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.

Diagnosis of goat tuberculosis using tuberculinization and molecular techniques

Tuberculosis is an infectious, chronic, and worldwide disease. It has been known since the beginning of humanity and still negatively influences public health and livestock, especially, in Brazil, in the northeast. Etiologic agents are the mycobacteria of the Mycobacterium tuberculosis complex, which is the most important in mammals' involvement. The state of Bahia has 68.7% of its territory located in the semiarid region and holds the largest goat herd in the country. Goat breeding is a social and economic activity that adds value to this region. Up to the present, data on goat tuberculosis is unknown in this state. Thus, this study seeks data on tuberculosis prevalence in goats in a semiarid region of Bahia by using the comparative tuberculin test and multiplex polymerase chain reaction (PCR). A total of 600 adult animals of both sexes were evaluated. A prevalence of 0.33% (2/600) and 33.33% (1/3) properties were found for positive animals. Each assessed property had a questionnaire to analyze the epidemiological data management and relevant aspects for the disease occurrence. To confirm the positive tuberculin test results, PCR was used to detect and identify the pathogenic mycobacteria involved in the infection. It is concluded that most of the properties performing goat breeding in the region show low technification levels and promote farming between different species. Low prevalence of the disease alerts preventive measures to avoid major proportion situations that could influence the goat breeding in the state.

Frequency of anergy in a group of patients with rheumatoid arthritis on immunosuppressive therapy / Frecuencia de anergia en un grupo de pacientes con artritis reumatoide y terapia inmunosupresora

ABSTRACT Background: Tuberculin is the globally accepted delayed cutaneous hypersensitivity test for the diagnosis of latent tuberculosis. The alteration of cellular immunity induced by disease-modifying drugs used in rheumatoid arthritis may give a false negative result, also known as cutaneous anergy. There are no studies that determine the frequency of anergy in patients with rheumatoid arthritis and on immunosuppressive therapy. Objective: To determine the frequency and possible factors associated with cutaneous anergy in a group of patients with rheumatoid arthritis and on immunosuppressive therapy. Methods: Cross-sectional analytical observational study including 100 patients with rheumatoid arthritis on immunosuppressive therapy. They were tested for delayed cutaneous hypersensitivity with tuberculin, and a control test with tetanus toxoid. The non-reactivity of both tests was defined as anergy. Results: The overall frequency of cutaneous anergy was 9% (n = 11). It occurred in 33% of men versus 6% of women. The mean age was 57 years, and 89% were over 50 years-old. Being female behaved as a protective variable for the generation of anergy, OR 0.795 [95% CI, 0.658 - 0.959, P<.05]. All patients with anergy were being treated with corticosteroids, 44% with methotrexate, and 33% with biological therapy. Treatment with moderate to high dose prednisone and biological therapy were independently associated as risk factors for presenting with anergy, OR 1.044 [95% CI, 1.008-1.080 P<.05] and OR 1.096 [95% CI, 1.016-1.182, P<.05], respectively. The overall positivity for tuberculin was 13%. Symptoms associated with disease activation were present in 38% of these. All cases (n= 1) of confirmed active tuberculosis were excluded. Conclusions: The high prevalence of cutaneous anergy in patients with RA in the present study, and the evidence presented here, supports the recommendation of a second diagnostic test (tuberculin booster or Interferon-Gamma Release Assays) for the diagnosis of latent TB in patients with RA on immunosuppressive therapy.

RESUMEN Antecedentes: La tuberculina es la prueba de hipersensibilidad cutánea tardía mundialmente aceptada para el diagnóstico de tuberculosis latente. La alteración de la inmunidad celular inducida por los fármacos modificadores de la enfermedad utilizados en la artritis reumatoide puede dar un resultado falso negativo, también conocido como anergia cutánea. No hay estudios que determinen la frecuencia de anergia en pacientes con artritis reumatoide y terapia inmunosupresora. Objetivo: Determinar la frecuencia y los posibles factores asociados con la anergia cutánea en un grupo de pacientes con artritis reumatoide y terapia inmunosupresora. Métodos: Estudio observacional analítico transversal que incluyó a 100 pacientes con artritis reumatoide con terapia inmunosupresora. Se les realizó una prueba de hipersensibilidad cutánea tardía con tuberculina y una prueba de control con toxoide tetánico. La no reactividad de ambas pruebas se definió como anergia. Resultados: La frecuencia general de anergia cutánea fue del 9% (n = 11). Ocurrió en el 33% de los hombres versus el 6% de las mujeres, la edad promedio fue de 57 anos y el 89% tenía más de 50 anos. El sexo femenino se comportó como una variable protectora para la generación de anergia (OR 0,795; IC 95%: 0,658-0,959; p < 0,05). Todos los pacientes con anergia usaron corticosteroides, el 44% fue tratado con metotrexato y el 33% con terapia biológica. El tratamiento con dosis de moderadas a altas de prednisona y terapia biológica se asoció de manera independiente como factor de riesgo para la presentación de anergia: OR 1,044 (IC 95%: 1,008-1,080; p < 0,05) y OR 1,096 (IC 95%: 1,016-1,182; p < 0,05), respectivamente. La positividad general para la tuberculina fue del 13%. Los síntomas asociados con la activación de la enfermedad estaban presentes en el 38% de ellos. Se excluyeron todos los casos de tuberculosis activa confirmada (n = 1). Conclusiones: La alta prevalencia de anergia cutánea en pacientes con artritis reumatoide en el presente estudio y la evidencia presentada respaldan la recomendación de una segunda prueba de diagnóstico (refuerzo de tuberculina o IGRA) para el diagnóstico de tuberculosis latente en pacientes con artritis reumatoide y terapia inmunosupresora.

La lectura de la reacción tuberculínica: un tema controversial / Reading the Tuberculin Reaction: A Controversial Issue

Roberto Koch, en 1882 demuestra la etiología de la TB y años después (1890) propone en el 10° Congreso Internacional de Medicina de Berlín la tuberculina como un "remedio" para la enfermedad. No funcionó, pero nos legó la denominada posteriormente tuberculina bruta o antigua (OT, old tuberculin) que se usó durante años como diagnóstico de infección por Mycobacterium tuberculosis y fue reemplazada por el Derivado Proteico Purificado (PPD) desarrollado por Florencia Seibert en 1934. La técnica de aplicación intradérmica de Mantoux (1908), sigue aún vigente

Tubercúlide papulonecrótica: um relato de caso / Papulonecrotic tuberculids: a case report / Tubercúlide papulonecrótica: un informe de caso

As tubercúlides são reações de hipersensibilidade cutânea aos antígenos do Mycobacterium tuberculosis. Este é o caso de uma mulher de 45 anos que procurou a Unidade Básica de Saúde (UBS) com um quadro de eritema nodoso com mais de 10 anos de evolução, de etiologia desconhecida, e que evoluía como nódulos em pescoço e membros, que se tornavam úlceras necróticas, cicatrizavam e recidivavam periodicamente. Biópsias das lesões evidenciavam um processo inflamatório granulomatoso com extensa necrose, sugestivo de tuberculose, mas sem a presença do bacilo. Após anos sem tratamento adequado, finalmente levantou-se a hipótese de tubercúlide papulonecrótica. A paciente iniciou tratamento com o esquema básico (2RHZE/4RH) e dessensibilização vacinal, recebendo alta por cura.

Las tubercúlides son reacciones de hipersensibilidad cutánea a los antígenos del Mycobacterium tuberculosis. Este es el caso de una mujer de 45 años que buscó la Unidad Básica de Salud (UBS) con un cuadro de eritema nodoso con más de 10 años de evolución, de etiología desconocida, y que evolucionaba como nódulos en cuello y miembros, que se tornaban úlceras necróticas, cicatrizaban y recidivaban periódicamente. Las biopsias de las lesiones evidenciaban un proceso inflamatorio granulomatoso con una extensa necrosis, sugestiva de tuberculosis, pero sin la presencia del bacilo. Después de años sin tratamiento adecuado, finalmente se levantó la hipótesis de tubercúlide papulonecrótica. La paciente inició tratamiento con el esquema básico (2RHZE / 4RH) y desensibilización vacunal, recibiendo alta por curación

The tuberculids are cutaneous hypersensitivity reactions to Mycobacterium tuberculosis antigens. This is the case of a 45-year-old woman who sought the Basic Health Unit (BHU) with erythema nodosum with a 10-year evolution, of unknown etiology, that evolved as nodules in the neck and limbs, which became necrotic ulcers, cicatrized and recurred periodically. Biopsies of the lesions revealed a granulomatous inflammatory process with extensive necrosis, suggestive of tuberculosis, but without the presence of the bacillus. After years without adequate treatment, the hypothesis of papulonecrotic tuberculids finally arose. The patient started treatment with the basic regimen (2RHZE/4RH) and vaccine desensitization, receiving discharge by cure.

Characteristic profile of antibody responses to PPD, ESAT-6, and CFP-10 of Mycobacterium tuberculosis in pulmonary tuberculosis suspected cases in Surabaya, Indonesia

Abstract Accurate and rapid diagnostic tools are important aspects of managing tuberculosis (TB) cases appropriately. However, the sensitivity and specificity of diagnostic kits based on immune response such as the tuberculin skin test (TST) and interferon gamma release assay (IGRA) are still debated. Thus, the exploration and assessment of specific biomarker-targeted antibodies are needed for the development of an accurate and rapid diagnostic tool. The present study was conducted in patients with a respiratory problem suspected to be TB at Dr. Soetomo Hospital, Surabaya, Indonesia. Among 102 patients tested by GeneXpert and AFB, 59 serum samples were from cases retrospectively determined to have active TB. A total of 102 serum of healthy controls (HC) was also collected. The PPD antigen and the recombinant CFP-10 and ESAT-6 proteins were prepared. Antibody responses against these proteins were evaluated by ELISA. All samples were also screened for the possibility of Mycobacterium avium-intracellulare complex (MAC) infection using Capilla MaC kit. The results showed that TB patients had a significantly higher concentration of IgG antibody in response to PPD than the HC. In addition, the receiver operating characteristic (ROC) curve analysis showed that PPD was acceptable for diagnostic purposes with an AUC value of 0.835 (95% CI 0.770-0.900, p < 0.0001). However, ESAT-6 and CFP-10 had low AUCs, and 32 samples from both groups showed a low concentration of IgA antibody against all antigens. The MAC detection results also showed that the concentration of IgA in the HC group was the highest. The current results indicate that PPD is a better antigen for antibody-based detection of TB than ESAT-6 and CFP-10. Based on the MAC detection assay, 53 people in the HC group were probably infected with rapidly growing nontuberculous mycobacteria (NTM), although antibody response to PPD was low.

Potencial do teste IGRA (Interferon Gama Release Assay) para o diagnóstico de tuberculose ocular. Revisão e análise comparativa com o teste tuberculínico cutâneo (PPD) / The potential of the IGRA (Interferon Gamma Release Assay) test for the diagnosis of ocular tuberculosis. Review and comparative analysis with the tuberculosis skin test

Resumo A detecção precisa da infecção latente por tuberculose está se tornando cada vez mais importante devido ao aumento do uso de medicamentos imunossupressores e da epidemia do vírus da imunodeficiência humana, o que aumentou o risco de reativação à tuberculose ativa (TB). O Teste IGRA QuantiFERON® TB Gold apresenta vantagens frente ao teste de PPD como por exemplo, requer somente uma coleta de amostra sanguínea ; não há necessidade que o paciente retorne ao laboratório para leitura e interpretação dos resultados; Os resultados são objetivos, não requerem interpretação do leitor ou interferência de critérios subjetivos; trata-se de um teste in vitro, portanto não há "efeito booster" (potenciação da reação tuberculínica); o teste não é afetado por vacinação prévia por BCG ou infecção por outras espécies de micobactérias. Limitações são descritas, apesar de raras, como reações cruzadas deste método com infecções por algumas espécies de micobactérias não-tuberculosis (incluindo Mycobacterium kansasii, Mycobacterium szulgai e Mycobacterium marinum). Ainda há poucos dados sobre o teste IGRA em certas populações, como por exemplo, em crianças, pacientes imunocomprometidos e mulheres grávidas. Nestes grupos, a interpretação do teste pode ser difícil e mais estudos se fazem necessários.

Abstract Precise detection of latent tuberculosis infection is becoming increasingly important due to increased use of immunosuppressive drugs and the human immunodeficiency virus epidemic , which increased the risk of reactivation to active tuberculosis (TB).The QuantiFERON® TB Gold IGRA Test has advantages over the skin test for TB, otherwise known as a Mantoux tuberculin test, for example, requires only a blood sample collection; there is no need for the patient to return to the laboratory for reading and interpretation of the results; The results are objective, do not require interpretation of the reader or interference of subjective criteria; it is an in vitro test, so there is no "booster effect" (potentiation of the tuberculin reaction); the test is not affected by prior BCG vaccination or infection with other species of mycobacteria. Limitations are described, although rare, as cross-reactions of this method with infections by some species of non-tuberculosis mycobacteria (including Mycobacterium kansasii, Mycobacterium szulgai and Mycobacterium marinum). There is still little data on the IGRA test in certain populations, such as in children, immunocompromised patients and pregnant women. In these groups, the interpretation of the test can be difficult and more studies are needed.

Early diagnosis and treatment of latent tuberculosis infection / Diagnóstico y tratamiento temprano de la infección de tuberculosis latente

Latent tuberculosis infection is a major health problem worldwide. People with latent tuberculosis infection have a lifetime risk of developing active tuberculosis approximately 5 % to 10%. Patients with latent tuberculosis infection were infected with Mycobacterium tuberculosis. Therefore, early diagnosis and treatment of a latent tuberculosis infection are very important. Patients with latent tuberculosis infection do not have the symptoms, signs, radiographic, and bacteriological evidence of active tuberculosis. Consequently, these patients are not contagious to others. Patients with latent tuberculosis infection usually have a positive tuberculin skin test or interferon-gamma release assays test. Systematic testing is recommended for all patients that are at risk for latent tuberculosis infection. The treatment of latent tuberculosis is recommended for patients that are at increased risk for developing active tuberculosis. The medications recommended to treat latent tuberculosis infection are isoniazid, rifampin, and a combination of isoniazidand rifapentine, and isoniazid and rifampin combination regimens. The most common side effect of these medications is hepatotoxicity. Therefore, patient monitoring during treatment should occur every month to evaluate medications side effects and adherence to medications. Post-treatment patient follow-up is very important, but serial or repeats chest radiography is not recommended.

La infección de tuberculosis latente es un gran problema de salud a nivel mundial. Las personas con infección de tuberculosis latente tienen un riesgo de desarrollar tuberculosis activa en aproximadamente 5 % a 10 % en toda su vida. Pacientes con infección de tuberculosis latente fueron infectados con Mycobacterium tuberculosis, por lo tanto, diagnóstico y tratamiento temprano de la infección de tuberculosis latente es muy importante. Pacientes con infección de tuberculosis latente son asintomáticos, no tienen signos físicos o radiográficos anormales, y no tienen evidencia bacteriológica de tuberculosis activa. Consecuentemente, estos pacientes no son contagiosos a otras personas. Pacientes con infección de tuberculosis latente usualmente son positivos para las pruebas de la tuberculina o Interferon-Gamma Release Assays. Pruebas sistemáticas son recomendadas para todos los pacientes que están en riesgo de presentar infección de tuberculosis latente. El tratamiento de tuberculosis latente es recomendado para los pacientes que tienen un elevado riesgo de desarrollar tuberculosis activa. Los medicamentos recomendados para el tratamiento de la infección de tuberculosis latente son isoniacida, rifampicina, y una combinación de isoniacida y rifapentin, y la combinación de isoniacida y rifampicina. El efecto secundario más común de estos medicamentos es hepatotoxicidad. Por lo tanto, la monitorización de estos pacientes durante el tratamiento debería ser cada mes, para evaluar efectos secundarios de los medicamentos y la adherencia al tratamiento. Es muy importante dar seguimiento después del tratamiento, pero hacer radiografías repetidas de pulmones no es recomendado.

Tuberculosis intestinal, un reto diagnóstico: a propósito de un caso / Intestinal tuberculosis, a diagnostic challenge: report of a case

La tuberculosis gastrointestinal es una patología rara y difícil de diagnosticar, que está asociada con diversos factores sociales y económicos, así como con el estado de salud de la víctima. Este relato de caso se realizó sobre la tuberculosis intestinal en el Departamento de Boyac, en el que se describen los principales aspectos clínicos, paraclínicos, el proceso de diagnóstico y el plan de manejo en el paciente. La afectación gastrointestinal de la tuberculosis tiene una baja incidencia, siendo el sexto lugar de compromiso. Los signos y síntomas manifestados por el paciente no son específicos ya menudo el personal de salud sospecha y primero se centra en otras enfermedades que son más frecuentes. A partir de este caso médico, se ponen de relieve las diversas sospechas diagnósticas que se plantearon en el curso de la enfermedad con el fin de lograr un diagnóstico de la tuberculosis intestinal, lo que proporciona una mayor orientación para que los médicos tengan en cuenta esta enfermedad en su práctica clínica.

Gastrointestinal tuberculosis is a rare and difficult pathology to diagnose, which is associated with various social and economic factors as well as the state of health of the sufferer. This case report was made about intestinal tuberculosis in the Department of Boyac , in which the main clinical, paraclinical, the process of diagnosis and management plan in place in the patient are described. Gastrointestinal involvement of tuberculosis has a low incidence, being the sixth place of commitment. Signs and symptoms manifested by the patient are not specific and often the health staff suspect and first focuses on other diseases that are more prevalent. From this medical case, the various diagnostic suspicions that were raised in the course of the disease are emphasized in order achieve a diagnosis of the intestinal tuberculosis, which provides a higher guidance for doctors to take this disease into account in their clinical practice.

Mycobacterium bovis en fauna silvestre de la cuenca lechera de Santa Fe, Argentina / Mycobacterium bovis in wildlife of the dairy regions of Santa Fe (Argentina)

El control y la erradicación de la tuberculosis bovina basados en la detección de los animales infectados y su inmediata faena permitió lograr progresos satisfactorios en varios países y regiones, pero no todos pudieron lograrlo debido principalmente a la presencia de fauna silvestre infectada con Mycobacterium bovis. La Argentina aplica desde 1999 estas mismas premisas y ha logrado avances en los rodeos lecheros, aunque no se ha evaluado el factor ambiental como la fauna silvestre. El objetivo de este trabajo fue determinar si la fauna silvestre de la cuenca lechera de Santa Fe está infectada con M. bovis. Se realizó la captura/sacrificio de fauna silvestre presente en 5 rodeos lecheros con altos niveles de reaccionantes positivos a la prueba de tuberculina. Sobre 95 mamíferos silvestres examinados, se aisló M. bovis de 7 individuos de comadreja overa (Didelphis albiventris), de uno de zorro gris (Lycolapex gimnocercus) y de uno de rata (Rattus norvegicus). Los sitios anatómicos que produjeron estos aislamientos variaron de acuerdo con las especies; en ninguno de los ejemplares evaluados se observaron lesiones macroscópicas de tuberculosis. Los espoligotipos de M. bovis aislados con mayor frecuencia de los animales silvestres correspondieron a los tipos 34 (4 aislamientos) y 12 (3 aislamientos); el primero es el más corrientemente aislado del ganado en Argentina. Se discute en este estudio el papel de la comadreja overa (D. albiventris) como hospedador circunstancial de M. bovis

Control eradication campaigns of bovine tuberculosis based on the «test and slaughter¼ approach were successful in many countries and regions; however, in some areas the infection persists and one of the main reasons is Mycobacterium bovis infection in wild life species. Argentina has applied the same approach since 1999, achieving progress in dairy cattle herds. Nonetheless, the wildlife role has never been investigated. The objective of this study was to determine if wildlife from the Santa Fe dairy area is infected with M. bovis. Wildlife species having a positive tuberculin skin test were captured in five dairy farms. Ninety five wildlife mammals were captured; M. bovis was recovered from 7 possums (Didelphys albiventris), from one fox (Lycolapex gimnocercus) and from one rat (Rattus norvegicus). None of the animals exhibited macroscopic lesions. The most frequently isolated M. bovis spoligotypes were types 34 (4 isolates) and 12 (3 isolates). Spoligotype 34 is the most frequently isolated type in Argentine cattle. The role of D. albiventris as spillover host of M. bovis is discussed in this study

Profilaxis con isoniazida en niños y jóvenes con infección latente por Mycobacterium tuberculosis / Prophylaxis with isoniazid in children and youths with latent Mycobacterium tuberculosis infection

Se presenta una revisión no sistemática sobre el control de los contactos de tuberculosis (TB) y la terapia preventiva con isoniazida (TPI) para niños y adolescentes, basada en la literatura oficial de entidades internacionales, artículos relevantes y pautas de países latinoamericanos. La Organización Mundial dela Salud recomienda las dos estrategias presentadas como muy importantes en la prevención de la TB en áreas endémicas. El artículo destaca las indicaciones de control de contactos de TB y enfatiza la interpretación del test tuberculínico en algunos de los países de Latinoamérica. Las barreras actuales y las perspectivas de la TPI frente a la TB multirresistente también se analizan. El tratamiento de la infección latente por tuberculosis (ILTB) se hace en la mayoría de los países con isoniazida (H), de ahí la denominación de quimioprofilaxis o TPI. Hay consenso en la comunidad científica en relación con que los niños, adolescentes y adultos jóvenes con test de tuberculina positivo constituyen un grupo prioritario para la TPI. Las principales acciones de control de la TB acorde con las estrategias a nivel de las unidades básicas son: registrar el tratamiento de los casos de ILTB, mantener actualizado el sistema de información, verificar el stock de medicamentos y realizar el seguimiento mensual de las consultas y eventuales reacciones adversas a la isoniazida...

Obtención y evaluación de un derivado proteico purificado de una cepa argentina de Mycobacterium avium subsp. paratuberculosis / Production and evaluation of a purified protein derivative from an Argentine strain of Mycobacterium avium subsp. paratuberculosis (MAP)

Los derivados proteicos purificados (PPD) son mezclas antigénicas no definidas obtenidas de distintas micobacterias. Los PPD bovino (PPDb) y PPD aviar (PPDa) son los antígenos que se emplean para evaluar la respuesta inmunitaria celular en infecciones como tuberculosis y paratuberculosis en el bovino. El PPDa comercial se produce a partir de Mycobacterium avium subsp. avium, y no a partir de la subespecie paratuberculosis. En este trabajo se seleccionó una cepa local de Mycobacterium avium subsp. paratuberculosis cuyo patrón molecular por RFLP es el más frecuente entre los aislamientos de nuestro país que han sido estudiados, y a partir de esta, se obtuvo un derivado proteico purificado: PPDj-IB. Se emplearon tanto el PPDa comercial como el PPDj-IB como antígenos en la prueba de liberación de gamma-interferón en animales de un tambo con paratuberculosis y en animales control. Aun cuando ambos PPD fueron capaces de estimular diferencialmente la liberación de la citoquina en el tambo infectado (respecto de los tambos control), no hubo diferencias significativas en los niveles de estimulación producidos y solo dos animales fueron positivos mediante el empleo de PPDj-IB. A partir del análisis por Western blot se demostró que el contenido de lipoarabinomano y del antígeno Apa/ModD era distinto en los PDD evaluados. Estas diferencias podrían explicar, en parte, las diferencias en los niveles de estimulación en términos individuales. Si bien el empleo de PPDj-IB no mejoró significativamente los resultados de la prueba de liberación de ?IFN, es importante destacar que se logró producir en el laboratorio un PPD apto para su empleo en ensayos in vitro.

Purified Protein Derivatives (PPDs) are non-defined antigens prepared from mycobacteria cultures. They are usually employed to evaluate the specific cellular immune response both in animals and humans. Bovine and avian PPDs are usually employed as antigens in mycobacterial infections such as tuberculosis and paratuberculosis. Nevertheless, PPD from Mycobacterium avium subsp. paratuberculosis, (PPDj) is neither commonly used nor frequently available. However, PPD from Mycobacterium avium subsp. avium is in fact used. We aimed to obtain and evaluate the performance of a PPDj from a local isolate of MAP using the ãInterferon-release assay. The stimulation of ãInterferon-release was significantly different between infected and control cattle when this antigen, named PPDj-IB, was used. Stimulation in the infected animals was similar with both antigens (PPDa and PPDj-IB). However, some animals were positively stimulated with PPDj-IB and not with PPDa. We demonstrated by Western blot that two antigenic molecules, lipoarabinoman and APA/ModD antigen were differentially represented in both PPDs. This could explain the difference in stimulation induction of ?IFN observed at individual level. Although PPDj-IB could not improve PPDa performance, we could easily produce an effective purified protein derivative for in vitro assays.

Parameter estimation and use of gamma interferon assay for the diagnosis of bovine tuberculosis in Brazil / Estimação dos parâmetros e uso do teste do interferon gama para o diagnóstico da tuberculose bovina no Brasil

This study aimed to evaluate the interference of tuberculin test on the gamma-interferon (INFg) assay, to estimate the sensitivity and specificity of the INFg assay in Brazilian conditions, and to simulate multiple testing using the comparative tuberculin test and the INFg assay. Three hundred-fifty cattle from two TB-free and two TB-infected herds were submitted to the comparative tuberculin test and the INFg assay. The comparative tuberculin test was performed using avian and bovine PPD. The INFg assay was performed by the BovigamTM kit (CSL Veterinary, Australia), according to the manufacturer's specifications. Sensitivity and specificity of the INFg assay were assessed by a Bayesian latent class model. These diagnostic parameters were also estimate for multiple testing. The results of INFg assay on D0 and D3 after the comparative tuberculin test were compared by the McNemar's test and kappa statistics. Results of mean optical density from INFg assay on both days were similar. Sensitivity and specificity of the INFg assay showed results varying (95% confidence intervals) from 72 to 100% and 74 to 100% respectively. Sensitivity of parallel testing was over 97.5%, while specificity of serial testing was over 99.7%. The INFg assay proved to be a very useful diagnostic method.(AU)

O presente estudo avalia a interferência do teste de tuberculinização no teste do interferon gama (INFg), estima a sensibilidade e a especificidade do INFg em condições brasileiras e simula a utilização dos testes múltiplos usando a tuberculinização comparada e o teste do INFg. Trezentos e cinquenta animais oriundos de dois rebanhos livres e dois rebanhos positivos foram submetidos à tuberculinização comparada e ao teste de INFg. A tuberculinização comparada foi realizada utilizando PPD aviária e bovina. O teste de INFg foi realizado utilizando o kit Bovigam® (CSL Veterinary, Austrália) de acordo com as especificações do fabricante. A sensibilidade e especificidade do teste de INFg foram calculadas pelo Modelo Bayesiano de Classe Latente. Esses parâmetros foram também estimados para os testes múltiplos. Os resultados do teste de INFg no D0 e D3 após o teste de tuberculinização foram comparados pelos testes estatísticos de McNemar e kappa. Os resultados das médias de densidade ótica do teste de INFg em ambos os dias foram similares. A sensibilidade e a especificidade do teste de INFg apresentaram resultados variando (95% intervalo de confiança) de 72 a 100% e 74 a 100%, respectivamente. A sensibilidade do teste em paralelo foi acima de 97,5% enquanto a especificidade do teste em série foi acima de 99,7%. O teste do INFg provou ser um método de diagnóstico muito útil.(AU)

Estudio del niño en contacto con paciente tuberculoso / Evaluation of children with tuberculosis contact

La tuberculosis (TBC) es una enfermedad de distribución mundial, producida por Mycobacterium tuberculosis (bacilo de Koch), que ha re-emergido desde la década de los 80 en relación a la pandemia de VIH. Chile es uno de los países latinoamericanos con menores tasas de prevalencia de TBC. En los niños, la TBC presenta algunas características distintas al adulto en cuanto a patogenia, clínica y probabilidad de progresión desde una infección latente a enfermedad, siendo más difícil realizar el diagnóstico y mayor la probabilidad de desarrollar enfermedad una vez infectados. Existe un Programa Nacional de Prevención y Control de la TBC que nos permite plantear estrategias de prevención y quimioprofilaxis. Este artículo esquematiza estas estrategias para orientar el estudio y manejo de niños que entran en contacto con pacientes con TBC.

Tuberculosis (TB) is a worldwide infectious disease, caused by Mycobacterium tuberculosis (Koch bacilli), that has re-emerged since the decade of the 80’s in relation to the pandemic of HIV infection. Chile has one of the lowest TB prevalence rates in Latin America. In children, TB exhibits some differences from adult disease in terms of pathogenesis, clinical manifestations and probability of progression from the infected state to disease, making it more difficult to diagnose and increasing the likelihood of developing the disease once the infection is acquired. There is a National Program for the Prevention and Control of TB that allows us to develop prevention and chemoprophylaxis strategies. This article summarizes these strategies to guide the study and management of children in contact with TB patients.

Tuberculosis en trabajadores de salud / Tuberculosis among health care workers

El objetivo del presente trabajo fue abordar la problemática de la infección por tuberculosis (TB) en Trabajadores de la Salud (TS) a través de la experiencia en un programa de prevención y tratamiento de la TB en un Hospital General de Agudos de la Ciudad de Buenos Aires. Los objetivos del Programa fueron implementar acciones de educación para la salud, pesquisa periódica de TS, detección de casos de TB y efectuar acciones de control. Se definió infección TB como PPD 2 UT = 10 mm. Se realizaron dos estudios de prevalencia de infección. En 1998 fue de 31.7% (n = 533) y en 2008 de 35% (n = 670). Enfermería tuvo el mayor porcentaje de infectados. En 2008 se advirtió un aumento de la infección TB en los médicos (p = 0.02). Se estudiaron 45 TS en el grupo que repitió PPD a los tres meses del primer estudio de prevalencia. Se detectaron ochos virajes tuberculínicos (17%), todos en enfermeras. Se evaluaron 163 TS que estuvieron en contacto con 8 casos de TB diagnosticados en TS, 4 de los cuales eran enfermeras. El 39.9% presentó PPD positiva, no se detectaron casos nuevos de TB y se documentaron cinco conversiones tuberculínicas en enfermeras. Se evaluaron 127 TS de sectores con bajo riesgo, el 25.9% presentó PPD positiva (p = 0.01 comparando con el 39.9% en el grupo anterior). A pesar de las limitaciones en el recurso humano para realizar estudios de incidencia de TB, la protección personalizada, la educación en TB y la quimioprofilaxis podrían reducir los riesgos de TB en TS.

The objective of this work was to address the problem of tuberculosis (TB) infection among Health Care Workers (HCW), based on an experience in a TB Prevention and Treatment Programme at a General Acute Hospital in Buenos Aires City. The objectives of the programme were to provide health education and periodic screening of HCW, to detect TB cases and to implement control measures. TB infection was defined by a = 10 mm reaction to 2 UT PPD. Two prevalence studies of TB infection were performed. In 1998 infection prevalence was 31.7% (n = 533), and in 2008 it was 35% (n = 670). Nurses presented the highest percentage. An increase in TB infection prevalence was observed in 2008 among physicians (p = 0.02). A sample of 45 HCW integrating the first prevalence study group was analysed by applying 2 UT PPD three month later. Eight tuberculin conversions were detected (17%), all of them in nurses; 163 HCW who had contact with other eight HCW who developed TB were evaluated, four of whom were nurses. PPD reactions were positive in 39.9% with no any new case of TB detected among them. In nurses, five tuberculin conversions were observed. Other 127 HCW from low risk areas were also evaluated, 25.9% of whom had positive reactions to 2 UT PPD, while this percentage was 39.9% in the previous group (p = 0.01).Despite the scarcity of human resources that limit the planning of TB incidence studies, personal protective measures, teaching HCW about TB and chemoprophylaxis might reduce the risk of TB in this group.

Intradermorreacciones y su aplicación: revisión bibliográfica / Skin and its application: literature review

Las intradermorreacciones consisten en la aplicación intradérmica de una sustancia conocida con la finalidad de evaluar la hipersensibilidad retardada (HSR). Se utilizan con fines diagnósticos y pronósticos en algunas enfermedades. En esta revision se identifican las características relevantes de estas pruebas

Correlación entre PCR en exudado nasal y la reacción de tuberculina para la detección de organismos del complejo Mycobacterium tuberculosis en bovinos / Correlation between PCR and tuberculin test for detection of Mycobacterium tuberculosis complex organisms in bovine cattle

En México, la tuberculosis (TB) es motivo de regionalización del país de acuerdo a la prevalencia, por tal motivo, la comercialización y/o exportación de bovinos, así como su movilización, es restringida. El diagnóstico oficial de la TB en bovinos en campo se realiza con la prueba de tuberculina, y posmorten con histopatología y/o por aislamiento del agente etiológico. Aunque la prueba de la tuberculina tiene baja especificidad, es suficiente para enviar animales reactores a sacrificio, lo que no garantiza que el animal esté infectado. Lo anterior, hace patente la necesidad de métodos más sensibles y específicos. En la presente investigación se analizaron muestras de exudado nasal de bovinos, para detectar microorganismos del complejo Mycobacterium tuberculosis mediante la prueba de reacción en cadena de la polimerasa (PCR). Todos los animales positivos a la tuberculina se consideraron como animales infectados y éstos fueron comparados con los positivos a PCR. Se muestrearon 420 animales provenientes de zonas de alta y baja prevalencia. El ADN de los exudados nasales se obtuvo con el método de extracción bromuro de cetiltrimetilamonio, y éste se utilizó en una PCR anidada para amplificar dos fragmentos (583 pb y 200 pb) de la secuencia IS6110 del complejo M. tuberculosis. La prueba de PCR logró detectar un mayor número de muestras positivas en las zonas de alta prevalencia (57 por ciento), comparada con las zonas de baja prevalencia (20 por ciento). La sensibilidad de la prueba de PCR fue del 90,5 por ciento y la especificidad del 58,3 por ciento, comparada con la prueba de tuberculina. Quedó demostrado que la prueba de PCR en secreciones nasales puede utilizarse en situaciones de compra-venta o en exposiciones ganaderas como un análisis de tamizaje para prevenir el contagio y la introducción de la enfermedad a rebaños sanos.

In Mexico, the bovine tuberculosis (TB) is associated with both regionalization of the country, considering the levels of prevalence of the disease and restrictions in commercialization and/or exportation of cattle. In Mexico, the diagnosis of the bovine tuberculosis is conducted by using the tuberculin test in live animals, bacteriologic isolation and histopathological analysis in postmortem. Although the low sensibility of tuberculin test, is used to sent the animal reactors to slaughter and maybe the animal is not infected. Considering that some diagnosis methods are not sufficiently reliable and specific to detect the presence of the casual agent of this disease, the use of the polymerase chain reaction (PCR) test was evaluated from bovine nasal mucus. For the detection of the Mycobacterium tuberculosis complex, PCR of nasal mucus was better than Caudal-fold Tuberculin Test (CTT). The sensibility of PCR compared with CTT was 90.5% and specifity was 58.3%. The PCR of nasal mucus can use in buy and sell operations and cattle expositions to prevent the contagious and the introduction the pathogens in health cattle.

Interpretación de la PPD, fundamentos fisiopatologicos y enfoque práctico / PPD interpretation: physiopathology background and practice assessment

La Tuberculosis (TB) es un problema de salud pública, y la PPD (Tuberculina) se constituye en una herramienta para la detección de la TB latente. La interpretación de la PPD a través de un modelo que involucre el componente fisiopatológico, el sistema inmune del paciente y sus factores de riesgo permite una decisión correcta sobre tratar o no una TB latente de alta prevalencia de TB. En esta revisión se introduce un modelo racional de interpretación de la Tuberculina.

Prevalência de tuberculose no rebanho bovino de Mossoró, Rio Grande do Norte / A survey of tuberculosis in the cattle from Mossoro, Rio Grande do Norte State

A tuberculose bovina é uma doença infecciosa crônica e debilitante que pode infectar humanos. Uma importante etapa para o controle é a determinação da prevalência nos rebanhos. O objetivo do presente trabalho foi determinar a prevalência da tuberculose bovina em Mossoró, RN. Inicialmente foi realizada uma avaliação de risco para a ocorrência da tuberculose bovina em 21 propriedades da região avaliada. Foram testadas 150 vacas leiteiras por meio do teste da prega caudal. Também foram avaliados outros 120 bovinos pelo teste da tuberculinização cervical comparada. Os resultados revelaram falta de conhecimento dos proprietários sobre o controle da doença, bem como o descuido no momento da aquisição de animais. A prevalência foi de 8,66% e 3,33% nos testes da prega caudal e cervical comparativo, respectivamente. Assim, foi verificada uma prevalência de tuberculose bovina bastante elevada, sendo superior à média nacional.

Bovine tuberculosis is an infectious chronic and debilitating disease that can infect humans. A key step for its controls is to determine the prevalence in the herd. The present study aimed to determine the prevalence of bovine tuberculosis at Mossoró, RN. Initially, it was done an evaluation for infection hazard by tuberculosis in bovines at 21 farms. It were tested 150 dairy cows by caudal-fold tuberculin test. Other 120 bovines were also tested by comparative cervical tuberculin test. The results revealed lack of knowledge by owners about the prevention of the disease, as well as negligence when they buy animals.The prevalence was 8.66% at the cervical test and 3.33% at caudal-fold tuberculin test and comparative cervical tuberculin test, respectively.Thus, it was verified a high prevalence of bovine tuberculosis, which is greater than the national mean prevalence.