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Background Close contact between an infectious and susceptible person is an important factor in respiratory disease transmission. Information on social contacts and mixing patterns in a population is crucial to understanding transmission patterns and informing transmission models of respiratory infections. Although West Africa has one of the highest burdens of respiratory infections, there is a lack of data on interpersonal contact and mixing patterns in this region. Methods Between January and November 2022, we conducted a cross-sectional, social contact survey within the population of the Central and Upper River Regions of The Gambia. Selected participants completed a questionnaire about their travel history and social contacts, detailing the number, intensity, location, frequency, duration, and age of contacts. We calculated age-standardized contact matrices to determine contact patterns in the population. Results Overall, individuals made an average of 12.7 (95% CI: 12.4–13.0) contacts per day. Contact patterns were mostly age-assortative and 84.5% of all contacts were physical. School-aged children (5–14 years) had the highest mean number of physical contacts (11.3, 95% CI: 10.9–11.8) while the < 1-year age group had the fewest contacts (9.4, 95% CI: 9.1–9.8). A large proportion of contacts (78%) occurred at home. Daily number of contacts increased with household size. While we did not observe any effect of gender on contact patterns, there were seasonal variations in contact type. Non-physical contacts were higher during the dry season compared to the rainy season. In contrast, there were more physical contacts in the rainy season compared to the dry season. Conclusions In rural Gambia, social contact patterns were primarily driven by household mixing. Most contacts were physical and mostly age-assortative, particularly among school-aged children. Our data can improve infectious disease transmission models of respiratory pathogens in high-transmission settings, which are valuable for optimizing the delivery of different interventions.

Background The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care. Methods A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care. Results All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%. Conclusions Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care.

Background Guidance exists to inform the content of statistical analysis plans in clinical trials. Though not explicitly stated, this guidance is generally focused on clinical trials in which the randomization units are individual patients and not groups of patients. There are critical considerations for the analysis of cluster randomized trials, such as accounting for clustering, the risk of imbalances between the arms due to post-randomization recruitment, and the need to use small sample corrections when the number of clusters is small. Methods This paper outlines the protocol for the development of a set of reporting guidelines for the content of statistical analysis plans for cluster randomized trials (including variations such as the stepped wedge cluster randomized trial and other cluster cross-over designs) by extending the minimum reporting analysis requirements as previously defined for individually randomized trials to cluster randomized trials. The guideline will be developed using a consensus-based approach, modifying existing reporting items from the guideline for individually randomized trials and extending to include new items. Discussion The guideline will be developed so it can be used independently of the guideline for individually randomized designs. The consensus guidelines will be published in an open-access journal, including key guidance as well as exploration and elaboration.

Infant DNA methylation profiles are associated with their mother's periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials. We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 μg folic acid, 5.2 μg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (-29.5 to -17.1) and 15.5% (-21.2 to -9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (-15.8 to -1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine. The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia. Clinicaltrials.gov Reference NCT03431597.

Background Although pneumococcal conjugate vaccines (PCVs) have been used widely in many low and middle-income countries, residual vaccine-type (VT) carriage persists in these settings. We examined the role of specific age groups in transmission and as reservoirs of VT pneumococcal infection in The Gambia. Methods Between January and November 2022, we conducted a nested, population-based, cross-sectional social contact and pneumococcal carriage survey in the Central and Upper River Regions of The Gambia. Participants completed questionnaires on carriage risk factors and social contacts. Nasopharyngeal swabs were collected from selected household members across all age groups. Streptococcus pneumoniae was isolated and serotyped using standard methods. We analysed matched contact and pneumococcal carriage data and estimated the proportions of VT carriage attributable to contact with different age groups. Results A total of 1638 participants were enrolled, of which 67% were children aged 0–14 years. Pneumococcal carriage prevalence was 59.6% (95% CI: 53.9 – 65.1%) in 0–4 year-olds and 36.1% (95% CI: 29.6 – 43.1%) in 5–14 year-olds. PCV13 VT carriage prevalence was not significantly different (10–13%) between these age groups. Among pneumococcal carriers, the proportion of VT carriage was significantly higher in 5- 14-year-olds [35.7% (95% CI: 25.9 – 46.9%)] compared to 0-4-year-olds [17.8% (95% CI: 13.9 – 22.6%, p-value < 0.001)]. The odds of VT carriage were 10% higher [AOR = 1.10, 95% CI: 1.01–1.20] for each additional physical contact with a child aged 10–14 years. We estimated that children aged 5–14 years contributed about 63% to the overall risk of exposure to VT pneumococci in the population. Conclusions In rural Gambia, school-aged children, particularly those aged 5–9 years, are the main drivers of VT pneumococcal transmission. In the context of high coverage of routine PCV vaccination in infants, this suggests waning PCV protection by school entry. A booster dose for children at school entry may support better control of VT circulation in the population.

Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the aetiology and epidemiology of enteric infections covering 27,567 Gambian children less than five years of age in the surveillance area. Fourteen children infected with NTS were traced back to their family compounds and anal swabs collected from 210 domestic animals present in their households. Identified NTSs were serotyped and genotyped by multi-locus sequencing typing. NTS was identified from 21/210 animal sources in the households of the 14 infected children. Chickens carried NTS more frequently than sheep and goats; 66.6%, 28.6% and 4.8% respectively. The most common NTS serovars were S. Colindale in humans (21.42%) and S. Poona in animals (14.28%). MLST on the 35 NTS revealed four new alleles and 24 sequence types (ST) of which 18 (75%) STs were novel. There was no overlap in serovars or genotypes of NTS recovered from humans or animal sources in the same household. Our results do not support the hypothesis that humans and animals in close contact in the same household carry genotypically similar Salmonella serovars. These findings form an important baseline for future studies of transmission of NTS in humans and animals in Africa.

Background:  Iron deficiency and its associated anaemia (IDA) are the leading forms of micronutrient malnutrition worldwide. Here we describe the rationale and design of the first clinical trial evaluating the efficacy and safety of an innovative nano iron supplement, iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in young children (IHAT-GUT trial). Oral iron is often ineffective due to poor absorption and/or gastrointestinal adverse effects. IHAT is novel since it is effectively absorbed whilst remaining nanoparticulate in the gut, therefore should enable supplementation with fewer symptoms. Methods: IHAT-GUT is a three-arm, double-blind, randomised, placebo-controlled phase II trial conducted in Gambian children 6-35 months of age. The intervention consists of a 12-week supplementation with either IHAT, ferrous sulphate (both at doses bioequivalent to 12.5 mg Fe /day) or placebo. The trial aims to include 705 children with IDA who will be randomly assigned (1:1:1) to each arm. The primary objectives are to test non-inferiority of IHAT in relation to ferrous sulphate at treating IDA, and to test superiority of IHAT in relation to ferrous sulphate and non-inferiority in relation to placebo in terms of diarrhoea incidence and prevalence. Secondary objectives are mechanistic assessments, to test whether IHAT reduces the burden of enteric pathogens, morbidity, and intestinal inflammation, and that it does not cause detrimental changes to the gut microbiome, particularly in relation to Lactobacillaceae , Bifidobacteriaceae and Enterobacteriaceae . Discussion: This trial will test the hypothesis that supplementation with IHAT eliminates iron deficiency and improves haemoglobin levels without inducing gastrointestinal adverse effects. If shown to be the case, this would open the possibility for further testing and use of IHAT as a novel iron source for micronutrient intervention strategies in resource-poor countries, with the ultimate aim to help reduce the IDA global burden. Registration: This trial is registered at clinicaltrials.gov ( NCT02941081 ).

Sub-Saharan Africa has a high burden of pneumococcal diseases. Pneumococcal carriage precedes invasive disease and transmission. The introduction of pneumococcal conjugate vaccines (PCVs) has significantly reduced global vaccine-type (VT) pneumococcal disease, but data on PCVs' long-term impact on VT serotypes in Africa are limited. We aimed to evaluate PCV13's long-term effect on pneumococcal carriage in rural Gambia. From January to November 2022, we conducted a population-based, cross-sectional pneumococcal carriage survey in Central and Upper River Regions of The Gambia. We collected data on demographic characteristics, clinical history, risk factors, and PCV status. Nasopharyngeal swabs were taken from randomly selected household members of all ages. Streptococcus pneumoniae was isolated and serotyped using standard methods. We measured the prevalence of pneumococcal carriage by specific age groups, PCV13 vaccination status, and the proportions of different pneumococcal outcomes among carriers. We performed multivariable logistic regression to examine factors associated with VT carriage. Overall, 4087 participants were enrolled; the prevalence of pneumococcal carriage was 32.1% (95% CI: 29.34% – 35.03%). The estimated prevalence of PCV13 VT carriage was 6.4% (95% CI: 5.48% - 7.47%). Children aged 5–9 years had the highest VT carriage prevalence at 13.6% (95% CI: 10.34% - 17.56%). Among fully PCV-vaccinated children under 10, the odds of VT carriage in 5–9-year-olds were 1.60 times higher than in infants aged 0–11 months [AOR = 1.60, 95% CI:1.06–2.41]. The prevalence of VT carriage was similar among fully PCV-vaccinated and unvaccinated children under 10 years of age. Serotypes 19F, 3 and 6A were the most abundant VTs; 19F and 3 were the most prevalent among <5 and 5–14-year-old children, respectively. Ten years after the introduction of PCV13 in the Gambia, residual VT carriage persists, particularly in age groups in whom direct protection from immunization in infancy has waned. A booster dose or catch-up vaccinations could aid control of VT circulation. •Substantial reductions in VT carriage were observed in children, with significant indirect effects on unvaccinated adults.•Residual carriage of vaccine-type pneumococci persists, especially among fully PCV-vaccinated children under 10 years of age.•Children aged 5–9 years were identified as primary reservoirs of VT carriage.•The prevalence of VT carriage was similar in fully PCV-vaccinated and unvaccinated children under 10 years of age.•Serotypes 3 and 19F were the most common VT serotypes among children aged 5–14 and those aged 0–4, respectively.

Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0–10 weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9 months (1 + 1 co-administration) or YF vaccine administered separately at age 10 months (1 + 1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9 months (3 + 0 separate). Blood samples were collected 28–35 days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres ≥ 1:8 were calculated with 95 % confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than − 10 %. Forty-eight, 66, and 98 participants enrolled in 3 + 0 separate, 1 + 1 co-administration, and 1 + 1 separate groups respectively had NA results. Per protocol analysis of the 3 + 0 separate, 1 + 1 co-administration, 1 + 1 separate, and the combined 1 + 1 separate and 3 + 0 separate groups found that 81 %, 85 %, 92 %, and 88 % of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1 + 1 co-administration and 1 + 1 separate groups was −7 % (95 % CI, −18 % to 3 %). The difference between 1 + 1 co-administration and 3 + 0 separate groups was 4 % (95 % CI, −10 % to 15 %). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9 months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613. •Overall, 86 % of participants had YF NA titres ≥1:8 at 1 month (mo) post-YF vaccination (YFV)•81 %, 92 %, & 85 % of infants who received YFV separately at 9 & 10 mo, and YFV/PCV at 9 mo respectively had YF NA titres ≥1:8•PCV13 co-administered with YF vaccine at 9 mo does not affect seroresponse to YF vaccine.•The difference in proportions comparing YFV/PCV co-administered at 9 mo and YFV given separately at 10 mo was −7 %•There was no statistical difference in the YF seroresponse when the YFV was co-administered with PCV or administered separately

ObjectivesAir pollution has been associated with increased mortality and morbidity in several studies with indications that its effect could be more severe in children. This study examined the relationship between short-term variations in criteria air pollutants and occurrence of sudden infant death syndrome (SIDS).DesignWe used a case-crossover study design which is widely applied in air pollution studies and particularly useful for estimating the risk of a rare acute outcome associated with short-term exposure.SettingThe study used data from the West Midlands region in the UK.ParticipantsWe obtained daily time series data on SIDS mortality (ICD-9: 798.0 or ICD-10: R95) for the period 1996–2006 with a total of 211 SIDS events.Primary outcome measuresDaily counts of SIDS events.ResultsFor an IQR increase in previous day pollutant concentration, the percentage increases (95% CI) in SIDS were 16 (6 to 27) for PM10, 1 (−7 to 10) for SO2, 5 (−4 to 14) for CO, −17 (−27 to –6) for O3, 16 (2 to 31) for NO2 and 2 (−3 to 8) for NO after controlling for average temperature and national holidays. PM10 and NO2 showed relatively consistent association which persisted across different lag structures and after adjusting for copollutants.ConclusionsThe results indicated ambient air pollutants, particularly PM10 and NO2, may show an association with increased SIDS mortality. Thus, future studies are recommended to understand possible mechanistic explanations on the role of air pollution on SIDS incidence and the ways in which we might reduce pollution exposure among infants.