[Show abstract][Hide abstract] ABSTRACT: A pilot study was conducted to assess the feasibility of using fNIRS as an alternative to behavioral assessments of cognitive development with infants in rural Africa. We report preliminary results of a study looking at working memory in 12-16-month-olds and discuss the benefits and shortcomings for the potential future use of fNIRS to investigate the effects of nutritional insults and interventions in global health studies.
Full-text · Article · Jan 2016 · Advances in Experimental Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.
Full-text · Article · Nov 2015 · Scientific Reports
[Show abstract][Hide abstract] ABSTRACT: Background: Maternal micronutrient deficiencies are commonly associated with clinical indicators of placental dysfunction.
Objective: We tested the hypothesis that periconceptional multiple-micronutrient supplementation (MMS) affects placental function.
Design: We conducted a double-blind, randomized, placebo-controlled trial of MMS in 17- to 45-y-old Gambian women who were menstruating regularly and within the previous 3 mo. Eligible subjects were pre–randomly assigned to supplementation with the UNICEF/WHO/United Nations University multiple micronutrient preparation (UNIMMAP) or placebo on recruitment and until they reached their first antenatal check-up or for 1 y if they failed to conceive. Primary outcome measures were midgestational indexes of utero-placental vascular-endothelial function [ratio of plasminogen-activator inhibitor (PAI) 1 to PAI-2 and mean uterine-artery resistance index (UtARI)] and placental active transport capacity at delivery [fetal to maternal measles antibody (MMA) ratio].
Results: We recruited 1156 women who yielded 415 pregnancies, of which 376 met all of the inclusion criteria. With adjustment for gestational age at sampling, there were no differences in PAI-1 to PAI-2 or MMA ratios between trial arms, but there was a 0.02-unit reduction in UtARI between 18 and 32 wk of gestation (95% CI: −0.03, −0.00; P = 0.040) in women taking UNIMMAP.
Conclusions: Placental vascular function was modifiable by periconceptional micronutrient supplementation. However, the effect was small and supplementation did not further affect other variables of placental function. This trial was registered at www.controlled-trials.com as ISRCTN 13687662.
Full-text · Article · Nov 2015 · American Journal of Clinical Nutrition
[Show abstract][Hide abstract] ABSTRACT: Background. There are large data gaps in the epidemiology of diseases caused by Salmonella enterica in West Africa. Regional surveillance of Salmonella infections is necessary, especially with the emergence and spread of multidrug-resistant clones.
Methods. Data on Salmonella isolated from various clinical specimens from patients from across The Gambia were collected and analyzed retrospectively from 2005 to April 2015. Antibiotic sensitivity testing of Salmonella isolates was performed by disk diffusion method. Serotyping and serogrouping of Salmonella isolates was performed using standard microbiology techniques.
Results. Two hundred three Salmonella isolates were isolated from 190 patients: 52% (106/203) from blood and 39% (79/203) from stool specimens. Salmonella was also isolated from urine, aspirates, cerebrospinal fluid, wounds, and abscesses. The prevalence of Salmonella in blood cultures was 0.8% (106/13 905). Of the serotyped salmonellae, 14% (21/152) were Salmonella enterica serovar Typhi, whereas 86% (131/152) were serovars other than Typhi (nontyphoidal Salmonella). Of the 102 typed NTS isolates, 40% (41) were Salmonella enterica serovar Typhimurium, 10% (10) were Salmonella enterica serovar Enteritidis, and 3% (3) were Salmonella enterica serovar Arizonae. Overall, 70% (142/203) of the salmonellae were pansusceptible. Multidrug resistance was found in 4% (9/203) of the isolates, 3 of which were Salmonella Enteritidis.
Conclusions. Salmonellae are associated with a wide spectrum of invasive and noninvasive infections across all ages in The Gambia. There is evidence of multidrug resistance in salmonellae that warrants vigilant monitoring and surveillance.
Full-text · Article · Nov 2015 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Fibroblast growth factor-23 (FGF23), a phosphate-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate (Phos) metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first two years of life. Infants born to mothers with normal (NIn=25,) and low (LIn=25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104 weeks(wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P≤0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52 wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P=0.04] and from 24 wk for TALP [44.7 (29.6) U/L, P=0.04]. After adjustment, infant Hb was the strongest negative predictor of C-FGF23 concentration [-21% (4%) RU/mL, P≤0.0001]. Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P≤0.0001] and I-FGF23 did not predict C-FGF23 over time [-0.5% (0.5%), P=0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research.
[Show abstract][Hide abstract] ABSTRACT: Background
Yoghurt is part of the diet of many people worldwide and is commonly recognized as a 'health food'. Epidemiological studies suggest yoghurt may be useful as part of weight management programs. In the absence of comprehensive systematic reviews, this systematic review investigated the effect of yoghurt consumption by apparently healthy adults on weight-related outcomes.Methods
An extensive literature search was undertaken, as part of a wider scoping review, to identify yoghurt studies. 13 631 records were assessed for their relevance to weight-related outcomes.Results22 publications were eligible according to the review protocol. Cohort studies (n=6) and cross-sectional studies (n=7) all showed a correlation between yoghurt and lower or improved body weight/composition. Six randomised controlled trials (RCTs) and one controlled trial had various limitations, including small size and short duration. One RCT showed significant effects of yoghurt on weight loss, but was confounded by differences in calcium intake. One trial showed non-significant weight gain and the remaining five trials showed non-significant weight losses that were greater in yoghurt consumers.Conclusions
Yoghurt consumption is associated with lower BMI, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs suggest weight reduction effects, but do not permit determination of a cause/effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient dense food) and its ease of introduction to most diets, suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health. Future carefully designed RCTs could provide proof of principle and large community-based studies could determine the practical impact of yoghurt on body weight/composition.International Journal of Obesity accepted article preview online, 07 October 2015. doi:10.1038/ijo.2015.202.
No preview · Article · Oct 2015 · International journal of obesity (2005)
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. OBJECTIVE To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. INTERVENTIONS Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. MAIN OUTCOMES AND MEASURES Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth. RESULTS Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, −1.2%, 95% CI, −11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, −0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 μg/L vs 14.4 μg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 μg/L vs 138.7 μg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use. CONCLUSIONS AND RELEVANCE Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight.
Full-text · Article · Sep 2015 · JAMA The Journal of the American Medical Association
[Show abstract][Hide abstract] ABSTRACT: Interindividual epigenetic variation that occurs systemically must be established prior to gastrulation in the very early embryo and, because it is systemic, can be assessed in easily biopsiable tissues. We employ two independent genome-wide approaches to search for such variants.
First, we screen for metastable epialleles by performing genomewide bisulfite sequencing in peripheral blood lymphocyte (PBL) and hair follicle DNA from two Caucasian adults. Second, we conduct a genomewide screen for genomic regions at which PBL DNA methylation is affected by season of conception in rural Gambia. Remarkably, both approaches identify the genomically imprinted VTRNA2-1 as a top environmentally responsive epiallele. We demonstrate systemic and stochastic interindividual variation in DNA methylation at the VTRNA2-1 differentially methylated region in healthy Caucasian and Asian adults and show, in rural Gambians, that periconceptional environment affects offspring VTRNA2-1 epigenotype, which is stable over at least 10 years. This unbiased screen also identifies over 100 additional candidate metastable epialleles, and shows that these are associated with cis genomic features including transposable elements.
The non-coding VTRNA2-1 transcript (also called nc886) is a putative tumor suppressor and modulator of innate immunity. Thus, these data indicating environmentally induced loss of imprinting at VTRNA2-1 constitute a plausible causal pathway linking early embryonic environment, epigenetic alteration, and human disease. More broadly, the list of candidate metastable epialleles provides a resource for future studies of epigenetic variation and human disease.
[Show abstract][Hide abstract] ABSTRACT: Both iron deficiency (ID) and malaria are common among African children. Studies show that the iron-regulatory hormone hepcidin is induced by malaria, but few studies have investigated this relationship longitudinally. We measured hepcidin concentrations, markers of iron status, and antibodies to malaria antigens during two cross-sectional surveys within a cohort of 324 Kenyan children ≤8 years old who were under intensive surveillance for malaria and other febrile illnesses. Hepcidin concentrations were the highest in the youngest, and female infants, declined rapidly in infancy and more gradually thereafter. Asymptomatic malaria and malaria antibody titres were positively associated with hepcidin concentrations. Recent episodes of febrile malaria were associated with high hepcidin concentrations that fell over time. Hepcidin concentrations were not associated with the subsequent risk of either malaria or other febrile illnesses. Given that iron absorption is impaired by hepcidin, our data suggest that asymp-tomatic and febrile malaria contribute to the high burden of ID seen in African children. Further, the effectiveness of iron supplementation may be sub-optimal in the presence of asymptomatic malaria. Thus, strategies to prevent and eliminate malaria may have the added benefit of addressing an important cause of ID for African children.
[Show abstract][Hide abstract] ABSTRACT: Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.
Full-text · Article · May 2015 · Nature Communications
[Show abstract][Hide abstract] ABSTRACT: In populations of European ancestry, the genetic contribution to body mass index (BMI) increases with age during childhood but then declines during adulthood, possibly due to the cumulative effects of environmental factors. How the effects of genetic factors on BMI change with age in other populations is unknown.
In a rural Gambian population (N=2535), we used a combined allele risk score, comprising genotypes at 28 'Caucasian adult BMI-associated' single nucleotide polymorphisms (SNPs), as a marker of the genetic influence on body composition, and related this to internally-standardised z-scores for birthweight (zBW), weight-for-height (zWT-HT), weight-for-age (zWT), height-for-age (zHT), and zBMI cross-sectionally and longitudinally.
Cross-sectionally, the genetic score was positively associated with adult zWT (0.018±0.009 per allele, p=0.034, N=1426) and zWT-HT (0.025±0.009, p=0.006), but not with size at birth or childhood zWT-HT (0.008±0.005, p=0.11, N=2211). The effect of the genetic score on zWT-HT strengthened linearly with age from birth through to late adulthood (age interaction term: 0.0083 z-scores/allele/year; 95% CI 0.0048 to 0.0118, p=0.0000032).
Genetic variants for obesity in populations of European ancestry have direct relevance to bodyweight in nutritionally deprived African settings. In such settings, genetic obesity susceptibility appears to regulate change in weight status throughout the life course, which provides insight into its potential physiological role.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Full-text · Article · Apr 2015 · Journal of Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity.
The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n = 3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n = 237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years).
The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P = 0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined.
This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants.
The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups.