Molecular epidemiology, susceptibility profiles, outcomes and transmission dynamics in patients with extensively drug-resistant tuberculosis (XDR-TB) in two provinces of South Africa
Doctoral Thesis
2017
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University of Cape Town
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Background: Recent gains in TB control in South Africa are being reversed by drug-resistant tuberculosis (MDR-TB and XDR-TB), which has a high mortality, is a threat to health care workers, and is prohibitively costly to treat. MDR-TB has been supplanted by XDR-TB, resistance beyond XDR-TB, and programmatically incurable TB. Short-term treatment-related outcomes of XDR-TB patients are known to be poor. However, there are no prospective data to inform longterm treatment-related outcomes, design of effective XDR-TB treatment regimens, and public health interventions required to interrupt transmission. In particular, the utility of certain costly drugs, e.g. capreomycin, for the treatment of XDR-TB remain unclear. There are also few data about how these characteristics differ in HIV-infected persons. Finally, little is known about the experiences of patients living with XDR-TB. This thesis aims to provide best practice evidence to promote drug-resistant TB control in high burden TB and HIV syndemic countries. Methods: We prospectively followed two cohorts of adult South African XDR-TB patients who received hospital and community treatment, which included a capreomycin and PAS-based regimen: (i) cohort A (n=107) from 3 provinces were diagnosed between August 2002 and February 2008 (retrospectively identified) and then prospectively followed up till August 2012; (ii) cohort B (n=273) from 2 provinces were prospectively identified between October 2008 and October 2012 and followed up till October 2014. Strain typing and drug susceptibility testing were performed and treatment-related outcomes were determined. In-depth interviews were conducted with therapeutically destitute patients from cohort B (n=12) and were home-discharged from hospital back to the community.
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Pietersen, G. 2017. Molecular epidemiology, susceptibility profiles, outcomes and transmission dynamics in patients with extensively drug-resistant tuberculosis (XDR-TB) in two provinces of South Africa. University of Cape Town.