RESUMO
INTRODUCTION: Environmental enteropathy (EE) is suspected to be a cause of growth faltering in children with sustained exposure to enteric pathogens, typically in resource-limited settings. A major hindrance to EE research is the lack of sensitive, non-invasive biomarkers. Current biomarkers measure intestinal permeability and inflammation, but not the functional capacity of the gut. Australian researchers have demonstrated proof of concept for an EE breath test based on using naturally 13C-enriched sucrose, derived from maize, to assay intestinal sucrase activity, a digestive enzyme that is impaired in villus blunting. Here, we describe a coordinated research project to optimise, validate and evaluate the usability of a breath test protocol based on highly enriched 13C-sucrose to quantify physiological dysfunction in EE in relevant target populations. METHODS AND ANALYSIS: We use the 13C-sucrose breath test (13C-SBT) to evaluate intestinal sucrase activity in two phases. First, an optimisation and validation phase will (1) confirm that a 13C-SBT using highly enriched sucrose tracers reports similar information to the naturally enriched 13C-SBT; (2) examine the dose-response relationship of the test to an intestinal sucrase inhibitor; (3) validate the 13C-SBT in paediatric coeliac disease (4) validate the highly enriched 13C-SBT against EE defined by biopsy in adults and (5) validate the 13C-SBT against EE defined by the urinary lactulose:rhamnose ratio (LR) among children in Peru. Second, a cross-sectional study will be conducted in six resource-limited countries (Bangladesh, India, Jamaica, Kenya, Peru and Zambia) to test the usability of the optimised 13C-SBT to assess EE among 600 children aged 12-15 months old. ETHICS AND DISSEMINATION: Ethical approval will be obtained from each participating study site. By working as a consortium, the test, if shown to be informative of EE, will demonstrate strong evidence for utility across diverse, low-income and middle-income country paediatric populations. TRIAL REGISTRATION NUMBER: NCT04109352; Pre-results.
Assuntos
Testes Respiratórios , Sacarose , Adolescente , Adulto , Austrália , Bangladesh , Isótopos de Carbono/análise , Criança , Estudos Transversais , Humanos , Índia , Jamaica , Quênia , Peru , Estudos Prospectivos , ZâmbiaRESUMO
OBJECTIVE: To estimate the burden of anemia attributable to malaria, inflammation, and deficiency of iron or vitamin A during low and high malaria seasons among Zambian children. STUDY DESIGN: From a cohort of children (n = 820), 4-8 years of age participating in a randomized controlled trial of pro-vitamin A, we estimated attributable fractions for anemia (hemoglobin of <110 or 115 g/L, by age) owing to current malaria or inflammation (C-reactive protein of >5 mg/L, or α-1 acid glycoprotein of >1 g/L, or both), and current or prior iron deficiency (ID; defined as low ferritin [<12 or 15 µg/L for age <5 or >5 years] or functional ID [soluble transferrin receptor of >8.3 mg/L] or both) and vitamin A deficiency (retinol of <0.7 µmol/L), during low and high malaria seasons, using multivariate logistic regression. Serum ferritin, soluble transferrin receptor, and retinol were adjusted for inflammation. RESULTS: The burden of anemia independently associated with current malaria, inflammation, ID, and vitamin A deficiency in the low malaria season were 12% (P < .001), 6% (P = .005), 14% (P = .001), and 2% (P = .07), respectively, and 32% (P < .001), 15% (P < .001), 10% (P = .06), and 2% (P = .06), respectively, in the high malaria season. In both seasons, functional ID was independently associated with more anemia (approximately 11%) than low ferritin (approximately 4%). Anemia and ID in the low malaria season, accounted for 20% (P < .001) and 4% (P = .095) of the anemia in the subsequent high malaria season. CONCLUSIONS: Anemia in this population is strongly linked to malaria, inflammation, and functional ID, and to a lesser extent, low iron stores. Integrated control strategies are needed.
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Anemia/epidemiologia , Inflamação/complicações , Deficiências de Ferro , Malária/complicações , Deficiência de Vitamina A/complicações , Anemia/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Efeitos Psicossociais da Doença , Feminino , Humanos , Malária/epidemiologia , Masculino , Prevalência , Saúde da População Rural , ZâmbiaRESUMO
Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the gold standard for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a populations dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.