Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda.

BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia.

SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages.

Spatial analysis of tuberculosis in an urban west African setting: is there evidence of clustering?

OBJECTIVES: To describe the pattern of tuberculosis (TB) occurrence in Greater Banjul, The Gambia with Geographical Information Systems (GIS) and Spatial Scan Statistics (SaTScan) and to determine whether there is significant TB case clustering. METHODS: In Greater Banjul, where 80% of all Gambian TB cases arise, all patients with TB registered at chest clinics between March 2007 and February 2008 were asked to participate. Demographic, clinical characteristics and GPS co-ordinates for the residence of each consenting TB case were recorded. A spatial scan statistic was used to identify purely spatial and space-time clusters of tuberculosis among permanent residents. RESULTS: Of 1145 recruited patients with TB, 84% were permanent residents with 88% living in 37 settlements that had complete maps available down to settlement level. Significant high- and low-rate spatial and space-time clusters were identified in two districts. The most likely cluster of high rate from both the purely spatial analysis and the retrospective space-time analysis were from the same geographical area. A significant secondary cluster was also identified in one of the densely populated areas of the study region. CONCLUSIONS: There is evidence of significant clustering of TB cases in Greater Banjul, The Gambia. Systematic use of cluster detection techniques for regular TB surveillance in The Gambia may aid effective deployment of resources. However, passive case detection dictates that community-based active case detection and risk factor surveys would help confirm the presence of true clusters and their causes.

Serum lipid profile of breast cancer patients.

The purpose of this study was to carry out a comparative study to investigate the effect of lipid profile, oestradiol and obesity on the risk of a woman developing breast cancer. This study was carried out at the Komfo Anokye Teaching Hospital (KATH), Peace and Love Hospital, Oduom, Kumasi and Redeemed Clinic, Nima, Accra between May 2002 and March 2003. In this study, 200 consented women comprising 100 breast cancer patients (43 pre- and 57 post-menopausal) and 100 controls (45 pre- and 55 post-menopausal) with similar age range (25 to 80 years) were assessed for lipid profile, oestradiol and BMI. There was a significant increase in Body Mass Index (BMI) (p = 0.011), Total Cholesterol (TC) (p < 0.001), triglyceride (p = 0.026) and low density lipoprotein (LDL-cholesterol) (p = 0.001) of the breast cancer patients compared to the controls. With the exception of oestradiol (EST) that decreased, the lipid profile generally increased with age in both subjects and controls with the subjects having a much higher value than the corresponding control. There was also a significant positive correlation between BMI and TC (r2 = 0.022; p = 0.002) and also between BMI and LDL-cholesterol (r2 = 0.031; p = 0.0003). Apart from EST and LDL-cholesterol that were increased significantly only in the postmenopausal phase in comparison to the controls, BMI, TC and TG were increased in both pre-menopausal and post menopausal phases with HDL-cholesterol remaining unchanged. This study confirms the association between dyslipidaemia, BMI and increased breast cancer risk.

Haematological values from a Gambian cohort--possible reference range for a West African population.

The objective of this study was to establish haematological reference ranges for the West African subregion using a Gambian cohort. We analysed full blood counts from 1279 subjects aged > or =1 year. Anthropometric and body composition measurements were performed. Haematological mean values, medians and 90% reference values were calculated and related to malnutrition in children and thinness and/or obesity in adults. Haemoglobin (Hb) and mean corpuscular volume (MCV) significantly increased with age (P < 0.00001). There were gender-related changes in Hb from 15 years of age (P = 0.001) and for MCV only in adults (P = 0.0002). Hb was significantly reduced in underweight and stunted children (P = 0.0001 and 0.0002, respectively) but was unaffected by thinness or obesity in adults. White blood cell (WBC) and platelet counts were highest under 5 years and declined significantly with age (P < 0.0001 and 0.0001). While, there were no gender-related differences with WBC, there were higher WBC counts in underweight (P = 0.0001) and stunted (P < 0.0001) children. Adult females had significantly higher mean platelet counts compared with males (P = 0.006). The mean and median values of haematological parameters in The Gambia are similar to other standards but the 90% reference range for each parameter encompasses lower values when compared with Western standards.

Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa.

BACKGROUND: Host-related and environment-related factors have been shown to play a role in the development of tuberculosis (TB), but few studies were carried out to identify their respective roles in resource-poor countries. METHODS: A multicentre case-control study was conducted in Guinée, Guinea Bissau, and The Gambia, from January 1999 to March 2001. Cases were newly detected smear positive TB patients. Two controls were recruited for each case, one within the household of the case, and one in the community. RESULTS: Regarding host-related factors, univariate analysis by conditional logistic regression of 687 matched pairs of cases and household controls showed that TB was associated with male sex, family history of TB, absence of a BCG scar, smoking, alcohol, anaemia, HIV infection, and history and treatment of worm infection. In a multivariable model based on 601 matched pairs, male sex, family history of TB, smoking, and HIV infection were independent risk factors of TB. The investigation of environmental factors based on the comparison of 816 cases/community control pairs showed that the risk of TB was associated with single marital status, family history of TB, adult crowding, and renting the house. In a final model assessing the combined effect of host and environmental factors, TB was associated with male sex, HIV infection, smoking (with a dose-effect relationship), history of asthma, family history of TB, marital status, adult crowding, and renting the house. CONCLUSION: TB is a multifactorial disorder, in which environment interacts with host-related factors. This study provided useful information for the assessment of host and environmental factors of TB for the improvement of TB control activities in developing countries.

Risk factors for defaulting from tuberculosis treatment: a prospective cohort study of 301 cases in the Gambia.

SETTING: An urban tuberculosis (TB) clinic, The Gambia. OBJECTIVE: To identify patient characteristics associated with increased rates of defaulting from treatment, specifically knowledge and cost factors amenable to intervention. DESIGN: Prospective cohort study of TB cases at least 15 years of age commencing treatment, interviewed by semi-structured questionnaire and followed for attendance at thrice-weekly directly observed treatment (DOT). RESULTS: Of 301 patients, 76 (25.2%) defaulted from treatment and 25 did not return for treatment. The defaulting rate was higher among those who said they were uncertain that their treatment would work (HR 3.64; 95%CI 1.42-9.31, P = 0.007) and among those who incurred significant time or money costs travelling to receive treatment (HR 2.67; 95%CI 1.05-6.81; P = 0.04). These factors had differing effects with respect to time: uncertainty over treatment success was important in the first 90 days of treatment, while increased cost of travelling to the clinic was important after 90 days. CONCLUSION: In The Gambia, risk groups for defaulting can be recognised at the start of treatment and are at highest risk at different times. Home-based self-administration of medications after 3 months of DOT should be considered as confidence in treatment success rises, and the costs of travelling to receive treatment start to take their toll.

Design and implementation of relational databases relevant to the diverse needs of a tuberculosis case contact study in the Gambia.

The data requirements of a large multidisciplinary tuberculosis case contact study are complex. We describe an ACCESS-based relational database system that meets our rigorous requirements for data entry and validation, while being user-friendly, flexible, exportable, and easy to install on a network or stand alone system. This includes the development of a double data entry package for epidemiology and laboratory data, semi-automated entry of ELISPOT data directly from the plate reader, and a suite of new programmes for the manipulation and integration of flow cytometry data. The double entered epidemiology and immunology databases are combined into a separate database, providing a near-real-time analysis of immuno-epidemiological data, allowing important trends to be identified early and major decisions about the study to be made and acted on. This dynamic data management model is portable and can easily be applied to other studies.