Molecular genotyping has shown Mycobacterium tuberculosis lineages to be geographically restricted and associated with distinct ethnic populations. Whether tuberculosis (TB) caused by some M. tuberculosis lineages can present with a differential clinical spectrum is controversial because of very limited clinical data. We recently reported on the discovery of RD Rio M. tuberculosis, a Latin American-Mediterranean sublineage that is the predominant cause of TB in Rio de Janeiro, Brazil. To investigate the clinical attributes of TB caused by RD Rio strains, we studied a cohort of TB cases from Belo Horizonte, Brazil, in which clinical information recorded on a standardized questionnaire was collected at the time of microbiological testing. These patients were referred for culture and drug susceptibility testing because of the clinical suspicion of "complicated" TB, as demonstrated by high rates of multidrug resistance (12%) and cavitary TB (80%). We performed spoligotyping and RD Rio genotyping on the M. tuberculosis strains and analyzed the clinical data from these patients. RD Rio M. tuberculosis accounted for 37% of the total TB burden. Multivariate analysis found a significant association between TB caused by RD Rio strains and pulmonary cavitation and residence in Belo Horizonte. Since cavitary TB is associated with higher sputum bacillary load, our findings support the hypothesis that RD Rio M. tuberculosis is associated with a more "severe" disease as a strategy to increase transmission. Future studies are needed to confirm these observations and to better define the contribution of RD Rio M. tuberculosis to the global TB epidemic.Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), is estimated to have infected one-third of the world's population and annually causes ϳ8 million new TB cases and Ͼ2 million deaths (16, 58). The challenges posed by TB have been further worsened by the emergence of multi-drugresistant and extensively drug-resistant M. tuberculosis strains.Molecular typing, based on genetic markers, permits the rapid detection and species level identification of mycobacteria within the M. tuberculosis complex (MTC), as well as provides useful tools for examining the transmission and evolution of these microorganisms (7,17,30,53). Genome-wide single nucleotide polymorphism (SNP) and deletion analyses have been used to organize the global M. tuberculosis population structure into overlapping phylogenies with major lineages that show distinct geographic distribution and that may be associated with specific host adaptation (1,21,23,24,27,28,50). Similar results have also been obtained with spoligotyping and IS6110-RFLP fingerprint analysis (18). The W/Beijing lineage, for example, is the predominant family in major SNP cluster II, accounts for ϳ10% of strains causing TB globally, and is localized mainly to Asia but has spread internationally. W/Beijing has been associated with outbreaks and multiple drug resistance (MDR) (4, 32) and also contributed significantly to the resurgence of...

OBJECTIVE: To analyze the profile of tuberculosis cases reported between 2002 and 2009 in the state of Minas Gerais, Brazil, according to sociodemographic, clinical, and laboratory characteristics, as well as to comorbidities and mortality. METHODS: This was a descriptive, epidemiological study based on data obtained from the Brazilian Case Registry Database and the Brazilian Mortality Database for the 2002-2009 period. RESULTS: There were 47,285 reported cases of tuberculosis, corresponding to a mean incidence of 22.3/100,000 population. The individuals diagnosed with tuberculosis were predominantly in the 20- to 49-year age bracket and male (62.4% and 67.0%, respectively). Individuals with a low level of education accounted for 18.5% of the cases. New cases, cases of recurrence, and cases of retreatment accounted for 83.7%, 5.7%, 5.7%, respectively. The rates of cure and treatment noncompliance were 66.2% and 11.2%, respectively; multidrug-resistant tuberculosis was identified in 0.2% of the cases; and the mortality rate was 12.9%. The directly observed treatment, short-course (DOTS) strategy was applied in 21.8% of the cases. Sputum smear microscopy and culture were performed in only 73.9% and 12.9% of the cases, respectively. Chest X-rays were performed in 90.5% of the cases. Pulmonary tuberculosis was the predominant form (in 83.9%). Comorbidity with alcoholism, HIV infection, and diabetes mellitus were identified in 17.2%, 8.3%, and 3.8%, respectively. CONCLUSIONS: During the study period, the numbers of new cases, cases of treatment noncompliance, and deaths were high, comorbidities were common, and there was a failure to perform adequately basic tests for the diagnosis of tuberculosis. Multidisciplinary approaches, expanded use of the DOTS strategy, better knowledge of the distribution of tuberculosis, and improvements in the databases are needed in order to achieve better control of the disease in the state of Minas Gerais.

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BackgroundWe aimed to characterize the genetic diversity of drug-resistant Mycobacterium tuberculosis (MTb) clinical isolates and investigate the molecular epidemiology of multidrug-resistant (MDR) tuberculosis from Minas Gerais State, Brazil.MethodsOne hundred and four MTb clinical isolates were assessed by IS6110-RFLP, 24-locus mycobacterial interspersed repetitive units variable-number tandem repeats (MIRU-VNTR), TB-SPRINT (simultaneous spoligotyping and rifampicin-isoniazid drug-resistance mutation analysis) and 3R-SNP-typing (analysis of single-nucleotide polymorphisms in the genes involved in replication, recombination and repair functions).ResultsFifty-seven different IS6110-RFLP patterns were found, among which 50 had unique patterns and 17 were grouped into seven clusters. The discriminatory index (Hunter and Gaston, HGDI) for RFLP was 0.9937. Ninety-nine different MIRU-VNTR patterns were found, 95 of which had unique patterns and nine isolates were grouped into four clusters. The major allelic diversity index in the MIRU-VNTR loci ranged from 0.6568 to 0.7789. The global HGDI for MIRU-VNTR was 0.9991. Thirty-two different spoligotyping profiles were found: 16 unique patterns (n = 16) and 16 clustered profiles (n = 88). The HGDI for spoligotyping was 0.9009. The spoligotyped clinical isolates were phylogenetically classified into Latin-American Mediterranean (66.34 %), T (14.42 %), Haarlem (5.76 %), X (1.92 %), S (1.92 %) and U (unknown profile; 8.65 %). Among the U isolates, 77.8 % were classified further by 3R-SNP-typing as 44.5 % Haarlem and 33.3 % LAM, while the 22.2 % remaining were not classified. Among the 104 clinical isolates, 86 were identified by TB-SPRINT as MDR, 12 were resistant to rifampicin only, one was resistant to isoniazid only, three were susceptible to both drugs, and two were not successfully amplified by PCR. A total of 42, 28 and eight isolates had mutations in rpoB positions 531, 526 and 516, respectively. Correlating the cluster analysis with the patient data did not suggest recent transmission of MDR-TB.ConclusionsAlthough our results do not suggest strong transmission of MDR-TB in Minas Gerais (using a classical 100 % MDR-TB identical isolates cluster definition), use of a smoother cluster definition (>85 % similarity) does not allow us to fully eliminate this possibility; hence, around 20–30 % of the isolates we analyzed might be MDR-TB transmission cases.

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