ABSTRACT
BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). RESULTS: In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations-L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance-D435Y plus L452P and L430P plus S493L-. CONCLUSION: Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Angola/epidemiology , Bacterial Proteins/genetics , DNA-Directed RNA Polymerases/genetics , Drug Resistance, Bacterial/genetics , Humans , Microbial Sensitivity Tests , Mutation , Mycobacterium tuberculosis/genetics , Tuberculosis/epidemiologyABSTRACT
Treatment for multidrug-resistant tuberculosis (MDR TB) is associated with adverse events (AE). Patients treated with an MDR TB regimen in Hospital Nossa Senhora da Paz, Cubal, Angola, were prospectively enrolled from May 2013 to July 2015. Baseline characteristics, AE, and clinical and microbiological outcomes were recorded. A total of 216 patients were treated with an MDR TB regimen and 179 (82.9%) patients developed at least one AE. The most common AE were elevation of liver enzymes (46.8% of patients), elevated creatinine (44.4% of patients), and ototoxicity (40.7% of patients). Previous TB treatment was associated with the occurrence of AE (OR 4.89, 95% CI: 2.09-11.46, P < 0.001) and months on treatment was associated to severe AE (OR 1.11 95% CI: 1.04-1.18, P = 0.001). Successful treatment was achieved in 117 (54.2%) patients. Incidence of AE was associated with an unsuccessful outcome (OR 1.23, 95% CI: 1.09-1.40, P = 0.001). Patients treated with MDR TB treatment frequently experience AE, and these are related with previous TB treatment and duration of treatment. Given the high percentage of patients experiencing AE and the low treatment success rates, more effective and less toxic drugs to treat MDR TB are urgently needed.
Subject(s)
Antitubercular Agents/adverse effects , Rural Population , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Adult , Angola , Antitubercular Agents/therapeutic use , Female , Humans , Male , Prospective Studies , Treatment Outcome , Tuberculosis, Pulmonary/microbiologyABSTRACT
We found high prevalence rates of multidrug-resistant tuberculosis among retreatment patients (71.1%) and persons with new cases (8.0%) in Angola. These findings are of concern but should be interpreted with caution. A national drug-resistance survey is urgently needed to determine the actual prevalence of multidrug-resistant tuberculosis in Angola.
