Mycobacterium W immunotherapy for treating pulmonary tuberculosis : a systematic review

Includes bibliographical references.Tuberculosis (TB) remains a major health problem in the developing world, accounting for approximately 2 million deaths per year. The search for appropriate and applicable therapies to reduce the burden of TB is essential. Mycobacterium w (M w) is a heat-killed immune-modulating vaccine designed to attenuate the effects of TB infection and reduce the time to sputum negativity, thereby improving cure rates and decreasing transmission rates

The diagnostic accuracy of pericardial and urinary lipoarabinomannan (LAM) assays in patients with suspected tuberculous pericarditis.

We evaluated the diagnostic accuracy of urinary and pericardial fluid (PF) lipoarabinomannan (LAM) assays in tuberculous pericarditis (TBP). From October 2009 through September 2012, 151 patients with TBP were enrolled. Mycobacterium tuberculosis culture and/or pericardial histology were the reference standard for definite TBP. 49% (74/151), 33.1% (50/151) and 17.9% (27/151) of patients had definite-, probable-, and non-TB respectively; 69.5% (105/151) were HIV positive. LAM ELISA had the following sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive values (95% confidence interval): urinary - 17.4% (9.1-30.7), 93.8% (71.7-98.9), 2.8 (0.1-63.3), 0.9 (0.8-0.9), 88.9% (56.5-98.0), and 28.3% (17.9-41.6); PF - 11.6% (6.0-21.3), 88% (70.0-95.8), 0.9 (0.08-12.0), 1.0 (0.9-1.1), 72.7% (43.4-90.1), and 26.6% (18.2-36.9). Sensitivity increased with a CD4 ≤ 100 cells/mm(3) from 3.5% to 50% (p < 0.001) for urinary LAM ELISA; for urinary LAM strip test, grade 1 and 2 cut-points performed similarly, irrespective of HIV status or CD4 count. For PF LAM strip tests, switching cut-points from grade 1 to 2 significantly reduced test sensitivity (54.5% versus 19.7%; p < 0.001). Urinary and PF LAM assays have low sensitivity but high specificity for diagnosis of TBP. The sensitivity of urinary LAM is increased in HIV-infected patients with a CD4 ≤ 100 cells/mm(3)

Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality

AbstractBackgroundTuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis.MethodsPatients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients.FindingsSeventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20–71) years. The median, follow up was for 11.97 (range: 0·03–74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4–58) days or 3.91(range: 0·5–8·96) log10CFU/mL, which overlapped with the range of 3.24–7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5·23months on directly observed therapy, a CD4+ count of ≤199.5/mL, and TTP≤14days (bacillary load≥5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion.InterpretationPatients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drives mortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study

Background: Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP. Methods: From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points. Results: Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001). Conclusions: uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test

Interventions for treating tuberculous pericarditis

CITATION: Wiysonge, C. S., et al. 2017. Interventions for treating tuberculous pericarditis. Cochrane Database of Systematic Reviews, 9:1-65, Art. CD000526, doi:10.1002/14651858.CD000526.pub2.The original publication is available at https://www.cochranelibrary.comBackground: Tuberculous pericarditis – tuberculosis infection of the pericardial membrane (pericardium) covering the heart – is becoming more common. The infection can result in fluid around the heart or fibrosis of the pericardium, which can be fatal. Objectives: In people with tuberculous pericarditis, to evaluate the effects on death, life‐threatening conditions, and persistent disability of: 1. 6‐month antituberculous drug regimens compared with regimens of 9 months or more; 2. corticosteroids; 3. pericardial drainage; and 4. pericardiectomy. Search methods: We searched the Cochrane Infectious Diseases Group trials register (January 2005); the Cochrane Controlled Trials Register (Issue 4, 2004); MEDLINE (1966 to January 2005); EMBASE (1980 to January 2005); and checked the reference lists of existing reviews. We also contacted organizations and individuals working in the field. Selection criteria: Randomized and quasi‐randomized controlled trials of treatments for tuberculous pericarditis. Data collection and analysis: Two reviewers independently assessed trial quality and extracted data. Meta‐analysis using fixed effects models calculated summary statistics, provided there was no statistically significant heterogeneity, and expressed results as risk ratio. Study authors were contacted for additional information. Main results: Four trials met the inclusion criteria, with a total of 469 participants. Treatments tested were adjuvant steroids and surgical drainage. Two trials with a total of 383 participants tested adjuvant steroids in participants with suspected tuberculous pericarditis in the pre‐HIV era. Fewer participants died in the intervention group, but numbers were small (risk ratio [RR] 0.65; 95% confidence interval [CI] 0.36 to 1.16, n = 350). One small trial tested steroids in HIV positive participants with effusion showed a similar pattern (RR 0.50; 95% CI 0.19 to 1.28, n = 58). One trial examined open surgical drainage compared with conservative management, and showed surgery relieved cardiac tamponade. Authors' conclusions: Steroids could have important clinical benefits, but the trials published to date are too small to demonstrate an effect. This requires large placebo controlled trials. Subgroup analysis could explore whether effusion or fibrosis modify the effects. Therapeutic pericardiocentesis under local anaesthesia and pericardiectomy also require further evaluation.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000526/fullPublisher's versio