PubMed | MRC Unit The Gambia, Center for Tropical and Infectious Diseases, Birmingham Heartlands Hospital, Weatherall Institute of Molecular Medicine and University of Kelaniya
Type: | Journal: American journal of hematology | Year: 2016
Anemia affects over 800 million women and children globally. Measurement of hepcidin as an index of iron status shows promise, but its diagnostic performance where hemoglobinopathies are prevalent is unclear. We evaluated the performance of hepcidin as a diagnostic test of iron deficiency in adolescents across Sri Lanka. We selected 2273 samples from a nationally representative cross-sectional study of 7526 secondary schoolchildren across Sri Lanka and analyzed associations between hepcidin and participant characteristics, iron indices, inflammatory markers and hemoglobinopathy states. We evaluated the diagnostic accuracy of hepcidin as a test for iron deficiency with estimation of the AUC
Prentice A.M.,London School of Hygiene and Tropical Medicine |
Nabwera H.,London School of Hygiene and Tropical Medicine |
Kwambana B.,MRC Unit the Gambia |
Antonio M.,MRC Unit the Gambia |
Moore S.E.,London School of Hygiene and Tropical Medicine
Science Translational Medicine | Year: 2013
New research implicates a dysfunctional gut microbiome in the etiology of severe childhood malnutrition and conf rms a role for antibiotics in its treatment.
Moore S.E.,MRC Unit The Gambia |
Moore S.E.,London School of Hygiene and Tropical Medicine |
Fulford A.J.C.,MRC Unit The Gambia |
Fulford A.J.C.,London School of Hygiene and Tropical Medicine |
And 5 more authors.
BMC Pregnancy and Childbirth | Year: 2012
Background: Recent observational research indicates that immune development may be programmed by nutritional exposures early in life. Such findings require replication from trials specifically designed to assess the impact of nutritional intervention during pregnancy on infant immune development. The current trial seeks to establish: (a) which combination of protein-energy (PE) and multiple-micronutrient (MMN) supplements would be most effective; and (b) the most critical periods for intervention in pregnancy and infancy, for optimal immune development in infancy.Methods/Design: The ENID Trial is a 2 x 2 x 2 factorial randomized, partially blind trial to assess whether nutritional supplementation to pregnant women (from < 20 weeks gestation to term) and their infants (from 6 to 12 months of age) can enhance infant immune development. Eligible pregnant women from the West Kiang region of The Gambia (pregnancy dated by ultrasound examination) are randomized on entry to 4 intervention groups (Iron-folate (FeFol = standard care), multiple micronutrients (MMN), protein-energy (PE), PE + MMN). Women are visited at home weekly for supplement administration and morbidity assessment and seen at MRC Keneba at 20 and 30 weeks gestation for a detailed antenatal examination, including ultrasound. At delivery, cord blood and placental samples are collected, with detailed infant anthropometry collected within 72 hours. Infants are visited weekly thereafter for a morbidity questionnaire. From 6 to 12 months of age, infants are further randomized to a lipid-based nutritional supplement, with or without additional MMN. The primary outcome measures of this study are thymic development during infancy, and antibody response to vaccination. Measures of cellular markers of immunity will be made in a selected sub-cohort. Subsidiary studies to the main trial will additionally assess the impact of supplementation on infant growth and development to 24 months of age.Discussion: The proposed trial is designed to test whether nutritional repletion can enhance early immune development and, if so, to help determine the most efficacious form of nutritional support. Where there is evidence of benefit from a specific intervention/combination of interventions, future research should focus on refining the supplements to achieve the optimal, most cost-effective balance of interventions for improved health outcomes.Trial registration: ISRCTN49285450. © 2012 Moore et al.; licensee BioMed Central Ltd.
PubMed | MRC Unit The Gambia, University of North Carolina at Chapel Hill and London School of Hygiene and Tropical Medicine
Type: | Journal: EBioMedicine | Year: 2016
Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection.This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint.Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis.These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria.National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat.
PubMed | University of Otago, MRC Unit The Gambia and London School of Hygiene and Tropical Medicine
Type: | Journal: New microbes and new infections | Year: 2016
Staphylococcus aureus and Streptococcus pneumoniae commonly colonize the upper respiratory tract and can cause invasive disease. Several studies suggest an inverse relationship between these two bacteria in the nasopharynx. This association is of particular concern as the introduction of pneumococcal conjugate vaccines (PCVs) that affect pneumococcal nasopharyngeal carriage become widespread. A cohort of children in rural Gambia were recruited at birth and followed for 1 year, before the introduction of PCV into the routine immunization program. Nasopharyngeal swabs were taken immediately after birth, every 2 weeks for the first 6 months and then every other month. The presence of S.aureus and S.pneumoniae was determined using conventional microbiologic methods. Prevalence of S.aureus carriage was 71.6% at birth, decreasing with age to reach a plateau at approximately 20% between 10 to 20 weeks of age. Carriage with any S.pneumoniae increased during the first 10 weeks of life to peak at approximately 90%, mostly of PCV13 serotypes. Although in the crude analysis S.aureus carriage was inversely associated with carriage of any S.pneumoniae and PCV13 serotypes, after adjusting by age and season, there was a positive association with any carriage (odds ratio 1.32; 95% confidence interval 1.07-1.64; p 0.009) and no association with carriage of PCV13 serotypes (odds ratio 0.99; 95% confidence interval 0.70-1.41; p 0.973). Among Gambian infants, S.aureus and S.pneumoniae are not inversely associated in nasopharyngeal carriage after adjustment for age. Further carriage studies following the introduction of PCV are needed to better understand the relationship between the two bacteria.
Andreas N.J.,Imperial College London |
Kampmann B.,Imperial College London |
Kampmann B.,MRC Unit The Gambia |
Mehring Le-Doare K.,Imperial College London |
And 2 more authors.
Early Human Development | Year: 2015
Breast milk is the perfect nutrition for infants, a result of millions of years of evolution, finely attuning it to the requirements of the infant. Breast milk contains many complex proteins, lipids and carbohydrates, the concentrations of which alter dramatically over a single feed, as well as over lactation, to reflect the infant's needs.In addition to providing a source of nutrition for infants, breast milk contains a myriad of biologically active components. These molecules possess diverse roles, both guiding the development of the infants immune system and intestinal microbiota.Orchestrating the development of the microbiota are the human milk oligosaccharides, the synthesis of which are determined by the maternal genotype. In this review, we discuss the composition of breast milk and the factors that affect it during the course of breast feeding.Understanding the components of breast milk and their functions will allow for the improvement of clinical practices, infant feeding and our understanding of immune responses to infection and vaccination in infants. © 2015 Elsevier Ireland Ltd.
PubMed | MRC Unit The Gambia and Medical Research Council MRC Elsie Widdowson Laboratory
Type: | Journal: The Journal of nutrition | Year: 2016
The WHO recommends exclusive breastfeeding (EBF) for the first 6 mo of life.The objective of this study was to assess the benefit of EBF to age 6 mo on growth in a large sample of rural Gambian infants at high risk of undernutrition.Infants with growth monitoring from birth to 2 y of age (n = 756) from the ENID (Early Nutrition and Immune Development) trial were categorized as exclusively breastfed if only breast milk and no other liquids or foods were given. EBF status was entered into confounder-adjusted multilevel models to test associations with growth trajectories by using >11,000 weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z score observations.Thirty-two percent of infants were exclusively breastfed to age 6 mo. The mean age of discontinuation of EBF was 5.2 mo, and growth faltering started at 3.5 mo of age. Some evidence for a difference in WAZ and WHZ was found between infants who were exclusively breastfed to age 6 mo (EBF-6) and those who were not (nEBF-6), at 6 and 12 mo of age, with EBF-6 children having a higher mean z score. The differences in z scores between the 2 groups were small in magnitude (at 6 mo of age: 0.147 WAZ; 95% CI: -0.001, 0.293 WAZ; 0.189 WHZ; 95% CI: 0.038, 0.341 WHZ). No evidence for a difference between EBF-6 and nEBF-6 infants was observed for LAZ at any time point (6, 12, and 24 mo of age). Furthermore, a higher mean WLZ at 3 mo of age was associated with a subsequent higher mean age at discontinuation of EBF, which implied reverse causality in this setting (coefficient: 0.060; 95% CI: 0.008, 0.120).This study suggests that EBF to age 6 mo has limited benefit to the growth of rural Gambian infants. This trial was registered at http://www.isrctn.com as ISRCTN49285450.
Efficacy and safety of hepcidin-based screen-and-treat approaches using two different doses versus a standard universal approach of iron supplementation in young children in rural Gambia: a double-blind randomised controlled trial
PubMed | MRC Unit The Gambia, ETH Zurich, University of North Carolina at Chapel Hill and MRC Unit The Gambia MRC International Nutrition Group
Type: Journal Article | Journal: BMC pediatrics | Year: 2016
Iron deficiency prevalence rates frequently exceed 50% in young children in low-income countries. The World Health Organization (WHO) recommended universal supplementation of young children where anaemia rates are >40%. However, large randomized trials have revealed that provision of iron to young children caused serious adverse effects because iron powerfully promotes microbial growth. Hepcidin - the master regulator of iron metabolism that integrates signals of infection and iron deficiency - offers the possibility of new solutions to diagnose and combat global iron deficiency. We aim to evaluate a hepcidin-screening-based iron supplementation intervention using hepcidin cut-offs designed to indicate that an individual requires iron, is safe to receive it and will absorb it.The study is a proof-of-concept, three-arm, double blind, randomised controlled, prospective, parallel-group non-inferiority trial. Children will be randomised to receive, for a duration of 12weeks, one of three multiple micronutrient powders (MNP) containing: A) 12mg iron daily; B) 12mg or 0mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not; C) 6mg or 0mg iron daily based on a weekly hepcidin screening indicating if iron can be given for the next seven days or not. The inclusion criteria are age 6-23 months, haemoglobin (Hb) concentration between 7 and 11g/dL, z-scores for Height-for-Age, Weight-for-Age and Weight-for-Height>-3 SD and free of malaria. Hb concentration at 12weeks will be used to test whether the screen-and-treat approaches are non-inferior to universal supplementation. Safety will be assessed using caregiver reports of infections, in vitro bacterial and P. falciparum growth assays and by determining the changes in the gut microbiota during the study period.A screen-and-treat approach using hepcidin has the potential to make iron administration safer in areas with widespread infections. If this proof-of-concept study shows promising results the development of a point-of-care diagnostic test will be the next step.ISRCTN07210906 , 07/16/2014.
A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screen-and-treat approaches using hepcidin as a biomarker for ready and safe to receive iron
PubMed | MRC Unit The Gambia, MRC Unit The Gambia & MRC International Nutrition Group, Weatherall Institute of Molecular Medicine and MRC Human Nutrition Research
Type: Journal Article | Journal: BMC pregnancy and childbirth | Year: 2016
Until recently, WHO recommended daily iron supplementation for all pregnant women (60mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40%. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for safe and ready to receive iron.This is a 3-arm randomised-controlled proof-of-concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60mg/d iron (reference arm); b) UNIMMAP containing 60mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7days or not; c) or UNIMMAP containing 30mg/d iron as in (b) for 12weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed.This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes.ISRCTN21955180.
PubMed | MRC Unit The Gambia, Imperial College London, Ministry of Health and Social Welfare and Toshiba Corporation
Type: Journal Article | Journal: Alimentary pharmacology & therapeutics | Year: 2016
In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF).To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa.We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls.In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), 70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality.Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.