Research Articles
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A research article reports the results of original research, assesses its contribution to the body of knowledge in a given area, and is published in a peer-reviewed scholarly journal. The faculty publications through published and on-going articles/researches are captured in this community
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Item TB-Diabetes Co-Morbidity in Ghana: The Importance of Mycobacterium Africanum Infection(PLOS, 2019) Asante-Poku, A.; Asare, P.; Yeboah-Manu, D.; et al.Background Diabetes Mellitus (DM) is a known risk factor for tuberculosis (TB) but little is known on TBDiabetes Mellitus (TBDM) co-morbidity in Sub-Saharan Africa. Methods 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. Results 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<0.001) and were more likely (p<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<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 byM. africanum Lineage 6 as opposed to Mtbss (odds ratio (OR) = 1.52; 95% confidence interval (CI): 0.92–2.42, p = 0.072). Conclusion Our findings confirms the importance of screening for diabetes during TB diagnosis and highlights the association between genetic diversity and diabetes in Ghana.Item Relevance of genomic diversity of Mycobacterium tuberculosis complex in Africa(Elsevier, 2022) Osei-Wusu, S.; Otchere, I.D.; Asare, P.; Ntoumi, F.; Zumla, A.; Asante-Poku, A.; Yeboah-Manu, D.Background: The diversity in the lineages of Mycobacterium tuberculosis complex (MTBC) was initially considered insignificant. However, comparative genomics analysis of MTBC have found genomic variation among the genotypes with potential phenotypic implications. Objective: Therefore, this viewpoint seeks to discuss the impact of the identified genotypic diversity on the physiology of MTBC and the potential implications on TB control. Results: Studies conducted in West Africa and other parts of Africa have unravelled the implications of the genomic diversity on phenotypes such as disease outcome, transmission dynamics and host immune response. The understanding of the phenotypic diversity among the different lineages of MTBC may be an important key to the fight against TB. Conclusion: The relevance of these differences has been observed in the design of new control tools such as diagnostics and anti-TB drugs/vaccines. This only points to the fact that the diversity in MTBC cannot be ignored in future studies especially clinical trials for new vaccines and new anti-TB drugs.Item Whole Genome Sequencing and Spatial Analysis Identifies Recent Tuberculosis Transmission Hotspots in Ghana(Frontiers in Medicine, 2020-05-19) Asare, P.; Otchere, I.D.; Bedeley, E.; Brites, D.; Loiseau, C.; Baddoo, N.A.; Asante-Poku, A.; Osei-Wusu, S.; Prah, D.A.; Borrell, S.; Reinhard, M.; Forson, A.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.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.Item Learning from epidemiological, clinical, and immunological studies on Mycobacterium africanum for improving current understanding of host–pathogen interactions, and for the development and evaluation of diagnostics, host-directed therapies, and vaccines for tuberculosis(International Journal of Infectious Diseases, 2017-03) Zumla, A.; Otchere, I.D.; Mensah, G.I.; Asante-Poku, A.; Gehre, F.; Maeurer, M.; Bates, M.; Mwaba, P.; Ntoumi, F.; Yeboah-Manu, D.Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host–pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)–those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host–M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB. © 2016 The Author(s)Item Significant under expression of the DosR regulon in M. tuberculosis complex lineage 6 in sputum(Tuberculosis, 2017-05) Ofori-Anyinam, B.; Dolganov, G.; Van, T.; Davis, J.L.; Walter, N.D.; Garcia, B.J.; Voskuil, M.; Fissette, K.; Diels, M.; Driesen, M.; Meehan, C.J.; Yeboah-Manu, D.; Coscolla, M.; Gagneux, S.; Antonio, M.; Schoolnik, G.; Gehre, F.; de Jong, B.C.Mycobacterium africanum lineage (L) 6 is an important pathogen in West Africa, causing up to 40% of pulmonary tuberculosis (TB). The biology underlying the clinical differences between M. africanum and M. tuberculosis sensu stricto remains poorly understood. We performed ex vivo expression of 2179 genes of the most geographically dispersed cause of human TB, M. tuberculosis L4 and the geographically restricted, M. africanum L6 directly from sputa of 11 HIV-negative TB patients from The Gambia who had not started treatment. The DosR regulon was the most significantly decreased category in L6 relative to L4. Further, we identified nonsynonymous mutations in major DosR regulon genes of 44 L6 genomes of TB patients from The Gambia and Ghana. Using Lebek's test, we assessed differences in oxygen requirements for growth. L4 grew only at the aerobic surface while L6 grew throughout the medium. In the host, the DosR regulon is critical for M. tuberculosis in adaptation to oxygen limitation. However, M. africanum L6 appears to have adapted to growth under hypoxic conditions or to different biological niches. The observed under expression of DosR in L6 fits with the genomic changes in DosR genes, microaerobic growth and the association with extrapulmonary disease. © 2017 The AuthorsItem Reduced transmission of Mycobacterium africanum compared to Mycobacterium tuberculosis in urban West Africa(International Journal of Infectious Diseases, 2018-08) Asare, P.; Asante-Poku, A.; Prah, D.A.; Borrell, S.; Osei-Wusu, S.; Otchere, I.D.; Forson, A.; Adjapong, G.; Koram, K.A.; Gagneux, S.; Yeboah-Manu, D.Objective: Understanding transmission dynamics is useful for tuberculosis (TB) control. A population-based molecular epidemiological study was conducted to determine TB transmission in Ghana. Methods: Mycobacterium tuberculosis complex (MTBC) isolates obtained from prospectively sampled pulmonary TB patients between July 2012 and December 2015 were characterized using spoligotyping and standard 15-locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) typing for transmission studies. Results: Out of 2309 MTBC isolates, 1082 (46.9%) unique cases were identified, with 1227 (53.1%) isolates belonging to one of 276 clusters. The recent TB transmission rate was estimated to be 41.2%. Whereas TB strains of lineage 4 belonging to M. tuberculosis showed a high recent transmission rate (44.9%), reduced recent transmission rates were found for lineages of Mycobacterium africanum (lineage 5, 31.8%; lineage 6, 24.7%). Conclusions: The study findings indicate high recent TB transmission, suggesting the occurrence of unsuspected outbreaks in Ghana. The observed reduced transmission rate of M. africanum suggests other factor(s) (host/environmental) may be responsible for its continuous presence in West Africa. © 2018 The Author(s)