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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. [ABSTRACT FROM AUTHOR]

• Comparative genomics studies of MTBC shows significant genomic diversity. • MTBC genomic diversity has significant implications on phenotypic profiles. • MTBC diversity is relevant in the design of new control tools. • Diversity in MTBC must be considered in choice of future clinical trial sites. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]