Treatment outcomes of multidrug-resistant tuberculosis patients in Gauteng, South Africa.

PURPOSE: Multidrug-resistant tuberculosis (MDR-TB) is associated with lengthy treatment, expensive and potentially toxic regimens, and high rates of treatment failure and death. This study describes the outcomes of 351 MDR-TB patients who started treatment between 2004 and 2007 at the provincial MDR-TB referral hospital in Johannesburg, South Africa, and investigates risk factors associated with death. METHODS: The study involved the assessment of factors associated with treatment outcomes using a retrospective review of patient records, drug-susceptibility data and spoligotyping of isolates. RESULTS: Treatment success (completion/cure) was recorded in 158 (48.8 %) patients, while 65 (20 %) died, 93 (28.7 %) defaulted, 8 (2.5 %) failed treatment, 11(3.1 %) were transferred out to other health facilities and 16 (4.6 %) had no recorded final outcome. The proportion of successful treatment increased significantly over time. Univariable and multivariable analysis (P = 0.05) identified the year of MDR-TB diagnosis and spoligotype-defined families as factors associated with treatment outcome. No associations were found between treatment outcome and human immunodeficiency virus (HIV) status, previous TB and additional MDR resistance to streptomycin or ethambutol. Molecular typing of the strains revealed a diverse group of spoligotypes, with Beijing, LAM4 and H3 making up the largest groups. CONCLUSIONS: This is the first published study to investigate treatment outcomes at this facility and to find a link between genotype and treatment outcome, suggesting that genotype determination could potentially serve as a prognostic factor.

Genotypic diversity of extensively drug-resistant tuberculosis (XDR-TB) in South Africa.

SETTING: The epidemiology of extensively drug-resistant tuberculosis (XDR-TB), an emerging threat to TB control, is not well understood. OBJECTIVE: To gain insight into the genotypic population structure of XDR Mycobacterium tuberculosis strains in South Africa using a molecular approach and thereby determine whether XDR-TB is mainly acquired or transmitted. DESIGN: Sputum isolates from patients with multidrug-resistant tuberculosis (MDR-TB) were submitted to the National Referral Laboratory for second-line drug susceptibility testing. The XDR-TB isolates were spoligotyped and these data were compared to the geographic origin of the isolate. RESULTS: Of the 699 MDR-TB isolates submitted for testing between June 2005 and December 2006, 101 (17%) patients had a culture that was resistant to either ofloxacin or kanamycin, and 41 (6%) were resistant to both drugs (XDR-TB). Spoligotyping of the XDR-TB isolates identified 17 genotypes. As a result of the high genotypic diversity and geographical distribution, we estimate that between 63% and 75% of cases developed XDR-TB through acquisition. CONCLUSION: Acquisition of extensive drug resistance appears to be the primary mechanism driving the XDR-TB epidemic in South Africa. This urgent TB control issue has to be addressed to prevent the spread of this potentially incurable disease.