[SWOT analysis: strengthening tuberculosis prevention and control in post COVID-19 pandemic, Hospital Muñiz, Buenos Aires]. / Análisis FODA: fortalecimiento de la prevención y el control de la tuberculosis en post pandemia de COVID-19, Hospital Muñiz, Buenos Aires.

INTRODUCTION: The Hospital Muñiz's "Strengthening Epidemiological Surveillance in Tuberculosis (VET) Project" is focused on improving operational outcomes, specifically by enhancing early TB diagnosis. Our primary aim is to promptly identify individuals with tuberculosis (TB) who seek care at our institution following the COVID-19 pandemic. METHODS: A SWOT analysis (Strengths, Weaknesses, Opportunities, and Threats) was carried out. It is an essential tool in strategic planning, which provides information for the implementation of actions and corrective measures in the generation of new improvement projects. The internal situation of the institution was evaluated to determine SWOT after the COVID-19 pandemic, in order to strengthen VET, through field epidemiological surveillance. RESULTS: There are trained personnel, the possibility of early diagnosis and its opportune control generated from the Febrile Emergency Unit. The on-call service has an adequate control of the TB population that enables coordination and joint work with other programs (HIV), response capacity of the institution to outbreaks, epidemics and pandemics. DISCUSSION: The application of this project will incorporate a strengthening activity in epidemiological surveillance, where the Muñiz Hospital, through a comprehensive approach and the identification of new cases, responds to the needs of the local population with TB. This will provide valid and reliable information for the prevention and control of TB in the institution after the COVID-19 pandemic.

Introducción: El proyecto de fortalecimiento en Vigilancia Epidemiológica en Tuberculosis (VET) del Hospital Muñiz, Buenos Aires (Argentina), busca mejorar los resultados operacionales relacionados en mayor medida al diagnóstico precoz de la enfermedad, estableciendo como objetivo la identificación oportuna de personas enfermas de tuberculosis (TB) que consultan posterior a la pandemia por COVID-19. Métodos: Se realizó un análisis FODA (Fortalezas, Oportunidades, Debilidades, Amenazas): una herramienta esencial en la planeación estratégica, que proporciona información necesaria para la implementación de acciones y medidas correctivas, generación de nuevos proyectos de mejora, donde se evaluó la situación interna de la institución para determinar las FODA presentadas después de la pandemia COVID-19, a fin de desarrollar un fortalecimiento en VET, mediante vigilancia epidemiológica de campo. Resultados: Se cuenta con personal capacitado, posibilidad de diagnóstico precoz y control oportuno, generado desde la Unidad Febril de Urgencias. El servicio de guardia presenta adecuado control de la población con TB, que posibilita la coordinación y trabajo en conjunto con otros programas ministeriales. Existe capacidad de respuesta de la institución ante los brotes, epidemias y pandemias. Discusión: La aplicación de este proyecto incorporará una actividad de fortalecimiento en vigilancia epidemiológica, donde el Hospital Muñiz, mediante el abordaje integral y la identificación de casos nuevos de respuesta a las necesidades de la población con TB. Se proporcionará así información válida y confiable para la prevención y control de la TB en la institución después de la pandemia por COVID-19.

[Monkeypox: characteristics in female population, Buenos Aires, Argentina]. / Viruela símica: características en población femenina, Buenos Aires, Argentina.

Monkeypox is a zoonotic viral disease caused by a virus of the genus Orthopoxvirus. As of January 1, 2022, it has been reported in 110 WHO Member States. It presents with fever, fatigue, painful lymphadenopathy, and rash. It lasts between 2 and 4 weeks. It is usually self-limited, but severe cases have been described in immunocompromised people. This study describes cases of monkeypox in women, diagnosed between June 2022 and February 2023, and it reports epidemiology, clinical aspects, and complications after infection. A retrospective observational study was carried out in the Febrile Emergency Unit (UFU), reviewing positive cases (RT-PCR) for monkeypox and the population with female biological sex was selected. They were questioned about gynecological complications, menstrual pattern, dyspareunia and pelvic pain. 340 consultations for monkeypox were made, 214 (63%) were positive, 211 cases (99%) male and 3 cases (1%) female. Among these cases is a trans woman, who was not included. The average age is 31 years, immunocompetent, with a negative serology report for HIV, syphilis, hepatitis B and C. Both cases had sexual intercourse without a barrier method. The most frequent symptoms are asthenia and skin lesions, especially in the upper and lower limbs, perianal and genital region. As a risk factor they presented unprotected sexual contact. Within the differential diagnoses, other sexually transmitted infections (STIs) should be considered. There were no gynecological complications reported during follow-up.

La viruela símica es una enfermedad viral zoonótica debida a un virus del género Orthopoxvirus. Desde el 1 de enero de 2022, se ha notificado en 110 Estados Miembros de la OMS. Se presenta con fiebre, astenia, linfoadenopatías dolorosas y exantema. Dura entre 2 y 4 semanas. Suele ser autolimitada y se han descrito casos graves en personas inmunocomprometidas. El presente trabajo describe casos de viruela símica en mujeres, diagnosticados entre junio del 2022 y febrero del 2023 Se realizó un estudio observacional retrospectivo en la Unidad Febril de Urgencias (UFU), revisando casos positivos (RT-PCR) para viruela símica y se seleccionó la población con sexo biológico femenino. Se consultó sobre complicaciones ginecológicas, patrón menstrual, dispareunia y dolor pélvico. Se realizaron 340 consultas por viruela símica, 214 (63%) fueron positivos, 211 casos (99%) de sexo masculino y 3 casos (1%) femeninos. Dentro de estos casos se encuentra una mujer trans, la cual no se incluyó. La edad promedio es de 31 años, inmunocompetentes, con reporte de serologías negativas para HIV, sífilis, hepatitis B y C. Ambos casos mantuvieron relaciones sexuales sin método de barrera. Los síntomas más frecuentes fueron astenia y lesiones en piel, sobre todo en miembros superiores e inferiores, región perianal y genital. Como factor de riesgo presentaron contacto sexual sin protección. Dentro de los diagnósticos diferenciales, debe tenerse en cuenta otras infecciones de transmisión sexual (ITS). En seguimiento epidemiológico no refirieron complicaciones ginecológicas.

Momentos históricos de la epidemiología en el Hospital Muñiz, Buenos Aires, Argentina / Historical events in epidemiology, at the Muñiz Hospital, Buenos Aires, Argentina

Resumen El hospital Muñiz es una institución con patrimonio histórico, cultural y sanitario. Se realiza aquí un análisis histórico de las diferentes epidemias/pandemias y bro tes, valorando los manejos epidemiológicos (vigilancia, prevención, control y gestión de emergencias) en la institución y el porqué de su arquitectura. Para tal fin se lleva a cabo una revisión sistemática de la literatura sobre la historia del hospital Muñiz y sus referentes desde 1980 hasta 2023, siguiendo el formato PRISMA. Se encontraron 36 publicaciones que cumplieron con los criterios metodológicos y epidemiológicos requeridos. La revisión muestra los problemas relevantes en salud, los eventos presentes en una epidemia/pandemia, la importancia de medidas de prevención y de evaluar la necesidad de un sistema de vigilancia epidemiológica continuo, así como el aporte de referentes históricos metodológicos que permita obtener información útil en el área de salud. Hemos abordado grandes momentos históricos en la epidemiología explicando el manejo de las enfermedades o epidemias/pandemias en el hospital Muñiz, las cuales se relacionaron en gran medida a la sociedad de la época (paradigmas). Cabe resaltar que el crecimiento poblacional extendió las enfermedades a lo largo del planeta generando amenazas y que las epide mias/pandemias transformaron las sociedades y muy posiblemente han cambiado decisivamente el curso de la historia, tal como paso con la pandemia por COVID-19.

Abstract The Muñiz hospital is an institution with historical, cultural and health heritage. A historical analysis of the different epidemics/pandemics and outbreaks is carried out here, assessing the epidemiological man agement (surveillance, prevention, control and emer gency management) in the institution and the reason for its architecture. To this end, a systematic review of the literature on the history of the Muñiz hospital and its references was carried out, since 1980 to 2023, following the PRISMA format. Thirty-six publications were found that met the required methodological and epidemiological criteria. The review shows the relevant health problems, the events present in an epidemic/ pandemic, the importance of preventive measures and to assess the need for a continuous epidemiological surveillance system, as well as the contribution of historical methodological references that allow obtaining useful information in the health area. We have addressed great historical moments in epidemiology, explaining the management of diseases or epidemics/pandemics at the Muñiz hospital, which were largely related to the society of the time (paradigms). It should be noted that population growth spread diseases throughout the planet, generating threats, and that epidemics/pan demics transformed societies and quite possibly have decisively changed the course of history, as happened with the COVID-19 pandemic.

[Historical events in epidemiology, at the Muñiz Hospital, Buenos Aires, Argentina]. / Momentos históricos de la epidemiología en el Hospital Muñiz, Buenos Aires, Argentina.

The Muñiz hospital is an institution with historical, cultural and health heritage. A historical analysis of the different epidemics/pandemics and outbreaks is carried out here, assessing the epidemiological management (surveillance, prevention, control and emergency management) in the institution and the reason for its architecture. To this end, a systematic review of the literature on the history of the Muñiz hospital and its references was carried out, since 1980 to 2023, following the PRISMA format. Thirty-six publications were found that met the required methodological and epidemiological criteria. The review shows the relevant health problems, the events present in an epidemic/ pandemic, the importance of preventive measures and to assess the need for a continuous epidemiological surveillance system, as well as the contribution of historical methodological references that allow obtaining useful information in the health area. We have addressed great historical moments in epidemiology, explaining the management of diseases or epidemics/pandemics at the Muñiz hospital, which were largely related to the society of the time (paradigms). It should be noted that population growth spread diseases throughout the planet, generating threats, and that epidemics/pandemics transformed societies and quite possibly have decisively changed the course of history, as happened with the COVID-19 pandemic.

El hospital Muñiz es una institución con patrimonio histórico, cultural y sanitario. Se realiza aquí un análisis histórico de las diferentes epidemias/pandemias y brotes, valorando los manejos epidemiológicos (vigilancia, prevención, control y gestión de emergencias) en la institución y el porqué de su arquitectura. Para tal fin se lleva a cabo una revisión sistemática de la literatura sobre la historia del hospital Muñiz y sus referentes desde 1980 hasta 2023, siguiendo el formato PRISMA. Se encontraron 36 publicaciones que cumplieron con los criterios metodológicos y epidemiológicos requeridos. La revisión muestra los problemas relevantes en salud, los eventos presentes en una epidemia/pandemia, la importancia de medidas de prevención y de evaluar la necesidad de un sistema de vigilancia epidemiológica continuo, así como el aporte de referentes históricos metodológicos que permita obtener información útil en el área de salud. Hemos abordado grandes momentos históricos en la epidemiología explicando el manejo de las enfermedades o epidemias/pandemias en el hospital Muñiz, las cuales se relacionaron en gran medida a la sociedad de la época (paradigmas). Cabe resaltar que el crecimiento poblacional extendió las enfermedades a lo largo del planeta generando amenazas y que las epidemias/ pandemias transformaron las sociedades y muy posiblemente han cambiado decisivamente el curso de la historia, tal como paso con la pandemia por COVID-19.

Análisis de los dos primeros años de pandemia COVID-19 en un hospital de enfermedades infecciosas, en Buenos Aires / Analysis of the first two years of the COVID-19 pandemic in an infectious diseases hospital in Buenos Aires

Resumen Introducción: En el Hospital Muñiz se instauró la Unidad Febril (UF), un dispositivo que opera durante la pandemia por COVID-19. Su implementación ha demos trado la importancia de políticas públicas en el sistema sanitario, además del posible desarrollo de estrategias en vigilancia y seguimiento epidemiológico que den apor tes en salud. Se realizó un análisis de los dos primeros años en pandemia en la UF-Muñiz. El objetivo de esta unidad es determinar qué pacientes tienen criterios de mal pronóstico y definir la internación. Una de las características más importantes de esta UF es la atención de una población con enfermedades infectocontagiosas por ser este un Hospital dedicado a este tipo de patologías. Métodos: Se realizó un estudio observacional trans versal, retrospectivo, con el objetivo de evaluar las inter naciones realizadas en la UF-Muñiz durante el periodo comprendido entre enero 2020 y diciembre 2021. Resultados: Se recibieron 153 546 consultas, se in ternaron 2872 pacientes. En 2020 se internaron 1001 pacientes COVID-19 positivos (76%), 87 con tuberculosis (TBC) (6.6%) y 102 con HIV (7.7%). En 2021 se internaron 991 pacientes COVID-19 positivos (66%), 151 con TBC (10%) y 157 con HIV (10.5%) Conclusiones: Solo el 1.9% de las consultas deriva ron en internación y correspondieron en su mayoría a pacientes COVID-19 positivos, le siguieron casos de HIV y TBC en una menor proporción. La enfermedad pulmo nar obstructiva crónica (EPOC) y la obesidad fueron las comorbilidades que con mayor frecuencia requirieron internación en pacientes COVID-19.

Abstract Introduction: At the Muñiz Hospital, the Febrile Unit (UF) was established, a device that operates during the COVID-19 pandemic. Its implementation has demon strated the importance of public policies in the health system, in addition to the possible development of epi demiological surveillance and monitoring strategies that provide health contributions. An analysis of the first two years of the pandemic at UF-Muñiz was carried out. The objective of this unit is to determine which patients have poor prognostic criteria and define hospitalization. One of the most important characteristics of this UF is the care of a population with infectious diseases because this is a Hospital dedicated to this type of pathology. Methods: A retrospective, cross-sectional observa tional study was carried out with the objective of evalu ating the hospitalizations made at UF-Muñiz during the period between January 2020 and December 2021. Results: 153 546 consultations were received, 2872 patients were admitted. In 2020, 1001 COVID-19 positive patients (76%) were admitted, 87 with tuberculosis (TB) (6.6%) and 102 with HIV (7.7%). In 2021, 991 positive CO VID-19 patients (66%) were admitted, 151 with TB (10%) and 157 with HIV (10.5%) Conclusions: Only 1.9% of the consultations led to hospitalization, and the majority corresponded to CO VID-19 positives, followed by HIV and TB cases in a smaller proportion. Chronic obstructive pulmonary dis ease (COPD) and obesity were the comorbidities that most frequently required hospitalization in COVID-19 patients.

[Analysis of the first two years of the COVID-19 pandemic in an infectious diseases hospital in Buenos Aires]. / Análisis de los dos primeros años de pandemia COVID-19 en un hospital de enfermedades infecciosas, en Buenos Aires.

INTRODUCTION: At the Muñiz Hospital, the Febrile Unit (UF) was established, a device that operates during the COVID-19 pandemic. Its implementation has demonstrated the importance of public policies in the health system, in addition to the possible development of epidemiological surveillance and monitoring strategies that provide health contributions. An analysis of the first two years of the pandemic at UF-Muñiz was carried out. The objective of this unit is to determine which patients have poor prognostic criteria and define hospitalization. One of the most important characteristics of this UF is the care of a population with infectious diseases because this is a Hospital dedicated to this type of pathology. METHODS: A retrospective, cross-sectional observational study was carried out with the objective of evaluating the hospitalizations made at UF-Muñiz during the period between January 2020 and December 2021. RESULTS: 153 546 consultations were received, 2872 patients were admitted. In 2020, 1001 COVID-19 positive patients (76%) were admitted, 87 with tuberculosis (TB) (6.6%) and 102 with HIV (7.7%). In 2021, 991 positive COVID-19 patients (66%) were admitted, 151 with TB (10%) and 157 with HIV (10.5%) Conclusions: Only 1.9% of the consultations led to hospitalization, and the majority corresponded to COVID-19 positives, followed by HIV and TB cases in a smaller proportion. Chronic obstructive pulmonary disease (COPD) and obesity were the comorbidities that most frequently required hospitalization in COVID-19 patients.

Introducción: En el Hospital Muñiz se instauró la Unidad Febril (UF), un dispositivo que opera durante la pandemia por COVID-19. Su implementación ha demostrado la importancia de políticas públicas en el sistema sanitario, además del posible desarrollo de estrategias en vigilancia y seguimiento epidemiológico que den aportes en salud. Se realizó un análisis de los dos primeros años en pandemia en la UF-Muñiz. El objetivo de esta unidad es determinar qué pacientes tienen criterios de mal pronóstico y definir la internación. Una de las características más importantes de esta UF es la atención de una población con enfermedades infectocontagiosas por ser este un Hospital dedicado a este tipo de patologías. Métodos: Se realizó un estudio observacional transversal, retrospectivo, con el objetivo de evaluar las internaciones realizadas en la UF-Muñiz durante el periodo comprendido entre enero 2020 y diciembre 2021. Resultados: Se recibieron 153 546 consultas, se internaron 2872 pacientes. En 2020 se internaron 1001 pacientes COVID-19 positivos (76%), 87 con tuberculosis (TBC) (6.6%) y 102 con HIV (7.7%). En 2021 se internaron 991 pacientes COVID-19 positivos (66%), 151 con TBC (10%) y 157 con HIV (10.5%) Conclusiones: Solo el 1.9% de las consultas derivaron en internación y correspondieron en su mayoría a pacientes COVID-19 positivos, le siguieron casos de HIV y TBC en una menor proporción. La enfermedad pulmonar obstructiva crónica (EPOC) y la obesidad fueron las comorbilidades que con mayor frecuencia requirieron internación en pacientes COVID-19.

[Monkeypox: Epidemiological surveillance in the Muñiz Outpatient Monitoring Unit, Buenos Aires]. / Viruela símica: Vigilancia epidemiológica en la Unidad de Monitoreo Ambulatorio Muñiz, Buenos Aires.

INTRODUCTION: Monkeypox (SV) is a zoonotic viral disease. Monkeypox virus belongs to the Orthopoxvirus genus of the Poxviridae family. In 1970 it was detected for the first time in humans, in the Democratic Republic of the Congo. It is currently considered an endemic disease in central and western Africa. It can present with fever, malaise, painful lymphadenopathy and rash, and last between 2 and 4 weeks. It is usually selflimited, although severe cases have been described, mainly in immunocompromised people, with lethality varies between 3% and 6% in endemic countries. The objectives of epidemiological surveillance in suspected cases of SV are: to describe the personal variables, time and place of the reported cases, to track and follow up their contacts, to identify outbreaks and perform clinical epidemiological follow-up. METHODS: A retrospective cohort study was conducted from June 9 to September 15, 2022. RESULTS: 82 patients with compatible symptoms have been treated, 56 cases were positive and 26 negative. Of the 26 negative cases, 7 cases (27%) corresponded to chickenpox, 4 cases (15%) to syphilis, and 2 cases (8%) to herpes zoster. CONCLUSIONS: The first symptoms began two to five days prior to consultation, the most frequent being fever, myalgia, asthenia, headache, and painful lymphadenopathy. Epidemiological surveillance of SV provides timely detection of cases, continuous and systematic follow-up of contacts through an integrated process between surveillance and laboratory, to generate timely, valid and reliable information, which allows guiding prevention and control measures.

Introducción: La viruela símica (VS) es una enfermedad viral zoonótica debida a un virus del género Orthopoxvirus, familia Poxviridae. En 1970 se detectó por primera vez en humanos en la República Democrática del Congo. Actualmente es endémica en áfrica central y occidental. Puede presentarse con fiebre, malestar general, linfo-adenopatías dolorosas y exantema, y durar entre 2 y 4 semanas. Suele ser autolimitada, aunque se han descrito casos graves, principalmente en personas inmunocomprometidas, con una letalidad que varía entre 3% y 6% en países endémicos. Los objetivos de la vigilancia epidemiológica en los casos sospechosos de VS son: describir las variables personales, tiempo y lugar de los casos notificados, realizar un rastreo y seguimiento de sus contactos, identificar brotes y realizar seguimiento clínico epidemiológico. Métodos: Se realizó un estudio de cohorte retrospectivo durante el 9 de junio al 15 de septiembre de 2022. Resultados: Se han atendido 82 pacientes con sintomatología compatible 56 casos fueron positivos y 26 negativos. De los 26 casos negativos, 7 casos (27%) correspondían a varicela, 4 caso s (15%) a sífilis y 2 casos (8%) a herpes zoster. Los primeros síntomas se iniciaron dos a cinco días previos a la consulta, siendo los más frecuentes fiebre, mialgia, astenia, cefalea y linfoadenopatía dolorosa. Conclusiones: La vigilancia epidemiológica de VS permite la detección de casos, el seguimiento continuo y sistemático de los contactos mediante un proceso integrado entre vigilancia y laboratorio, para generar información oportuna, válida y confiable, que permite orientar medidas de prevención y control.

Viruela símica: vigilancia epidemiológica en la Unidad de Monitoreo Ambulatorio Muñiz, Buenos Aires / Monkeypox: epidemiological surveillance in the Muñiz Outpatient Monitoring Unit, Buenos Aires

Resumen Introducción: La viruela símica (VS) es una enfermedad viral zoonótica debida a un virus del género Orthopoxvirus, familia Poxviridae. En 1970 se detectó por primera vez en humanos en la República Democrática del Congo. Actualmente es endémica en África central y occidental. Puede presentarse con fiebre, malestar general, linfo-adenopatías dolorosas y exantema, y durar entre 2 y 4 semanas. Suele ser autolimitada, aunque se han descrito casos graves, principalmente en personas inmunocomprometidas, con una letalidad que varía entre 3% y 6% en países endémicos. Los objetivos de la vigilancia epidemiológica en los casos sospecho sos de VS son: describir las variables personales, tiempo y lugar de los casos notificados, realizar un rastreo y seguimiento de sus contactos, identificar brotes y realizar seguimiento clínico epidemiológico. Métodos: Se realizó un estudio de cohorte retrospectivo durante el 9 de junio al 15 de septiembre de 2022. Resultados: Se han atendido 82 pacientes con sintomatología compatible 56 casos fueron positivos y 26 negativos. De los 26 casos negativos, 7 casos (27%) correspondían a varicela, 4 caso s (15%) a sífilis y 2 casos (8%) a herpes zoster. Los primeros síntomas se iniciaron dos a cinco días previos a la consulta, siendo los más frecuentes fiebre, mialgia, astenia, cefalea y linfoadenopatía dolorosa. Conclusiones: La vigilancia epidemiológica de VS permite la detección de casos, el seguimiento continuo y sistemático de los contactos mediante un proceso integrado entre vigilancia y laboratorio, para generar información oportuna, válida y confiable, que permite orientar medidas de prevención y control.

Abstract Introduction: Monkeypox (SV) is a zoonotic viral disease. Monkeypox virus belongs to the Ortho poxvirus genus of the Poxviridae family. In 1970 it was detected for the first time in humans, in the Democratic Republic of the Congo. It is currently considered an endemic disease in central and western Africa. It can pres ent with fever, malaise, painful lymphadenopathy and rash, and last between 2 and 4 weeks. It is usually self-limited, although severe cases have been described, mainly in immunocompromised people, with lethality varies between 3% and 6% in endemic countries. The objectives of epidemiological surveillance in suspected cases of SV are: to describe the personal variables, time and place of the reported cases, to track and follow up their contacts, to identify outbreaks and perform clinical epidemiological follow-up. Methods: A retrospective cohort study was conducted from June 9 to September 15, 2022. Results: 82 patients with compatible symptoms have been treated, 56 cases were positive and 26 negative. Of the 26 negative cases, 7 cases (27%) corresponded to chickenpox, 4 cases (15%) to syphilis, and 2 cases (8%) to herpes zoster. Conclusions: The first symptoms began two to five days prior to consultation, the most frequent being fever, myalgia, asthenia, headache, and painful lymphadenopathy. Epidemiological surveillance of SV provides timely detection of cases, continuous and systematic follow-up of contacts through an integrated process between surveillance and laboratory, to generate timely, valid and reliable information, which allows guiding prevention and control measures.

Practical Pharmacological Aspects of Drugs Used for the Treatment of Drug-Resistant Tuberculosis in Adults and Children / Aspectos farmacológicos prácticos de las drogas para el tratamiento de la tuberculosis drogorresistente en adultos y pediatría

ABSTRACT The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practical pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.

RESUMEN La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.

Aspectos farmacológicos prácticos de las drogas para el tratamiento de la tuberculosis drogorresistente en adultos y pediatría / Practical Pharmacological Aspects of Drugs Used for the Treatment of Drug-Resistant Tuberculosis in Adults and Children

La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.

The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practi cal pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.

Tratamiento de la tuberculosis drogorresistente en adultos y niños. Revisión narrativa / Treatment of drug-resistant tuberculosis in adults and children. A narrative review

Resumen Desde 2018 han surgido a la luz de la evidencia importantes cambios en el tratamiento de la tuberculosis drogorresistente. El descubrimiento de nuevas drogas antituberculosis, como la bedaquilina y los derivados de nitroimidazopiranos, así como la utilización de drogas repropuestas, llevó a la recomendación de organismos internacionales de nuevos esquemas de tratamiento de la tuberculosis monorresistente y multidro gorresistente que son totalmente orales y así dejan de lado el uso prolongado de inyectables, con su inherente toxicidad e incomodidad. Algunas de las definiciones de tuberculosis drogorresistente han cambiado. También está en revisión el tiempo de su tratamiento y con algunos nuevos esquemas en estudio, como el BpaL (bedaquilina, pretomanid y linezolid), se ha logrado una duración similar a la del tratamiento de la tuberculosis pansensible. En esta revisión bibliográfica narrativa describimos las nuevas definiciones, algunos aspectos diagnósticos básicos, los aspectos farmacológicos y la nueva clasificación de las drogas a utilizar en el tratamiento de la tuberculosis drogorresistente, así como los esquemas actualmente propuestos para tratarla, contextualizados con la realidad nacional. Finalizamos con una breve reseña de los estudios clínicos en curso de nuevos esquemas acortados de tratamiento.

Abstract Since 2018, important changes in the treatment of drug-resistant tuberculosis have been produced in the light of new evidence. The discovery of new anti-tuberculosis drugs, such as bedaquiline and nitroimidazopirane derivatives, as well as the use of repurposed drugs, led to international organizations to recommend new, totally oral, treatment regimens for mono-resistant and multidrug-resistant tuberculosis, leaving aside the prolonged use of injectables, with their inherent toxicity and discomfort. Some definitions of drug-resistant tuberculosis have changed. The duration of treatment is also under review, leading some new regimens under study, such as BPaL (bedaquiline, pretomanid and linezolid), to a duration similar to that for treating susceptible tuberculosis. In this narrative review, we describe the new definitions, some basic diagnostic aspects, the pharmacological aspects, and the new classification of drugs to be used in the treatment of drug-resistant tuberculosis as well as the cur rently proposed schemes to treat it available within the Argentinean context. Finally, we include a brief review of ongoing clinical trials on new shortened treatments.

[Treatment of drug-resistant tuberculosis in adults and children. A narrative review]. / Tratamiento de la tuberculosis drogorresistente en adultos y niños. Revisión narrativa.

Since 2018, important changes in the treatment of drug-resistant tuberculosis have been produced in the light of new evidence. The discovery of new anti-tuberculosis drugs, such as bedaquiline and nitroimidazopirane derivatives, as well as the use of repurposed drugs, led to international organizations to recommend new, totally oral, treatment regimens for mono-resistant and multidrug-resistant tuberculosis, leaving aside the prolonged use of injectables, with their inherent toxicity and discomfort. Some definitions of drug-resistant tuberculosis have changed. The duration of treatment is also under review, leading some new regimens under study, such as BPaL (bedaquiline, pretomanid and linezolid), to a duration similar to that for treating susceptible tuberculosis. In this narrative review, we describe the new definitions, some basic diagnostic aspects, the pharmacological aspects, and the new classification of drugs to be used in the treatment of drug-resistant tuberculosis as well as the currently proposed schemes to treat it available within the Argentinean context. Finally, we include a brief review of ongoing clinical trials on new shortened treatments.

Desde 2018 han surgido a la luz de la evidencia importantes cambios en el tratamiento de la tuberculosis drogorresistente. El descubrimiento de nuevas drogas antituberculosis, como la bedaquilina y los derivados de nitroimidazopiranos, así como la utilización de drogas repropuestas, llevó a la recomendación de organismos internacionales de nuevos esquemas de tratamiento de la tuberculosis monorresistente y multidrogorresistente que son totalmente orales y así dejan de lado el uso prolongado de inyectables, con su inherente toxicidad e incomodidad. Algunas de las definiciones de tuberculosis drogorresistente han cambiado. También está en revisión el tiempo de su tratamiento y con algunos nuevos esquemas en estudio, como el BpaL (bedaquilina, pretomanid y linezolid), se ha logrado una duración similar a la del tratamiento de la tuberculosis pansensible. En esta revisión bibliográfica narrativa describimos las nuevas definiciones, algunos aspectos diagnósticos básicos, los aspectos farmacológicos y la nueva clasificación de las drogas a utilizar en el tratamiento de la tuberculosis drogorresistente, así como los esquemas actualmente propuestos para tratarla, contextualizados con la realidad nacional. Finalizamos con una breve reseña de los estudios clínicos en curso de nuevos esquemas acortados de tratamiento.

La Unidad Febril de Urgencias del Hospital Muñiz frente a COVID-19, HIV y tuberculosis / The Febrile Emergency Unit at Muñiz Hospital facing COVID-19, HIV and tuberculosis

Resumen Para hacer frente a la pandemia causada por el SARS CoV-2, en la Ciudad Autónoma de Buenos Aires se establecieron Unidades Febriles de Urgencias anexas a los hospitales de alta compleji dad. Se realizó un estudio observacional y retrospectivo con el objeto de evaluar el perfil de las personas que consultaron durante el período comprendido entre las semanas epidemiológicas 28 y 42, 2020. Se recibieron 12 571 consultas, el promedio de edad fue 38.2 años y 6801 (54.1%) pacientes eran varones. Se realizaron 9501 hisopados (RT-PCR para SARS-CoV-2) y 2499 (26.3%) fueron confirmados positivos. La edad media de los confirmados para COVID-19 fue 37.9 años, 1367 (54.7%) eran varones y 143 (5.7%) requirieron internación en la primera consulta. Tantos como 6097 (48.5%) participantes contaban con obra social o medicina prepaga. Consultaron solo 160 pacientes con HIV, se diagnosticó coinfección HIV/COVID-19 en 39/160 (24.4%) infectados con HIV y requirieron internación 9/39 (23.1%) coinfectados. Consultaron 128 pacientes con tuberculosis (TB), se diagnosticó coinfección TB/COVID-19 en 31/128 (24.2%) y requirieron internación 8/31 (25.8%) coinfectados. La triple asociación HIV/TB/COVID-19 fue constatada en 2 pacientes. Contrariamente a lo esperado, las dos principales enfermedades atendidas en el hospital, TB y HIV, estuvieron poco representadas en la consulta, pero el requerimiento de internación para los coinfectados fue elevado. Esto puede deberse a consulta tardía por restricciones de movilidad y asistencia durante la cuarentena. Nuestros datos también indican que el sector público de la ciudad debió absorber demanda insatisfecha del sector privado.

Abstract Febrile Emergency Units were annexed to tertiary hospitals to face the pandemic caused by SARS CoV-2 in Buenos Aires City. We performed a retrospective observational study in order to evaluate the profile of people consulting the Unit annexed to the Muñiz Hospital, during the period comprising epidemiological weeks 28 to 42, 2020. The total number of consultations was 12 571; 6801 (54.1%) patients were male, and the average age was 38 years. A total of 2499 (26.3 %) of 9501 swabs resulted positive for SARS-CoV-2 when analyzed by RT-PCR. The average age of confirmed COVID-19 patients was 37.9 years; 1367 (54.7%) were male and 143 (5.7%) required hospitalization at the first consultation. As many as 6097 (48.5%) participants were beneficiaries of social security or prepaid medicine. Only 160 (1.3%) were HIV positive, with COVID-19 coinfection diagnosed in 39/160 (24.4%), of which 9 (23.1%) required hospitalization. Only 128 (1%) had tuberculosis (TB); TB/CO VID-19 coinfection was diagnosed in 31 of them (24.2%), and 8/31 (25.8%) required hospitalization. The triple association HIV/TB /COVID-19 was reported in only 2 patients. Contrary to expectations, TB and HIV, the two main diseases treated in our hospital, were under-represented in this Emergency Unit, but the requirement of hospitalization for coinfected patients was quite frequent. This may be due to late consultation caused by mobility and assistance restrictions during quarantine. Interestingly, our data also indicate that the city's public sector had to absorb unsatisfied demand from the private sector and suburban population.

[The Febrile Emergency Unit at Muñiz Hospital facing COVID-19, HIV and tuberculosis]. / La Unidad Febril de Urgencias del Hospital Muñiz frente a COVID-19, HIV y tuberculosis.

Febrile Emergency Units were annexed to tertiary hospitals to face the pandemic caused by SARS CoV-2 in Buenos Aires City. We performed a retrospective observational study in order to evaluate the profile of people consulting the Unit annexed to the Muñiz Hospital, during the period comprising epidemiological weeks 28 to 42, 2020. The total number of consultations was 12 571; 6801 (54.1%) patients were male, and the average age was 38 years. A total of 2499 (26.3 %) of 9501 swabs resulted positive for SARS-CoV-2 when analyzed by RT-PCR. The average age of confirmed COVID-19 patients was 37.9 years; 1367 (54.7%) were male and 143 (5.7%) required hospitalization at the first consultation. As many as 6097 (48.5%) participants were beneficiaries of social security or prepaid medicine. Only 160 (1.3%) were HIV positive, with COVID-19 coinfection diagnosed in 39/160 (24.4%), of which 9 (23.1%) required hospitalization. Only 128 (1%) had tuberculosis (TB); TB/COVID-19 coinfection was diagnosed in 31 of them (24.2%), and 8/31 (25.8%) required hospitalization. The triple association HIV/TB /COVID-19 was reported in only 2 patients. Contrary to expectations, TB and HIV, the two main diseases treated in our hospital, were under-represented in this Emergency Unit, but the requirement of hospitalization for coinfected patients was quite frequent. This may be due to late consultation caused by mobility and assistance restrictions during quarantine. Interestingly, our data also indicate that the city's public sector had to absorb unsatisfied demand from the private sector and suburban population.

Para hacer frente a la pandemia causada por el SARS CoV-2, en la Ciudad Autónoma de Buenos Aires se establecieron Unidades Febriles de Urgencias anexas a los hospitales de alta complejidad. Se realizó un estudio observacional y retrospectivo con el objeto de evaluar el perfil de las personas que consultaron durante el período comprendido entre las semanas epidemiológicas 28 y 42, 2020. Se recibieron 12 571 consultas, el promedio de edad fue 38.2 años y 6801 (54.1%) pacientes eran varones. Se realizaron 9501 hisopados (RT-PCR para SARS-CoV-2) y 2499 (26.3%) fueron confirmados positivos. La edad media de los confirmados para COVID-19 fue 37.9 años, 1367 (54.7%) eran varones y 143 (5.7%) requirieron internación en la primera consulta. Tantos como 6097 (48.5%) participantes contaban con obra social o medicina prepaga. Consultaron solo 160 pacientes con HIV, se diagnosticó coinfección HIV/COVID-19 en 39/160 (24.4%) infectados con HIV y requirieron internación 9/39 (23.1%) coinfectados. Consultaron 128 pacientes con tuberculosis (TB), se diagnosticó coinfección TB/COVID-19 en 31/128 (24.2%) y requirieron internación 8/31 (25.8%) coinfectados. La triple asociación HIV/TB/COVID-19 fue constatada en 2 pacientes. Contrariamente a lo esperado, las dos principales enfermedades atendidas en el hospital, TB y HIV, estuvieron poco representadas en la consulta, pero el requerimiento de internación para los coinfectados fue elevado. Esto puede deberse a consulta tardía por restricciones de movilidad y asistencia durante la cuarentena. Nuestros datos también indican que el sector público de la ciudad debió absorber demanda insatisfecha del sector privado.

Tuberculosis Exacerbates HIV-1 Infection through IL-10/STAT3-Dependent Tunneling Nanotube Formation in Macrophages.

The tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb), and HIV-1 act synergistically; however, the mechanisms by which Mtb exacerbates HIV-1 pathogenesis are not well known. Using in vitro and ex vivo cell culture systems, we show that human M(IL-10) anti-inflammatory macrophages, present in TB-associated microenvironment, produce high levels of HIV-1. In vivo, M(IL-10) macrophages are expanded in lungs of co-infected non-human primates, which correlates with disease severity. Furthermore, HIV-1/Mtb co-infected patients display an accumulation of M(IL-10) macrophage markers (soluble CD163 and MerTK). These M(IL-10) macrophages form direct cell-to-cell bridges, which we identified as tunneling nanotubes (TNTs) involved in viral transfer. TNT formation requires the IL-10/STAT3 signaling pathway, and targeted inhibition of TNTs substantially reduces the enhancement of HIV-1 cell-to-cell transfer and overproduction in M(IL-10) macrophages. Our study reveals that TNTs facilitate viral transfer and amplification, thereby promoting TNT formation as a mechanism to be explored in TB/AIDS potential therapeutics.

Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery.

OBJECTIVES: No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery. METHODS: This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015. Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery. RESULTS: 57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS: The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Tuberculosis is associated with expansion of a motile, permissive and immunomodulatory CD16(+) monocyte population via the IL-10/STAT3 axis.

The human CD14(+) monocyte compartment is composed by two subsets based on CD16 expression. We previously reported that this compartment is perturbed in tuberculosis (TB) patients, as reflected by the expansion of CD16(+) monocytes along with disease severity. Whether this unbalance is beneficial or detrimental to host defense remains to be elucidated. Here in the context of active TB, we demonstrate that human monocytes are predisposed to differentiate towards an anti-inflammatory (M2-like) macrophage activation program characterized by the CD16(+)CD163(+)MerTK(+)pSTAT3(+) phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. This process is dependent on STAT3 activation, and loss-of-function experiments point towards a detrimental role in host defense against TB. Importantly, we provide a critical correlation between the abundance of the CD16(+)CD163(+)MerTK(+)pSTAT3(+) cells and the progression of the disease either at the local level in a non-human primate tuberculous granuloma context, or at the systemic level through the detection of the soluble form of CD163 in human sera. Collectively, this study argues for the pathogenic role of the CD16(+)CD163(+)MerTK(+)pSTAT3(+) monocyte-to-macrophage differentiation program and its potential as a target for TB therapy, and promotes the detection of circulating CD163 as a potential biomarker for disease progression and monitoring of treatment efficacy.

Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina / First Series of Patients With XDR and Pre-XDR TB Treated With Regimens That Included Meropenen-clavulanate in Argentina

La tuberculosis extensamente resistente (TB-XDR) y pre-XDR comprometen seriamente el pronóstico de la enfermedad, y su tratamiento requiere inevitablemente el uso de fármacos del grupo V (Organización Mundial de la Salud [OMS]). Se analizó retrospectivamente la evolución de todos los pacientes con TB pre-XDR y XDR asistidos en un servicio especializado durante 2012 y 2013, medicados con regímenes que incluyeron por lo menos 6 meses de meropenem-clavulanato (MPC), capreomicina, moxifloxacina, linezolid, clofazimina, isoniacida en alta dosis, PAS y en un caso bedaquilina. Fueron tratados 10 pacientes, 9 de ellos con un extenso patrón de resistencia a un mínimo de 6 fármacos y uno por reacciones adversas e interacciones medicamentosas que generaron una situación análoga. Ocho de los 10 pacientes tratados, hicieron la conversión bacteriológica del esputo (2 cultivos mensuales consecutivos negativos) en un lapso de 2 a 7 meses, en tanto que 2 fallecieron. No se observaron reacciones adversas atribuibles a la administración prolongada del MPC

XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group V drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreomycin, moxifloxacin, linezolid, clofazimine, high-dose isoniazid, PAS, and bedaquiline in 1 case, were retrospectively analyzed. Ten patients were treated, 9 with an extensive pattern of resistance to at least 6 drugs, and 1 because of adverse reactions and drug interactions leading to a similar situation. Eight of the 10 patients treated achieved bacteriological sputum conversion (2 consecutive negative monthly cultures) over a period of 2–7 months, while 2 died. No adverse reactions attributable to prolonged administration of MPC were observed

First series of patients with XDR and pre-XDR TB treated with regimens that included meropenen-clavulanate in Argentina.

XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group V drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreomycin, moxifloxacin, linezolid, clofazimine, high-dose isoniazid, PAS, and bedaquiline in 1 case, were retrospectively analysed. Ten patients were treated, 9 with an extensive pattern of resistance to at least 6 drugs, and 1 because of adverse reactions and drug interactions leading to a similar situation. Eight of the 10 patients treated achieved bacteriological sputum conversion (2 consecutive negative monthly cultures) over a period of 2-7 months, while 2 died. No adverse reactions attributable to prolonged administration of MPC were observed.