Prevalencia de infección tuberculosa latente e incidencia de viraje tuberculínico en contactos escolares mayores de 5 años en la Ciudad Autónoma de Buenos Aires / Prevalence of latent tuberculosis infection and incidence of tuberculin conversion among school contacts older than 5 years in the City of Buenos Aires

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

Introduction. Tuberculosis continues to be a common problem in settings of socioeconomic vulnerability. Our primary objective was to establish the prevalence of latent infection and tuberculin conversion among school contacts of tuberculosis cases. Population and methods. In a programmatic area in the south of the City of Buenos Aires, the prevalence of latent infection and tuberculin conversion was assessed in 691 children and adolescents using the tuberculin skin test. The association between loss to follow-up by the health care team and the demographic, school, and baseline care characteristics was studied, and the level of adherence when isoniazid chemoprophylaxis was indicated was described. Results. According to established definitions, the prevalence of latent infection was between 3.4% (95% confidence interval [CI]: 2.3­5.2) and 11.6% (95% CI: 9.3­14.4) in the 610 contacts with at least one skin test. The incidence of tuberculin conversion was between 0.3% and 6.8% in the 294 assessed participants. Age older than 18 years, a higher prevalence of unmet basic needs in the school district, attending the afternoon school shift, negative sputum smear results in the index case, and absence of baseline skin test were associated with contact lost to follow-up. Conclusions. The incidence of tuberculin conversion among school contacts was low. Adherence to isoniazid treatment remains limited. Factors associated with loss of contact tracing were identified, which may guide strategies necessary to improve this process.

Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

The past, present and future of tuberculosis treatment / 浙江大学学报·医学版

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

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.

Resistencia de Mycobacterium tuberculosis a quinolonas y fármacos inyectables en el departamento del Atlántico, 2013-2016 / Resistance of Mycobacterium tuberculosis to quinolone and injectable drugs in Atlántico department, 2013-2016

Introducción: En el departamento del Atlántico los estudios de resistencia del Mycobacterium tuberculosis se han limitado a drogas de segunda línea. Objetivo: Determinar prevalencia de resistencia a amikacina, kanamicina, capreomicina y ofloxacina en casos de tuberculosis resistente a isoniacida, rifampicina o a ambas drogas, en el periodo 2013 a 2016 en el departamento del Atlántico. Métodos: Estudio transversal de 194 aislamientos resistentes a isoniacida, rifampicina o ambas, por metodología Genotype MTBDR plus versión 2, enviados al Instituto Nacional de Salud en el periodo 2013 al 2016 para ser confirmados y procesados para drogas de segunda línea. La proporción de resistencia, se hizo según variables sociodemográficas, clínica y de vigilancia en salud pública. Resultados: Las comorbilidades frecuentes encontradas fueron desnutrición con el 18,56 por ciento, seguido de infección concomitante VIH-tuberculosis con el 13,40 por ciento. La ofloxacina en casos no tratados obtuvo la mayor resistencia global con el 1,50 por ciento (IC 95 por ciento 0,18-5,33). En los que fueron previamente tratados la resistencia global a capreomicina fue del 8,10 por ciento (IC 95 por ciento 2,7-17,8). En los resistentes a rifampicina, un caso fue extensivamente resistente y dos casos resistentes en los multidrogorresistente. Conclusiones: Se encontró baja resistencia a fluoroquinolonas y fármacos inyectables en pacientes no tratados resistentes a isoniacida, rifampicina o ambas, que muestra que todavía no constituye un problema mayor en el departamento del Atlántico. Se debe complementar su seguimiento con buen manejo tanto físico como psicológico y un equipo de salud fortalecido que actúe prontamente y ayude a la adherencia del paciente a los tratamientos(AU)

Introduction: In Atlántico department, resistance studies of Mycobacterium tuberculosis have been limited to second-line drugs. Objective: Determine prevalence of resistance to amikacin, kanamycin, capreomycin and ofloxacin in cases of tuberculosis resistant to isoniazid, rifampicin or both, in the period 2013 to 2016 in Atlántico department. Methods: Cross-sectional study of 194 isolations resistant to isoniazid, rifampicin or both, by Genotype MTBDR plus version 2 methodology, that were sent to the National Institute of Health from 2013 to 2016 to be confirmed and processed for second-line drugs. The resistance ratio was made according to sociodemographic, clinical and public health surveillance variables. Results: The common comorbilities found were malnutrition with 18.56 percent, followed by concomitant HIV-tuberculosis infection with 13.40 percent. Ofloxacin in non-treated cases achieved the highest overall resistance with 1.50 percent (95 percent CI 0.18-5.33). In those previously treated, global resistance to capreomycin was 8.10 percent (95 percent CI 2.7-17.8). In the ones resistant to rifampicin, one case was extensively resistant and two cases were resistant in multi-drugs resistant. Conclusions: Low resistance to fluoroquinolones and injectable drugs was found in non-treated patients who were resistant to isoniazid, rifampicin or both, showing that it is not yet a major problem in Atlántico department. Its follow-up should be complemented with good physical and psychological management and a strengthened health team that acts promptly and helps the patient adherence to treatments(AU)

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

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

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

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.

Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente / WHO consolidated guidelines on drug-resistant tuberculosis treatment

Las cepas del bacilo tuberculoso con farmacorresistencia (TB-DR) son más difíciles de tratar que las farmacosensibles y amenazan el progreso mundial hacia los objetivos establecidos por la Estrategia Fin de la TB, de la Organización Mundial de la Salud (OMS). Por lo tanto, existe una necesidad imperiosa de contar con recomendaciones de política basadas en la evidencia sobre el tratamiento y la atención a los pacientes con TB-DR, de acuerdo con la evidencia más reciente y completa disponible. A este respecto, las Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente cumplen el mandato de la OMS de informar a los profesionales de la salud de los Estados Miembros sobre cómo mejorar el tratamiento y la atención de los pacientes con TB-DR.

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.

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

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

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

Tuberculosis o colagenosis: un dilema diagnóstico / Tuberculosis or collagenosis: a diagnostic dylemma

Introducción: Colagenosis y tuberculosis comparten síntomas y signos, pero además, el trastorno autoinmune y los tratamientos inmunosupresores que reciben los pacientes con colagenosis, los hacen más vulnerables a esta infección, lo que puede constituir un dilema diagnóstico. Objetivo: Contribuir al conocimiento de la relación entre tuberculosis y colagenosis. Presentación de casos: Se presentan tres adolescentes con tuberculosis, atendidos en el Centro de Referencia Nacional para la Tuberculosis Infantil. Dos enfermos tenían diagnóstico previo de colagenosis (artritis idiopática juvenil y polimiositis) con tratamiento esteroideo en exacerbaciones o continuo desde hacía un año, respectivamente. El tercero presentó un síndrome febril prolongado con pleuresía y pericarditis, con sospecha de lupus eritematoso diseminado. Se diagnosticó tuberculosis por test de mantoux hiperérgico. El tratamiento fue prolongado con esteroides, drogas antituberculosas y pericardiotomía al inicio del proceso, con evolución tórpida y fallo de tratamiento. Todo el tiempo se trató de descartar una enfermedad del colágeno. Se confirmó por cultivo la tuberculosis en los tres pacientes y la evolución final fue satisfactoria. Se exponen las características de cada enfermo y se analiza la relación entre ambas entidades. Conclusiones: Se presentan tres casos que ejemplifican la relación entre tuberculosis y colagenosis(AU)

Introduction: Collagenosis and tuberculosis share similar symptoms and manifestations; and in addition, the autoimmune disorder and inmunosuppressive treatments that patients with collagenosis receive make them more vulnerable to this infection which can constitute a diagnostic dylemma. Objective: To contribute to a better knowledge on the relation among tuberculosis and collagenosis. Cases presentation: Three adolescents suffering collagenosis are presented. They were attended in the National Reference Center for Children Tuberculosis. Two of the patients had previous diagnostic of collagenosis (juvenile idiopatic arthritis and polymyositis) with steroids treatment in exacerbations or continuous since a year ago. The third patient presented a prolonged febrile syndrome with pleurisy and pericarditis, with suspicions of disseminated lupus erythematosus. Tuberculosis was diagnosed by the test of hyperergic Mantoux. The treatment was prolonged with steroids, antiturberculosis drugs and pericardiotomy at the beginning of the process, with bad evolution and failure of the treatment. All the time it was intended to rule out collagen disease. Tuberculosis was confirmed by culturing in the three patients and final evolution was satisfactorily. Characteristics of each patient were exposed and it was analyzed the relation among both diseases. Conclusions: Three cases that exemplify the relation among tuberculosis and collagenosis(AU)

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.

Isoniazid preventive therapy uptake and completion among HIV infected children in two referral hospitals, northwest Ethiopia

Introduction: Isoniazid prevention therapy alone can reduce the risk of tuberculosis in people with HIV regardless of CD4 count or antiretroviral treatment. In Ethiopia, there is scarcity of evidence on implementation of isoniazid prevention therapy and factors associated with its uptake.Objective: The study aimed to assess isoniazid preventive therapy implementation and factors associated with isoniazid completion among human immunodeficiency virus infected children in Felege-Hiwot and Gondar University Referral Hospitals in Northwest Ethiopia.Methods: A facility-based cross-sectional study using a combination of face-to-face interviews of caregivers/parents and retrieval of client records was conducted in May 2014. Trained nurses with experience in human immunodeficiency virus infection and tuberculosis care conducted the document review and interviews. Data were entered onto Epi Info version 3.5.4 for windows, cleaned and exported to Statistical Package for Social Sciences version 20.0 for windows for analysis. Results: A total of 454 HIV infected children (51.8% females and 48.2% males) were studied. Nearly a third, 168 (37%),of children were provided isoniazid prevention therapy and 67.9% completed the full course. Isoniazid completion was associated with distance from hospital (p<0.005), explanation of the reasons to take isoniazid pills (p<0.001), thinking isoniazid may be dangerous to child's health (p<0.001), believing that the chance of getting sick from tuberculosis is high for the child (p<0.001), disclosure of human immunodeficiency virus infection status (p<0.04) and isoniazid preventive therapy disclosure status (p<0.001).Conclusions: Uptake of isoniazid preventive therapy was low among human immunodeficiency virus infected children. In addition, isoniazid therapy completion was very low. The hospitals and Regional Health Bureau should avail isoniazid preventive therapy in the nearby health facilities and strengthen adequate counseling on the role of isoniazid preventive therapy for tuberculosis

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.