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.

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 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.

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.

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.

Tuberculosis congénita - el desafío parte con la madre / Congenital tuberculosis - the challenge starts with the mother

La tuberculosis es la enfermedad infecciosa por un solo agente que provoca más muertes en el mundo. A la fecha, no hay un registro de casos de embarazadas con tuberculosis en el mundo ni en Chile, y menos de los casos de tuberculosis congénita. El diagnóstico en ambas situaciones suele ser tardío y con malos resultados clínicos. Se presenta una revisión de la literatura con relación a tuberculosis perinatal y dos casos clínicos de los binomios madre e hijo afectados.

Tuberculosis is the single agent infectious disease that causes the most deaths in the world. To date, there is no record of pregnant women with tuberculosis in the world or in Chile, even less of congenital tuberculosis. Diagnosis in both situations is usually late and with poor clinical results. A literature review is presented in relation to perinatal tuberculosis and two clinical cases of affected mother and child binomials.

Eficiencia del tratamiento de casos nuevos de tuberculosis sensible en Chile / Treatment efficiency in new cases of susceptible tuberculosis in Chile

Resumen La terapia de la tuberculosis con el esquema primario recomendado por la OMS no logra la curación de todos los casos a nivel mundial, pero en general alcanza un éxito de curación de al menos el 85% de los casos en el año 2018. El mismo año en Chile la eficiencia del tratamiento es solo de 76%, principalmente por la alta proporción de muertes y pérdida de seguimiento durante la terapia. Datos preliminares muestran que la cohorte ingresada en 2019 tuvo un éxito de tratamiento cercano a 74%. En Chile los fracasos de tratamiento son infrecuentes, debido principalmente a la vigilancia nacional de la susceptibilidad a fármacos. Para reducir la letalidad es necesario reforzar las estrategias para el diagnóstico precoz de la tuberculosis, mediante nuevos algoritmos que incorporen la biología molecular y la radiología en casos sospechosos de esta enfermedad, fomentar el adecuado manejo de las comorbilidades, establecer una adecuada red de apoyo social y disponer de centros de hospitalización cuando se requieren. Además, se debe fortalecer la adherencia a la terapia de los pacientes con estrategias de incentivo y facilitación de la asistencia.

Tuberculosis therapy with the primary regimen recommended by the World Health Organization does not cure all cases globally, but it reached success in at least 85% of cases in the year 2018. The same year in Chile, treatment efficiency is achieved in only 76%, mainly due to the high proportion of deaths and loss of follow-up during therapy. Preliminary data show that in the 2019 cohort the success was achieved only in about 74% of new cases. Treatment failures in Chile are rare due to national surveillance of drug susceptibility. To reduce fatality, it is necessary to reinforce the strategies for early diagnosis of tuberculosis through new algorithms. Such strategies should include molecular biology and radiology in suspected TB cases, to promote proper management of comorbidities, establish an adequate social support network and have centers available for prolonged hospitalization when needed. In addition, patient's adherence to therapy should be strengthened with strategies that encourage and facilitate attendance.

Clinical outcomes and molecular characterization of drug-resistant tuberculosis in pre- and extensively drug-resistant disease based on line probe assays

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) represents a significant impact in transmission, outcome, and health costs. The World Health Organization recommends implementation of rapid diagnostic methods for multidrug-resistance detection. This study was performed to evaluate the frequency of pre- and extensively drug resistant tuberculosis (pre-XDR-TB and XDR-TB) among MDR-TB patients, the pattern of resistance mutations for fluoroquinolones and the clinical outcome. Adult patients followed at a Brazilian regional reference center for TB, from January 2013 to June 2019 were included. Stored Mycobacterium tuberculosis (Mtb) cultures were recovered, the DNA was extracted, and the susceptibility test was performed using the line probe assay for second line antimycobacterial drugs, Genotype MTBDRsl version 2.0 (Hain Lifescience, CmbH, Germany). Among 33 MDR-TB included patients, we diagnosed XDR-TB or pre-XDR in five (15%) cases. Of these, mutations related to fluoroquinolones resistance were observed in four Mtb isolates, including one who had no phenotypic resistance profile. In two other patients with phenotypic resistance to ofloxacin, genotypic resistance was not found. Case fatality rate was 60% in pre/XDR-TB group, compared to 3.6% in the remaining of patients. This study observed few cases of pre-XDR and XDR-TB among a MDR-TB cohort. Phenotypic and genotypic assays presented good agreement. Clinical outcome was more favorable for patients with susceptibility to fluoroquinolones and injectable drugs.

Drug-Resistant Mycobacterium tuberculosis Isolates from New and Previously Treated TB Patients in China, 2017-2019

Abstract INTRODUCTION: Mycobacterium tuberculosis (MTB) is a causative agent of tuberculosis (TB) that causes death worldwide. METHODS: MTB was subjected to phenotypic drug-susceptibility tests (DST), and drug-resistant genes were sequenced. RESULTS: Previously treated patients were more likely to have positive smear results and exhibit drug resistance. New patients were more likely to be mono SM-resistant and less likely to be INH- and RIF-resistant. The most common mutations were katG (S315T), rpoB (S450L), rpsL (K43R), and embB (M306V). CONCLUSIONS: The proportion of mono-SM-resistant TB among new patients was higher.

Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of / 生物医学与环境科学（英文）

Objective@#To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the @*Methods@#MDR-LAMP assay was evaluated using 100 @*Results@#The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of @*Conclusion@#MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of

A case of tuberculosis verrucosa cutis in Brazil undiagnosed for 15 years

ABSTRACT Tuberculosis verrucosa cutis is a rare medical condition that is caused by the inoculation of Mycobacterium tuberculosis into the skin of a previously sensitized individual. This clinical form of tuberculosis corresponds to 1-2% of all cases of tuberculosis and due to the paucibacillary characteristic of the lesions, patients can be misdiagnosed, accounting for the chronification of the skin infection. Herein, we report the case of a 26-year-old male farmer, presenting plaques with verrucosa and hyperkeratosis features in the left thigh and buttocks during 15 years. M. tuberculosis was identified by PCR and the patient was treated with standard anti-tuberculosis drugs, with subsequent improvement of the skin lesions.

Fatores associados à subnotificação de casos de tuberculose multirresistente no Estado do Rio de Janeiro, Brasil: relacionamento probabilístico entre sistemas de informação / Factors associated with underreporting of cases of multidrug-resistant tuberculosis in the state of Rio de Janeiro, Brazil: probabilistic database linkage / Factores asociados a la subnotificación de casos de tuberculosis resistente a múltiples fármacos en el estado de Río de Janeiro, Brasil: relación probabilística entre sistemas de información

Neste estudo, estimou-se a proporção e os fatores associados à subnotificação da tuberculose multirresistente (TB-MDR) no Estado do Rio de Janeiro, Brasil, assim como a proporção de óbitos nesse grupo. Realizou-se um estudo de coorte retrospectiva, utilizando a técnica de relacionamento probabilístico entre sistemas de informação. Os casos com resultado do teste de sensibilidade às drogas (TSA) com padrão TB-MDR registrados no Sistema Gerenciador de Ambiente Laboratorial (GAL), no período 2010 a 2017, foram relacionados com casos notificados no Sistema de Tratamentos Especiais de Tuberculose (SITETB). Regressões logísticas simples e múltipla foram realizadas para estimar os fatores associados à subnotificação. Para verificar o óbito, foi realizada a busca dos casos no Sistema de Informações sobre Mortalidade (SIM) e no portal do Tribunal de Justiça do Estado do Rio de Janeiro. Dos 651 casos TB-MDR no GAL, 165 não haviam sido notificados no SITETB, perfazendo uma subnotificação de 25,4% na amostra. Entre os casos subnotificados, 61 (37%) foram encontrados nos registros de óbito. Na análise múltipla, ter o exame solicitado por um hospital (OR = 2,86; IC95%: 1,72-4,73) esteve associado à subnotificação. No geral, o tempo médio entre a solicitação do exame e a liberação do resultado foi de 113 dias. Entre os casos notificados, o tempo médio entre a solicitação do exame e o início do tratamento foi de 169 dias. Diante disso, é urgente fortalecer as ações de vigilância epidemiológica na TB-MDR, estabelecer e monitorar núcleos de vigilância hospitalar e as rotinas de notificação de TB nos hospitais, rever etapas operacionais, além de unificar os diversos sistemas de informação tornando-os mais ágeis e integrados.

This study estimated the proportion of underreporting of multidrug-resistant tuberculosis (MDR-TB) and associated factors in the State of Rio de Janeiro, Brazil, as well as the proportion of deaths in this group. A retrospective cohort study was conducted using probabilistic database linkage. Cases with the results of the drug sensitivity test (DST) with MDR-TB pattern recorded in the Laboratory Environment Management System (GAL) from 2010 to 2017 were linked to cases reported to the Special TB Treatments System (SITETB). Simple and multiple logistic regressions were performed to estimate factors associated with underreporting. Death was verified by search for cases in the Mortality Information System (SIM) and in the portal of the Rio de Janeiro State Court of Justice. Of the 651 cases of MDR-TB in the GAL, 165 had not been reported to the SITETB, meaning an underreporting rate of 25.4% in the sample. Among the unreported cases, 61 (37%) were identified in the death records. In the multiple analysis, the fact that the test was ordered by a hospital (OR = 2.86; 95%CI: 1.72-4.73) was associated with underreporting. Overall, the mean turnaround time between ordering the test and releasing the result was 113 days. Among reported cases, the mean time between ordering the test and initiating treatment was 169 days. The results underline the urgent need to strengthen epidemiological surveillance activities for MDR-TB, establish and monitor hospital surveillance centers and routine TB reporting in hospitals, review operational stages, and integrate various information systems to make them more agile and integrated.

En este estudio se estimó la proporción y los factores asociados a la subnotificación de la tuberculosis resistente a múltiples fármacos (TB-MDR) en el Estado de Río de Janeiro, Brasil, así como la proporción de óbitos en ese grupo. Se realizó un estudio de cohorte retrospectiva, utilizando la técnica de relación probabilística entre sistemas de información. Los casos con resultado del test de sensibilidad a las drogas (TSA) con patrón TB-MDR, registrados en el Sistema Gerenciador de Ambiente Laboratorial (GAL), en el período 2010 a 2017, se relacionaron con casos notificados en el Sistema de Tratamientos Especiales de Tuberculosis (SITETB). Se realizaron regresiones logísticas simples y múltiples para estimar los factores asociados a la subnotificación. Para verificar el óbito, se realizó la búsqueda de los casos en el Sistema de Información sobre Mortalidad (SIM) y en el portal del Tribunal de Justicia del Estado de Río de Janeiro. De los 651 casos TB-MDR en el GAL, 165 no habían sido notificados en el SITETB, lo que equivale a una subnotificación de un 25,4% en la muestra. Entre los casos subnotificados, 61 (37%) se encontraron en los registros de óbito. En el análisis múltiple, que el examen haya sido solicitado por un hospital (OR = 2,86; IC95%: 1,72-4,73) estuvo asociado a la subnotificación. En general, el tiempo medio entre la solicitud del examen y la llegada del resultado fue de 113 días. Entre los casos notificados, el tiempo medio entre la solicitud del examen y el inicio del tratamiento fue de 169 días. Ante esto, es urgente fortalecer las acciones de vigilancia epidemiológica en la TB-MDR, establecer y supervisar núcleos de vigilancia hospitalaria y las rutinas de notificación de TB en los hospitales, revisar etapas operacionales, además de unificar los diversos sistemas de información haciéndolos más ágiles e integrados.

Trends in primary multidrug-resistant tuberculosis in the State of Rio de Janeiro: a retrospective study conducted during 2000-2019

Abstract INTRODUCTION: We analyzed the trends in primary multidrug-resistant tuberculosis (MDR-TB). METHODS: We performed a time series analysis of primary MDR-TB cases reported in the State of Rio de Janeiro (RJ) during 2000-2019. The annual percent change and the average annual percentage change (AAPC) were computed using joinpoint regression analysis. RESULTS: The percentage of cases increased from 7.69% in 2000 to 38.42% in 2018. We observed an upward trend during this period (AAPC = 9.4; 95% confidence interval 1.4-18.0, p < 0.001). CONCLUSIONS: The trend indicates the increasing occurrence of MDR-TB transmission sources in RJ during 2000-2019.

Unilateral choroidal tuberculoma as an initial manifestation of presumed ocular tuberculosis: a case report / Tuberculoma coroidal unilateral como manifestação inicial de tuberculose ocular presumida: relato de caso

ABSTRACT Choroidal tuberculomas are present in patients with ocular tuberculosis. They usually occur in a patient with previous history of tuberculosis, and are rarely the initial presentation, with no prior systemic manifestations. We present a patient with unilateral choroidal tuberculoma as the initial presentation of presumed ocular tuberculosis, which enabled earlier initiation of treatment.

RESUMO Os tuberculomas de coroide apresentam-se em pacientes com tuberculose ocular. Geralmente, ocorrem em indivíduos com história prévia de tuberculose e raramente têm apresentação inicial sem manifestações sistêmicas anteriores. Relatamos o caso de um paciente com tuberculoma de coroide unilateral com apresentação inicial de tuberculose ocular presumida, permitindo o início mais precoce do tratamento.

Factores de éxito del tratamiento de la tuberculosis multidrogorresistente relacionados con el paciente y el personal sanitario en Colombia / Patient- and provider-related factors in the success of multidrug tuberculosis treatment in Colombia / Fatores de êxito do tratamento da tuberculose multirresistente relacionados com o paciente e com a equipe de saúde na Colômbia

RESUMEN Objetivo. Identificar los factores asociados con el éxito del tratamiento de tuberculosis multidrogorresistente (TB-MDR) relacionados con los pacientes y el personal sanitario en seis municipios de Colombia con mayor número de casos. Métodos. Mediante regresiones logísticas bifactorial y multifactorial se analizó la asociación entre el tratamiento exitoso (curación o cumplimiento del tratamiento) y las características de los pacientes, y de los médicos, profesionales de enfermería y psicólogos vinculados al tratamiento. Se exploró la importancia del conocimiento en el manejo de los casos de TB-MDR mediante grupos focales con esos profesionales. Resultados. De los 128 casos con TB-MDR, 63 (49,2%) tuvieron un tratamiento exitoso. Solo 52,9% de los médicos y profesionales de enfermería tenía conocimientos satisfactorios sobre TB-MDR. La regresión logística mostró que ser negativo al VIH, estar afiliado al régimen de aseguramiento de salud contributivo, estar atendido por un médico del sexo masculino y por profesionales de enfermería con conocimientos suficientes se asociaron con un desenlace exitoso del tratamiento (p ≤ 0,05). El análisis cualitativo mostró la necesidad de profundizar y sistematizar la capacitación del personal sanitario que atiende los casos de TB-MDR. Conclusiones. En el éxito del tratamiento de los casos de TB-MDR influyen algunas características de los pacientes y el personal sanitario. Se requiere fortalecer los conocimientos sobre TB-MDR de médicos y enfermeros, y reforzar el seguimiento de los pacientes con TB-MDR positivos al VIH y de los que pertenecen al régimen subsidiado, dada su menor probabilidad de éxito al tratamiento.

ABSTRACT Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusions. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians' and nurses' knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

RESUMO Objetivo. Identificar os fatores associados ao êxito do tratamento da tuberculose multirresistente (TBMR) relacionados ao paciente e à equipe de saúde nos seis municípios da Colômbia com o maior número de casos. Métodos. Mediante regressão logística bifatorial e multifatorial, analisou-se a associação entre o êxito do tratamento (cura ou completude do tratamento) e as características dos pacientes e dos médicos, profissionais de enfermagem e psicólogos envolvidos neste. Explorou-se a importância do conhecimento no manejo de casos de TBMR mediante grupos focais com os mesmos profissionais. Resultados. Dos 128 casos de TBMR, 63 (49.2%) lograram êxito no tratamento. Somente 52.9% dos médicos e profissionais de enfermagem tinham conhecimentos satisfatórios sobre TBMR. A regressão logística demonstrou que soronegatividade para o HIV, cobertura pelo sistema de saúde sob o regime de contribuinte, atendimento por um médico do sexo masculino e atendimento por profissionais de enfermagem com conhecimento suficiente foram fatores associados ao êxito do tratamento (p ≤ 0,05). A análise qualitativa demonstrou necessidade de aprofundar e sistematizar a capacitação do pessoal de saúde que atende casos de TBMR. Conclusões. Algumas características do paciente e da equipe de saúde influenciam no êxito do tratamento de casos de TBMR. É preciso fortalecer os conhecimentos dos médicos e profissionais de enfermagem sobre a TBMR e reforçar o seguimento dos pacientes com TBMR que vivem com HIV e os filiados ao sistema de saúde colombiano pelo regime subsidiado, os quais têm menor probabilidade de êxito do tratamento.