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Documento de consenso sobre diagnóstico, tratamiento y prevención de la tuberculosis
Abstract
Pulmonary TB should be suspected in patients with respiratory symptoms longer than 2–3 weeks. Immunosuppression may modify clinical and radiological presentation. Chest X-ray shows very suggestive, albeit sometimes atypical, signs of TB. Complex radiological tests (CT scan, MR) are more useful in extrapulmonary TB.At least 3 serial representative samples of the clinical location are used for diagnosis whenever possible. Bacilloscopy and liquid medium cultures are indicated in all cases. Genetic amplification techniques are coadjuvant in moderate or high TB suspicion.Administration of isoniazid, rifampicin, ethambutol and pyrazinamide (HREZ) for 2 months and HR for 4 additional months is recommended in new cases of TB, except in cases of meningitis in which treatment should continue for up to 12 months and up to 9 months in spinal TB with neurological involvement, and in silicosis. Appropriate adjustments with antiretroviral treatment should be made in HIV patients. Combined therapy is recommended to avoid development of resistance. An antibiogram to first line drugs should be performed in all the initial isolations of new patients. Treatment control is one of the most important activities in TB management.The Tuberculin Skin Test (TST) is positive in TB infection when ≥5mm, and Interferon-Gamma Release Assays (IGRA) are recommended in combination with TT. The standard treatment schedule for infection is 6 months with isoniazid. In pulmonary TB, respiratory isolation is applied for 3 weeks or until 3 negative bacilloscopy samples are obtained.
... The diagnosis of LTBI with TT uses techniques that study an individual's sensitivity to different MT antigens 8 . The technique consists of intradermal inoculation of a purified protein derivative (TT), which contains a mixture of more than 200 antigens present in MT, in the vaccine strain, BCG and in environmental mycobacteria. ...
... The main defect lies in the cross reactivity, the effect of which is a low specificity in individuals vaccinated with BCG and in those infected by atypical mycobacteria, while the tests based on interferon gamma release assay (IGRA) are more specific when using specific MT antigens. The main virtue of the IGRA lies in the antigens used to stimulate the T cells: the protein -kD Early-Secreted Antigenic Target (ESAT-6) protein and the 10-kD Culture Filtrate Protein (CFP-10), codified in difference region 1 1,8 . ...
... These specific MT antigens are not present in the BCG vaccine bacilli or in most environmental mycobacteria 9 . In other words, the capacity of the TT and IGRA to predict the development of TB is very poor, as many individuals with positive TT or IGRA results do not go onto develop a tuberculosis infection 8,10,11 . However, even with this limitation, IGRAs have significantly improved the diagnosis of a TB infection 7,8,10 . ...
Objectives: A high prevalence of prison inmates have a positive tuberculin skin test (TST) and sometimes unnecessary treatment for latent tuberculosis infection (LTBI) is prescribed. The prison tuberculosis prevention and control program has not generalized the use of QuantiFERON (QFT) in prisons. We set out to describe the implementation and usefulness of QFT in a population of inmates with positive TST, and to detect false positives and avoid unnecessary treatments. We also analysed the sociodemographic variables of the inmate population. Material and methods: All the positive TST tests between December 2020 and December 2021 from an average population of 300 inmates in Burgos prison were analysed. The QFT value was measured in all the positive cases. Sociodemographic variables were analysed and finally the number of inmates with positive TST, but with a negative QFT result and therefore not requiring LTBI treatment, was evaluated. Results: A total of 41 inmates were included in the study, with a mean age of 44 years. The proportion between Spanish inmates and foreigners was similar. Of all the positive TST, 48.8% were QFT negative. Discussion: It was observed that QFT is a safe method for the diagnosis of LTBI in prisons and that its use would contribute to a more specific selection of inmates who actually need chemoprophylactic treatment for LTBI.
... Dentro de las patologías más frecuentes asociadas se encuentran la diabetes mellitus tipo 2 (21%), desnutrición (14%), el VIH/SIDA (6%) y alcoholismo (5.4%). Los principales factores de riesgo de adquirir TB son: 13,32 • Diabetes. La coexistencia de enfermedades transmisibles y crónicas no transmisibles aumenta el riesgo por el efecto de una sobre la otra. ...
... Lo habitual es que el paciente presente los síntomas clásicos de esta forma: cansancio, tos y dificultad respiratoria (neumonía, TB miliar), estridor o sibilancias (adenopatías mediastínicas, granuloma endobronquial), expectoración, dolor en punta de costado (pleuresía), anorexia, baja de peso, febrícula o fiebre prolongada, sudoración nocturna y hemoptisis de varias semanas de duración. 15,32,34 La TB pleural puede presentarse de manera aislada o concomitante con una TB pulmonar, en la exploración física muestra semiología de derrame pleural. Radiológicamente Rev Mex Patol Clin Med Lab 2020; 67 (2): 93-112 www.medigraphic.com/patologiaclinica ...
... En ocasiones el derrame pleural puede presentarse como un empiema, el cual excepcionalmente puede fistulizar a través de la pared torácica. 32 La TB puede afectar los ganglios hiliares y mediastínicos, es muy frecuente en niños en quienes puede ser la única manifestación de TB. 32 La afección endobronquial es otra de las formas de la TB torácica, que al igual que las anteriores puede presentarse sola o combinada con otras. Esta forma se diagnostica mediante broncoscopia. ...
... En la actualidad el diagnóstico de la TB pulmonar es un problema global debido a la ausencia de pruebas rápidas, sensibles, específicas y con un costo adecuado (WHO, 2007; Suen y cols, 2015). Existen varios métodos de diagnóstico entre los que se incluyen: el cultivo de esputo, microscopía con tinción ácido-alcohol resistente (Ziehl-Neelsen), radiografía de pecho, métodos moleculares de diagnóstico directo como la Reacción en Cadena de la Polimerasa (PCR, por sus siglas en inglés), determinación de adenosina desaminasa (la cual se encuentra elevada en TB), Test de tuberculina en piel (TST, por el por sus siglas en inglés) y el Ensayo de Liberación de Interferón Gamma (IGRA, por sus siglas en inglés) (González-Martín, 2010). La reactividad inmune a Mtb es evaluada por TST e IGRA (Salgame y cols, 2015). ...
... El TST presenta algunas limitaciones como son su baja sensibilidad en las personas inmunodeprimidas que provoca resultados falsos negativos, los errores en su administración y la subjetividad en la interpretación de los resultados. Además, en los pacientes vacunados con BCG (Bacilo de Calmette-Guérin) la interpretación del TST es complicado por la interferencia de la vacunación en el mismo y la dificultad de discernir entre el efecto de la vacuna y la infección tuberculosa (González-Martín, 2010). Para intentar superar estos problemas, se desarrollaron otras técnicas de laboratorio para el diagnóstico de la infección tuberculosa. ...
... Además, incorporan controles para detectar alergia y excluir así, a los falsos negativos. Tanto el TST como el IGRA pueden ser erróneamente negativos en el caso de inmunosupresión o si la infección inicial ocurrió hace mucho tiempo (González-Martín, 2010). ...
Síntesis
La tuberculosis es una de las principales causas de muerte a nivel mundial, la Tuberculosis latente amenaza a 1,7 mil millones de personas en el mundo, y puede ser reactivada, entre otras causas, por la aparición de nuevas enfermedades como la producida por el Virus de Inmunodeficiencia Humana. La latencia del Mycobacterium tuberculosis está mediada por un grupo de proteínas, la mayoría codificadas por genes del Regulador de Seguridad de Latencia, donde la proteína Rv2626c es el miembro más fuertemente regulado de este operón. Los objetivos del presente trabajo, fueron obtener mediante procedimientos de fermentación y purificación, la proteína recombinante rRv2626c clonada y expresada en Streptomyces lividans TK24 y su caracterización físico-química en términos de pureza, identidad y secuencia de aminoácidos. Además, se evaluó el impacto de posibles modificaciones de la proteína recombinante en comparación con la proteína nativa y su influencia, en la conservación de la antigenicidad e inmunogenicidad. Para ello, se desarrolló un proceso de cultivo donde se seleccionaron medios de cultivo factibles y de producción nacional. Por otro lado, se estableció una escala de fermentación a nivel de zaranda que permitió obtener la proteína clonada y expresada a través de una purificación por cromatografía de afinidad en columna basada en la interaccion Strep-tag/biotina. La proteína purificada migra como una banda única en Electroforesis en Gel de Poliacrilamida en condiciones no reductoras y reveladas con tinción de plata, lo que muestra un alto grado de pureza, mientras que en solución, el dímero, de 30,9 kDa, es la isoforma prevaleciente sobre el monómero, de 15,6 kDa. El análisis de Espectrometría de Masas con fuente de ionización MALDI de la proteína rRv2626c corroboró los resultados de la electroforesis con respecto al peso molecular del dímero, de aproximadamente 32 kDa y se confirmó una coincidencia del 92.1% en la secuencia de la proteína recombinante rRv2626c cuando se compara con la proteína nativa presente en M. tuberculosis. Adicionalmente se determinó que el extremo N-terminal difiere solo del nativo en dos mutaciones y que en el extremo C-terminal ocurrió la hidrólisis inespecífica de 12 amino ácidos, atribuido fundamentalmente al deterioro (menor de 1 ng), ocasionado por estrés, durante la conservación y purificación de la proteína. De manera general, solo se afectó un aminoácido, en la posición 141 del epitope 13, mientra que los otros 12 epitopes relevantes en su función biológica no se afectaron. La antigenicidad se corroboró con sueros de voluntarios humanos, donde las respuestas de anticuerpos fueron significativamente más altas en pacientes con tuberculosis en comparación con donantes negativos, que se enfrentaron a la proteína rRv2626c (por la prueba de Mantoux p <0,001), mientras que el suero de los ratones inmunizados con la rRv2626c también mostró un patrón de identificación positivo frente a la proteína nativa. La proteína purificada indujo una potente respuesta inmune en el ratón y los anticuerpos resultantes reconocieron la proteína de referencia reRv2626c (expresada en E. coli). Por último, el rendimiento específico de rRv2626c en la cepa S. lividans TK24 es sostenible. Integrando todos los resultados, estos corroboran que la proteína rRv2626c es un antígeno prometedor para el desarrollo de nuevas formulaciones de vacunas contra la tuberculosis.
... A flow-chart detailing the contact-tracing study procedure and the final diagnosis of the children recruited is represented in Figure 1. Contact-tracing studies were conducted according to Spanish guidelines [17,18]. TST, IGRAs, and chest radiography were performed in the first visit during the contact-tracing study. ...
... TST was performed using 2 tuberculin units of PPD RT23 (Statens Serum Institut, Copenhagen, Denmark) and evaluated within 48-72 h by specialized nurses and physicians. Indurations ≥ 5 mm were considered positive according to the Spanish Pneumology and Thoracic Surgery Society guidelines [17,18]. T-SPOT.TB and QFN-G-IT were done and interpreted according to the manufacturer's instructions. ...
Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9–12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79–11.94)] and active TB [aOR (95% CI): 3.40 (1.45–7.98)]. Moreover, IGRAs’ sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response.
... Se seleccionaron aquellos pacientes a los que durante este periodo se les realizó una TC de tórax por sospecha de infección tuberculosa realizada antes de obtenerse la confirmación microbiológica (resultado del cultivo). Se reservó su uso para las formas extrapulmonares de tuberculosis y para aquellos casos en los que habiendo sospecha clínica de tuberculosis pulmonar, los resultados de la radiografía simple y de laboratorio no llevaran a un diagnóstico (AIII) (19) . Se realizó un cruce entre la base de datos de cultivos y la base de datos de TC de tórax del mismo periodo. ...
... En el diagnóstico de sospecha de tuberculosis pulmonar debe utilizarse la radiografía simple de tórax, que, pese a no mostrar hallazgos específicos, permite hacer un diagnóstico de sospecha. La TC es útil en formas extrapulmonares de tuberculosis, así como en los casos en los que hay sospecha clínica y los resultados de la radiografía simple y la microbiología no permiten realizar el diagnóstico (19) . ...
Introducción:
El objetivo de este estudio fue desarrollar un modelo predictivo sobre la presencia de tuberculosis pulmonar activa utilizando datos clínico-epidemiológicos y hallazgos de radiografía simple (Rx) y tomografía computadorizada (TC) de tórax.
Material y métodos:
Se realizó un estudio observacional, retrospectivo, descriptivo y analítico, que recopiló 22 variables clínico-epidemiológicas, 11 hallazgos radiológicos en Rx de tórax y 23 en la TC, que se realizaron en pacientes con sospecha clínica de tuberculosis pulmonar durante un período de 10 años. Se aplicó un modelo de regresión logística multivariado a los predictores potenciales de cultivo positivo, obteniendo un modelo predictivo.
Resultados:
Se recogieron 1.540 pacientes con sospecha clínica de tuberculosis a los que se les realizó Rx y TC torácico. El cultivo fue positivo en 101 casos. Se utilizó un proceso de eliminación hacia atrás para obtener el mejor conjunto de variables predictivas. Se obtuvieron 24 variables que fueron significativas (6 clínicas, 5 de Rx y 13 de TC) y se les asignó una puntuación. A la suma de estas puntuaciones se restó la edad en años multiplicada por 0,03. El modelo sugiere el diagnóstico de tuberculosis pulmonar activa en pacientes con una puntuación superior a 1,845. Obtuvo una sensibilidad de 85,1%, especificidad de 83,6%, valor predictivo positivo de 26,6%, y valor predictivo negativo de 98,7%. El área bajo la curva ROC fue de 0,9163.
Conclusión:
Este sistema de puntuación basado en criterios clínico-epidemiológicos y hallazgos radiológicos puede ayudar a diagnosticar tuberculosis pulmonar activa en casos de sospecha diagnóstica.
... Entre los órganos extrapulmonares más afectados por la tuberculosis en pacientes VIH están los ganglios linfáticos, tanto periféricos como intratorácicos o intraabdominales. La presencia de adenopatías significativas en cualquier territorio junto con fiebre u otras manifestaciones en pacientes positivos al VIH debe sugerir como primera posibilidad diagnóstica la TBC 3 . ...
... Las adenopatías tienden a crecer gradualmente y en principio son de consistencia rígida e indolora. Con el tiempo pueden sufrir necrosis, fluctuar y presentar signos inflamatorios con fistulización y drenaje de caseum al exterior, lo que se conoce como escrófula 3 . ...
The tuberculosis (TB) is an infect-contagious worldwide distribution disease caused by Mycobacterium Tuberculosis and other atypical Mycobacteria. Lymph node involvement is late, and its associated clinical manifestations are usually unspecifics, therefore the diagnosis of tuberculosis lymph node is often delayed and is an unexpected finding in numerous occasions. This article aims to carry out a literature review of lymph node tuberculosis and to emphasize that TB must be taken into account as differential diagnosis in cervical masses, which often occur with few associated symptoms. In this article we present two cases of lymph node TB diagnosed in our department in last months, both cases presented exclusively as cervical mass of slow growth, without any accompanying pulmonary symptoms and were diagnosed as TB after the surgical removal of the lesion and its histopathological study.
... Existen numerosos trabajos sobre hábitos de prevención de enfermedades entre escolares (González-Martín et al. 2010), sin embargo, los que investigan la alfabetización científica de los futuros docentes sobre enfermedades infecciosas, y más específicamente, los modelos que utilizan para explicar los mecanismos de infección, son prácticamente inexistentes. Investigar acerca de estas cuestiones resulta pertinente si pretendemos que los docentes promuevan hábitos de salud adecuados entre los escolares. ...
... El estudio plantea el aprendizaje de temas de salud desde un enfoque que permita el desarrollo de prácticas científicas y de destrezas de pensamiento crítico para la toma de decisiones y la adquisición de hábitos adecuados. La mayor parte de la investigación en este campo en nuestro país pone el foco de atención en la promoción de hábitos de prevención entre el alumnado de primaria (González Martín et al. 2010, Rello y Ricart 2009, mientras que los estudios que exploran la alfabetización de los futuros docentes en estos temas son prácticamente inexistentes. Destacamos una investigación realizada en Inglaterra que examina el nivel de formación de futuros docentes de primaria en temas de salud, en la que se pone de relieve que la mayoría no están adecuadamente preparados para abordar problemas de salud pública en el aula. ...
... 5 Drugs used against the M. tuberculosis complex Drugs called "first line" treatments include those administered as the first choice and are isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and, for historical reasons, also streptomycin (S). [5][6][7] The first four are those recommended by the WHO for a 6-month regimen (2HREZ + 4HR). In cases of resistance, allergy, intolerance, hepatic toxicity or interaction with one or more of these drugs, second-line drugs should be used, including rifamycins (rifabutin, rifapentine), quinolones (ofloxacin, levofloxacin, moxifloxacin), aminoglycosides (amikacin, tobramycin), capreomycin, cycloserine, linezolid, isoniazid analogues (ethionamide, prothionamide), clofazimine, PAS or thiacetazone. ...
... In cases of resistance, allergy, intolerance, hepatic toxicity or interaction with one or more of these drugs, second-line drugs should be used, including rifamycins (rifabutin, rifapentine), quinolones (ofloxacin, levofloxacin, moxifloxacin), aminoglycosides (amikacin, tobramycin), capreomycin, cycloserine, linezolid, isoniazid analogues (ethionamide, prothionamide), clofazimine, PAS or thiacetazone. [5][6][7] In cases of MDR-TB or XDR-TB, recently developed drugs may also be used, such as bedaquiline and/or delamanid. 8 ...
Mycobacteria are a large group of microorganisms, multiple species of which are major causes of morbidity and mortality, such as tuberculosis and leprosy. At present, the emergence and spread of multidrug-resistant strains of Mycobacterium tuberculosis complex are one of the most serious health problems worldwide. Furthermore, in contrast to M. tuberculosis and Mycobacterium leprae, non-tuberculous mycobacteria (NTM) are more frequently isolated and, in many cases, treatment is based on drug susceptibility testing. This article is a review of the different methods to determine the in vitro drug susceptibility of M. tuberculosis complex and the most relevant NTM isolates. The molecular techniques currently used for rapid detection of resistance of clinical specimens are also analysed.
... Las formas clínicas más frecuentes de TBE son la ganglionar y pleural, aunque el bacilo puede multiplicarse en cualquier tipo de tejido. Es importante destacar que aproximadamente en el 61% de los casos de TBE reportados el diagnóstico se realiza sobre bases clínicas, solo en un 10%-15% se logra realizar el diagnóstico por aislamiento en medio de cultivo, lo cual se explica por la baja concentración bacilar que tiene este tipo de muestra [1,2,14]. ...
... La forma clínica de las lesiones presentadas por nuestro paciente en pabellón auricular fue clasificada como lupus vulgar ulcerativo; la lesión del pene apareció mucho después que las del pabellón auricular y se catalogó también como lupus vulgar ulcerativo probablemente por autoinoculación a partir de las primeras. El paciente evolucionó satisfactoriamente una vez iniciado el tratamiento antituberculoso, recomendado en la literatura para las diferentes formas clínicas de TBC, tanto en pacientes inmunocompetentes como inmunodeficientes, ya que se describe para ambos casos una evolución favorable [12,14,16]. ...
Resumen:
La tuberculosis cutánea (TBC) es una enfermedad infecciosa poco común (1-2% de los casos) que ha sufrido un incremento debido a la pandemia por el virus de la inmunodeficiencia humana o al aumento creciente de la inmunosupresión farmacológica. Se describe un caso inusual de TBC en paciente cubano con síndrome de inmunodeficiencia adquirida (SIDA), que presentó lesiones ulcerativas/exudativas en pabellón auricular izquierdo y pene. Las muestras de secreción y tejido de las lesiones, fueron cultivados previa
descontaminación. Para el cultivo se utilizó el método convencional en medio Löwenstein-Jensen (L-J) y el método automatizado Bact/Alert 3D. Pasadas 2-3 semanas se detectó la presencia de una cepa micobacteriana no pigmentada, de crecimiento lento, la cual fue identificada como Mycobacterium tuberculosis por la determinación del TB Ag MPT64 Bioline. Según las características clínicas del
paciente y de las lesiones, fue diagnósticado como tuberculosis cutis luposa variedad lupus vulgar ulcerativo y mutilante. Al paciente se le administró tratamiento antituberculoso y terapia antirretroviral logrando mejorar su calidad de vida. El diagnóstico oportuno de las infecciones extrapulmonares por Mycobacterium logra evitar diseminación de la infección, tanto en pacientes inmunocompetentes como inmunodeficientes.
... But its absence requires Ziehl-Neelsen (ZN) stain confirmation of acid-fast bacilli (AFB), with 5000-10,000 bacilli/cc. [6] Negative ZN cases are confirmed by GeneXpert for Mycobacterium tuberculosis DNA (GeneXpert MTB). Our study includes EPTB involving different systems and rare sites, presenting with non-classical symptoms that may pose a diagnostic challenge. ...
Background
Pulmonary tuberculosis may result in haematogenous and lymphatic extension in case of failure of early detection, or immunocompromised status, leading to extrapulmonary tuberculosis. Rare sites of extrapulmonary tuberculosis include the gastrointestinal tract, musculoskeletal system, genital tract, middle ear and pericardium. Histopathological findings of macro-confluent granuloma with or without caseous necrosis, along with detection of acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining, and GeneXpert for detection of Mycobacterium tuberculosis DNA, are key in establishing a diagnosis of tuberculosis.
Methodology
Biopsy-proven extrapulmonary granulomatous lesions were included in this study. Histopathological evaluation of all extrapulmonary biopsy specimens sent to the Department of Pathology were done for the presence of granuloma and necrosis, and ZN staining for AFB was done in all the cases of granulomatous lesions with or without the presence of necrosis. The same cases, with biopsy specimens sent in normal saline, were re-evaluated in a molecular laboratory with the help of GeneXpert MTB to detect the DNA of Mycobacterium tuberculosis. All biopsy specimens from extrapulmonary sites which were sent to the Department of Pathology were used for DNA extraction.
Results
Out of the 10 cases of extrapulmonary granulomatous lesions, 8 showed caseous necrosis on microscopy, and 7 showed the presence of acid-fast bacilli on Ziehl-Neelsen staining. GeneXpert detected DNA of Mycobacterium tuberculosis in 9 cases.
Conclusion
Extrapulmonary tuberculosis rarely occurs as primary, and mostly spreads from lung parenchyma via a haematogenous route. Tuberculosis of the gastrointestinal tract, peritoneum, lymph nodes, and solid viscera are together termed abdominal tuberculosis. Entities like tuberculosis of the pericardium and ear are extremely rare. Extrapulmonary tuberculosis should be a differential in cases of chronic non-responding cases with diagnostic dilemmas. To avoid diagnostic delay, in cases of high suspicion, one should go for biopsy along with ZN staining for diagnostic confirmation as this is cost-effective, followed by GeneXpert for Mycobacterium tuberculosis in highly suspected cases with absent caseous necrosis and negative ZN staining.
... En Colombia para el año 2019, se notificaron al Sivigila 14.684 casos de tuberculosis de todas las formas, siendo la forma pulmonar la que más casos aportó con el 83,32 y un 16,68% para la tuberculosis extrapulmonar 6 . Se han descrito múltiples factores asociados, donde las condiciones sociodemográficas, y comorbilidades del paciente, se consideran los mayores factores de riesgo para adquirir la enfermedad 7 . ...
Resumen
La Tuberculosis (TB) es una enfermedad infectocontagiosa de relevancia mundial con predominio de afectación a nivel pulmonar, sin embargo, existen otras formas de presentación menos frecuentes, como la Tuberculosis miliar (TM). Se expone el caso de un paciente masculino de 63 años, heterosexual, con antecedente de tabaquismo y consumo de alcohol, que presenta cuadro de dolor abdominal y fiebre, con hallazgos de masa en colon, requirió laparotomía e hemicolectomía derecha, manejo con antibioticoterapia y posterior egreso por evolución favorable; sin embargo días después reingresa con presencia de masa a nivel faríngea y síntomas respiratorios, se recibe reporte histopatológico de colon y faringe compatible con enfermedad granulomatosa, además hallazgo radiológico de tórax y confirmación microbiología por baciloscopia de infección por Mycobacterium tuberculosis (MT). Con el presente caso se describe una presentación atípica de tuberculosis miliar, con múltiple compromiso de órgano, en paciente inmunocompetente, así como destacar la importancia de la sospecha clínica y del tratamiento oportuno.
Abstract Tuberculosis (TB) is an infectious and contagious disease of global relevance with a predominance of affectation at the lung level, however, there are other less frequent forms of presentation, such as miliary tuberculosis (TM). The case of a 63-year-old male patient, heterosexual, with a history of smoking and alcohol consumption, presents with symptoms of abdominal pain and fever, with findings of a mass in the colon, required laparotomy and right hemicolectomy, management with antibiotic therapy and subsequent discharge due to a favorable evolution; However, days later he was readmitted with the presence of a mass at the pharyngeal level and respiratory symptoms, a histopathological report of the colon and pharynx compatible with granulomatous disease was received, as well as a radiological finding of the chest and microbiological confirmation by smear microscopy of infection by Mycobacterium tuberculosis (MT). With this case we present the description of an atypical presentation of miliary tuberculosis, with multiple organ involvement, in an immunocompetent patient, as well as highlighting the importance of clinical suspicion and timely treatment. Keywords: Tuberculosis, Miliary tuberculosis, fever, abdominal pain.
... La Hoja de Ruta para la Eliminación de la Tuberculosis en Latinoamérica y el Caribe resalta la búsqueda activa de casos de TBP, mediante la identificación del SR y la focalización de estas acciones en poblaciones vulnerables, dentro de las que se encuentran las personas privadas de libertad 1,2 . ...
Objective:
To evaluate mass screening campaigns for tuberculosis in prisoners in Ecuador.
Material and method:
Cross-sectional study of Chronic Cough (CC) detected amongst inmates who entered two prisons in Ecuador between January and December 2016 (n = 12,365). The time distribution of the CCs was analyzed with the uniformity test and its relationship with the diagnosed cases of PTB, the prevalence of PTB was calculated. A logistic regression model was performed to determine the factors modifiers of PTB positivity.
Results:
1.332 chronic cougher were recorded, the positivity rate was 17.3% (95% CI, 15.1-19.4), and the prevalence was 1.9% (95% CI, 1.6 - 2.1). There was an absence of uniformity in the detection and diagnosis by epidemiological weeks; there was a positive correlation between CC and PTB cases. The positivity rate was associated with the prison with the highest density (adjusted OR 3.8; 95% CI, 2.5-5.5).
Discussion:
Massive screening campaigns are not enough to control tuberculosis in Ecuador's prisons. The incidence found is high. It is necessary to strengthen the diagnostic process to treat all the cases found and thus break the chain of transmission.
... Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/bync-nd/4.0/). sensibilidad, para posteriormente continuar con rifampicina e isoniazida durante 4 meses más 3,4 . ...
... To perform the TST, we used a 2-TU dosage of PPD-RT (Statens Serum Institut, Copenhagen, Denmark). The performance and interpretation of the results of the Mantoux test were carried out following the Spanish guidelines 46 . IGRAs testing was performed using the commercially available enzyme-linked immunosorbent assay (ELISA) QuantiFERON-TB Gold In-Tube test (QFT, Qiagen, Hilden, Germany) and/or the Enzyme-Linked Immunospot (ELISPOT) assay T-SPOT.TB blood test (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, UK) following the manufacturer's protocol. ...
Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.
... The polymerase chain reaction (PCR) has facilitated the diagnosis and management of tuberculosis. 5 Management of caries spine has remained controversial and divided between those who favor the exclusive medical means of treatment and others who support surgical intervention along with medical treatment. Adequate rest and anti-tuberculous therapy is the cornerstone of management. ...
Objective: To compare short term outcome of combined surgical and medical management versus medical management alone in caries spine. Material and Methods: This study was conducted from August 2015 to August 2018, on 68 patients randomly divided into two groups of 34 each. All were diagnosed cases of Caries spine based on history, clinical examination, ESR and imaging appearances. Group A underwent surgical intervention along with Anti-Tuberculous Treatment (ATT) while Group B received medical treatment (ATT) alone. Outcome was assessed at six months by Frankel grading. Results: There were 37 (54.41%) males and 31 (45.59%) females with mean age of 34.84 ± 10.6 years. The thoracic spine was the commonest site in 33 (48.5%) patients, followed by lumbar in 20 (20.8%), dorso-lumbar in seven (10.3%) and cervical in four (5.88%) patients. The ESR fell from 85mm/hr to 24.46mm/hr in Group A and to 41.92mm/hr in Group B (p = 0.0124). Overall improvement in Frankel grade was seen in 25 (73.5%) patients in Group A and 12 (35.3%) in group B. In group A, improvement seen from grade A in two (8%), grade B in three (12%), grade C in 12(48%), Grade D in seven (28%) patients, (p = 0.000) while eight (23.5%) patients remained same and only one (2.5%) deteriorated from baseline neurological status. In Group B, 16 (47%) patients remained same and six (17.6%) deteriorated. Major complications encountered were respiratory infections in four (10%) and wound infection in two (5%) patients while none expired. Conclusion: Surgery combined with antituberculous therapy was found to be beneficial in patients suffering from caries spine and to be recommended to patients desiring rapid recovery.
... 36 Additionally, these requirements increase in active catabolism state as in TB; in HIV the need is higher due to malabsorption and increased use of micronutrients. 37,38 In Malawi, the dose used was DRI of micronutrients; in contrast, a study in Tanzania that used doses 4-10 times higher than the DRI, reduced the recurrence of TB in HIV. 16,18 Zinc: possibly does not demonstrate early sputum conversion supported by the study carried out in Tanzania; in contrast, in Indonesia achieved earlier conversion using higher concentrations of vitamins 18,23 and Ginawi ensures that it was faster in the first two months. ...
Background:
Multiple researchers have suggested the influence of micronutrients in the cure and survival of tuberculosis.
Objective:
To determine the effectiveness of micronutrients in the cure and treatment of pulmonary tuberculosis.
Methods:
Systematic search of randomized controlled trials (RCTs) in databases of people under treatment for active pulmonary tuberculosis, that must have received oral micronutrients for at least four weeks compared with placebo. The synthesis of the variables was shown in standardized mean difference (MD) and/or risk difference (RD). The random effects model was used and was reported in forest plot of the estimates of the effect with a 95 % CI.
Results:
Sixteen of 246 studies were included, in total 4398 people. Zinc showed (RD, 0.04; 95 % CI, 0.00-0.08) in mortality, increases muscle mass index (MD, 1.20; 95 % CI, 0.04-2.36) and gains weight (MD, 3.10; 95 % CI, 0.66-5.54). Zinc plus vitamin A increases the weight (MD, 3.10; 95 % CI, 2.78-3.42), improving karnofsky scale (MD, 2.50; 95 % CI, 2.22-2.78). Additionally, vitamin D accelerate the sputum conversión time (RD, 0.38; 95 % CI, 0.03-0.73). Hemoglobin (Hb) with vitamin A and zinc achieves statistically significant changes (MD, 0.69; 95 % CI, 0.28-1.09) and (MD, 0.52; 95 % CI, 0.21-0.83) and reduces area of cavitations in chest X-ray (MD, -0.33; 95 % CI, -0.60--0.06).
Conclusions:
The consumption of micronutrients could achieve weight gain, hemoglobin, accelerated sputum conversion and improvement in quality of life. There are no changes in mortality that may be attributable to the suboptimal dose, larger studies are suggested with adequate doses.
... Furthermore, radiology is considered a very valuable tool to aid in the diagnosis of extrapulmonary TB, as obtaining samples for microbiological analysis may not be possible in these cases [46]. ...
Background Tuberculosis (TB) is considered a multisystemic disease showing many extrapulmonary presentations. TB uveitis is one of the common forms of extrapulmonary TB. The lung is still the first organ to be attacked by TB, and pulmonary TB is the only infectious form of the disease.
Aim The aim of the study was to detect the prevalence of active pulmonary TB among patients with TB uveitis.
Patients and methods The present study included 37 patients with diagnosis of ocular TB on the basis of previous history, ocular examination, and exclusion of other suspected causes of uveitis. In addition, positive tuberculin skin test, or positive interferon-gamma release assays were carried out. All included patients were subjected to sputum examination for acid-fast bacilli and plain radiography of chest P-A view, and certain cases had a bronchoalveolar lavage. Patients with active pulmonary TB were detected. Both groups (patients with active pulmonary TB and patients with free chest) were compared with regard to all the previously mentioned studied parameters.
Results The mean age of the studied patients was 34.8±12.5 years. All the studied patients showed positive tuberculin test with a mean of 18.5±3.4 mm. With regard to the Quantiferon Gold test, 34 patients (91.9%) had positive results. Concerning radiography, only 10 (27%) patients had normal radiograph, the rest of the patients showed various radiological lesions. Thirty (81.1%) patients were diagnosed to have active pulmonary TB. Sputum examination for acid-fast bacilli revealed that 22 (59.5%) patients had positive results; an additional eight patients (who had negative results on sputum examination) showed positive results when they underwent a bronchoalveolar lavage. There was no statistically significant difference with regard to all the previously mentioned parameters between patients with active pulmonary TB and patients with a free chest.
Conclusion The present study revealed that a considerable percentage of the patients with TB uveitis had active pulmonary TB.
... El tratamiento de la TBEP es el convencional para la TB, sólo que dependiendo de la localización se adaptan la cantidad de medicamentos a utilizar, la duración y, en los casos que así lo requieran, el empleo de la cirugía correctiva. Por ejemplo, en el caso de TPEP con compromiso neurológico la reco� mendación es un tratamiento de 12 meses, dado que en estos pacientes los esquemas cortos se asocian a mayor riesgo de recaídas 5,6 . ...
... Diagnostic tests for tuberculosis is difficult because of the procedures that are performed to obtain a result are complex. The tuberculin test is one of the most common method worldwide, but obtaining reliable results takes up to one week [6]. With the help of information technologies, these procedures can be streamlined for the best care and treatment of patients. ...
... Diagnostic tests for tuberculosis is difficult because of the procedures that are performed to obtain a result are complex. The tuberculin test is one of the most common method worldwide, but obtaining reliable results takes up to one week [6]. With the help of information technologies, these procedures can be streamlined for the best care and treatment of patients. ...
This paper presents a web system named TBDiagnostic for data acquisition, analysis and diagnosis of pulmonary tuberculosis. With the help of an artificial intelligence model, which generates a prediction of the diagnosis of tuberculosis, the system allows the user to generate a fast and accurate diagnosis of a person with symptoms of tuberculosis. The system allows to storage patient records and generate reports on these records. This system could help physicians who treat the disease especially in health centers and hospitals with limited infrastructure and data as it is the case of developing countries.
... El departamento del Meta registra una prevalencia de tuberculosis y de infección concomitante con el HIV superior a la nacional (5 Municipios sin reporte de casos la tuberculosis y de las actividades conjuntas con el de HIV. En este sentido, en algunos estudios y análisis de los programas de tuberculosis, se han dado recomendaciones para subsanar las fallas (34)(35)(36). ...
Introduction. One third of the increase in tuberculosis cases is attributed to the spread of HIV.
Objective. To describe the Tb/HIV coinfection in the department of Meta from 2010 to 2015.
Materials and methods. We conducted an observational, descriptive and retrospective study. After selecting 219 cases for analysis, two new databases were constructed and analyzed in three phases: Identification of sociodemographic and clinical characteristics, indicators by municipality (prevalence and therapeutic success) and stratification in epidemiological scenarios according to the prevalence (burden) of the illness.
Results. Sixty percent of the municipalities corresponded to scenario 2. People with Tb/HIV coinfection who had not been treated previously, had 2.39 times more probability of having therapeutic success compared to those previously treated, this association being statistically significant (RP=2,39; 95% CI 1,3-9,6; p=0,01).
Conclusion. Stratification by epidemiological scenarios is useful for planning prevention and control activities.
... Current Spanish consensus document about the treatment of tuberculosis recommend a 9-month standard treatment for tuberculous spondylitis and there is no specific pattern for tuberculous osteoarthritis of other location [6]. In addition, there is no optimal duration of therapy for patients with bone and soft tissue tuberculosis in which all caseous material cannot be removed with surgery and all studies about antituberculous treatment duration for osteoarticular tuberculosis have been performed in spinal tuberculosis. ...
... This reduces morbimortality and stops transmission to other members of the community 2 . Concomitantly, the analysis of contacts will enable to extend this Self-administered treatment for tuberculosis strategy by identifying subclinical cases or those cases with latent infections and a higher risk of developing TB in the future, continuing the epidemiological cycle 3 . However, the lack of adherence to the treatment of a significant amount of patients compromises these objectives favoring relapses and the development of pharmacological resistance. ...
Tuberculosis (TB) has a higher incidence in populations with socio-economic deficits and requires prolonged antibiotic therapy to heal, which hinders adherence to the treatment, with an abandonment rate ranging between 15 and 30% in those with self-administered treatment. Objectives: to assess the rate of abandonment and to identify predisposing factors in patients monitored at the hospital with self-administered treatment, implemented with weekly controls during the attack phase, and then monthly controls (consolidation phase) until completing the planned schedule. Materials and methods: all the patients who started treatment between January 1st and December 31st, 2015 were included. A descriptive analysis of the results obtained up to December 31st, 2016 was performed. An interruption ≥ 14 days during the attack phase and ≥ 2 months during the consolidation phase was defined as abandonment by comparing the characteristics of this group with the compliant group using the chi-square test. Results: 73 patients (38 males) aged 34±15 years were included, 32 were Argentine (44%), and the rest was comprised of: 33 Bolivians, 5 Paraguayans, 2 Peruvians and 1 Chilean. In 47 cases (64%), TB was pulmonary. The extrapulmonary damage included: 11 pleural, 5 nodal, 3 bone (one with a concomitant impact on the psoas and another one on the lung), 2 laryngeal and pulmonary, 2 peritoneal, 2 meningeal and 1 intestinal. In all the cases (except for one that started treatment empirically), the disease was confirmed by direct AFB smear or culture, or by finding granulomas in biopsies performed in a compatible clinical context. Fifty-two patients completed the treatment (71.2%), 1 patient passed away and 20 abandoned it (27.4%); of the latter, 4 restarted and completed the treatment. The most frequent comorbidities were alcoholism (n = 7), diabetes (n = 6), and HIV positives (n = 6). Compared to the group that completed the treatment, alcoholism was a significant predictive factor for abandonment (2 in 52 vs. 5 in 20; p
... Esto disminuye la morbimortalidad e interrumpe su trasmisión a otros miembros de la comunidad 2 . Concomitantemente el estudio de contactos nos permitirá extender esta estrategia identificando casos subclínicos o aquellos con infección latente y mayor riesgo de desarrollar TBC en el futuro, continuando el ciclo epidemiológico 3 . ...
La tuberculosis (TBC), además de su mayor prevalencia en la población con deficiencias socio-económicas, requiere de antibioticoterapia prolongada para su curación lo cual dificulta la adherencia al tratamiento, con una proporción de abandonos que alcanza entre 15 y 30% en aquellos con tratamiento autoadministrado. Objetivos: Evaluar la proporción de abandonos e identificar los factores predisponentes, en los pacientes seguidos en el hospital con la modalidad de tratamiento autoadministrado, instrumentado con controles semanales durante la fase de ataque, y luego mensuales (fase de consolidación) hasta completar el esquema previsto. Materiales y métodos: Se incluyó a todos los pacientes que iniciaron tratamiento entre el 1 de enero y el 31 de diciembre de 2015. Se realizó el análisis descriptivo de los resultados obtenidos al 31 de diciembre de 2016. Se definió abandono a la interrupción ≥ 14 días en la fase de ataque, y ≥ 2 meses en la de consolidación, comparando las características de este grupo respecto del grupo cumplidor, mediante la prueba de χ2. Resultados: Se incluyeron 73 pacientes (38 hombres), edad 34±15 años, 32 argentinos (44%), el resto: 33 bolivianos, 5 paraguayos, 2 peruanos y 1 chileno. En 47 casos (64%) la TBC fue pulmonar. La afectación extrapulmonar incluyó: 11 pleural, 5 ganglionar, 3 ósea (uno con afectación concomitante del psoas y otro del pulmón), 2 laríngea y pulmonar, 2 peritoneal, 2 meníngea y 1 intestinal. En todos los casos (excepto uno que inició tratamiento en forma empírica), se demostró la enfermedad por estudio directo para BAAR o cultivos, o por hallazgo de granulomas en biopsias realizadas en un contexto clínico compatible. Completaron el tratamiento 52 pacientes (71.2%), 1 fallecido y 20 abandonaron (27.4%), de los cuales 4 reiniciaron y completaron el tratamiento. Las comorbilidades halladas con más frecuencia fueron alcoholismo (n = 7), diabetes (n = 6), y VIH positivos (n = 6). Comparando con el grupo que completó tratamiento, el alcoholismo resultó un factor predictivo significativo de abandono (2 en 52 vs 5 en 20; p
Tuberculosis (TB) is a disease caused by Mycobacterium species. The organism resides within the host in a clinically inactive or latent. Individuals with LTB not pose
a risk to public health. The standard test for the diagnosis of TB infection is the tuberculin test. Currently, the type of antigen used in the tuberculin PPD.
Descriptive, observational and prospective study in 2012 in the General Hospital of Zone 18, IMSS. All patients suspected of pulmonary tuberculosis clinically and radiologically detected in internal medicine, were concern to Epidemiology for revaluation, application of PPD and sampling for BAAR and culture. Eligible born in the States most predominant for the study were considered one of the positive PPD figures, finding that reactions > 10 mm that were predominant in the sample are for those born in Veracruz, Yucatan, Federal, Tabasco, Chiapas and Quintana Roo.
We present the case of a 44-year-old male patient with a family history of lymphoma and hyperthyroidism. He started the disease three months before admission to hospital with pain in the right leg, abdominal pain, weight loss and night sweats. He was diagnosed in his hospitalization with ascites in a cavity of undetermined etiology, and multiple polygastric and fossa lymph nodes right iliac. At 6 months, the symptoms persist and a nodule is added on the penis, left testicular edema and purulent discharge from the right inguinal node, being diagnosed orchiepididymitis. Initially he had negative markers for tuberculosis (TB), however, a lymph node biopsy was performed and the analysis with Xpert MTB/RIF where it resulted positive. The patient improved considerably with anti-TB treatment and antibiotics for purulent discharge.
Introducción:
La tuberculosis es una de las 10 principales causas de muerte a nivel mundial. En 2020, causó 1,5 millones muertes. Se estima que llegó a 10,0 millones de nuevos casos durante el mismo año.
Reporte de caso:
varón de 93 años, antecedente de TBC pulmonar hace 15 años y contacto TBC actual. Presenta disnea y dolor pleurítico por 4 meses. Toracocentesis concluye exudado, biopsia pleural compatible con pleuritis granulomatosa no caseificante. Recibe esquema antituberculoso, desarrollando RAFA hepática. Se realiza reto farmacológico para diseñar un nuevo esquema de tratamiento. Paciente logra recuperarse. Se concluye que el manejo de tuberculosis debe individualizarse según paciente.
Introduction:
People who consume drugs have a higher risk of latent tuberculosis infection (LTBI). Our objective was to study the characteristics of people who use drugs and who attended the Centers for Drug Dependence Care and Follow-up of Barcelona during 2017-2021 and presented LTBI or did not perform the reading of the tuberculin skin test (TST) after the test had been done.
Methods:
A cross-sectional, descriptive study in Centers for Drug Dependence Care and Follow-up of Barcelona was performed during 2017-2021. The sociodemographic and epidemiological profile of people who use drugs that underwent a TST was analyzed and were examined the factors associated with LTBI. Additionally, the same sociodemographic and epidemiological analyses were made in PWUD that did not perform the reading of the TST after the test had been done. Adjusted odds ratios (ORa) and 95% confidence intervals (95% CI) were calculated.
Results:
Nine hundred forty-eight persons were profiled. The prevalence of LTBI was 22.9%, and the following factors were associated with it: be older than 41 years; be users of CAS Baluard, or CAS Horta-Guinardó; coming from a WHO region of high TB incidence; be homeless; and low territorial socioeconomic index. The following factors were associated with not performing the reading of the TST after the test had been done: be users from the CAS Baluard, Barceloneta, Nou Barris and Robadors; be homeless and low TSI.
Conclusions:
This study improves TB control and highlights the need for this LTBI control program in CASs.
El espectro clínico y formas de presentación de la tuberculosis genital son muy variables e inespecíficas, por lo que es necesario un elevado grado de sospecha para llegar a su diagnóstico. A continuación, se presenta el caso de una paciente de 19 años de edad sin antecedente de tuberculosis pulmonar previa con fuerte sospecha enfermedad pélvica inflamatoria con absceso tubo-ovárico, a la cual se le practicó una laparotomía y cuyas biopsias finales diagnosticaron tuberculosis en anexos. Se inicia tratamiento específico para el buen pronóstico de la evolución clínica. Introducción La tuberculosis (TB) es una enfermedad infectocontagiosa causada por el Mycobacterium tuberculosis y caracterizada por la formación de granulomas en los tejidos. A pesar de las campañas de erradicación de la OMS, la tuberculosis sigue siendo uno de los problemas sanitarios más importantes en el mundo. Cada día, casi 4.000 personas pierden la vida a causa de la tuberculosis y cerca de 28.000 padecen de esta enfermedad prevenible y curable (1). Aunque los pulmones son los órganos afectados por excelencia, se reconoce como una enfermedad sistémica. Las formas extrapulmonares representan cerca del 20% del número total de casos de TB. Por orden de frecuencia las formas extrapulmonares más prevalentes son la pleural y ganglionar. La afectación genital es poco frecuente, con incidencia variable, oscilando entre 1-19% (2). La tuberculosis es conocida como la gran simuladora que mimetiza una variedad de padecimientos. En el contexto de tuberculosis genital las manifestaciones clínicas son variadas, inespecíficas, tardías o inexistentes. No existiendo ningún signo o síntoma clínico exclusivo de la enfermedad, siendo esta una patología de difícil diagnóstico. Como mencionado anteriormente esta es una enfermedad infrecuente y por lo tanto poco sospechada, por lo que no es inusual llegar al diagnóstico durante o después de una laparotomía por otra causa (3). A continuación, se presenta un caso clínico al inicio diagnosticado de enfermedad pélvica inflamatoria complicada, y a través de la biopsia de pieza quirúrgica se llegó a determinar su etiología tuberculosa. Informe de caso Paciente de sexo femenino indígena de 19 años de edad, llega al servicio de urgencias del Hospital Regional de Pedro Juan Caballero, con cuadro de aproximadamente 2 meses de evolución de dolor modero en hipogastrio de inicio insidioso, que irradia a la fosa iliaca derecha (FID), que horas antes del ingreso se intensifica, al cuadro se agrega leucorrea y sensación febril no graduada intermitente en varias oportunidades. Los antecedentes revelaron: menarquia: 13 años, gesta I, Parto I, Fecha última menstruación (FUM) no precisada. Al examen físico se constata dolor a la palpación superficial, profunda y signo de rebote en FID, movilización de cuello uterino dolorosa. El hemograma se encontraba dentro de rango, marcador tumoral CA125: 76,76 u/m (rango normal 1,90 – 16,30 u/ml), Beta HCG negativo. La ecografía transvaginal reveló: útero aumentado de tamaño, ovarios de tamaño y estructura conservada, trompa derecha tortuosa, de calibre aumentado y con contenido grumoso en su interior, sugerente de piosalpinx derecho. Espacio de Douglas con escasa presencia de líquido libre (vol inf 10 cc). Tomografía computarizada (TC) tórax no se identifican procesos de consolidación ni imágenes nodulares intraparenquimatosas, no se reconocen adenomegalia (sin contraste EV). TC de abdomen y pelvis: no se observan signos de adenopatía retroperitoneal ni líquido libre y útero aumentado de tamaño, mide 135x65 mm asociado con escaso líquido en fondo de saco de Douglas. En vista de la clínica y con el diagnóstico de abdomen agudo quirúrgico de origen anexial se realizó laparotomía exploradora con incisión media infraumbilical. Se tomó muestra para biopsia de la pieza quirúrgica. Se realiza salpingooforectomía derecha, egresando a las 96 horas sin complicaciones. Dos meses posquirúrgicos retorna a consultorio con estudio histopatológico que encuentran estroma ovárico y tubárico con extenso infiltrado inflamatorio granulomatoso con células gigantes de Langhans y focos de necrosis central de tipo caseoso. Coloración de Ziehl-Nielsen BAAR 2 +. Además, refiere decaimiento del estado general, tos de semanas de evolución al inicio seca que con el paso de los días se vuelve productiva con expectoración blanquecina y sensación febril intermitente en varias oportunidades con predominio vespertino, pérdida de peso de aproximadamente de 8 kg y leucorrea. Al examen físico se constata abdomen blando, depresible, no doloroso, sin defensa muscular ni signos de irritación, signo de Frankel negativo, presencia de leucorrea blanquecina no fétida. En la auscultación respiratoria se encuentra murmullo vesicular disminuido en todo el campo pulmonar, sin ruidos sobreagregados. Se solicita hemograma que revela anemia microcítica hipocrómica, leucocitos 9.100 mm3, neutrófilos segmentados 80%, linfocitos. Tinción con Ziehl-Nielsen demuestra tomada de secreción vaginal revela la presencia de bacilos. Nueva ecografía informa dos imágenes nodulares, hipoecogénicas, de bordes regulares que miden 29x25 mm y 29x23 mm en región anexial derecha. En radiografía de tórax se observa infiltrado pulmonar con patrón miliar. Inició terapia anti-TBC, con buena tolerancia y respuesta al tratamiento, actualmente sin evidencia de enfermedad. Discusión La afectación del aparato genital femenino por alguna de las bacterias del complejo Mycobacterium tuberculosis es conocida como tuberculosis genital o pélvica. Su incidencia en el mundo es variable y no está precisamente determinada; 80-90% son diagnosticadas entre los 20 y 40 años, tan sólo un 10% de los diagnósticos se realiza en la posmenopausia (4) (5). La tuberculosis es ante todo una infección del aparato respiratorio, la entrada de la bacteria, que también puede ser llamada de bacilo de Koch al aparato genital femenino se da mediante diseminación hematógena y su posterior asentamiento en estos órganos durante la infección primaria. Cada una de las porciones genitales de la mujer son muy distintamente sensibles a la afección tuberculosa. La trompa de Falopio constituye el primer foco de TB genital en 90% de las pacientes, seguido por el útero (50-60%), ovarios (20-30%), cuello uterino (5-15%) y finalmente la vagina (1%) (6). La tuberculosis genital femenina, incluso en la actualidad, se reconoce muy tardíamente en gran parte de los casos por su curso pobre en síntomas y por la falta de signos específicos. A menudo es silente, cuando presenta manifestación clínica pueden ser agrupadas en tres espectros siendo la más frecuente la esterilidad (47%), seguida de la salpingooforitis (32%) caracterizada por su refractariedad al tratamiento antibiótico, y por último el sangrado uterino anormal (11%) (6). Es absolutamente improbable poder diferenciar las manifestaciones clínicas de una anexitis tuberculosa de las correspondientes a una salpingitis no específica sin el uso de exámenes complementares. Frecuentemente se llega al diagnóstico a través del estudio histológico donde se observan lesiones granulomatosas características con células epitelioides y células gigantes multinucleadas (7). El único diagnóstico de certeza de la forma extrapulmonar es el hallazgo de M. tuberculosis en muestra de tejido a través de biopsia o cultivo de material endometrial. La epidemiología y otros exámenes de laboratorio como PPD o tuberculina, radiología, CA-125, análisis de ADA en líquidos ascítico, aunque son orientadores, no son específicos. Cabe mencionar que es una afección poco frecuente en la práctica diaria por lo que en la mayoría de los casos no es llevada en cuenta en el momento de realizar el diagnóstico diferencial, gran parte de los casos son diagnósticas después de una laparotomía, solo el 50% de los casos se diagnostican sin intervención quirúrgica. Como mencionado anteriormente esta patología aumenta el marcador tumoral del cáncer de ovario CA-125, por lo tanto, se debe tener en cuenta en el diagnóstico diferencial el cáncer de ovario (8). El tratamiento de la TB extrapulmonar (excepto en la meningoencefálica) es semejante a la forma pulmonar. Los regímenes de tratamiento se dividen en dos fases, la inicial o intensiva (Bactericida) y la de continuación o mantenimiento (Esterilizante). La fase inicial o intensiva consiste en la administración diaria de los antibacilares Rifampicina (R), Isoniacida (H), Pirazinamida (Z) y Etambutol (E), descansando los domingos durante dos meses, tiene como objetivo la rápida conversión bacteriológica (negativización) del esputo en los casos pulmonares frotis positivo, con mejoría de los síntomas clínicos. En la fase de continuación se administran a diario la Rifampicina e Isoniacida, excepto los domingos durante 4 meses, donde el efecto esterilizador del tratamiento elimina los bacilos restantes y evita las recaídas. El principal determinante del resultado terapéutico es la adhesión al tratamiento prescrito (1). La intervención quirúrgica se considera en los casos de recidiva de las lesiones tras el tratamiento, resistencia o aumento de las masas anexiales y persistencia del dolor. Se tiende a realizar histerectomía total con doble anexectomía, en mujeres premenopáusicas en las cuales no existe afectación de los ovarios, estos deben ser conservados. Las plastias tubáricas para restablecer la permeabilidad están contraindicadas por el alto porcentaje de fracasos y la posibilidad de embarazos ectópicos (9). La afección tiene muy buen pronóstico en cuanto a curación de lesiones, sin embargo, puede generar distorsión anatómica del aparato reproductor, teniendo repercusión en la fertilidad de pacientes jóvenes. Según estudios 5% de las pacientes logran desarrollar un embarazo, y sólo en un 2% de las pacientes llega a término (7). Conclusión La tuberculosis pulmonar constituye un verdadero problema de salud pública en los países en vías de desarrollo, a pesar de esto la infección del aparato genital femenino por el bacilo de Koch es poco frecuente. Es fundamental ejecutar acciones que permitan llegar al diagnóstico etiológico de manera a encaminar un tratamiento adecuado. Lo más importante para llevar a cabo estas acciones es la sospecha diagnóstica y siendo esta una patología no habitual, de manifestaciones tardías e inespecíficas, esto se ve dificultado. En el caso presentado anteriormente la clínica estaba orientada a un cuadro inflamatorio agudo, su estado de gravedad imponía la intervención quirúrgica de urgencia, no danto tiempo de verificar todos los exámenes para precisar el diagnóstico. Haciendo un análisis retrospectivo este reporte de caso plantea la importancia de pensar en la tuberculosis genital, una vez descartadas otras posibilidades diagnósticas. Dejar de considerar la posibilidad de TB genital puede llevar a intervenciones desnecesarias, ineficaces y no rectificables.
Background
Diabetes mellitus (DM) is one of the leading chronic diseases globally and one of the most common causes of death, morbidity, and poor quality of life. According to the WHO, DM is also one of the main risk factors for developing active tuberculosis (TB). Subjects with DM are at a higher risk of infections, in addition to frequent micro and macrovascular complications, and therefore sought to determine whether poor glycemic control is linked to a higher risk of developing TB.
Methods
We used a retrospective cohort of diabetic subjects to predict the incidence of TB. All DM patients were recruited from Ciutat Vella (the inner-city of Barcelona) from January 2007 until December 2016, with a follow-up period until December 2018 (≥2 years). Data were extracted from Barcelona's Primary Care medical record database - SIDIAP, and linked to the Barcelona TB Control Program. The incidence of TB and the impact of glycemic control were estimated using time-to-event curves analyzed by Cox proportional hazard regression. Hazard ratios (HRs) and 95% confidence intervals (CIs), unadjusted and adjusted by potential confounding variables, were also assessed, which included age, sex, diabetes duration, macrovascular and microvascular signs, BMI, smoking habit, alcohol consumption and geographical origin.
Results
Of 8,004 DM patients considered for the study (equating to 68,605 person-years of follow-up), 84 developed TB [incidence rate = 70 (95% CI: 52–93) per 100,000 person-years]. DM subjects with TB were younger (mean: 52.2 vs. 57.7 years old), had higher values of glycosylated hemoglobin (HbA1c) (7.66 vs. 7.41%) and total triglycerides (122 vs. 105 mg/dl), and had twice the frequency of diabetic nephropathy (2.08 vs. 1.18%). The calculated incidence rate increased with increasing HbA1c: 120.5 (95% CI 77.2–179.3) for HbA1c ≥ 7.5%, 143 (95% CI 88.3–218.1) for HbA1c ≥ 8% and 183.8 (95% CI 105–298) for HbA1c ≥ 9%. An increase in the risk of TB was also observed according to a poorer optimization of glycemic control: adjusted HR 1.80 (95% CI 0.60–5.42), 2.06 (95% CI 0.67–6.32), and 2.82 (95% CI 0.88–9.06), respectively.
Conclusion
Diabetic subjects with worse glycemic control show a trend toward a higher risk of developing TB.
Medication-resistant tuberculosis is a considerable across-the-board public health challenge that menace’s the substantial advance made in tuberculosis heedfulness and precluding in current decades. Multidrug-resistant tuberculosis is caused by organisms that are resistant to the consummate effective anti-tuberculosis medications (isoniazid and rifampicin). Tuberculosis organisms resistant to the antibiotics used in its treatment are extendedly and happen in entire countries studied. Medication resistance noticed as a sequence of insufficient treatment and once tuberculosis organisms obtain resistance they can disseminate from person to person in the similar way as medication-sensitive tuberculosis. Multidrug-resistant tuberculosis sequences from either infection with organisms which are previously medication-resistant or perhaps advance in the program of a patient's treatment. Rifampicin-resistant tuberculosis is caused by bacteria that do not answered to rifampicin, one of the consummate influential anti- tuberculosis medications. These patients necessitated multidrug-resistant tuberculosis treatment. Extendedly medication-resistant tuberculosis is a figure of tuberculosis caused by organisms that are resistant to isoniazid and rifampicin (i.e. multidrug-resistant tuberculosis) as well as every fluoroquinolone and any of the second–line anti- tuberculosis injectable drugs (amikacin, kanamycin or capreomycin). Extendedly medication-resistant tuberculosis can elaborate when second-line medications are used incorrectly or wrongly managed and upon become ineffective.
Background:
China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China.
Methods:
Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach.
Results:
In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5-10 mm, and 6 preschool children received preventive treatment for LTBI.
Conclusions:
Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.
El Mal de Pott es una presentación de la tuberculosis extrapulmonar. Los datos clínicos más comunes que puede presentar son: dolor, limitación funcional, contractura muscular, fiebre nocturna, en etapas avanzadas presenta una giba dorsal, absceso vertebral y alteración neurológica. Con mayor frecuencia afecta las articulaciones intervertebrales torácicas y lumbares. Se describe el caso clínico de paciente de 60 años que manifiesta cuadro clínico de dolor lumbar que irradia a extremidad inferior derecha, imposibilitando la bipedestación y deambulación. Se solicita radiografía de columna lumbar, en donde presenta pinzamiento de L4, L5 y Resonancia Magnética en la que se observó signos sugestivos de Mal de Pott. El diagnóstico es complejo y el pronóstico dependerá del diagnóstico precoz evitando así complicaciones vertebrales irreversibles.
Objectives
To identify new potential host biomarkers in blood to discriminate between active TB patients, uninfected (NoTBI) and latently infected contacts (LTBI).
Methods
A blood cell count was performed to study parent leukocyte populations. Peripheral blood mononuclear cells (PBMCs) were isolated and a multi-parameter flow cytometry assay was conducted to study the distribution of basal and Mycobacterium tuberculosis (Mtb)-stimulated lymphocytes. Differences between groups and the area under the ROC curve (AUC) were investigated to assess the diagnostic accuracy.
Results
Active TB patients presented higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than LTBI and NoTBI contacts (p<0.0001; AUC>0.8). Lymphocyte subsets with differences (p >0.05; AUC >0.7) between active TB and both contact groups include the basal distribution of Th1/Th2 ratio, Th1-Th17, CD4⁺ Central Memory (TCM) or MAIT cells. Expression of CD154 is increased in Mtb-activated CD4⁺ TCM and Effector Memory T cells in active TB and LTBI compared to NoTBI. In CD4⁺ T cells, expression of CD154 showed a higher accuracy than IFNγ to discriminate Mtb-specific activation.
Conclusions
We identified different cell subsets with potential use in tuberculosis diagnosis. Among them, distribution of CD4 TCM cells and their expression of CD154 after Mtb-activation are the most promising candidates.
Tuberculosis in the neonatal stage has a high morbidity and mortality, is difficult to diagnose and involves the mother-child binomial and their environment. The particular characteristics of the immune system in pregnant women and the newborn, impact the clinical presentation of this disease. Its diagnosis is complex and the establishment of treatment must be timely and cannot be postponed. Relevant aspects for the diagnosis and management of the newborn exposes to the tuberculosis are covered.
La tuberculosis es extrapulmonar ocurre entre el 10 a 20 % de los pacientes no inmunodeprimidos, y aunque la afectación es más frecuente es en el pulmón, pero puede afectar cualquier órgano y provocar daño severo al mismo que infecta. la localización vertebral es la más común. El problema es que en nuestro país a pesar contar con medicamento adecuado para tratarla y la gratuidad de su tratamiento, la mayoría de los paciente deja el tratamiento anti fímico por la falta de concientización. La metodología de esta investigación fue recopilación de información de una historia clínica en una clínica privada, seguir su evolución intrahospitalaria y extra hospitalaria, además de control posterior de sus complicaciones. El objetivo principal de este estudio es ayudar a nuestros médicos a incitar la concientización a los pacientes de que no solo es importante el saber tratar la tuberculosis sino terminarlo en su totalidad para evitar resistencias medicamentosas. A continuación se presenta dos casos de una paciente de diferentes edades de la costa ecuatoriana, con tuberculosis extra pulmonar el cual dejaron el tratamiento y presentaron complicaciones. Es importante la concientización al paciente para que finalice el tratamiento anti fímico y la detección temprana de signos y síntomas de complicaciones por dejar la medicación.
Resumen
Diversos estudios han evidenciado una resistencia cruzada entre isoniacida y etionamida, 2 de los fármacos utilizados en el tratamiento de la tuberculosis multirresistente. El objetivo del presente estudio fue determinar la resistencia cruzada entre ambos fármacos en aislados de Mycobacterium tuberculosis obtenidos en un hospital de Lima (Perú), con alta proporción de pacientes con tuberculosis. Se calculó la frecuencia de mutaciones asociadas con la resistencia a la isoniacida (INH) evaluando el gen katG y la región promotora inhA mediante la prueba molecular Genotype MTBDRplus v2.0. El método gold standard conocido como agar proporciones en placa (APP) permitió la identificación de resistencia a INH y etionamida. De 107 aislamientos resistentes a INH, 54 fueron multirresistentes (identificados mediante la prueba Genotype MTBDRplus) y 49 (es decir, el 45,8% del total) también fueron resistentes a etionamida por el método APP. En los aislamientos resistentes a INH, se encontraron mutaciones en el gen katG en el 50,5% (54/107); en la región promotora inhA en el 23,3% (25/107), y un 14,0% (15/107) presentaron mutaciones en ambos. Un 12,1% (13/107) fueron resistentes a INH por ausencia de banda wild type y banda de mutación. La mutación C-15T en la región promotora inhA presentó una fuerte asociación con la resistencia a etionamida y alcanzó el 73,4% (36/49) de los aislamientos resistentes a dicho fármaco. Los resultados del presente estudio sugieren que la identificación de mutaciones relacionadas con resistencia a INH, sobre todo en la región promotora inhA, podría ser de gran utilidad para identificar la resistencia cruzada a etionamida y mejorar el tratamiento de las personas afectadas por tuberculosis.
The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.
Se explica la historia y epidemiología de la tuberculosis
Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.
Resumen
La meningitis crónica es una inflamación de las meninges que determina anomalías en el líquido cefalorraquídeo (LCR) que duran por lo menos un mes. Las etiologías más comunes de la meningitis crónica son infecciosas, autoinmunes y neoplásicas. Esta revisión tiene como objetivo presentar los conocimientos actuales sobre la etiología, el curso de la enfermedad y el manejo diagnóstico y terapéutico de los pacientes. Revisaremos las etiologías más comunes de la meningitis crónica aunque, todavía hoy, a pesar del avance tecnológico, la etiología de un tercio de los pacientes no llega a aclararse, lo que refleja el reto diagnóstico de este síndrome para el médico. Sin embargo, afortunadamente la mayoría de los pacientes con meningitis idiopática crónica tiene un pronóstico relativamente bueno.
The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacilli smear microscopy, tested by the real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTi me MTB PCR) and cultured in mycobacterial media. Seventeen patients tested positive by PCR (5 were acid-fast bacilli smear-positive and 12 acid-fast bacilli smear-negative) and Mycobacterium tuberculosis was recovered from cultures for 12 of them. Patients testing positive by PCR and negative by culture (n = 5) were treated and deemed to have responded to anti-tuberculosis therapy. There were no PCR-negative/culture-positive cases, and no patient testing positive for nontuberculous mycobacteria (n = 20) yielded a positive PCR result. The data indicated that routine testing of respiratory specimens from patients with presumptive tuberculosis by the RealTi me MTB PCR improves the tuberculosis diagnostic yield and may reduce the time to anti-tuberculosis treatment initiation. Based on our data, we propose a novel mycobacterial laboratory algorithm for tuberculosis diagnosis.
Antecedentes:
La tuberculosis es una enfermedad infectocontagiosa causada principalmente por Mycobacterium tuberculosis (M. tuberculosis), que se puede manifestar en pulmonar (TBP) en el 85% de los casos y el resto en forma extrapulmonar (TBEP). Actualmente es un problema de salud pública y el mejor diagnóstico a nivel laboratorio es el cultivo (diagnóstico estándar de referencia).
Material y métodos:
Se realizó un estudio observacional y retrospectivo basado en el aislamiento de M. tuberculosis en muestras extrapulmonares por cultivo, utilizando el equipo BACTEC MGIT-960 y pruebas de identificación y farmacosensibilidad.
Resultados:
Se cultivaron 654 muestras obteniendo una positividad del 5.5% (36 aislamientos), 7 de pacientes menores de 15, y 3 en pacientes mayores de 60 años. De acuerdo al órgano/tejido afectado: 30.6% piel, 27.8% renal, 11.1% cavidad torácica (excepto pulmón), aparato digestivo y articulaciones, respectivamente, y 8.3% del sistema nervioso central. Del total de los aislamientos del complejo M. tuberculosis se incluyó una cepa de M. bovis. En cuanto a los resultados de farmacosensibilidad se obtuvo una sensibilidad del 100% para etambutol y rifampicina, del 94.5% para isoniacida y 44.0% para pirazinamida.
Conclusiones:
Se demostró la importancia del cultivo para el diagnóstico y pruebas de farmacosensibilidad en pacientes con sospecha de TBEP.
The MB/BacT mycobacterium detection system was evaluated for its performance in the susceptibility testing of Mycobacterium tuberculosis. Eighty-three M. tuberculosis isolates were processed. Results for all isoniazid-, rifampin- and streptomycin-susceptible, isoniazid-resistant, and rifampin-resistant M. tuberculosis isolates with the MB/BacT system agreed 100% with those obtained by the agar proportion method. The agreements between the two methods for streptomycin- and ethambutol-resistant isolates were 96.4 and 90.4%, respectively. The susceptibility test results were obtained in 7 days, on average. These data demonstrate that the MB/BacT system is an accurate, nonradiometric method for rapid susceptibility testing of M. tuberculosis.
To evaluate the utility of two gene amplification systems in historical paraffin-embedded pleural biopsy (PEB) tissues from patients with pleural tuberculosis, and to compare the results to those obtained with conventional histologic and microbiological methods.
A retrospective study. Patients and methods: Seventy-four formalin-fixed PEB tissues collected and stored over 12 years (1984 through 1995) were retrieved. Gene amplifications were performed in 57 tissues from patients with diagnoses of pleural tuberculosis and in 17 from patients with carcinoma as controls, using the first version of the Amplified Mycobacterium tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) and the LCx Mycobacterium tuberculosis Assay (LCxMTB; Abbott Laboratories; Abbott Park, IL).
The sensitivities of the AMTDT and LCxMTB were 52.6% and 63.2%, respectively (p = not statistically significant). The specificity of both tests was 100%. Twenty tissue samples (35.1%) were positive by both systems, and 10 tissues (17.5%) were positive only by the AMTDT, while 16 tissues (28.1%) were positive only by the LCxMTB. Both tests gave negative results for 11 specimens (19.3%). When both tests were used, a positive diagnosis was achieved in 80.7% of the samples. Diagnosis of 73.7% of patient conditions had previously been made by smear examination of pleural biopsy and sputum, pleural liquid, or biopsy culture. The overall diagnostic yield with both culture and amplification techniques was 96.5% (55 of 57 patients) for pleural tuberculosis, with amplification techniques adding 22.8% of the diagnoses.
Amplification techniques are useful in archival PEB tissues, providing additional diagnoses beyond culturing, although the sensitivity should be improved, possibly by standardizing protocols.
A new DNA probe assay (INNO LiPA Mycobacteria; Innogenetics, Ghent, Belgium) for the simultaneous identification, by means
of reverse hybridization and line-probe technology, of Mycobacterium tuberculosis complex, Mycobacterium kansasii,Mycobacterium xenopi, Mycobacterium gordonae, the species of the Mycobacterium avium complex (MAC),Mycobacterium scrofulaceum, and Mycobacterium chelonae was evaluated on a panel of 238 strains including, besides representatives of all the taxa identifiable by the system, a
number of other mycobacteria, some of which are known to be problematic with the only other commercial DNA probe system (AccuProbe;
Gen-Probe, San Diego, Calif.), and two nocardiae. The new kit, which includes a control probe reacting with the whole genus
Mycobacterium, correctly identified 99.6% of the strains tested; the one discrepancy, which remained unresolved, concerned an isolate identified
as MAC intermediate by INNO LiPA Mycobacteria and as Mycobacterium intracellulare by AccuProbe. In five cases, because of an imperfect checking of hybridization temperature, a very slight, nonspecific, line
was visible which was no longer evident when the test was repeated. Two strains whose DNA failed amplification at the first
attempt were regularly identified when the test was repeated. Interestingly, the novel kit dodged all the pitfalls presented
by the strains giving anomalous reactions with AccuProbe. A unique feature of INNO LiPA Mycobacteria is its ability to recognize
different subgroups within the species M. kansasii and M. chelonae, while the declared overlapping reactivity of probe 4 with some M. kansasii and Mycobacterium gastri organisms and of probe 9 with MAC, Mycobacterium haemophilum, andMycobacterium malmoense, may furnish a useful aid for their identification. The turnaround time of the method is approximately 6 h, including a preliminary
PCR amplification.
Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru.
We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes.
The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83).
Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes.
Our objective was to evaluate the feasibility of a molecular assay based on a real-time PCR technique, carried out with a LightCycler instrument (Roche Biochemicals), to identify Mycobacterium tuberculosis bacilli and to detect rifampin and isoniazid resistance in DNA extracts from sputum samples. We studied three genes: rpoB, which is associated with rifampin resistance, and katG and inhA, which are associated with isoniazid resistance. A total of 205 sputum samples collected from 108 patients diagnosed with pulmonary tuberculosis with positive auramine-rhodamine-staining (AR) sputum samples, were tested. The sensitivities of the LightCycler PCR assay for the positive AR specimens was 97.5% (200 of 205) for rpoB and inhA genes and 96.5% (198 of 205) for the katG gene. For the total number of patients tested, the sensitivity was 100% (108 of 108 patients) for rifampin, whereas the sensitivity was 98.1% (106 of 108 patients) for isoniazid. Full agreement was found with the Bactec MGIT 960 method and the genotype inferred from the LightCycler data for rifampin. The phenotypic method for isoniazid reported 13 resistant strains (> or = 0.1 microg/ml). In seven (53.8%) strains there was a concordance between both methods, but we found that six (46.2%) strains reported as resistant by the phenotypic method were determined to be susceptible by real-time PCR. For the 75 strains reported as susceptible by the phenotypic method, the concordance with the LightCycler data was 100%. Our results demonstrate that rifampin-resistant M. tuberculosis could be detected in DNA extracted from auramine-rhodamine-positive sputum samples in a single-tube assay that took less than 3 h to perform for a collection of auramine-rhodamine-positive specimens obtained from patients with culture-documented pulmonary tuberculosis. Similarly, this occurs in half of the isoniazid-resistant M. tuberculosis DNA extracted from auramine-rhodamine-positive specimens.
Forty-nine AIDS patients, most of who were antiretroviral therapy (ARV) naive, with active tuberculosis, were treated with Rifampin 600 mg, Isoniazid 400 mg and Pirazinamide 2 g daily. They also received ARV, consisting of Efavirenz (600 mg/day) plus 2 NRTIs. All patients were prospectively followed for at least 24 months. Baselines were: male/female ratio 2:1, mean age 34.7 +/- 9.4 yrs; weight 51 +/- 9.0 kg, viral load 5.6 +/- 0.6 logs, CD4 cell count 101 +/- 128 cells/ mm3. Follow up mean values of data logs of VL and CD4+ cell /mm3 counts were: VL 1.7 and CD4+ 265; VL 1.3 and CD4+ 251; VL 1.4 and CD4+ 326 at 6, 12 and 24 months, respectively. Weight gain changes were: 5 +/- 9.9 +/- 12 and 21 +/- 16 kg respectively at 6, 12 and 24 months. A non-concomitant ARV regimen was introduced at least three weeks after TB treatment initiation. Severe adverse reactions included rash (two), toxic hepatitis (six), Immune Reconstitution Syndrome (seven), and four deaths. We conclude that Efavirenz at a daily dose of 600 mg is sufficient and safe to treat HIV/TB patients using a Rifampin containing regimen.
A major difficulty associated with the use of standard therapy with isoniazid for latent tuberculosis infection is poor patient adherence to therapy because of the prolonged course required. Shorter courses of therapy involving > or =2 drugs have been proposed as an alternative to standard therapy, but they have not undergone enough testing.
We performed a meta-analysis to determine the equivalence of daily short-course therapy with rifampin plus isoniazid for 3 months and standard therapy with isoniazid for 6-12 months. The end points that were evaluated were development of active tuberculosis, severe adverse drug reactions, and death. We searched published information in the Cochrane Library, MEDLINE, and Embase databases, as well as unpublished information in the Cambridge Scientific Abstracts Internet database, Conference Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also scanned the reference lists of articles. We only included trials in which individuals were randomly allocated to receive treatment. Two reviewers independently applied the criteria for trial selection, assessed trial quality, and extracted data.
Five trials comprising 1926 adults from Hong Kong, Spain, and Uganda were identified. The mean duration of follow-up varied from 13 to 37 months. Overall, development of active tuberculosis was equivalent in association with both regimens (pooled risk difference, 0%; 95% confidence interval [CI], -1% to 2%; percentage of total variation across the studies that is the result of heterogeneity rather than chance [I2], 0%; P=.86). Severe adverse effects were reported with a similar frequency for both regimens (pooled risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant heterogeneity detected (I2, 78%; P=.001). However, a subanalysis of high-quality trials (including 74% of the sample size) suggested that both regimens were equally safe. In 3 trials (comprising 1390 patients) that provided data on mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, -4% to 2%; I2, 2.7%; P=.38).
Short-course therapy with rifampin plus isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy, the proportion of severe side effects that occurred, and mortality.
The demand for reliable drug-susceptibility testing (DST) increases with the expansion of antituberculosis drug-resistance surveillance, and with the need for an appropriate treatment of multidrug-resistant tuberculosis, whose incidence gradually increases in many parts of the world. However, the reliability of DST results obtained through widely used methods does not meet acceptable levels, except for DST to isoniazid and rifampicin.
In general, susceptibility results are highly predictable, while resistance results show low predictive values when the resistance prevalence is <10%. Poor reliability stems from a weak correlation with clinical response and a low reproducibility due to the poor standardisation of the complex and fragile test procedures. Therefore, in vitro criteria of resistance for susceptibility testing should be carefully determined with representative clinical samples of Mycobacterium tuberculosis isolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results.
The critical concentration of some drugs is close to the minimal inhibitory concentration for wild susceptible strains and, thus, drug-susceptibility testing is prone to yield poorly reproducible results. These issues call for physicians' attention when using the results from drug-susceptibility testing for case management.
Introduction. The Mycobacteriology Spanish Working Group (MSWG) has conducted an epidemiological, descriptive and retrospective study to try to know the level of first line drug resistances in Mycobacterium tuberculosis strains in Spain. Material and methods. Data were obtained from a total of 1083 strains isolated between October and November 2006 in 120 microbiology laboratories from 16 autonomous communities and Melilla. Results. A primary resistance rate of 8.3% and 4.9% was obtained for isoniazid (INH). The probability of suffering resistant tuberculosis was major in the immigrant population with a resistance rate of 12%. Repeating these surveillance studies in later years is recommended.
At the beginning of the last quarter of the twentieth Century, tuberculosis seemed to be a disease in decay in the developed world. The image was that of a slow but progressive decrease in the prevalence of the disease due to the availability of a very effective therapy and the increasing development of hygienic measures. However, some years later, an increase in the number of cases of tuberculosis was detected in the USA. This fact, together with the appearance of cases of multidrug-resistant tuberculosis, which were very difficult to treat, increased the interest of the scientific community in this half-forgotten disease. In 1993, the WHO declared tuberculosis a global emergency because of the increasing number of cases throughout the world, and more measures were taken in the fight against the disease. The fact that tuberculosis is mainly a respiratory disease that can be transmitted airborne or by droplets makes any person in contact with a patient who suffers from active respiratory tuberculosis susceptible to infection. However, because of the nature of transmission and the immune response of the host against the pathogen, some population groups, such as closed communities (correctional facilities, shelters, jails, hospitals, miners and others) seem to present unique characteristics. This is also the case in patients with underlying conditions that make the risk of active tuberculosis higher, either by immunosuppression or by local factors (silicosis, transplantation, diabetes, malignancies, drug abuse). The following pages describe the special characteristics of tuberculous diseases in these groups, with a Special emphasis on protective measures.
The tuberculin skin test (TST) was formerly the only test for detecting latent tuberculosis infection; however, interferon-γ–release assays (IGRAs) have emerged as attractive alternatives. Two IGRAs, QuantiFERON-TB Gold (Cellestis, Carnegie, Australia) and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom), are now commercially available, and their use is expanding. Although IGRAs are intended for diagnosing latent tuberculosis infection, active tuberculosis is used as a surrogate standard to estimate accuracy in the absence of a gold standard for latent tuberculosis infection.
In a recent meta-analysis (1), Menzies and colleagues showed that IGRAs have high specificity, especially in populations who have received bacille Calmette-Guerin (BCG) vaccination. However, the sensitivity of both TST and IGRAs was suboptimal, and none of these tests could distinguish between latent tuberculosis and active disease. Since the publication of this meta-analysis, the evidence base for IGRAs has rapidly grown with publication of several guidelines and statements (2–6). We present an updated meta-analysis that will provide helpful information for clinicians and for agencies developing updated guidelines.
PURPOSE: To review reported inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) in persons infected with HIV-1 and to explore the mechanisms leading to these reactions.
DATA SOURCES: MEDLINE search of biomedical literature reporting inflammatory reactions after HAART. Bibliographies of retrieved reports were also reviewed.
STUDY SELECTION: Articles describing patients infected with HIV-1 who had immunologic and virologic responses to HAART and subsequently developed inflammatory reactions.
DATA EXTRACTION: Data on the immune status, clinical characteristics, and therapeutic management of patients who were seropositive for HIV-1 and had inflammatory reactions after HAART. DATA SYNTHESIS: Inflammatory reactions involving opportunistic infections, AIDS-associated malignant conditions, and other noninfectious diseases have recently been described in patients infected with HIV-1. These conditions often appeared shortly after the introduction of HAART and were associated with pronounced reductions in plasma HIV-1 viral load and increases in CD4(+) T-lymphocyte counts. Clinical presentation was often atypical of that in patients with untreated HIV-1 infection, probably because of restored immunity. Most cases improved despite continuation of HAART, although some patients required anti-inflammatory drugs or specific antimicrobial agents.
CONCLUSIONS: Clinicians caring for patients who are infected with HIV-1 and receiving HAART must be aware of this new and diverse clinical syndrome. As more HAART recipients are studied, new presentations will probably be observed.
Despite the huge advance that highly active antiretroviral therapy has represented for the prognosis of infection by human immunodeficiency virus (HIV), opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. This is often the case because of severe immunodepression, poor adherence to antiretroviral therapy, failure of therapy, or the fact that patients are unaware of their HIV-positive status and debut with an opportunistic infection.
This article updates the guidelines on treatment of acute episodes of various opportunistic infections in HIV-infected patients, including infections due to parasites, fungi, viruses, mycobacteria, and bacteria. This edition has a new chapter on imported parasite infections as well as additional information on endemic mycoses in the chapter on fungal infections, taking into account the growing number of immigrants in our setting. Lastly, the chapter on the immune reconstitution syndrome has also been updated, providing relevant data on a phenomenon that has clinical and diagnostic repercussions in patients who start antiretroviral therapy while they are severely immunodepressed (English version available at http://www.gesida.seimc.org).
In clinical microbiology, Mycobacterium tuberculosis is a difficult microorganism to manipulate because of the risk of exposure to this mostly air-borne transmitted pathogen which requires level 3 biosafety. At present, most laboratory accidents involving mycobacteria can be reduced by carrying out suitable microbiologic procedures, the use of safety and protection devices, and the design of appropriate installations. Current legislation defines the level of responsibility of healthcare institutions and laboratory personnel and specifically stipulates the level of biosafety required for processing specimens containing mycobacteria. Adherence to primary and secondary safety recommendations, systematic monitoring of laboratory personnel, and the design of proactive plans to prevent accidents help to minimize the risk of infection and provide adequate protection for the community.
Background and Objective
Tuberculosis is an occupationaldisease in health care workers. Theobjective of our study was to review tuberculosiscases in health care professionals from a generalhospital and to determine their incidence in relationto the general population.
Patients and method
This was a retrospective studyof tuberculosis cases among health care workers ina university hospital from 1988 to 2002, evaluatingthe annual cumulative incidence.
Results
21 tuberculosis cases were found in healthcare workers. Pulmonary disease was themost frequent type (62%) followed by pleural effusion(28%). The most affected professional categorywere medical residents (38%) with theemergency service (48%) being the work placewith the highest risk. The cumulative incidencein our hospital was higher in relation to the generalpopulation although there was a variabilitybetween both populations.
Conclusions
There is risk of tuberculosis transmissionamong health care workers, principally in theemergency service and the pathology and microbiologicaldepartments. A concerted effort is neededto maintain prevention measures in the workplace where there is a high risk of infection.
Objective
To determine if isoniazid- and/or rifampicin-free antituberculosis treatment regimens are safe and effective and to identify any factors that might require changes in the regimens.
Patients and methods
We carried out a retrospective study of patients treated with isoniazid- and/or rifampicin-free regimens between 1995 and 2005 at 2 specialized hospitals in Barcelona, Spain. Predictive factors were studied by logistic regression and the odds ratio; 95% confidence intervals were calculated.
Results
Eighty-five patients were included in the study: 35% were immigrants and 34% were infected with human immunodeficiency virus. The reason for omitting isoniazid or rifampicin was toxicity (53%), followed by multidrug resistance (39%). Rifampicin-free regimens were most common (42%). A change in the isoniazid- and/or rifampicin-free regimen was required in 30% of cases, but was not associated with being an immigrant. The rate of toxicity with these regimens was higher (36%), although progress was always satisfactory. Clinical course was satisfactory in 77% of patients and they were discharged.
Conclusions
Isoniazid- and/or rifampicin-free regimens with adequate follow-up showed similar treatment outcomes compared with standardized treatment regimens. Although these regimens were more toxic, patient progress was good.
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy in resource-limited countries. We aimed to assess whether a 4-week course of prednisone would reduce morbidity in patients with paradoxical TB-IRIS without excess adverse events.
A randomized, double-blind, placebo-controlled trial of prednisone (1.5 mg/kg per day for 2 weeks then 0.75 mg/kg per day for 2 weeks). Patients with immediately life-threatening TB-IRIS manifestations were excluded.
The primary combined endpoint was days of hospitalization and outpatient therapeutic procedures, which were counted as one hospital day.
One hundred and ten participants were enrolled (55 to each arm). The primary combined endpoint was more frequent in the placebo than the prednisone arm {median hospital days 3 [interquartile range (IQR) 0-9] and 0 (IQR 0-3), respectively; P = 0.04}. There were significantly greater improvements in symptoms, Karnofsky score, and quality of life (MOS-HIV) in the prednisone vs. the placebo arm at 2 and 4 weeks, but not at later time points. Chest radiographs improved significantly more in the prednisone arm at weeks 2 (P = 0.002) and 4 (P = 0.02). Infections on study medication occurred in more participants in prednisone than in placebo arm (27 vs. 17, respectively; P = 0.05), but there was no difference in severe infections (2 vs. 4, respectively; P = 0.40). Isolates from 10 participants were found to be resistant to rifampicin after enrolment.
Prednisone reduced the need for hospitalization and therapeutic procedures and hastened improvements in symptoms, performance, and quality of life. It is important to investigate for drug-resistant tuberculosis and other causes for deterioration before administering glucocorticoids.
Background:
Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis (TB). It is known that treatment of latent TB infection (LTBI), also referred to as TB preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This present study is an update of the original review.
Objectives:
To determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons.
Search strategy:
This review was updated using the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway and AIDSDRUGS (publication date from 01 July 2002 to 04 April 2008). We also scanned reference lists of articles and contacted authors and other researchers in the field in an attempt to identify additional studies that may be eligible for inclusion in this review.
Selection criteria:
We included randomized controlled trials in which HIV positive individuals were randomly allocated to TB preventive therapy or placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis.
Data collection and analysis:
Three reviewers independently applied the study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and mean differences for continuous data.
Main results:
12 trials were included with a total of 8578 randomized participants. TB preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active TB (RR 0.68, 95% CI 0.54 to 0.85). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.89, 95% CI 0.64 to 1.24). Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short-course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Although there was reduction in mortality with INH monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with INH plus rifampicin versus placebo regardless of tuberculin skin test status (RR 0.69, 95% CI 0.50 to 0.95), overall, there was no evidence that TB preventive therapy versus placebo reduced all-cause mortality (RR 0.94, 95% CI 0.85 to 1.05).
Authors' conclusions:
Treatment of latent tuberculosis infection reduces the risk of active TB in HIV positive individuals especially in those with a positive tuberculin skin test. The choice of regimen will depend on factors such as availability, cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis, the optimal duration of TB preventive therapy, the influence of level of immunocompromise on effectiveness and combination of anti-tuberculosis chemoprophylaxis with antiretroviral therapy are needed.
The increasing emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) in the era of human immunodeficiency virus (HIV) infection presents a major threat to effective control of TB. Drug resistance in Mycobacterium tuberculosis arises from spontaneous chromosomal mutations at low frequency. Clinical drug-resistant TB largely occurs as a result of man-made selection during disease treatment of these genetic alterations through erratic drug supply, suboptimal physician prescription and poor patient adherence. Molecular mechanisms of drug resistance have been elucidated for the major first- and second-line drugs rifampicin, isoniazid, pyrazinamide, ethambutol, the aminoglycosides and the fluoroquinolones. The relationship between drug resistance in M. tuberculosis strains and their virulence/transmissibility needs to be further investigated. Understanding the mechanisms of drug resistance in M. tuberculosis would enable the development of rapid molecular diagnostic tools and furnish possible insights into new drug development for the treatment of TB.
Tuberculosis (TB) is the most common pulmonary complication of the human immunodeficiency virus (HIV)-infection, worldwide. The World Health Organization estimates that there are 5.6 million persons in the world co-infected with Mycobacterium tuberculosis and HIV. 1 Over 90% of these dually-infected individuals reside in developing nations. In sub-Saharan Africa, an area endemic for both infections, TB produces a tremendous burden of disease. In comparison, TB is still a relatively infrequent cause of pulmonary disease among HIV seropositive patients in the USA and other industrialized countries. However, its importance as a pulmonary complication of HIV-infection has increased significantly over the last few years, primarily because of its association with nosocomial outbreaks of multidrug resistant TB 2 and its relatively high frequency in certain high risk populations (i.e., injection drug users)? Nosocomial outbreaks of MDR-TB have highlighted the importance of rapidly identifying and isolating potentially infectious TB patients. Unfortunately, our ability to recognize TB in the setting of HIV infection is limited because of the often 'atypical' clinical and radiographic presentation of TB and the many other possible causes of pneumonia. Early in the HIV epidemic, reports describing the clinical and radiographic presentation of TB concentrated on the findings in patients with advanced HIV infection. These patients were reported to have 'atypical' radiographic presentations, which were consistent with primary TB. 4,5 That is, they were characterized by lower zone infiltrates, thoracic adenopathy, and lack of cavitation. In one of the earliest reports, Pitchenik and Rubinson 4 described a 'typical' radiographic pattern in only one (6%) of 17 acquired immune deficiency syndrome (AIDS) patients. Studies from the US, 6 Zambia, 7 Rwanda, 8 and South Africa 9 have documented that HIV
Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean +/- SD: 15 +/- 11 d versus 109 +/- 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.
Effective control of tuberculosis (TB) requires early identification, isolation, and treatment of persons with active TB.
Knowledge of the molecular genetic basis of resistance to antituberculous agents has advanced rapidly since we reviewed this topic 3 years ago. Virtually all isolates resistant to rifampin and related rifamycins have a mutation that alters the sequence of a 27-amino-acid region of the beta subunit of ribonucleic acid (RNA) polymerase. Resistance to isoniazid (INH) is more complex. Many resistant organisms have mutations in the katG gene encoding catalase-peroxidase that result in altered enzyme structure. These structural changes apparently result in decreased conversion of INH to a biologically active form. Some INH-resistant organisms also have mutations in the inhA locus or a recently characterized gene (kasA) encoding a beta-ketoacyl-acyl carrier protein synthase. Streptomycin resistance is due mainly to mutations in the 16S rRNA gene or the rpsL gene encoding ribosomal protein S12. Resistance to pyrazinamide in the great majority of organisms is caused by mutations in the gene (pncA) encoding pyrazinamidase that result in diminished enzyme activity. Ethambutol resistance in approximately 60% of organisms is due to amino acid replacements at position 306 of an arabinosyltransferase encoded by the embB gene. Amino acid changes in the A subunit of deoxyribonucleic acid gyrase cause fluoroquinolone resistance in most organisms. Kanamycin resistance is due to nucleotide substitutions in the rrs gene encoding 16S rRNA. Multidrug resistant strains arise by sequential accumulation of resistance mutations for individual drugs. Limited evidence exists indicating that some drug resistant strains with mutations that severely alter catalase-peroxidase activity are less virulent in animal models. A diverse array of strategies is available to assist in rapid detection of drug resistance-associated gene mutations. Although remarkable advances have been made, much remains to be learned about the molecular genetic basis of drug resistance in Mycobacterium tuberculosis. It is reasonable to believe that development of new therapeutics based on knowledge obtained from the study of the molecular mechanisms of resistance will occur.
Although isoniazid (INH) is commonly used for treating tuberculosis (TB), it is also effective as preventive therapy.
The objective of this review was to estimate the effect of 6 and 12 month courses of INH for preventing TB in HIV-negative people at increased risk of developing active TB.
We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We hand-searched Science Citation Index and Index Medicus.
Randomised trials of INH preventive therapy for 6 months or more compared with placebo. Follow-up for a minimum of 2 years. Trials enrolling patients with current or previously treated active TB, or with known HIV infection, were excluded. Criteria were applied by two reviewers independently.
Trial quality was assessed by two reviewers independently, and data extracted by one reviewer using a standardized extraction form.
Eleven trials involving 73,375 patients were included. Trials were generally of high quality. Treatment with INH resulted in a relative risk (RR) of developing active TB of 0.40, (95% confidence interval ¿CI¿ 0.31 to 0.52), over two years or longer. There was no significant difference between 6 and 12 month courses (RR of 0.44, 95% CI 0.27 to 0.73 for six months, and 0.38, 95% CI 0.28 to 0.50 for 12 months). Preventive therapy reduced deaths from TB, but this effect was not seen for all cause mortality. INH was associated with hepatotoxicity in 0.36% of people on 6 months treatment and in 0.52% of people treated for 12 months.
Isoniazid is effective for the prevention of active TB in diverse at-risk patients, and six and 12 month regimens have a similar effect.
To review reported inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) in persons infected with HIV-1 and to explore the mechanisms leading to these reactions.
MEDLINE search of biomedical literature reporting inflammatory reactions after HAART. Bibliographies of retrieved reports were also reviewed.
Articles describing patients infected with HIV-1 who had immunologic and virologic responses to HAART and subsequently developed inflammatory reactions.
Data on the immune status, clinical characteristics, and therapeutic management of patients who were seropositive for HIV-1 and had inflammatory reactions after HAART.
Inflammatory reactions involving opportunistic infections, AIDS-associated malignant conditions, and other noninfectious diseases have recently been described in patients infected with HIV-1. These conditions often appeared shortly after the introduction of HAART and were associated with pronounced reductions in plasma HIV-1 viral load and increases in CD4(+) T-lymphocyte counts. Clinical presentation was often atypical of that in patients with untreated HIV-1 infection, probably because of restored immunity. Most cases improved despite continuation of HAART, although some patients required anti-inflammatory drugs or specific antimicrobial agents.
Clinicians caring for patients who are infected with HIV-1 and receiving HAART must be aware of this new and diverse clinical syndrome. As more HAART recipients are studied, new presentations will probably be observed.
This article reviews a previously published meta-analysis of 1264 titles or abstracts and 70 selected studies for evaluation
of the efficacy of bacillus Calmette-Guérin (BCG) vaccine in preventing tuberculosis. Following review, data from 26 studies
were included in the analysis. These 26 studies reveal that vaccination with BCG significantly reduces the risk of tuberculosis
by an average of 50%. This level of protection persists across a number of subgroups defined by age at vaccination and study
design. Vaccination with BCG was significantly associated with a reduction in the incidence of pulmonary tuberculosis and
extrapulmonary disease. In general, the results of this meta-analysis lend weight and confidence to arguments favoring the
use of BCG vaccine.
With the advent of the human immunodeficiency virus (HIV) protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug interactions with antiretroviral agents is becoming increasingly recognized. Every clinician involved in the care of HIV-infected persons should have a broad knowledge of these drug-drug interactions and their underlying mechanisms. This paper will review currently known clinically relevant interactions with antiretroviral agents reported thus far. Alternative strategies will be proposed where possible, in order to improve patient safety and the therapeutic efficacy of the antiretroviral agents. It must be emphasized, however, that in many cases these proposals are not backed up by authoritative clinical consensus panels and that clinical experience with many of these combinations is limited.
We estimated the effect of remote BCG vaccination on tuberculin reactivity and the booster effect among hospital employees.
Cross-sectional survey at a university hospital. All personnel employed during a 24-month period were included in the study. Employees were administered 2-step tuberculin testing, and BCG vaccination scars were verified.
Of 665 hospital employees studied, 239 (36%) had been vaccinated with BCG in childhood. Significant tuberculin reactions (> or =5 mm) were more frequent among BCG-vaccinated (60%) than among nonvaccinated (29%) employees (odds ratio [OR], 3.6; 95% confidence interval [CI], 2.6-5.2). The predictive value of tuberculosis infection increased with increasing reaction size and greater age (from 37% in subjects 30 years or younger with indurations > or =5 mm to 100% in subjects 50 years or older with indurations > or =15 mm). Among 374 employees with a negative tuberculin test reaction who underwent a second test, 39 (43%) of 91 vaccinated subjects had a positive booster reaction in contrast to 51 (22%) of 232 nonvaccinated subjects (OR, 3.4; 95% CI, 2-5.7). Neither different size criteria nor different definitions of the booster effect had an impact on the predictive value of tuberculosis infection.
Remote BCG vaccination largely influences the tuberculin reaction and the boosting phenomenon among hospital employees. The interpretation of the results of 2-step tuberculin testing in a BCG-vaccinated subject must take into account age, size of the reaction, and local prevalence of tuberculosis infection. No single criterion, however, can accurately separate reactions caused by true infection from those caused by BCG vaccination.
The purpose of this study was to evaluate the capability of clinical, gray-scale sonographic, and color Doppler sonographic features for differentiating tuberculous and pyogenic epididymal abscesses.
Retrospective analysis was performed in 10 cases of tuberculous epididymal abscess and in 13 cases of pyogenic epididymal abscess. The following clinical, gray-scale sonographic, and color Doppler sonographic features were analyzed: patient's age; duration of symptoms; scrotal tenderness; presence of sinus tract; concurrent tuberculosis in other organs; location, size, and echogenicity of the abscess; hyperechoic rim; testicular involvement; hydrocele; and blood flow in the epididymal lesion.
Tuberculous epididymal abscess had a longer duration of symptoms (p = 0.0001) and a lower frequency of scrotal tenderness (p = 0.0048) than pyogenic epididymal abscess. The size of the abscess was larger in tuberculous epididymal abscess than in pyogenic epididymal abscess (p = 0.0002). The degree of blood flow in the peripheral portion of the abscess was lower in tuberculous epididymal abscess (p = 0.001). The patient's age, location and echogeninicity of the abscess, presence of sinus tract, hyperechoic rim, testicular involvement, and hydrocele did not differ between the tuberculous and pyogenic epididymal abscesses.
Some clinical findings, gray-scale sonography, and color Doppler sonography were useful in differentiating tuberculous epididymal abscess from pyogenic epididymal abscess. The presence of long-term scrotal swelling without tenderness and a lower degree of blood flow in the peripheral portion of a large abscess are suggestive of tuberculous epididymal abscess.
To determine whether rifampicin reduces serum concentrations of nevirapine and whether nevirapine modifies serum concentrations of rifampicin, levels of these agents were determined at steady state by high-performance liquid chromatography in 10 HIV-infected patients with tuberculosis. The median area under the curve (AUC) 0-12h of nevirapine before and after rifampicin was 56.2 and 32.8 microg/ml per hour, respectively ( p =.04). This represents a 31% reduction in serum nevirapine concentrations. The C(max) decreased from 5.6 to 4.5 microg/ml ( p =.04), which represented a 36% reduction. A 21% decrease in the C(min) was not statistically significant. Exposure to rifampicin did not significantly differ between those patients who were receiving and were not receiving nevirapine. However, our study shows that rifampicin reduces serum exposure to nevirapine. The clinical implications for this reduction remain to be established. Given that the lowest trough serum concentration of nevirapine exceeded by more than 40 times the protein binding adjusted median infective dose (IC(50)) of wild-type HIV in all patients, we suggest that there is no need to increase nevirapine dosage when it is given with rifampicin.
To evaluate the pharmacokinetic interactions between efavirenz and rifampicin (rifampin) in patients with HIV infection and tuberculosis.
Nonblind, randomised, pharmacokinetic study.
24 patients (21 male, 3 female; mean age 37 years) with HIV infection and tuberculosis.
Patients were randomised to one of the following treatments: group A (n = 16) received antituberculosis drugs without rifampicin, plus highly active antiretroviral therapy (HAART) including efavirenz 600 mg once daily, on days 1 to 7. Patients were then switched to rifampicin in bodyweight-adjusted fixed-dose combination plus HAART including efavirenz 600 mg once daily (group A-1; n = 8) or efavirenz 800 mg once daily (group A-2; n = 8). Group B (n = 8) received rifampicin in bodyweight-adjusted fixed-dose combination on days 1 to 7; on day 8, HAART including efavirenz 800 mg once daily was added. Blood samples were obtained on days 7 and 14.
Plasma concentrations of efavirenz and rifampicin were quantified by using validated high performance liquid chromatography assays, and pharmacokinetic parameter values were determined by noncompartmental methods. The differences between pharmacokinetic parameters on days 7 and 14 were used to assess interactions.
There was a correlation between the pharmacokinetic parameters of efavirenz and the dose/kg administered. For efavirenz, mean (median) peak concentration, trough concentration and area under the concentration-time curve over the administration interval decreased 24% (24%), 25% (18%) and 22% (10%), respectively, in the presence of rifampicin. Large interpatient variability was observed, suggesting that plasma concentration monitoring of efavirenz may be advisable. Overall, the pharmacokinetics of efavirenz 800 mg plus rifampicin were similar to those of efavirenz 600 mg without rifampicin. The pharmacokinetics of rifampicin did not change substantially in the presence of efavirenz. Differences in patients' bodyweight appeared to cause further differences in exposure to efavirenz. Plasma concentrations of efavirenz in patients weighing <50 kg were similar to those previously described in HIV-infected patients without concomitant tuberculosis. However, plasma concentrations in patients weighing >or=50 kg were almost halved compared with those in patients weighing <50 kg.
Although the minimal effective efavirenz plasma concentration that assures virological success is not currently known, it may be advisable to increase the dosage of efavirenz to 800 mg once daily when it is coadministered with rifampicin. Rifampicin can be used with efavirenz without dosage modification.
The proportion of extrapulmonary tuberculosis cases in the United States has increased from 16% of tuberculosis cases, in
1991, to 20%, in 2001. To determine associations between the demographic, clinical, and life style characteristics of patients
with tuberculosis and the occurrence of extrapulmonary tuberculosis, a retrospective case-control study was conducted. This
study included 705 patients with tuberculosis, representing 98% of the culture-proven cases of tuberculosis in Arkansas from
1 January 1996 through 31 December 2000. A comparison between 85 patients with extrapulmonary tuberculosis (case patients)
and 620 patients with pulmonary tuberculosis (control patients) showed women (OR, 1.98; 95% CI, 1.25–3.13), non-Hispanic blacks
(OR, 2.38; 95% CI, 1.42–3.97), and HIV-positive persons (OR, 4.93; 95% CI, 1.95–12.46) to have a significantly higher risk
for extrapulmonary tuberculosis than men, non-Hispanic whites, and HIV-negative persons. This study expands the knowledge
base regarding the epidemiology of extrapulmonary tuberculosis and enhances our understanding of the relative contribution
of host-related factors to the pathogenesis of tuberculosis.
Individuals with HIV infection are at an increased risk of developing active tuberculosis. It is known that treatment of latent tuberculosis infection (LTBI), also referred to as preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in human immunodeficiency virus (HIV) negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified.
To determine the effectiveness of tuberculosis preventive therapy in reducing the risk of active tuberculosis and death in persons infected with HIV.
We searched the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS and AIDSDRUGS. We also scanned reference lists of articles and contacted authors and other researchers in the field.
We included studies in which HIV positive individuals were randomly allocated to preventive therapy for TB and placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis.
Two reviewers independently applied study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and weighted mean difference for continuous data.
11 trials were included with a total of 8,130 randomized participants. Preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active tuberculosis (RR 0.64, 95% CI 0.51 to 0.81). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.83, 95% CI 0.58 to 1.18.). Limited data suggest that the initial protective effect against tuberculosis may decline over the short to medium term. Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short -course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Overall, there was no evidence that preventive therapy versus placebo reduced all-cause mortality (RR 0.95, 95% CI 0.85 to 1.06), although a favourable trend was found in people with a positive tuberculin test (RR 0.80, 95% CI 0.63 to 1.02).
Treatment of latent tuberculosis infection (LTBI) reduces the risk of active tuberculosis in HIV positive individuals with a positive tuberculin skin test. The choice of regimen will depend on factors such as cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis and the influence of level of immunocompromise on effectiveness are needed.