Clinical Epidemiology of HIV associated Tuberculosis in Khayelitsha, a South African Township

Abstract

HIV is the strongest risk factor for TB and TB is the most common cause of death amongst HIV-infected persons in high burden settings. Khayelitsha, the setting for studies in this thesis, is a high HIV/TB burden and transmission setting. The increased susceptibility to TB infection in HIV-infected persons represents a challenge in TB epidemic control. The absence of a gold standard test for latent TB infection (LTBI) makes it difficult to accurately measure the burden of LTBI. A review conducted in this thesis demonstrated a paucity of data on risk factors for LTBI in HIV-infected persons. This thesis contributes to existing knowledge through describing the prevalence of LTBI in a high HIV/TB burden setting and identifying risk factors for infection, in HIV-infected and uninfected persons, using the tuberculin skin test and interferon gamma release assays (IGRA), as well as identifying risk factors for indeterminate IGRA results. HIV co-infection also increases the risk of progression from LTBI to active disease and blurs the distinction between latent and active TB. This makes diagnosis challenging as passive case-finding, reliant upon clinical symptoms, is often utilized in high burden settings. In order to effectively interrupt transmission, early and accurate diagnosis and treatment of TB cases is crucial. The limitation of smear microscopy in HIV-infected persons, due to paucibacillary disease, along with the operational challenges of performing TB culture, highlight the need for new diagnostic tests. This thesis measures the prevalence of, and risk factors for, subclinical TB disease and highlights the clinical relevance of this intermediary disease state and the need for intensified case-finding and better diagnostic tools to diagnose TB in HIV-infected persons. A novel method is also evaluated to improve the accuracy of an existing diagnostic test, the T-SPOT.TB in the diagnosis of active TB in HIV co-infected persons.