated with lower post-dose lactulose when rhamnose excretion was constant (p=0.003). CONCLUSIONS: This non-invasive two saccharide permeability protocol measures changes in intestinal permeability in children with EED and permits the identification of individuals for interventional trials.

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