[Control and management strategies in multidrug-resistant tuberculosis: literature reviewEstrategias de control y atención de la tuberculosis multirresistente: una revisión de la literatura]. / Estratégias de controle e atenção à tuberculose multirresistente: uma revisão da literatura.

OBJECTIVE: To identify control and patient management strategies for multidrug-resistant tuberculosis (MDR-TB). METHODS: An integrative review of the literature was performed through research in three health databases (LILACS, PubMed and CINAHL) and one multidisciplinary database (Scopus). Original articles published in English, Spanish or Portuguese, from 2006 to 2016, describing strategies to implement MDR-TB patient care, were included. The information collected was organized according to the strategies identified by the investigators, which were grouped into theme categories. RESULTS: Based on a sample of 13 articles, four categories were identified: a) DOTS-plus: reorganization of health services, improvement of local structures, standardization of professional protocols and behaviors, provision of directly observed treatment; b) service decentralization: bringing health professionals closer to patients, especially in areas with high disease burden; c) use of communication tools: software and telephone calls that allowed consultations with specialists and/or optimization of care within multiprofessional teams; d) social protection of patients: establishment of mechanisms to provide emotional, social and/or economic support to patients under treatment, strengthening adherence to drug therapy. CONCLUSIONS: Several strategies were identified beyond pharmacological measures, supporting the idea that the control of MDR-TB requires mechanisms that allow comprehensive care, consistent with the peculiarities and potentialities of the different scenarios where the disease occurs.

OBJETIVO: Identificar estrategias de control de la tuberculosis multirresistente (TBMR) y de atención a los pacientes afectados. MÉTODOS: Se realizó una revisión integrativa de la literatura en tres bases de datos del área de la salud (LILACS, PubMed y CINAHL) y en uma base de datos multidisciplinaria (Scopus). Se seleccionaron artículos originales que registraran las estrategias utilizadas para la atención al paciente con TBMR, publicados en inglés, español o portugués entre 2006 y 2016. Se organizaron los datos de acuerdo a las estrategias de implementación de la TBMR identificadas por los investigadores, que fueron agrupadas en categorías temáticas. RESULTADOS: Con base en una muestra de 13 artículos, se identificaron cuatro categorías: a) DOTS-plus: reorganización de los servicios de salud, mejoramiento de la estructura local, estandarización de protocolos y comportamientos profesionales, administración de tratamiento supervisado; b) descentralización del servicio: aproximación entre profesionales de la salud y pacientes en tratamiento, principalmente en los lugares con alta carga de la enfermedad; c) uso de herramientas de comunicación: programas informáticos y llamadas telefónicas que permitieran la realización de consultas con especialistas o la optimización de la asistencia dentro de los equipos multiprofesionales; d) protección social de los pacientes: creación de mecanismos que proporcionaron apoyo emocional, social o económico a los pacientes en tratamiento, fortaleciendo la adhesión al tratamiento farmacológico. CONCLUSIONES: Se identificaron diversas estrategias que van más allá de los aspectos farmacológicos, lo que corroboró la idea de que el control de la TBMR exige mecanismos que posibiliten una atención integral de acuerdo a las particularidades y potencialidades de los diferentes escenarios donde ocurre la enfermedad.

[Tuberculosis]. / Tuberkulose.

Tuberculosis is a bacterial infectious disease that is usually transmitted by inhalation of droplets containing the bacteria. The World Health Organization (WHO) estimates that approximately 10 million patients were newly diagnosed with tuberculosis in 2017. Rapid diagnosis relies on a combination of imaging and microbiological, molecular, and, rarely, immunological tests. Genotypic methods enable early diagnosis and allow highly accurate prediction of drug resistance. Phenotypic (culture-based) methods are the diagnostic gold standard. Standard management of patients with pan drug-susceptible pulmonary tuberculosis includes a combination of rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampicin and isoniazid for additional 4 months, which leads to cure rates of >80%. With individualized treatment schemes, similar cure rates can be achieved for patients with multidrug-resistant tuberculosis.

Modular programming for tuberculosis control, the "AuTuMN" platform.

BACKGROUND: Tuberculosis (TB) is now the world's leading infectious killer and major programmatic advances will be needed if we are to meet the ambitious new End TB Targets. Although mathematical models are powerful tools for TB control, such models must be flexible enough to capture the complexity and heterogeneity of the global TB epidemic. This includes simulating a disease that affects age groups and other risk groups differently, has varying levels of infectiousness depending upon the organ involved and varying outcomes from treatment depending on the drug resistance pattern of the infecting strain. RESULTS: We adopted sound basic principles of software engineering to develop a modular software platform for simulation of TB control interventions ("AuTuMN"). These included object-oriented programming, logical linkage between modules and consistency of code syntax and variable naming. The underlying transmission dynamic model incorporates optional stratification by age, risk group, strain and organ involvement, while our approach to simulating time-variant programmatic parameters better captures the historical progression of the epidemic. An economic model is overlaid upon this epidemiological model which facilitates comparison between new and existing technologies. A "Model runner" module allows for predictions of future disease burden trajectories under alternative scenario situations, as well as uncertainty, automatic calibration, cost-effectiveness and optimisation. The model has now been used to guide TB control strategies across a range of settings and countries, with our modular approach enabling repeated application of the tool without the need for extensive modification for each application. CONCLUSIONS: The modular construction of the platform minimises errors, enhances readability and collaboration between multiple programmers and enables rapid adaptation to answer questions in a broad range of contexts without the need for extensive re-programming. Such features are particularly important in simulating an epidemic as complex and diverse as TB.

High pre-diagnosis attrition among patients with presumptive MDR-TB: an operational research from Bhopal district, India.

BACKGROUND: Pre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014). METHODS: Study was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme). RESULTS: Of 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST. CONCLUSION: High pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required.

Additional Drug Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Korea: Implications for Regimen Design.

Detailed information on additional drug resistance patterns of multidrug-resistant tuberculosis (MDR-TB) is essential to build an effective treatment regimen; however, such data are scarce in Korea. We retrospectively analyzed the results of phenotypic drug susceptibility testing (DST) of culture confirmed-TB patients from January 2010 to December 2014 in 7 university hospitals in Korea. MDR-TB was identified among 6.8% (n = 378) of 5,599 isolates. A total of 57.1% (n = 216) of the MDR-TB patients had never been treated for TB. Strains from MDR-TB patients showed additional resistance to pyrazinamide (PZA) (35.7%), any second-line injectable drug (19.3%), and any fluoroquinolone (26.2%). Extensively drug resistant TB comprised 12.4% (n = 47) of the MDR-TB patients. Of 378 MDR-TB patients, 50.3% (n = 190) were eligible for the shorter MDR-TB regimen, and 50.0% (n = 189) were fully susceptible to the 5 drugs comprising the standard conventional regimen (PZA, kanamycin, ofloxoacin, prothionamide, and cycloserine). In conclusion, the proportion of new patients and the levels of additional drug resistance were high in MDR-TB patients. Considering the high levels of drug resistance, the shorter MDR-TB treatment regimen may not be feasible; instead, an individually tailored regimen based on the results of molecular and phenotypic DST may be more appropriate in MDR-TB patients in Korea.

Scenario Analysis for Programmatic Tuberculosis Control in Western Province, Papua New Guinea.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are major health problems in Western Province, Papua New Guinea. While comprehensive expansion of TB control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. We parameterized our previously described mathematical model of Mycobacterium tuberculosis dynamics in Western Province, following an epidemiologic assessment. Five hypothetical scenarios representing alternative programmatic approaches during the period from 2013 to 2023 were developed with local staff. Bayesian uncertainty analyses were undertaken to explicitly acknowledge the uncertainty around key epidemiologic parameters, and an economic evaluation was performed. With continuation of existing programmatic strategies, overall TB incidence remained stable at 555 cases per 100,000 population per year (95% simulation interval (SI): 420, 807), but the proportion of incident cases attributable to MDR-TB increased from 16% to 35%. Comprehensive, provincewide strengthening of existing programs reduced incidence to 353 cases per 100,000 population per year (95% SI: 246, 558), with 46% being cases of MDR-TB, while incorporating programmatic management of MDR-TB into these programs reduced incidence to 233 cases per 100,000 population per year (95% SI: 198, 269) with 14% MDR-TB. Most economic costs were due to hospitalization during the intensive treatment phase. Broad scale-up of TB control activities in Western Province with incorporation of programmatic management of MDR-TB is vital if control is to be achieved. Community-based treatment approaches are important to reduce the associated economic costs.

[New drugs for treatment of tuberculosis]. / Neue Medikamente zur Behandlung der Tuberkulose.

New effective drugs for the treatment of tuberculosis (TB) are necessary for two main reasons: firstly, it would be desirable to reduce the duration of TB treatment from 6 to 4 months and secondly, new drugs are urgently needed for the treatment of multidrug-resistant strains of Mycobacterium tuberculosis. For the first time since 1960 the two new drugs bedaquiline and delamanid were approved and licensed in 2014 for the treatment of multidrug-resistant M. tuberculosis; however, efforts to reduce the duration of treatment to 4 months using fluoroquinolones have not been successful. Further new drugs are currently in phase 2 and phase 3 studies; therefore, new treatment options can be expected within the next few years.

Construction of a mathematical model for tuberculosis transmission in highly endemic regions of the Asia-Pacific.

We present a mathematical model to simulate tuberculosis (TB) transmission in highly endemic regions of the Asia-Pacific, where epidemiology does not appear to be primarily driven by HIV-coinfection. The ten-compartment deterministic model captures many of the observed phenomena important to disease dynamics, including partial and temporary vaccine efficacy, declining risk of active disease following infection, the possibility of reinfection both during the infection latent period and after treatment, multidrug resistant TB (MDR-TB) and de novo resistance during treatment. We found that the model could not be calibrated to the estimated incidence rate without allowing for reinfection during latency, and that even in the presence of a moderate fitness cost and a lower value of R0, MDR-TB becomes the dominant strain at equilibrium. Of the modifiable programmatic parameters, the rate of detection and treatment commencement was the most important determinant of disease rates with each respective strain, while vaccination rates were less important. Improved treatment of drug-susceptible TB did not result in decreased rates of MDR-TB through prevention of de novo resistance, but rather resulted in a modest increase in MDR-TB through strain replacement. This was due to the considerably greater relative contribution of community transmission to MDR-TB incidence, by comparison to de novo amplification of resistance in previously susceptible strains.

[Treatment of tuberculosis: what is new?] / Therapie der Tuberkulose: Was gibt es Neues?

Never before have so many people around the world been simultaneously affected by tuberculosis. Tuberculosis is the leading cause of death from a bacterial infectious disease worldwide. The World Health Organization's ambitious goal from 2014 of achieving global elimination of tuberculosis does not seem realistic, but on current trends, tuberculosis could be eliminated in the European Union by 2040. Since the beginning of 2022, there have been more innovations for the treatment of tuberculosis than in no other comparable time period before. One month of rifapentine and isoniazid is effective in treating latent tuberculosis infection. However, rifapentine is licensed in the USA but not in the EU and must be imported for individual cases. The duration of the standard treatment for tuberculosis can be shortened to four months but this treatment regimen is also based on rifapentine, in addition to isoniazid, pyrazinamide, and moxifloxacin. The approval of rifapentine in Europe is a much-needed step towards shortening the treatment of tuberculosis. With new drugs an even shorter standard treatment of only 2 months is possible. The treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR-/RR-TB) has been shortened to six months, the same length as the standard treatment available in Germany. The combination of bedaquiline, pretomanid, linezolid ± moxifloxacin, cured around 90% of affected patients were cured in studies with a treatment duration of six months. With 19 drugs in clinical trials, the treatment of tuberculosis is expected to continue to improve rapidly in the coming years.

Effectiveness and Safety of Short-term Regimen for Multidrug-resistant Tuberculosis Treatment: A Systematic Review of Cohort Studies.

This systematic review explores the effectiveness and safety of a short-term regimen (STR) in treating multidrug-resistant tuberculosis (MDR-TB). We use several cohort studies which were searched using standardized Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The keywords were used based on problem, intervention, comparison, and outcome consisted of MDR-TB and STR. Seven cohort studies were selected from 314 studies. The result showed that STR has better therapeutic efficacy and shorter duration than the 2011 World Health Organization regimen for MDR-TB with success rates above 50% in respective studies. The most effective regimen was kanamycin-high-dose isoniazid-clofazimine-ethambutol-prothionamide-pyrazinamide-gatifloxacin in the intensive phase for four months and clofazimine-ethambutol-pyrazinamide-gatifloxacin-prothionamide in the continuation phase for eight months. Gastrointestinal problems, ototoxicity, dysglycemia, and liver problems were the most reported side effects. STR provides good effectiveness in MDR-TB treatment in terms of treatment success rate and short therapy duration.

Treatment outcome and mortality among patients with multidrug-resistant tuberculosis in tuberculosis hospitals of the public sector.

This study was conducted to evaluate treatment outcome, mortality, and predictors of both in patients with multidrug-resistant tuberculosis (MDR-TB) at 3 TB referral hospitals in the public sector of Korea. We included MDR-TB patients treated at 3 TB referral hospitals in 2004 and reviewed retrospectively their medical records and mortality data. Of 202 MDR-TB patients, 75 (37.1%) had treatment success and 127 (62.9%) poor outcomes. Default rate was high (37.1%, 75/202), comprising 59.1% of poor outcomes. Male sex (adjusted odds ratio [aOR], 2.91; 95% confidence interval [CI], 1.13-7.49), positive smear at treatment initiation (aOR, 5.50; 95% CI, 1.22-24.90), and extensively drug-resistant TB (aOR, 10.72; 95% CI, 1.23-93.64) were independent predictors of poor outcome. The all-cause mortality rate was 31.2% (63/202) during the 3-4 yr after treatment initiation. In conclusion, the treatment outcomes of patients with MDR-TB at the 3 TB hospitals are poor, which may reflect the current status of MDR-TB in the public sector of Korea. A more comprehensive program against MDR-TB needs to be integrated into the National Tuberculosis Program of Korea.

Prevalence of Multidrug-Resistant Tuberculosis in HIV/Tuberculosis Co-Infected Patients.

Tuberculosis (TB) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Patients with multidrug-resistant (MDR)-TB have poor outcomes. This study aimed to determine the prevalence of MDR-TB in HIV/TB co-infected patients in the Korea. We reviewed the medical records of HIV/TB co-infected patients at two university hospitals between January 1998 and December 2020. During the study period, a total of 87 HIV/TB co-infected patients were identified, and drug susceptibility test results were available for 44 of them. The prevalence of MDR-TB in the study population was 15.9% (7/44, 95% confidence interval, 5.1 - 26.7).

Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): a protocol for a randomised controlled trial.

INTRODUCTION: Treatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB. METHODS AND ANALYSIS: A double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression. ETHICS: Ethical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT). DISSEMINATION: Findings of the study will be published in peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12616000215426.

Multidrug-resistant pulmonary tuberculosis among young Korean soldiers in a communal setting.

The goal of this study was to evaluate the prevalence of first-line anti-tuberculosis drug resistance and risk factors associated with multidrug-resistant tuberculosis (MDR TB) among young soldiers in the Korean military, which has a strict tuberculosis control program. All patients with culture-confirmed pulmonary tuberculosis during their service at the Armed Forces Capital Hospital from January 2001 to December 2006 were enrolled in the study. Drug resistant Mycobacterium tuberculosis was isolated from 18 patients (12.2%) and multidrug-resistant M. tuberculosis was isolated from 12 patients (8.1%). Previous treatment of tuberculosis and the presence of a cavity on the patient's chest computed tomography scan were associated with MDR TB; military rank, smoking habits, and positive acid-fast bacilli smears were not associated with MDR TB. In a multiple logistic regression analysis, previous treatment of tuberculosis was a significant independent risk factor for MDR TB (odds ratio 6.12, 95% confidence interval 1.53-24.46). The prevalence of drug resistant tuberculosis among young soldiers in the Korean military was moderately high and the majority of resistant cases were found in patients who had undergone previous treatment of tuberculosis. Based on our results, we suggest that relapsed tuberculosis cases within communal settings should be cautiously managed until the drug susceptibility tests report is completed, even if previous treatment results were satisfactory.

Trend of multidrug and fluoroquinolone resistance in Mycobacterium tuberculosis isolates from 2010 to 2014 in Korea: a multicenter study.

BACKGROUND/AIMS: This study was conducted to evaluate the recent prevalence and trend of anti-tuberculosis (TB) drug resistance with a focus on multidrug-resistance (MDR) and fluoroquinolone resistance in South Korea. METHODS: We retrospectively reviewed the drug susceptibility testing results of culture-confirmed Mycobacterium tuberculosis isolates collected from 2010 to 2014 at seven tertiary hospitals in South Korea. RESULTS: A total of 5,599 cases were included: 4,927 (88.0%) were new cases and 672 (12.0%) were previously treated cases. The MDR rate has significantly decreased from 6.0% in 2010 to 3.0% in 2014 among new cases, and from 28.6% in 2010 to 18.4% in 2014 among previously treated cases (p < 0.001 and p = 0.027, respectively). The resistance rate to any f luoroquinolone was 0.8% (43/5,221) in non-MDR-TB patients, as compared to 26.2% (99/378) in MDR-TB patients (p < 0.001). There was no significant change in the trend of fluoroquinolone resistance among both nonMDR-TB and MDR-TB patients. Among the 43 non-MDR-TB patients with fluoroquinolone resistance, 38 (88.4%) had fluoroquinolone mono-resistant isolates. CONCLUSION: The prevalence of MDR-TB has significantly decreased from 2010 to 2014. The prevalence of fluoroquinolone resistance among non-MDR-TB patients was low, but the existence of fluoroquinolone mono-resistant TB may be a warning on the widespread use of fluoroquinolone in the community.

Extensively resistant tuberculosis, Colombia, 2006-2016 / Serie de casos: tuberculosis extremadamente resistente a drogas en Colombia, 2006-2016

Introducción. La tuberculosis extremadamente resistente a los medicamentos (TB-XDR) es el resultado de deficiencias en la administración del tratamiento y en la prevención de la transmisión de la enfermedad; además, es un reto para los programas nacionales de control de la tuberculosis. Objetivo. Describir las características clínicas y epidemiológicas de los casos de TB-XDR diagnosticados en Colombia. Materiales y métodos. Se trata de un estudio de serie de casos, de pacientes con diagnóstico de TB-XDR, de 2006 a 2016 en Colombia. Las fuentes de información fueron el formato único de vigilancia y la base de datos del Laboratorio Nacional de Referencia. Se analizaron las variables: entidad territorial de procedencia, sexo, edad, régimen de afiliación, forma de tuberculosis, coinfección tuberculosis-HIV, patrón de sensibilidad a los fármacos de segunda línea y resultado (vivo o muerto). Resultados. En el período de estudio, se diagnosticaron 51 casos de TB-XDR, 28 hombres y 23 mujeres, con un promedio anual de cinco casos. En los departamentos de Antioquia, Valle del Cauca y Atlántico, se presentaron 46 (90 %) de los casos. El rango de edad fue de 5 a 81 años y, la mediana, de 40 años. De los 51 pacientes, 32 (63 %) estaban afiliados al régimen subsidiado de salud y 46 (90 %) presentaron tuberculosis pulmonar; de los 22 a quienes se les practicó la prueba para HIV, en tres (13,6 %) había coinfección con HIV, y 29 (57 %) murieron. Los fármacos a los cuales hubo mayor resistencia, fueron ofloxacina en 45 (88 %) casos y amikacina en 43 (84 %). Conclusión. La TB-XDR se presentó principalmente en formas pulmonares, lo cual aumenta la probabilidad de transmisión en la comunidad y se refleja en la aparición de tuberculosis resistente en menores de 15 años. La población más afectada es la económicamente activa, con una gran mortalidad. El Programa Nacional de Prevención y Control de la Tuberculosis debe generar estrategias para evitar la propagación de cepas resistentes.

Competitive fitness of Mycobacterium tuberculosis in vitro.

Background: While, bacteria resistance mutations can affect competitive fitness, given our multidrug-resistant (MDR) prevalence, we conducted this study to determine the impact of MDR on the competitive fitness of Mycobacterium tuberculosis (MTB) complex MDR strains. We conducted a cross-sectional study at the University Clinical Research Center (UCRC) from January to December 2017. New TB patients over aged of 18 were recruited at University teaching hospital and health reference centers of Bamako in USTTB Ethical committee approved protocols. Methods: MDR and drug-susceptible (wild-type [WT]) MTB strains (T1 and Beijing) and MTB H37Rv were competed on solid media in UCRC's Tuberculosis Laboratory. Competitive and individual cultures were incubated for 14 days at 37°C with 7% CO2. Number of generation, generation time, and relative competitive fitness (W) of the strains were calculated. Data were analyzed with Epi-Info 7.1.5.2 software (CDC). P value was considered significant when it was <0.05. Scientific calculator (CS-82TL) was used for competitive fitness parameters calculations. Results: We performed 24 competitive cultures and 10 individual cultures. In individual cultures, strains' generation number was for Beijing (WT: 4.60 and mutant MR: 4.40), T1 (WT: 2.69 and MR: 2.37), and H37Rv: 2.91. Generation number of WT strains was less than those of MDR strains in both individual and competitive culture. Relative competitive fitness was below 1 (W<1) in 83.3%. Conclusion: MDR strains were less competitive than WT strains in 83.3% of cases. Resistant mutation impacts bacteria fitness.

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment / Papel do polimorfismo rs4073 do gene IL8 na toxicidade do sistema nervoso central em pacientes em tratamento para tuberculose multirresistente

ABSTRACT Objective: To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). Methods: A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. Results: The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. Conclusions: The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

RESUMO Objetivo: Determinar o papel do polimorfismo rs4073 do gene IL8 na previsão do risco de toxicidade do sistema nervoso central (SNC) em pacientes em tratamento farmacológico padrão para tuberculose multirresistente (TBMR). Métodos: Amostras de sangue de uma coorte de 85 pacientes com TBMR que assinaram um termo de consentimento livre e esclarecido e que estavam recebendo tratamento com medicamentos antituberculosos de segunda linha foram amplificadas para o gene IL8 (rs4073) e genotipadas. Todos os pacientes foram avaliados clinicamente quanto a evidências de toxicidade do tratamento e categorizados de acordo com os achados. Foram avaliadas as associações brutas e ajustadas. Resultados: As principais queixas enquadraram-se nas seguintes categorias: toxicidade do SNC; toxicidade gastrointestinal; toxicidade cutânea; e toxicidade ocular e ototoxicidade. Sintomas de toxicidade gastrointestinal foram relatados por 59% dos pacientes, e sintomas de toxicidade do SNC foram relatados por 42,7%. Foram identificados os seguintes genótipos de IL8 (rs4073): AA, em 64 dos participantes; AT, em 7; TT, em 11. Houve associação significativa entre o modelo dominante de herança e toxicidade do SNC no modelo bruto (p = 0,024; OR = 3,57; IC95%: 1,18-10,76) e no ajustado (p = 0,031; OR = 3,92; IC95%: 1,13-13,58). O genótipo AT+TT do gene IL8 (rs4073) apresentou risco 3,92 vezes maior de toxicidade do SNC que o genótipo AA. Conclusões: O genótipo AT+TT tende a se associar a um maior risco de características clínicas adversas durante o tratamento da TBMR.

Drug-resistant tuberculosis: integrative review of nursing care in primary health care / Tuberculosis farmacorresistente: revisión integradora de los cuidados de enfermería en la atención primaria de salud / Tuberculose drogarresistente: revisão integrativa dos cuidados de enfermagem na atenção primária à saúde

ABSTRACT Objectives: to identify, in the scientific literature, the care that should be provided to individuals with drug-resistant tuberculosis by nurses in primary health care. Methods: integrative review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses study selection flowchart. Data collection was conducted in November 2022, across ten databases. Results: six studies emphasized that nurses should perform directly observed treatment; two highlighted the importance of integrated care management between tuberculosis and human immunodeficiency virus; two demonstrated comprehensive nursing consultation using the nursing process; one emphasized person-centered care, with discharge planning and improved hospital communication with primary health care services. Final Considerations: the care that nurses should provide to individuals with drug-resistant tuberculosis in primary health care, for care resolution, is evidence-based.

RESUMEN Objetivos: identificar, en la literatura científica, los cuidados que deben brindarse a las personas con tuberculosis farmacorresistente por parte de los enfermeros en la atención primaria de salud. Métodos: revisión integradora, utilizando el flujo de selección de estudios del Preferred Reporting Items for Systematic Reviews and Meta-Analyses. La recolección de datos se realizó en noviembre de 2022, en diez bases de datos. Resultados: seis estudios enfatizaron que el enfermero debe llevar a cabo el tratamiento directamente observado; dos resaltaron la importancia de la gestión del cuidado integrado entre la tuberculosis y el virus de la inmunodeficiencia humana; dos evidenciaron la consulta de enfermería comprensiva utilizando el proceso de enfermería; uno destacó los cuidados centrados en la persona, con planificación de alta y una mejor comunicación hospitalaria con los servicios de atención primaria de salud. Conclusiones: los cuidados que deben brindarse por parte de los enfermeros a las personas con tuberculosis farmacorresistente en la atención primaria de salud, para la resolutividad del cuidado, están basados en evidencia científica.

RESUMO Objetivos: identificar, na literatura científica, os cuidados que devem ser prestados às pessoas com tuberculose drogarresistente pelos enfermeiros na atenção primária à saúde. Métodos: revisão integrativa, utilizando o fluxograma de seleção de estudos Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A coleta de dados foi realizada em novembro de 2022, em dez bases de dados. Resultados: seis estudos enfatizaram que o enfermeiro deve realizar o tratamento diretamente observado; dois trouxeram a importância da gestão do cuidado integrado entre tuberculose e vírus da imunodeficiência humana; dois evidenciaram a consulta de enfermagem abrangente com utilização do processo de enfermagem; um salientou os cuidados centrados na pessoa, com planejamento de alta e melhor comunicação hospitalar com os serviços de atenção primária à saúde. Considerações Finais: os cuidados que devem ser prestados pelos enfermeiros às pessoas com tuberculose drogarresistente na atenção primária à saúde, para resolutividade do cuidado, são baseados em evidências científicas.

Molecular Diagnosis of Tuberculosis.

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.