Delay in the diagnosis of pulmonary tuberculosis in The Gambia, West Africa: A cross-sectional study.

OBJECTIVES: To investigate the pattern of tuberculosis (TB) care initiation and risk factors for TB diagnostic delay in The Gambia. METHODS: In this cross-sectional study, adult patients diagnosed with pulmonary TB (pTB) in public facilities in the Greater Banjul Area of The Gambia were consecutively recruited from October 2016 to March 2017. Diagnostic delay was defined as >21 days from the onset of at least one symptom suggestive of pTB to diagnosis. Logistic regression analyses were used to investigate risk factors for diagnostic delay. RESULTS: Overall, 216 pTB patients were included in the study; the median (Interquartile Range (IQR)) age was 30 (23-39) years and 167 (77%) were male patients. Of the 216 patients, 110 (50.9%) of them initiated care-seeking in the formal and informal private sector and 181/216 (83.8%) had TB diagnostic delay. The median (IQR) duration from the onset of symptoms to TB diagnosis was 34 (28-56) days. Age groups 18-29 years (aOR 3.2; 95% CI 1.2-8.8 [p = 0.02]) and 30-49 years (aOR 5.1; 95% CI 1.6-16.2 [p = 0.006]) and being employed (aOR 4.2; 95% CI 1.7-10.5 [p = 0.002]) were independent risk factors for TB diagnostic delay. CONCLUSION: There is considerable TB diagnostic delay in The Gambia, and this is likely to be worsened by the COVID-19 pandemic

Assessment of agro-ecological influence on the seed quality of groundnut (Arachis hypogaea) in The Gambia

A survey was conducted to assess the quality of groundnut seed produced and stored under ambient environment across various agro-ecologies of The Gambia, with a view to understanding regions with comparative advantage for its production and storage. Seed production activities of 60 seed growers in 26 communities were collected using structured questionnaires, interviews and observations. The Global Positioning System (GPS) coordinates of the communities were geo-referenced to identify the geographical positioning of the production sites. Samples of the groundnut pods were taken from the seed stores, threshed and subjected to seed quality analysis. Descriptive analysis was used to categorize the seed sources, hectarage cultivated, while seed quality data were subjected to analysis of variance of Nested Design. Means of significant factors were separated using Duncan Multiple Range Test (DMRT) at 5% significant level. The study showed that groundnut seed production is better concentrated in regions with optimum and sustainable rainfall that will reduce abiotic stress during seed development like the Lower River Region, West Coast Region and Central River Region. Fleur-11 variety was identified as one of the most promising varieties for groundnut cultivation in The Gambia and Tropical Africa

Killer-cell immunoglobulin-like receptors and malaria caused by Plasmodium falciparum in The Gambia

The relevance of innate immune responses to Plasmodium falciparum infection, in particular the central role of natural killer (NK) cell-derived interferon gamma (IFN-γ), is becoming increasingly recognised. Recently, it has been shown that IFN-γ production in response to P. falciparum antigens is in part regulated by killer-cell immunoglobulin-like receptor (KIR) genes, and a study from malaria-exposed Melanesians suggested an association between KIR genotypes and susceptibility to infection. This prompted us to determine and compare the frequencies of 15 KIR genes in Gambian children presenting with either severe malaria (n = 133) or uncomplicated malaria (n = 188) and in cord-blood population control samples (n = 314) collected from the same area. While no significant differences were observed between severe and uncomplicated cases, proportions of individuals with KIR2DS2+C1 and KIR2DL2+C1 were significantly higher among malaria cases overall than in population control samples. In an exploratory analysis, activating KIR genes KIR2DS2, KIR3DS1 and KIR2DS5 were slightly higher in children in disease subgroups associated with the highest mortality. In addition, our data suggest that homozygosity for KIR genotype A might be associated with different malaria outcomes including protection from infection and higher blood parasitaemia levels in those that do get infected. These findings are consistent with a probable role of KIR genes in determining susceptibility to malaria, and further studies are warranted in different populations

Discovery and Validation of Biomarkers to Guide Clinical Management of Pneumonia in African Children

Background Pneumonia is the leading cause of death in children globally. Clinical algorithms remain suboptimal for distinguishing severe pneumonia from other causes of respiratory distress such as malaria or distinguishing bacterial pneumonia and pneumonia from others causes, such as viruses. Molecular tools could improve diagnosis and management. Methods We conducted a mass spectrometry–based proteomic study to identify and validate markers of severity in 390 Gambian children with pneumonia (n = 204) and age-, sex-, and neighborhood-matched controls (n = 186). Independent validation was conducted in 293 Kenyan children with respiratory distress (238 with pneumonia, 41 with Plasmodium falciparum malaria, and 14 with both). Predictive value was estimated by the area under the receiver operating characteristic curve (AUC). Results Lipocalin 2 (Lpc-2) was the best protein biomarker of severe pneumonia (AUC, 0.71 [95% confidence interval, .64–.79]) and highly predictive of bacteremia (78% [64%–92%]), pneumococcal bacteremia (84% [71%–98%]), and “probable bacterial etiology” (91% [84%–98%]). These results were validated in Kenyan children with severe malaria and respiratory distress who also met the World Health Organization definition of pneumonia. The combination of Lpc-2 and haptoglobin distinguished bacterial versus malaria origin of respiratory distress with high sensitivity and specificity in Gambian children (AUC, 99% [95% confidence interval, 99%–100%]) and Kenyan children (82% [74%–91%]). Conclusions Lpc-2 and haptoglobin can help discriminate the etiology of clinically defined pneumonia and could be used to improve clinical management. These biomarkers should be further evaluated in prospective clinical studies

Implementation of a sustainable project in the Tanbi Wetland Complex, Banjul (The Gambia)

The aim of this on-going study is creating a design for a boardwalk that is part of an ecotouristic project in the Tanbi Wetland National Park (TWNP). This mangrove area is located adjacent to the capital of The Gambia, Banjul. The nature reserve was listed as a Ramsar site in 2007 (an "Area of International Importance") but it is under great human pressure, such as through the dumping of municipal waste in the mangrove swamps, the erosion of banks by speedboats from tourist water sports, etc. In this way, the mangrove habitats are degraded and can even be destroyed.The entire project is supported by the City of Ostend, which has a city link with Banjul since 2003. As the City of Ostend co-finances the entire project, a cost calculation will be carried out.The boardwalk project aims at creating awareness, both for the people of Banjul and for tourists visiting Gambia. Eco-education also plays an important role in this process; local students can visit the TWNP and learn about the mangroves and their importance. The TWNP is located close to hotels and tourist areas in Banjul. The local boats could be used for excursions in the small creeks, combined with the boardwalk-excursion. Guided tours by local inhabitants make visitors aware of the problems affecting the nature reserve.The project includes a pedestrian walk-on bridge with a length of approximately one kilometer, two observation towers that can be used by birdwatchers, a platform where oyster women can prepare local products for visitors, a pontoon for moor canoes, etc. Another proposition is to build an openair museum, the “Sea Life Center”, located in seven different huts across the entire boardwalk. It portrays the different habitats and their ecological and socio-ecological components present in and around the mangrove.During the calculation of the wood structure the Belgian standards (NBN) and Eurocode (EC) were followed where possible. The Australian standards (AUS) were also consulted, in contrast to the Belgian standards, they have standards specifically for boardwalks. These standards are used when designing constructions. Design values were obtained from tests carried out according to the standard. We drew every boardwalk model using Google Sketchup Pro 7.1, a 3D software tool.During a 5-week stay in Banjul in January-February 2011, the mangrove area will be mapped using a surveying device. The Trimble Pathfinder Pro XRT equipped with an OmniSTAR license allows measurements with an accuracy up to 20 centimeters. Based on the maps that were made, implementation plans are composed, making construction possible by the inhabitants of Banjul

BR-squared: a practical solution to the winner’s curse in genome-wide scans

The detrimental effects of the winner’s curse, including overestimation of the genetic effects of associated variants and underestimation of sufficient sample sizes for replication studies are well-recognized in genome-wide association studies (GWAS). These effects can be expected to worsen as the field moves from GWAS into whole genome sequencing. To date, few studies have reported statistical adjustments to the naive estimates, due to the lack of suitable statistical methods and computational tools. We have developed an efficient genome-wide non-parametric method that explicitly accounts for the threshold, ranking, and allele frequency effects in whole genome scans. Here, we implement the method to provide bias-reduced estimates via bootstrap re-sampling (BR-squared) for association studies of both disease status and quantitative traits, and we report the results of applying BR-squared to GWAS of psoriasis and HbA1c. We observed over 50% reduction in the genetic effect size estimation for many associated SNPs. This translates into a greater than fourfold increase in sample size requirements for successful replication studies, which in part explains some of the apparent failures in replicating the original signals. Our analysis suggests that adjusting for the winner’s curse is critical for interpreting findings from whole genome scans and planning replication and meta-GWAS studies, as well as in attempts to translate findings into the clinical setting

Health seeking behaviour, health system experience and tuberculosis case finding in Gambians with cough

BACKGROUND: Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis. METHODS: During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing ≥ 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray. RESULTS: 122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0 – 106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks. CONCLUSION: The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear

Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations

Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference.

Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner