Rapid detection of Mycobacterium tuberculosis DNA and genetic markers for Isoniazid resistance in Ziehl-Neelsen stained slides.

BACKGROUND: Early diagnosis of tuberculosis (TB) and identification of strains of Mycobacterium tuberculosis resistant to anti-TB drugs are considered the main factors for disease control. OBJECTIVES: To standardise a real-time polymerase chain reaction (qPCR) assay technique and apply it to identify mutations involved in M. tuberculosis resistance to Isoniazid (INH) directly in Ziehl-Neelsen (ZN) stained slides. METHODS: Were analysed 55 independent DNA samples extracted from clinical isolates of M. tuberculosis by sequencing. For application in TB diagnosis resistance, 59 ZN-stained slides were used. The sensitivity, specificity and Kappa index, with a 95% confidence interval (CI95%), were determined. FINDINGS: The agreement between the tests was, for the katG target, the Kappa index of 0.89 (CI95%: 0.7-1.0). The sensitivity and specificity were 97.6% (CI95%: 87.7-99.9) and 91.7% (CI95%: 61.5-99.5), respectively. For inhA, the Kappa index was 0.92 (CI95%: 0.8-1.0), the sensitivity and specificity were 94.4% (CI95%: 72.7-99.8) and 97.3% (CI95%: 85.8-99.9), respectively. The use of ZN-stained slides for drug-resistant TB detection showed significant results when compared to other standard tests for drug resistance. MAIN CONCLUSIONS: qPCR genotyping proved to be an efficient method to detect genes that confer M. tuberculosis resistance to INH. Thus, qPCR genotyping may be an alternative instead of sequencing.

Frequency of the Mycobacterium tuberculosis RDRio genotype and its association with multidrug-resistant tuberculosis.

BACKGROUND: In recent decades, Mycobacterium tuberculosis with the RDRio genotype, frequently isolated from tuberculosis patients in Rio de Janeiro, has become part of the Latin American - Mediterranean (LAM) family and has been associated with multidrug-resistant tuberculosis (MDR-TB). The aim of this study was to investigate the frequency of M. tuberculosis RDRio in the state of Minas Gerais, Brazil, and its relationship with MDR-TB. METHODS: For convenience, 172 susceptible and 63 MDR M. tuberculosis isolates were taken from pulmonary samples from patients diagnosed between January 2007 and December 2011. The DNA extracted from these isolates was analyzed by spoligotyping, PCR-RFLP to characterize fbpC103/Ag85C103, multiplex PCR to detect RDRio and RD174, and MIRU-VNTR 24 loci. RESULTS: Among the 235 isolates, the RDRio pattern was identified in 122 (51.9%) isolates (IC 0.45-0.58), with 100 (42.5%) wild-type and 13 (5.5%) mixed pattern isolates, whereas RD174 was identified in 93 of the 122 RDRio positive samples (76.3%). The LAM family and the LAM9 lineage were the most frequently identified among the isolates in this study. Among the 63 MDR isolates, 41 (65.1%) were RDRio and 28 (44.4%) RD174. CONCLUSION: The association of both deletions with MDR proved to be statistically significant, corroborating the few reports that have associated RDRio with MDR.

Multicenter evaluation of TB-SPRINT 59-Plex Beamedex®: accuracy and cost analysis.

BACKGROUND: Molecular tests can allow the rapid detection of tuberculosis (TB) and multidrug-resistant TB (MDR-TB). TB-SPRINT 59-Plex Beamedex® is a microbead-based assay developed for the simultaneous spoligotyping and detection of MDR-TB. The accuracy and cost evaluation of new assays and technologies are of great importance for their routine use in clinics and in research laboratories. The aim of this study was to evaluate the performance of TB-SPRINT at three laboratory research centers in Brazil and calculate its mean cost (MC) and activity-based costing (ABC). METHODS: TB-SPRINT data were compared with the phenotypic and genotypic profiles obtained using Bactec™ MGIT™ 960 system and Genotype® MTBDRplus, respectively. RESULTS: Compared with MGIT, the accuracies of TB-SPRINT for the detection of rifampicin and isoniazid resistance ranged from 81 to 92% and 91.3 to 93.9%, respectively. Compared with MTBDRplus, the accuracies of TB-SPRINT for rifampicin and isoniazid were 99 and 94.2%, respectively. Moreover, the MC and ABC of TB-SPRINT were USD 127.78 and USD 109.94, respectively. CONCLUSION: TB-SPRINT showed good results for isoniazid and rifampicin resistance detection, but still needs improvement to achieve In Vitro Diagnostics standards.

Correlation between the BACTEC MGIT 960 culture system with Genotype MTBDRplus and TB-SPRINT in multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil.

BACKGROUND: The accurate detection of multidrug-resistant tuberculosis (MDR-TB) is critical for the application of appropriate patient treatment and prevention of transmission of drug-resistant Mycobacterium tuberculosis isolates. The goal of this study was to evaluate the correlation between phenotypic and molecular techniques for drug-resistant tuberculosis diagnostics. Molecular techniques used were the line probe assay genotype MTBDRplus and the recently described tuberculosis-spoligo-rifampin-isoniazid typing (TB-SPRINT) bead-based assay. Conventional drug susceptibility testing (DST) was done on a BACTECTM MGIT 960 TB. METHOD: We studied 80 M. tuberculosis complex (MTC) clinical isolates from Minas Gerais state, of which conventional DST had classified 60 isolates as MDR and 20 as drug susceptible. FINDINGS: Among the 60 MDR-TB isolates with MGIT as a reference, sensitivity, specificity, accuracy, and kappa for rifampicin (RIF) resistance using TB-SPRINT and MTBDRplus, were 96.7% versus 93.3%, 100.0% versus 100.0%, 97.5% versus 95.0% and 0.94 versus 0.88, respectively. Similarly, the sensitivity, specificity, accuracy, and kappa for isoniazid (INH) resistance were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively. Finally, the sensitivity, specificity, accuracy, and kappa for MDR-TB were 85.0% and 83.3%, 100.0% and 100.0%, 88.8% and 87.5% and 0.74 and 0.71 for both tests, respectively. MAIN CONCLUSIONS: Both methods exhibited a good correlation with the conventional DST. We suggest estimating the cost-effectiveness of MTBDRplus and TB-SPRINT in Brazil.

Genetic diversity and molecular epidemiology of multidrug-resistant Mycobacterium tuberculosis in Minas Gerais State, Brazil.

BACKGROUND: We aimed to characterize the genetic diversity of drug-resistant Mycobacterium tuberculosis (MTb) clinical isolates and investigate the molecular epidemiology of multidrug-resistant (MDR) tuberculosis from Minas Gerais State, Brazil. METHODS: One hundred and four MTb clinical isolates were assessed by IS6110-RFLP, 24-locus mycobacterial interspersed repetitive units variable-number tandem repeats (MIRU-VNTR), TB-SPRINT (simultaneous spoligotyping and rifampicin-isoniazid drug-resistance mutation analysis) and 3R-SNP-typing (analysis of single-nucleotide polymorphisms in the genes involved in replication, recombination and repair functions). RESULTS: Fifty-seven different IS6110-RFLP patterns were found, among which 50 had unique patterns and 17 were grouped into seven clusters. The discriminatory index (Hunter and Gaston, HGDI) for RFLP was 0.9937. Ninety-nine different MIRU-VNTR patterns were found, 95 of which had unique patterns and nine isolates were grouped into four clusters. The major allelic diversity index in the MIRU-VNTR loci ranged from 0.6568 to 0.7789. The global HGDI for MIRU-VNTR was 0.9991. Thirty-two different spoligotyping profiles were found: 16 unique patterns (n = 16) and 16 clustered profiles (n = 88). The HGDI for spoligotyping was 0.9009. The spoligotyped clinical isolates were phylogenetically classified into Latin-American Mediterranean (66.34 %), T (14.42 %), Haarlem (5.76 %), X (1.92 %), S (1.92 %) and U (unknown profile; 8.65 %). Among the U isolates, 77.8 % were classified further by 3R-SNP-typing as 44.5 % Haarlem and 33.3 % LAM, while the 22.2 % remaining were not classified. Among the 104 clinical isolates, 86 were identified by TB-SPRINT as MDR, 12 were resistant to rifampicin only, one was resistant to isoniazid only, three were susceptible to both drugs, and two were not successfully amplified by PCR. A total of 42, 28 and eight isolates had mutations in rpoB positions 531, 526 and 516, respectively. Correlating the cluster analysis with the patient data did not suggest recent transmission of MDR-TB. CONCLUSIONS: Although our results do not suggest strong transmission of MDR-TB in Minas Gerais (using a classical 100 % MDR-TB identical isolates cluster definition), use of a smoother cluster definition (>85 % similarity) does not allow us to fully eliminate this possibility; hence, around 20-30 % of the isolates we analyzed might be MDR-TB transmission cases.

In-house PCR with DNA extracted directly from positive slides to confirm or exclude the diagnosis of tuberculosis: focus on biosafety.

The possibility to obtain DNA from smears is a valuable alternative to remedy the lack of samples when they are totally used for bacilloscopy; this technique solves the biosafety problem related to a possible accident with the transportation of flasks containing potentially transmissible clinical samples. Hence, the purpose of this study was to utilize the insertion sequence IS6110 for amplification of DNA from a smear-positive sample for tuberculosis (TB) diagnosis. Among the 52 positive bacilloscopies, sensitivity, specificity, positive predictive value and negative predictive value were 52.3%, 100%, 100% and 89.7%, respectively whereas accuracy was 90.7%. The IS6110-based PCR for TB diagnosis developed in DNA extracted from a positive smear is a fast, simple, specific, and safe method.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease.

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Factors Associated with the Effectiveness of Regimens for the Treatment of Tuberculosis in Patients Coinfected with HIV/AIDS: Cohort 2015 to 2019.

(1) Background: Infection with the Human Immunodeficiency Virus (HIV) is a significant challenge for tuberculosis (TB) control, with increasing mortality rates worldwide. Moreover, the loss to follow-up is very high, with low adherence to treatment, resulting in unfavorable endpoints. This study aimed to analyze the effectiveness of TB treatment in patients coinfected with HIV/AIDS and its associated factors. (2) Methods: Patients coinfected with TB and HIV/AIDS at a Reference Hospital for infectious diseases were followed up for a maximum of one year from the start of TB treatment until cure or censorship (death, abandonment, and transfer) from 2015 to 2019. The Cox proportional model was used to identify risk factors for effectiveness. (3) Results: Of the 244 patients included in the cohort, 58.2% (142/244) had no treatment effectiveness, 12.3% (30/244) died, and 11.1% (27/244) abandoned treatment. Viral suppression at the onset of TB treatment (HR = 1.961, CI = 1.123-3.422), previous use of Antiretroviral Therapy (HR = 1.676, CI = 1.060-2.651), new cases (HR = 2.407, CI = 1.197-3.501), not using illicit drugs (HR = 1.763, CI = 1.141-2.723), and using the basic TB regimen (HR = 1.864, CI = 1.084-3.205) were significant variables per the multivariate Cox regression analysis. (4) Conclusion: TB treatment for most TB patients coinfected with HIV/AIDS was not effective. This study identified that an undetectable viral load at the beginning of the disease, previous use of ART, not using illicit drugs and not having previously taken anti-TB treatment are factors associated with successful TB treatment.

A systematic review and repeatability study on the use of deep learning for classifying and detecting tuberculosis bacilli in microscopic images.

Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent. This disease usually affects the lungs (pulmonary TB) and can be cured in most cases with a quick diagnosis and proper treatment. Microscopic sputum smear is widely used to diagnose and manage pulmonary TB. Despite being relatively fast and low cost, it can be exhausting because it depends on manually counting TB bacilli (Mycobacterium tuberculosis) in microscope images. In this context, different Deep Learning (DL) techniques are proposed in the literature to assist in performing smear microscopy. This article presents a systematic review based on the PRISMA procedure, which investigates which DL techniques can contribute to classifying TB bacilli in microscopic images of sputum smears using the Ziehl-Nielsen method. After an extensive search and a careful inclusion/exclusion procedure, 28 papers were selected from a total of 400 papers retrieved from nine databases. Based on these articles, the DL techniques are presented as possible solutions to improve smear microscopy. The main concepts necessary to understand how such techniques are proposed and used are also presented. In addition, replication work is also carried out, verifying reproducibility and comparing different works in the literature. In this review, we look at how DL techniques can be a partner to make sputum smear microscopy faster and more efficient. We also identify some gaps in the literature that can guide which issues can be addressed in other works to contribute to the practical use of these methods in laboratories.

Cost analysis of GenoType® MTBDRplus and GenoType® MTBDRsl at the State Laboratory of São Paulo, Brazil.

BACKGROUND: We aimed to evaluate the costs of GenoType® MTBDRplus and MTBDRsl incurred during the diagnosis of first- and second-line drug-resistant tuberculosis (TB) in São Paulo, Brazil. METHODS: Mean and activity-based costs of GenoType® were calculated in a referral laboratory for TB in Brazil. RESULTS: The mean cost value and activity-based cost of GenoType® MTBDRplus were USD 19.78 and USD 35.80 and those of MTBDRsl were USD 54.25 and USD 41.85, respectively. CONCLUSIONS: The cost of GenoType® MTBDRplus was reduced owing to the high number of examinations performed and work optimization.

Nontuberculous mycobacteria in patients of a specialty hospital.

The incidence and clinical characteristics of NTM diseases in Brazil remain relatively unknown. The present study describes the diagnosis of NTM isolates, the clinical presentation and treatment outcomes. We analyzed NTM isolates in patients of a tertiary hospital in the Southeast region of Brazil, from January 2008 to July 2019. The ATS/IDSA criteria for diagnosis and treatment of these patients was applied. Mycobacterium kansasii were identified in 13/113 (11.5%) patients. In 59/113 (52.2%) patients who met the ATS criteria for disease, 29/59 (49.1%) received treatment, and 22/29 (75.8%) were cured. The major species identified was M. kansasii. The most frequent symptoms among the treated patients were dyspnea and cough, and the proportion of cured patients was high.

Molecular characterization of nontuberculous Mycobacteria in a tuberculosis and HIV reference unit in the State of Amazonas, Brazil.

BACKGROUND: In recent years, the prevalence of nontuberculous mycobacterial (NTM) infections has increased in different regions of the world. The American Thoracic Society (ATS) recommends standardized identification criteria, reinforcing the need for faster and less complicated clinical and laboratory techniques. METHODS: In this retrospective study, NTM species isolated from pulmonary, extrapulmonary, and disseminated samples from patients treated at a TB/HIV reference unit in the State of Amazonas from 2011 to 2014 were identified through a combination of molecular techniques. RESULTS: To identify the molecular technique, 50 cryopreserved NTM cultures were recovered and subcultivated in culture medium. The potentially pathogenic NTM species identified were M. avium, M. intracellulare, M. kansasii, M. chelonae, M. abscessus, M. fortuitum, and M. peregrinum. Results of GenoType® showed moderate agreement with those of genomic sequencing (kappa = 0.60), whereas the results obtained by the PRA-hsp65 technique disagreed with the results obtained by sequencing (kappa = 0.49). CONCLUSIONS: Our findings highlight that GenoType CM is a good method for the identification of NTM, as well as the need for the application of standardized criteria, such as those set forth by the ATS.

The Medication Experience of TB/HIV Coinfected Patients: Qualitative Study.

Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pharmacotherapy and the stigma related to both diseases are complex. The patients' subjective experiences with diseases and medications are of utmost importance in pharmaceutical care practice. This study aimed to understand the subjective medication experience of TB and HIV/AIDS coinfected patients. The study was based on descriptive research of a qualitative and quantitative nature using data collected during pharmaceutical care appointments and from medical records from September 2015 to December 2016 at a tertiary infectious diseases referral hospital in Southeastern Brazil. Data from 81 patients were analyzed. Regarding patient subjective medication experience, the following responses to the quantitative questionnaire were most frequent: preference for a route of administration (12.4%) and for non-pharmacological therapy (50.6%); concerns about price (11.1%) and adverse effects (18.5%); and association of a worsening of their health status with a change in medication dosage (23.5%). In the thematic analysis, adversity and socially constructed aspects were more prominent. Resolvability, associated with the patient's understanding of relief from signs and symptoms and health recovery, was observed; however, feelings of ambivalence permeated the other aspects, hence leading to treatment abandonment. The evaluation of patient medication experience can be a path to understanding and intervening in the phenomenon of treatment abandonment among TB and HIV/AIDS coinfected individuals.

Spoligotyping of clinical Mycobacterium tuberculosis isolates from the state of Minas Gerais, Brazil.

We performed spoligotyping on 114 strains of the Mycobacterium tuberculosis (Mtb) complex that had been isolated from patients in Minas Gerais Health Units during 2004. A total of 82/114 (72%) clinical isolates were clustered and 32/114 (28%) were unique. Seven shared types containing nine strains were newly created. A total of nine patterns corresponded to unreported orphan strains, as evaluated against all of the strains recorded in the SITVIT2 proprietary database in the Institut Pasteur de la Guadeloupe. The major clades were composed of isolates that belong to the following genotypes: Latin-America and Mediterranean (63/114, 55.3%) (the ill-defined T superfamily) (12/114, 10.5%), Haarlem (8/114, 7%), X clade (6/114, 5.3%), S clade (3/114, 2.6%) and the East-African Indian and Manu types, each with 1/114 (0.9%) isolates. A considerable number of strains (n = 20, 17.5%) showed patterns that did not fall within any of the previously described major clades. We conclude the bulk of tuberculosis (TB) (92/114, 80.7%) in our location is recent evolutionary strains that belong to the principal genetic groups 2/3. Further studies on epidemiology of TB are required to understand Mtb biodiversity and TB transmission in this region.

Pulmonary functional assessment: longitudinal study after treatment of pulmonary tuberculosis.

Even when treated adequately, pulmonary tuberculosis can lead to pulmonary sequelae. Patients treated for PTB between 2012 and 2016 answered a standardized questionnaire and underwent chest radiography and spirometry, measurement of absolute pulmonary volume, Diffusing Capacity for Carbon Monoxide (DLCO) and the 6-min walk test (6MWT) on two occasions: within the first year after the end of treatment (follow-up 1), and one and two years after follow-up 1 (follow-up 2). A total of 55 patients they underwent spirometry, 23 (41.82%) had obstructive ventilatory disorder (OVD) and eight (14.5%) had moderate OVD. In total, 29 patients underwent pulmonary function tests (PFTs) and 24 patients underwent the 6MWT on two occasions. The functional changes after PTB treatment appear not to have varied between one and two years of follow-up. There was a correlation between low FEV1 and low DLCO (p<0.001); low DLCO and low 6MWT (p<0.001) and radiographic abnormalities and low FEV1 (p=0.033). The most frequently observed change in spirometry was found in patients with OVD.

[Performance assessment of primary healthcare services in tuberculosis control in a city in Southeast Brazil]. / Avaliação do desempenho dos serviços de atenção primária à saúde no controle da tuberculose em metrópole do Sudeste do Brasil.

The World Health Organization highlights the importance of health services organization and performance in tuberculosis (TB) control activities. This study aimed to assess the performance of primary healthcare services in Belo Horizonte, Minas Gerais State, Brazil, in TB control activities in the dimensions Structure and Process, before and after the use of a validated instrument called Stratification by Degree of Clinical Risk and Tuberculosis Treatment Dropout (ERTB). This was a descriptive and prospective study with two interviews (455 professionals), the second of which after the ERTB. Performance classification was: ≤ 49.9%, critical; 50-79.9%, unsatisfactory, and ≥ 80%, satisfactory. The comparative assessment used the McNemar statistical test with p < 0.05. After risk stratification, most of the variables in each dimension improved significantly. The authors conclude that it was possible to identify satisfactory performance in most of the variables assessed in the Structure and Process dimensions in primary healthcare services in Belo Horizonte in relation to TB control activities, using a standardized questionnaire.

A Organização Mundial da Saúde destaca a importância da organização e do desempenho dos serviços de saúde nas ações de controle da tuberculose. O objetivo deste estudo foi avaliar o desempenho dos serviços de atenção primaria à saúde em Belo Horizonte, Minas Gerais, Brasil, em relação às ações de controle da tuberculose nos eixos Estrutura e Processo, antes e após a utilização do instrumento validado denominado Estratificação por Grau de Risco Clínico e de Abandono do Tratamento da Tuberculose (ERTB). Estudo descritivo e prospectivo, no qual foram realizadas duas entrevistas (455 profissionais), tendo a segunda ocorrido após a ERTB. A classificação do desempenho seguiu os valores: ≤ 49,9%, críticos; entre 50% e 79,9%, insatisfatórios; e, ≥ 80%, satisfatórios. Na avaliação comparativa, foi utilizado o teste estatístico de McNemar, com p < 0,05. Após a estratificação de risco, a maior parte das variáveis de cada eixo melhorou significativamente. Nós concluímos que, por meio de um questionário padronizado, foi possível identificar o desempenho satisfatório dos serviços de atenção primária à saúde em Belo Horizonte em relação às ações de controle da tuberculose, na maioria das variáveis avaliadas nos eixos Estrutura e Processo.

La Organización Mundial de la Salud destaca la importancia de la organización y del desempeño de los servicios de salud en acciones de control de la tuberculosis. El objetivo de este estudio fue evaluar el desempeño de los servicios de atención primaria en salud en Belo Horizonte, Minas Gerais, Brasil, en relación con las acciones de control de la tuberculosis respecto a los ejes Estructura y Proceso, antes y después de la utilización del instrumento validado, denominado Estratificación por Grado de Riesgo Clínico y de Abandono del Tratamiento de la Tuberculosis (ERTB). Se trata de un estudio descriptivo y prospectivo, donde se realizaron dos entrevistas (455 profesionales), siendo que la segunda se produjo tras la ERTB. La clasificación del desempeño siguió los valores: ≤ 49,9%, críticos; entre 50 y 79,9%, insatisfactorios; y, ≥ 80%, satisfactorios. En la evaluación comparativa, se utilizó el test estadístico de McNemar, con p < 0,05. Tras la estratificación de riesgo, la mayor parte de las variables de cada eje mejoró significativamente. Concluimos que fue posible identificar el desempeño satisfactorio en la mayoría de las variables evaluadas en los ejes Estructura y Proceso de los servicios de atención primaria en salud en Belo Horizonte, en relación con las acciones de control de la tuberculosis mediante un cuestionario estandarizado.

Assessment of factors associated with potential drug-drug interactions in patients with tuberculosis and HIV/AIDS.

INTRODUCTION: The concomitant use of antituberculosis and antiretroviral drugs, as well as drugs to treat other diseases, can cause drug-drug interactions. This study aimed to describe potential drug-drug interactions (pDDI) in patients with TB and HIV/AIDS co-infection, as well as to analyze possible associated factors. METHODS: This study was performed in a reference hospital for infectious and contagious diseases in the southeastern region of Brazil and evaluated adult patients co-infected with tuberculosis and HIV/AIDS. A cross-sectional study was conducted in which sociodemographic, clinical, and pharmacotherapeutic characteristics were assessed. The pDDI were identified using the Drug-Reax software. Association analysis was performed using either a chi-squared test or a Fisher's exact test. Correlation analysis was performed using the Spearman's coefficient. RESULTS: The study included 81 patients, of whom 77 (95.1%) were exposed to pDDI. The most frequent interactions were between antituberculosis and antiretroviral drugs, which can cause therapeutic ineffectiveness and major adverse reactions. A positive correlation was established between the number of associated diseases, the number of drugs used, and the number of pDDI. An association was identified between contraindicated and moderate pDDI with excessive polypharmacy and hospitalization. CONCLUSIONS: We found a high frequency of pDDI, especially among those hospitalized and those with excessive polypharmacy. These findings highlight the importance of pharmacists in the pharmacotherapeutic monitoring in these patients.

The impact of the stratification by degree of clinical severity and abandonment risk of tuberculosis treatment.

OBJECTIVE: Evaluate the impact of the instrument of the "Stratification by Degree of Clinical Severity and Abandonment Risk of Tuberculosis Treatment" (SRTB) on the tuberculosis outcome. METHODS: This study was a pragmatic clinical trial involving patients with a confirmed diagnosis of tuberculosis treated at one of the 152 primary health care units in the city of Belo Horizonte, Brazil, between May of 2016 and April of 2017. Cluster areas for tuberculosis were identified, and the units and their respective patients were divided into intervention (use of SRTB) and nonintervention groups. RESULTS: The total sample comprised 432 participants, 223 and 209 of whom being allocated to the nonintervention and intervention groups, respectively. The risk of treatment abandonment in the nonintervention group was significantly higher than was that in the intervention group (OR = 15.010; p < 0.001), regardless of the number of risk factors identified. Kaplan-Meier curves showed a hazard ratio of 0.0753 (p < 0.001). CONCLUSIONS: The SRTB instrument was effective in reducing abandonment of tuberculosis treatment, regardless of the number of risk factors for that. This instrument is rapid and easy to use, and can be adapted to different realities. Its application showed characteristics predisposing to a non-adherence to the treatment and established bases to mitigate its impact.

Cost-effectiveness of Xpert®MTB/RIF in the diagnosis of tuberculosis: pragmatic study.

INTRODUCTION: The intensification of research and innovation with the creation of networks of rapid and effective molecular tests as strategies for the end of tuberculosis are essential to avoid late diagnosis and for the eradication of the disease. We aimed to evaluate the cost-effectiveness of Xpert®MTB/RIF (Xpert) in the diagnosis of drug-resistant tuberculosis in reference units, in scenarios with and without subsidies, and the respective cost adjustment for today. METHODS: The analyses were performed considering as criterion of effectiveness, negative culture or clinical improvement in the sixth month of follow-up. The comparison was performed using two diagnostic strategies for the drug susceptibility test (DST), BactecTMMGITTM960 System, versus Xpert. The cost effectiveness and incremental cost-effectiveness ratio (ICER) were calculated and dollar-corrected for American inflation (US$ 1.00 = R$ 5,29). RESULTS: Subsidized Xpert had the lowest cost of US$ 33.48 (R$67,52) and the highest incremental average efficiency (13.57), thus being a dominated analysis. After the inflation was calculated, the mean cost was DST-MGIT=US$ 74.85 (R$ 396,73) and Xpert = US$ 37.33 (R$197,86) with subsidies. CONCLUSIONS: The Xpert in the diagnosis of TB-DR in these reference units was cost-effective with subsidies. In the absence of a subsidy, Xpert in TB-DR is not characterized as cost effective. This factor reveals the vulnerability of countries dependent on international organizations' subsidy policies.

Donor-Derived Tuberculosis: A Case Report and the Role of Communication Gaps in Transplantation Safety.

Donor-derived tuberculosis (DD-TB) accounts for less than 5% of TB cases and is considered a rare event. In the transplant setting, the frequency of active TB is estimated to be 20 to 74 times higher than that in the general population, and it is associated with high mortality. In this context, the main strategy to minimize the risk of DD transmission is to identify high-risk donors. Despite screening recommendations, failures may result in a breakdown of safety that ends in the transmission of potentially fatal diseases. This report describes a case of DD-TB and emphasizes communication gaps that may occur between organ procurement organizations and transplant centers. Failure in reporting results, lack of exchanging information regarding recipients from the same donor, and inefficient communication between organ procurement organizations and transplant centers are lacks that may be prevented by a more efficient approach towards screening protocols and communication.