Epidemic spread of multidrug-resistant (MDR) tuberculosis in Johannesburg, South Africa.
Résumé
Numerous reports have documented isolated transmission events or clonal "outbreaks" of multidrug-resistant Mycobacterium tuberculosis strains, but knowledge of their epidemic spread remains limited. In this study, we evaluated drug resistance, strain diversity and clustering rates in patients diagnosed with multidrug-resistant (MDR) tuberculosis (TB) at the National Health Laboratory Service (NHLS) Central TB laboratory in Johannesburg, South Africa, between March 2004 and December 2007. Phenotypic drug susceptibility testing was done using the indirect proportion method while each isolate was genotyped using a combination of spoligotyping and 12-MIRU typing. Isolates from 434 MDR-TB patients were evaluated, of which 238 (54.8%) were resistant to four first-line drugs (isoniazid, rifampicin, ethambutol and streptomycin). Spoligotyping identified 56 different strains and 28 clusters of variable size (2-71 cases per cluster) with a clustering rate of 87.1%. Ten clusters included 337 (77.6%) of all cases, with strains of the Beijing genotype being most prevalent (16.4%). Combined analysis of spoligotyping and 12-MIRU typing increased the discriminatory power (HGDI=0.962) and reduced the clustering rate to 66.8%. Resolution of Beijing genotype strains were further enhanced when using the 24-MIRU-VNTR typing method by identifying 15 sub-clusters and 16 unique strains from twelve 12-MIRU clusters. High levels of clustering among a variety of strains suggest true epidemic spread of MDR-TB in the study setting, emphasizing the urgency of early diagnosis and effective treatment to reduce transmission within this community.