Laboratory-based study of drug resistance and genotypic profile of multidrug-resistant tuberculosis isolates in Salvador, Bahia, Brazil

Abstract Background: Surveillance of multidrug resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) is essential to guide disease dissemination control measures. Brazil contributes to a significant fraction of tuberculosis (TB) cases worldwide, but only few reports addressed MDR/XDR-TB in the country. Methods: This cross-sectional, laboratory-based study describes the phenotypic resistance profiles of isolates obtained between January 2008 and December 2011 in Bahia, Brazil, and sociodemographic, epidemiological, and clinical characteristics (obtained from mandatory national registries) of the corresponding 204 MDR/XDR-TB patients. We analyzed the mycobacterial spoligotyping and variable number of tandem repeats of mycobacterial interspersed repetitive units in 12-loci profiles obtained from Salvador. Results: MDR/XDR-TB patients were predominantly male, had a median age of 43 years, belonged to black ethnicity, and failed treatment before MDR-TB diagnosis. Nearly one-third of the isolates had phenotypic resistance (evaluated by mycobacteria growth indicator tube assay) to second-line anti-TB drugs (64/204, 31%), of which 22% cases (14/64) were diagnosed as XDR-TB. Death was a frequent outcome among these individuals and was associated with resistance to second-line anti-TB drugs. Most isolates successfully genotyped belonged to the Latin-American Mediterranean (LAM) Family, with an unprecedented high proportion of LAM10-Cameroon subfamily bacilli. More than half of these isolates were assigned to a unique cluster by the genotyping methods performed. Large clusters of identical genotypes were also observed among LAM SIT42 and SIT376 strains. Conclusions: We highlight the need for strengthening local and national efforts to perform early detection of TB drug resistance and to prevent treatment discontinuation to limit the emergence of drug-resistant strains.

Rapid molecular test for tuberculosis: impact of its routine use at a referral hospital / Teste rápido molecular para tuberculose: avaliação do impacto de seu uso na rotina em um hospital de referência

ABSTRACT Objective: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. Methods: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. Results: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. Conclusions: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.

RESUMO Objetivo: Avaliar o impacto do teste rápido molecular automatizado Xpert MTB/RIF, utilizado para a detecção de Mycobacterium tuberculosis e sua resistência à rifampicina, em condições de rotina, em um hospital de referência no estado da Bahia. Métodos: Estudo descritivo retrospectivo utilizando o banco de dados do Laboratório de Micobacteriologia do Hospital Especializado Octávio Mangabeira, localizado na cidade de Salvador, e um programa de georreferenciamento. Entre junho de 2014 e março de 2015, foram incluídas no estudo 3.877 amostras de escarro coletadas de pacientes sintomáticos respiratórios em condições de rotina. Todas as amostras coletadas foram submetidas tanto à baciloscopia quanto a Xpert MTB/RIF. Os pacientes foram estratificados por sexo, idade e georreferenciamento. Resultados: Das 3.877 amostras de escarro analisadas, Xpert MTB/RIF detectou a presença de M. tuberculosis em 678 pacientes (17,5%). Desses, 60 (8,8%) apresentaram resistência à rifampicina. O Xpert MTB/RIF detectou 254 pacientes com baciloscopia negativa, representando um acréscimo diagnóstico de 59,9%. Conclusões: A implantação do Xpert MTB/RIF, sob condições de rotina, teve um impacto significativo no aumento da detecção de casos de tuberculose em pacientes com baciloscopia negativa.

Multidrug-resistant tuberculosis

Despite the efforts made worldwide to reduce the number of cases of drug-susceptible tuberculosis, multidrug-resistant tuberculosis (MDR-TB) constitutes an important public health issue. Around 440,000 new cases of MDR-TB are estimated annually, although in 2008 only 7% of these (29,423 cases) were notified. The laboratory tests for diagnosing resistance may be phenotypic (based on culture growth in the presence of drugs) or genotypic (i.e. identification of the presence of mutations that confer resistance). The urgent need for a rapid means of detecting resistance to anti-TB drugs has resulted in the development of many genotypic methods over recent years. The treatment of MDR-TB is expensive, complex, prolonged (18-24 months) and associated with a higher incidence of adverse reactions. Some basic principles must be observed when prescribing an adequate treatment regimen for MDR-TB: (a) the association of at least four drugs (three of which should not have been used previously); (b) use of a fluoroquinolone; and (c) use of an injectable anti-TB drug. In Brazil, the therapeutic regimen for MDR-TB has been standardized and consists of five drugs: terizidone, levofloxacin, pyrazinamide, ethambutol and an aminoglycoside (streptomycin or amikacin). Pulmonary resection is an important tool in the coadjuvant treatment of MDR-TB. While a recent meta-analysis revealed an average cure rate of MDR-TB of 69%, clinical studies are currently being conducted with new drugs and with drugs already available on the market but with a new indication for TB, with encouraging results that will enable more effective treatment regimens to be planned in the future.

III Diretrizes para Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia / III Brazilian Thoracic Association Guidelines on Tuberculosis

Diariamente novos artigos científicos sobre tuberculose (TB) são publicados em todo mundo. No entanto, é difícil para o profissional sobrecarregado na rotina de trabalho acompanhar a literatura e discernir o que pode e deve ser aplicado na prática diária juntos aos pacientes com TB. A proposta das "III Diretrizes para TB da Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)" é revisar de forma crítica o que existe de mais recente na literatura científica nacional e internacional sobre TB e apresentar aos profissionais da área de saúde as ferramentas mais atuais e úteis para o enfrentamento da TB no nosso país. As atuais "III Diretrizes para TB da SBPT" foram desenvolvidas pela Comissão de TB da SBPT e pelo Grupo de Trabalho para TB a partir do texto das "II Diretrizes para TB da SBPT" (2004). As bases de dados consultadas foram LILACS (SciELO) e PubMed (Medline). Os artigos citados foram avaliados para determinação do ...

New scientific articles about tuberculosis (TB) are published daily worldwide. However, it is difficult for health care workers, overloaded with work, to stay abreast of the latest research findings and to discern which information can and should be used in their daily practice on assisting TB patients. The purpose of the III Brazilian Thoracic Association (BTA) Guidelines on TB is to critically review the most recent national and international scientific information on TB, presenting an updated text with the most current and useful tools against TB to health care workers in our country. The III BTA Guidelines on TB have been developed by the BTA Committee on TB and the TB Work Group, based on the text of the II BTA Guidelines on TB (2004). We reviewed the following databases: LILACS (SciELO) and PubMed (Medline). The level of evidence of the cited articles was determined, and 24 recommendations ...

Prevalência de TB ativa e TB latente em internos de um hospital penal na Bahia / Prevalence of active and latent TB among inmates in a prison hospital in Bahia, Brazil

OBJETIVO: Estimar as prevalências de TB latente e TB ativa entre custodiados de um hospital penal na Bahia. MÉTODOS: Foram avaliados através de estudo de corte transversal com coleta prospectiva de dados 237 internos no Hospital Penal da Bahia entre julho de 2003 e abril de 2004. Um questionário padronizado foi preenchido por estudantes de medicina. Os indivíduos foram sistematicamente submetidos aos seguintes exames: teste tuberculínico, radiografia de tórax em incidência póstero-anterior, baciloscopia e cultura para micobactérias. Os eventos de interesse foram TB ativa e TB latente. RESULTADOS: A média de idade foi de 36,6 anos, sendo 89,9 por cento homens. Tabagismo e alcoolismo foram relatados por 70.0 por cento e 43.9 por cento dos internos, respectivamente. História de tratamento para TB foi relatada por 11,3 por cento dos indivíduos. Dos internos avaliados, 36,3 por cento relataram tosse e 31,4 por cento, expectoração. Outros sintomas menos frequentemente referidos foram astenia (26,2 por cento), perda de peso (23,1 por cento), inapetência (17,7 por cento), febre (11,3 por cento) e hemoptise (6,7 por cento). Nenhum dos 86 internos testados apresentou sorologia anti-HIV positiva. Entre os 156 submetidos ao teste tuberculínico, a prevalência de TB latente foi de 61,5 por cento (146 casos). Do total, 6 casos de TB ativa foram detectados (prevalência de 2,5 por cento). A presença de tosse foi um determinante de TB ativa (razão de prevalência = 8,8; IC95 por cento: 1,04-73,9; p = 0,025). CONCLUSÕES: A população de internos do Hospital Penal da Bahia tem altas prevalências de TB latente e ativa. Estes achados justificam a necessidade de implantação de políticas públicas especificamente direcionadas para o controle da TB nesta população

OBJECTIVE: To determine the prevalence of latent and active TB among detainees in a prison hospital in Bahia, Brazil. METHODS: A cross-sectional study with prospective data collection was carried out comprising 237 inmates in the Bahia State Prison Hospital between July 2003 and April 2004. A standardized questionnaire was applied and completed by medical students. The detainees were systematically submitted to the following tests: tuberculin skin test, chest X-ray (anteroposterior), sputum smear microscopy and culture for mycobacteria. The events of interest were active TB and latent TB. RESULTS: The mean age of the participants was 36.6 years, and 89.9 percent were male. Smoking and alcohol consumption were reported by 70.0 percent and 43.9 percent of the inmates, respectively. A history of treatment for TB was reported by 11.3 percent of the inmates. Of the inmates evaluated, 36.3 percent reported cough and 31.4 percent reported expectoration. Other less common symptoms were asthenia (in 26.2 percent), weight loss (in 23.1 percent), loss of appetite (in 17.7 percent), fever (in 11.3 percent) and hemoptysis (in 6.7 percent). Of the 86 inmates tested, none presented positive HIV serology. The prevalence of latent TB was 61.5 percent (96 of the 156 inmates submitted to tuberculin skin tests), whereas that of active TB was 2.5 percent (6 of the 237 inmates evaluated). The presence of cough was a determinant of active TB (prevalence ratio = 8.8; 95 percent CI: 1.04-73.9; p = 0.025). CONCLUSIONS: Active and latent TB are highly prevalent among inmates hospitalized in the Bahia State Prison Hospital. Our findings justify the need to implement public policies specifically directed towards the control of TB in this population.

Anti-tuberculosis drug resistance in strains of Mycobacterium tuberculosis isolated from patients in a tertiary hospital in Bahia

Anti-tuberculosis drug resistance, particularly multiresistance, is a crucial issue in the control of tuberculosis (TB). This study estimated the prevalence of primary and acquired anti-tuberculosis drug resistance in strains of Mycobacterium tuberculosis isolated from hospitalized patients, to identify the risk factors for resistance, and to evaluate the its impact on hospital mortality for tuberculosis. Strains of Mycobacterium tuberculosis from 217 patients hospitalized for TB were analyzed. Subjects were recruited sequentially at a TB reference hospital in Salvador, Bahia, Brazil from July 2001 to July 2003. Multiresistant (MR) strains were defined as strains resistant to rifampicin and isoniazid. Of a total of 217 strains isolated, 41 (19.0 percent, 95 percentCI: 14.1-24.5 percent) were resistant to at least one drug. Prevalence of primary resistance was 7.0 percent (10/145), while a prevalence of 43.1 percent (31/72) was found for acquired resistance. Primary resistance to one drug alone was found in 2.1 percent (3/145) and acquired monoresistance in 5.6 percent (4/72). Prevalence of MR strains in general was 14.3 percent (31/217), of which 4.2 percent (6/145) consisted of primary MR and 34.7 percent (25/72) of acquired MR. Three strains showed resistance to more than one drug, but were not classified as MR. In the multivariate analysis, abandoning treatment remained strongly associated with resistance (adjusted OR: 7.21; 95 percentCI: 3.27-15.90; p<0.001) following adjustment for 3 potential confounders (gender, alcohol dependence and HIV-infection). An association was found between resistance and mortality from tuberculosis, even after adjustment for HIV status, age, sex and alcohol dependence (adjusted OR: 7.13; 95 percentCI: 2.25-22.57; p<0.001). High prevalences of resistance, principally acquired resistance including MR, were found in patients hospitalized for TB in Bahia. This finding was strongly associated with having abandoned...

Prevalence of HIV infection in patients hospitalized for tuberculosis in Bahia, Brazil

HIV infection is an important risk factor for the development of tuberculosis (TB), and also affects its morbidity and mortality. This study estimated the prevalence of HIV infection in patients hospitalized for TB in Bahia (in northeastern Brazil) and to evaluate its impact on in-hospital mortality. A total of 375 patients with TB, admitted consecutively to a TB reference hospital in Salvador (Bahia, Brazil), were evaluated between July 2001 and July 2003. Anti-HIV serology was performed in all patients irrespective of clinical and/or epidemiological data suggestive of HIV infection. Death during hospitalization was the principal event-dependent variable. Mean age of patients was 41.4 ± 16.2 years and the male/female ratio was 3.4:1.0. The prevalence of HIV infection was 8.8 percent (95 percentCI: 6.2-12.0 percent). Patients in the HIV-positive group were younger than those in the HIV-negative group (37.1 versus 41.9 years; p=0.05). In-hospital mortality was 10.9 percent for the whole group (95 percentCI: 9.4-15.9 percent), but was significantly greater in the HIV-positive group compared to the HIV-negative group (27.3 percent versus 9.4 percent; RR=2.9; 95 percentCI: 1.5-5.6; p=0.002). The prevalence of HIV infection in patients hospitalized for TB in Bahia (northeastern Brazil) is relatively high (8.8 percent) and mortality is significantly higher (2.9-fold) in the HIV-positive group. These findings justify carrying out HIV testing, as recommended by the Brazilian Ministry of Health, in all TB patients, particularly those requiring hospitalization.

Paragonimiasis: first case reported in Brazil

The authors present a case from a 59 years old white female Brazilian patient, based in Salvador-Bahia, Brazil's northeastern side area, who experienced irritative cough and progressive dyspnea, and, after 18 months, was admitted to a hospital with respiratory insufficiency. The physical exam showed diffuse rales in both hemithoraces. Initial leukogram showed 14,400 cells/mL with 14 percent of eosinophils and chest X-ray showed peribronchovascular infiltrate, predominating in the lower half of the lung fields, and small opaque nodules. The high-resolution computed tomography scan of the chest (HRCT) presented compatible pattern with airways disease, especially from the small airways, with air trapping, tree sprouting images, central lobular nodules and bronchiectasis, making the results compatible with bronchiolitis and bronchiectasis. The transbroncho biopsy unveiled granulomatous lesion with necrosis, where was noticed a structure compatible to a parasitic case, and the research of the parasite eggs in the sputum was positive to paragonimus. After the praziquantel use, the patient presented a thick ferruginous expectoration and the result for BAAR examination was positive. The PCR exam and the sputum culture confirmed M. tuberculosis, and then the treatment for M. tuberculosis was initiated. The authors warn that this infection may have been a consequence of economics globalization process, where the importation of parasitized crustaceans might be the cause. However, there is the need of an accurate examination for the possibility of paragonimus specimens in this area of Brazil.

Infection with the Mycobacterium avium complex in patients without predisposing conditons: a case report and literature review

Nontuberculous Mycobacteria (NTM), especially Mycobacterium avium-intracellulare complex (MAC), has been considered responsible for human disease, especially in HIV patients. Nevertheless, it has been diagnosed in immunocompetent elderly men, frequently with previous pulmonary disease: chronic obstructive lung disease (COPD), complications of tuberculosis, pulmonary fibrosis and bronchiectasis. We relate the case of a female patient, 51 years old, with continuously acid fast bacilli (AFB) smears and with three previous treatments, which were conducted at the multiresistant tuberculosis (MRTB) service. MAC was identified in the sputum culture, and she received treatment for one year. The posterior sputum exams were negative. The cavity lesions observed in the high-resolution computed tomography (HRCT) were reduced, and some of the nodule lesions became bronchiectasis, even after the end of treatment. We agree with the literature reports that indicate that MAC is the cause of bronchiectasis. It is necessary to identify the type of mycobacteria in immunocompetent individuals with positive AFB smears that do not become negative with tuberculosis treatment.

Nontuberculosis mycobacteria at a multiresistant tuberculosis reference center in Bahia: clinical epidemiological aspects

OBJETIVO: Examine the prevalence and clinical/epidemiological aspects of patients with nontuberculous mycobacteria (NTM) isolated from sputum provided by an outpatient clinic specializing in the treatment of multiresistant tuberculosis (MRTB) in Bahia, Brazil. METHODS: All patients followed at the MRTB outpatient clinic of the Octávio Mangabeira Specialized Hospital (HEOM) were evaluated retrospectively from July 1998 to July 2003. All patients underwent direct examinations and cultures to identify the mycobacteria species found during initial and subsequent evaluations. The following variables were recorded: age, gender, clinical symptoms and signs, pre-existing lung disease, prior TB treatment, HIV serology, and NTM species. Categorical and quantitative variables were respectively characterized using proportions and measures ± SD. RESULTS: NTM were isolated in 19 of 231 patients (8.2 percent; 95 percentCI: 5.2 percent-12.3 percent), with the following species distribution: 58 percent (11/19) M. chelonae/abscessus; 16 percent (3/19) M. avium-intracellular complex; 16 percent (3/19) M. kansasii; and 11 percent (2/19) M. fortuitum. HIV serology was positive for just one patient (5 percent), from whom M. chelonae/abscessus was isolated. Productive coughing was observed in all cases. American Thoracic Society (ATS) diagnostic criteria for NTM lung disease were observed in 14 patients (74 percent). CONCLUSION: The prevalence of NTM isolated from patients referred to the MRTB outpatient clinic in Bahia was 8.2 percent (CI 95 percent: 5.2 percent-12.3 percent); rapid-growth mycobacteria (M. chelonae/M. fortuitum) were the most frequently isolated (68 percent).

Quimioprofilaxia na prevenção da tuberculose / Chemoprophylaxis in the prevention of tberculosis

A quimioprofilaxia da tuberculose constitui-se numa medida terapêutica para a prevenção da infecção pelo Mycobacterium tuberculosis ou para evitar o desenvolvimento da doença nos indivíduos infectados. Geralmente baseia-se na administração de isoniazida. Entretanto, o uso de rifampicina e pirazinamida vem sendo recentemente introduzido. Este trabalho tem como objetivo revisar os resultados dos principais estudos que avaliaram as indicações da quimioprofilaxia com isoniazida e sua associação com outras drogas, sua efetividade na prevenção da tuberculose considerando os diversos grupos de risco, e as alternativas do uso de outros esquemas. Procedeu-se à revisão sistemática da literatura, com ênfase em ensaios clínicos e meta-análises. Foram consultados também os documentos oficiais. Foram selecionados aqueles estudos que envolveram ensaios clínicos ramdomizados com uso de isoniazida, rifampicina ou pirazinamida em pacientes HIV positivos ou negativos. Concluiu-se que a isoniazida continua sendo efetiva na prevenção da tuberculose na população de indivíduos HIV negativos e de HIV positivos. A dose padrão de 5 a 15 mg/kg/dia tem mostrado proteção similar para períodos de tratamento de seis e doze meses. O risco de desenvolver hepatite foi menor que 1 por cento, sendo recomendada sua utilização com acompanhamento nos indivíduos com idade superior a 35 anos e usuários de álcool. Os estudos com esquemas de tratamento utilizando outros medicamentos não foram conclusivos, sendo necessária a realização de novos estudos para avaliação da efetividade desses esquemas em populações de alto risco de desenvolver tuberculose.

Penicillin at the late stage of leptospirosis: a randomized controlled trial

There is evidence that an early start of penicillin reduces the case-fatality rate of leptospirosis and that chemoprophylaxis is efficacious in persons exposed to the sources of leptospira. The existent data, however, are inconsistent regarding the benefit of introducing penicillin at a late stage of leptospirosis. The present study was developed to assess whether the introduction of penicillin after more than four days of symptoms reduces the in-hospital case-fatality rate of leptospirosis. A total of 253 patients aged 15 to 76 years with advanced leptospirosis, i.e., more than four days of symptoms, admitted to an infectious disease hospital located in Salvador, Brazil, were selected for the study. The patients were randomized to one of two treatment groups: with intravenous penicillin, 6 million units day (one million unit every four hours) for seven days (n = 125) and without (n = 128) penicillin. The main outcome was death during hospitalization. The case-fatality rate was approximately twice as high in the group treated with penicillin (12 percent; 15/125) than in the comparison group (6.3 percent; 8/128). This difference pointed in the opposite direction of the study hypothesis, but was not statistically significant (p = 0.112). Length of hospital stay was similar between the treatment groups. According to the results of the present randomized clinical trial initiation of penicillin in patients with severe forms of leptospirosis after at least four days of symptomatic leptospirosis is not beneficial. Therefore, more attention should be directed to prevention and earlier initiation of the treatment of leptospirosis

Electrocardiographic alterations in patients hospitalized with leptospirosis in the Brazilian City of Salvador

OBJECTIVE: To report the frequency and types of electrocardiographic alterations in patients with leptospirosis in the first 24 hours of hospitalization. METHODS: We analyzed the electrocardiograms of 157 patients admitted to the Hospital Couto Maia in the city of Salvador, in the State of Bahia, Brazil, from March 1998 to June 1999. The electrocardiograms were performed in the first 24 hours after hospital admission, independent of the clinical manifestations of the patients. RESULTS: The mean ± SD for patients' age was 35.5± 13.7 (median = 32) years, and jaundice was present in 95.5 percent of them. Alterations in the electrocardiogram were detected in 68.2 percent (107/157) of the patients (95 percent confidence interval = 60.6 percent - 75.1 percent). Atrial fibrillation was the most frequent arrhythmia, occurring in 10.8 percent (17/157) of the patients. Other frequent findings were alterations in ventricular repolarization detected in 38.9 percent (61/157) of patients and first-degree atrioventricular block in 10.2 percent (16/157). The patients with atrial fibrillation were older and had higher levels of creatinine and aminotransferases. CONCLUSION: In this sample, approximately 2/3 of the patients had electrocardiographic alterations after hospital admission. Of the major arrhythmias, atrial fibrillation was the most frequent, and the patients with this arrhythmia had evidence of more severe disease. The relation between the presence and type of electrocardiographic alteration and the prognosis of leptospirosis is yet to be assessed

Chest radiograph abnormalities in patients hospitalized with leptospirosis in the city of Salvador, Bahia, Brazil

This study was designed to estimate the prevalence of pulmonary radiograph abnormalities and describe the distribution of the patterns of radiographic alterations among patients hospitalized with leptspirosis. Chest radiographs of 139 patients hospitalized with leptospirosis in Couto Maia Hospital, in Salvador, Bahia, Brazil, between July, 1997, and July, 1999, were analyzed. The radiographs were requested soon after hospital admission, independent of the clinical manifestations of the patients. Only the first radiograph was considered. Pulmonary radiograph alterations were recorded in 35/139 patients (25.2 percent); 95 percent mid-point confidence interval = 18.5 percent to 32.9 percent. Among the patients with radiograph alterations, alveolar infiltrate was seen in 26/35 (74.3 percent). The lesions were bilateral in 54.3 percent and located in the inferior lobes in 45.5 percent. Pleural effusion, represented by blunting of the costo-phrenic angle, was detected in 8.6 percent of the patients. The pattern of the pulmonary alterations, predominantly bilateral alveolar infiltrates, is consistent with the evidence that the basic pulmonay alteration in leptospirosis is a generalized capillaritis.