Molecular epidemiology of Mycobacterium africanum in Ghana

BACKGROUND: Mycobacterium africanum comprises two phylogenetic lineages within the M. tuberculosis complex (MTBC) and is an important cause of human tuberculosis (TB) in West Africa. The reasons for this geographic restriction of M. africanum remain unclear. Here, we performed a prospective study to explore associations between the characteristics of TB patients and the MTBC lineages circulating in Ghana. METHOD: We genotyped 1,211 MTBC isolates recovered from pulmonary TB patients recruited between 2012 and 2014 using single nucleotide polymorphism typing and spoligotyping. Associations between patient and pathogen variables were assessed using univariate and multivariate logistic regression. RESULTS: Of the 1,211 MTBC isolates analysed, 71.9 % (871) belonged to Lineage 4; 12.6 % (152) to Lineage 5 (also known as M. africanum West-Africa 1), 9.2 % (112) to Lineage 6 (also known as M. africanum West-Africa 2) and 0.6 % (7) to Mycobacterium bovis. Univariate analysis revealed that Lineage 6 strains were less likely to be isoniazid resistant compared to other strains (odds ratio = 0.25, 95 % confidence interval (CI): 0.05-0.77, P < 0.01). Multivariate analysis showed that Lineage 5 was significantly more common in patients from the Ewe ethnic group (adjusted odds ratio (adjOR): 2.79; 95 % CI: 1.47-5.29, P < 0.001) and Lineage 6 more likely to be found among HIV-co-infected TB patients (adjOR = 2.2; 95 % confidence interval (CI: 1.32-3.7, P < 0.001). CONCLUSION: Our findings confirm the importance of M. africanum in Ghana and highlight the need to differentiate between Lineage 5 and Lineage 6, as these lineages differ in associated patient variables

Tobacco use in older adults in Ghana: sociodemographic characteristics, health risks and subjective wellbeing

BACKGROUND: Tobacco use over the life-course threatens to increase disease burden in older adulthood, including lower income countries like Ghana. This paper describes demographic, socioeconomic, health risks and life satisfaction indices related to tobacco use among older adults in Ghana. METHODS: This work was based on the World Health Organization’s multi-country Study on global AGEing and adult health (SAGE), conducted in six countries including Ghana. Wave one of SAGE in Ghana was conducted in 2007-2008 as collaboration between WHO and the University of Ghana Medical School through the Department of Community Health. A nationally representative sample of 4305 older adults aged 50 years and above were interviewed. Associations between tobacco consumption and sociodemographic, socioeconomic, health risk and life satisfaction were evaluated using chi-square and odds ratio (OR). Logistic regression analyses, adjusted for age, sex and other variables, were conducted to determine predictors of tobacco consumption in older persons. RESULTS: Overall prevalence of current daily smokers among older adults in Ghana was 7.6%. Tobacco use (i.e. ever used tobacco) was associated with older males, (AOR = 1.10, CI 1.05-1.15), older adults residing in rural locations (AOR = 1.37, CI 1.083-1.724), and older adults who used alcohol (AOR = 1.13, CI 0.230-2.418). Tobacco use was also associated (although not statistically significant per p-values) with increased self-reporting of angina, arthritis, asthma, chronic lung disease, depression, diabetes, hypertension, and stroke. Older adults who used tobacco and with increased health risks, tended to be without health insurance (AOR = 1.41, CI 1.111-1.787). Satisfaction with life and daily living was much lower for those who use tobacco. Regional differences existed in tobacco use; the three northern regions (Upper East, Northern and Upper West) had higher proportions of tobacco use among older adults in the country. Quitting tobacco use was higher in the 70+ years age group, in women, among urban residents and in those with at least secondary education. Quitting tobacco use also increased with increasing income levels. CONCLUSIONS: Tobacco use among older adults in Ghana was associated with older men living in rural locations, chronic ill-health and reduced life satisfaction. A high proportion of older adults have stopped using tobacco, demonstrating the possibilities for effective public health interventions. Health risk reduction strategies through targeted anti-smoking health campaigns, improvement in access to health and social protection (such as health insurance) will reduce health risks among older persons who use tobacco

Whole genome sequencing and spatial analysis identifies recent tuberculosis transmission hotspots in Ghana

Whole genome sequencing (WGS) is progressively being used to investigate the transmission dynamics of; Mycobacterium tuberculosis; complex (MTBC). We used WGS analysis to resolve traditional genotype clusters and explored the spatial distribution of confirmed recent transmission clusters. Bacterial genomes from a total of 452 MTBC isolates belonging to large traditional clusters from a population-based study spanning July 2012 and December 2015 were obtained through short read next-generation sequencing using the illumina HiSeq2500 platform. We performed clustering and spatial analysis using specified R packages and ArcGIS. Of the 452 traditional genotype clustered genomes, 314 (69.5%) were confirmed clusters with a median cluster size of 7.5 genomes and an interquartile range of 4-12. Recent tuberculosis (TB) transmission was estimated as 24.7%. We confirmed the wide spread of a Cameroon sub-lineage clone with a cluster size of 78 genomes predominantly from the Ablekuma sub-district of Accra metropolis. More importantly, we identified a recent transmission cluster associated with isoniazid resistance belonging to the Ghana sub-lineage of lineage 4. WGS was useful in detecting unsuspected outbreaks; hence, we recommend its use not only as a research tool but as a surveillance tool to aid in providing the necessary guided steps to track, monitor, and control TB

Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests distinct ecological niches.

Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches

Molecular epidemiology and whole genome sequencing analysis of clinical Mycobacterium bovis from Ghana.

BACKGROUND: Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. METHODS: Mycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis isolates were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. RESULTS: Mycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR = 2.7,p = 0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients with available HIV status, the odds of isolating M. bovis from HIV patients (2/119) was 3.3 higher relative to non-HIV patients (4/774). Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p<0.0001, OR = 124.4,95% CI = 30.1-508.3). Two (13.3%) of the M. bovis isolates were INH resistant due to the S315T mutation in katG whereas one (6.7%) was RIF resistant with Q432P and I1491S mutations in rpoB. M. bovis from Ghana resolved as mono-phyletic branch among mostly M. bovis from Africa irrespective of the host and were closest to the root of the global M. bovis phylogeny. M. bovis-specific amino acid mutations were detected among MTBC core genes such as mce1A, mmpL1, pks6, phoT, pstB, glgP and Rv2955c. Additional mutations P6T in chaA, G187E in mgtC, T35A in Rv1979c, S387A in narK1, L400F in fas and A563T in eccA1 were restricted to the 5 clinical M. bovis from Ghana. CONCLUSION: Our data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups

TB-diabetes co-morbidity in Ghana : the importance of Mycobacterium africanum infection

Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TB-Diabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa.; Consecutive TB cases registered at a tertiary facility in Ghana were recruited from September 2012 to April 2016 and screened for DM using random blood glucose and glycated hemoglobin (HbA1c) level. TB patients were tested for other clinical parameters including HIV co-infection and TB lesion location. Mycobacterial isolates obtained from collected sputum samples were characterized by standard methods. Associations between TBDM patients' epidemiological as well as microbiological variables were assessed.; The prevalence of DM at time of diagnosis among 2990 enrolled TB cases was 9.4% (282/2990). TBDM cases were significantly associated with weight loss, poor appetite, night sweat and fatigue (p&lt;0.001) and were more likely (p&lt;0.001) to have lower lung cavitation 85.8% (242/282) compared to TB Non-Diabetic (TBNDM) patients 3.3% (90/2708). We observed 22.3% (63/282) treatment failures among TBDM patients compared to 3.8% (102/2708) among TBNDM patients (p&lt;0.001). We found no significant difference in the TBDM burden attributed by M. tuberculosis sensu stricto (Mtbss) and Mycobacterium africanum (Maf) and (Mtbss; 176/1836, 9.6% and Maf; 53/468, 11.3%, p = 0.2612). We found that diabetic individuals were suggestively likely to present with TB caused by M. africanum Lineage 6 as opposed to Mtbss (odds ratio (OR) = 1.52; 95% confidence interval (CI): 0.92-2.42, p = 0.072).; Our findings confirms the importance of screening for diabetes during TB diagnosis and highlights the association between genetic diversity and diabetes. in Ghana

Tuberculous tenosynovitis of the flexor tendons of the wrist: a case report

Abstract Background Tuberculous tenosynovitis poses a significant public health challenge, especially in developing countries. It usually affects the flexor tendons of the wrist. Case presentation We present a case of a 65-year-old Ghanaian female. She presented a progressively enlarging mass over the volar aspect of the right wrist and palm. She did not have a previous history of tuberculosis. However, her erythrocyte sedimentation rate was high and Mantoux (purified protein derivative) test was strongly positive (more than 15 mm). Radiograph of ulna, radius, and wrist showed osteopenic changes around the distal radius. Excision biopsy of the mass was done and samples sent for histopathology comment. The findings were an inflamed, thickened synovia with rice bodies: suggestive of tuberculous tenosynovitis. Anti-tuberculous chemotherapy was commenced on the second postoperative day. Conclusion Tuberculous tenosynovitis of the wrist is uncommon. However, in developing countries like Ghana where tuberculosis is prevalent, it should be part of the differential diagnosis of compound palmar ganglion in order to prevent delayed diagnosis and treatment

Tuberculous tenosynovitis of the flexor tendons of the wrist: A case Report.

<div>Introduction Tuberculous tenosynovitis of the flexor tendons of the wrist also referred to, as a compound palmar ganglion is uncommon. It has a classical clinical presentation and histopathology confirms it. Case Presentation We present a case of a 65 year old Ghanaian female with a two-year history of a progressively enlarging dumbbell shaped mass over the volar surface of the right wrist and palm. She did not have a previous history of tuberculosis. However, her Erythrocyte Sedimentation Rate (ESR) was high and Mantoux test was strongly positive (more than 15mm). Radiograph of ulna, radius and wrist showed osteopenic changes of the distal radius. Findings at excision biopsy were inflamed, thickened synovia and rice bodies. Tissue samples were submitted for histological and microbial studies. Anti-tuberculous therapy was commenced on the second postoperative day. Conclusion Tuberculous tenosynovitis of the wrist is uncommon. However in developing countries like Ghana where tuberculosis is prevalent, it should be part of the differential diagnosis of compound palmar ganglion in order to prevent delayed diagnosis and treatment.</div