RESUMO
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.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Tuberculose , Humanos , Pulmão , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium tuberculosis/genética , Micobactérias não Tuberculosas/genética , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
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.
Assuntos
Predisposição Genética para Doença , Fatores Inibidores da Migração de Macrófagos , Tuberculose , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos/genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Tuberculose/genéticaRESUMO
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.
Assuntos
Farmacorresistência Bacteriana Múltipla , Tipagem Molecular , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/farmacologia , Brasil , Genes Bacterianos , Marcadores Genéticos , Técnicas de Genotipagem , Humanos , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Análise de Sequência de DNARESUMO
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.
Assuntos
Antituberculosos/uso terapêutico , Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Brasil/epidemiologia , Coinfecção/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tuberculose Pulmonar/tratamento farmacológico , Adulto JovemRESUMO
Spoligotyping has shown Mycobacterium tuberculosis strains to be composed of different lineages, and some of them are not just geographically restricted but also affect specific ethnic populations and are associated with outbreaks and drug resistance. We recently described a particular subtype within the Latin American-Mediterranean (LAM) family, called RD(Rio), widespread in Brazil. Moreover, recent data also indicate that RD(Rio) is present in many countries on all continents and is associated with cavitary disease and multidrug resistance (MDR). To further explore the relationship between RD(Rio) and MDR, we conducted a study in a tuberculosis (TB) reference center responsible for the care of MDR patients in Rio Grande do Sul, the southernmost Brazilian state. From a collection of 237 clinical isolates, RD(Rio) alone was responsible for one-half of all MDR cases, including one large group composed of strains with identical IS6110-restriction fragment length polymorphism (RFLP) and having the LAM5 signature. We additionally had complete data records for 96 patients and could make comparisons between the presence and absence of RD(Rio). No difference in clinical, radiological or laboratory features was observed, but a significantly greater number of cases with MDR were described in patients infected with an RD(Rio) strain (P = 0.0015). Altogether, RD(Rio) was responsible for 38% of all TB cases. These data support and confirmed previous findings that RD(Rio) is the main agent responsible for TB in Brazil and is associated with drug resistance. Considering that RD(Rio) is a globally distributed genotype, such findings raise concern about the increase in MDR in certain human populations.
Assuntos
Farmacorresistência Bacteriana Múltipla , Tipagem Molecular , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Polimorfismo de Fragmento de Restrição , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Brasil/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Epidemiologia Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , PrevalênciaRESUMO
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.
Assuntos
Antibióticos Antituberculose/uso terapêutico , Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Brasil/epidemiologia , Perfilação da Expressão Gênica , Genoma Bacteriano/genética , Humanos , Isoniazida/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos Retrospectivos , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Sequenciamento Completo do Genoma , Adulto JovemRESUMO
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.
Assuntos
Resistência a Medicamentos/genética , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Mycobacterium tuberculosis/efeitos dos fármacos , Brasil , Resistência a Medicamentos/imunologia , Estudo de Associação Genômica Ampla/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/microbiologiaRESUMO
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.
Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Brasil/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Repetições Minissatélites , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Polimorfismo de Nucleotídeo Único , Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Sequenciamento Completo do GenomaRESUMO
A prospective study was designed to evaluate the clinical usefulness of spoligotyping applied directly to sputum samples. Patients suspected of having tuberculosis were recruited at the Hospital Sanatorio Partenon in Porto Alegre, Brazil. Of the 197 samples included in the analysis, 175 (88.8%) yielded a spoligotyping result that fully matched that obtained from culture. Low bacillary samples presented lower accuracy (50%). From 135 Mycobacterium tuberculosis spoligopatterns, we identified 44 different spoligotypes, of which 21 were shared patterns and 23 were unique. T1 was the most frequent subfamily. The genotyping strategy proposed here presents a short turnaround time and could be helpful in providing rapid information on strain identities in a clinical setting.
Assuntos
Técnicas de Tipagem Bacteriana/métodos , DNA Bacteriano/genética , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose/diagnóstico , Humanos , Mycobacterium tuberculosis/genética , Estudos Prospectivos , Escarro/química , Tuberculose/microbiologiaRESUMO
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.
Assuntos
Pneumopatias/epidemiologia , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Comorbidade , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Tempo , Tuberculose/epidemiologia , Tuberculose/microbiologiaRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Adulto Jovem , Tuberculose Pulmonar/prevenção & controle , Tuberculose Pulmonar/diagnóstico por imagem , Prisioneiros/estatística & dados numéricos , Radiologia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricosRESUMO
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.
RESUMO
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.
Assuntos
Interleucina-17/genética , Interleucina-6/genética , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/imunologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Humanos , Interleucina-17/imunologia , Interleucina-6/imunologia , Masculino , Polimorfismo de Nucleotídeo Único , Risco , Tuberculose Pulmonar/microbiologiaRESUMO
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.
Assuntos
Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Escarro/microbiologia , Coinfecção , DNA Bacteriano , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , América Latina/epidemiologia , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/classificação , Micobactérias não Tuberculosas/genética , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
A retrospective analysis of sixteen patients with pulmonary nodules diagnosed as histoplasmoma by histopathologic evidence of Histoplasma capsulatum var capsulatum was done in an endemic area for histoplasmosis. Brazilian literature was reviewed. All patients were white, nine were men, mean age at diagnosis was 50.8 years. Six (37.5%) patients had a relevant epidemiologic story. The pulmonary nodules were 0.7-2.7 cm in diameter, presenting as granulomatous lesions with caseous necrosis. Twelve (75%) patients had solitary nodules. Histoplasmoma as a rule is a solitary nodule of up to 3 cm in an asymptomatic patient. The diagnosis is made from histopathologic evidence of the fungus, which is accomplished using a special fungus stain, Gomori-Grocott methenamine silver. Cultures or seromycology do not help the diagnosis.
Assuntos
Histoplasmose/patologia , Pneumopatias Fúngicas/patologia , Nódulo Pulmonar Solitário/patologia , Adolescente , Adulto , Idoso , Animais , Brasil , Criança , Feminino , Histoplasma/isolamento & purificação , Humanos , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Nódulo Pulmonar Solitário/microbiologiaRESUMO
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.
Assuntos
Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica/métodos , Granzimas/genética , Mycobacterium tuberculosis/patogenicidade , Reação em Cadeia da Polimerase em Tempo Real , Receptores de IgG/genética , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Área Sob a Curva , Asma/diagnóstico , Asma/genética , Brasil , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Marcadores Genéticos , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/genética , Valor Preditivo dos Testes , Curva ROC , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
This report describes epidemiological, clinical and laboratorial aspects of 111 cases of disseminated histoplasmosis from Rio Grande do Sul over a 25-year period (1977-2002). AIDS and non-AIDS patients were analyzed was the predisposing disease in 63.1% of the patients. In both groups there were mostly men, without evidence of exposure to microfoci contaminated with Histoplasma capsulatum. The main clinical features were systemic (fever and weight loss were present in 97.1 and 92.7% of AIDS and non-AIDS cases), followed by respiratory and mucocutaneous manifestations. Seromycology (positive in 54.5% and 65.3% in AIDS and non-AIDS cases) was useful as a screening test. The high index of cutaneous involvement in AIDS patients (44.3%) compared with North American reports (p <0.01) suggests that different strains of Histoplasma capsulatum may induce different clinical manifestations of the same disease.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Histoplasma/isolamento & purificação , Histoplasmose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Histoplasmose/diagnóstico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Fiberoptic bronchoscopy is a useful procedure in the diagnosis of histoplasmosis, when the clinical material is adequately processed. Ten cases of disseminated histoplasmosis in patients with AIDS are presented here, with a mycological evaluation in culture, Mycosel and Sabouraud's chloramphenicol agar of clinical specimens obtained through fiberoptic bronchoscopy. The yield of Mycosel culture was 60%, while in Sabouraud's chloramphenicol agar it was 20%, supporting the importance of selective medium in the isolation of Histoplasma capsulatum var capsulatum from potentially contaminated clinical specimens, as well as the importance of clinical information for the laboratory as the key for a correct diagnosis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Líquido da Lavagem Broncoalveolar/microbiologia , Histoplasma/isolamento & purificação , Histoplasmose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Broncoscopia/métodos , Meios de Cultura , Humanos , Pneumopatias Fúngicas/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
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.