Theses & Dissertations Open Access 2013 RUF-31699

Molecular Characterisation of Multidrug Resistant Tuberculosis Human Isolates in Kampala

George William Muyombya

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Abstract

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Strains of Mycobacteria tuberculosis complex that are resistant to the two first line drugs rifampicin and isoniazid are increasing in Kampala. Archived human multidrug resistant tuberculosis isolates collected from Kampala between 1997 and 2007 were analysed. We used regions of deletion to determine the species involved. Spoligotyping was employed to identify strain types in relation to the international SpolDB4 database. Epidemiological linkages between isolates were also ascertained by comparing the numerical 15-loci MIRU-VNTR outputs to the MIRU-VNTRPlus database to elucidate clustered strains. The predominant species were M. tuberculosis of the “modern” type (98.7%), “ancestral” M. tuberculosis (1.03%) and M. bovis “classical” (1.03%). A strain diversity of 46.9% was revealed by SpolDB4. Predominant spoligotype strain lineages were T2-Uganda (20.4%) and CAS1-Delhi (12.2%). Spoligotype clusters were split by the 15-loci MIRUVNTR typing, forming two MIRU-VNTR clusters each having two strains. Predominant MIRU-VNTR strain lineages were Uganda I (29.6%) and CAS1- Dehli (11.2%). Majority (98%) of the strains were unclustered. These data suggest that MDR-TB strains circulating in Kampala are endemic, genetically diverse and epidemiologically independent.

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