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Summary: Objectives: Streptococcus pneumoniae is the leading cause of bacterial pneumonia and associated bacteremia during HIV infection. Rapid diagnostic assays may limit inappropriate therapy. Methods: Clinical signs and symptoms and sera and urine were collected prospectively from 70 adults with pneumococcal pneumonia, including 47 with HIV co-infection. Pneumococcal C-polysaccharide antigen was detected in urine using the Binax® immunochromatographic test (ICT). A systematic review of 24 published studies was conducted. Results: Clinical symptoms, signs, and laboratory parameters except leukocytosis, were similar in HIV-infected and HIV-seronegative pneumonia. The performance of the urine antigen ICT was independent of HIV-status (sensitivity 81%, specificity 98%, positive (PPV) and negative predictive values (NPV) 98%, and 82%, respectively). The sensitivity of sputum Gram''s stain was 58% (34/59) with sputum unable to be provided by 16%. The CRP response was identical in HIV-infected (mean±SD) 133±88 vs. seronegative 135±104mg/L (p =0.9). In the systematic review, the ICT performance revealed 74% sensitivity (95% CI 72–77%) and 94% specificity (95% CI 93–95%). Urine antigen testing increases etiologic diagnosis by 23% (range: 10–59%) when testing adults with community acquired pneumonia of unknown etiology. Conclusions: Urinary antigen detection provides a credible rapid diagnostic test for pneumococcal pneumonia regardless of HIV-status. CRP response to acute infection is similar in HIV co-infection and increases diagnostic certainty. [Copyright &y& Elsevier]

Summary: Background: Sputum smear microscopy is the most widely available diagnostic test for pulmonary tuberculosis in countries with a high burden of the disease. Improving its accuracy is crucial to achievement of case-detection targets established by the Millennium Development Goals. Unfortunately, many patients are unable to submit all of the specimens needed for examination or to return for treatment because standard sputum collection and reporting requires several clinic visits. To inform policy recommendations by a WHO-convened Expert Group, we aimed to assess the accuracy of sputum smear examination with strategies for obtaining sputum on 1 day compared with strategies for obtaining sputum over 2 days. Methods: We did a systematic review and meta-analysis of research articles comparing the accuracy of front-loaded or same-day microscopy and standard sputum smear microscopy for diagnosis of culture-confirmed pulmonary tuberculosis. We searched Medline, Embase, Biosis, and Web of Science for articles published between Jan 1, 2005, and Feb 14, 2012. Two investigators identified eligible articles and extracted data for individual study sites. We generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when four or more studies were available. Findings: We identified eight relevant studies from five articles enrolling 7771 patients with suspected tuberculosis in low-income countries. Compared with the standard approach of examination of two smears with Ziehl-Neelsen light microscopy over 2 days, examination of two smears taken on the same day had much the same sensitivity (64% [95% CI 60 to 69] for standard microscopy vs 63% [58 to 68] for same-day microscopy) and specificity (98% [97 to 99] vs 98% [97 to 99]). We noted similar results for studies employing light-emitting diode fluorescence microscopy and for studies examining three smears, whether they were compared with two-smear strategies or with one another. Interpretation: Same-day sputum smear microscopy is as accurate as standard smear microscopy. Data from tuberculosis programmes are needed to document the changes required in the health system to successfully implement the strategy and understand its effects. Funding: WHO and US National Institutes of Health. [Copyright &y& Elsevier]

Summary: WHO has previously recommended sputum-smear examination at the end of the second month of treatment in patients with recently diagnosed pulmonary tuberculosis, and, if positive, extension of the intensive therapy phase. We did a systematic review and meta-analysis to assess the accuracy of a positive sputum smear or culture during treatment for predicting failure or relapse in pulmonary tuberculosis. We searched PubMed, Embase, and the Cochrane Library for studies published in English through December, 2009. We included randomised controlled trials, cohort, and case-control studies of previously untreated pulmonary tuberculosis patients who had received a standardised regimen with rifampicin in the initial phase. Accuracy results were summarised in forest plots and pooled by use of a hierarchical regression approach. 15 papers (28 studies) met the inclusion criteria. The pooled sensitivities for both 2-month smear (24% [95% CI 12–42%], six studies) and culture (40% [95% CI 25–56%], four studies) to predict relapse were low. Corresponding specificities (85% [95% CI 72–90%] and 85% [95% CI 77–91%]) were higher, but modest. For failure, 2-month smear (seven studies) had low sensitivity (57% [95% CI 41–73%]) and higher, although modest, specificity (81% [95% CI 72–87%]). Both sputum-smear microscopy and mycobacterial culture during tuberculosis treatment have low sensitivity and modest specificity for predicting failure and relapse. Although we pooled a diverse group of patients, the individual studies had similar performance characteristics. Better predictive markers are needed. [Copyright &y& Elsevier]

Abstract: IL-24 is a newly described member of the IL-10 family. We previously demonstrated that PBMC from TB patients exhibited low levels of IL-24 and IFN-γ compared to subjects with latent tuberculosis infection (LTBI). In order to investigate the role of IL-24 in IFN-γ expression in TB patients, we stimulated PBMC from individuals with LTBI or TB patients with the Mtb-specific antigen, early secretory antigenic target-6 (ESAT-6) and measured cytokine expression using quantitative real-time PCR (qPCR). Exogenous IL-24 increased IFN-γ expression in PBMC obtained from TB patients while neutralization of IL-24 reduced IFN-γ expression in PBMC from subjects with LTBI. Exogenous IL-24 enhanced IFN-γ expression by increasing expression of IL-12 family cytokines, including IL-12α, IL-12β, IL-23α and IL-27, and by reducing FOXP3 expression in PBMC from TB patients. This is the first demonstration that IL-24 may play an important role in IFN-γ expression following infection with Mtb. [Copyright &y& Elsevier]

Summary: In low-income and middle-income countries, direct (unconcentrated) sputum smear microscopy is the primary method for diagnosing pulmonary tuberculosis. The method is fast, inexpensive, and specific for Mycobacterium tuberculosis in high incidence areas. The main limitations of direct microscopy are its relatively low sensitivity, especially in individuals co-infected with HIV, and variable quality of the test in programme conditions. Thus, there is a need to identify methods to improve the sensitivity of microscopy. Physical and chemical sputum processing methods, including centrifugation, sedimentation, and bleach, have been studied and found to show promise. We did a systematic review to assess the ability of different processing methods to improve the sensitivity of microscopy. By searching many sources, we identified 83 studies. Overall, by comparison with direct smears, the results suggested that centrifugation with any of several chemical methods (including bleach) is more sensitive, that overnight sedimentation preceded by chemical processing is more sensitive, and that specificity is similar. There were insufficient data to determine the value of sputum processing methods in patients with HIV infection. Operational studies are needed to determine whether the increased sensitivity provided by processing methods is sufficient to offset their increased cost, complexity, and potential biohazards, and to examine their feasibility. [Copyright &y& Elsevier]

Summary: Most of the world''s tuberculosis cases occur in low-income and middle-income countries, where sputum microscopy with a conventional light microscope is the primary method for diagnosing pulmonary tuberculosis. A major shortcoming of conventional microscopy is its relatively low sensitivity compared with culture, especially in patients co-infected with HIV. In high-income countries, fluorescence microscopy rather than conventional microscopy is the standard diagnostic method. Fluorescence microscopy is credited with increased sensitivity and lower work effort, but there is concern that specificity may be lower. We did a systematic review to summarise the accuracy of fluorescence microscopy compared with conventional microscopy. By searching many databases and contacting experts, we identified 45 relevant studies. Sensitivity, specificity, and incremental yield were the outcomes of interest. The results suggest that, overall, fluorescence microscopy is more sensitive than conventional microscopy, and has similar specificity. There is insufficient evidence to determine the value of fluorescence microscopy in HIV-infected individuals. The results of this review provide a point of reference, quantifying the potential benefit of fluorescence microscopy, with which the increased cost and technical complexity of the method can be compared to determine the possible value of the method under programme conditions. [Copyright &y& Elsevier]