Consequences of Mycobacterium tuberculosis genetic diversity in the context of HIV co-infection for laboratory diagnosis of tuberculosis in Africa

Willy Ssengooba’s thesis evaluates the consequences of the genetic diversity of Mycobacterium tuberculosis, the causative agent of tuberculosis, for diagnosis of this disease tuberculosis in Africa, often in HIV co-infected patients. It addresses three main sub-themes around M. tuberculosis genetic diversity; laboratory diagnosis, clinical presentation of tuberculosis disease and resistance to anti-tuberculosis drugs. For the first two sub-themes, he looked at how to best use molecular assays in practice given the various disease presentations especially in HIV-positive patients who often have bloodstream infections (mycobacteremia). He further looked at additional attributes of molecular assays and the extent to which genetic diversity of M. tuberculosis may influence the reliability and interpretation of results of molecular assays. Under the drug resistance theme, he evaluated the extent of variations and risk factors of drug-resistant tuberculosis in sub-Saharan Africa in a systematic review and meta-analysis. Furthermore, he determined the diversity of drug resistance-conferring mutations that could be picked up by molecular tests (existing or under development) in a country with a drug-resistant tuberculosis epidemic that is typical for the African region. Lastly he investigated to what extent this diversity is affected by HIV-coinfection given the fitness cost differences between different resistance-conferring mutations.