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      Pneumocystis jirovecii ( Pj) quantitative PCR to differentiate Pj pneumonia from Pj colonization in immunocompromised patients

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          Abstract

          Conventional polymerase chain reaction (PCR) in respiratory samples does not differentiate between Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii ( Pj) colonization. We used Pj real-time quantitative PCR (qPCR) with the objective to discriminate PCP from Pj colonization in immunocompromised patients. All positive Pj qPCR [targeting the major surface glycoprotein (MSG) gene] obtained in respiratory samples from immunocompromised patients presenting pneumonia at the Grenoble University Hospital, France, were collected between August 2009 and April 2011. Diagnoses were retrospectively determined by a multidisciplinary group of experts blinded to the Pj qPCR results. Thirty-one bronchoalveolar lavages and four broncho aspirations positive for the Pj qPCR were obtained from 35 immunocompromised patients. Diagnoses of definite, probable, and possible PCP, and pneumonia from another etiology were retrospectively made for 7, 4, 5, and 19 patients, respectively. Copy numbers were significantly higher in the “definite group” (median 465,000 copies/ml) than in the “probable group” (median 38,600 copies/ml), the “possible group” (median 1,032 copies/ml), and the “other diagnosis group” (median 390 copies/ml). With the value of 3,160 copies/ml, the sensitivity and specificity of qPCR for the diagnosis of PCP were 100 % and 70 %, respectively. With the value of 31,600 copies/ml, the sensitivity and specificity were 80 % and 100 %, respectively. The positive predictive value was 100 % for results with more than 31,600 copies/ml and the negative predictive value was 100 % for results with fewer than 3,160 copies/ml. qPCR targeting the MSG gene can be helpful to discriminate PCP from Pj colonization in immunocompromised patients, using two cut-off values, with a gray zone between them.

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          Most cited references23

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          Pneumocystis pneumonia.

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            Colonization by Pneumocystis jirovecii and its role in disease.

            Although the incidence of Pneumocystis pneumonia (PCP) has decreased since the introduction of combination antiretroviral therapy, it remains an important cause of disease in both HIV-infected and non-HIV-infected immunosuppressed populations. The epidemiology of PCP has shifted over the course of the HIV epidemic both from changes in HIV and PCP treatment and prevention and from changes in critical care medicine. Although less common in non-HIV-infected immunosuppressed patients, PCP is now more frequently seen due to the increasing numbers of organ transplants and development of novel immunotherapies. New diagnostic and treatment modalities are under investigation. The immune response is critical in preventing this disease but also results in lung damage, and future work may offer potential areas for vaccine development or immunomodulatory therapy. Colonization with Pneumocystis is an area of increasing clinical and research interest and may be important in development of lung diseases such as chronic obstructive pulmonary disease. In this review, we discuss current clinical and research topics in the study of Pneumocystis and highlight areas for future research.
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              Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis.

              Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.
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                Author and article information

                Contributors
                +33-4-76765291 , +33-4-76765569 , mmaillet@chu-grenoble.fr
                +33-4-76765291 , +33-4-76765569 , ppavese@chu-grenoble.fr
                Journal
                Eur J Clin Microbiol Infect Dis
                Eur. J. Clin. Microbiol. Infect. Dis
                European Journal of Clinical Microbiology & Infectious Diseases
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0934-9723
                1435-4373
                30 August 2013
                2014
                : 33
                : 3
                : 331-336
                Affiliations
                [1 ]GRID grid.410529.b, ISNI 0000 0001 0792 4829, Infectious Diseases Department, , CHU de Grenoble, ; BP 218, 38 043 Grenoble cedex 9, France
                [2 ]GRID grid.410529.b, ISNI 0000 0001 0792 4829, Infectious Agents Department, Parasitology-Mycology Laboratory, , CHU Grenoble, ; Grenoble, France
                [3 ]GRID grid.410529.b, ISNI 0000 0001 0792 4829, Public Health Department, , CHU Grenoble, ; Grenoble, France
                [4 ]GRID grid.410529.b, ISNI 0000 0001 0792 4829, Hematology Department, , CHU Grenoble, ; Grenoble, France
                [5 ]GRID grid.410529.b, ISNI 0000 0001 0792 4829, Internal Medicine Department, , CHU Grenoble, ; Grenoble, France
                Article
                1960
                10.1007/s10096-013-1960-3
                7101903
                23990137
                0512d28c-98bb-45c2-94d0-2098d7274f88
                © Springer-Verlag Berlin Heidelberg 2013

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 3 July 2013
                : 12 August 2013
                Categories
                Article
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2014

                Infectious disease & Microbiology
                immunocompromised patient,gray zone,respiratory sample,allergic bronchopulmonary aspergillosis,pneumocystis jirovecii

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