Inflammatory bowel disease and mycobacteria: how much can we trust isoniazid prophylaxis during antitumor necrosis factor therapy?

OBJECTIVES: Isoniazid (INH) prophylaxis is recommended for the prevention of tuberculosis (TB) reactivation before or/and during initiation of treatment with tumour necrosis factor antagonists (anti-TNF agents). Nonetheless, the long-term effectiveness of chemoprophylaxis is not clear. In this study, we aimed to evaluate the characteristics of patients who developed TB reactivation in spite of INH prophylaxis associated with anti-TNF treatment. PATIENTS AND METHODS: In this retrospective study, medical records of 1263 patients with inflammatory bowel disease were reviewed. Baseline TB screening tests (purified protein derivative test and/or QuantiFERON-TB Gold test) were performed on all patients before initiation of anti-TNF therapy. Patients with purified protein derivative of more than 5 mm and/or a positive result of the QuantiFERON-TB Gold test received INH prophylaxis for 9 months. We analysed the data of patients diagnosed with TB reactivation during the anti-TNF treatment despite INH chemoprophylaxis. RESULTS: Overall, 175 patients underwent anti-TNF treatment. Sixty of these 175 patients had pretreatment testing showing latent TB infection and therefore were treated concomitantly with INH for 9 months in addition to their anti-TNF treatment. TB reactivation occurred in four of these 60 co-INH/anti-TNF treated patients. Active TB was diagnosed after 37.5±27 (range: 18-84) months of anti-TNF treatment. In two of the four patients that active TB was diagnosed, was also detected other Mycobacterium spp.: M. bovis in one patient and M. genavense in the other one. CONCLUSION: INH chemoprophylaxis may not prevent the reactivation of TB during anti-TNF therapy in the long-term. Patients should be carefully and periodically screened for TB reactivation during anti-TNF therapy.

Interleukin-27 improves the ability of adenosine deaminase to rule out tuberculous pleural effusion regardless of pleural tuberculosis prevalence.

BACKGROUND: Interleukin-27 (IL-27) has been proposed to be useful for diagnosing tuberculous pleural effusion (TPE). Adenosine deaminase (ADA) has been long used for the same purpose. The aim of this study was to compare the performance of IL-27, ADA, and their product (IL-27 • ADA) in the diagnosis of TPE. METHODS: Pleural fluid samples from patients with exudative pleural effusions were assessed for IL-27 and ADA levels. Receiver operating characteristic (ROC) curves were constructed to compare the overall diagnostic accuracy of IL-27, ADA, and IL-27 • ADA. Curves of false-positive (FPR) and false-negative (FNR) rates as a function of TPE prevalence were also constructed, and mean rates of false results in low (1-10%), intermediate (11-40%), and high (41-70%) prevalences were estimated to evaluate the ability of the three markers in ruling in or ruling out TPE. RESULTS: We studied 121 exudates. IL-27 and ADA were higher in TPEs compared with non-TPEs and they presented similar accuracies for the diagnosis of TPE. The product of IL-27 and ADA (IL-27 • ADA) was more accurate than ADA for the same purpose. IL-27 and IL-27 • ADA presented the lowest overall FPR and FNR, respectively. The FPR of IL-27, ADA and IL-27 • ADA was > 9%, even in high prevalence settings. Although their FNR was < 2% in low prevalence settings, only IL-27 • ADA exhibited sufficiently low FNR (< 1%) in intermediate and high prevalences. CONCLUSIONS: ADA, IL-27, and IL-27 • ADA cannot reliably 'rule in' TPE in any prevalence setting. TPE can be 'ruled out' by each of the biomarkers in low prevalence settings. In intermediate and high prevalence settings, IL-27 • ADA is a reliable 'rule out' test in the diagnostic approach to TPEs.

Tuberculosis extrapulmonar, una revisión / Extrapulmonary tuberculosis

Hasta en un 25% de los casos de tuberculosis existe afectación extrapulmonar. Esta afectación es producida por la diseminación hematógena y linfática del bacilo de M. tuberculosis hacia otros órganos. Las localizaciones más frecuentes son la ganglionar, pleural y osteo-articular. El problema de estas formas de tuberculosis radica en la dificultad para llegar a su diagnóstico definitivo, ya que tanto los síntomas clínicos, como las pruebas de imagen pueden ser inespecíficos. La mayoría de las veces es necesario recurrir a pruebas diagnósticas invasivas como PAAF guiada con ecografía o TAC, para la recolección de muestras biológicas para su diagnóstico. A pesar del auge y el avance, en los últimos años, de los métodos moleculares para la detección precoz de ADN de la micobacteria, el cultivo sigue siendo el gold estándar que permite el diagnóstico microbiológico definitivo. El tratamiento de estas formas de tuberculosis, no va diferir de las pautas de tratamiento de las formas pulmonares. Se recomienda utilizar los mismos regímenes de antibióticos con una duración de 6 meses y únicamente prolongar la duración en las tuberculosis con afectación del sistema nervioso y en la espondilitis tuberculosa con afectación neurológica (AU)

Up to 25% of tuberculosis cases present extrapulmonary involvement. This is produced by haematogenous and lymphatic spread of the M. tuberculosis bacillus to other organs. The most common locations are the lymph nodes, pleura and the osteoarticular system. The problem with these types of tuberculosis is the difficulty in establishing a definitive diagnosis, since the clinical symptoms and results of imaging tests may be vague. It is often necessary to resort to invasive diagnostic testing such as ultrasound or CAT-guided FNAB, used to collect biological samples for diagnosis. Despite the growing use of and advances in recent years of molecular methods for early detection of mycobacteria DNA, cultures continue to be the gold standard that enable a firm microbiological diagnosis to be made. Treatment for these types of tuberculosis do not differ from treatment regimens for pulmonary forms of the same disease. The same antibiotic regimens for 6 months are recommended, and any extension of this period is advisable solely in tuberculosis affecting the central nervous system and in Pott’s disease (AU)

Tuberculosis transmission and use of methamphetamines in Snohomish County, WA, 1991-2006.

OBJECTIVES: We investigated a cluster of tuberculosis (TB) cases among persons using methamphetamines in Snohomish County, Washington, to determine the extent of the outbreak, examine whether methamphetamine use contributed to TB transmission, and implement strategies to prevent further infections. METHODS: We screened contacts to find and treat persons with TB disease or infection. We then formed a multidisciplinary team to engage substance abuse services partners and implement outreach strategies including novel methods for finding contacts and a system of incentives and enablers to promote finding, screening, and treating patients with TB and their infected contacts. RESULTS: We diagnosed and completed treatment with 10 persons with TB disease. Eight of 9 adult patients and 67% of their adult contacts reported using methamphetamines. Of the 372 contacts, 319 (85.8%) were screened, 80 (25.1%) were infected, 71 (88.8%) started treatment for latent infection, and 57 (80.3%) completed treatment for latent infection. CONCLUSIONS: Collaborative approaches integrating TB control, outreach, incentives, and enablers resulted in high rates of treatment adherence and completion among patients and infected contacts. TB control programs should collaborate with substance abuse programs to address addiction, overcome substance abuse-related barriers to treatment, treat TB, and prevent ongoing transmission.