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Sub-Saharan Africa has continued leading in the prevalence and incidence of tuberculosis (TB). The epidemiological triad of infectious diseases includes a susceptible host, pathogen/agent, and environment. Sub- Saharan Africa has the highest prevalence and incidence of TB. It is imperative that all aspects of vertices of the infectious disease triad are analysed to better understand why this is so. Many studies have been done to address this intriguing reality though these have mainly addressed pathogen and environmental components of the triad regarding TB infection. The host factors have not been exhaustively studied in this high TB burden region probably due to lack of the necessary expertise and technologies among African scholars yet three components of the triad interact to determine the disease outcome. Amongst host factors, genetic structure of the host greatly affects progression of disease following exposure. Studies have revealed that Africa is the most genetically diverse region of the world in addition to being the origin of modern humans therefore it would be important to study genetics of sub-Saharan African population in relation to TB. This review seeks to analyze contribution of host genetics to the observed variation in susceptibility to TB infection in this region.