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Abstract
BackgroundPneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-β-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients.MethodsThis was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4+ cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria.ResultsAll patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum.ConclusionIn this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.
Highlights
Pneumocystis jirovecii pneumonia (PCP) is one of the most common Human immunodeficiency virus (HIV)-related opportunistic infections
Twenty-one HIV-infected patients matched for blood CD4+ cell counts who were admitted to the Department of Infectious Diseases at Sahlgrenska University Hospital during the same time period and who had not received a clinical diagnosis of PCP were identified through the Swedish National Registry for HIV-care and randomly selected as negative control subjects provided that they had a serum sample collected at the time of HIV diagnosis stored at − 80 °C
We found that the median Cycle threshold (Ct) values were higher, i.e. the concentrations of Pneumocystis jirovecii (Pj) DNA in the serum samples were lower in the Pj PCRpositive control patients than in the patients with PCP
Summary
Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. Pneumonia caused by the fungus Pneumocystis jirovecii (Pj) is one of the most common HIV-related opportunistic infections [1]. The diagnosis of Pneumocystis pneumonia (PCP) formerly relied solely on immunofluorescent staining and microscopic examination of the microorganism in samples from the lower respiratory tract, but polymerase chain reaction (PCR) methodology has been found to be more sensitive for the detection of Pj in respiratory specimens [2]. The invasive procedure of a diagnostic bronchoscopy may be the only alternative to obtain respiratory specimens from HIV-infected patients for PCP diagnosis
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