RESUMO
After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB.
Assuntos
Mycobacterium tuberculosis/genética , Polimorfismo de Nucleotídeo Único/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Brasil , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Humanos , Filogenia , Grupos PopulacionaisRESUMO
After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. The Guarani-Kaiowá people are an indigenous population in Paraguay and the Brazilian state of Mato Grosso do Sul. This community, marginalized in Brazilian society, experiences severe poverty. Like other South American indigenous populations, their TB prevalence is high, but the disease has remained largely unstudied in their communities. Herein, Mycobacterium tuberculosis isolates from local clinics were whole genome sequenced, and a population genetic framework was generated. Phylogenetics show M. tuberculosis isolates in the Guarani-Kaiowá people cluster away from selected reference strains, suggesting divergence. Most cluster in a single group, further characterized as M. tuberculosis sublineage 4.3.3. Closer analysis of SNPs showed numerous variants across the genome, including in drug resistance-associated genes, and with many unique changes fixed in each group. We report that local M. tuberculosis strains have acquired unique polymorphisms in the Guarani-Kaiowá people, and drug resistance characterization is urgently needed to inform public health to ensure proper care and avoid further evolution and spread of drug-resistant TB
Assuntos
Humanos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Polimorfismo de Nucleotídeo Único/genética , Mycobacterium tuberculosis/genética , Filogenia , Brasil , Farmacorresistência Bacteriana Múltipla/genética , Grupos Populacionais , GenótipoRESUMO
Adolfo Lutz Institute in Sao Paolo State performs mycobacterial identification for many healthcare units, and in 2008 identified a possible outbreak involving patients submitted to bronchoscopy at the same hospital. This study aimed to analyse the clonality of isolates. Mycobacterium abscessus subsp. massiliense isolated from 28 patients, water from one bronchoscope and water from four automated endoscope reprocessing machines presented high similarity by pulsed-field gel electrophoresis. This strain was not found in the water supply, and it was hypothesized that an infected patient contaminated the bronchoscope, with further false-positive cultures from subsequent patients.
Assuntos
Broncoscópios/microbiologia , Broncoscopia/efeitos adversos , Surtos de Doenças , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium abscessus/isolamento & purificação , Brasil/epidemiologia , Eletroforese em Gel de Campo Pulsado , Genótipo , Hospitais , Humanos , Epidemiologia Molecular , Tipagem Molecular , Mycobacterium abscessus/classificação , Mycobacterium abscessus/genética , Microbiologia da ÁguaRESUMO
OBJECTIVES: To describe the prevalence, associated factors, treatment outcomes and transmission of extensively drug-resistant (XDR) tuberculosis (TB) in the state of São Paulo, Brazil, for 2011 to 2013. METHODS: Drug susceptibility testing to first- and second-line drugs was performed by BACTEC MGIT 960 and molecular typing, by IS6110 restriction fragment length polymorphism. Clinical, epidemiologic and demographic data were obtained from surveillance information systems for TB. Patients were divided into three groups: multidrug resistant (MDR) TB (resistance to at least isoniazid and rifampicin), pre-XDR-TB (MDR-TB resistant to a fluoroquinolone or to at least one of the second-line injectable drugs) and XDR-TB (MDR-TB resistant to a fluoroquinolone and to at least one of the second-line injectables). RESULTS: Among the 313 MDR-TB patients identified, the prevalence of XDR-TB and pre-XDR-TB was 10.2% (n = 32) and 19.2% (n = 60), respectively. Compared to MDR-TB patients, XDR-TB patients were more likely to be female (odds ratio (OR) = 2.74, 95% confidence interval (CI), 1.29-5.83), have a history of TB (OR = 5.16; 95% CI, 1.52-17.51) and present higher death rates (OR= 3.74; 95% CI 1.70-8.25). XDR-TB transmission was observed in households, between neighbours and between a patient and a healthcare worker in a hospital. CONCLUSIONS: The prevalence of XDR-TB in the state of São Paulo is close to that estimated globally. Most of the XDR-TB patients were treated previously for TB and presented the lowest successful outcome rates. Because transmission of XDR-TB occurred, it is important that timely diagnosis of drug resistance is performed.
Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/transmissão , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Brasil/epidemiologia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Humanos , Masculino , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Avaliação de Resultados em Cuidados de Saúde , Polimorfismo de Fragmento de Restrição , Prevalência , Vigilância em Saúde Pública , Fatores de RiscoRESUMO
SETTING: A cohort of household contacts of tuberculosis (TB) index cases from four public health clinics in São Paulo, Brazil. OBJECTIVE: To measure the association between diabetes mellitus (DM) among household contacts and recent-transmission TB (RT TB). DESIGN: Index TB cases (n = 263) identified from 2001 to 2002 in São Paulo, whose household contacts (n = 1383) were monitored for active TB until December 2010. RESULTS: From 2001 to 2010, there were 29 cases of RT TB among household contacts (cumulative incidence 2.1%, 95%CI 1.4-2.9). DM in household contacts was associated with RT TB (OR 3.96, 95%CI 1.33-11.79) even after adjustment for human immunodeficiency virus (HIV) status, smoking and alcohol use (adjusted OR [aOR] 3.21, 95%CI 1.01-10.19). HIV infection was also associated with RT TB (OR 6.40, 95%CI 1.40-29.40; aOR 4.81, 95%CI 0.96-24.18). Household contact DM was not associated with non-RT TB (OR 1.27, 95%CI 0.30-5.40). The time to diagnosis of TB was shorter in household contacts with and without DM (P = 0.035) and in household contacts with and without HIV (P = 0.0002). CONCLUSION: Household contact DM was associated with an increased risk of RT TB in a cohort in Brazil, lending support to the active screening of household contacts with DM for TB in Brazil.
Assuntos
Busca de Comunicante , Diabetes Mellitus/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Adolescente , Brasil/epidemiologia , Características da Família , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/métodos , Fatores de Risco , Fatores de Tempo , Tuberculose/diagnóstico , Tuberculose/transmissão , Adulto JovemRESUMO
BACKGROUND: Mycobacterium tuberculosis genotypes resistant to reactive nitrogen intermediates (RNI) predominate in certain urban communities, suggesting that this phenotype influences disease transmission. OBJECTIVE: To compare different M. tuberculosis genotypes for resistance to RNI generated in vitro. DESIGN: We genotyped 420 M. tuberculosis isolates from a neighborhood in Sao Paulo, Brazil, and analyzed them for susceptibility to RNI generated in acidified sodium nitrite (ASN) solution. RESULTS: Seventy-one (43%) of 167 recent-infection strains and 68 (43%) of 158 endogenous infection strains showed moderate- to high-level ASN resistance. CONCLUSION: ASN resistance of M. tuberculosis is not necessarily a determining factor for enhanced transmission.
Assuntos
DNA Bacteriano/genética , Predisposição Genética para Doença , Mycobacterium tuberculosis/genética , Espécies Reativas de Nitrogênio/farmacologia , Tuberculose/genética , População Urbana , Brasil/epidemiologia , Genótipo , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Polimorfismo de Fragmento de Restrição , Prevalência , Estudos Retrospectivos , Tuberculose/epidemiologia , Tuberculose/microbiologiaRESUMO
SUMMARY: We investigated an outbreak caused by non-tuberculous mycobacteria (NTM) related to breast implant surgery in the city of Campinas, Brazil, by means of a retrospective cohort and molecular epidemiological study. A total of 492 records of individuals having breast surgery in 12 hospitals were evaluated. Twelve isolates were analysed using four different molecular typing methods. There were 14 confirmed cases, 14 possible cases and one probable case. One probable, nine possible and 12 confirmed cases were included in a cohort study; all occurred in eight of the hospitals and the confirmed cases in five. Univariate analysis showed that patients who had had breast reconstruction surgery in hospitals A and B were more likely to have NTM infections. No risk factor was independently associated with NTM infection in the multivariate model. The isolates obtained from patients at each hospital showed different molecular patterns, excluding isolates from hospital C that repeatedly showed the same genotype for approximately one year. In conclusion, this outbreak was caused by polyclonal strains at different institutions, and in one hospital a unique genotype caused most cases. No specific risk factors were found.
Assuntos
Implante Mamário/efeitos adversos , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Mycobacterium/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Adulto , Técnicas de Tipagem Bacteriana , Brasil/epidemiologia , Estudos de Coortes , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Epidemiologia Molecular , Análise Multivariada , Infecções por Mycobacterium/microbiologia , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/microbiologiaRESUMO
A cluster of cases of post-augmentation mammaplasty surgical site infections occurred between 2002 and 2004 in Campinas, in the southern region of Brazil. Rapidly growing mycobacteria were isolated from samples from 12 patients. Eleven isolates were identified as Mycobacterium fortuitum and one as Mycobacterium porcinum by PCR-restriction digestion of the hsp65 gene. These 12 isolates, plus six additional M. fortuitum isolates from non-related patients, were typed by pulsed-field gel electrophoresis (PFGE) and three PCR-based techniques: 16S-23S rRNA internal transcribed spacer (ITS) genotyping; randomly amplified polymorphic DNA (RAPD) PCR; and enterobacterial repetitive intergenic consensus (ERIC) PCR. Four novel M. fortuitum allelic variants were identified by restriction analysis of the ITS fragment. One major cluster, comprising six M. fortuitum isolates, and a second cluster of two isolates, were identified by the four methods. RAPD-PCR and ITS genotyping were less discriminative than ERIC-PCR. ERIC-PCR was comparable to PFGE as a valuable complementary tool for investigation of this type of outbreak.
Assuntos
Técnicas de Tipagem Bacteriana , Mamoplastia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium fortuitum/classificação , Mycobacterium fortuitum/isolamento & purificação , Infecção da Ferida Cirúrgica/microbiologia , Proteínas de Bactérias/genética , Brasil , Chaperonina 60 , Chaperoninas/genética , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/genética , DNA Espaçador Ribossômico/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Humanos , Mycobacterium fortuitum/genética , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Técnica de Amplificação ao Acaso de DNA Polimórfico , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
SETTING: A low-income neighborhood of Sao Paulo, Brazil. OBJECTIVE: To determine the incidence, risk factors and transmission patterns of multidrug-resistant tuberculosis (MDR-TB). DESIGN: Prospective longitudinal study of patients with pulmonary TB (PTB). METHODS: Sputum culture-confirmed patients with PTB were recruited between March 2000 and May 2002. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with MDR-TB. Mycobacterium tuberculosis isolates were tested for drug susceptibility and typed by IS6110-RFLP analysis. RESULTS: Of 420 patients, respectively 71% and 27% were new and previously treated; 15.5% of the patients' M. tuberculosis isolates were resistant to at least one drug; of these, 11% and 27% were found among new and previously treated cases, respectively. Respectively 1% and 16.7% of the new and previously treated cases were MDR-TB. RFLP analysis showed that new transmission of MDR strains was uncommon. By multivariate logistic regression analysis, previous TB and hospitalization in the 24 months before TB diagnosis were identified as independent predictors of MDR-TB. CONCLUSIONS: The results showed an intermediate level of MDR-TB incidence in a neighborhood of Sao Paulo and identified predictors that can be targeted for intervention by national and local TB control programs.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Fragmento de Restrição , Pobreza , Estudos Prospectivos , Fatores de Risco , População UrbanaRESUMO
SETTING: Four hundred and sixty-eight isoniazid (INH) resistant Mycobacterium tuberculosis isolates recovered from a selected Brazilian population. OBJECTIVE: To check for susceptibility to other chemotherapeutic drugs used in TB treatment, and to ascertain mutations involved in INH and rifampicin (RMP) resistance. DESIGN: Antimicrobial susceptibility to RMP, streptomycin and ethambutol (EMB) was evaluated by the resistance ratio method and pyrazinamide (PZA) by activity assay. Single strand conformation polymorphism (SSCP) and sequence analysis were performed in samples from this panel to confirm mutations in codon 315 of the katG and in a 69-bp region of the rpoB gene. RESULTS: Combined resistance to INH+RMP, INH+ PZA, INH+EMB, and INH+RMP+PZA was shown in respectively 272 (58.1%), 126 (26.9%), 47 (10%), 116 (24.8%) isolates. No katG mutation was found in 19 (39.6%) of 48 strains tested. Ser315Thr substitution was found in 29 (60.4%). All RMP-resistant strains tested (n = 25) showed rpoB mutations. S531L substitution was found in 15 (60%). CONCLUSION: INH-resistant strains isolated from selected Brazilian populations frequently show resistance to other first-line anti-tuberculosis drugs. rpoB mutation was responsible for RMP resistance in all strains. Among INHr strains, katG mutations were shown in only 60.4%. Genetic approaches targeting the rpoB gene but not the katG gene have a high sensitivity to detect resistance among Brazilian M. tuberculosis strains.