Molecular characterization of drug resistant Mycobacterium tuberculosis isolates from different regions in South Africa

[摘要] ENGLISH ABSTRACT: Application of molecular fingerprinting highlights transmission as the driving force behind thedrug resistant epidemic in South Africa. Different strains dominate within different geographicalregions, which is a reflection of micro-epidemics of drug resistance in the different regions.Cluster analysis shows that strains within the same strain family are different. The Beijing drugresistant strain family is the most dominant strain family (31%) in the Western Cape and ofparticular concern is the highly transmissible Beijing cluster 220 strain in the Western Capecommunities. This cluster is widespread in the region and was previously identified in a MDRoutbreak in a high school in Cape Town. Results suggest that the spread of Beijing drug resistantcluster 220 in the community was due to a combination of acquisition of drug resistant markersand transmission. This study also indicate that atypical Beijing can acquire drug resistance andbecome fit amongst HIV infected individuals. This is contrary to believe that atypical Beijingstrains are not frequently associated with drug resistance and are attenuated. This implies thatHIV levels the playing field for all drug resistant strains.Mechanisms leading to the evolution of MDR-TB and XDR-TB in a mine setting with a wellfunctioningTB control program which exceeds the target for cure rates set by the WHO wereinvestigated. Despite the excellent control program, an alarming increase in the number of drugresistant cases was observed in 2003 and subsequent years. Phylogenetic analysis showssequential acquisition of resistance to first and second-line anti-TB drugs leading to thedevelopment of MDR and XDR-TB. Contact tracing indicate extensive transmission of drugresistant TB in the shafts, hospital and place of residence. This study shows that despite exceeding the WHO cure rate target, it was not possible to control the spread and amplificationof drug resistance. In summary, as a top priority, future TB control plans need to addressdiagnostic delay more vigorously.

[发布机构] Stellenbosch University