MRC Unit the Gambia

Banjul, Gambia

MRC Unit the Gambia

Banjul, Gambia
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Dodd P.J.,University of Sheffield | Prendergast A.J.,Queen Mary, University of London | Prendergast A.J.,Zvitambo Institute for Maternal and Child Health Research | Beecroft C.,University of Sheffield | And 3 more authors.
Thorax | Year: 2017

Background: Children (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB incidence. Objectives: Determine the impact of HIV infection and ART on risk of incident TB disease in children. Methods: We searched MEDLINE and Embase for studies measuring HIV prevalence in paediatric TB cases ('TB cohorts') and paediatric HIV cohorts reporting TB incidence ('HIV cohorts'). Study quality was assessed using the Newcastle-Ottawa tool. TB cohorts with controls were meta-analysed to determine the incidence rate ratio (IRR) for TB given HIV. HIV cohort data were meta-analysed to estimate the trend in log-IRR versus CD4%, relative incidence by immunological stage and ART-associated protection from TB. Results: 42 TB cohorts and 22 HIV cohorts were included. In the eight TB cohorts with controls, the IRR for TB was 7.9 (95% CI 4.5 to 13.7). HIV-infected children exhibited a reduction in IRR of 0.94 (95% credible interval: 0.83-1.07) per percentage point increase in CD4%. TB incidence was 5.0 (95% CI 4.0 to 6.0) times higher in children with severe compared with non-significant immunosuppression. TB incidence was lower in HIV-infected children on ART (HR: 0.30; 95% CI 0.21 to 0.39). Following initiation of ART, TB incidence declined rapidly over 12 months towards a HR of 0.10 (95% CI 0.04 to 0.25). Conclusions: HIV is a potent risk factor for paediatric TB, and ART is strongly protective. In HIV-infected children, early diagnosis and ART initiation reduces TB risk. © 2017 BMJ Publishing Group Limited.

Johnson W.,Loughborough University | Elmrayed S.A.A.,Medical Research Council MRC | Sosseh F.,MRC Unit the Gambia | Prentice A.M.,MRC Unit the Gambia | And 3 more authors.
American Journal of Clinical Nutrition | Year: 2017

Background: Maternal nutritional status is a key determinant of small for gestational age (SGA), but some knowledge gaps remain, particularly regarding the role of the energy balance entering pregnancy. Objective: We investigated how preconceptional and gestational weight trajectories (summarized by individual-level traits) are associated with SGA risk in rural Gambia. Design: The sample comprised 670 women in a trial with serial weight data (7310 observations) that were available before and during pregnancy. Individual trajectories from 6 mo before conception to 30 wk of gestation were produced with the use of multilevel modeling. Summary traits were expressed as weight z scores [weight z score at 3 mo preconception (zwt-3 mo), weight z score at conception, weight z score at 3 mo postconception, weight z score at 7 mo postconception (zwt+7 mo), and conditional measures that represented the change from the preceding time] and were related to SGA risk with the use of Poisson regression with confounder adjustment; linear splines were used to account for nonlinearity. Results: Maternal weight at each time point had a consistent nonlinear relation with SGA risk. For example, the zwt-3 mo estimate was stronger in women with values ≤0.5 (RR: 0.736; 95% CI: 0.594, 0.910) than in women with values >0.5 (RR: 0.920; 95% CI: 0.682, 1.241). The former group had the highest observed SGA prevalence. Focusing on weight change, only conditional zwt+7 mo was associated with SGA and only in women with values >.-0.5 (RR: 0.579; 95% CI: 0.463, 0.724). Conclusions: Protection against delivering an SGA neonate offered by greater preconceptional or gestational weight may be most pronounced in more undernourished and vulnerable women. Independent of this possibility, greater second-and third-trimester weight gain beyond a threshold may be protective. This trial was registered at ISRCTN49285450. Am J Clin Nutr 2017;105:1474-82. © 2017 American Society for Nutrition.

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

Okomo U.,MRC Unit The Gambia | Ogugbue M.,University of Calabar | Inyang E.,University of Calabar | Meremikwu M.M.,University of Calabar
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics | Year: 2017

BACKGROUND: Female sexual dysfunction is the persistent or recurring decrease in sexual desire or arousal, the difficulty or inability to achieve an orgasm, and/or the feeling of pain during sexual intercourse. Impaired sexual function can occur with all types of female genital mutilation (FGM) owing to the structural changes, pain, or traumatic memories associated with the procedure.OBJECTIVES: To conduct a systematic review of randomized and nonrandomized studies into the effects of sexual counseling with or without genital lubricants on the sexual function of women living with FGM.SEARCH STRATEGY: Cochrane Central Register of Controlled Trials, MEDLINE, African Index Medicus, SCOPUS, LILACS, CINAHL,, Pan African Clinical Trials Registry, and other databases were searched to August 2015. The reference lists of retrieved studies were checked for reports of additional studies, and lead authors contacted for additional data.SELECTION CRITERIA: Studies of girls and women living with any type of FGM who received counselling interventions for sexual dysfunction were included.DATA COLLECTION AND ANALYSIS: No relevant studies that addressed the objective of the review were identified.CONCLUSIONS: Despite a comprehensive search, the authors could not find evidence of the effects of sexual counseling on the sexual function of women living with FGM. Studies assessing this intervention are needed.PROSPERO REGISTRATION: CRD42015024593. © 2017 International Federation of Gynecology and Obstetrics. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

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.

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 as ISRCTN49285450.

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.

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