Detection of non-tuberculosus mycobacteria (NTMs) in lung samples using 16S rRNA.

BACKGROUND: Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease caused by NTM is hampered by its clinical similarity with tuberculosis (TB) and by the lack of an accurate and rapid laboratory diagnosis. OBJECTIVES: Detect DNA from NTMs directly from lung samples using real-time polymerase chain reaction (qPCR) for amplification of 16S rRNA. Additionally, DNA sequencing (hsp65 and rpoB genes) was used to identify the species of MNTs. METHODS: A total of 68 sputum samples (54 with suspected NTMs and 14 with TB) from patients treated at a referral hospital were used. FINDINGS: Of these, 27/54 (50%) were qPCR positive for NTMs and 14/14 TB patients (controls) were qPCR negative with an almost perfect concordance (Kappa of 0.93) with the Mycobacterium spp. culture. Sequencing confirmed the presence of NTM in all positive samples. The most common species was Mycobacterium gordonae (33%), followed by Mycobacterium abscessus (26%), Mycobacterium fortuitum (22%), Mycobacterium avium (15%) and Mycobacterium peregrinum (4%). MAIN CONCLUSIONS: The qPCR technique for detecting NTMs targeting 16S rRNA has the potential to detect NTMs and rapidly differentiate from Mycobacterium tuberculosis. However, it is necessary to identify the species to help in the differential diagnosis between disease and contamination, and to guide the choice of the therapeutic scheme.

Detection of non-tuberculosus mycobacteria (NTMs) in lung samples using 16S rRNA

BACKGROUND Non-tuberculous mycobacteria (NTMs) cause diseases known as mycobacteriosis and are an important cause of morbidity and mortality. The diagnosis of pulmonary disease caused by NTM is hampered by its clinical similarity with tuberculosis (TB) and by the lack of an accurate and rapid laboratory diagnosis. OBJECTIVES Detect DNA from NTMs directly from lung samples using real-time polymerase chain reaction (qPCR) for amplification of 16S rRNA. Additionally, DNA sequencing (hsp65 and rpoB genes) was used to identify the species of MNTs. METHODS A total of 68 sputum samples (54 with suspected NTMs and 14 with TB) from patients treated at a referral hospital were used. FINDINGS Of these, 27/54 (50%) were qPCR positive for NTMs and 14/14 TB patients (controls) were qPCR negative with an almost perfect concordance (Kappa of 0.93) with the Mycobacterium spp. culture. Sequencing confirmed the presence of NTM in all positive samples. The most common species was Mycobacterium gordonae (33%), followed by Mycobacterium abscessus (26%), Mycobacterium fortuitum (22%), Mycobacterium avium (15%) and Mycobacterium peregrinum (4%). MAIN CONCLUSIONS The qPCR technique for detecting NTMs targeting 16S rRNA has the potential to detect NTMs and rapidly differentiate from Mycobacterium tuberculosis. However, it is necessary to identify the species to help in the differential diagnosis between disease and contamination, and to guide the choice of the therapeutic scheme.

Rastreio radiológico para tuberculose em uma penitenciária do sul do Brasil / Radiological screening for tuberculosis in a prison in the south of Brazil

Introdução: Conhecer o perfil da população privada de liberdade da Penitenciária Modulada de Osório (PMO), do ponto de vista radiológico e estimar a prevalência da tuberculose ativa no presídio.Métodos: Foi realizada análise retrospectiva de 677 radiografias de tórax obtidas para rastreio de tuberculose e de dados da ficha de atendimento do setor de Radiologia no período de julho a outubro de 2019.Resultados: Foram detectadas 150 radiografias alteradas, o que representa 22% dos 677 exames. Dos 150 exames alterados, 109 (16% do total e 72% dos alterados) apresentavam lesões com características de doença granulomatosa. Dos 677 pacientes, 11,5% referiram tratamento atual ou prévio para tuberculose e estes representam 38% dos casos com radiografias alteradas. Foram detectados 50 pacientes sem história prévia de tuberculose com lesões de aspecto muito provavelmente devido a tuberculose com características de doença ativa (7,3% do total), os quais foram encaminhados para investigação como casos novos. Em relação ao questionário aplicado, não foi observada diferença significativa entre os pacientes que referiam ou negavam tosse entre os com exames normais e alterados.Conclusões: Os indivíduos privados de liberdade apresentaram alta prevalência de alterações radiológicas com aspecto sugestivo de doença granulomatosa. Estes achados permitem inferir que na Penitenciária Modulada de Osório há elevada prevalência de tuberculose, provavelmente em níveis semelhantes a outras casas prisionais do Brasil.

Introduction: To determine the radiologic profile of 'the prisoners at Osório Modular Prison and estimate the prevalence of active tuberculosis in the institution.Methods: We retrospectively analyzed 677 chest radiographs obtained for tuberculosis screening and data from the medical records of prisoners seen at the Radiology Department from July to October 2019.Results: Of 677 radiographs, 150 (22%) showed abnormalities. Of these, 109 (16% of total or 72% of abnormal radiographs) showed lesions characteristic of granulomatous disease. Of all 677 patients, 11.5% reported current or previous treatment of tuberculosis, accounting for 38% of all abnormal radiographs. Fifty patients with no previous history of tuberculosis had lesions that were most likely due to active tuberculosis (7.3% of total), and were referred for further investigation as new cases. The responses to the questionnaire revealed no significant difference between patients who reported or denied coughing when comparing those with normal vs abnormal radiographs.Conclusions: Individuals deprived of liberty had a high prevalence of radiologic abnormalities suggestive of granulomatous disease. These findings allow us to infer that there is a high prevalence of tuberculosis at Osório Modular Prison, probably at levels comparable to those of other prison facilities in Brazil.

Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates.

Treatment of drug-resistant tuberculosis requires extended use of more toxic and less effective drugs and may result in retreatment cases due to failure, abandonment or disease recurrence. It is therefore important to understand the evolutionary process of drug resistance in Mycobacterium tuberculosis. We here in describe the microevolution of drug resistance in serial isolates from six previously treated patients. Drug resistance was initially investigated through phenotypic methods, followed by genotypic approaches. The use of whole-genome sequencing allowed the identification of mutations in the katG, rpsL and rpoB genes associated with drug resistance, including the detection of rare mutations in katG and mixed populations of strains. Molecular docking simulation studies of the impact of observed mutations on isoniazid binding were also performed. Whole-genome sequencing detected 266 single nucleotide polymorphisms between two isolates obtained from one patient, suggesting a case of exogenous reinfection. In conclusion, sequencing technologies can detect rare mutations related to drug resistance, identify subpopulations of resistant strains, and identify diverse populations of strains due to exogenous reinfection, thus improving tuberculosis control by guiding early implementation of appropriate clinical and therapeutic interventions.

Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil.

Genomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.

Macrophage migration inhibitory factor - 794 CATT5-8 microsatellite polymorphism and susceptibility of tuberculosis.

PURPOSE: The establishment of candidate genetic determinants associated with tuberculosis (TB) is a challenge, considering the divergent frequencies among populations. The objective of this study was to evaluate the association between MIF - 794 CATT 5-8 polymorphism and susceptibility to TB. METHODS: Case-control study. Patients > 18 years, with pulmonary TB were included. The control group consisted of blood donors and household contacts, not relatives, healthy and > 18 years. MIF - 794 CATT 5-8 were genotyped using sequencing of PCR and capillary electrophoresis. RESULTS: 126 patients and 119 controls were included. The genotype 5/5 was more frequent among cases (15.1%) than in controls (5.9%) (p = 0.019). Cases had more frequently the allele 5 (29.4%) as compared with controls (19.3%) (p = 0.010). Prevalence of 7/X + 8/X genotypes was not different between cases and controls (p = 0.821). There was no difference between patients with alleles 7 and 8 and those with alleles 5 and 6 (p = 0.608). CONCLUSIONS: The genotype 5/5 and the allele 5 of MIF - 794 CATT 5-8 were more frequent among TB patients than in controls.

First insights into circulating XDR and pre-XDR Mycobacterium tuberculosis in Southern Brazil.

Drug-resistant tuberculosis (DR-TB) is major problem in the fight against TB. Multidrug resistant (MDR) TB patients have a reduced treatment success rates and for, extensively drug-resistant (XDR) TB the cure rate does not exceed 25% in many countries. To evaluate the pre-XDR-TB and XDR-TB prevalence and transmission in Rio Grande do Sul State, in southern Brazil, we performed a retrospective WGS-based analysis of 87 MDR-TB cases, aiming to identify resistance-conferring mutations and its phylogenetic distinctiveness. Using a five SNP threshold for genomic clustering, 60 strains were genomically linked within 10 clusters, including 14 likely transmission events identified by retrospective conventional epidemiological investigation. Moreover, five likely transmission events involved 17 patients deprived of liberty in the same prison establishment. Mutations associated with isoniazid and rifampicin resistance were identified respectively in 97.70% and 98.85% of MDR M.tb strains, more frequently in katG and rpoB genes. In total, we identified eight (9.19%) pre-XDR and four (4.59%) XDR M.tb strains. Resistance to ofloxacin was observed in seven (8.04%) strains, all of them presenting resistance-conferring mutations. Phenotypic resistance from capreomycin and kanamycin was found in seven (8.04%) and four (4.59%) strains respectively, but no classic mutations associated with resistance to these drugs was identified. The results put in evidence a scenario involving multiple phylogenetically distinctive clades associated with pre-XDR and XDR-TB in the largest state of southern Brazil, while stressing the potential of using WGS to predict anti-TB drug resistance and need to halt MDR-TB transmission in the region.

Nontuberculous mycobacterial lung disease in a high tuberculosis incidence setting in Brazil.

OBJECTIVE: The incidence of lung disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. In Brazil, there are few studies about nontuberculous mycobacterial lung disease (NTMLD), and its prevalence is yet to be known. Our objective was to determine the specific etiology of the disease in the state of Rio Grande do Sul, Brazil, as well as the frequency and diversity of NTM species in our sample of patients. METHODS: This is a retrospective analysis of the medical records of patients diagnosed with NTMLD treated in a referral center located in the city of Porto Alegre, Brazil, between 2003 and 2013. RESULTS: Our sample comprised 100 patients. The most prevalent NTM species were Mycobacterium avium complex (MAC), in 35% of the cases; M. kansasii, in 17%; and M. abscessus, in 12%. A total of 85 patients had received previous treatment for tuberculosis. Associated conditions included structural abnormalities in the lungs, such as bronchiectasis, in 23% of the cases; COPD, in 17%; and immunosuppressive conditions, such as AIDS, in 24%. CONCLUSIONS: MAC and M. kansasii were the most prevalent species involved in NTMLD in the state, similarly to what occurs in other regions of Brazil. Data on regional epidemiology of NTMLD, its specific etiology, and associated conditions are essential to establish appropriate treatment, since each species requires specific regimens. Most patients with NTMLD had received previous tuberculosis treatment, which might lead to development of resistance and late diagnosis.

Nontuberculous mycobacterial lung disease in a high tuberculosis incidence setting in Brazil / Doença pulmonar por micobactérias não tuberculosas em uma região de alta incidência de tuberculose no Brasil

ABSTRACT Objective: The incidence of lung disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. In Brazil, there are few studies about nontuberculous mycobacterial lung disease (NTMLD), and its prevalence is yet to be known. Our objective was to determine the specific etiology of the disease in the state of Rio Grande do Sul, Brazil, as well as the frequency and diversity of NTM species in our sample of patients. Methods: This is a retrospective analysis of the medical records of patients diagnosed with NTMLD treated in a referral center located in the city of Porto Alegre, Brazil, between 2003 and 2013. Results: Our sample comprised 100 patients. The most prevalent NTM species were Mycobacterium avium complex (MAC), in 35% of the cases; M. kansasii, in 17%; and M. abscessus, in 12%. A total of 85 patients had received previous treatment for tuberculosis. Associated conditions included structural abnormalities in the lungs, such as bronchiectasis, in 23% of the cases; COPD, in 17%; and immunosuppressive conditions, such as AIDS, in 24%. Conclusions: MAC and M. kansasii were the most prevalent species involved in NTMLD in the state, similarly to what occurs in other regions of Brazil. Data on regional epidemiology of NTMLD, its specific etiology, and associated conditions are essential to establish appropriate treatment, since each species requires specific regimens. Most patients with NTMLD had received previous tuberculosis treatment, which might lead to development of resistance and late diagnosis.

RESUMO Objetivo: A incidência de doença pulmonar causada por micobactérias não tuberculosas (MNT) tem aumentado em todo o mundo. No Brasil, há poucos estudos sobre doença pulmonar por MNT, e sua prevalência ainda não é conhecida. Nosso objetivo foi determinar a etiologia específica da doença no estado do Rio Grande do Sul, bem como a frequência e a diversidade das espécies de MNT em nossa amostra de pacientes. Métodos: Análise retrospectiva dos prontuários de pacientes diagnosticados com doença pulmonar por MNT atendidos em um centro de referência localizado na cidade de Porto Alegre, RS, entre 2003 e 2013. Resultados: Nossa amostra foi composta por 100 pacientes. As espécies de MNT mais prevalentes foram Mycobacterium avium complex (MAC, complexo M. avium), em 35% dos casos; M. kansasii, em 17%; e M. abscessus, em 12%. Um total de 85 pacientes havia feito tratamento anterior para tuberculose. Condições associadas incluíram anormalidades estruturais nos pulmões, como bronquiectasias, em 23% dos casos; DPOC, em 17%; e condições imunossupressoras, como AIDS, em 24%. Conclusões: MAC e M. kansasii foram as espécies mais prevalentes envolvidas na doença pulmonar por MNT no estado, à semelhança do que ocorre em outras regiões do Brasil. Dados sobre a epidemiologia regional da doença pulmonar por MNT, sua etiologia específica e condições associadas são fundamentais para se estabelecer um tratamento adequado, já que cada espécie requer um esquema específico. A maioria dos pacientes com doença pulmonar por MNT havia feito tratamento anterior para tuberculose, o que pode levar a desenvolvimento de resistência e diagnóstico tardio.

Análise das abordagens antitabágicas para pacientes em tratamento da tuberculose / Analysis of the anti-tobacco approaches for patients undergoing tuberculosis treatment

O presente trabalho teve como objetivos avaliar se os pacientes atendidos no Ambulatório de Tisiologia do Hospital Sanatório Partenon (HSP) recebem ou já receberam abordagens antitabágicas nos serviços de saúde. Descrever o perfil sociodemográfico dos pacientes, conhecer o número de pacientes em tratamento para tuberculose (TB) que faziam uso de tabaco, identificar os tipos de abordagens sobre tabagismo oferecidas nos serviços de saúde, reconhecer e identificar o padrão de uso do tabaco antes e após diagnóstico de TB. Estudo transversal, quantitativo, que entrevistou 35 pacientes maiores de 18 anos, em tratamento para TB pulmonar. A análise dos dados foi realizada com a ajuda do programa de análises estatísticas SPSS Windows versão 16.0, sendo realizadas análises descritivas de frequência. Após análise, constatou-se que a média de idade foi de 38,9 anos, predominância do sexo masculino e baixo nível de escolaridade. Vinte e três (65,7%) pacientes referiram fazer uso do tabaco antes do diagnóstico de TB, sendo que desses, 16 (69,6%) alteraram o padrão do uso após diagnóstico. Quanto à realização de abordagens nos serviços de saúde, a maioria 17 (58,6%), relatou ter recebido algum tipo de abordagem no serviço especializado, sendo o médico o profissional mais citado em ambos os serviços. Com este estudo, conclui-se que o tabagismo vem sendo abordado com mais frequência no serviço especializado, após o diagnóstico de outra doença.

The aim of this study is to evaluate whether patients treated at the Outpatient Clinic of the Hospital Sanatorio Partenon (HSP) receive or have already received anti-smoking approaches in the health services. To describe the sociodemographic profile of the patients, to know the number of patients under treatment for tuberculosis (TB) who made use of tobacco, to identify the types of approaches on smoking offered in health services, to recognize and identify the pattern of tobacco use before and after the diagnosis of TB. A cross-sectional, quantitative study that interviewed 35 patients over 18 years of age in treatment for pulmonary tuberculosis. Data analysis was performed with the help of the statistical analysis program SPSS Windows version 16.0, with descriptive frequency analyzes being performed. After analysis, it was found that the mean age was 38.9 years, predominantly male and with a low level of schooling. Twenty-three (65.7%) patients reported using tobacco before the diagnosis of tuberculosis, of which, 16 (69.6%) changed the pattern of use after diagnosis. Regarding the implementation of approaches in health services, the majority 17 (58.6%) reported having received some type of approach in the specialized service, with the physician being the most cited professional in both services. With this study, it is concluded that smoking is being approached more frequently in the specialized service, after the diagnosis of another disease.

First detection of Mycobacterium triplex in Latin America.

In this study we describe the first isolation of Mycobacterium triplex in Latin America. This species causes infections in humans, with very few reports from around the world. We isolated two sputum specimens of a patient with a 6-year history of human immunodeficiency and tuberculosis treatment failure. All tests used confirmed M. triplex and the patient responded well to drug therapy for 18months.

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population.

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2-330 T>G (rs2069762); IL4-590 C>T (rs2243250); IL6-174 G>C (rs1800795); IL10-592 A>C (rs1800872); IL10-1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil.

We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RD(Rio), and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C((-17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers.

A real-time PCR signature to discriminate between tuberculosis and other pulmonary diseases.

The goal of this study was to identify a host gene signature that can distinguish tuberculosis (TB) from other pulmonary diseases (OPD). We conducted real-time PCR on whole blood samples from patients in Brazil. TB and OPD patients (asthma and non-TB pneumonia) differentially expressed granzyme A (GZMA), guanylate binding protein 5 (GBP5) and Fc gamma receptor 1A (CD64). Receiver operating characteristic, tree classification and random forest analyses were applied to evaluate the discriminatory power of the three genes and find the gene panel most predictive of patients' disease classification. Tree classification produced a model based on GBP5 and CD64 expression. In random forest analysis, the combination of the three genes provided a robust biosignature to distinguish TB from OPD with 95% specificity and 93% sensitivity. Our results suggest that GBP5 and CD64 in tandem may be the most predictive combination. However, GZMA contribution to the prediction model requires further investigation. Regardless, these three genes show promise as a rapid diagnostic marker separating TB from OPD.

Tuberculosis recurrence in a high incidence setting for HIV and tuberculosis in Brazil.

BACKGROUND: To compare epidemiological data between recurrent cases after cure (RC), distinguishing relapse from reinfection, after dropout (RD) and new cases (NC) in an ambulatory setting in a TB-endemic country. METHODS: Records of patients who started treatment for pulmonary TB between 2004 and 2010 in a TB clinic were reviewed. Epidemiological data were analyzed. Spoligotyping and MIRU patterns were used to determine relapse or reinfection in 13 RC available. RESULTS: Of the eligible group (1449), 1060 were NC (73.2%), among the recurrent cases, 203 (14%) were RC and 186 (12.8%) were RD. Of RC, 171 (84.2%) occurred later than 6 months after a previous episode, 13 had available DNA, in 4 (30.7%) the disease was attributed to reinfection and in 9 (69.3%), to relapse. Comparing RC to NC, HIV (p < 0.0001) was independent risk factor for RC. When RC and RD were compared, alcohol abuse (p = 0.001) and treatment noncompliance (p = 0.006) were more frequent in RD. CONCLUSIONS: HIV is the sole more important associated factor for RC. This finding points the need to improve the approach to manage TB in order to decrease the chance for exposure especially in vulnerable people with increased risk of developing disease and to improve DOTS strategy to deal with factors associated to treatment noncompliance.

Scedosporium apiospermum eumycetoma successfully treated with oral voriconazole: report of a case and review of the Brazilian reports on scedosporiosis.

We describe a case of white-grain eumycetoma caused by Scedosporium apiospermum in an immunocompetent host that was successfully treated with oral voriconazole, and we review the Brazilian reports on scedosporiosis.