RESUMO
SETTING: Pyrazinamide (PZA), an important first-line drug for anti-tuberculosis treatment, demonstrates potent activity against semi-dormant bacilli in acidic environments. However, the diagnosis of PZA resistance is often impeded by technical difficulties. OBJECTIVE: To characterise mutations in the pncA and rpsA genes among PZA-resistant and PZA-susceptible clinical Mycobacterium tuberculosis isolates circulating in Kazakhstan. The potential use of genotyping to identify PZA resistance was also investigated. DESIGN: PZA drug susceptibility testing and pncA and rpsA gene sequencing were performed on 77 clinical M. tuberculosis isolates; mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing was performed on 74 clinical M. tuberculosis isolates. RESULTS: Of the 77 clinical M. tuberculosis isolates, 41 (53.2%) were phenotypically resistant to PZA, whereas 36 (46.7%) were susceptible; 48 (62.3%) of these isolates were also multidrug-resistant (MDR). Furthermore, 38 (49.3%) clinical isolates showed mutations in the pncA gene and its flanking region; the majority of these isolates (n = 36, 94.7%) were also MDR. Gene sequencing showed that only synonymous substitutions affecting rpsA occurred. MIRU-VNTR typing revealed that 78.4% of isolates were of the Beijing genotype. CONCLUSIONS: Sequencing revealed that mutations in pncA, but not in rpsA, occurred in PZA-resistant M. tuberculosis isolates circulating in the territory of Kazakhstan.
Assuntos
Amidoidrolases/genética , Antituberculosos/farmacologia , Mycobacterium tuberculosis/genética , Pirazinamida/farmacologia , Adolescente , Adulto , Idoso , Criança , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Feminino , Genótipo , Humanos , Cazaquistão , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Repetições Minissatélites , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Proteínas Ribossômicas/genética , Análise de Sequência de DNA/métodos , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto JovemRESUMO
A total of 60 Mycobacterium tuberculosis isolates collected from patients in prisons in Kazakhstan and 125 from the civilian sector were examined using mycobacterial interspersed repetitive units-variable number of tandem repeat analysis in 2012. The proportion of tuberculosis strains with unique genotypes isolated from the civilian patients was 50.4%, while that in the prison patients was 31.7%. This difference was statistically significant (χ(2) 4.42, P 0.035), and may reflect a low genetic diversity of M. tuberculosis strains isolated from prison patients. The frequencies of mutations in the rpoB531 and katG315 genes of the M. tuberculosis strains isolated from the civilians and in the penitentiary system were not significantly different (rpoB531: 82.4% vs. 88.3%, and katG315: 98.4% vs. 100%, respectively).
Assuntos
DNA Bacteriano/genética , Mycobacterium tuberculosis/genética , Prisioneiros , Prisões , Tuberculose/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Técnicas de Tipagem Bacteriana , Distribuição de Qui-Quadrado , Análise por Conglomerados , Farmacorresistência Bacteriana/genética , Genótipo , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Epidemiologia Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Fenótipo , Valor Preditivo dos Testes , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
SETTING: Kazakhstan is a country with a low HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome) burden, but a high prevalence of multidrug-resistant tuberculosis (MDR-TB). METHODS: We describe the epidemiology of multidrug resistance and HIV among TB patients, using the 2007-2011 national electronic TB register. RESULTS: HIV test results were available for 97.2% of TB patients. HIV prevalence among TB patients increased from 0.6% in 2007 to 1.5% in 2011. Overall, 41.6% of patients had a positive smear at diagnosis, 38.6% a positive culture and 51.7% either a positive smear or culture. Drug susceptibility testing (DST) results were available for 92.7% of culture-positive cases. Socio-economic factors independently associated with both HIV and MDR-TB were urban residency, drug use, homelessness and a history of incarceration. In adjusted analysis, HIV positivity was not associated with MDR-TB (OR 1.0, 95%CI 0.86-1.2). Overall, among TB patients with DST and HIV test results available, 65.0% were positive for neither HIV nor MDR-TB, 33.5% only for MDR-TB, 0.9% only for HIV and 0.6% for both HIV and MDR-TB. Among injection drug users, 12.5% were positive for HIV and MDR-TB. CONCLUSION: We showed increasing HIV prevalence among TB patients in Kazakhstan. HIV was not an independent risk factor for MDR-TB, but risk factors were largely overlapping and we did identify subgroups at particular risk of HIV-MDR-TB co-infection, notably drug users. Enhanced efforts are necessary to provide care to these socially vulnerable populations.