The challenges of management of TB/HIV co-infection in resource limited countries

This thesis addresses some challenges in medical care of dually infected Tuberculosis (TB) and HIV patients. It outlines some measures that could mitigate the impact of this co-pandemic in resource-limited areas of sub-Saharan Africa.;Three main clinical aspects of management of TB-HIV disease presented here include diagnostic challenges, mortality outcomes and the tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In chapter 1 we describe the epidemiology of TB and HIV and challenges in management of both infections. In chapter 2 we describe studies concerning the diagnosis of pulmonary diseases in HIV-infected persons. From these studies we recommend that bronchoscopy, where available, should be used to diagnose TB and co-morbid respiratory disease in patients infected with HIV who are sputum Acid Fast Bacilli negative. No single factor or combination of clinical, laboratory or radiographic factors was found to predict bacteriologically confirmed TB. We also recommend that in Kampala, Uganda, mycobacterial speciation may not be routinely needed to confirm TB. We found that the Xpert MTB/RIF molecular test improved the accuracy and shortened the time to TB diagnosis. Further operational and cost effectiveness studies are however needed.;Despite ART, many patients with TB-HIV still die while on treatment. In chapter 3 we show that not being on antiretroviral therapy (ART) and having a positive serum cryptococcal antigen test were associated with an increased risk of death. Finally in chapter 4 we present studies on TB-IRIS, a syndrome, thought to arise from a dysregulated immune activation among patients TB-HIV and low CD4 counts starting ART. Two forms of disease are recognized: the unmasking TB-IRIS and the paradoxical TB-IRIS. In one study we found low frequency of ART-associated TB and unmasking TB-IRIS while paradoxical TB-IRIS occurred in 21% of patients with TB-HIV starting ART. TB-IRIS was not associated with increased mortality.;In conclusion, TB-HIV co-infection is a common cause of morbidity and mortality. Improved diagnostic techniques and tests present an opportunity for early, rapid and accurate diagnosis. Other co-morbid illnesses in TB-HIV co-infected patients need to be treated early to improve clinical outcomes. We need better tools to diagnose, treat and prevent TB-HIV infections.