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.

Tuberculose pulmonar causada pelo uso de infliximab em paciente com Doença de Crohn / Pulmonary tuberculosis caused by the use of infliximab in a patient with Crohn's Disease

A doença de Crohn é uma patologia caracterizada pela inflamação transmural do trato gastrointestinal, compondo o espectro das doenças inflamatórias intestinais. Nos casos mais graves, dispõe de tratamento com uso de agentes biológicos e imunomoduladores que podem à reativação ou exacerbação de doenças infecciosas preexistentes. Este relato de caso trata de uma paciente do sexo feminino de 24 anos, diagnosticada com Doença de Crohn há 10 anos, evoluindo com necessidade de tratamento com infliximab e, após período de menos de 1 ano, apresentou odinofagia progressiva, dor abdominal e diarreia, além de perda ponderal, sudorese noturna e febre diária. Tomografia computadorizada de tórax evidenciou árvore em brotamento, sendo confirmado diagnóstico de tuberculose pulmonar pelo Teste Rápido Molecular no escarro e provável tuberculose laríngea e intestinal.

Crohn's disease is a pathology characterized by transmural inflammation of the gastrointestinal tract, comprising the spectrum of Inflammatory Bowel Diseases. In the most severe cases, treatment using biological agents and immunomodulators may be available, which can lead to the reactivation or exacerbation of preexisting infectious diseases. This case report is about a 24-year-old female patient, diagnosed with Crohn's disease 10 years ago, evolving in need of treatment with Infliximab and, after a period of less than 1 year, she presented progressive odynophagia, abdominal pain and diarrhea, in addition to weight loss, night sweats and daily fever. Chest computer tomography showed a tree in bud, and the diagnosis of pulmonary tuberculosis was confirmed by the Rapid Molecular Test in the sputum and probable laryngeal and intestinal tuberculosis.

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.

Características clínicas e epidemiológicas de casos de infecção pulmonar por Mycobacterium kansasii no Rio de Janeiro, no período de 2006 a 2016 / Clinical and epidemiological characteristics of M. kansasii pulmonary infections from Rio de Janeiro, Brazil, between 2006 and 2016

RESUMO Objetivo Avaliar características clínicas, tomográficas e microbiológicas dos pacientes com doença pulmonar causada pela M. kansasii (DPMK) atendidos em unidade ambulatorial no período 2006-2016. Métodos Estudo descritivo, em que foram analisados 38 pacientes. Foram analisadas as características demográficas, clínico-radiológicas, laboratoriais e terapêuticas. Resultados A média de idade foi 64 anos (DP=10,6; IIQ=57-72; mediana=65,0) e 22 (57,9%) eram pacientes do sexo masculino. Comorbidade pulmonar estava presente em 89,5%. A comorbidade mais frequente foi a bronquiectasia (78,9%). Tratamento anterior para tuberculose pulmonar (TBP) foi relatado em 65,9%. O esquema terapêutico mais utilizado foi rifampicina, isoniazida e etambutol (44,7%). A tomografia de tórax (TCT) mostrou bronquiectasia (94,1%), distorção arquitetural (76,5%), espessamento de septo (67,6%) e cavidades (64,7%). A doença foi bilateral em 85,2%. Houve 10,7% de resistência à rifampicina, 67,9% resistentes ao etambutol e sensibilidade à claritromicina. Conclusão Em pacientes com doença pulmonar estrutural, é importante a busca de DPMNT, principal diagnóstico diferencial com TBP. TC de tórax demonstra diferentes padrões que se sobrepõem ao de doença estrutural causada por TBP ou outras enfermidades pulmonares. Destaca-se a resistência ao etambutol, fármaco componente do esquema preconizado.

ABSTRACT Objective To evaluate clinical, tomographic, and microbiological characteristics of pulmonary disease caused by M. kansasii (MKPD) in patients treated at an outpatient unit from 2006-2016. Methods We studied thirty eight patients, and analyzed socio-demographic, clinical-radiological, laboratory, and therapeutic characteristics. Results The mean age was 64 years (SD = 10.6; IIQ = 57-72; median = 65.0), and 22 (57.9%) male patients. Pulmonary comorbidity was present in 89.5% of the patients. The most frequent comorbidity was bronchiectasis (78.9%). Previous treatment for pulmonary tuberculosis (PTB) was found in 65.9%. The most used therapeutic regimen was rifampicin, isoniazid and ethambutol (44.7%). Chest tomography (CT) showed bronchiectasis (94.1%), architectural distortion (76.5%), septum thickening (67.6%), and cavities (64.7%). Disease was bilateral in 85.2%. We observed 10.7% resistance to rifampicin, 67.9% resistance to ethambutol, and sensitivity to clarithromycin. Conclusion In patients with structural lung disease, it is important to search for NTM, the main differential diagnosis with PTB. Chest CT showed different patterns that overlapped with structural disease caused by PTB or other lung diseases. We observed resistance to ethambutol, a drug component of the recommended regimen.

Enfermedad por bacilo de Calmette-Guérin a distancia en un lactante: Presentación de un caso / Distant bacillus Calmette-Guérin disease in an infant: Case report

La vacuna con el bacilo de Calmette-Guérin es una vacuna atenuada utilizada para prevenir formas graves de tuberculosis. Se aplica a los recién nacidos en países con alta prevalencia de tuberculosis. Pueden presentarse, después de su aplicación, complicaciones a nivel local, como supuración o adenopatías regionales. La enfermedad por diseminación del bacilo es infrecuente y ocurre, por lo general, en pacientes con alteraciones inmunitarias subyacentes. Se presenta el caso de un niño de 5 meses que ingresó por un cuadro de 2 meses de evolución con detención del aumento de peso y nódulos subcutáneos. Se sospechó enfermedad por diseminación del bacilo y se diagnosticó por la biopsia de las lesiones. Se realizó el tratamiento con tres drogas antituberculosas, y se recuperó clínicamente. Si bien se realizaron estudios inmunológicos, no logró demostrarse ninguna inmunodeficiencia como afección predisponente.

The bacillus Calmette-Guérin vaccine is an attenuated vaccine historically used to prevent severe forms of tuberculosis. It is applied to all newborns in countries with high prevalence of tuberculosis. Local complications, such as suppuration or regional adenopathies, may occur after application. Disease due to the spread of the bacillus is infrequent, usually occurring in a patient with an underlying immune alteration. We present the case of a 5-month-old child who was admitted due to a 2-month evolution with weight loss and subcutaneous nodules. Disease was suspected to be due to bacillus Calmette-Guérin dissemination, being diagnosed by biopsy of the lesions. Treatment was carried out with three antituberculous drugs, evolving towards clinical recovery. Although immunological studies were carried out, no immunodeficiency could be demonstrated as a predisposing condition.

Anterior uveitis as a manifestation of ocular tuberculosis / Uveíte anterior como manifestação de tuberculose ocular

ABSTRACT Tuberculosis (TB) is an infectious disease of great magnitude in the world. Of patients with extrapulmonary disease, ocular manifestations are rare but among reported cases the most common ocular manifestation is uveitis. The diagnosis of ocular TB should be made as early as possible so that treatment is initiated and the risks of ocular complications are minimized. The objective of this study is to report an ocular TB case that presented as anterior uveitis. A 52-year-old female patient, a nursing technician at a large hospital, presented a history of low visual acuity associated with myiodesopsia for 4 days. Her ophthalmologic history included an iridotomy due to narrow angle in both eyes. On examination, the best corrected visual acuity was 20/100, right eye, and 20/80, left eye. Among the most significant ocular alterations were granulomatous keratic precipitates, anterior chamber reaction, flare and light vitreitis, corresponding to anterior uveitis. Based on clinical history and ophthalmologic examination, tests were ordered that corroborated the diagnosis of ocular TB. Thereafter, antituberculous therapy was instituted with a good response in 15 days, including improvement in visual acuity. The patient was followed-up by ophthalmology and infectology. Intraocular TB should be considered in the differential diagnosis of any type of intraocular inflammation. The diagnosis of presumed ocular TB is a clinical challenge with the diagnosis modalities currently available. The faster the onset of treatment, the better the visual prognosis of the affected patient.

RESUMO A tuberculose (TB) é uma doença infecciosa de grande magnitude no mundo. Dos pacientes com doença extrapulmonar, as manifestações oculares são raras, mas entre os casos relatados, a manifestação ocular mais comum é a uveíte. O diagnóstico de TB ocular deve ser feito o mais precoce possível para que o tratamento seja iniciado e os riscos de complicações oculares sejam minimizados. O objetivo deste estudo é relatar um caso de TB ocular que se apresentou como uveíte anterior. Uma paciente do sexo feminino, 52 anos, técnica de enfermagem de um hospital de grande porte, apresentou história de baixa acuidade visual associada à miodesopsia por 4 dias. Sua história oftalmológica incluía uma iridotomia devido ao ângulo estreito em ambos os olhos. No exame, a melhor acuidade visual corrigida foi 20/100, olho direito, e 20/80, olho esquerdo. Dentre as alterações oculares mais significativas, destacam-se precipitados ceráticos granulomatosos, reação de câmara anterior, flare e vitreíte leve, correspondendo à uveíte anterior. Com base na história clínica e no exame oftalmológico, foram solicitados exames que corroboram o diagnóstico de TB ocular. Posteriormente, a terapia antituberculosa foi instituída com uma boa resposta em 15 dias, incluindo melhora na acuidade visual. A paciente foi acompanhada pelas especialidades: oftalmologia e infectologia. A TB intraocular deve ser considerada no diagnóstico diferencial de qualquer tipo de inflamação intraocular. O diagnóstico presumível de tuberculose ocular é um desafio clínico com as modalidades de diagnóstico atualmente disponíveis. Quanto mais rápido o início do tratamento, melhor o prognóstico visual do paciente afetado.

Post-surgical atypical mycobacteriosis in 125 patients in Rio de Janeiro

Abstract INTRODUCTION: The growing incidence of post-surgical atypical mycobacteriosis (PSAM) may be related to the increased use of low- and medium-complexity video-assisted surgery. METHODS: Between April 2007 and June 2009, 125 patients were referred from the State Health Department of Rio de Janeiro for the treatment of confirmed, probable, or suspected PSAM. RESULTS: Laparoscopic cholecystectomy was the most frequent surgical procedure (48.8%) among patients. Clarithromycin, ethambutol, and terizidone were used to treat 113 patients for a mean duration of 226 days. CONCLUSIONS: Despite the need for multidrug therapy and long treatment duration, most included patients adhered to treatment and experienced cure without relapse.

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.

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.

Endometritis tuberculosa sin foco primario y dolor pélvico crónico / Tuberculous endometritis with no primary focus and chronic pelvic pain

Antecedentes: La tuberculosis genital y la endometritis tuberculosa es una forma de tuberculosis que continúa siendo frecuente en los países en desarrollo y habitualmente es secundaria a un foco primario pulmonar. Puede cursar de forma asintomática, o bien, producir síntomas como infertilidad primaria o secundaria, alteraciones menstruales o dolor pélvico crónico, entre otros. Caso clínico: Se presenta el caso de una paciente de 47 años en estudio por ginecología y urología por dolor pélvico crónico y sintomatología urinaria inespecífica de aproximadamente 6 meses de evolución. La ecografía transvaginal muestra contenido intracavitario escaso sugerente de piometra e imágenes trabeculares compatibles con sinequias uterinas. Mediante aspirado endometrial se extrae pus y muestra endometrial que se remite para estudio anatomopatológico. Tras el informe anatomopatológico que diagnostica inflamación crónica granulomatosa necrotizante, se solicita estudio por PCR y cultivo para micobacteriumm tuberculosis, siendo ambos positivos para el microorganismo. De este modo, se diagnosticó como endometritis tuberculosa sin existir afectación de otros órganos tras el estudio completo. Se realizó tratamiento con etambutol hidrocloruro, isoniacida, pirazinamida y rifampicina durante 2 meses y pirazinamida e isonicida durante 7 meses adicionales. Al final del tratamiento, la paciente mostraba clara mejoría de los síntomas y a la ecografía desaparición de la colección intracavitaria uterina.

Background: Genital tuberculosis and endometritis tuberculosa is a form of tuberculosis which remains prevalent in developing countries and is usually secondary to a pulmonary primary focus. It may be asymptomatic, or may produce symptoms such as primary or secondary infertility, menstrual disorders or chronic pelvic pain, among others. Clinical case: We present the case of a patient of 47-year who was studied by ginecology and urology for chronic pelvic pain and unspecific urinary symptoms since about 6 months. In transvaginal ultrasound pyometra and trabecular images compatible with uterine synechiae were observed. Endometrial samples were obtaining and sent for histopathologic examination which was informed of chronic necrotizing granulomatous inflammation. We asked for PCR and culture for tuberculosis micobacteriumm, both being positive for the microorganism. Thus, she was diagnosed of endometritis tuberculosa without involvement of other organs after complete study. She performed a treatment with ethambutol hydrochloride, isoniazid, rifampicin and pyrazinamide for 2 months and pyrazinamide and isoniazid for 7 months. At the end of treatment, the patient showed clear improvement of symptoms and disappearance of uterine intracavitary collection in the ultrasonographic study.

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.

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.

First Case of Mycobacterium longobardum Infection

Mycobacterium longobardum is a slow-growing, nontuberculous mycobacterium that was first characterized from the M. terrae complex in 2012. We report a case of M. longobardum induced chronic osteomyelitis. A 71-yr-old man presented with inflammation in the left elbow and he underwent a surgery under the suspicion of tuberculous osteomyelitis. The pathologic tissue culture grew M. longobardum which was identified by analysis of the 65-kDa heat shock protein and full-length 16S rRNA genes. The patient was cured with the medication of clarithromycin and ethambutol without further complications. To the best of our knowledge, this is the first report of a M. longobardum infection worldwide.

Efficacy of the 6-month thrice-weekly regimen in the treatment of new sputum smear-positive pulmonary tuberculosis under clinical trial conditions.

Background. Under the Revised National Tuberculosis Control Programme of India, patients with new smear-positive pulmonary tuberculosis are treated with a thrice-weekly regimen of antitubercular drugs (2H3R3Z3E3/4H3R3 [H isoniazid, R rifampicin, Z pyrazinamide and E ethambutol]) for 6 months. We conducted a retrospective analysis of the efficacy and tolerability of this regimen under clinical trial conditions in HIV-negative patients with newly diagnosed smear-positive pulmonary tuberculosis. Methods. We retrospectively analysed the data on patients assigned to the control regimen (2H3R3Z3E3/4H3R3) in two clinical trials during 2001–06 at the National Institute for Research in Tuberculosis, Chennai, India. Results. Of the 268 patients treated with this regimen, data for efficacy analysis were available for 249. At the end of treatment, of 249 patients, 238 (96%) had a favourable status. Treatment failure occurred in the remaining 11: 7 in whom the organisms were initially drug-susceptible and 4 with initial drug resistance. Of the 238 patients who had a favourable status at the end of treatment, 14 (6%) had recurrence of tuberculosis during the following 24 months. In the intention-to-treat analysis, 245 (94%) of 262 patients had a favourable status at the end of treatment. Of the 28 patients with initial drug resistance, 24 (86%) had a favourable outcome. Only 4 of these 24 patients were found to have recurrence of tuberculosis in 2 years of follow-up. Among the 221 patients initially infected with drug-susceptible organisms, drug resistance did not develop in any of the 7 patients in whom the treatment failed or the 10 who had recurrence of tuberculosis. Further, 5 of the 7 patients in whom the treatment failed continued to excrete drug-susceptible bacilli at 6 months. Adverse drug reactions were observed in 38 (14%) of the 262 patients. Only 3 (1.1%) needed a modification in the treatment. Conclusion. This thrice-weekly 6-month regimen of antitubercular drugs, when administered under full supervision, is associated with a high rate of favourable treatment outcomes in HIV-negative patients with newly diagnosed sputum smearpositive pulmonary tuberculosis. There are few adverse drug reactions in these patients.

Clinical response of newly diagnosed HIV seropositive & seronegative pulmonary tuberculosis patients with the RNTCP Short Course regimen in Pune, India.

Background & objectives In the Revised National Tuberculosis Control Programme (RNTCP) in India prior to 2005, TB patients were offered standard DOTS regimens without knowledge of HIV status. Consequently such patients did not receive anti-retroviral therapy (ART) and the influence of concomitant HIV infection on the outcome of anti-tuberculosis treatment remained undetermined. This study was conducted to determine the results of treatment of HIV seropositive pulmonary tuberculosis patients with the RNTCP (DOTS) regimens under the programme in comparison with HIV negative patients prior to the availability of free ART in India. Methods Between September 2000 and July 2006, 283 newly diagnosed pulmonary TB patients were enrolled in the study at the TB Outpatient Department at the Talera Hospital in the Pimpri Chinchwad Municipal Corporation area at Pune (Maharashtra): they included 121 HIV seropositive and 162 HIV seronegative patients. They were treated for tuberculosis as per the RNTCP in India. This study was predominantly conducted in the period before the free ART become available in Pune. Results At the end of 6 months of anti-TB treatment, 62 per cent of the HIV seropositive and 92 per cent of the HIV negative smear negative patients completed treatment and were asymptomatic; among smear positive patients, 70 per cent of the HIV-seropositive and 81 per cent of HIV seronegative pulmonary TB patients were cured. Considering the results in the smear positive and smear negative cases together, treatment success rates were substantially lower in HIV positive patients than in HIV negative patients, (66% vs 85%). Further, 29 per cent of HIV seropositive and 1 per cent of the HIV seronegative patients expired during treatment. During the entire period of 30 months, including 6 months of treatment and 24 months of follow up, 61 (51%) of 121 HIV positive patients died; correspondingly there were 6 (4%) deaths among HIV negative patients. Interpretation & conclusions The HIV seropositive TB patients responded poorly to the RNTCP regimens as evidenced by lower success rates with chemotherapy and high mortality rates during treatment and follow up. There is a need to streamline the identification and management of HIV associated TB patients in the programme with provision of ART to achieve high cure rates for TB, reducing mortality rates and ensuring a better quality of life.

Standardized Combination Antibiotic Treatment of Mycobacterium avium Complex Lung Disease

PURPOSE: The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease. MATERIALS AND METHODS: This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006. RESULTS: All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response. CONCLUSION: Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease.

Incomplete immunological recovery following anti-tuberculosis.

Background & objectives: Mycobacterium tuberculosis infection has been shown to result in increased HIV replication and disease progression in HIV-infected individuals through increased immune activation. The objective of this study was to correlate plasma levels of immune activation markers with the presence of tuberculosis (TB) in HIV-infected and uninfected individuals, and to study the changes following anti-tuberculosis treatment. Methods: Plasma markers of immune activation - neopterin, beta-2-microglobulin (β2M) and soluble tumour necrosis factor alpha receptor type I (sTNFα-RI) were measured by ELISA in 42 HIV positive TB patients (HIV+TB+) undergoing a six-month course of TB chemotherapy. Thirty seven HIV+ persons without active TB, 38 TB patients without HIV infection, and 62 healthy volunteers served as controls. Results: Plasma levels of all three markers were elevated in HIV+ individuals, more so in those with active TB. When HIV+ individuals were further categorized based on CD4+ T cell counts, HIV+TB+ patients with CD4+ T cells counts < 200 cells/μl were found to have the highest levels at baseline with a steep fall in neopterin and sTNFα-RI during treatment, but in most instances the levels did not drop to normal. β2M levels remained persistently high despite completing TB treatment. Interpretation & conclusions: The fi ndings of the study suggest that both HIV and TB act synergistically to activate the host immune system. Although ATT was effective in clearing M. tuberculosis infection, a high proportion of HIV+ TB patients continued to have levels well above the normal range, indicating that underlying immune activation persists despite TB treatment. None of the markers were specific enough to be used to assess cure of TB.

Tuberculose: como eu trato / Tuberculosis: how I deal

Historicamente, o Brasil teve papel pioneiro na organização das ações de controle da tuberculose. Desde os primeiros anos do século XX, por meio de estratégias diagnósticas e terapêuticas padronizadas simples e efetivas, baseadas na patobiologia da doença e nas características do agente etiológico, o Programa de Controle da Tuberculose vem contribuindo para o controle da doença e para a organização do sistema público de saúde. A padronização terapêutica em todo o território nacional, associada à garantia de fornecimento gratuito dos medicamentos a todos os doentes identificados, são instrumentos fundamentais para a redução do impacto da tuberculose na população. Os esquemas medicamentosos padronizados para cada situação, previamente testados e validados, possibilitam a cura da maior parte dos doentes. Atualmente, os maiores obstáculos ao controle desejado da doença incluem a infecção pelo HIV e o desenvolvimento de bacilos resistentes aos principais agentes quimioterápicos.

Historically, Brazil has had a major role in the organization of tuberculosis control activities. Since the beginning of the XX Century, using simple and effective standardized diagnostic and therapeutic strategies, based on an understanding of the pathophysiology of the disease and on the characteristics of the etiologic agent, the Tuberculosis Control Program has contributed to the control of the disease and to the organization of the public health system. Nationwide standardization of the treatment, along with the quarantee of free medicines to all patients, are fundamental tools for reducing the impact of the disease. A structured approach to care lead to the cure of the majority of the patients. At present, the major obstacles to the desired level of tuberculosis control include HIV infection and the development of Mycobacterium tuberculosis strains resistant to the most important anti tubercular drugs.