Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Hemoptisis secundaria a tuberculosis pulmonar complicada con pseudoaneurisma de Rasmussen. Reporte de un caso en pediatría. / Hemoptysis in Pulmonary Tuberculosis Complicated by Rasmussen's Pseudoaneurysm. A Pediatric Case Report.

Presentamos el caso de un niño de 12 años que consultó por hemoptisis, sin otros sín- tomas asociados. Se realizó radiografía de tórax (patológica), laboratorio con aumen- to moderado de reactantes de fase aguda, PPD (negativa), esputos x 3 con bacilosco- pias negativas y tomografía de tórax con contraste i.v. que mostró imágenes de árbol en brote en todos los lóbulos y una imagen de dilatación vascular de una rama de la ar- teria pulmonar en lóbulo superior izquierdo. Se plantearon diagnósticos diferenciales: malformación vascular primaria o lesión secundaria a infección. La angiografía digital permitió confirmar el pseudoaneurisma y embolizarlo. Luego de 17 días, 2/3 cultivos de esputo fueron positivos para Mycobacterium tuberculosis. El niño realizó tratamiento antituberculoso con drogas de primera línea con evolución clínica favorable. Este caso resalta la importancia de considerar el pseudoaneurisma de Rasmussen en- tre las posibles complicaciones de un paciente con tuberculosis y hemoptisis recurren- te o masiva.

We present the case of a 12-year-old boy admitted to the hospital due to hemoptysis without other symptoms. We performed a Thorax X-Ray (pathological), laboratory with elevated acute phase reactants, TST (negative), sputum x 3 with negative smear and computed tomography angiography showing a tree-in-bud pattern in all lobes, and di-latation of a brunch of the pulmonary artery in the upper left lobe. We considered pri-mary vascular anomaly or lesion due to infection as a differential diagnosis. The patient underwent digital angiography and therapeutic embolization of this pseudoaneurysm. After seventeen days, 2/3 of the sputum cultures were positive for Mycobacterium tu-berculosis. The patient received standard anti-TB therapy with favorable evolution. This case highlights the importance of considering complications such as Rasmussen's pseudoaneurysm in patients with pulmonary tuberculosis and recurrent or massive hemoptysis.

Factores de riesgo asociados a la farmacorresistencia y al tratamiento no exitoso de la tuberculosis en Chile 2014-2018 / Risk factors and predictors of drug resistance in tuberculosis: A comprehensive analysis of cases in Chile (2014-2018)

OBJETIVOS: Determinar los factores de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso de tuberculosis en Chile durante el 20142018. METODOLOGÍA: Estudio transversal observacional analítico que incluye los pacientes notificados con tuberculosis (TB) que ingresaron a tratamiento durante el 2014-2018 en Chile, contenidos en el registro nacional TB. Se determinaron variables demográficas, clínicas y grupos de riesgos asociados a la farmacorresistencia y al tratamiento no exitoso en pacientes con TB mediante regresión logística. RESULTADOS: Entre los años 2014-2018 se notificaron 13.1761 pacientes con TB en Chile, de los cuales 3,4% (n = 445) son farmacorresistentes. El 43,1% de estos son TB resistente a rifampicina (TB-RR), multidrogorresistente (TB-MDR) y extensamente resistente (TB-XDR). Los factores de riesgo que generaron mayor probabilidad de presentar farmacorresistencia fueron la recaída (OR: 4,27; IC 95% 2,94; 6,20), extranjero (OR: 3,97; IC 95% 2,86; 5,52), TB pulmonar (OR: 2,92; IC 95% 1,71; 4,99) y VIH (OR: 1,97; IC 95% 1,33; 2,90). Frente a la probabilidad de generar un tratamiento no exitoso, las variables que presentaron mayor probabilidad fueron situación de calle (OR: 3,33; IC 95% 2,45; 4,52), drogadicción (OR: 1,91; IC 95% 1,52; 2,41), extranjero (OR: 1,51; IC: 95% 1,25; 1,83), farmacorresistencia (OR: 2,81; IC 95% 1,87; 4,20), VIH (OR: 3,24; IC: 95% 2,61; 4,02), no pertenecer a un pueblo indígena (OR: 1,43; IC: 95% 1,00; 2,06) alcoholismo (OR: 1,25; IC 95% 1,01; 1,54), TB pulmonar (OR: 1,43; IC 95% 1,20; 1,70) y sexo masculino (OR: 1,44; IC 95% 1,25; 1,65). CONCLUSIONES: Los factores de riesgo identificados como la recaída y la coinfección con VIH como predictores de farmacorresistencia destaca la complejidad del manejo de la enfermedad. Asimismo, la presencia de situaciones de calle, drogadicción y alcoholismo resalta la necesidad de enfoques específicos y personalizados para abordar la tuberculosis en distintos grupos poblacionales. Estos resultados subrayan la importancia de abordar estos factores de riesgo en la gestión y tratamiento de la tuberculosis en Chile, sugiriendo la necesidad de estrategias específicas y personalizadas.

OBJECTIVE: Determine the risk factors associated with drug resistance and unsuccessful treatment of tuberculosis in Chile between 2014 and 2018. METHODOLOGY: Analytical observational cross-sectional study including patients diagnosed with Tuberculosis (TB) who entered treatment during 2014-2018, contained in the national TB records. Demographic, clinical variables, and risk groups associated with drug resistance and unsuccessful treatment in TB patients were determined using logistic regression. RESULTS: Between 2014 and 2018, 13,1761 TB patients were reported in Chile, of whom 3.4% (n = 445) were drug-resistant. From this, 43.1% are rifampicin-resistant TB (RR-TB), multidrug-resistant (MDR-TB), and extensively drug-resistant (XDR-TB). The risk factors that generated the highest probability of drug resistance were relapse (OR: 4.27; CI95% 2.94; 6.20), foreigner (OR: 3.97; CI95% 2.86; 5.52), pulmonary TB (OR: 2.92; CI95% 1.71; 4.99) and HIV (OR: 1.97; CI: 95% 1.33; 2.90). Regarding the probability of unsuccessful treatment against TB, the highest probability were street situation (OR: 3.33; CI: 95% 2.45; 4.52), drug addiction (OR: 1.91; CI 95% 1.52; 2.41), foreigner (OR: 1.51; CI 95% 1.25; 1.83), drug resistance (OR: 2.81; CI 95% 1.87; 4.20), HIV (OR: 3.24; CI: 95% 2.61; 4.02), not belonging to an indigenous people (OR: 1.43; CI 95% 1.00; 2.06) alcoholism (OR: 1.25; CI 95% 1.01; 1.54), pulmonary TB (OR: 1.43; CI 95% 1.20; 1.70) and male sex (OR: 1.44; CI 95% 1.25; 1.65). CONCLUSIONS: The risk factors identified as relapse and coinfection with HIV as predictors of drug resistance highlight the complexity of disease management. Likewise, the presence of street situations, drug addiction, and alcoholism highlights the need for specific approaches to address tuberculosis in different population groups, suggesting the need for personalized strategies.

Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients / 中华流行病学杂志

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

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.

The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.

Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

An improved extraction and nonradioactive thin-layer chromatography detection method of mycolic acid / 生物工程学报

Mycolic acids (MAs), i.e. 2-alkyl, 3-hydroxy long-chain fatty acids, are the hallmark of the cell envelope of Mycobacterium tuberculosis and are related with antibiotic resistance and host immune escape. Nowadays, they've become hot target of new anti-tuberculosis drugs. There are two main methods to detect MAs, 14C metabolic labeling thin-layer chromatography (TLC) and liquid chromatograph mass spectrometer (LC-MS). However, the user qualification of 14C or the lack of standards for LC-MS hampered the easy use of this method. TLC is a common way to analyze chemical substance and can be used to analyze MAs. In this study, we used tetrabutylammonium hydroxide and methyl iodide to hydrolyze and formylate MAs from mycobacterium cell wall. Subsequently, we used diethyl ether to extract methyl mycolate. By this method, we can easily extract and analyze MA in regular biological labs. The results demonstrated that this method could be used to compare MAs of different mycobacterium in different growth phases, MAs of mycobacteria treated by anti-tuberculosis drugs or MAs of mycobacterium mutants. Therefore, we can use this method as an initial validation for the changes of MAs in researches such as new drug screening without using radioisotope or when the standards are not available.

Effectiveness of one-stage total knee arthroplasty in treatment of advanced active knee tuberculosis / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of one-stage total knee arthroplasty (TKA) in the treatment of advanced active knee tuberculosis.@*METHODS@#The clinical data of 38 patients with advanced active knee tuberculosis who received one-stage TKA between January 2011 and December 2020 were retrospectively analyzed. There were 20 males and 18 females. The age ranged from 20 to 84 years, with an average of 52.8 years. The body mass index ranged from 17 to 36 kg/m 2, with an average of 23.05 kg/m 2. The preoperative C reactive protein (CRP) was (23.49±4.72) mg/L, erythrocyte sedimentation rate (ESR) was (45.95±8.82) mm/1 h. The Hospital for Special Surgery (HSS) score was 48.8±9.1. During the operation, the infected lesions of the knee joint were completely removed, and the operative area was repeatedly soaked with 3% hydrogen peroxide solution and 0.5% povidone iodine solution. The intraoperative pathological examination confirmed the tuberculosis of the knee joint, and systemic anti-tuberculosis treatment was performed. The operation time, postoperative hospitalization stay, postoperative anti-tuberculosis chemotherapy time, and complications were recorded. CRP and ESR were recorded and compared before and after operation. Anteroposterior and lateral X-ray films of the knee joint were taken to evaluate whether the prosthesis had signs of loosening and sinking, and to determine whether there was recurrence of tuberculosis. The knee joint function was evaluated by HSS score. With treatment failure due to any reason as the end event, the survival time of prosthesis was analyzed by Kaplan-Meier survival curve.@*RESULTS@#All operations were successfully completed without fracture, vascular and nerve injury, deep vein thrombosis, and other complications. All incisions healed by first intention after operation. The operation time ranged from 80 to 135 minutes, with an average of 102.76 minutes; postoperative hospitalization stay was 5-16 days, with an average of 9.7 days; the duration of postoperative anti-tuberculosis chemotherapy ranged from 1 to 18 months, and the median duration was 12 months. All 38 cases were followed up 3-133 months (mean, 63.7 months). At last follow-up, CRP was (4.88±1.24) mg/L and ESR was (13.00±2.97) mm/1 h, both of which were significantly lower than those before operation ( t=20.647, P<0.001; t=20.886, P<0.001). During the follow-up, 3 patients (7.89%) had tuberculosis recurrence. Two patients had tuberculosis recurrence due to withdrawal of anti-tuberculosis chemotherapy at 1 and 2 months after operation, respectively. One patient was cured after debridement, preservation of prosthesis and anti-tuberculosis chemotherapy for 12 months, and 1 patient was cured after oral administration of anti-tuberculosis drugs for 12 months. Another 1 patient had recurrent tuberculosis and mixed infection ( Corynebacterium gehreni) at 2 months after operation, and the infection was not controlled after debridement, and finally the thigh was amputated. Except for the patients with recurrent infection, no complications such as prosthesis loosening, periprosthetic fracture, and periprosthetic infection were found. At last follow-up, the HSS score of the knee joint was 86.8±4.8, and the knee joint function significantly improved when compared with that before operation ( t=-31.198, P<0.001). Prosthesis survival time was (122.57±5.77) months [95% CI (111.25, 133.88) months], and the 10-year survival rate was 92.1%.@*CONCLUSION@#One-stage TKA combined with postoperative antituberculous chemotherapy in the treatment of advanced active knee tuberculosis can achieve satisfactory infection control and joint function.

Tuberculosis preventive practices among treatment supporters in Lagos, Nigeria

Context: Tuberculosis (TB) treatment support is one of the recommended strategies to enhance treatment adherence and outcomes. Treatment supporters are at risk of contracting TB and adequate knowledge of TB and good preventive practices are required for their protection. Aims: This study aimed at assessing the knowledge and preventive practices of TB treatment supporters at Directly Observed Treatment Short-course (DOTS) centers in Lagos Mainland Local Government Area of Lagos state, Nigeria. Settings and design: This cross-sectional study was conducted among 196 TB treatment supporters selected from five DOTS centers in Lagos. Methods: Data were obtained using an adapted pretested questionnaire. Statistical analysis used: Bivariate and multivariate analyses were performed to determine the factors associated with self-protection practices. A P < 0.05 was considered statistically significant. Results: The mean age of the participants was 37.3 ± 12.1 years. More than half of the respondents were females (59.2%) and immediate family members (61.3%). Overall, 22.5% had good knowledge of TB, while 53.0% had positive attitudes toward TB. Only 26.0% adequately protected themselves from infection. The caregiver's level of education (P = 0.001) and their relationship to the patient (P = 0.001) were significantly associated with good preventive practices in bivariate analysis. Not being related to the patient was a predictor of adequate TB prevention practices (adjusted odds ratio = 2.852; P = 0.006; 95% confidence interval = 1.360-5.984). Conclusions: This study revealed low levels of TB knowledge and fair preventive practices, especially among caregivers who are relatives. There is, therefore, a need to improve population literacy about TB and its prevention and a more focused orientation of relatives who volunteer as treatment supporters, through health education, with periodic monitoring during clinic visits, of how they prevent TB.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

Factors of abandonment of tuberculosis treatment in the public health network / Factores de abandono al tratamiento de la tuberculosis en la red pública de salud

ABSTRACT This study determines the factors of abandonment of tuberculosis treatment in the public health network of Cali, Colombia, during years 2016 to 2018. We conducted an operational case-control investigation including 224 patients with tuberculosis (112 abandoned treatment and 112 completed it). We found that treatment abandonment for tuberculosis is driven by factors related to the individuals and health services that facilitate non-adherence and drive them away from the care provided in medical institutions.

RESUMEN Este estudio determina los factores de abandono al tratamiento de la tuberculosis en la red pública de salud de Cali, Colombia, durante los años 2016 a 2018. Se realizó una investigación operativa de casos y controles en la que se incluyeron 224 pacientes con tuberculosis (112 abandonaron el tratamiento y 112 lograron completarlo). Se encuentra que el abandono del tratamiento para la tuberculosis está impulsado por factores relacionados con el individuo y los servicios de salud que facilitan la no adherencia y los alejan de la atención brindada en las instituciones médicas.

Avances en tuberculosis en el 54° congreso chileno de enfermedades respiratorias. 1ra parte: nuevos esquemas acortados para tuberculosis drogoresistente ¿son adecuados para todos? / New shortened schemes for drug-resistant tuberculosis: are they suitable for everyone?

En esta presentación se realiza un recorrido a través de los diferentes esquemas terapéuticos de la tuberculosis drogo-resistente. Se muestra como los investigadores utilizan los nuevos fármacos disponibles y desarrollan diferentes esquemas cada vez más acortados y de administración por vía oral exclusiva, con la intención de lograr una mayor eficacia de curación de la tuberculosis resistente, con menos efectos colaterales y menor letalidad. La búsqueda de esquemas con una duración similar a las terapias de casos sensibles de tuberculosis (esquemas primarios de 6 meses) es el objetivo principal. Las pruebas moleculares como el Xpert ayudan enormemente a seleccionar los esquemas de terapia, según el perfil de susceptibilidad de los casos (resistencia a isoniazida, rifampicina, fluorquinolonas y combinaciones). Las terapias actuales de la tuberculosis drogo-resistente se basan en nuevos fármacos como fluorquinolonas, bedaquilina y linezolid, pero otros fármacos como pretomanid y delamanid también están siendo recomendados.

This presentation takes a tour through the different therapeutic schemes of drug-resistant tuberculosis. It shows how researchers use the new drugs available and develop different increasingly shortened schedules and exclusive oral administration, with the intention of achieving greater efficacy in curing resistant tuberculosis, with fewer side effects and lower lethality. The search for regimens with a duration similar to therapies of sensitive cases of tuberculosis (primary regimens of 6 months) is the main objective. Molecular tests, such as Xpert, greatly help in selecting therapy regimens, according to the susceptibility profile of the cases (resistance to isoniazid, rifampicin, fluorquinolones and combinations). Current drug-resistant tuberculosis therapies are based on new drugs such as fluorquinolones, bedaquiline and linezolid, but other drugs such as pretomanid and delamanid are also being recommended.

Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Tuberculosis pulmonar y laríngea: una forma poco frecuente de presentación en la edad pediátrica / Pulmonary and laryngeal tuberculosis: a rare presentation in pediatrics / Tuberculose pulmonar e laríngica: uma apresentação pouco frequente na idade pediátrica

Introducción: la tuberculosis (TB) es una enfermedad infectocontagiosa granulomatosa crónica, producida por Mycobacterium tuberculosis. En Uruguay se ha notificado un aumento en el número de casos, con una incidencia reportada en 2017 de 28,6/100.000 habitantes, siendo de 6,67/100.000 en menores de 15 años. La tuberculosis laríngea es una forma poco frecuente y evolucionada de tuberculosis, que suele manifestarse con disfonía crónica. Su diagnóstico requiere un alto índice de sospecha. Objetivo: describir un caso clínico de presentación poco frecuente en la edad pediátrica. Caso clínico: adolescente de 13 años, sana, vacunas vigentes, con antecedentes de conductas sexuales activas y papilomatosis laríngea diagnosticada por laringoscopía directa como causa de disfonía crónica. Consulta en emergencia por dolor abdominal, constatándose al examen clínico adelgazamiento asociado a síntomas respiratorios y síndrome tóxico bacilar asociado a disfonía crónica de cuatro meses de evolución, por lo cual se plantea tuberculosis laríngea e ingresa para estudio. Niega contacto de tuberculosis. En la radiografía de tórax se constata lesión cavernosa en vértice pulmonar izquierdo. Las baciloscopías de esputo fueron positivas (directo y cultivo) confirmando el planteo de TB pulmonar y laríngea. Se realizó tratamiento antituberculoso supervisado con excelente evolución posterior. Conclusiones: la tuberculosis es una enfermedad reemergente en nuestro país, que requiere un alto índice de sospecha. Su diagnóstico sigue siendo un desafío para los pediatras ya que la confirmación diagnóstica no siempre es posible. En este caso clínico la sospecha clínica frente a una disfonía crónica asociada a síntomas respiratorios fue fundamental para establecer el diagnóstico, a pesar de no contar con nexo epidemiológico.

Introduction: tuberculosis (TB) is an infectious, chronic granulomatous disease caused by Mycobacterium tuberculosis. An increase in the number of cases has been reported in Uruguay, with an incidence reported in 2017 of 28.6/100,000 inhabitants, being 6.67/100,000 in children under 15 years of age. Laryngeal tuberculosis is a rare and evolved form of tuberculosis, which usually shows chronic dysphonia, which requires high levels of suspicion. Objective: to describe a clinical case with a rare presentation in pediatric age. Clinical case: 13-year-old female adolescent, healthy, fully vaccinated, with a history of active sexual behaviors and laryngeal papillomatosis diagnosed by direct laryngoscopy as a cause of chronic dysphonia. The emergency consultation was caused by abdominal pain, confirming the clinical examination weight loss associated with respiratory symptoms and bacillary toxic syndrome associated with chronic dysphonia of four months of evolution, for which laryngeal tuberculosis was considered and she was admitted for screening. She denies having been in contact with tuberculosis. The chest X-ray revealed a cavernous lesion in the left pulmonary apex and sputum smears were positive (direct and culture), confirming the suggestion of pulmonary and laryngeal TB. Supervised anti-tuberculosis treatment was performed with excellent subsequent evolution. Conclusions: tuberculosis is a re-emerging disease in our country, which requires a high level of suspicion. Its diagnosis remains a challenge for pediatricians since diagnostic confirmation is not always possible. In this clinical case, clinical suspicion of chronic dysphonia associated with respiratory symptoms were key factors to establish the diagnosis, despite not having a clear epidemiological link.

Introdução: a tuberculose (TB) é uma doença infecciosa granulomatosa crônica causada pelo Mycobacterium tuberculosis. No Uruguai, houve aumento do número de casos notificados, com uma incidência notificada em 2017 de 28,6/100.000 habitantes, sendo 6,67/100.000 casos de menores de 15 anos. A tuberculose laríngea é uma forma rara e evoluída de tuberculose, que geralmente se manifesta com disfonia crônica, exigindo alto índice de suspeita. Objetivo: descrever um caso clínico de apresentação pouco frequente em idade pediátrica. Caso clínico: menina adolescente de 13 anos, saudável, totalmente vacinada, com história de comportamentos sexuais ativos e papilomatose laríngea diagnosticada por laringoscopia direta como causa de disfonia crônica. Consulta de urgência por dor abdominal, comprovando emagrecimento associado a sintomas respiratórios e síndrome bacilar tóxica associada a disfonia crônica de quatro meses de evolução, para a qual foi considerada tuberculose laríngea e a paciente foi internada para estudo. Ele nega contato com tuberculose. A radiografia de tórax revelou lesão cavernosa em ápice pulmonar esquerdo e as baciloscopias de escarro foram positivas (direta e cultura) confirmando a sugestão de TB pulmonar e laríngea. O tratamento antituberculose supervisionado foi realizado com excelente evolução subsequente. Conclusões: a tuberculose é uma doença reemergente em Uruguai e requer alto índice de suspeita. Seu diagnóstico permanece um desafio para o pediatra, pois a confirmação diagnóstica nem sempre é possível. Neste caso clínico, a suspeita clínica de disfonia crônica associada a sintomas respiratórios foi fundamental para o estabelecimento do diagnóstico, apesar de não ter vínculo epidemiológico.

Clinical and epidemiological features of tuberculosis isolated from critically ill patients / Tuberculosis en la unidad de cuidados intensivos: características clínicas y epidemiológicas

Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p;<;0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p;<;0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.

La tuberculosis (TB) aún representa un problema mayor de salud pública. En Uruguay, contrariamente a la tendencia mundial, se ha observado un incremento en el número de casos desde 2006. Aunque la incidencia de casos de multidrogorresistencia (MDR) es baja y no se han reportados casos de resistencia a fármacos de primera y segunda línea de tratamiento (XDR), se ha observado un incremento en el número de casos con TB grave, que requieren internación en unidad de terapia intensiva (CTI). Como primer objetivo del presente trabajo, se analizó la estructura genética de cepas de Mycobacterium tuberculosis aisladas de pacientes internados en CTI. Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad. Observamos un incremento estadísticamente significativo del genotipo Haarlem en los pacientes internados en CTI (53,3 vs. 34,7%; p;<;0,05). Además, investigamos la asociación del desenlace clínico con el genotipo, y encontramos una mayor incidencia de disfunción hepática en los pacientes infectados con la cepa Haarlem (p;<;0,05). La cohorte presentada en este trabajo corresponde a una de las series con mayor número de pacientes con tuberculosis que requirieron internación en CTI.

Eritema indurado de Bazin como una reactivación de una tuberculosis latente en una paciente con tratamiento biológico anti-factor de necrosis tumoral / Erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient receiving anti-tumor necrosis factor treatment

Resumen El eritema indurado de Bazin es una tuberculosis cutánea rara, considerada una tuberculide o reacción de hipersensibilidad a Mycobacterium tuberculosis. El tratamiento con agentes biológicos es un factor de riesgo conocido para la reactivación de tuberculosis, especialmente en áreas de alta incidencia como Latinoamérica, por lo que existen protocolos de búsqueda y tratamiento antes del inicio de este tipo de terapias. Se presenta un caso clínico de eritema indurado de Bazin como reactivación de una infección tuberculosa latente en una paciente con artritis reumatoide que recibía tratamiento con golimumab.

Abstract Erythema induratum of Bazin is a rare form of cutaneous tuberculosis, considered as part of the spectrum of tuberculids or hipersensitivity reactions to Mycobacterium tuberculosis. Treatment with biologic agents is a known risk factor for tuberculosis reactivation, especially in areas of high incidence like Latin America, which is why screening and treatment protocols must be followed before these therapies are initiated. We present a case of erythema induratum of Bazin as a reactivation of latent tuberculosis infection in a patient with rheumatoid arthritis treated with golimumab.

Construction of EF-G knockdown strain of Mycobacterium smegmatis and drug resistance analysis / 生物工程学报

As the only translational factor that plays a critical role in two translational processes (elongation and ribosome regeneration), GTPase elongation factor G (EF-G) is a potential target for antimicrobial agents. Both Mycobacterium smegmatis and Mycobacterium tuberculosis have two EF-G homologous coding genes, MsmEFG1 (MSMEG_1400) and MsmEFG2 (MSMEG_6535), fusA1 (Rv0684) and fusA2 (Rv0120c), respectively. MsmEFG1 (MSMEG_1400) and fusA1 (Rv0684) were identified as essential genes for bacterial growth by gene mutation library and bioinformatic analysis. To investigate the biological function and characteristics of EF-G in mycobacterium, two induced EF-G knockdown strains (Msm-ΔEFG1(KD) and Msm-ΔEFG2(KD)) from Mycobacterium smegmatis were constructed by clustered regularly interspaced short palindromic repeats interference (CRISPRi) technique. EF-G2 knockdown had no effect on bacterial growth, while EF-G1 knockdown significantly retarded the growth of mycobacterium, weakened the film-forming ability, changed the colony morphology, and increased the length of mycobacterium. It was speculated that EF-G might be involved in the division of bacteria. Minimal inhibitory concentration assay showed that inhibition of EF-G1 expression enhanced the sensitivity of mycobacterium to rifampicin, isoniazid, erythromycin, fucidic acid, capreomycin and other antibacterial agents, suggesting that EF-G1 might be a potential target for screening anti-tuberculosis drugs in the future.