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

Objectives
1. To determine the variation and risk factors for drug-resistant tuberculosis in sub-Saharan Africa.
2. To evaluate the clinical utility of a novel molecular assay in various combinations with existing methods for diagnosis of HIV-related tuberculosis.
3. To determine the clinical predictors of mycobacteremia among HIV-infected smear- negative adults in a high prevalence HIV/TB setting in relation to the utility of a lateral flow urinary lipoarabinomannan assay.
4. To evaluate the comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals with suspected tuberculosis in Uganda
5. To determine the phenotypic and genotypic diversity of Mycobacterium tuberculosis isolates from blood and sputum of the same HIV-infected adult TB patient.
6. To determine whether specific resistance-conferring mutations with known differential consequences for bacterial fitness differ in their ability to cause disease in HIV-infected versus non-HIV-infected patients.