RESUMO De acordo com estudos realizados, cerca de 10 milhões de pessoas desenvolveram tuberculose em 2018. Desse total, 1,5 milhão de pessoas morreram devido à doença. Procurando estudar o comportamento das sequências do genoma da Mycobacteruim tuberculosis (MTB), bactéria responsável por desenvolver a Tuberculose (TB), foi realizada uma análise aplicando o k-mer (frequência de palavras do DNA). Os valores de k variaram de 1 a 10, pois devido a análise ter sido feita no comprimento total das sequencias, onde cada sequencia é composta por aproximadamente 4 milhões de pares de bases, valores de k acima de 10, a análise é interrompida, como consequência da capacidade do programa. O intuito do trabalho foi de verificar a formação da árvore filogenética em cada k-mer analisado. Os resultados obtidos evidenciaram a formação de grupos distintos em alguns k-mers analisados, levando-se em consideração a linha de corte. Entretanto, em todos os grupos formados as cepas multidroga resistente (MDR) e extensivamente resistente à droga (XDR) permaneceram juntas e separadas das demais cepas.

Abstract According to studies carried out, approximately 10 million people developed tuberculosis in 2018. Of this total, 1.5 million people died from the disease. To study the behavior of the genome sequences of Mycobacterium tuberculosis (MTB), the bacterium responsible for the development of tuberculosis (TB), an analysis was performed using k-mers (DNA word frequency). The k values ranged from 1 to 10, because the analysis was performed on the full length of the sequences, where each sequence is composed of approximately 4 million base pairs, k values above 10, the analysis is interrupted, as consequence of the program's capacity. The aim of this work was to verify the formation of the phylogenetic tree in each k-mer analyzed. The results showed the formation of distinct groups in some k-mers analyzed, taking into account the threshold line. However, in all groups, the multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains remained together and separated from the other strains.

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

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

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

Resumo Objetivo: analisar a prevalência de tuberculose, coronavírus, condições crônicas e vulnerabilidades entre migrantes e refugiados no Brasil. Método: trata-se de estudo transversal, do tipo inquérito eletrônico, realizado com migrantes internacionais durante a pandemia de COVID-19. Para a análise, aplicou-se estatística descritiva, com cálculo de medidas de posição e de dispersão. Quanto às variáveis categóricas, estimaram-se as frequências relativas e absolutas. Resultados: participaram do estudo 553 migrantes e refugiados, verificando-se prevalência de 3,07% de tuberculose, 7,2% de COVID-19 e 27,3% de condições crônicas. Entre as vulnerabilidades, 32% referiram desemprego, 37,6% mudaram para o Brasil em decorrência da situação social do seu país e 33,6% residiam em asilo e ou abrigo. Conclusão: a tuberculose, as doenças crônicas e a COVID-19 apresentaram maior prevalência em migrantes e refugiados que na população em geral. Por tratar-se de uma população ainda com grande dificuldade de acesso aos serviços de saúde e aos sistemas de proteção social, o estudo subsidiará, com base em evidências, as políticas públicas, o atendimento do enfermeiro e a incorporação de novas rotinas no serviço.

Abstract Objective: to analyze the prevalence of tuberculosis, coronavirus, chronic conditions and vulnerabilities among migrants and refugees in Brazil. Method: this is a cross-sectional study of the electronic survey type conducted with international migrants during the COVID-19 pandemic. Descriptive statistics was applied for the analysis, with calculation of position and dispersion measures. Regarding the categorical variables, relative and absolute frequencies were estimated. Results: the study participants were 553 migrants and refugees, verifying 3.07%, 7.2% and 27.3% prevalence of tuberculosis, COVID-19 and chronic conditions, respectively. Among the vulnerabilities, 32% reported unemployment, 37.6% moved to Brazil as a result of the social situation in their countries and 33.6% were living as refugees or sheltered people. Conclusion: tuberculosis, chronic diseases and COVID-19 presented higher prevalence values in migrants and refugees than in the general population. As this is a population group that still has significant difficulty accessing health services and social protection systems, based on diverse evidence, the study will subsidize public policies, Nursing care and the incorporation of new routines in the service.

Resumen Objetivo: analizar la prevalencia de tuberculosis, coronavirus, condiciones crónicas y vulnerabilidades en inmigrantes y refugiados en Brasil. Método: se trata de un estudio transversal, del tipo encuesta electrónica, realizado con migrantes internacionales durante la pandemia de COVID-19. Para el análisis se aplicó estadística descriptiva, con cálculo de medidas de posición y dispersión. En cuanto a las variables categóricas, se estimaron las frecuencias relativas y absolutas. Resultados: participaron del estudio 553 inmigrantes y refugiados, la prevalencia de tuberculosis era del 3,07%, de COVID-19 del 7,2% y de condiciones crónicas del 27,3%. Entre las vulnerabilidades, el 32% reportó desempleo, el 37,6% emigró a Brasil por la situación social de su país y el 33,6% vivía en un asilo o albergue. Conclusión: la tuberculosis, las enfermedades crónicas y el COVID-19 fueron más prevalentes en inmigrantes y refugiados que en la población general. Por tratarse de una población que aún tiene grandes dificultades para acceder a los servicios de salud y sistemas de protección social, el estudio contribuirá, con base en la evidencia, a las políticas públicas, la atención de enfermería y la incorporación de nuevas rutinas en el servicio.

ABSTRACT The general objective of the research was to identify the factors that influence adherence to treatment in patients with tuberculosis: Integrative review. An integrative review was carried out, which was characterized by the scientific inquiry on a particular subject based on the review of existing knowledge. The approach adopted was the one proposed by PRISMA, which was based on 27 items to determine the validity of the articles to be used in the development of the review, some of these are: eligibility criteria, sources of information, data extraction process, certainty of the evidence, among others. It is concluded that, the integrative review allowed to know that adherence to tuberculosis treatment is an issue that continues to be relevant for health personnel. Its prevalence is strongly anchored in resource-poor countries, and it is in these areas that it affects more severely.

RESUMEN El objetivo general de la investigación fue identificar los factores que influyen en la adherencia al tratamiento de pacientes con tuberculosis: Revisión integrativa. Se realizó una revisión integrativa, la cual se caracterizó por la indagación científica sobre una materia en particular a partir de la revisión del conocimiento existente. El enfoque adoptado fue el propuesto por PRISMA, el cual se basó en 27 ítems para determinar la validez de los artículos a utilizar en el desarrollo de la revisión, algunos de estos son: criterios de elegibilidad, fuentes de información, proceso de extracción de datos, certeza de la evidencia, entre otros. Se concluye que, la revisión integrativa permitió conocer que la adherencia al tratamiento de la tuberculosis es un tema que continúa siendo relevante para el personal sanitario. Su prevalencia está fuertemente anclada en países de escasos recursos, y es en estas zonas en las que afecta más gravemente.

BACKGROUND: Progressive interventions have recently improved programmatic outcomes in drug-resistant tuberculosis (DR-TB) care in South Africa (SA). Amidst these, a shorter regimen was introduced in 2017 with weak evidence, and has shown mixed results. Outcomes still fall short of national targets, and the coronavirus disease 2019 pandemic has undermined progress to date OBJECTIVES: To describe the outcomes of participants treated for DR-TB using a shorter, compared with a longer, regimen in a deeply rural SA setting, and to explore other factors affecting these outcomes METHODS: This retrospective cohort study describes outcomes in short and long DR-TB treatment regimens, over 5 years, at two rural treatment sites in SA. Characteristics were analysed for outcome correlates using multivariable logistic regression models RESULTS: Of 282 treatment episodes, 62% were successful, with higher success in shorter (69%) compared with longer regimens (58%). Mortality was approximately 21% in both groups. Characteristics included high proportions of HIV co-infection (61%). Injectables (adjusted odds ratio (aOR) 3.00, 95% confidence interval (CI) 1.48 - 6.09), bedaquiline (aOR 3.16, 95% CI 1.36 - 7.35), increasing age (aOR 0.97, 95% CI 0.95 - 0.99) and HIV viraemia defined as final HIV-RNA viral load >1 000 copies/mL (aOR 0.16, 95% CI 0.07 - 0.37) were all significantly and independently associated with treatment success. Injectables (aOR 0.22, 95% CI 0.08 - 0.57), bedaquiline (aOR 0.05, 95% CI 0.01 - 0.19), increasing age (aOR 1.09, 95% CI 1.05 - 1.13), extra-pulmonary TB (aOR 8.15, 95% CI 1.62 - 41.03) and HIV viraemia (aOR 9.20, 95% CI 3.22 - 26.24) were all significantly and independently associated with mortality CONCLUSION: In a rural context, treating DR-TB amid limited resources and a high burden of HIV co-infection, we found that after considering controls, a short regimen was no different to a longer regimen in terms of success or mortality. Therefore, by alleviating burdens on multiple stakeholders, a short regimen is likely to be favourable for rural patients, clinicians, and healthcare systems. Besides other previously described correlates of outcomes, HIV viraemia emerged as a novel marker for reliably predicting poor outcomes in DR-TB with HIV co-infection, and a pragmatic target for intervention

Introducción. La tuberculosis continúa siendo un problema frecuente en contextos de vulnerabilidad socioeconómica. El objetivo principal fue establecer la prevalencia de infección latente y viraje tuberculínico en contactos escolares de casos de tuberculosis. Población y métodos. En un área programática del sur de la ciudad, se evaluó la prevalencia de infección y viraje tuberculínico de 691 niñas, niños y adolescentes utilizando la prueba cutánea de tuberculina. Se investigó la asociación entre pérdida de seguimiento por parte del equipo de salud y características demográficas, escolares y asistencia inicial, y se describió el grado de adherencia cuando la quimioprofilaxis con isoniacida fue indicada. Resultados. Según las definiciones consideradas, la prevalencia de infección latente fue entre el 3,4 % (IC95 %: 2,3-5,2) y el 11,6 % (IC95 %: 9,3-14,4) de los 610 contactos con al menos una prueba cutánea aplicada. La incidencia de viraje tuberculínico se encontró entre el 0,3 % y el 6,8 % de los 294 evaluados. La edad mayor de 18 años, la mayor prevalencia de necesidades básicas insatisfechas en la comuna escolar, la pertenencia al turno escolar vespertino, la negatividad en la baciloscopia del caso índice y la ausencia de aplicación de la prueba cutánea inicial se asociaron con pérdida de seguimiento del contacto. Conclusiones. La incidencia de viraje tuberculínico en contactos escolares fue baja. La adherencia a isoniacida continúa siendo limitada. Se identificaron factores asociados con la pérdida de seguimiento de contactos que podrían orientar estrategias necesarias para mejorar este proceso.

Resumen Introducción: A diferencia de lo descrito en países desarrollados, en los que se informan las enfermedades crónicas no transmisibles como causa de hospitalización en pacientes con VIH, en este estudio las principales causas de admisión hospitalaria y muerte fueron las infecciones oportunistas, particularmente la tuberculosis, algo similar a lo reportado en otros países de ingresos bajos en América y África Occidental, aun con la disponibilidad de la terapia antirretroviral. Objetivos: Se determinaron las causas más frecuentes de morbilidad y mortalidad hospitalaria en pacientes con VIH. Material y métodos: Se analizaron los datos demográficos, clínicos y de laboratorio de pacientes ingresados con diagnóstico de VIH durante un año, en un hospital de Guayaquil, Ecuador. Resultados: De 151 pacientes, el 76% era del sexo masculino, con 37 años en promedio. El 56.3% conocía el diagnóstico de infección por VIH. Las principales causas de hospitalización y muerte fueron las enfermedades definitorias de sida, entre las que las formas meníngeas, como criptococosis, toxoplasmosis, sífilis y leucoencefalopatía en conjunto, siguen a la tuberculosis; el 93.5% de los fallecidos tenía recuento de CD4 menor de 200 células/mm3 (p = 0.007). Conclusión: De manera similar a lo informado en pacientes adultos jóvenes con VIH en países de bajos ingresos económicos, las infecciones oportunistas fueron la principal causa de hospitalización y muerte, relacionada con inmunosupresión intensa, estadios avanzados de la enfermedad y falta de terapia antirretroviral. Los resultados refuerzan la importancia del diagnóstico precoz y el tratamiento de la infección por VIH, así como la profilaxis de las infecciones oportunistas prevenibles.

Abstract Introduction: Unlike what has been described in developed countries where chronic non-communicable diseases are reported as the cause of hospitalization in patients with HIV, in this study the main cause of hospital admission and death were opportunistic infections, particularly tuberculosis similar to what was reported in other low-income countries in the Americas and West Africa even with the availability of antiretroviral therapy. Aim: The most frequent causes of hospital morbidity and mortality in patients with HIV were determined. Material and methods: The demographic, clinical, and laboratory data of patients admitted with a diagnosis of HIV for one year in a Guayaquil General Hospital were analyzed. Results: Of 151 patients, 76% were male with an average age of 37 years old. 56.3% knew the diagnosis of HIV infection. The main cause of hospitalization and death were AIDS-defining diseases where the meningeal forms: cryptococcosis, toxoplasmosis, syphilis and leukoencephalopathy together follow tuberculosis, and 93.5% of the deceased had a CD4 count of fewer than 200 cells/ mm3 (p = 0.007). Conclusion: Similar to what was reported in young adult patients with HIV in low-income countries, opportunistic infections were the main cause of hospitalization and death, related to severe immunosuppression, advanced stages of the disease, and without antiretroviral therapy. The results reinforce the importance of early diagnosis and treatment of HIV infection and the prophylaxis of preventable opportunistic infections.

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

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

Abstract Objectives: The number of women in prison is rapidly increasing every year and it is important to establish what factors are related to the probability of presenting STDs in this population to enable health control policies to be established. Material and method: An analysis was carried out on the open database of the national prison population survey conducted in 2016 in all Peruvian prisons. The study was based on the census and all female and male adults in prison were surveyed using a validated questionnaire. Results: The sample consisted of 4,574 inmates in 67 institutions, covering 98.8% of the inmate population. It was found that presenting tuberculosis (PR: 2.64; CI 95%, 1.32-5.26), HIV/AIDS (PR 6.54, CI 95% 1.52-28.18), hepatitis (PR: 4.01; CI 95%, 1.23-13.11) and drug use (PR: 2.44; CI 95%, 1.32-4.52), are statistically related (P ≤0.05) are factors associated with the presence of STDs in the multivariate model with a P ≤0.05. Discussion: The inclusion of associated factors (tuberculosis, HIV/AIDS, hepatitis and drug use) should be part of the strategy to control and treat STD in women's prisons in Peru.

Resumen Objetivos: El número de mujeres en condición de prisión se incrementa rápidamente todos los años, por lo que es importante establecer cuáles son los factores que se relacionan con la probabilidad de presentar infecciones de trasmisión sexual (ITS) en esta población para establecer políticas de control sanitario. Material y método: Se realizó un análisis de la base de datos abierta de la encuesta nacional de población penitenciaria del año 2016 realizada en todas las prisiones del Perú. El estudio fue censal y se entrevistaron a todas las mujeres y hombres adultos en situación de cárcel mediante un cuestionario validado. Resultados: La muestra abarcó a 4.574 internas de 67 establecimientos penitenciarios, cubriendo el 98,8% de la población peni- tenciaria. Se encontró que haber presentado tuberculosis (razón de prevalencia ajustada [RPa]: 1,32; intervalo de confianza [IC] del 95%, 1,32-5,26), presentar virus de la inmunodeficiencia humana (VIH)/sida o síndrome de inmunodeficiencia adquirida (RPa: 1,52; IC del 95%, 1,52-28,18), hepatitis (RPa: 4,01; IC del 95%, 1,23-13,11) y consumo de drogas (Rpa: 2,44; IC del 95%, 1,32-4,52) son factores asociados a la presencia de ITS en el modelo multivariado con un valor p ≤0,05. Discusión: Incluir los factores asociados identificados (tuberculosis, VIH/sida, hepatitis y consumo de drogas) debe ser parte de la estrategia de control y tratamiento de las ITS en las prisiones femeninas del Perú.

Resumo O manejo da Tuberculose (TB) enfrentou barreiras geradas pela pandemia do coronavírus (2020-2021), provocando elevação nas mortes pela doença no mundo. Desse modo, o objetivo do estudo foi analisar o impacto da COVID-19 na morbimortalidade da TB no Brasil. Trata-se de um estudo retrospetivo, observacional e quantitativo, de base documental com procedimento comparativo-estatístico. A coleta de dados teve como universo de pesquisa o Sistema de Informação de Agravos de Notificação (Sinan Net) e do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS). Os resultados demonstraram diminuição no número de notificações da doença entre 2019 e 2021 (10%). No entanto, a taxa de mortalidade aumentou, passando de 7.93% para 11.38%. A doença teve predomínio entre os pacientes do sexo masculino (70.13%), na faixa etária de 20 a 59 anos (77.38%), na cor/raça parda (49.34%) e com baixa escolaridade (41.38%). A maioria dos casos eram pulmonares (84.73%), novos (79.62%) e evoluíram para cura (53.38%). Um pequeno percentual dos casos, eram resistentes (0.48%), principalmente a drogas de primeira linha. O estudo evidenciou o aumento na morbimortalidade da Tuberculose com o avento da pandemia do COVID-19. A co-infeção, a reativação da TB, a desestruturação do esquema de combate a Tuberculose, comprometeu o tratamento, a orientação ao paciente, a deteção precoce o que contribuiu para o aumento da morbidade da Tuberculose no período estudado.

Abstract Tuberculosis (TB) management faced challenges caused by the coronavirus pandemic (2020-2021), causing an increase in deaths from this illness worldwide. This study aimed to analyze the impact of COVID-19 on TB morbidity and mortality in Brazil. It is a retrospective, observational, quantitative, documentary-based study with a comparative-statistical approach. The research was based on the Sistema de Informação de Agravos de Notificação (Sinan Net) and Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS). These results revealed a decrease in the number of notifications of the disease between 2019 to 2021 (10%). However, the mortality rate increased from 7.93% to 11.38%. There was a predominance of the illness among male patients (70.13%), in the age group of 20 to 59 years (77.38%), of brown color/race (49.34%), and with a poor school education (41.38%). Most cases were pulmonary (84.73%), new ones (79.62%), and progressed to cure (53.38%). A smaller number of cases were resistant (.48%), especially first-line drugs. This study shows the increase in Tuberculosis morbimortality with the advent of the pandemic of COVID-19. The patients’ treatment and orientation were compromised by levels of co-infection, the reactivation of TB, and the dysfunction of the plan to prevent Tuberculosis. Consequently, the early detection of cases has contributed to a rise in Tuberculosis morbimortality in the period studied.

Computer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv.

Computer-aided drug planning strategies have contributed to the research and development of new anti-tuberculosis (TB) drugs to avoid resistance and reduce treatment time and the number of drugs used in therapy. The aim of work was to carry out a docking study to identify the possible mechanism of action of the hits LabMol73, 84, 86 and 93 previously tested in the Microplate Assay Blue Alamar (MABA), Low Oxygen Recovery Assay (LORA) assays in sensitive strains from M.tb. H37Rv and resistant to the standard drugs rifampicin and isoniazid, due to the promising inhibitory result against these strains, suggesting a different mechanism of action from existing drugs. The reverse virtual screening was performed on the Pharmmapper platform, which identifies targets by pharmacophoric model. The most promising targets have been validated. The DM was performed in the OpenEye Maestro program for analysis of poses and energy score. Sixteen targets M.tb. H37Rv were identified and only nine demonstrated viability for computational testing. The most promising results were observed in the mycolic acid cyclopropane synthase (PDB:1L1E) and pantothenate synthetase (PDB:1N2B) targets. Since, in the target 1L1E score results obtained were between -6.998 to -7.767 kcal/mol. In the 1N2B target the results were between -6.421 to -7.293 kcal/mol, presenting themselves as the most promising targets due to their similar score scores between the two targets suggesting that the mechanism of action may be the inhibition of one of these targets. These targets proved to be promising for elucidating the mechanism of action of the analyzed nitro heteroaryl chalcones, as they corroborate the assay against resistant strains, demonstrating that standard drugs have activity against other targets and also because mycolic acid and pantothenate are directly linked to virulence and resistance of M.tb. H37Rv.

Abstract The treatment of ocular tuberculosis (TB) remains controversial worldwide. The development of guidelines for ocular TB can facilitate the approach and management of these patients. These guidelines should be developed regionally, considering the local TB epidemiology. The objectives of this consensus are: to initiate an interdisciplinary discussion about the epidemiology, pathophysiology, clinical presentation, diagnosis, workup and treatment of patients with ocular TB, to establish a treatment algorithm and define which patients should be treated in Chile and how and, to analyze and discuss the published data regarding chemoprophylaxis for patients with latent TB who need to start immunosuppressive treatment due to inflammatory ocular conditions.

Resumen Introducción: El tratamiento de la tuberculosis (TB) ocular es un tema que genera controversia en el mundo. Para el correcto manejo de estos pacientes, es necesario el desarrollo de guías que consideren la epidemiología de la TB ocular en cada nación. El objetivo de este consenso fue discutir de forma interdisciplinaria la epidemiología, fisiopatología, clínica, diagnóstico, estudio y tratamiento de los pacientes con TB ocular, para establecer un algoritmo de tratamiento y proponer qué pacientes deben ser tratados en Chile y con qué tratamiento. Además, se establecieron acuerdos para efectuar quimioprofilaxis de los pacientes con TB latente que tienen indicación de tratamiento inmunosupresor por enfermedades inflamatorias oculares.

Resumen Presentamos el caso de un hombre de 40 años, HIV positivo con regular adherencia al tratamiento, que consultó por episodios febriles intermitentes de dos años de evolución, agregando en los últimos dos meses dolor abdominal difuso progresivo y adenomegalias ge neralizadas indoloras. En el laboratorio presentó panci topenia, coagulopatía, hipoalbuminemia y reactantes de fase aguda aumentados. La tomografía computarizada (TC) de tórax, abdomen y pelvis únicamente evidenció hepato-esplenomegalia y adenomegalias generalizadas. Se realizaron múltiples exámenes microbiológicos, in cluyendo cultivos para Mycobacterium sp. de distintas muestras, todos con resultados negativos, a excepción de la RT-PCR para VHH-8. Se tomó biopsia escisional de ganglio iliaco izquierdo con hallazgos compatibles con enfermedad de Castleman. A pesar de reiniciar terapia antirretroviral, la sintomatología progresó, iniciando tratamiento con corticoides y ganciclovir. Luego de una semana, desarrolló falla mulitorgánica y anasarca, que contraindicaron los fármacos iniciados. Se realizó nueva TC de tórax que mostró infiltrados con patrón en árbol en brote en lóbulo superior derecho asociado a derra me pleural bilateral, y a nivel abdominal, progresión de hepato-esplenomegalia y ascitis. Pasó a unidad de cui dados intensivos 48 horas después por falla hepática ful minante. El paciente falleció en pocas horas. Se recibió postmortem el cultivo del aspirado traqueal positivo para Mycobacterium tuberculosis y la punción-biopsia hepática con granulomas no necrotizantes. Nuestro objetivo es remarcar la importancia de pesquisar tuberculosis activa en nuestro país frente a la sospecha de enfermedad de Castleman antes de iniciar tratamiento, y resaltar que la TBC también puede presentarse como complicación infecciosa elevando la morbimortalidad.

Abstract We present the case of a 40-year-old man, HIV posi tive with regular adherence to treatment, who consulted for intermittent febrile episodes during a two-years period, progressive diffuse abdominal pain and painless generalized lymphadenopathy in the last two months. Laboratory analysis showed pancytopenia, altered co agulation tests, hypoalbuminemia, and increased acute phase reactants. Computed tomography (CT) of the chest, abdomen and pelvis revealed hepato-splenomegaly and generalized lymphadenopathy. Multiple microbiological tests were performed, including cultures for Mycobacte rium sp. from different samples, with negative results, except for the RT-PCR for HHV-8. An excisional biopsy of the left iliac lymph node was taken with findings compatible with Castleman’s disease. Despite restarting antiretroviral therapy, the symptoms progressed, starting treatment with steroids and ganciclovir. After a week, he developed multiple organ failure and anasarca, which contraindicated the drugs previously started. A new CT of the chest showed infiltrates with a tree-in-bud pattern in the right upper lobe with bilateral pleural effusion, and at the abdominal level, progression of hepatospleno megaly and ascites. He was transferred to the intensive care unit 48 hours later due to fulminant hepatic fail ure. The patient died within a few hours. Postmortem recieved culture results of the tracheal aspirate were positive for tuberculosis (TB) and the histopathology of the liver biopsy showed non-necrotizing granulomas. Our objective is to highlight the importance of screening for active TB, in our country, when Castleman’s disease is suspected, before starting treatment, and to stand out that TB can also present as an infectious complication, increasing morbidity and mortality.