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

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

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

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

Características clínicas de la hepatotoxicidad asociada a la pirazinamida en pacientes de un hospital de Lima, Perú / Clinical characteristics of pyrazinamide-associated hepatotoxicity in patients at a hospital in Lima, Peru

RESUMEN Con el objetivo de determinar las características de la enfermedad hepática inducida por el medicamento (DILI) se realizó un estudio de pacientes adultos con diagnóstico de tuberculosis y esquema de tratamiento antituberculoso con pirazinamida. El análisis de causa efecto de la DILI fue mediante el proceso de reexposición. Se encontraron 10 pacientes con DILI asociada a pirazinamida, la mediana de edad y de estancia hospitalaria fue de 40,5 años (rango 22-76) y 41 días (rango 11-130), respectivamente. La mediana de presentación del evento fue de 14 días (rango 3-46), 4 pacientes presentaron ictericia, 5 tuvieron patrón hepatocelular, 3 mixtas y 2 colestásicos. La presentación de la DILI fue leve en 6 casos (60%) y moderados en 3 (30%). En conclusión, la DILI asociada a la pirazinamida requiere estancia hospitalaria prolongada, se presenta con ictericia en un poco más de un tercio de los casos siendo el patrón predominante el hepatocelular.

ABSTRACT In order to determine the characteristics of drug-induced liver injury (DILI), adult patients diagnosed with tuberculosis and with an anti-tuberculosis treatment scheme including pyrazinamide were studied. The re-exposure process was used for the cause-effect analysis of the DILI. A total of 10 patients were found with pyrazinamide-associated DILI; the median age and hospital stay were 40.5 years (from 22 to 76 years) and 41 days (from 11 to 130 days), respectively. The median time in which the events appeared was 14 days (from 3 to 46 days); jaundice was observed in 4 patients and radiological patterns such as hepatocellular, mixed and cholestatic were found in 5, 3 and 2 patients, respectively. Mild presentation of DILI was observed in 6 cases (60%) and moderate in 3 (30%). In conclusion, pyrazinamide-associated DILI required prolonged hospital stay, presented jaundice in little more than a third of the cases, and radiologically, the hepatocellular pattern predominated.

Disseminated tuberculosis associated with reactive arthritis of Poncet in an immunocompetent patient

Abstract Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment.

Sensibilidad a drogas de primera línea frente a cepas de M. tuberculosis del CRN Micobacterias, Guayas, 2016 / Sensitivity to first-line drugs against strains of M. tuberculosis of the CRN Micobacterias, Guayas, 2016

Objetivo: Determinar el perfil de sensibilidad de Mycobacterium tuberculosis a drogas de primera línea en cepas que llegan de diferentes unidades de salud de la provincia del Guayas. Materiales y métodos. Se trabajó con 614 cepas de Mycobacterium tuberculosis, las cuales se le realizó las pruebas de sensibilidad a drogas de primera (rifampicina, isoniacida, estreptomicina y etambutol) por el por el método de proporciones (Rist, Canetti, Grosset) y pirazinamida evaluada por el método Wayne. Resultado: Se realizó perfil de sensibilidad a 614 cepas, de las cuales el 70 % (n=427) es sensible a todas las drogas, 20 % (n=124) presentó resistencia al menos a una droga, el restante corresponden a cepas MDR. TB-Monorresistente tiene mayor incidencia (n=83) que la MDR (n=12) en pacientes sin tratamiento previo. Por otro lado en pacientes antes tratado la TB-Monorresistente es menor a la MDR (n=41 y n=51 respectivamente). Conclusiones: el método de proporciones sigue siendo la técnica de referencia. Se observa mayor sensibilidad a drogas de primera línea en pacientes sin tratamiento previo. Es de importancia clínica llevar un correcto seguimiento a pacientes que presenten algún tipo de resistencia, pero es prioridad preventiva la no conversión de los pacientes sensibles a fin de evitar la diseminación de cepas resistentes.

Objective: Difine first line susceptibility drug profile of Mycobacterium tuberculosis, to diferent strain from Province Guayas health establishments. Material and Methods.614 Mycobacterium tuberculosis strain were analized by first line susceptibility drug test (rifampicin, isoniazid, streptomycin, ethambutol) used proportions method (Rist, Canetti, Grosset) and pyrazinamide Wayne´s methods. Results: 614 strain were studied, 70 % strains (n=427) result sensible, 20 % (n=124) have at least resistence one drug; the residue responds to MDR strains. The TB-Monoresistence haved more incidence (n=83) than MDR (n=12) in virgin treatments patients. Nevertheless; in previous treatment patients, the TB-Monoresistence is smaller than MDR (n=41 y n=51 respectively). Conclutions: The proportion method is the reference technique. The analize shown biggest sensibility in virgin treatment patients for first line drugs. Is very important have a correct control of resistant pactients, but is preventive priority the non conversion of sensibility patients to avoid dissemination resistance strain.

The impact of ocular tuberculosis on vision after two months of intensive therapy

ABSTRACT Tuberculosis is an infectious disease of global importance with major economic and social burden accounting for 25% of all avoidable deaths in developing countries. Extrapulmonary involvement may occur either in association with clinically apparent pulmonary tuberculosis or in isolation. This cross-sectional descriptive study aimed to evaluate the impact of ocular tuberculosis in visual acuity at baseline and after two months of intensive anti-tuberculous therapy. A sample of 133 pulmonary tuberculosis patients, seven disseminated tuberculosis, and three pleural tuberculosis patients was evaluated. All patients underwent routine ophthalmic evaluation, including assessment of visual acuity, biomicroscopy, applanation tonometry, indirect ophthalmoscopy, and fluorescent angiography as appropriate. None of the patients had impaired visual acuity due to tuberculosis. A rate of 4.2% (6/143) of ocular involvement was found. None of the patients with ocular involvement were HIV-infected. Of the six patients with ocular involvement, five met the diagnostic criteria for probable and one for possible ocular lesions. As for the type of ocular lesions, two patients had bilateral findings: one had sclerouveitis and the second had choroidal nodules. The other four patients presented with unilateral lesions: peripheral retinal artery occlusion in the right eye (one case), choroidal nodules in the left eye (one case), and choroidal nodules in the right eye (two cases). Patients progressed favorably after two month of intensive therapy, with no significant reduction in vision.

Osteomielitis por Mycobacterium tuberculosis / Mycobacterium tuberculosis osteomyelitis

Resumen Introducción: en Uruguay se ha notificado un aumento en el número de casos de tuberculosis en niños con formas pulmonares y extrapulmonares. La infección osteoarticular representa 10%-15% de las formas extrapulmonares. Objetivo: alertar sobre una etiología poco habitual de osteomielitis cuya forma de presentación genera dificultades diagnósticas. Caso clínico: niña de 18 meses, previamente sana. Consulta por edema e impotencia funcional de tobillo derecho de tres meses de evolución, en apirexia. La radiografía muestra múltiples imágenes geódicas en el sector distal de la diáfisis con secuestro en peroné derecho. Se realiza punción ósea obteniéndose líquido serohemático. El cultivo de dicha muestra y el hemocultivo fueron negativos. Luego de recibir clindamicina 21 días más gentamicina 10 días por via intravenosa y dos limpiezas quirúrgicas, se otorga alta con cefuroxime acetil vía oral. El cultivo de la muestra ósea desarrolló Mycobacterium tuberculosis. Se inició tratamiento con isoniacida, rifampicina y piracinamida. No fue identificado el caso índice. Discusión: la presentación clínica de la tuberculosis ósea es generalmente insidiosa lo que generando dificultades y retraso en el diagnóstico. Sólo la biopsia permite confirmar el diagnóstico. La situación epidemiológica actual obliga a descartar posible etiología tuberculosa ante un proceso inflamatorio osteoarticular de evolución tórpida. El tratamiento oportuno y adecuado requiere alto índice de sospecha y realización sistemática de punción ósea y/o articular.

Summary Introduction: in Uruguay, an increase in the number of cases of TB with pulmonary and extra-pulmonary involvement in children has been reported. Osteoarticular infections represent 10%-15% of extra-pulmonary involvement. Objective: to warn about an uncommon etiology of osteomyelitis whose presentation results in diagnostic difficulties. Clinical case: 18 month-old girl, previously healthy. Consultation was due to edema and right ankle functional insuficiency with three-month evolution, under apyrexia. X-ray imaging revealed multiple geodesic images in the distal portion of diaphysis, as well as a small sequestrum in right fibula. Through a bone puncture, serohematic fluid was extracted. Culture and hemoculture were negative. Treatment consisted of 21 days of intravenous clindamycin and 10 days of gentamicin. Two surgical debridements were performed. Progressive recovery followed. The child was discharged under cefuroxime axetil oral suspension and later a bone culture showed positive results for Mycobacterium TB. Treatment with isoniazid, rifampin and pyrazinamide was started. Index case could not be identified. Discussion: clinical presentation of bone tuberculosis is generally insidious. This explains difficulties and delays in diagnosis. It is remarkable that only biopsy allows the confirmation of diagnosis. The present epimediologic condition forces us to rule out possible TB etiology in the presence of an inflammatory osteoarticular process of lethargic evolution. Timely and accurate treatment requires a high degree of suspicion, as well as the performance of systematic bone and/or joint puncture.

Estimated rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a ­four-drug fixed-dose combination regimen at a tertiary health care facility in the city of Rio de Janeiro, Brazil / Estimativas das taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com esquema de dose fixa combinada de quatro drogas em uma unidade de saúde terciária na cidade do Rio de Janeiro

ABSTRACT Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

RESUMO Objetivo: Estimar as taxas de recidiva, cura e abandono de tratamento em pacientes com tuberculose pulmonar tratados com o esquema de dose fixa combinada (DFC) de quatro drogas e avaliar possíveis fatores associados. Métodos: Estudo observacional retrospectivo com 208 pacientes com diagnóstico confirmado de tuberculose pulmonar registrados no Programa de Controle da Tuberculose Hospitalar do Instituto de Doenças do Tórax, localizado na cidade do Rio de Janeiro. Os pacientes tratados entre janeiro de 2007 e outubro de 2010 receberam o esquema rifampicina-isoniazida-pirazinamida (RHZ), e aqueles tratados entre novembro de 2010 e junho de 2013 receberam o esquema rifampicina-isoniazida-pirazinamida-etambutol em DFC (RHZE/DFC). Os dados dos pacientes sobre recidiva e óbito foram obtidos no Sistema de Informação de Agravos de Notificação e no Sistema de Informação de Mortalidade, respectivamente. O período de acompanhamento foi de dois anos após o encerramento do tratamento. Resultados: As taxas de cura, abandono e óbito foram de 90,4%, 4,8% e 4,8%, respectivamente. Houve 7 casos de recidivas durante o período de acompanhamento. Não houve diferenças significativas na taxa de recidiva entre os grupos de tratamento RHZ e RHZE/DFC (p = 0,13). Não foram identificados fatores associados com a ocorrência de recidiva, nem houve diferenças estatisticamente significativas na ocorrência dos efeitos adversos ou nas taxas de cura, abandono e óbito entre os grupos de tratamento. Conclusões: A adoção do esquema de tratamento RHZE/DFC não produziu diferenças estatisticamente significativas nas taxas de recidiva, cura e abandono nem na ocorrência de efeitos adversos em comparação com o esquema RHZ.

In vitro antimicrobial efficacy of a fixed-dose combination of RHZE against M. tuberculosis

ABSTRACT The use of drugs in fixed-dose combination (FDC) is now recommended by the World Health Organization (WHO) due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB) in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance.

Determinação simultânea de Rifampicina, Isoniazida, Pirazinamida e Etambutol em comprimidos com doses fixas combinadas / Method for simultaneously determining the Rifampin, Isoniazid, Pyrazinamide and Ethambutol in the combined fixed-dose tablets

Os comprimidos utilizados no tratamento da tuberculose possuem quatro fármacos associados, isoniazida, pirazinamida, etambutol e rifampicina, e são distribuídos gratuitamente pelo Sistema Único de Saúde. Os métodos analíticos oficiais para analisar este medicamento estão especificados na Farmacopeia Americana 36a edição e na Farmacopeia Internacional 4a edição. Porém, estes compêndios oficiais não possuem monografias para análise simultânea dos quatro fármacos. O objetivo deste estudo foi desenvolver uma metodologia para determinar simultaneamente os princípios ativos em comprimidos dose fixa combinada, utilizando-se cromatografia a líquido de alta eficiência com detector de ultravioleta-visível, pois é de grande importância para o controle da qualidade do medicamento. O método desenvolvido utilizou coluna cromatográfica C18 (250 x 4,6) mm e 5 μm, fase móvel constituída de fase aquosa (85 % tampão formiato de amônio 0,3 mol/L pH 5, 15 % metanol e 0,005 mol/L de Cu2+ ou 250 mg/L de CuSO4.5H2O) e fase orgânica (metanol, 0,1 % de trietilamina e 0,2 % de ácido fórmico). O fluxo foi de 1,0 mL/min e comprimento de onda de 265 nm para isoniazida, pirazinamida e o etambutol e de 335 nm para rifampicina. Este método apresentou desvio padrão relativo inferior a 2,0 % na precisão e linearidade para os quatro fármacos estudados.

Tablets containing isoniazid, pyrazinamide, ethambutol and rifampicin are used for tuberculosis treatment, and theyare freely distributed by the Brazilian National Health System. The official analytical methods for testing those substances in fixed-dose combined tablet are described in the United States Pharmacopeia and theInternational Pharmacopoeia. None of these official compendiums refers to the methodologies forconducting the simultaneous analysis of these four drugs. This study aimedatdeveloping an analytical methodology to determine simultaneously allof four drugs in tablets for tuberculosis treatment, bymeans ofhigh performance liquid chromatography with ultraviolet-visible detector. The developed method used a chromatographic column with octadecylsilane stationary phase (250 mm x 4.6 mm x 5 μm particle size). The mobile phase was aqueous (85 % ammonium formate buffer pH 5, 15 % methanol and 250 mg CuSO4.5H2O), and organic phase (methanol, 0.1 % triethylamine and 0.2 % formic acid). The flow was 1.0 mL/min, at a wavelength of 265 nm or, when the equipment allowed, a wavelength of 265 nm for isoniazid, pyrazinamide and ethambutol and 335 nm for rifampicin. The developed methodology showed satisfactory results regarding the precision parameter, with relative standard deviation lower than 2.0 % for the studied drugs.

A experiência brasileira com a implementação do 4: 1 dose fixa combinada para o tratamento da tuberculose / The brazilian experience of implementing RHZE fixed-dose combination for tuberculosis treatment / La experiencia brasileña con la implementación del 4:1 a dosis fija combinada para el tratamiento de la tuberculosis

Em 2009, o Programa Nacional de Controle da Tuberculose recomendou a mudança do regime para o tratamento da tuberculose sensível. As mudanças consistiram na inclusão do etambutol, a redução das dosagens de isoniazida e pirazinamida e a modificação da formulação de cápsula para comprimido em dose fixa combinada. O processo de mudança foi viabilizado por apoio técnico, político e financeiro, que garantiu o abastecimento interno e o treinamento dos profissionais de saúde. A presente análise do caso brasileiro permitiu elencar lições aprendidas com o processo e formular recomendações para a sustentabilidade desta e de futuras inovações tecnológicas no diagnóstico, prevenção e tratamento da tuberculose.

In 2009, the Brazilian National Tuberculosis Program recommended changing the regimen for the treatment of sensitive tuberculosis by replacing RHZE with RHZ, involving reduced doses of isoniazid and pyrazinamide in a fixed-dose combination formulation. The process of change was made possible by the financial, political and technical support that ensured national drug provision and the training of healthcare professionals. In this analysis of the Brazilian case, we present the lessons learned with the implementation process and we formulate recommendations for the sustainability of this and other future technological innovations in the diagnosis, prevention and treatment of tuberculosis.

En 2009, el Programa Nacional de Control de la Tuberculosis recomendó el cambio de régimen para el tratamiento de la tuberculosis sensible. Los cambios consistieron en la inclusión del etambutol, la reducción de las dosis de isoniazida y pirazinamida y la modificación de la formulación de cápsula para comprimido a dosis fija combinada. El proceso de cambio fue viable por el gracias al apoyo técnico, político y financiero, que garantizó el abastecimiento interno y la capacitación de los profesionales de salud. El presente análisis del caso brasileño permitió registrar las lecciones aprendidas con el proceso y formular recomendaciones para la sustentabilidad de esta y de futuras innovaciones tecnológicas en el diagnóstico, prevención y tratamiento de la tuberculosis.

Cutaneous tuberculosis: diagnosis, histopathology and treatment - Part II

The evolution in the knowledge of tuberculosis' physiopathology allowed not only a better understanding of the immunological factors involved in the disease process, but also the development of new laboratory tests, as well as the establishment of a histological classification that reflects the host's ability to contain the infectious agent. At the same time, the increasing bacilli resistance led to alterations in the basic tuberculosis treatment scheme in 2009. This article critically examines laboratory and histological investigations, treatment regimens for tuberculosis and possible adverse reactions to the most frequently used drugs.

Polaciúria incapacitante para a vida usual. Relato de tuberculose da bexiga. A tuberculose permanece no rol do diagnóstico diferencial da maioria das doenças / Incapacitating pollakiuria affecting daily life. A case report of tuberculosis of the bladder. Tuberculosis remains on the list of the differential diagnoses for most diseases

A tuberculose (TB) é dos mais graves problemas de saúde humano e associa-se a pobreza, incipiência do sistema de saúde, deficiência de gestão que dificulta a diminuição de doenças de determinismo social, epidemia do vírus da imunodeficiência humana e imunodeficiência adquirida e multirresistência do M. tuberculosis. O acometimento extrapulmonar ocorre em 15% dos casos de TB e pode evoluir com amesma sintomatologia geral do acometimento pulmonar, com variações na dependência de sua localização e gravidade. Este relato apresenta paciente com hematúria e polaciúria incapacitante para a vida social, associada inicialmente à neoplasia, e determinada pela TB geniturinária, com diagnóstico após histopatologia de espécime clínico obtido da bexiga, em que o tempo longo para o diagnóstico foi determinante para grave sequela. Objetiva alertar para a TB como doença permanente no Brasil ea necessidade de ser considerada sempre como diagnóstico diferencial de doenças pulmonares ou extrapulmonares.

Tuberculosis (TB) is among the most serious human health concerns and is associated with poverty, limited availability of health care services and bad management, all of which negatively affect the possibility of reducing socially-determined diseases, such as HIV/AIDS epidemics and multidrug resistant M. tuberculosis. Extrapulmonary involvement occurs in 15% of TB cases and can develop with the same overall symptomatology of exclusively pulmonary involvement, with smaller variations depending on location and severity. This report presents a patient with hematuria and pollakiuria with incapacitating effects on social life, initially thought of as a malignancy and later identified as genitourinary TB. Diagnosis was based on histopathology of clinical specimens from the bladder. Time elapsed between onset and diagnosis led to considerable sequelae. This report aims at raising awareness of TB as a permanent concern in Brazil and of the need to always considered it as a differential diagnosis of pulmonary or extrapulmonary disease.

Mastitis tuberculosa / Tuberculosis of the breast

Se informa un caso de mastitis granulomatosa causada por Mycobacterium tuberculosis en una paciente inmunocompetente con lesiones inflamatorias crónicas de la mama, diagnosticada por la detección de ADN de la micobacteria mediante la técnica de reacción en cadena de la polimerasa de la secuencia de inserción IS6110 presente en el complejo M. tuberculosis , en una biopsia de mama embebida en parafina. La tuberculosis primaria de la mama es rara, incluso en países con alta prevalencia de tuberculosis, y debe sospecharse en pacientes con mastitis granulomatosa crónica de causa no clara. El pilar del tratamiento es la quimioterapia antituberculosa y, ocasionalmente, la cirugía.

We report a case of granulomatous mastitis caused by Mycobacterium tuberculosis in an immunocompetent woman with chronic inflammatory lesions of the breast. It was diagnosed by detection of mycobacteria DNA using polymerase chain reaction technique targeting IS6110 insertion element of M. tuberculosis complex in a paraffin-embedded histological specimen. The primary breast tuberculosis is rare, even in countries where the incidence and prevalence of pulmonary and extra pulmonary tuberculosis are high. It should be suspected in female patients with chronic granulomatous mastitis with no apparent cause. The cornerstone of treatment is antituberculous chemotherapy, and surgery is rarely required.

Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia / Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil

OBJETIVO: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses) utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. MÉTODOS: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade > 18 anos) tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. RESULTADOS: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47%) relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. CONCLUSÕES: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%).

OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months) involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. RESULTS: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. CONCLUSIONS: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

Protocolo 6: manejo de la tuberculosis en atención primaria de la salud / Protocol 6: management of tuberculosis in primary health care

La Tuberculosis es una enfermedad infectocontagiosa, producida por el Mycobacterium tuberculosis, o Bacilo de Koch, que se transmite por vía aérea, cuando una persona enferma expulsa bacilos al hablar, toser, estornudar, reír o cantar. La tuberculosis afecta principalmente los pulmones (TuberculosisPulmonar), pero también puede afectar cualquier órgano del cuerpo (Tuberculosi sextra-pulmonar). La tuberculosis afecta principalmente los pulmones (TuberculosisPulmonar), pero también puede afectar cualquier órgano del cuerpo (Tuberculosis extra-pulmonar La tuberculosis (TB) sigue siendo un gran problema de salud en la mayoría de los países del mundo, a pesar de los esfuerzos realizados para combatirla, apoyados por la existencia del conocimiento de la cadena de transmisión y de contar con medicamentos muy activos para prevenir y curar la enfermedad.

Resistência primária e adquirida à pirazinamida em pacientes com tuberculose pulmonar atendidos em um hospital de referência no Recife / Primary and acquired pyrazinamide resistance in patients with pulmonary tuberculosis treated at a referral hospital in the city of Recife, Brazil

OBJETIVO: Verificar a resistência primária e adquirida à pirazinamida em cepas de Mycobacterium tuberculosis provenientes de amostras de escarro de pacientes com tuberculose pulmonar. MÉTODOS: Estudo prospectivo e descritivo realizado no período entre abril e novembro de 2011 em um hospital de referência para o tratamento de tuberculose em Recife (PE). Culturas, testes de sensibilidade a fármacos e testes da pirazinamidase foram realizados em um laboratório particular na mesma cidade. RESULTADOS: Dos 71 pacientes incluídos no estudo, 37 eram virgens de tratamento e 34 eram casos de retratamento. Desses, 0 (0,0%) e 14 (41,2%), respectivamente, apresentaram cepas resistentes à pirazinamida. Desses 14 isolados, 10 (90,9%) apresentaram resultados negativos no teste da pirazinamidase. Dos 60 isolados que apresentaram resultados positivos para o teste da pirazinamidase, 56 (93,3%) eram sensíveis à pirazinamida. CONCLUSÕES: A elevada frequência de cepas resistentes à pirazinamida em pacientes em retratamento da tuberculose destaca a necessidade da realização de testes de sensibilidade à pirazinamida antes de se escolher um novo esquema de tratamento.

OBJECTIVE: To determine primary and acquired resistance to pyrazinamide in Mycobacterium tuberculosis strains isolated in sputum samples from patients with pulmonary tuberculosis. METHODS: This was a prospective, descriptive study conducted between April and November of 2011 at a referral hospital for tuberculosis in the city of Recife, Brazil. Cultures, drug sensitivity tests, and tests of pyrazinamidase activity were conducted in a private laboratory in Recife. RESULTS: Of the 71 patients included in the study, 37 were treatment-naïve and 34 represented cases of retreatment. Pyrazinamide-resistant strains were isolated in 14 (41.2%) of the 34 patients who had previously been treated for tuberculosis and in none of the 37 treatment-naïve patients. Of the 14 isolates, 10 (90.9%) tested negative for pyrazinamidase activity. A total of 60 isolates tested positive for pyrazinamidase activity. Of those, 56 (93.3%) were found to be sensitive to pyrazinamide. CONCLUSIONS: The high frequency of pyrazinamide-resistant strains (41.2%) in patients previously treated for tuberculosis highlights the need for drug susceptibility testing prior to the adoption of a new treatment regimen.

Tratamiento directamente observado de la tuberculosis en un hospital de la Ciudad de Buenos Aires / Directly observed treatment for tuberculosis in a Buenos Aires City hospital

Se describe la experiencia en la aplicación del tratamiento directamente observado de tuberculosis (TDO) en el período 1/1/1979-31/12/2009 y la comparación de los resultados obtenidos en el periodo 1979-1999 versus los de 2000- 2009. En un hospital de la Ciudad de Buenos Aires, 582 pacientes HIV negativos recibieron inicialmente rifampicina, isoniazida, pirazinamida y etambutol o estreptomicina. En la segunda fase 424 de estos pacientes tratados entre 01/01/1979 y 31/12/1999 (G1), recibieron esquemas bisemanales con rifampicina/isoniazida o isoniazida/estreptomicina y otros 158 pacientes, tratados entre 01/01/2000 y 31/12/2009 (G2) recibieron un esquema bisemanal o trisemanal con rifampicina/isoniazida. Se siguieron las recomendaciones de los programas de control de la Nación y la Ciudad. Los pacientes bajo TDO tuvieron tasas de tratamiento completo más elevadas (82.8% versus 48.7%), (p < 0.0001) con respecto a otros 483, que siguieron tratamiento autoadministrado (AUTO); la edad promedio fue de 36.3 ± 15.3 años, 63.1% eran varones y 69.4% tenían nacionalidad argentina. Presentaron tratamiento previo el 8.9%, comorbilidades el 6.1% y el 70.6% de las formas pulmonares fueron confirmadas bacteriológicamente. El 9.5% presentó efectos adversos a drogas y el sexo masculino presentó mayor frecuencia de abandonos (p = 0.004). Con respecto al G1, en el G2 hubo menor proporción de pacientes argentinos (48.7% vs. 77.1%), (p ≤ 0.0001), mayor frecuencia de comorbilidades (10.7% vs. 4.4%), (p = 0.005), de formas clínicas pulmonares con confirmación bacteriológica (95% vs. 87%), (p = 0.02) y de efectos adversos a drogas (17% vs. 6.6%), (p ≤ 0.0001). Hallamos tasas de cumplimiento total elevadas en TDO (82.8%), similares a las otras publicaciones.

The outcomes of directly observed therapy of tuberculosis (DOT) between 1/1/1979 and 12/31/2009 were analyzed. Results obtained in the 1979-1999 period were compared with those achieved in the 2000-2009 period. In a Buenos Aires City hospital, 582 HIV negative TB patients received rifampin, isoniazid, pyrazinamide and ethambutol or streptomycin in the initial stage, followed by a second stage where patients were included in two groups: G1 composed by 424 patients (period 1/1/1979-12/31/1999) who received either rifampin and isoniazid or rifampin and streptomicin twice a week, and G2, with 158 patients (period 1/1/2000-12/31/2009) who received either rifampin and isoniazid twice or three times a week. National and Buenos Aires City TB Control Programs recommendations were followed. Patients who underwent DOT had higher completeness rates than those included in self-administered therapy (82.8% vs. 48.7%), (p <0.0001). Mean age: 36.3±15.3 years, males: 63.1% and 69.4% were Argentine citizens. A 8.9% had been previously treated, 6.1% had co-morbidities. A 70.6% of pulmonary cases was bacteriologically confirmed, 82.8% of them completed the treatment, while 11.5% defaulted. Adverse effects to antituberculosis drugs were observed in 9.5% of cases; male patients showed higher rates of non adherence. G2 had a lower proportion of native people (48.7% vs. 77.1%), (p ≤ 0.0001), higher frequency of co-morbidities (10.7% vs. 4.4%), (p = 0.005), of bacteriologically confirmed pulmonary cases (95% vs. 87%), (p = 0.02) and more adverse effects than G1 (17% vs. 6.6%), (p ≤ 0.0001). In coincidence with other experiences, this work shows high treatment success rates in patients treated under DOT strategy.

Resposta paradoxal após o início de tratamento para tuberculose: relato de caso / Paradoxical response after initiation of tuberculosis treatment: case report

JUSTIFICATIVA E OBJETIVOS: A reação paradoxal pode ser identificada em até 30% de todos os pacientes após o início de tratamento para tuberculose, embora seu diagnóstico permaneça um desafio, já que não existem testes confiáveis que o corroborem. O objetivo deste estudo foi relatar um caso em que o diagnóstico de reação paradoxal foi realizado.RELATO DO CASO: Paciente do sexo masculino, 31 anos,um mês após o início de uso de fármacos para tratamento de tuberculose miliar, com diagnóstico realizado por lavado broncoalveolar, apresentou plegia no membro inferior direito, parestesia no membro superior direito e membro inferior esquerdo, incontinência urinária e fecal. Ressonância nuclear magnética do encéfalo evidenciou múltiplas áreas com hipersinal em T2, predominando em substância branca subcortical em ambos os hemisférios, com realce de lesões nodulares, sugestivas de infecção oportunista. Antivírus da imunodeficiência humana 1/2 foi negativo. PCR DNA para M. tuberculosis no líquor foi negativa. Iniciou-se, então, dexametasona. O paciente apresentou melhora significativa, porém permaneceu com incontinência urinária.Tomografia computadorizada de crânio realizada posteriormente não evidenciou quaisquer alterações. CONCLUSÃO: Apesar de sua elevada prevalência, continua difícilr ealizar o diagnóstico de reação paradoxal após o início de tratamento para tuberculose. Mais estudos são necessários para melhor definir os parâmetros diagnósticos e para orientar diretrizes terapêuticas mais efetivas.

BACKGROUND AND OBJECTIVES: Paradoxical response can be identified in up to 30% of all patients after initiation of tuberculosis treatment, although your diagnosis still remains a challenge, mainly because do not exist trustworthy tests to confirm it. These study aimed to describe a case were the diagnosis of a paradoxical response was made.CASE REPORT: Male patient, 31 year-old, a month after the initiation of miliary tuberculosis treatment, with the diagnosis realized by bronchoalveolar lavage, presented right lower limb plegia, right upper limb paresthesia, urge and fecal incontinence. Brain Magnetic Resonance Imaging evidenced hyper signs of T2 in multiple areas, in which predominated in white subcortical substance, beyond enhancing nodular lesions, suggesting an opportunistic infection. Anti human immunodeficiency virus 1/2 was negative. PCR DNA to M. tuberculosis in liquor was negative. After, dexamethasone treatment was started. The patient presented a significant improvement, but urge incontinence remained unchanged. Brain computed tomography realized after not evidence any alteration. CONCLUSION: Despite paradoxical response presents high occurrence, it continuous to be difficult to make the diagnosis of paradoxical response after initiation of tuberculosis treatment. Further studies are necessary in order to improve the diagnostic parameters and to orientate more effective therapeutic consensus.