Utilidad de GeneXpert MTB/RIF en el diagnóstico de tuberculosis frente a la baciloscopia / Utility of GeneXpert MTB/RIF in the Diagnosis of Tuberculosis Compared to Sputum Smear Microscopy

Introducción: La implementación de un método diagnóstico adecuado y eficiente es crucial para la detección temprana de la tuberculosis. Esto no solo permite un control efectivo de la enfermedad para evitar su transmisión y progresión hacia estadios más graves, además previene el desarrollo de resistencia a los fármacos en los pacientes.Objetivo: Evaluar la utilidad de la prueba molecular GeneXpert MTB/RIF en el diag-nóstico de Mycobacterium tuberculosis complex, en comparación con la bacilos-copia, utilizando el cultivo como referencia.Material y Métodos: Se realizó un estudio descriptivo, observacional y no expe-rimental de corte transversal, se incluyeron 253 muestras de pacientes de ambos sexos y de variados rangos de edad, que fueron evaluadas mediante baciloscopia, GeneXpert MTB/RIF y cultivo. El estudio se centró en muestras procesadas en un Hospital público de la ciudad de Quito durante el período de enero de 2021 a mayo de 2022Resultados: La prueba molecular GeneXpert MTB/RIF mostró una sensibilidad del 94,7% y una especificidad del 93,9% para el diagnóstico de Mycobacterium tu-berculosis complex. Además, se identificó un caso de resistencia a la rifampicina.Conclusión: Este estudio confirma la eficacia de la prueba molecular GeneXpert MTB/RIF sobre la baciloscopia para el diagnóstico oportuno de Mycobacterium tu-berculosis complex. Sin embargo, es esencial considerar las diversas condiciones de las muestras y pacientes para optimizar la precisión diagnóstica

Introduction: Implementing an appropriate and efficient diagnostic method is cru-cial for the early detection of tuberculosis. This not only allows for effective control of the disease to prevent its transmission and progression to more severe stages but also prevents the development of drug resistance in patients.Objective: To evaluate the utility of the GeneXpert MTB/RIF molecular test in diag-nosing Mycobacterium tuberculosis complex, compared to sputum smear micros-copy, using culture as the reference. Material and Methods: A descriptive, observational, and non-experimental cross-sectional study was conducted, including 253 samples from patients of both sexes and various age ranges, which were assessed using sputum smear micros-copy, GeneXpert MTB/RIF, and culture. The study focused on samples processed at a Quito ́s Public Hospital during the period from January 2021 to May 2022.Results: The GeneXpert MTB/RIF molecular test showed a sensitivity of 94.7% and a specificity of 93.9% for the diagnosis of Mycobacterium tuberculosis com-plex. Additionally, a case of resistance to rifampicin was identified.Conclusion: This study confirms the effectiveness of the GeneXpert MTB/RIF mo-lecular test over sputum smear microscopy for the timely diagnosis of tuberculosis. However, it is essential to consider the diverse conditions of the samples and pa-tients to optimize diagnostic accuracy

Study on the mutation characteristics of streptomycin genes of Multidrug-Resistant Mycobacterium Tuber-culosis in Jiangxi Province / 实用医学杂志

Objective To understand the molecular characteristics of Streptomycin(SM)resistance in multidrug-resistant tuberculosis(MDR-TB)in Jiangxi Province,and to explore the relationship between SM resistant genes(rpsL,rrs and gidB)mutations and SM resistant phenotypes in Beijing genotype TB.Methods 106 non-replicated MDR-TB isolates were collected from Gaoxin Branch of The First Affiliated Hospital of Nanchang University and Jiangxi Provincial Chest Hospital from January to December 2021,and tested for drug-resistance phenotypes,whether they were Beijing genotype or not and the characteristics of rpsL,rrs and gidB gene mutations.Chi-square test was performed to determine whether rpsL,rrs and gidB mutations were related to genotypes and drug-resistance phenotypes.Results Among 106 cases of MDR-TB,76 cases were resistant to SM.A total of 58 cases had rpsL 43A>G mutation,8 cases had 88A>G mutation,5 cases had rrs mutation,and 3 cases had gidB mutation.Statistical analysis showed that the coincidence rate of gene mutation and phenotypic drug-resistance detection was 89.6%,and the specificity and sensitivity were 86.7%and 90.8%,respectively.The isolated rate of Beijing genotype TB was 88.7%,and the drug-resistant gene mutations were mainly concentrated in rpsL and rrs,while the drug-resistant mutations of non-Beijing genotype were mainly concentrated in gidB;in addition,Beijing genotype bacteria were more prone to gene mutations(P = 0.013),but there was no difference in phenotypic drug-resistance.Conclusions Mutations in rpsL,rrs,and gidB genes have a good coincidence rate with phenotypic drug-resistance,and molecular biology can be used to detect directly drug-resistance genes to predict bacterial resistance;TB genotypes are strongly associated with streptomycin resistance characteristics.

Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020 / 实用医学杂志

Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.

Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

As redes vivas na produção do cuidado com o usuário na centralidade do tratamento para tuberculose multidroga resistente / Las redes vivas en la producción del cuidado con el usuario en la centralidad del tratamiento para la tuberculosis multidrogo resistente / Live networks in care production with the user at the center of the treatment for multidrugresistant tuberculosis

Vivenciamos a trajetória de uma usuária-guia no tratamento para tuberculose multidroga resistente (TB-MDR). As narrativas das redes vivas na produção de cuidado apontam para os seguintes itens: 1) cuidar no ato de viver: suplantar os estigmas e cultivar vínculos que ajudem a superar os discursos fomentados pelo medo, preconceitos, exclusão e invisibilidade dos sujeitos; 2) redes vivas de cuidado: os entremeios da norma; e 3) as interfaces de atenção usuário-trabalhador da saúde: como desmistificar o julgamento dos trabalhadores da saúde, que, subordinados a protocolos limitantes, muitas vezes estigmatizam o usuário como "abandonador de tratamento"?. A usuária-guia vislumbrou que cuidar é se desterritorializar, é colocar os desejos como potência para transformação, saindo do modus operandi rumo à criatividade, tendo o usuário no centro do processo. (AU)

Presenciamos la trayectoria de una usuaria-guía en el tratamiento para tuberculosis multidrogo resistente (TB-MDR). Las narrativas de las Redes Vivas en la producción de cuidado señalan: 1) cuidar en el acto de vivir: suplantar los estigmas y cultivar vínculos que ayuden a superar los discursos fomentados por el miedo, prejuicios, exclusión e invisibilidad de los sujetos. 2) Redes Vivas de cuidado: los entresijos de la norma y 3) las interfaces de atención usuario-trabajador de la salud: ¿cómo desmistificar el juicio de los trabajadores de la salud quienes, subordinados a protocolos limitantes, muchas veces estigmatizan al usuario como "abandonador de tratamiento"? La usuaria-guía vislumbró que cuidar es desterritorializarse, es colocar los deseos como potencia para trasformación, saliendo del modus operandi rumbo a la creatividad, colocando al usuario en el centro del proceso. (AU)

We followed the trajectory of a guiding user undergoing treatment for multidrug-resistant tuberculosis (MDR-TB). The narratives of Live Networks in care production showed: 1) Caring in the act of living: Overcoming stigmas and cultivating bonds that help overcome discourses fostered by fear, prejudice, exclusion and invisibility of subjects; 2) Live Networks of care: The in-betweens of the norm; and 3) Interfaces of user-health worker care: How can we demystify the judgment of health workers who, subordinated to limiting protocols, often stigmatize the user as someone who "abandons the treatment"? The guiding user perceived that caring means deterritorializing oneself, expressing one's desires as power for transformation, and leaving the modus operandi towards creativity, with the user at the center of the process. (AU)

Strengthening Multidrug-Resistant Tuberculosis Epidemiological Surveillance in Rio de Janeiro: a multidimensional analysis

ABSTRACT This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4−18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.

Tuberculosis farmacorresistente y diabetes: estudio de casos y controles en un hospital peruano

Introducción: la tuberculosis farmacorresistente sigue siendo endémica y un importante problema de salud pública a nivel mundial, lo que resulta en una alta morbilidad. Las personas con diabetes son más susceptibles a las infecciones debido a la inmunosupresión, por lo que es importante reconocer los factores que predisponen a la tuberculosis farmacorresistente. Objetivo: identificar a la diabetes como factor asociado a la tuberculosis farmacorresistente en pacientes del Programa de prevención y control de la tuberculosis de un hospital peruano nivel II-2 del 2015 al 2021. Metodología: se realizó un estudio analítico de casos y controles, pareados por edad y sexo, se incluyó 66 pacientes con tuberculosis farmacorresistente (casos) y 198 pacientes con tuberculosis sensible (controles). Se utilizó la prueba de chi-cuadrado para el análisis bivariado y el cálculo del Odds Ratio. Se utilizó la regresión logística múltiple para el análisis multivariado. Resultados: el 9,1% de los casos y el 4% de los controles tenían diabetes, con OR 2,48 (IC 95% 0,68 - 8,47) y sin diferencias significativas. En el análisis multivariado, la diabetes fue estadísticamente significativa, aumentando el OR a 3,40 (IC 95% 1,01 - 11,49; p= 0,01). Conclusión: la diabetes se asoció con un mayor riesgo de tuberculosis farmacorresistente en pacientes del Programa de prevención y control de la tuberculosis en un hospital peruano nivel II-2.

Introduction: Drug-resistant tuberculosis continues to be endemic and a major public health problem worldwide, resulting in high morbidity. People with diabetes are more susceptible to infections due to immunosuppression, threfpre it is important to recognize the factors that predispose to drug-resistant tuberculosis. Objective: To identify diabetes as a factor associated with drug-resistant tuberculosis in patients of the Tuberculosis Prevention and Control Program of a level II-2 Peruvian hospital from 2015 to 2021. Methodology: An analytical case-control study was carried out, matched by age and sex, including 66 patients with drug-resistant tuberculosis (cases) and 198 patients with sensitive tuberculosis (controls). The chi-square test was used for the bivariate analysis and Odds Ratio calculation was also made. Multiple logistic regression was used for multivariate analysis. Results: 9.1% of the cases and 4% of the controls had diabetes, with OR 2.48 (95% CI 0.68 - 8.47) and without significant differences. In the multivariate analysis, diabetes was statistically significant, increasing the OR to 3.40 (95% CI 1.01 - 11.49; p= 0.01). Conclusion: Diabetes was associated with an increased risk of drug-resistant tuberculosis in patients of the Tuberculosis Prevention and Control Program at a level II-2 Peruvian hospital.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China.@*METHODS@#A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined.@*RESULTS@#BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan).@*CONCLUSION@#BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.

Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway / 中国医学科学院学报

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model / 中南大学学报(医学版)

Objective:Multidrug-resistant tuberculosis(MDR-TB)has a high mortality and is always one of the major challenges in global TB prevention and control.Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients.For follow-up data,the Cox proportional hazards regression model is an important multifactor analysis method.However,the method has significant limitations in its application,such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model.Therefore,Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy,and compare the differences between these 2 methods in their application. Methods:Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1,2017 to March 31,2021.Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors.Conventional and Bayesian Cox regression models were established to estimate the hazard ratios(HR)and their 95% confidence interval(95% CI)for the factors affecting the death of MDR-TB patients.The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable.The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. Results:The median survival time(1st quartile,3rd quartile)of the 388 MDR-TB patients included in the study was 10.18(4.26,18.13)months,with the longest survival time of 31.90 months.Among these patients,a total of 12 individuals died of MDR-TB and the mortality was 3.1%.The median survival time(1st quartile,3rd quartile)for the deceased patients was 4.78(2.63,6.93)months.The majority of deceased patients,accounting for 50%,experienced death within the first 5 months of anti-TB therapy,with the last mortality case occurring within the 13th month of therapy.The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications(HR=6.96,95% CI 2.00 to 24.24,P=0.002)and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up(HR=0.19,95% CI 0.05 to 0.77,P=0.020).In the results of Bayesian Cox regression model,the iterative history plot and Blue/Green/Red(BGR)plot for each parameter showed the good model convergence,and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture(HR=0.33,95% CI 0.08 to 0.87).Additionally,compared to patients without complications,those with comorbidities had an approximately 6.80-fold increase in the risk of death(HR=7.80,95% CI 1.90 to 21.91).Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up(HR=0.10,95% CI 0.01 to 0.30).The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model,except for parameter standard deviations of receiving regular follow-up(Bayesian model was 0.77;conventional model was 0.72)and pulmonary cavities(Bayesian model was 0.73;conventional model was 0.73). Conclusion:The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients.Complications are the main risk factors of death in MDR-TB patients,while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death.For data with a small sample size and low incidence of outcome,the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

Relationship between plasma exosomal miR-346 and treatment outcomes in patients with multidrug resistant pulmonary tuberculosis / 中国热带医学

@#Abstract： Objective　To investigate the relationship between plasma exosomal microRNA (miRNA)-346 and treatment outcomes in patients with multidrug-resistant tuberculosis (MDR-TB), to provide more reference basis for the treatment of MDR-TB patients. Methods　A total of 406 patients with MDR-TB admitted to Tuberculosis Control and Prevention Institute of Shaanxi Provincial between January 2018 and May 2021 were selected as the study subjects. General clinical data of the patients were collected and analyzed. The expression level of plasma exosomal miR-346 was detected by real-time fluorescence quantitative polymerase chain reaction. The predictive value of plasma exosomal miR-346 for treatment outcome was analyzed using receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between the expression of plasma exosomal miR-346 and treatment outcome was analyzed using a multivariable logistic regression model. After standard treatment, patients were divided into good treatment outcome group (n=226) and poor treatment outcome group (n=180) according to the treatment outcome. Results　Typical exosomes were identified by transmission electron microscopy, particle size analysis and Western blot, that is, plasma exosomes were successfully extracted. In the poor treatment outcome group, more patients were complicated with diabetes or HIV infection, and the proportion of patients with pulmonary cavity, acid-fast bacilli smear positive rate >1+, previous treatment history and fluoroquinolone resistance was also significantly increased, and the levels of white blood cells, neutrophils, and monocytes were significantly increased, while the level of albumin was significantly decreased, with statistical significance (P>0.05). Compared with the good treatment outcome group [0.61 (0.46, 0.74)], the expression level of plasma exosomal miR-346 in the poor treatment outcome group [1.23 (0.60, 2.02)] was significantly higher (Z=-13.185, P<0.001). ROC curve analysis showed that the area under the curve of plasma exosomal miR-346 to predict adverse outcomes of MDR-TB treatment was 0.881 (95%CI: 0.846-0.915), with a sensitivity of 78.3% and specificity of 86.7%. The corresponding cut-off value was 0.81. Multivariate logistic regression analysis showed that diabetes, AIDS virus infection, pulmonary cavity, AFB smear positive degree>1+, previous treatment history, fluoroquinolones resistance and high expression of plasma exosomal miR-346 were independent influencing factors for poor treatment results of MDR-TB (P<0.05). Conclusions　High expression of plasma exosomal miR-346 is associated with the high risk of adverse outcome of MDR-TB treatment, and it is promising to be a useful marker for predicting the outcome of MDR-TB treatment.

Cuidado à pessoa com tuberculose multirresistente no contexto de municípios: realidade e validação de ferramenta para a gestão do cuidado / Care for individuals with multidrug-resistant tuberculosis in the context of municipalities: reality and validation of a care management tool

A Tuberculose Multirresistente (TBMDR) é uma condição de saúde grave. Trata-se de uma forma resistente aos dois principais medicamentos utilizados na terapia, cuja assistência envolve diferentes pontos de atenção: Centro de Referência, Atenção Secundária e Atenção Primária à Saúde, e que exige uma organização resolutiva, articulada e coordenada do Sistema de Saúde, visando a uma atenção integral às pessoas acometidas. Tendo em vista esse panorama e a necessidade de comunicação, este estudo teve por objetivo analisar a Gestão do Cuidado às pessoas acometidas por TBMDR, nos níveis primário e secundário de atenção, e validar as informações a serem compartilhadas na Rede de Atenção à Saúde. Trata-se de um estudo dividido em duas etapas. Na primeira, foi realizado um estudo descritivo-analítico com uso de método qualitativo, obtendo uma descrição densa dos contextos envolvidos no cuidado a essa condição de saúde. A segunda foi um estudo metodológico, de abordagem qualitativa, por meio do qual foram validadas, mediante a Técnica Delphi junto aos profissionais de saúde, as informações a serem compartilhadas na "Caderneta de Controle do Tratamento". Os resultados descritivos permitiram a caracterização dos profissionais envolvidos na assistência, apontaram os esforços deles em suprir as fragilidades encontradas pela pessoa com TBMDR durante o tratamento, bem como o envolvimento da família no processo. Quanto à estrutura operacional, o centro comunicador foi o serviço especializado diante da falta de um sistema de informação capaz de integrar as redes de atenção, sendo que a pessoa em tratamento permanece com papel ativo na condução de informações entre os serviços de saúde, na descontinuidade dos benefícios sociais que auxiliam na adesão ao tratamento. Por fim, os resultados apontam para as potencialidades da APS na condução do cuidado, marcado pelo cuidado humanizado e centrado nas necessidades das pessoas, e o apoio emocional como um forte aliado no tratamento. Nessa perspectiva, a Caderneta validada tem por objetivo proporcionar maior integração entre os profissionais envolvidos na assistência. Os juízes sugeriram mudanças quanto aos dados cadastrais e perfil da pessoa com TBMDR. Assim, espera-se que o uso da Caderneta possa subsidiar a prática de cuidado colaborativa dos profissionais de saúde, auxiliando na comunicação, no controle dos casos e no planejamento da assistência.

Multidrug-resistant Tuberculosis (MDR-TB) is a serious health condition, characterized by resistance to the two main drugs used in therapy, requiring care coordination across different points of care: Reference Centers, Secondary Care, and Primary Health Care. This demands a comprehensive, coordinated, and integrated approach within the healthcare system to provide comprehensive care for affected individuals. Considering this scenario and the need for communication, this study aimed to analyze the Care Management for individuals with MDRTB at the primary and secondary care levels and to validate the information to be shared within the Health Care Network. This study was divided into two phases. The first phase involved a descriptive-analytical study using a qualitative method to obtain a thorough description of the care contexts for this health condition. The second phase was a methodological study with a qualitative approach, in which healthcare professionals validated the information to be shared in the "Treatment Control Booklet" through the Delphi Technique. The descriptive results allowed for the characterization of professionals involved in care, highlighted their efforts to address the challenges faced by individuals with MDR-TB during treatment, and emphasized the involvement of families in the process. Regarding the operational structure, the specialized service served as the communication hub, but there was a lack of an information system capable of integrating care networks, leaving the individual in treatment with an active role in information exchange between healthcare services. Discontinuity of social benefits that support treatment adherence was also identified. Finally, the results pointed to the potential of Primary Health Care (PHC) in care management, marked by humanized care focused on individual needs and emotional support as a strong ally in treatment. From this perspective, the validated booklet aims to enhance integration among healthcare professionals involved in care. Judges suggested changes regarding personal data and the profile of individuals with MDR-TB. It is expected that the use of the booklet will support collaborative healthcare practice among professionals, aiding in communication, case management, and care planning

Analysis of catastrophic costs incurred by patients with multidrug-resistant tuberculosis in an outpatient clinic in the state of Rio de Janeiro

ABSTRACT Background: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro. Methods: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges. Results: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%. Conclusions: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.

Multidrug-resistant tuberculous orchiepididymitis: a brief case report

ABSTRACT Tuberculosis (TB) is one of the leading causes of death by infectious diseases worldwide. Multidrug-resistant tuberculosis is a growing problem, especially in countries with high TB prevalence. Although the lungs are the organs most frequently affected by this disease, Mycobacterium tuberculosis can harm any organ, including the urogenital tract, causing extrapulmonary tuberculosis, which leads to a challenging diagnosis and consequent treatment delays. In this article, we present a case of orchiepididymitis caused by multidrug-resistant TB (MDR-TB) with a significantly delayed diagnosis, the proposed treatment according to the resistance profile, and the clinical outcomes.

Drug-Resistant Tuberculosis and COVID-19: A Scoping Review on a New Threat to Antimicrobial Resistance / Tuberculosis Resistente a Medicamentos y COVID-19: Una Revisión de Alcance de una Nueva Amenaza a la Resistencia Antimicrobiana / Tuberculose droga-resistente e COVID-19: revisão de escopo de uma nova ameaça à resistência microbiana a medicamentos

ABSTRACT Objective: To assess the impact of COVID-19 on the morbidity and mortality associated with drug-resistant tuberculosis (DR-TB). Methods: A comprehensive review of articles published in international databases since December 2019 was conducted. The findings are presented in a narrative format, supplemented with tables, diagrams, and a map created using ArcGIS software. Results: Thirty-five studies were selected, highlighting the significant consequences of COVID-19 on TB and DR-TB treatment progress. Four main thematic areas were identified: Clinical and epidemiological aspects of the interaction between COVID-19 and DR-TB; Management of physical resources and the team; Challenges and circumstances; Perspectives and possibilities. Conclusions: This study revealed that the COVID-19 pandemic significantly negatively impacted the control of long-standing diseases like TB, particularly in the context of morbidity and mortality related to DR-TB.

RESUMEN Objetivo: Evaluar el impacto de COVID-19 en la morbilidad y mortalidad asociada con la tuberculosis resistente a medicamentos (DR-TB). Métodos: Se realizó una revisión integral de artículos publicados en bases de datos internacionales desde diciembre de 2019. Los hallazgos se presentaron de forma narrativa, complementados con tablas, diagramas y un mapa creado con el software ArcGIS. Resultados: Se seleccionaron 35 estudios que destacaron las consecuencias significativas de COVID-19 en el progreso del tratamiento de la TB y la DR-TB. Se identificaron cuatro áreas temáticas principales: "Aspectos clínicos y epidemiológicos de la interacción entre COVID-19 y DR-TB", "Gestión de recursos físicos y del equipo", "Desafíos y circunstancias" y "Perspectivas y posibilidades". Conclusiones: Este estudio reveló que la pandemia de COVID-19 tuvo un impacto negativo significativo en el progreso del control de enfermedades antiguas como la TB, especialmente en el contexto de la morbilidad y mortalidad relacionada con la DR-TB.

RESUMO Objetivo: Avaliar o impacto da COVID-19 na morbimortalidade associada à tuberculose resistente a medicamentos (DR-TB). Métodos: Realizou-se uma revisão abrangente de artigos publicados em bases de dados internacionais a partir de dezembro de 2019. As evidências foram apresentadas de maneira narrativa, com o suporte de tabelas, diagramas e um mapa elaborado no software ArcGIS. Resultados: Foram selecionados 35 estudos que destacaram as consequências significativas da COVID-19 nos avanços no tratamento da TB e da DR-TB. Quatro áreas temáticas foram identificadas: "Aspectos clínicos e epidemiológicos da interação entre COVID-19 e DR-TB", "Gestão de recursos físicos e da equipe", "Desafios e circunstâncias" e "Perspectivas e potencialidades". Conclusões: Este estudo evidenciou que a pandemia de COVID-19 teve um impacto negativo significativo na progressão do controle de uma doença ancestral como a TB, especialmente no contexto da morbimortalidade por DR-TB.

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

ABSTRACT 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.

A study of adverse drug reactions in patients receiving treatment for multidrug-resistant tuberculosis in a tertiary care center

Background: The emergence of multidrug-resistant tuberculosis (MDR-TB) (defined as resistance to at least isoniazid and rifampin) poses a threat to global TB control. Second line drugs are frequently associated with very high rates of unacceptable adverse drug reactions (ADRs), needing frequent interruption and change of regimen. Different studies have stated varying incidence of these adverse effects leading to discontinuation of ATT. Aims and Objectives: This study intends to find out the occurrence of side effects of anti-TB drugs in patients receiving MDR treatment. Material and Methods: The present prospective cross-sectional observational study was carried out at Drug-Resistant TB Center at Govt. Medical College Kota for a period of July 2018 to June 2019. Patients with adverse events after the introduction of treatment of MDR-TB were included in the study. We monitored the patients with adverse events after starting treatment till the patients were admitted and later followed up by recalling the patients at monthly intervals. Results: Out of total 148 patients majority patients (64.81%) were in the young age group (20–39 years) with male: female ratio 2:1. Out of the 148 patients, 112 patients developed at least one or more types of ADR and a total of 15 types of ADR. Gastrointestinal upset was the most common ADR reported (62.16%) followed by joint pain (41.89%) and headache (36.48%). About 60.74% of all ADRs were managed by symptomatic treatment. 32 (21.62%) patients required change of regimen.Twelve patients (8%) discontinued treatment due to adverse reactions. Conclusion: Treatment of MDR-TB with second-line antitubercular drugs is associated with high rate of adverse effects experienced in more than half of patient in this study. Ototoxicity and neuropsychiatric symptoms are major adverse effects lead to important drug withdrawl from the regimen. The health care professionals should be alert during the intensive phase of the treatment, identify symptoms at the earliest and hence help in minimizing morbidity.

Adverse reactions of linezolid in the treatment of multidrug-resistant pulmonary tuberculosis / 中华传染病杂志

Objective:To analyze the adverse reactions of patients with multidrug-resistant pulmonary tuberculosis treated with linezolid, and to provide reference for clinical rational use of drugs.Methods:A total of 189 patients with multidrug-resistant pulmonary tuberculosis who were admitted to Hunan Chest Hospital between June 2019 and June 2020 were retrospectively included, and were divided into the linezolid group and the control group. The control group was given a standardized anti-tuberculosis treatment without linezolid, and the linezolid group was given linezolid in addition to standardized regimens. The occurrences of hematological toxicity, peripheral neuritis, optic neuritis and other adverse reactions in the two groups after anti-tuberculosis treatment were recorded. The risk factors for adverse reactions of linezolid were analyzed. Statistical analysis was performed using independent samples t test and chi-square test, and logistic regression was used to analyze the risk factors for adverse reactions of linezolid. Results:A total of 189 patients with MDR-TB were included in this study, including 108 in the linezolid group and 81 in the control group. There were no significant differences in baseline characteristics between the linezolid and control groups. The frequencies of leukopenia, anemia, thrombocytopenia, peripheral neuritis and optic neuritis in the linezolid group were 20.4%(22/108), 47.2%(51/108), 21.3%(23/108), 20.4%(22/108) and 13.9%(15/108), respectively, which were all significantly higher than those in the control group (8.6%(7/81), 27.2%(22/81), 9.9%(8/81), 1.2%(1/81) and 4.9%(4/81), respectively), and the differences were all statistically significant ( χ2=4.90, 7.86, 4.40, 15.86 and 4.10, respectively, all P<0.050). Patients older than 45 years of age was independent risk factor for leukopenia (odds ratio ( OR)=3.08, 95% confidence interval ( CI) 1.03 to 9.25, P<0.050) and thrombocytopenia ( OR=2.41, 95% CI 1.09 to 5.35, P<0.050) after linezolid administration. The higher value of white blood cell at baseline ( OR=0.48, 95% CI 0.30 to 0.76, P=0.002) was an independent protective factor for leukopenia associated with linezolid. Conclusions:Pancytopenia, peripheral neuritis and optic neuritis are prone to appear when linezolid is used to treat patients with multidrug-resistant pulmonary tuberculosis. In clinical practice, closely monitoring the adverse reactions during the use of linezolid for anti-tuberculosis treatment is needed.

Tendência temporal da tuberculose drogarresistente (TBDR) e dos tipos de resistência no estado de Pernambuco, Brasil / Temporal trend of Drug-Resistant Tuberculosis (DRTB) and resistance types in the state of Pernambuco, Brazil

Resumo Introdução A tuberculose drogarresistente (TBDR) é um dos grandes desafios para a saúde pública. Objetivo Este estudo analisou a tendência temporal da TBDR e a razão da proporção dos tipos de resistência no estado de Pernambuco, no período de 2002 a 2014. Método Trata-se de um estudo observacional do tipo tendência temporal de série histórica utilizando dados do Sistema de Informação de Tratamentos Especiais da Tuberculose e análise pelo modelo autorregressivo de médias móveis de ordem 2. Resultados Foram notificados 298 novos casos de TBDR, com incidência variando entre 0,06 e 0,71/100 mil habitantes. Pelo menos 1 caso foi notificado em 40 dos 185 municípios do estado. A tendência temporal da TBDR e da proporção entre os tipos de resistência não apresentou comportamento linear. Nos últimos cinco anos, houve uma tendência ascendente, concentrando 71,1% dos casos da série histórica. Em 2014, foi observado um crescimento expressivo tanto da TBDR primária como da secundária, quando comparado ao ano de 2002. Conclusão Apesar da baixa incidência e de a tendência da TBDR não ter comportamento linear, o aumento de casos nos últimos anos da série histórica pode ser considerado um sinal de alerta para os programas de controle da doença em Pernambuco.

Abstract Background Drug-Resistant Tuberculosis (DRTB) is one of the most relevant challenge to public health. Objective This study analyzed the temporal trend of the DRTB and resistance types in the state of Pernambuco, from 2002 to 2014. Method This was an observational study of the temporal trend type of a historical series using data from the Special Treatment Information System of Tuberculosis (SITE-TB) and also analysis by the autoregressive moving average models of order 2. Results A total of 298 new DRTB cases were reported, ranging from 0.06 to 0.71 per 100,000 inhabitants. At least one case was reported in 40 of the 185 municipalities in the state. The temporal trend of DRTB and the proportion between resistance types did not present a linear behavior. In the last 5 years, there has been an upward trend, concentrating 71.1% of the historical series. In 2014, there was an expressive growth of both primary and secondary DRTB, when compared to the year 2002. Conclusion Despite the low incidence and tendency of DRTB not to be linear, the increase in cases in the last years of the historical series can be considered as a warning sign for the disease control programs of Pernambuco.

Validación de la reacción en cadena de la polimerasa en tiempo real (qPCR) acoplada a curvas melting como herramienta alternativa para el diagnóstico de Tuberculosis Mutidrogorresistente / Validation of the real time polymerase chain reaction (qPCR) coupled to melting curves as an alternative tool for the diagnosis of Multi-Drug Resistant Tuberculosis

INTRODUCCIÓN: la tuberculosis es una enfermedad infecto-contagiosa, causada por diversas especies del Complejo Mycobacterium tuberculosis, actualmente se estima que un tercio de la población mundial se encuentra afectada por lo que representa una amenaza para la salud pública, principalmente por el surgimiento de cepas Multidrogorresistentes (TB-MDR). En Bolivia se reportaron 7.538 personas enfermas con Tuberculosis, los últimos datos sobre TB-MDR indican un aumento de 0,2% por año, en 2019 se registró un 3,1% de TB-MDR. Actualmente en nuestro país se emplean métodos moleculares para la identificación de este agente infeccioso; no obstante, existen muy pocos o ningún trabajo acerca de la aplicación de métodos moleculares para la detección precisa y efectiva de cepas TB-MDR que otorguen validez a los resultados emitidos. Este trabajo resuelve el cuestionamiento de, si la PCR en tiempo real (RT-qPCR) acoplada a curvas melting es una herramienta de diagnóstico alternativo aplicable, para la identificación de Tuberculosis Multidrogorresistente MATERIALES Y MÉTODOS: se trabajó con 74 cepas de Mycobaterium tuberculosis fenotípicamente identificadas por cultivo (método de las proporciones, Canetti Rist) como gold standar. El material genético para las pruebas moleculares se obtuvo por el método de columnas, se utilizaron dos controles primarios para la determinación de resistencia a los fármacos Isoniacida y Rifampicina, tanto los controles como las muestras se procesaron por RT-qPCR acoplada a curvas melting, mediante cambios de temperatura de disociación. RESULTADOS: los parámetros de test diagnóstico de la prueba demostraron sensibilidad: 67.4%, especificidad: 83.3%, Exactitud: 73.97%, VPP: 85.3%, VPN: 64.1% para Isoniacida. Mientras que para Rifampicina: Sensibilidad: 97%, especificidad: 20%, exactitud: 58.9%, VPP: 55.4% y VPN: 87.5%. CONCLUSIÓN: el método evaluado para la determinación de resistencia a Isoniacida presenta un equilibrio entre sensibilidad y especificidad, por lo que representa una alternativa diagnóstica confiable, mientras que para resistencia a Rifampicina presenta una alta sensibilidad que es muy útil para países endémicos como el nuestro.

INTRODUCTION: tuberculosis is an infectious-contagious disease, caused by various species of the Mycobacterium tuberculosis Complex, it is estimated that one third of the world population is affected by what represents a threat to public health, mainly by the emergence of multidrugresistant strains (MDR-TB). In Bolivia, 7,538 people are reported sick with Tuberculosis, the latest data on MDR-TB indicate an increase of 0.2% per year, in 2018 there was 3.1% of MDR-TB. Currently in our country molecular methods are used to identify this infectious agent; however, there is very little or no work on the application of molecular methods for the precise and effective detection of MDR-TB strains that give validity to the results issued. This work resolves the question of whether real-time PCR (RT-qPCR) coupled to melting curves is an applicable alternative diagnostic tool for the identification of multidrug-resistant tuberculosis MATERIALS AND METHODS: we worked with 74 strains of Mycobaterium tuberculosis phenotypically identified by culture (method of proportions, Canetti Rist) as a gold standar. The genetic material for molecular methods was obtained by the column assay, two primary controls were used for the determination of resistance to the drugs Isoniazid and Rifampicin, both the controls and the samples were processed by RT-qPCR coupled to melting curves, by means of temperature changes of dissociation. RESULTS: the diagnostic test parameters of the test demonstrated sensitivity: 67.4%, specificity: 83.3%, Accuracy: 73.97%, PPV: 85.3%, NPV: 64.1% for Isoniazid. While for Rifampicin: Sensitivity: 97%, Specificity: 20%, Accuracy: 58.9%, PPV: 55.4% and NPV: 87.5% CONCLUSION: the method evaluated for the determination of resistance to Isoniazid presents a balance between sensitivity and specificity, therefore it represents a reliable diagnostic alternative, while for resistance to Rifampicin it presents a high sensitivity that is very useful for endemic countries such as ours.