Performance of centralized versus decentralized tuberculosis treatment services in Southern Brazil, 2006-2015.

BACKGROUND: Tuberculosis (TB) control programs face the challenges of decreasing incidence, mortality rates, and drug resistance while increasing treatment adherence. The Brazilian TB control program recommended the decentralization of patient care as a strategy for combating the disease. This study evaluated the performance of this policy in an area with high default rates, comparing epidemiological and operational indicators between two similar municipalities. METHODS: This study analyzed epidemiological and operational indicators on new cases of pulmonary tuberculosis reported in the Brazilian Notifiable Diseases Information System between 2006 and 2015. In addition, to characterize differences between the populations of the two studied municipalities, a prospective cohort study was conducted between 2014 and 2015, in which patients with new cases of culture-confirmed pulmonary tuberculosis were interviewed and monitored until the disease outcome. A descriptive analysis, the chi-square test, and a Poisson regression model were employed to compare TB treatment outcomes and health care indicators between the municipalities. RESULTS: Two thousand three hundred nine cases were evaluated, of which 207 patients were interviewed. Over the 2006-2015 period, TB incidence per 100,000 population in the municipality with decentralized care was significantly higher (39%, 95% CI 27-49%) in comparison to that of the municipality with centralized care. TB treatment default rate (45%, 95% CI 12-90%) was also higher in the municipality with decentralized care. During the two-year follow-up, significant differences were found between patients in centralized care and those in decentralized care regarding treatment success (84.5 vs. 66.1%), treatment default (10.7 vs. 25.8%), illicit drug use (27.7 vs. 45.9%), and homelessness (3.6 vs. 12.9%). The operational indicators revealed that the proportion of control smear tests, medical imaging, and HIV tests were all significantly higher in the centralized care. However, a significantly higher proportion of patients started treatment in the early stages of the disease in the municipality with decentralized care. CONCLUSIONS: These data showed a low success rate in TB treatment in both municipalities. Decentralization of TB care, alone, did not improve the main epidemiological and operational indicators related to disease control when compared to centralized care. Full implementation of strategies already recommended is needed to improve TB treatment success rates.

Genomic characterization of variants on mycolic acid metabolism genes in Mycobacterium tuberculosis isolates from Santa Catarina, Southern Brazil.

Mycobacterium tuberculosis has a complex cell wall containing mycolic acids (MA), which play an important role in pathogenesis, virulence, and survival by protecting the cell against harsh environments. Studies have shown that genes encoding enzymes involved in MA synthesis are essential to mycobacterial functionality. Here, we used whole-genome sequencing to evaluate mutations in genes related to MA metabolism in M. tuberculosis isolates from pulmonary tuberculosis patients of the Florianópolis Metropolitan Area, Santa Catarina, Brazil, and assessed associations with clinical, epidemiological, and genotypic data. The mutations Rv3057c Asp112Ala (104/151), Rv3720 His70Arg (104/151), and Rv3802c Val50Phe (105/151) were identified in about 69% of the isolates and were related to the LAM lineage. SIT 216/LAM5 (13.2%, 20/151) had the highest frequency and presented the mutations accD2 Lys23Glu, kasA Gly269Ser, mmaA4 Asn165Ser, otsB1 Asp617Asn, Rv3057c Asp112Ala, Rv3720 His70Arg, Rv3802c Val50Phe, and tgs4 Ala216Glu. All SIT 73/T isolates (6.6%, 10/151) showed a characteristic and exclusive gene mutation pattern: amiD Rv3376 3790075G > A, fbpA-aftB 4266941G > A, echA11 Asn220fs, and otsB2 Ser110Arg. SITs 20/LAM1, 64/LAM6, 50/H3, 137/X2, and 119/X1 were also related to specific mutations. SITs from the LAM lineage differed in mutation profile from those of the T, Haarlem, and X lineages. Isolates from patients who had treatment failure showed mutations that do not seem to have a pattern related to this outcome. It was possible to identify a broad repertoire of single-nucleotide polymorphisms in genes related to MA metabolism in M. tuberculosis isolates. This study also described, for the first time, the variability between different SITs/sublineages of Lineage 4 circulating in Florianópolis Metropolitan Area.

Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil.

Mycobacterium tuberculosis (M.tb), the pathogen responsible for tuberculosis (TB) poses as the major cause of death among infectious diseases. The knowledge about the molecular diversity of M.tb enables the implementation of more effective surveillance and control measures and, nowadays, Whole Genome Sequencing (WGS) holds the potential to produce high-resolution epidemiological data in a high-throughput manner. Florianópolis, the state capital of Santa Catarina (SC) in south Brazil, shows a high TB incidence (46.0/100,000). Here we carried out a WGS-based evaluation of the M.tb strain diversity, drug-resistance and ongoing transmission in the capital metropolitan region. Resistance to isoniazid, rifampicin, streptomycin was identified respectively in 4.0% (n = 6), 2.0% (n = 3) and 1.3% (n = 2) of the 151 studied strains by WGS. Besides, resistance to pyrazinamide and ethambutol was detected in 0.7% (n = 1) and reistance to ethionamide and fluoroquinolone (FQ) in 1.3% (n = 2), while a single (0.7%) multidrug-resistant (MDR) strain was identified. SNP-based typing classified all isolates into M.tb Lineage 4, with high proportion of sublineages LAM (60.3%), T (16.4%) and Haarlem (7.9%). The average core-genome distance between isolates was 420.3 SNPs, with 43.7% of all isolates grouped across 22 genomic clusters thereby showing the presence of important ongoing TB transmission events. Most clusters were geographically distributed across the study setting which highlights the need for an urgent interruption of these large transmission chains. The data conveyed by this study shows the presence of important and uncontrolled TB transmission in the metropolitan area and provides precise data to support TB control measures in this region.

Author Correction: Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Molecular epidemiology of Mycobacterium tuberculosis strains from prison populations in Santa Catarina, Southern Brazil.

The Tuberculosis (TB) notification rates are 5 to 81 times higher in prisons worldwide when compared to the general population. The state of Santa Catarina (SC) has few epidemiological data regarding TB in prisons. The aim of this study was to evaluate the molecular epidemiology of circulating strains in prisons of SC. The study comprised 95 clinical samples from six prisons. Among the cases included, all subjects were male, predominantly caucasians, and young adults, with low education level. The positive smear in the TB diagnosis comprised 62.0% of cases. About 50% of subjects had some condition associated with TB. The Spoligotyping results showed that the most frequent lineages were LAM (50.7%), T (22.2%) and S (11.6%). The 12-loci MIRU generated 62 different genotypes. The MSTs showed evolutionary relationships between Mycobacterium tuberculosis spoligotypes from SC and evolutionary relationships between the prison isolates and studied parameters. This first study on TB in prison units of SC highlighted the predominance of SIT216/LAM5, and SIT34/S. Interestingly, his profile was found to be different from that observed in a previous study performed with the state's general population. This data shows the need for continued surveillance of episodes of TB occurring among prison inmates in an emerging country like Brazil.