Universal pattern of RpoB gene mutations among multidrug-resistant isolates of Mycobacterium tuberculosis complex from Africa

SETTING: Multidrug-resistant tuberculosis (MDR-TB) presents an increasing b urden in Southern Africa. Rapid diagnostic tests for drug resistance to rif ampicin have been developed based on mutation analysis of the rpoB gene. Ho wever, geographic differences of underlying mutations have recently been su ggested. OBJECTIVE: Drug-resistant strains of Mycobacterium tuberculosis complex fro m Africa were analysed for geographic differences in frequency and location of rpoB mutations. DESIGN: A random sample of rifampicin-resistant strains was collected from 87 patients with pulmonary MDR-TB treated in 12 hospitals from six differen t regions of South Africa. In addition, 18 isolates of M. tuberculosis comp lex from Namibia, Sierra Leone, and Uganda, including 13 isolates of M. afr icanum, were analyzed. Point mutations were detected by direct sequence ana lysis of the rpoB gene. RESULTS: Missense mutations were identified for 91 isolates (87%). Double m utations were present in eight (8%) MDR-TB isolates, two of which carried o ne mutation outside a previously described diagnostic region. We found no g eographic differences regarding the frequency and pattern of single rpoB ge ne mutations. CONCLUSION: Our results confirm that molecular genetic analysis of rifampic in resistance based on a core region within the rpoB gene is universally ap plicable to strains of M. tuberculosis complex from different geographic re gions.