Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats

Abstract 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 Bonferronis 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.

Resumo 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.

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. 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.

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.

Psoríase vulgar em remissão após profilaxia com isoniazida para tuberculose latente: relato de caso / Psoriasis vulgar in remission after prophylaxis with isoniazid for latent tuberculosis: case report / Psoriasis vulgar en remisión tras profilaxis con isoniazida para tuberculosis latente: reporte de caso

Introdução: A psoríase é uma patologia sistêmica, multifatorial e com lesões cutâneas bem características. Objetivo: Investigar a possibilidade de existir uma correlação entre a infecção latente pelo Mycobacterium tuberculosis e a patogênese da Psoríase, a fim de contribuir com a terapêutica de casos de Psoríase grave ou refratários. Material e Método: Relato de caso de psoríase vulgar não responsiva aos tratamentos de primeira linha, em que a Isoniazida para ILTB induziu à remissão sustentada do quadro clínico. Baseada no caso, foi realizada uma revisão sobre o uso da Isoniazida no tratamento da ILTB nos pacientes com psoríase e que obtiveram regressão das lesões psoriáticas. O estudo utilizou dados da plataforma Pubmed. Resultados: Dos 50 artigos encontrados, 08 foram selecionados para leitura completa. Foram descritos apenas quatro casos como este na literatura internacional. Os achados desse estudo mostram que a possibilidade de existir uma correlação entre a infecção latente pelo Mycobacterium tuberculosis e a patogênese da Psoríase, a fim de contribuir com a terapêutica de casos de Psoríase grave ou refratários, ainda é incerta. Conclusão: Pesquisas mais detalhadas são necessárias para elucidar o real mecanismo dos anti tuberculínicos (especialmente a Isoniazida) no tratamento da Psoríase, quanto a possibilidade de existir uma correlação entre a infecção pelo Mycobacterium tuberculosis e a patogênese da Psoríase. Se isto for comprovado, teremos um grande incremento no arsenal terapêutico destinado aos pacientes com Psoríase grave ou refratários (AU)

Introduction: Psoriasis is a systemic pathology, multifactorial and with well characteristic skin lesions. Objective: To investigate the possibility of a correlation between latent infection by Mycobacterium tuberculosis and the pathogenesis of Psoriasis, in order to contribute to the therapy of severe or refractory Psoriasis cases. Material and Method: Case report of vulgar psoriasis not responsive to first-line treatments, in which Isoniazid for LTBI induced sustained remission of the clinical picture. Based on the case, a review was performed on the use of Isoniazid in the treatment of LTBI in patients with psoriasis and who obtained regression of psoriatic lesions. The study used data from the Pubmed platform. Results: Of the 50 articles found, 08 were selected for full reading. Only four cases like this have been described in the international literature. The findings of this study show that the possibility of a correlation between latent infection by Mycobacterium tuberculosis and the pathogenesis of Psoriasis, in order to contribute to the therapy of severe or refractory Psoriasis cases, is still uncertain. Conclusion: More detailed research is needed to elucidate the real mechanism of anti tuberculins (especially Isoniazid) in the treatment of Psoriasis, the possibility of a correlation between infection by Mycobacterium tuberculosis and the pathogenesis of Psoriasis. If this is proven, we will have a large increase in the therapeutic arsenal for patients with severe or refractory psoriasis (AU)

Introducción: La psoriasis es una patología sistémica, multifactorial, con lesiones cutáneas muy características. Objetivo: Investigar la posibilidad de una correlación entre la infección latente por Mycobacterium tuberculosis y la patogenia de la Psoriasis, con el fin de contribuir al tratamiento de casos severos o refractarios de Psoriasis. Material y Método: Reporte de caso de psoriasis vulgar sin respuesta a tratamientos de primera línea, en el cual Isoniazida para ITBL indujo remisión sostenida del cuadro clínico. En base al caso se realizó una revisión sobre el uso de Isoniazida en el tratamiento de la ITBL en pacientes con psoriasis y que lograron la regresión de las lesiones psoriásicas. El estudio utilizó datos de la plataforma Pubmed. Resultados: De los 50 artículos encontrados, 08 fueron seleccionados para lectura completa. Solo cuatro casos como este han sido descritos en la literatura internacional. Los hallazgos de este estudio muestran que la posibilidad de una correlación entre la infección latente por Mycobacterium tuberculosis y la patogenia de la Psoriasis, para contribuir al tratamiento de casos severos o refractarios de Psoriasis, es aún incierta. Conclusión: Se necesita una investigación más detallada para dilucidar el mecanismo real de los fármacos antituberculínicos (especialmente la Isoniazida) en el tratamiento de la Psoriasis, en cuanto a la posibilidad de una correlación entre la infección por Mycobacterium tuberculosis y la patogenia de la Psoriasis. De demostrarse esto, tendremos un gran incremento en el arsenal terapéutico destinado a pacientes con psoriasis severa o refractaria (AU)

Avalição da eficácia do tratamento profilático com isoniazida na incidência da tuberculose activa em pacientes hiv positivos menores de 15 anos no período de 2021 a 2017 em moçambique / Evaluation of the efficacy of prophylactic treatment with isoniazid on the incidence of active tuberculosis in HIV-positive patients under 15 years of age in the period from 2021 to 2017 in mozambique

Introdução: A Tuberculose (TB) continua sendo um grande problema de saúde pública em Moçambique, constando na lista das principais causas de morte nas nossas unidades sanitárias. A Organização Mundial de Saúde (OMS) recomenda o tratamento profiláctico com isoniazida (TPI) em pessoas infectadas pelo vírus de imunodeficiência humana (HIV) em países com alta carga de doença e escassez de recursos para prevenir casos novos de TB. O TPI é uma estratégia usada para prevenir o desenvolvimento de TB activa em pessoas vivendo com o HIV. Objectivo: Avaliar a eficácia de TPI na prevenção da TB activa em paciente HIV positivos menores de 15 anos de idade, nas Unidades Sanitárias das Províncias de Cabo Delgado e Maputo Província, no período entre 2012 à 2017. Metodologia: Foi realizado um estudo de coorte retrospectivo de pacientes menores de 15 anos de idade que fizeram o TPI e outro grupo de pacientes que não fez o TPI, que estão inscritos nos Serviços TARV e que foram seguidos por um período de 72 meses. Resultados: Dos 7200 pacientes incluídos no estudo, 4945 (68,7%) fizeram o TPI e destes só 3 (0,1%) é que desenvolveram uma TB activa. Dos restantes 2255 que correspondem a 31,3% que não fizeram o TPI, 127 (5,6%) desenvolveram uma TB activa. A Província de Maputo é que teve maior número de pacientes que fizeram TPI com cerca de 78,9% (3906) em relação a Província de Cabo Delgado com cerca de 21,1% (1039/4945). Conclusão: A incidência da TB foi maior no grupo de pacientes que não fez o TPI, com cerca de 5,6 % em relação ao grupo de pacientes que fez o TPI que foi na ordem de 0,1 %. Com base nestas evidências apoiamos o TPI em pacientes HIV positivos. Recomendação: Outros estudos são necessários para responder perguntas cruciais no uso do TPI. Incentivar aos clínicos a rastrear a TB em pacientes menores de 15 anos HIV positivo, e fazer TPI quando apresentar critérios.

Introduction: Tuberculosis (TB) remains a major public health problem in Mozambique, appearing on the list of the main causes of death in our health units. The World Health Organization (WHO) recommends prophylactic treatment with isoniazid (IPT) in people infected with the human immunodeficiency virus (HIV) in countries with a high disease burden and a shortage of resources to prevent new cases of TB. ICT is a strategy used to prevent the development of active TB in people living with HIV. Objective: To evaluate the eficacy of IPT in the prevention of active TB in HIV positive patients under 15 years of age, in the Health Units of the Provinces of Cabo Delgado and Maputo Province, in the period between 2012 and 2017. Methodology: We conducted a retrospective cohort study of patients under 15 years of age who underwent IPT and another group of patients who did not undergo IPT, who are enrolled in ART Services and who were followed for a period of 72 months.. Results: Of the 7200 patients included in the study, 4945 (68.7%) underwent IPT and of these only 3 (0.1%) developed active TB. Of the remaining 2255, corresponding to 31.3% who did not have the ICT, 127 (5.6%) developed active TB. Maputo Province had the highest number of patients who underwent IPT with around 78.9% (3906) compared to Cabo Delgado Province with around 21.1% (1039/4945). Conclusion: The incidence of TB was highest in the group of patients who did not have the TPI, with about 5.6%, in group of patients who had the TPI which was in 0.1% order based on this evidence we support the TPI in HIV positive patients. Recommendation: Further studies are needed to answer crucial questions in the use of ICT. Encourage clinicians to screen for TB in HIV-positive patients under the age of 15 and perform IPT when presenting criteria.

Discourses of health professionals on latent tuberculosis infection and the use of isoniazid / Discursos de profesionales de la salud sobre infección tuberculosis latente y uso de isoniazida / Discursos de profissionais de saúde sobre infecção latente por tuberculose e uso de isoniazida

ABSTRACT Objective to understand the collective thinking and action of health workers in relation to Latent Tuberculosis Infection and its treatment with Isoniazid. Method qualitative study with 22 health professionals from four cities in Brazil and the Federal District. Data collection occurred through a semi-structured group interview in March 2019, with an average duration of one hour and thirty minutes. Content analysis was performed using the Collective Subject Discourse technique. Results the professionals' discourses revealed uncertainties related to the prevention and treatment of Latent Tuberculosis Infection, the "fear of error" and inadequate forms of use of Isoniazid 300 mg, the power of the decision on the treatment of Latent Tuberculosis Infection, the difficulties of integration between services and the organization of care flows. Conclusion although the emphasis in the professionals' discourse considers objective aspects in the management of Latent Tuberculosis Infection, subjective manifestations related to the need to address the fears that affect the decision about treatment and possible medication errors were identified, among others, and to think about this process in a collaborative way, which considers autonomy in acting, both of professionals and of the person with Latent Tuberculosis Infection.

RESUMEN Objetivo comprender el pensamiento y la acción colectiva de los trabajadores de la salud en relación con la Infección Latente de Tuberculosis y el uso de Isoniazida en el enfrentamiento de la enfermedad. Método estudio cualitativo con 22 profesionales de la salud de cuatro ciudades de Brasil y del Distrito Federal. La recolección de datos ocurrió a través de una entrevista colectiva semiestructurada, en marzo de 2019, con una duración promedio de una hora y treinta minutos. El análisis de contenido se realizó mediante la técnica del Discurso del Sujeto Colectivo. Resultados los discursos de los profesionales revelaron incertidumbres relacionadas con la prevención y el tratamiento de la Infección Tuberculosa Latente, el "miedo a equivocarse" y las formas inadecuadas de uso de Isoniazida 300 mg, el poder de decisión sobre el tratamiento de la Infección Tuberculosa Latente, las dificultades para la integración de servicios y la organización de los flujos de atención. Conclusión aunque el énfasis en el discurso de los profesionales considera aspectos objetivos en el manejo de la Infección Tuberculosa Latente, se identificaron manifestaciones subjetivas relacionadas con la necesidad de abordar los miedos que afectan la decisión sobre el tratamiento y posibles errores de medicación, entre otros, y pensar sobre este proceso de forma colaborativa, que considera la autonomía de actuación, tanto de los profesionales como de la persona con Infección Tuberculosa Latente.

RESUMO Objetivo compreender o pensar e o agir coletivo de trabalhadores da saúde em relação à Infecção Latente por Tuberculose e ao uso da Isoniazida no enfrentamento da doença. Método estudo qualitativo com 22 profissionais de saúde de quatro cidades do Brasil e do Distrito Federal. A coleta de dados ocorreu mediante realização de entrevista coletiva semiestruturada, em março de 2019, com duração média de uma hora e trinta minutos. Realizou-se análise de conteúdo pela técnica do Discurso do Sujeito Coletivo. Resultados os discursos dos profissionais revelaram incertezas relacionadas à prevenção e ao tratamento da Infecção Latente por Tuberculose, ao "medo de errar" e formas inadequadas de uso da Isoniazida 300 mg, ao poder da decisão sobre o tratamento da Infecção Latente por Tuberculose, às dificuldades da integração entre os serviços e à organização de fluxos assistenciais. Conclusão embora a ênfase no discurso dos profissionais considere aspectos objetivos no manejo da Infecção Latente por Tuberculose, foram identificadas, dentre outras, manifestações subjetivas relacionadas à necessidade de trabalhar os receios que afetam a decisão sobre o tratamento e os possíveis erros de medicação, e de pensar esse processo de forma colaborativa, que considere autonomia no agir, tanto dos profissionais quanto da pessoa com Infecção Latente por Tuberculose.

Pyrazinamide-isoniazid hybrid: synthesis optimisation, characterisation, and antituberculous activity / Híbrido pirazinamida-isoniacida: optimización de síntesis, caracterización y actividad antituberculosa / Híbrido pirazinamida-isoniazida: otimização da síntese, caracterização e atividade antituberculose

Abstract Over time, the effective resistance mechanisms to various first- and second-line drugs against the disease of tuberculosis make its treatment extremely difficult. This work presents a new approach to synthesizing a hybrid of antituberculosis medications: isoniazid (INH) and pyrazinamide (PZA). The synthesis was performed using ultrasound-assisted synthesis to obtain an overall yield of 70%, minimizing the reaction time from 7 to 1 h. The evaluation of the biological activity of the hybrid (compound 2) was tested using the tetrazolium microplate assay (TEMA), showing inhibition in the growth of Mycobacterium tuberculosis H37Rv at a concentration of 0.025 mM at pH 6.0 and 6.7.

Resumen Debido a los grandes mecanismos de resistencia a lo largo del tiempo de diversos fármacos de primera y segunda línea contra la enfermedad de la tuberculosis, el tratamiento sigue dificultándose. Este trabajo presenta un nuevo enfoque para sintetizar un híbrido de fármacos antituberculosos: isoniazida (INH) y pirazinamida (PZA). La síntesis fue asistida por ultrasonido con el fin de obtener un rendimiento global del 70%, minimizando el tiempo de reacción de 7 a ' h. La evaluación de la actividad biológica del híbrido (compuesto 2) se probó usando el ensayo de microplaca de tetrazolio (TEMA), que mostró una inhibición en el crecimiento de Mycobacterium tuberculosis H37Rv a una concentración de 0,025 mM a pH 6,0 y 6,7.

Resumo Devido aos grandes mecanismos de resistência ao longo do tempo a diversos fármacos de primeira e segunda linha contra a tuberculose, o que torna seu tratamento extremamente difícil. Este trabalho apresenta uma nova abordagem para sintetizar um híbrido de fármacos antituberculose: isoniazida (INH) e pirazinamida (PZA) A síntese foi realizada utilizando a síntese assistida por ultrassom de forma a obter um rendimento global de 70%, minimizando o tempo de reação de 7 h para ' h. A avaliação da atividade biológica do híbrido (composto 2) foi testada utilizando o ensaio de microplaca de tetrazólio (TEMA), mostrando uma inibição no crescimento de Mycobacterium tuberculosis H37Rv na concentração de 0,025 mM em pH 6,0 e 6,7.

RDRioMycobacterium tuberculosis strains associated with isoniazid resistance in Northern Mexico.

BACKGROUND: It has been established that the genomic background of Mycobacterium tuberculosis may influence disease progression, in particular for the Beijing family and the Latin American and Mediterranean (LAM)/RDRio strains. The purpose of this study was to evaluate the prevalence of the LAM/RDRio genotype in cases of tuberculosis from Mexico and their drug susceptibility profile. METHODS: Two hundred eighteen M. tuberculosis isolates were screened by 43-spacer spoligotyping. The LAM/RDRio genotype was confirmed by multiplex PCR, and the drug susceptibility testing was carried out in solid Löwenstein-Jensen media. RESULTS: Among the LAM strains identified, 24 (63.1%) were confirmed as M. tuberculosis RDRio. All RDRio strains shared the RD174 deletion, that was associated with isoniazid resistance (p=0.0264). CONCLUSIONS: We documented for the first time the isolation of the LAM/RDRio genotype in pulmonary cases of tuberculosis in Mexico, and we found resistance to the first-line anti-tuberculosis drug isoniazid in these strains.

RDRioMycobacterium tuberculosis strains associated with isoniazid resistance in Northern Mexico / Identificación del genotipo Mycobacterium tuberculosis RDRio en el norte de México y su asociación con la resistencia a isoniazida

Background: It has been established that the genomic background of Mycobacterium tuberculosis may influence disease progression, in particular for the Beijing family and the Latin American and Mediterranean (LAM)/RDRio strains. The purpose of this study was to evaluate the prevalence of the LAM/RDRio genotype in cases of tuberculosis from Mexico and their drug susceptibility profile. Methods: Two hundred eighteen M. tuberculosis isolates were screened by 43-spacer spoligotyping. The LAM/RDRio genotype was confirmed by multiplex PCR, and the drug susceptibility testing was carried out in solid Löwenstein-Jensen media. Results: Among the LAM strains identified, 24 (63.1%) were confirmed as M. tuberculosis RDRio. All RDRio strains shared the RD174 deletion, that was associated with isoniazid resistance (p=0.0264). Conclusions: We documented for the first time the isolation of the LAM/RDRio genotype in pulmonary cases of tuberculosis in Mexico, and we found resistance to the first-line anti-tuberculosis drug isoniazid in these strains.(AU)

Introducción: El genotipo de Mycobacteriumtuberculosis podría influir en la fisiopatología y la evolución de la tuberculosis, en particular los genotipos Beijing y LAM/RDRio. El propósito de este estudio fue evaluar la prevalencia del genotipo LAM/RDRio en casos de tuberculosis pulmonar en México y determinar su perfil de sensibilidad a los fármacos antituberculosos. Métodos: Se evaluaron 218 cepas de M. tuberculosis mediante spoligotyping. El genotipo LAM/RDRio se confirmó mediante PCR múltiple. Las pruebas de sensibilidad a fármacos antituberculosos se realizaron en medio sólido de Löwenstein-Jensen. Resultados: Entre las cepas LAM identificadas, 24 (63,1%) fueron confirmadas como M. tuberculosis RDRio y se asociaron significativamente con resistencia a isoniazida (p = 0,0264). Todos los aislamientos RDRio presentaron la deleción del locus RD174. Conclusión: En este estudio documentamos por primera vez el aislamiento del genotipo RDRio en casos de tuberculosis pulmonar en México, encontrando una asociación estadísticamente significativa entre este genotipo y la resistencia a isoniazida.(AU)

Synthesis and antileishmanial activity of naphthoquinone-based hybrids / Síntesis y actividad antileishmania de híbridos naftoquinónicos / Síntese e atividade antileishmania de híbridos naftoquinónicos

SUMMARY Introduction: Leishmaniasis is a disease caused by protozoa of the genus Leishmania and is considered endemic in 98 countries. Treatment with pentavalent antimonials has a high toxicity, which motivates the search for effective and less toxic drugs. α- and β-lapachones have shown different biological activities, including antiprotozoa. In recent studies, the isonicotinoylhydrazone and phthalazinylhydrazone groups were considered innovative in the development of antileishmania drugs. Molecular hybridization is a strategy for the rational development of new prototypes, where the main compound is produced through the appropriate binding of pharmacophoric subunits. Aims: To synthesize four hybrids of α- and β-lapachones, together with the isonicotinoylhydrazone and phthalazinylhydrazone groups and to determine the antileishmania activity against the promastigotic forms of L. amazonensis, L. infantum and L. major. Results: β-lapachone derivatives were more active against all tested leishmania species. βACIL (IC50 0.044μM) and βHDZ (IC50 0.023μM) showed 15-fold higher activity than amphotericin B. The high selectivity index exhibited by the compounds indicates greater safety for vertebrate host cells. Conclusion: The results of this work show that the hybrids βACIL and (3HDZ are promising molecules for the development of new antileishmania drugs.

RESUMEN Introducción: Leishmaniasis es una enfermedad causada por protozoos del género Leishmania y se considera endémica en 98 países. El tratamiento con antimoniales pentavalentes tiene una alta toxicidad, lo que motiva la búsqueda de fármacos eficaces y menos tóxico. α- y β-lapachones han mostrado diferentes actividades biológicas, incluido los antiprotozoarios. En estudios recientes, los grupos isonicotinoilhidra-zona y ftalazinilhidrazona se consideraron innovadores en el desarrollo de fármacos antileishmania. La hibridación molecular es una estrategia para el desarrollo racional de nuevos prototipos, donde el compuesto principal se produce a través de la unión apropiada de subunidades farmacofóricas. Objetivos: Sintetizar cuatro híbridos de α- y β-lapachones, junto con los grupos isonicotinoilhidrazona y ftalazinilhidrazona y determinar la actividad antileishmania frente a las formas promastigotas de L. amazonensis, L. infantum y L. major. Resultados: Los derivados de β-lapachone fueron más activos contra todas las especies de leishmania probadas. La βACIL (CI50 0,044μM) y βHDZ (CI50 0,023μM) mostraron actividad 15 veces mayor que la anfotericina B. El alto índice de selectividad que presentan los compuestos indica una mayor seguridad para las células huésped del vertebrado. Conclusión: Los resultados de este trabajo demuestran que los híbridos (ACIL y (HDZ son moléculas prometodoras para el desarrollo de nuevos fármacos antileishmania.

RESUMO Introdução: A leishmaniose é uma doença causada por protozoários do género Leishmania e é considerada endémica em 98 países. O tratamento com antimoniais pentavalentes apresenta alta toxicidade, o que motiva a pesquisa por medicamentos eficazes e menos tóxicos. α- e β-lapachones tém mostrado diferentes atividades biológicas, incluindo antiprotozoários. Em estudos recentes, os grupos isonicotinoilhi-drazona e ftalazinilhidrazona foram considerados inovadores no desenvolvimento de drogas antileishmania. A hibridização molecular é uma estratégia para o desenvolvimento racional de novos protótipos, onde o composto principal é produzido através da ligação apropriada de subunidades farmacofóricas. Objetivos: Sintetizar quatro híbridos de α- e β-lapachones, juntamente com os grupos isonicotinoil-hidra-zona e ftalazinilhidrazona e determinar a atividade antileishmania contra as formas promastigóticas de L. amazonensis, L. infantum e L. major. Resultados: Os derivados de β-lapachona foram mais ativos contra todas as espécies de leishmania testadas. BACIL (IC50 0,044 μM) e βHDZ (IC50 0,023 μM) apresentaram atividade 15 vezes maior do que a anfotericina B. O alto índice de seletividade dos compostos indica maior segurança para células hospedeiras de vertebrados. Conclusaõ: Os resultados deste trabalho mostram que os híbridos βACIL e βHDZ são moléculas promissoras para o desenvolvimento de novos fármacos antileishmania.

Efectividad y seguridad de un jarabe de isoniazida 50 mg/mL para uso pediátrico / Effectiveness and safety of a 50 mg/mL isoniazid syrup for pediatric use

Introducción: La tuberculosis pediátrica ha sido una epidemia mundial oculta durante décadas con dificultades para su control, entre las que se encuentra el difícil cumplimiento terapéutico debido a la correcta administración del tratamiento en niños que no pueden deglutir presentaciones farmacéuticas sólidas. El tratamiento de la tuberculosis es una terapia combinada, por lo que en su diseño se tiene que tener en cuenta el volumen final a administrar de todas las formulaciones así como su palatabilidad para favorecer la adherencia terapéutica.Objetivo: Evaluación de la efectividad y seguridad de una fórmula magistral de isoniazida 50 mg/mL.Material y métodos: Estudio observacional retrospectivo de 5 años de duración, incluyendo a todos los pacientes que recibieron dicha fórmula.Se registraron las siguientes variables: edad, sexo, indicación, reacciones adversas y evolución. Bases de datos: Silicon® (soporte informático de dispensación) y IANUS® (historia clínica electrónica). La efectividad se valoró mediante criterios clínicos, radiológicos y/o analíticos. Para la detección de reacciones adversas se realizaron analíticas de sangre y se evaluó la aparición de síntomas asociados a la ingesta de sorbitol que contiene la fórmula.Resultados: Composición de la fórmula (100 mL): isoniazida 5 g, agua conservans 50 mL (contiene Nipagin® 0,08% y Nipasol® 0,02%) y sorbitol 70% 50 mL. El periodo de caducidad establecido fue de 30 días coincidiendo con el referenciado en la bibliografía. El pH de la fórmula orale líquida (FOL) elaborada fue de 6,45±0,05 que corresponde con el de máxima estabilidad del principio activo. (AU)

Introduction: Pediatric tuberculosis has been a global epidemic hidden for decades with difficulties in its control, among which is difficult compliance with treatment due to the correct administration of treatment in children who cannot swallow solid pharmaceutical presentations. The treatment of tuberculosis is a combined therapy, so its design must take into account the final volume to be administered of all the formulations as well as its palatability to promote therapeutic adherence.Objective: Evaluation of the effectiveness and safety of a magisterial formula of isoniazid 50 mg/mL.Material and methods: A 5-year retrospective observational study, including all patients who received this formula.The following variables were recorded: age, sex, indication, adverse reactions and evolution. Databases: Silicon® (dispensing computer support) and IANUS® (electronic medical record). The effectiveness was assessed using clinical, radiological and/or analytical criteria. To detect adverse reactions, blood tests were performed and the appearance of symptoms associated with the intake of sorbitol containing the formula was evaluated.Results: Composition of the formula (100 mL): isoniazid 5 g, preservative water 50 mL (contains Nipagin® 0.08% and Nipasol® 0.02%) and sorbitol 70% 50 mL.The established expiration period was 30 days, coinciding with that referenced in the bibliography. The pH of the elaborated liquid oral formula (LOF) was 6.45±0.05, which corresponds to the maximum stability of the active principle. (AU)

Experiencia piloto con esquema rifapentina-isoniazida semanal por 3 meses para tratamiento de la infección tuberculosa latente en el Programa Nacional de Tuberculosis de Chile / Pilot experience with weekly rifapentine-isoniazid treatment for 3 months for latent tuberculosis infection at the Tuberculosis National Program of Chile

INTRODUCCIÓN: La prevención de la tuberculosis activa en los grupos de riesgo es clave para el control y eliminación de la tuberculosis. El tratamiento de la infección tuberculosa latente (TITL) con rifapentina e isoniazida en dosis semanales por 12 semanas es más corto que con otros esquemas, tiene menor hepatotoxicidad, mejor adherencia y es costo-efectivo. El OBJETIVO del estudio es evaluar la factibilidad de implementar este esquema a nivel programático en Chile. MÉTODOS: Se hizo una intervención piloto en territorios seleccionados entre mayo de 2018 y marzo de 2019. En esos territorios se reemplazó el esquema normado de TITL con isoniazida 6 meses por el esquema rifapentina-isoniazida 12 semanas. Además, se amplió la población objetivo, incluyendo a contactos mayores de 14 años. El tratamiento consistió en la administración conjunta de isoniazida y rifapentina por vía oral con frecuencia semanal, por 12 semanas, de forma supervisada por personal de salud. RESULTADOS: Ingresaron 238 pacientes al piloto, de los cuales 53% fueron mujeres y 54,2% fueron mayores de 14 años. Del total de pacientes, 203 (85,3%) completaron el tratamiento, 22 (9,2%) lo abandonaron, 8 (3,4%) presentaron reacciones adversas y 5 tuvieron otros motivos de egreso. CONCLUSIÓN: Tanto el TITL con rifapentinaisoniazida por 3 meses en dosis semanales supervisadas, como la incorporación de contactos adultos a TITL, son factibles de implementar a nivel programático en Chile.

INTRODUCTION: Prevention of active tuberculosis in risk groups is crucial in tuberculosis control and elimination. Treatment of latent tuberculosis (TITL) with rifapentine and isoniazid in weekly doses for 12 weeks is shorter than other pharmacological treatments, with less liver toxicity, better patient compliance and it is cost-effective. The OBJECTIVE of this study is to evaluate the feasibility to implement this treatment at a programmatic level in Chile. METHODS: A pilot intervention was conducted in selected territories between May 2018 and March 2019. Within these territories, the regulated treatment with isoniazid 6 months was replaced by the 12 weeks treatment with weekly rifapentine-isoniazide. Additionally, the target population was expanded to include contacts over 14 years old, currently not included in the national guidelines. Treatment consisted in oral administration of rifapentine and isoniazide together once a week for 12 weeks, under supervision of trained health workers. RESULTS: From 238 patients entered to the protocol, 53% of them were women and 54.2% were older than 14 years-old. Out of the total number of patients, 203 (85.3%) completed treatment, 22 (9.2%) abandoned, 8 (3.4%) had adverse drug reactions, and 5 ended treatment for different causes. CONCLUSION: Both TITL with rifapentine-isoniazide in 12 supervised weekly doses, and the inclusion of adult contacts in TITL, are feasible to implement at a programmatic level in Chile.

Una aproximación a la tuberculosis resistente a isoniazida: ¿un problema subestimado en Colombia? / An appraisal of the isoniazid resistant tuberculosis in Colombia: a underestimated problem in Colombia?

Objetivo: Describir las características clínicas y desenlaces al tratamiento de los pacientes con tuberculosis resistente a isoniazida (Hr-TB) en una institución del suroccidente colombiano. Materiales y métodos: Se realizó un estudio observacional retrospectivo. Se incluyeron pacientes con confirmación diagnóstica, aislamiento microbiológico, pruebas de susceptibilidad a fármacos y evidencia de Hr-TB. Resultados: Se incluyeron 32 pacientes con Hr-TB entre 2006-2018 que corresponden al 6% (32/528) de resistencia del total de casos. El 78% (n=25) fueron casos nuevos, resistencia primaria, y el 22% (n=7) previamente tratados, resistencia adquirida. La comorbilidad más frecuente fue infección por VIH (n=9). El patrón de Hr-TB mostró en 23 (72%) casos con alto nivel, 4 (12%) de bajo nivel y 5 (16%) con bajo y alto nivel. El análisis de resultados al tratamiento se realizó a 22 pacientes, presentando el 50% cura, el 41% tratamiento completo y 9% muerte relacionada con la tuberculosis. Conclusiones: La Hr-TB predomina en los casos nuevos, lo que supone un obstáculo al tratamiento donde no se realizan las pruebas de susceptibilidad de forma rutinaria.

Objective: To describe the clinical characteristics and outcomes to the treatment of patients with isoniazid-resistant tuberculosis (Hr-TB) in an institution in southwest Colombia. Materials and methods: A retrospective observational study was conducted. Patients with diagnostic confirmation, microbiological isolation, drug susceptibility tests, and evidence of Hr-TB were included. Results: Thirty-two patients with Hr-TB were included between 2006-2018, corresponding to 6% (32/528) of resistance in total cases. 78% were new cases, primary resistance, and 22% previously treated, acquired resistance. The most frequent comorbidity was HIV infection (n = 9). The pattern of Hr-TB showed in 23 (72%) cases with high level, 4 (12%) of low level and 5 (16%) with low and high level. The analysis of treatment results was performed on 22 patients, presenting 50% cure, 41% completed treatment, and 9% death related to tuberculosis. Conclusions: Hr-TB predominates in new cases, which is an obstacle to treatment where susceptibility tests are not performed routinely.

RDRioMycobacterium tuberculosis strains associated with isoniazid resistance in Northern Mexico.

BACKGROUND: It has been established that the genomic background of Mycobacterium tuberculosis may influence disease progression, in particular for the Beijing family and the Latin American and Mediterranean (LAM)/RDRio strains. The purpose of this study was to evaluate the prevalence of the LAM/RDRio genotype in cases of tuberculosis from Mexico and their drug susceptibility profile. METHODS: Two hundred eighteen M. tuberculosis isolates were screened by 43-spacer spoligotyping. The LAM/RDRio genotype was confirmed by multiplex PCR, and the drug susceptibility testing was carried out in solid Löwenstein-Jensen media. RESULTS: Among the LAM strains identified, 24 (63.1%) were confirmed as M. tuberculosis RDRio. All RDRio strains shared the RD174 deletion, that was associated with isoniazid resistance (p=0.0264). CONCLUSIONS: We documented for the first time the isolation of the LAM/RDRio genotype in pulmonary cases of tuberculosis in Mexico, and we found resistance to the first-line anti-tuberculosis drug isoniazid in these strains.

Diagnosis and treatment of latent tuberculosis infection in patients undergoing treatment with immunobiologic agents: a four-year experience in an endemic area / Impacto do diagnóstico e tratamento de tuberculose latente em pacientes submetidos à terapia imunobiológica: experiência de quatro anos em área endêmica

ABSTRACT Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

RESUMO Objetivo: Descrever a incidência de tuberculose ativa e a ocorrência de eventos adversos do tratamento com isoniazida em pacientes diagnosticados com tuberculose latente (TBL), portadores de doenças inflamatórias crônicas e tratados com agentes imunobiológicos em uma área endêmica no Brasil. Métodos: O diagnóstico de TBL foi feito com base em anamnese, exame clínico, radiografia de tórax e teste tuberculínico (TT). O tratamento profilático foi realizado segundo diretrizes brasileiras com isoniazida por seis meses. Resultados: Foram estudados 101 pacientes entre julho de 2011 e julho de 2015. Desses, 55 (54,46%) eram mulheres (média de idade = 53,16 ± 1,76 anos) e 46 (45,54%) eram homens (média de idade = 45,39 ± 2,13 anos), sendo que 79 (78,22%) foram tratados com agentes imunobiológicos e 22 (21,78%) com outros agentes imunomoduladores ou imunossupressores. Na triagem para TBL, 53 pacientes (52,48%) apresentaram TT ≥ 10 mm. A radiografia de tórax alterada por imagens compatíveis com TBL foi observada em 36 pacientes (35,64%). O tratamento profilático com isoniazida mostrou uma eficácia de 95,05% (96/101). É relevante mencionar que 84 (83,17%) dos pacientes não apresentaram nenhum efeito adverso à isoniazida e, desses, 83 (98,81%) completaram o tratamento profilático (p = 0,002). Tuberculose ativa foi diagnosticada em 5 (6,33%) dos 79 pacientes tratados com agentes imunobiológicos e em 1 (4,55%) dos 22 pacientes tratados com outros imunomoduladores/imunossupressores. Conclusões: O uso de isoniazida por seis meses mostrou-se seguro e eficaz no tratamento da TBL nesses pacientes, o que é essencial para reduzir o risco de desenvolvimento de tuberculose ativa.

Fluconazol como alternativa terapéutica en infecciones asociadas a Mycobacterium tuberculosis / Fluconazole as a therapeutic alternative in infections associated with Mycobacterium tuberculosis

Mycobacterium tuberculosis (M. tuberculosis) es un microorganismo cuya importancia como agente infeccioso ha permanecido a través de los años, pero que se ha convertido en una emergencia y un grave problema de salud pública, como respuesta a la evolución en su comportamiento ante los antimicrobianos de primera línea para su tratamiento y al surgimiento de cepas multi-resistentes, lo que amerita el uso de alternativas terapéuticas que permitan su control. El objetivo del trabajo fue evaluar el comportamiento in vitro de M. tuberculosis ante el antimicótico fluconazol, para su posible uso como alternativa terapéutica. Para ello, se evaluaron 6 cepas de M. tuberculosis: 2 resistentes a rifampicina, 2 resistentes a isoniazida y 2 sensibles a ambos antimicrobianos, Se utilizó el método de Concentración Inhibitoria Mínima, utilizando la técnica en microplaca con Azul de Alamar y la técnica de dilución en tubo. Ambas metodologías mostraron sensibilidad ante bajas concentraciones de fluconazol (0,0625 µg/ml). Todas las cepas fueron sensibles a la combinación fluconazol/isoniazida; mientras que, a la combinación fluconazol/rifampicina mostraron resistencia, indicando el efecto antagónico de la rifampicina sobre el fluconazol. Los resultados permiten concluir y sugerir el posible uso terapéutico del fluconazol ante las infecciones asociadas por M. tuberculosis.

Mycobacterium tuberculosis (M. tuberculosis) is a microorganism whose importance as an infectious agent has remained over the years but which has become a recent emergency and a serious public health problem in response to the evolution in its behavior against first-line antimicrobials, for its treatment and the emergence of multi-resistant strains, which require the use of therapeutic alternatives that allow its control. The objective of the work was to evaluate the in vitro behavior of M. tuberculosis before the antifungal agent fluconazole, for its possible use as a therapeutic alternative. To this, six strains were evaluated M. tuberculosis: 2 resistants to rifampicin, 2 resistants to isoniazid and 2 sensitive to both antimicrobials. We used the method of Minimum Inhibitory Concentration, using the microplate technique with Alamar Blue and the tube technique. Both methodologies showed sensitivity to low concentrations of fluconazole (0.0625 µg/ml). All strains were sensitive to the fluconazole / isoniazid combination; whereas, when exposed to the fluconazole / rifampicin combination, the strains showed resistance, indicating the antagonistic effect of rifampicin on fluconazole. The results allow us to conclude and suggest the possible therapeutic use of fluconazole against infections associated with M. tuberculosis.

Desarrollo de infección tuberculosa latente y efectos adversos de la isoniazida durante tratamiento con biológico por enfermedad de Crohn / Development of latent tuberculosis and adverse effects with isoniazid during biologist therapy´s in Crohn´s disease / Desenvolvimento de tuberculose latente durante e efeitos adversos da isoniazida o tratamento com biológicos para a doença de Crohn

Los fármacos anti factor de necrosis tumoral alfa (TNF-α) bloquean una de las citoquinas implicadas en la patogénesis de la Enfermedad Inflamatoria intestinal (EII). Su uso se relaciona con aumento de tuberculosis (TB), por lo que el despistaje previo es obligatorio. En la infección tuberculosa latente (ITBL) se utiliza isoniazida como quimioprofilaxis, fármaco que no se encuentra libre de reacciones adversas. Se presenta y discute el caso de una paciente con reacción adversa en piel secundaria al uso de isoniazida.

Anti-tumor necrosis factor alfa drugs are responsible for blocking one of the cytoquines implicated on inflammatory bowel disease pathogenesis. Its use has been linked to an increase in tuberculosis cases which is why screening before starting treatment is mandatory. Latent tuberculosis is treated with isoniazid as chemoprophylaxis although its use may provoke adverse effects. A case is presented of a patient with skin adverse reaction due to the use of isoniazid.

Os medicamentos anti factor de necrose tumoral alfa (TNF-α ) bloqueiam uma das citocinas envolvidas na patogénese da doença inflamatória intestinal (DII). A sua utilização está associada com um aumento da tuberculose (TB), de modo que a despistagem anterior dessa doença é necessária. Na TB latente, frequentemente se utiliza a isoniazida é usado como quimioprofilaxia, uma droga que não está livre de reações adversas. Apresentamos e discutimos o caso de uma paciente com reação adversa na pele secundária ao uso da isoniazida.

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country.

OBJECTIVES: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. METHODS: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. RESULTS: Sixty-nine JIA patients with current age of 17.4±5.8 years, mean disease duration of 5.0±4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). CONCLUSION: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Latent tuberculosis infection screening in juvenile idiopathic arthritis patients preceding anti-TNF therapy in a tuberculosis high-risk country / Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti-TNF em um país de alto risco para tuberculose

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

Resumo Objetivo: Avaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF. Métodos: Trata-se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti-TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti-TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses. Resultados: Incluíram-se 69 pacientes com AIJ com idade atual de 17,4 ± 5,8 anos, com média de duração da doença de 5 ± 4,9 anos; 47 pacientes receberam um único anti-TNF, enquanto 22 foram transferidos para outro anti-TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos). Conclusão: A avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti-TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.