Rural Gambia Research Articles

'Some anti-malarials are too strong for your body, they will harm you.' Socio-cultural factors influencing pregnant women's adherence to anti-malarial treatment in rural Gambia.

BackgroundDespite declining prevalence of malaria in The Gambia, non-adherence to anti-malarial treatment still remains a challenge to control efforts. There is limited evidence on the socio-cultural factors that influence adherence to anti-malarial treatment in pregnancy. This study explored perceptions of malaria in pregnancy and their influence on adherence to anti-malarial treatment in a rural area of The Gambia.MethodsAn exploratory ethnographic study was conducted ancillary to a cluster-randomized trial on scheduled screening and treatment of malaria in pregnancy at village level in the Upper River Region of The Gambia from June to August 2014. Qualitative data were collected through interviewing and participant observation. Analysis was concurrent to data collection and carried out using NVivo 10.ResultsAlthough women had good bio-medical knowledge of malaria in pregnancy, adherence to anti-malarial treatment was generally perceived to be low. Pregnant women were perceived to discontinue the provided anti-malarial treatment after one or 2 days mainly due to non-recognition of symptoms, perceived ineffectiveness of the anti-malarial treatment, the perceived risks of medication and advice received from mothers-in-law.ConclusionImproving women’s knowledge of malaria in pregnancy is not sufficient to assure adherence to anti-malarial treatment. Addressing structural barriers such as unclear health workers’ messages about medication dosage, illness recognition, side effects of the medication and the integration of relatives, especially the mothers-in-law, in community-based programmes are additionally required.

Establishing a Biomarker of Cortical Specialisation in infants in The Gambia and UK

Brain and nervous system development in human infants during the first 1000 days ‐ which includes pregnancy and the first two years of life ‐ is critical, and risk of compromised development during this time can have a deep impact on physical growth and cognitive function into adulthood. Recent research has shown that under nutrition in infancy is linked to lifelong effects on adult health, however we still have a comparatively poor understanding of how nutrition effects brain development during early life. The development of non‐invasive brain imaging techniques, such as functional near infrared Spectroscopy (fNIRS), has allowed a recent shift in the use of neuroimaging towards the study of the developing brain in situations where this development may be at risk or compromised in some way. Furthermore, objective measures of brain function may provide information that to date has been unavailable with existing behavioural paradigms.Recent fNIRS research in typically developing infants has shown robust and consistent activation to social vs non‐social visual and auditory stimuli in the inferior frontal, anterior temporal and posterior superior temporal – temporo parietal junction (pST‐TPJ) regions of the cortex. Having established this signature response in infants from 4 to 6 months of age, here we apply this paradigm to the investigation of social responses in infants from the first days of life to the first year in two different settings: urban European and rural Gambian. This is a cross sectional study of infants in the Gambia and UK at 0–2, 4–8 and 12–16 months of age (0–2 months ‐ N = 14 UK & N = 19 Gambia; 4 – 8 mths ‐ N = 64 UK & N = 24 Gambia; 12 – 16 months – N = 15 UK & N = 22 Gambia). Results reveal robust and consistent socially selective responses from 4 – 16 mths of life to both the visual and auditory stimuli. In contrast at 0–2 mths of age a stronger response is evidenced to the non‐social auditory stimuli in the Gambian infants. In ongoing analyses we are investigating whether these brain responses also differ in the 0–2 month olds in the UK.These findings provide a key biomarker of cortical specialization over the first year of life. We believe this method could be applied to the study of compromised development in global health research where infants are exposed to a broad range of adversity early in life including poverty, malnourishment and recurrent infections.Support or Funding InformationBill and Melinda Gates Foundation, Medical Research Council UK

Pre‐Pregnancy Energy Balance, Gestational Weight Gain, and Small‐for‐Gestational Age in Rural Gambia: the Early Nutrition and Immune Development Trial (ISRCTN49285450)

BackgroundThe importance of periconceptional micronutrient status is widely recognised. Less however is known about the consequence of weight change patterns, indicative of energy balance, preceding conception, and the impact this may have on fetal growth and development. This is particularly pertinent in low‐ and middle‐income countries in which marked seasonality results in many women experiencing negative energy balance (i.e., losing weight) as they enter pregnancy.ObjectiveTo investigate the impact of energy balance entering pregnancy on gestational weight gain and risk of small‐for‐gestational (SGA) in rural Gambia, where there are distinct wet/hungry (June–October) and dry/harvest (November–May) seasons.MethodsThe sample comprised 599 mother‐infant dyads participating in a randomized trial of maternal nutritional supplementation, which from previous analyses we know to have had minimal effect on gestational weight gain and birth outcomes. Briefly, non‐pregnant women of reproductive age in the West Kiang region of The Gambia were invited to participate and visited monthly, for recording of their date of last menstrual period and weight. Once pregnant, women attended the clinic at a baseline “booking” visit early in gestation and subsequently at 20 and 30 weeks of gestation. Neonatal anthropometry were collected at home visits within 72 hours of birth. Pre‐pregnancy energy balance (negative or positive) was defined according to weight change (negative or positive, respectively) in the three months preceding conception. Gestational weight gain was defined according to change in weight between conception and 30 weeks of gestation. The primary outcome was SGA (< 10th percentile of INTERGROWTH‐21st standards). Regression models with adjustment for confounders were used to test the associations between 1) pre‐pregnancy energy balance and gestational weight gain, 2) gestational weight gain and SGA, and 3) pre‐pregnancy energy balance and SGA, with and without adjustment for gestational weight gain.Results260 women (43%) were in negative energy balance entering pregnancy and 339 women (57%) were in positive energy balance. As expected, energy balance was patterned by seasonality; 43% of the 260 women in negative energy balance were in the wet/hungry season (at the point of conception), while only 27% of the 339 women in positive energy balance were in the wet/hungry season (p < 0.001). However, even after adjusting for pre‐pregnancy height and body mass index, women in negative pre‐pregnancy energy balance demonstrated greater gestational weight gain (beta = 1.75 kg, p < 0.001), which in turn was related to decreased risk of SGA (odds ratio = 0.94, p = 0.017). Subsequently, the association between pre‐pregnancy energy balance and SGA was weak and non‐significant (p‐value > 0.8), both before and after adjusting for gestational weight gain.ConclusionWomen in negative energy balance entering pregnancy, as a result of being in the wet/hungry season, may demonstrate greater gestational weight gain because they then spend mid‐ to late‐pregnancy in the dry/harvest season. Subsequently, they may have no increased risk of adverse birth outcomes compared to women in positive energy balance entering pregnancy.Support or Funding InformationThe ENID trial is supported by the Medical Research Council (UK), through core funding to the MRC International Nutrition Group (MC‐A760‐5QX00).

High genetic diversity of Staphylococcus aureus strains colonising the nasopharynx of Gambian villagers before widespread use of pneumococcal conjugate vaccines.

BackgroundWith the global efforts of reducing pneumococcal disease through widespread introduction of pneumococcal vaccines, concerns have emerged on the potential increase of morbidity and mortality from S. aureus disease. Little is known however, of the carriage rates of S. aureus or of its’ relationship with carriage of S. pneumoniae in rural Africa, and West Africa in particular where very high rates of carriage of S. pneumoniae have been reported. This study aims to evaluate the prevalence, antibiotic susceptibility patterns and genotypes of S. aureus isolated from the nasopharynx of healthy individuals in rural Gambia before the introduction of routine use of pneumococcal conjugate vaccines in the country.ResultsOverall prevalence of S. aureus nasopharyngeal carriage was 25.2 %. All S. aureus isolates tested were susceptible to methicillin. Resistant was observed for sulphamethoxazole-trimethoprim (15 %) and tetracycline (34.3 %). We found 59 different sequence types (ST), 35 of which were novel. The most prevalent sequence types were ST 15 (28 %) and ST 5 (4 %). Eighty two percent (494/600) of study individuals were S. pneumoniae carriers with S. pneumoniae carriage rates decreasing with increasing age groups. S. aureus carriage among pneumococcal carriers was slightly lower than among non-pneumococcal carriers (24.3 versus 29.3 %; p = 0.324). There were no associations of carriage between these two bacteria across the 4 age groups. However, analysis of pooled data children < 2 years and children 2 to < 5 years of age showed a statistically significant inverse association (24.1 and 50.0 % for S. aureus carriage among S. pneumoniae carriers and non-carriers respectively; p = 0.015).ConclusionsWe report that nasopharyngeal carriage of S. aureus in rural Gambia is high in all age groups, with approximately 1 out of 4 individuals being carriers in the pre-pneumococcal vaccination era. There are indications that nasopharyngeal carriage of S.aureus could be inversely related to carriage of S. pneumoniae amongst younger children in The Gambian and that S. aureus clones in The Gambia show significant genetic diversity suggesting worldwide dissemination. Findings from this study provide a useful background for impact studies evaluating the introduction of pneumococcal vaccines or other interventions targeting the control of S. aureus infections and disease.

The economic burden of childhood pneumococcal diseases in The Gambia.

BackgroundStreptococcus pneumoniae is a common cause of child death. However, the economic burden of pneumococcal disease in low-income countries is poorly described. We aimed to estimate from a societal perspective, the costs incurred by health providers and families of children with pneumococcal diseases.MethodsWe recruited children less than 5 years of age with outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and bacterial meningitis at facilities in rural and urban Gambia. We collected provider costs, out of pocket costs and productivity loss for the families of children. For each disease diagnostic category, costs were collected before, during, and for 1 week after discharge from hospital or outpatient visit.ResultsA total of 340 children were enrolled; 100 outpatient pneumonia, 175 inpatient pneumonia 36 pneumococcal sepsis, and 29 bacterial meningitis cases. The mean provider costs per patient for treating outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and meningitis were US$8, US$64, US$87 and US$124 respectively and the mean out of pocket costs per patient were US$6, US$31, US$44 and US$34 respectively. The economic burden of outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and meningitis increased to US$15, US$109, US$144 and US$170 respectively when family members’ time loss from work was taken into account.ConclusionThe economic burden of pneumococcal disease in The Gambia is substantial, costs to families was approximately one-third to a half of the provider costs, and accounted for up to 30 % of total societal costs. The introduction of pneumococcal conjugate vaccine has the potential to significantly reduce this economic burden in this society.Electronic supplementary materialThe online version of this article (doi:10.1186/s12962-016-0053-4) contains supplementary material, which is available to authorized users.

Factors Associated with Non-Participation and Non-Adherence in Directly Observed Mass Drug Administration for Malaria in The Gambia.

IntroductionThe potential benefits of Mass Drug Administration (MDA) for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors that may affect participation and adherence to MDA programs.MethodologyThis social science study was ancillary to a one-round directly observed MDA campaign with dihydroartemisinin-piperaquine, carried out in 12 villages in rural Gambia between June and August 2014. The social science study employed a mixed-methods approach combining qualitative methods (participant observation and in-depth interviewing) and quantitative methods (structured follow-up interviews among non-participating and non-adhering community members).ResultsOf 3942 people registered in the study villages, 67.9% adhered to the three consecutive daily doses. For the remaining villagers, 12.6% did not attend the screening, 3.5% was not eligible and 16% did not adhere to the treatment schedule. The main barriers for non-participation and adherence were long and short-term mobility of individuals and specific subgroups, perceived adverse drug reactions and rumors, inconveniences related to the logistics of MDA (e.g. waiting times) and the perceived lack of information about MDA.ConclusionWhile, there was no fundamental resistance from the target communities, adherence was 67.9%. This shows the necessity of understanding local perceptions and barriers to increase its effectiveness. Moreover, certain of the constraining factors were socio-spatially clustered which might prove problematic since focal areas of residual malaria transmission may remain allowing malaria to spread to adjacent areas where transmission had been temporarily interrupted.

Nasopharyngeal colonization of Gambian infants by Staphylococcus aureus and Streptococcus pneumoniae before the introduction of pneumococcal conjugate vaccines.

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.

Remedial after-school support classes offered in rural Gambia (The SCORE trial): study protocol for a cluster randomized controlled trial.

BackgroundLow education levels are endemic in much of the developing world, particularly in rural areas where traditional government-provided public services often have difficulty reaching beneficiaries. Providing trained para-teachers to teach regular after-school remedial education classes has been shown to improve literacy and numeracy in children of primary school age residing in such areas in India. This trial investigates whether such an intervention can also be effective in a West African setting with similarly low learning levels and difficult geographic access.Methods/DesignDesign: cluster-randomized controlled trial.Clusters: villages or groups of villages with 15–300 households and at least 15 eligible children in the Lower River and North Bank Regions of The Gambia.Participants: children born between 1 September 2007 and 31 August 2009 planning to enter the first grade, for the first time, in the 2015–2016 school year in eligible villages. We anticipate enrolling approximately 150 clusters of villages with approximately 6000 children as participants.Intervention: a program providing remedial after-school lessons, focusing on literacy and numeracy, 5 to 6 days a week for 3 years to eligible children, based on the intervention evaluated in the Support To Rural India’s Public Education System (STRIPES) trial (PLoS ONE 8(7):e65775).Control: both the intervention and control groups will receive small bundles of useful materials during annual data collection as recompense for their time. If the education intervention is shown to be cost-effective at raising learning levels, it is expected that the control group villages will receive the intervention for several years after the trial results are available.Outcomes: the primary outcome of the trial is a composite mathematics and language test score. Secondary outcomes include school attendance, enrollment, performance on nationally administered exams, parents’ spending on education, spillover learning to siblings and family members, and school-related time use of parents and children. Subgroup analyses of the primary outcome will also be carried out based on ethnic group, gender, distance from the main highway, parents’ education level, and school type.The trial will run by independent research and implementation teams and supervised by a Trial Steering Committee.DiscussionAlong with the overall impact of the intervention, we will conduct a cost-effectiveness analysis.There are no major ethical issues for this study.Trial registrationCurrent controlled trials ISRCTN12500245. 1 May 2015.

Cohort Profile: The Kiang West Longitudinal Population Study (KWLPS)-a platform for integrated research and health care provision in rural Gambia.

Cohort Profile: The Kiang West Longitudinal Population Study (KWLPS)-a platform for integrated research and health care provision in rural Gambia.

Early life nutritional programming of health and disease in The Gambia.

Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism

Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-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 metabolism.Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2years 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 104weeks (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 52wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P=0.04] and from 24wk for TALP [44.7 (29.6) U/L, P=0.04]. 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.

Child Mortality after Discharge from a Health Facility following Suspected Pneumonia, Meningitis or Septicaemia in Rural Gambia: A Cohort Study.

ObjectiveTo measure mortality and its risk factors among children discharged from a health centre in rural Gambia.MethodsWe conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2–59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors.FindingsOne hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2–11 and 12–59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5–13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5–11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality.ConclusionGambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely malnourished children.

High rate of respiratory viral co-infection in children with lower and upper respiratory tract infections in rural Gambia

High rate of respiratory viral co-infection in children with lower and upper respiratory tract infections in rural Gambia

Risk factors for malaria in children presenting with fever or history of fever in rural Gambia

Successful control of malaria depends upon the detailed knowledge of its epidemiology, including the knowledge of environmental, behavioral, socio-economic and socio-demographic factors that influence its prevalence, and on the knowledge and use of preventive measures. We carried out a cross-sectional study to assess the risk factors for malaria in children presenting with fever in rural Gambia. Three hundred and seventy-six children aged 5 months to 10 years presenting to Farafenni health centre, the Gambia with fever or history of fever were enrolled. The socio-demographic characteristics, clinical findings, and knowledge and use of preventive measures in malaria were documented. Finger-prick blood sampling for malaria was obtained and two sets of smears (thick and thin) were prepared and stained with Giemsa stain. One hundred and eighty two children (48.4%) had malaria. The significant risk factors associated with malaria were non-use of insecticide treated bed nets [χ2 = 8.82, P = 0.01, (95% confidence interval 0.10–0.67)] and age [χ2 = 9.18, P = 0.004, (95% confidence interval 0.31–0.78)]. There were no significant associations identified between the development of malaria and parental education, occupation, knowledge of the cause of malaria, type of roof or wall in the home, or whether the parents reared livestock.

Risk factors for mortality in childhood pneumonia in a rural West African region

Pneumonia is a major killer of children worldwide. It is responsible for 19% of under-five-year-old mortality, of which 70% occurs in sub-Saharan Africa and South East Asia. A substantial proportion of deaths attributed to pneumonia is caused by failure to recognise factors at presentation that affect prognosis. The present study was aimed to assess for factors at presentation that determine mortality among children with WHO ARI defined severe pneumonia. This was a prospective observational study of consecutive children aged 2 to 59 months admitted with severe pneumonia at a major health centre in rural Gambia to de- termine the risk factors for mortality using logistic regression analysis. Four hundred and twenty (27.6%) out of the 1517 under- five admissions during the study period fulfilled the criteria of severe pneumonia using the WHO ARI criteria. Fifteen of the 420 cases died giving case fatality of 36 per 1000 admissions, with pneumonia accounting for 21.4% of all 70 deaths during the period. Although age ranges 12-23 months and 36-47 months, overcrowding, hypothermia at presentation, oedematous PEM, severe wasting, grunting respiration, convulsion, somnolence and hypoxaemia were significantly associated with mortality (p < 0.05); only convulsions ( OR = 16.64, 95% CI 1.028-1.033) and severe wasting (OR = 5.05, 95% CI 1.459-20.484,) were independent determinants of mortality. We conclude that children with severe pneumonia who in addition have severe wasting and convulsion are at increased risks of dying and should be managed in better equipped secondary or tertiary health facilities.

Seasonality of Pneumococcal Nasopharyngeal Carriage in Rural Gambia Determined within the Context of a Cluster Randomized Pneumococcal Vaccine Trial.

BackgroundWe conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage.Methods636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected.ResultsPrevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis.ConclusionsIn areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data.

Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment.

BackgroundInterindividual 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.ResultsFirst, 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.ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0660-y) contains supplementary material, which is available to authorized users.

Progressive influence of body mass index-associated genetic markers in rural Gambians

BackgroundIn 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...

Health & Demographic Surveillance System Profile: Farafenni Health and Demographic Surveillance System in The Gambia.

The Farafenni Health and Demographic Surveillance System (Farafenni HDSS) is located 170 km from the coast in a rural area of The Gambia, north of the River Gambia. It was set up in 1981 by the UK Medical Research Council Laboratories to generate demographic and health information required for the evaluation of a village-based, primary health care programme in 40 villages. Regular updates of demographic events and residency status have subsequently been conducted every 4 months. The surveillance area was extended in 2002 to include Farafenni Town and surrounding villages to support randomized, controlled trials. With over three decades of prospective surveillance, and through specific scientific investigations, the platform (population ≈ 50,000) has generated data on: morbidity and mortality due to malaria in children and during pregnancy; non-communicable disease among adults; reproductive health; and levels and trends in childhood and maternal mortality. Other information routinely collected includes causes of death through verbal autopsy, and household socioeconomic indicators. The current portfolio of the platform includes tracking Millennium Development Goal 4 (MDG4) attainments in rural Gambia and cause-of-death determination.

Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniae serotype 1 genotypes in healthy Gambians before and after the 7-valent pneumococcal conjugate vaccine.

Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease. However, this invasive serotype is hardly found in nasopharyngeal asymptomatic carriage and therefore large epidemiological studies are needed to assess the dynamics of serotype 1 infection. Within the context of a large cluster randomized trial conducted in rural Gambia to assess the impact of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary analysis describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1 and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS) were collected before PCV-7 vaccination (December 2003–May 2004) and up to 30 months after PCV-7 vaccination. The post-vaccination time was divided in three periods to ensure an equal distribution of the number of samples: (1) July 2006–March 2007, (2) April 2007–March 2008 and (3) April 2008–Feb 2009. S. pneumoniae serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of 12,319 NPS samples collected. In the pre-vaccination period, prevalence of serotype 1 was 0.47% in both study arms. In the post-vaccination periods, prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and 0.165% in period 2, while prevalence in partly vaccinated villages was between 0.17% in period 3 and 1.34% in period 2. Overall, four different genotypes were obtained, with ST3081 the most prevalent (60.71%), followed by ST618 (29.76%). ST3081 was found only in post-vaccination period 2 and 3, while ST618 had disappeared in post-vaccination period 3. Distribution of these major genotypes was similar in both study arms. Emergence of ST3081 and concomitant disappearance of ST618 may suggest a change in the molecular epidemiology of pneumococcal serotype 1 in this region. This change is not likely to be associated with the introduction of PCV-7 which lacks serotype 1, as it was observed simultaneously in both study arms. Future population-based epidemiological studies will provide further evidence of substantive changes in the pneumococcal serotype 1 epidemiology and the likely mechanisms.