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Background: Drug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence., Methods: Retrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute - Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis., Results: Of the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36-5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14-0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62-3.57, p < 0.001), along with no illicit drug use and primary drug resistance., Conclusions: The implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion., (© 2024. The Author(s).)

Background: Among chronic condition problems, tuberculosis still represents a serious public health problem globally., Objective: To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis., Methods: The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program., Results: We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%., Conclusion: Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.

Background: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil., Methods: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population., Findings: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined., Interpretation: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains., Funding: National Institutes of Health., Translation: For the Portuguese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The duration of the protective effect of tuberculosis preventive therapy (TPT) is controversial. Some studies have found that the protective effect of TPT is lost after cessation of therapy among people with human immunodeficiency virus (HIV) in settings with very high tuberculosis incidence, but others have found long-term protection in low-incidence settings., Methods: We estimated the incidence rate (IR) of new tuberculosis disease for up to 12 years after randomization to 4 months of rifampin or 9 months of isoniazid, among 991 Brazilian participants in a TPT trial in the state of Rio de Janeiro, with an incidence of 68.6/100 000 population in 2022. The adjusted hazard ratios (aHRs) of independent variables for incident tuberculosis were calculated., Results: The overall tuberculosis IR was 1.7 (95% confidence interval [CI], 1.01- 2.7) per 1000 person-years (PY). The tuberculosis IR was higher among those who did not complete TPT than in those who did (2.9 [95% CI, 1.3-5.6] vs 1.1 [.4-2.3] per 1000 PY; IR ratio, 2.7 [1.0-7.2]). The tuberculosis IR was higher within 28 months after randomization (IR, 3.5 [95% CI, 1.6-6.6] vs 1.1 [.5-2.1] per 1000 PY between 28 and 143 months; IR ratio, 3.1 [1.2-8.2]). Treatment noncompletion was the only variable associated with incident tuberculosis (aHR, 3.2 [95% CI, 1.1-9.7])., Conclusions: In a mostly HIV-noninfected population, a complete course of TPT conferred long-term protection against tuberculosis., Competing Interests: Potential conflicts of interest . C. V. and D. M. report grants from the Canadian Institutes of Health Research, the TBTrials Consortium, and the Canada Research Chairs Program. A. T. reports grants from CNPq (National Council for Scientific and Technological Development), Brazilian Ministry of Science, Technology and Innovation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In this paper, we presented a mathematical model for tuberculosis with treatment for latent tuberculosis cases and incorporated social implementations based on the impact they will have on tuberculosis incidence, cure, and recovery. We incorporated two variables containing the accumulated deaths and active cases into the model in order to study the incidence and mortality rate per year with the data reported by the model. Our objective is to study the impact of social program implementations and therapies on latent tuberculosis in particular the use of once-weekly isoniazid-rifapentine for 12 weeks (3HP). The computational experimentation was performed with data from Brazil and for model calibration, we used the Markov Chain Monte Carlo method (MCMC) with a Bayesian approach. We studied the effect of increasing the coverage of social programs, the Bolsa Familia Programme (BFP) and the Family Health Strategy (FHS) and the implementation of the 3HP as a substitution therapy for two rates of diagnosis and treatment of latent at 1% and 5%. Based of the data obtained by the model in the period 2023-2035, the FHS reported better results than BFP in the case of social implementations and 3HP with a higher rate of diagnosis and treatment of latent in the reduction of incidence and mortality rate and in cases and deaths avoided. With the objective of linking the social and biomedical implementations, we constructed two different scenarios with the rate of diagnosis and treatment. We verified with results reported by the model that with the social implementations studied and the 3HP with the highest rate of diagnosis and treatment of latent, the best results were obtained in comparison with the other independent and joint implementations. A reduction of the incidence by 36.54% with respect to the model with the current strategies and coverage was achieved, and a greater number of cases and deaths from tuberculosis was avoided., (© 2024. The Author(s), under exclusive licence to the Society for Mathematical Biology.)

Background: Leprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas., Objectives: To estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT., Methods: The statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables., Results: The overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio., Conclusions: The relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide., Trial Registration: ClinicalTrials.gov: NCT00669643., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT., Methodology: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC)., Results: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs., Conclusion: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Araujo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the association between the availability of GeneXpert®MTB/RIF in municipalities and the proportion of people who have access to this diagnostic technology for tuberculosis (TB), as well as the resistance detected by the surveillance system in Brazil., Methods: We analysed 4998 Brazilian municipalities that reported 432,937 new TB cases between 2015 and 2020. We compared municipalities with and without the availability of GeneXpert®MTB/RIF regarding the effective access to GeneXpert®MTB/RIF diagnosis and the prevalence of detected resistance., Results: Municipalities with at least one GeneXpert®MTB/RIF system had three times (95% CI 2.9-3.0) the access to diagnostic tests and 80.4% (95% CI 70.6%-90.2%) higher detection of resistance, compared with municipalities without this technology. We estimated that there have been 1890 cases of undetected resistance during this period in the country., Conclusions: The availability of GeneXpert®MTB/RIF system in the municipality increased the sensitivity of the surveillance for detecting TB resistance., Public Health Implications: It is a priority to strengthen laboratory networks and narrow the gap in access to rapid diagnosis in remote areas to improve the detection and control of drug-resistant tuberculosis., (© 2023 John Wiley & Sons Ltd.)

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone ( folP1 ), rifampin ( rpoB ), and ofloxacin resistance ( gyrA ) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relationship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group.

Background: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert., Methods: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months., Results: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p<0.01) in arm 1. Compared to the MGIT group, culture conversion after 6 months was higher for Xpert in arm 1 (90.9% vs. 79.3%, p=0.39) and LPA in arm 2 (80.0% vs. 83.0%, p=0.81)., Conclusions: In the Xpert arm, there was a significant reduction in days to the start of appropriate anti-TB treatment and a trend towards greater culture conversion in the sixth month.

Background: Leprosy post-exposure prophylaxis (LPEP) with single dose rifampicin (SDR) can be integrated into different leprosy control program set-ups once contact tracing has been established. We analyzed the spatio-temporal changes in the distribution of index cases (IC) and co-prevalent cases among contacts of leprosy patients (CP) over the course of the LPEP program in one of the four study areas in Brazil, namely the municipality of Alta Floresta, state of Mato Grosso, in the Brazilian Amazon basin., Methods: Leprosy cases were mapped, and socioeconomic indicators were evaluated to explain the leprosy distribution of all leprosy cases diagnosed in the period 2016-2018. Data were obtained on new leprosy cases [Notifiable diseases information system (Sinan)], contacts traced by the LPEP program, and socioeconomic variables [Brazilian Institute of Geography and Statistics (IBGE)]. Kernel, SCAN, factor analysis and spatial regression were applied to analyze changes., Results: Overall, the new case detection rate (NCDR) was 20/10 000 inhabitants or 304 new cases, of which 55 were CP cases among the 2076 examined contacts. Changes over time were observed in the geographic distribution of cases. The highest concentration of cases was observed in the northeast of the study area, including one significant cluster (Relative risk = 2.24; population 27 427, P-value < 0.001) in an area characterized by different indicators associated with poverty as identified through spatial regression (Coefficient 3.34, P-value = 0.01)., Conclusions: The disease distribution was partly explained by poverty indicators. LPEP influences the spatial dynamic of the disease and results highlighted the relevance of systematic contact surveillance for leprosy elimination., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme., Competing Interests: The authors have declared that no competing interests exist.

Background: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence., Methodology: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040., Principal Findings: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme., Conclusions: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Novartis Foundation and International Federation of Anti-Leprosy Association partners provided technical input in the design phase of the LPEP program and ensured overall programme coordination. All authors are either staff of the Novartis Foundation (Arielle Cavaliero, Zaahira Gani, and Ann Aerts), work as paid consultants for the programme described here (David J Blok, Peter Steinmann, Anuj Tiwari, Tanja Barth-Jaeggi, Marc Bonenberger, Helena Grete, Christa Kasang, Liesbeth Mieras, Unnati R Saha, Wim H van Brakel, Bart Vander Plaetse, and Jan Hendrik Richardus), act as national programme coordinators (Mohammad A Arif, Nand Lal Banstola, Rabindra Baskota, Teky Budiawan, Eliane Ignotti, Deusdedit V Kamara, Pratap R Manglani, Blasdus F Njako, Tiara Pakasi, Nayani D Suriyarachchi, Aye Tin Maung, Tin Shwe, and Millawage S D Wijesinghe) or serve on the Steering Committee of the programme (David Blaney, Paul Saunderson, W Cairns S Smith, René Stäheli, Jan van Berkel, Marcos Virmond). The funder had no role in the interpretation of findings or decision to publish this manuscript. Author Aye Tin Maung was unavailable to confirm his authorship contributions. On his behalf, the corresponding author has reported his contributions to the best of his knowledge.

Background: Weight change may inform tuberculosis treatment response, but its predictive power may be confounded by human immunodeficiency virus (HIV)., Methods: We prospectively followed up adults with culture-confirmed, drug-susceptible, pulmonary tuberculosis receiving standard 4-drug therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) in Brazil. We examined median weight change 2 months after treatment initiation by HIV status, using quantile regression, and unsuccessful tuberculosis treatment outcome (treatment failure, tuberculosis recurrence, or death) by HIV and weight change status, using Cox regression., Results: Among 547 participants, 102 (19%) were HIV positive, and 35 (6%) had an unsuccessful outcome. After adjustment for confounders, persons living with HIV (PLWH) gained a median of 1.3 kg (95% confidence interval [CI], -2.8 to .1) less than HIV-negative individuals during the first 2 months of tuberculosis treatment. PLWH were at increased risk of an unsuccessful outcome (adjusted hazard ratio, 4.8; 95% CI, 2.1-10.9). Weight change was independently associated with outcome, with risk of unsuccessful outcome decreasing by 12% (95% CI, .81%-.95%) per 1-kg increase., Conclusions: PLWH gained less weight during the first 2 months of tuberculosis treatment, and lack of weight gain and HIV independently predicted unsuccessful tuberculosis treatment outcomes. Weight, an easily collected biomarker, may identify patients who would benefit from alternative treatment strategies., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction and Objective: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil., Material and Methods: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing., Results: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p<0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1-18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5-12.7; p 0.005) significantly increased the risk of hepatotoxicity., Conclusion: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.

Background: The multidrug therapy (MDT) for leprosy treatment adopted by Brazil in the 1990s was important for reducing leprosy in the country; however, recurrent cases remained problematic. Mechanisms involved in leprosy recurrence are heterogeneous and can be sorted into three groups: insufficient therapy, bacillary persistence and new infections. This study aimed to analyse the time interval of leprosy recurrence in relation to the therapeutic scheme in the state of Acre. The hypotheses were as follows: 1) treatments (a) rifampicin, ofloxacin and minocycline (ROM) and (b) dapsone (DDS) have a short leprosy recurrence time, 2) treatments based on MDT have a long leprosy recurrence time, 3) there is a dose-response relationship between MDT and the time interval between leprosy episodes., Methods: This retrospective cohort study included 201 patients with a second episode of clinical leprosy at the reference centers for leprosy control in the state of Acre. Exposure was the type of therapeutic scheme as follows: 1) ROM, 2) DDS, 3) MDT 0-9 doses , 4) MDT 10-19 doses , 5) MDT 20-29 doses , and 6) MDT 30+ doses . Outcome was the time interval between release from treatment and a diagnosis of a recurrent leprosy case. Incidence rate ratios and relative risk Poisson regressions adjusted by age and sex were calculated with 95% confidence intervals., Results: The 201 patients studied during this retrospective follow-up resulted in a total of 224 cases of recurrent leprosy. Incidence rate ratios within this therapeutic scheme were as follows: 3.3 (2.39, 4.2; ROM/MDT 30+ ), 1.12 (0.33, 1.92; DDS/MDT 30+ ), 2.17 (1.39, 2.94; MDT 0-9 /MDT 30+ ), 1.94 (1.13, 2.75; MDT 10-19 /MDT 30+ ) and 1.26 (0.47, 2.05; MDT 20-29 /MDT 30+ ). Relative risk Poisson regressions showed a protective effect of MDT 30+ in comparison with ROM (0.22; 0.07, 0.72), MDT 0-9 (0.42; 0.21, 0.85), and MDT 10-19 (0.44; 0.21, 0.92). No differences among MDT 30+ and DDS (0.71; 0.36, 1.41) and MDT 20-29 (0.76; 0.38, 1.49) were observed., Conclusions: New infection is an important-yet neglected-mechanism in leprosy recurrence in the state of Acre and can challenge the leprosy elimination plan in Brazil. MDT with few doses might be associated with leprosy recurrence due to insufficient therapy or bacillary persistence.

Objectives: Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network., Methods: From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA., Results: Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases., Conclusions: This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF) and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil.

Multidrug-resistant tuberculosis (MDR-TB) (resistance to at least isoniazid and rifampicin) will influence the future of global TB control. 88% of estimated MDR-TB cases occur in middle- or high-income countries, and 60% occur in Brazil, China, India, the Russian Federation and South Africa. The World Health Organization collects country data annually to monitor the response to MDR-TB. Notification, treatment enrolment and outcome data were summarised for 30 countries, accounting for >90% of the estimated MDR-TB cases among notified TB cases worldwide. In 2012, a median of 14% (interquartile range 6-50%) of estimated MDR-TB cases were notified in the 30 countries studied. In 15 of the 30 countries, the number of patients treated for MDR-TB in 2012 (71 681) was >50% higher than in 2011. Median treatment success was 53% (interquartile range 40-70%) in the 25 countries reporting data for 30 021 MDR-TB cases who started treatment in 2010. Although progress has been noted in the expansion of MDR-TB care, urgent efforts are required in order to provide wider access to diagnosis and treatment in most countries with the highest burden of MDR-TB., (The content of this work is ©World Health Organization. Design and branding are ©ERS 2015.)

Background: Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints)., Methods and Findings: We conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (p<0.001), resulting in an increased bacteriologically confirmed notification rate of 59% (95% CI = 31%, 88%). However, the overall notification rate did not increase (15%, 95% CI =  -6%, 37%), and we observed no change in the notification rate for those without a test result (-3%, 95% CI = -37%, 30%). Median time to treatment decreased from 11.4 d (interquartile range [IQR] = 8.5-14.5) to 8.1 d (IQR = 5.4-9.3) (p = 0.04), although not among confirmed cases (median 7.5 [IQR = 4.9-10.0] versus 7.3 [IQR = 3.4-9.0], p = 0.51). Prevalence of rifampicin resistance detected by Xpert was 3.3% (95% CI = 2.4%, 4.3%) among new patients and 7.4% (95% CI = 4.3%, 11.7%) among retreatment patients, with a 98% (95% CI = 87%, 99%) positive predictive value compared to phenotypic drug susceptibility testing. Missing data in the information systems may have biased our primary endpoints. However, sensitivity analyses assessing the effects of missing data did not affect our results., Conclusions: Replacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment., Trial Registration: ClinicalTrials.gov NCT01363765. Please see later in the article for the Editors' Summary.

Background: In recent years, first-line therapy for Mycobacterium ulcerans infection in French Guiana has consisted of antibiotics active against this organism. Two regimens are used comprising rifampicin associated with clarithromycin or amikacin., Patients and Methods: We describe four patients presenting apparent worsening of their lesions during treatment: ulceration of a nodular lesion in a 32-year-old woman and worsening of an ulcerated lesion in three patients aged 16, 27 and 79 years., Discussion: In these 4 patients, we concluded that the symptoms were caused by a paradoxical response or a reaction, a phenomenon already described in tuberculosis and leprosy. Such worsening is transient and must not be misinterpreted as failure to respond to treatment. The most plausible pathophysiological hypothesis involves the re-emergence of potentially necrotizing cellular immunity secondary to the loss of mycolactone, a necrotizing and immunosuppressive toxin produced by M. ulcerans, resulting from the action of the antibiotics., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background Methods: for assessing the level of understanding of trial-related information during the informed consent (IC) process in developing countries are lacking., Purpose: To assess the understanding and retention of trial-related information presented in the IC process by administering an informed consent assessment instrument (ICAI) to participants in a clinical trial for a new tuberculosis (TB) regimen being conducted in Rio de Janeiro (Brazil). Methods The format of the ICAI was based on the language and structure of the United States National Cancer Institute's IC comprehension checklist. The ICAI was designed to assess points of the RioMAR study IC process that addressed the principles of research ethics requested by Brazilian Regulatory Authority: autonomy, beneficence, non-maleficence, and justice. Briefly, (1) Is the respondent participating in a clinical trial? (2) Are two different treatments being evaluated? (3) Is the treatment arm chosen by chance? (4) Is an HIV test required? (5) Are liver function tests required? (6) Can participants leave the study at any time? (7) Are the risks and benefits of taking part in the study clear? (8) May pregnant women participate in the study? (9) Can one of the study drugs reduce the effectiveness of contraceptives? (10) Are patients paid to participate in the study? The ICAI was applied at two time points: immediately after enrollment in the clinical trial and 2 months later., Results: A total of 61 patients who enrolled in the RioMAR study participated in this study. The percentage of correct answers to all questions was 82% at the time of the first ICAI; 31 participants (51%) did not recall that an HIV test was required (question 4) and 43 (70%) did not know that they could leave the study (question 6). Other individual questions were answered correctly by at least 76% of participants. There was no association between incorrect answers and age, gender, monthly family income, neighborhood, or level of education (p > 0.07). When the responses to the first and the second ICAI questions were compared, 15% or more of participants had conflicting answers to 5 of the 10 questions., Limitations: The ICAI uses dichotomous responses, leading to a 50% chance of guessing the correct answers. Two questions were asked only of women. Finally, only 6 of the 10 questions on the current version of the ICAI apply to most trials; others are trial-specific., Conclusions: The ICAI may be adapted to an individual trial and may prove to be a useful tool following a consent discussion to identify issues not fully understood by the research participants, thus prompting study staff to re-explain topics, possibly in a more elementary manner.

Infected wounds determined by cats' bites represent high costs to public health, and their adequate treatment relies on the knowledge of the antimicrobial susceptibility of bacterial agents found in the oral microbiota. Members of the genus Staphylococcus sp. belong to the microbiota of the oral mucosa of cats and are frequently involved in secondary infections of these wounds. This study aimed to evaluate the antimicrobial susceptibility of Staphylococcus species isolated from oral mucosa of cats. Samples were collected from 200 clinically healthy cats and processed by standard bacteriological methods and tested for susceptibility to a panel of 16 antimicrobials. A total of 212 staphylococci isolates were obtained from 141 of the 200 cats (70.5%), and more than one colony was recognized in 53 cases. Coagulase-negative species were most frequently found (89.6%) distributed among Staphylococcus xylosus (50.9%), Staphylococcus felis (27.4%), Staphylococcus simulans (6.1%) and Staphylococcus sciuri (5.2%). Coagulase-positive species (10.4%) were distributed among Staphylococcus aureus (4.7%) and Staphylococcus intermedius group (SIG) (5.7%). Regarding to antimicrobial resistance, 178 isolates (83.9%) were resistant to at least one antimicrobial, and rifampicin showed the best results with 100% of sensitive strains. Conversely, high rates of resistance were observed for penicillin and tetracycline (56.1%). The 212 staphylococci isolates and 30 (14.1%) strains were resistant to methicillin (on the disc susceptibility test) and may be preliminarily considered as methicilin-resistant staphylococci. In conclusion, this study reports important rates of antimicrobial resistance among the species of Staphylococcus isolated from clinical specimens of cats, which must be considered for the treating of cats' bites in humans., (© 2012 Blackwell Verlag GmbH.)

Setting: Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil., Objectives: To compare QuantiFERON®-TB Gold In-Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens., Design: Participants in the trial were invited to undergo serial QFT-GIT. Within-subject differences at different time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points., Results: Of 215 participants, 118 completed treatment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant difference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non-adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment., Conclusion: Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions.

A review of the records of patients seen between 2004 and 2011 at the Dermatology Clinic of the São Paulo University Medical School showed that only two leprosy patients had been co-infected with tuberculosis (TB). One patient showed a type 1 leprosy reaction during the first 3 months of treatment of pleural TB and in the other patient, pulmonary TB was diagnosed during the first 3 months of treatment of a type 1 leprosy reaction. Both patients showed normal cellular immune response tests, including those of the interferon-gamma (IFN-γ)/interleukin 12 (IL-12) axis. Although both mycobacterial infections are endemic in developing countries like Brazil, the co-infection has hardly been reported in the last decade. There is no suitable explanation for this observation. The reports on the interaction between the two mycobacteria are highly speculative: some studies suggest that leprosy, especially the anergic form, would predispose to TB, whereas other investigations suggested an antagonism between the two diseases.

Objective: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months) involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes., Methods: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil., Results: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated., Conclusions: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

Unlabelled: Recently antimicrobials of the fluoroquinolone class (pefloxacin and ofloxacin) were found far more effective against Mycobacterium leprae in studies with both mice and patients than dapsone and clofazimine. As multicentre trial participants, we evaluated the therapeutic efficacy, in terms of rate of relapse, of two new multidrug regimens containing ofloxacin, comparing them to 1 year and 2 years of standard WHO-MDT regimen in multibacillary (MB) leprosy patients. A total of 198MB patients were recruited to participate in a randomized, double-blind trial. Among those, 53 patients were treated with 1 year of WHO-MDT (a regimen including dapsone, clofazimine, and rifampin), 55 patients received 1 year of WHO-MDT plus an initial 1 month of daily ofloxacin, 63 patients were treated with 1 month of daily rifampin and daily ofloxacin, whereas 27 were treated with 2 years of WHO-MDT. Patients were regularly monitored for signs of relapse, in at least 7 years follow-up after being released from treatment., Results: Relapse occurred in those treated with 1-month regimen alone at a significant higher rate (P < 0.001): 388%, whereas in the other three regimens that included WHO-MDT it ranged from 0 to 5%. This study found that a short-course treatment for MB patients with rifampicin-ofloxacin combination had a higher failure rate. The addition of one month of daily ofloxacin to 12 months MB WHO-MDT did not increase its efficacy.

Background: With 254,525 new cases reported in 2007, leprosy is the worlds' second most widespread form of mycobacteriosis. According to the WHO, eradication of leprosy as a public health problem (defined by less than one case per 10,000 people) has been globally achieved. High endemic zones, however, still subsist. Leprosy rates among children, which reflect a country's endemic level, ranged from 0.55 to 19.2 % in 2006. Due to world population migrations, cases of leprosy are now seen in mainland France, in both children and adults., Patients and Methods: We describe three leprosy patients aged under 15 years treated at the Dermatology Unit of Saint Louis Hospital between 1st January 2002 and 31st December 2008. The three cases described account for 3 % of new patients treated for leprosy at Saint Louis Hospital over this 7-year period. All were born in an endemic country. Lesions appeared 18 months after arrival in France in two cases and clinical diagnosis was made in only one case. Due to absence of sensory loss in the lesions, diagnosis was reliant upon histopathological examination in two cases., Conclusion: Leprosy should be suspected in children from endemic countries presenting skin lesions, particularly hypochromic lesions, even if there is no sensory loss, regardless of how long they have been living in France., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Setting: Randomised controlled trial of latent tuberculosis infection (LTBI) treatment in 10 clinics in Canada, Saudi Arabia and Brazil., Objective: To identify early predictors of LTBI treatment adherence, including pre-treatment characteristics., Design: Patients randomised to 4 months of rifampicin (RMP; n = 420) or 9 months of isoniazid (n = 427) were monitored for adherence using an electronic device. Outcomes were 1) treatment completion, defined as intake of >or=80% of the prescribed doses, and further categorised as completed within the allotted time or not; and 2) treatment regularity, measured by the time interval between doses. Relative risk (RR) and adjusted odds ratios (aOR) of patients' pre-treatment characteristics and adherence at first follow-up visit were calculated., Results: Completion of treatment was higher with RMP (aOR 4.3, 95%CI 2.7-6.8). Early predictors (first follow-up visit) of non-adherence were late first visit attendance (RR for completion in time 0.9, 95%CI 0.8-0.98), >20% of missed doses (RR 0.4, 95%CI 0.3-0.6) and greater variation of hours between doses (0.209 vs. 0.131, P < 0.001). Serious adverse events were not associated with irregularity of treatment., Conclusion: The shorter RMP regimen was associated with better adherence. Patients with poor adherence could be identified at the first follow-up visit from their punctuality in follow-up, missed doses and variability of pill-taking.

Background: Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients agedor=10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST>or=15 mm regardless of previous BCG vaccination., Objective: To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment., Design: Retrospective cohort study. Contacts aged between 12 and 15 years and those aged>or=15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study., Results: TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100000 population. Risk of TB was greater among the 349 contacts with TST>or=5 mm (5.4%) compared to the 318 contacts with TST<5 mm (0.9%; RR 6.04, 95%CI 1.7-20.6)., Conclusion: The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration>or=5 mm was the only variable that predicted the development of TB disease within 2years.

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > or = 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Objective: To describe the clinical and therapeutic aspects of pulmonary tuberculosis and compare the adverse effects of the treatment and its outcome in elderly and nonelderly patients., Methods: This was a case-control study of 117 elderly individuals (over the age of 60 years) and 464 nonelderly individuals (aged 15-49 years). All subjects presented pulmonary tuberculosis that had been diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 1980 and 1996., Results: In the elderly group, pulmonary tuberculosis was found to be correlated with diabetes (OR = 3.98; 95% CI = 2.07-7.65; p = 0.001), lung disease (OR = 7.24; 95% CI = 3.64-14.46; p = 0.001) and heart disease (OR = 5.86; 95% CI = 2.88-11.95; p = 0.001). Smoking (OR = 2.07; 95% CI = 1.26-3.42; p = 0.002) and alcohol abuse (OR = 1.63; 95% CI = 1.01-2.68; p = 0.041) were also more common in the elderly group. In the elderly group, the treatment more frequently resulted in adverse reactions (OR = 1.62; 95% CI = 1.04-2.54; p = 0.024), especially gastrointestinal reactions (OR = 1.64; 95% CI = 1.01-2.77; p = 0.047), and treatment efficacy was lower: cure rate, 51%; mortality rate, 24%. Treatment adherence was low (approximately 77%) in both groups., Conclusions: In the elderly group, adverse reactions were more common, treatment outcomes were less favorable, there was a greater frequency of clinical complications and deaths related to drug toxicity, and the prevalence of concomitant diseases was higher.

Introduction: The WHO MDT for leprosy treatment was officially introduced in Brazil in 1991 and comprises three drugs: dapsone, rifampicin and clofazimine. There are few good studies on the frequency of side-effects attributable to MDT in Brazil., Methods: A retrospective and descriptive study carried out in a LCP in Vitória, State of Espirito Santo, Brazil. A specific and detailed protocol about side-effects was prepared and filled in from the patient records., Results: One hundred ninety four patients' records were analysed looking for side-effects attributable to MDT. Side-effects were attributed to at least one MDT component in 88 (45%) patients and 85 had side-effects due to dapsone, 24 due to rifampicin and 18 due to clofazimine. 185 episodes were identified. The suspected drug was stopped in 47 out of 88 episodes (24% patients); 46 had dapsone stopped, 5 had rifampicin stopped and no-one had clofazimine stopped., Conclusion: Side-effects attributed to MDT is more frequent than previously described, resulting in interruption of treatment in many patients.

The article aimed at assessing multidrug-resistant tuberculosis control in Brazil, based on the experiences of reference institutions, and the most relevant studies carried out to determine local and national resistance rates. Control measures and the current situation of treatment and diagnoses after the implementation of the national guidelines, which were revised in 2004, are considered. The first national survey on resistance to anti-tuberculosis drugs was performed in the middle of last decade. From its outcomes, a regimen to treat all cases of multidrug-resistant tuberculosis was validated and adopted. Government measures enabled the implementation of a surveillance system, whose outcomes are also commented.

Objective: To identify risk factors for recurrence of tuberculosis., Methods: We studied a cohort of 610 patients with active pulmonary tuberculosis who were enrolled for treatment between 1989 and 1994 and cured using a three-drug treatment regimen of rifampin, isoniazid and pyrazinamide (RHZ). The risk factors studied were age, gender, race, duration of symptoms, lesion cavitation, extent of disease, diabetes mellitus, alcoholism, HIV infection, delayed negative sputum conversion, treatment compliance, and medication doses. In order to detect recurrence, the patients were monitored through the Rio Grande do Sul State Healt Department Information System for 7.7 +/- 2.0 years after cure. Data were analyzed using the Student's t-test, the chi-square test or Fisher's exact test, and Cox regression models., Results: There were 26 cases of recurrence (4.3%), which corresponds to 0.55/100 patients-year. The recurrence rate was 5.95 and 0.48/100 patients-year in HIV-positive and HIV-negative patients, respectively (p < 0.0001). In the multivariate analysis, HIV infection [RR = 8.04 (95% CI: 2.35-27.50); p = 0.001] and noncompliance [RR = 6.43 (95% CI: 2.02-20.44); p = 0.002] proved to be independently associated with recurrence of tuberculosis., Conclusions: Recurrence of tuberculosis was more common in HIV-positive patients and in patients who did not comply with the self-administered treatment (RHZ regimen). Patients presenting at least one of these risk factors can benefit from the implementation of a post-treatment surveillance system for early detection of recurrence. An alternative to prevent noncompliance with tuberculosis treatment would be the use of supervised treatment.

Leprosy is an infectious disease of prevalence still high in endemic areas in Brazil. The neurological presentation depends on the involved nerve and is usually associated with skin lesions and the formation of multiple abscesses. We present a case of isolated tuberculoid leprosy, discuss the occurrence, the differential diagnosis and the treatment of this rare presentation and reaffirm the importance of considering leprosy in the differential diagnosis of patients with polyneuropathy or nerve enlargement with no skin lesions.

A case-control study in Rio de Janeiro in 1994 included 552 patients with a positive culture for Mycobacterium tuberculosis and reported a 1.8% resistance rate to rifampicin and isoniazid. Prior treatment for tuberculosis (the exposure factor) was associated with resistance. The binomial proportion was used to test the hypothesis of no dependence between the observed associations based on prior exposure to the drugs. This test showed a greater than expected dependence between resistances to rifampicin and isoniazid.

Introduction: In developing countries, there is little information about the risk factors that predict noncompliance with tuberculosis (TB) treatment in hospitals., Objective: This study analyzes possible factors associated with noncompliance with TB treatment among patients treated at HAA., Design: A retrospective cohort study was made including all patients who initiated TB treatment at HAA, from January to December 1998. A standard form was used to review medical records and to collect data on each patient. This data was evaluated in comparison with data from the state TB control program., Results: Of the 341 patients included in the study, 186 (61.2%) were considered cured and 67 (22%) were non-compliant. The factors associated with noncompliance were: previous anti-TB treatment (RR = 1.95, 95% CI 1.29 to 2.93), prescription of drugs other than the standard first-line regimen proposed by the Brazilian Health Ministry (Rifampin + Isoniazide + Pyrazinamide) (RR = 0.54, 95% CI 0.35 to 0.83), the need for hospitalization (RR = 2.19, 95% CI 1.46 to 3.29) and non-inclusion in the hospital s TB Control Program for treatment follow up (RR = 0.54, 95% CI 0.35 to 0.82)., Setting: Anuar Auad Hospital (HAA) Goiânia, Goiás, Brazil., Conclusion: Our results indicate the importance of establishing Tuberculosis Control Programs in hospitals, while paying special attention to patients with risk factors for noncompliance with TB treatment.

In Brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (SSL-PB). Only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose ROM (rifampin, ofloxacin and minocycline) regimen has been recommended. In this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of SSL-PB leprosy cases enrolled between December 1997-1998. Patients were recruited at health centers located in the following regions: Southeast = Rio de Janeiro; North = Amazon and Rondônia states and Center-West = Goiás state. Eligible cases were newly detected, untreated single-lesion leprosy patients without thickened nerve involvement, and were assessed by clinical, bacilloscopic and histopathological exams. The Mitsuda skin test and anti-PGL-I serology (ELISA) were also performed. Of the 299 SSL-PB leprosy patients, 259 (86.6%) fulfilled the criteria for single-dose ROM intervention. Our results showed that patients recruited from different sites had similar features, considering the clinical and immunological profiles. There was a predominance of adults (mean age 32.4; S.D. = 16.0), and a BCG scar was detected in 76.7% of the children (< or = 15 years old). Only 7 cases were diagnosed as the multibacillary type, representing less than 3% of the patients being misclassified. Our data indicate that in Brazil SSL-PB case ascertainment based on clinical and bacilloscopic criteria can be accurately defined under a routine control program; 75.0% of SSL-PB cases were Mitsuda positive (> or = 5 mm) and seropositivity for anti-PGL-I was detected in 17.3% of the patients. These data are compatible with effective cell-mediated immunity and low bacillary load, suggesting favorable clinical outcomes for most SSL-PB participants of this cohort.

The purpose of this study was to analyze the prevalence and risk factors for drug resistance among hospitalized patients in two tertiary care centers, an acquired immunodeficiency syndrome (AIDS) reference center and a sanatorium, in Rio de Janeiro, Brazil. From 1993-1994, 389 patients were diagnosed as having tuberculosis (TB). Isolates from 265 patients were tested for in vitro susceptibility to rifampin and isoniazid. Resistance to one or more drugs was detected in 44 patients (16.6%) and was significantly more common among recurrent cases in both hospitals (p=0.03 in the AIDS center and p=0.001 in the sanatorium). Twenty seven patients (10.2%) had isolates resistant to both isoniazid and rifampin. Multi-drug resistance was associated with human immunodeficiency virus (HIV) infection among patients who had never been treated for TB. In conclusion, drug-resistant TB is high in hospitalized patients in Rio de Janeiro, especially among HIV infected patients. Therefore, measures to control TB and prevent nosocomial transmission need urgently to be set up in the Brazilian hospitals.

Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF.