Evaluation of PCR in Bronchoalveolar Lavage Fluid for Diagnosis of Pneumocystis jirovecii Pneumonia: A Bivariate Meta-Analysis and Systematic Review

Abstract

BackgroundAs a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP.ObjectiveWe undertook a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays in BALF for PJP.MethodsEligible studies from PubMed, Embase and Web of Science reporting PCR assays in BALF for diagnosing PJP were identified. A bivariate meta-analysis of the method’s sensitivity, specificity, and positive and negative likelihood ratios with a 95% confidence interval (CI) were analyzed. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operating characteristics (SROC) curve was used to evaluate overall performance. Subgroup analyses were carried out to analysis the potential heterogeneity.ResultsSixteen studies published between 1994 and 2012 were included. The summary sensitivity and specificity values (95% CI) of PCR in BALF for diagnosis of PJP were 98.3% (91.3%–99.7%) and 91.0% (82.7%–95.5%), respectively. The positive and negative likelihood ratios were 10.894 (5.569–21.309) and 0.018 (0.003–0.099), respectively. In a setting of 20% prevalence of PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was positive, and the probability of PJP would be less than 0.5% if it was negative. The area under the SROC curve was 0.98 (0.97–0.99).ConclusionsThe method of PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP. However, clinical practice for the diagnosis of PJP should consider the consistent respiratory symptoms, radiographic changes and laboratory findings of the suspected patients.

Performances of Four Real-Time PCR Assays for Diagnosis of Pneumocystis jirovecii Pneumonia

“…Although microscopic detection of trophic forms or cysts in pulmonary samples continues to be the gold standard, the use of highly sensitive techniques, such as realtime PCR, has largely improved PCP diagnosis. Indeed, real-time PCR is currently considered an essential method for PCP diagnosis (14,15).…”

Investigation of Pneumocystis jirovecii Pneumonia and Colonization in Iatrogenically Immunosuppressed and Immunocompetent Patients

“…Bu nedenle PCP kliniği bulunan bu tür hastaların tanısında genellikle PCR tabanlı moleküler yöntemler tercih edilmektedir 8 . Bizim çalışmamızda da, P.jirovecii varlığının saptanması için mtLSUrR-NA genine yönelik nPCR yöntemi kullanılmıştır.…”

“…Diğer taraftan, boyama yöntemleriyle negatif saptanan hastalardan sekizi "olası PCP" olgusu olarak kabul edilmiştir. Bu hastaların dosyaları incelendiğinde; böbrek tx sonrası pnömoni gelişen iki hasta ile RA ve BDH tanılı hastaların ampirik anti-PCP tedavisine yanıt verdikleri, tedavi İmmün sistemi baskılanmış hastalarda gözlenen P.jirovecii varlığının, immün sistemi sağlam kişilere oranla daha fazla olduğu bilinmektedir 1,2,8 . Kortikosteroid kullanımı en önemli risk faktörleri arasında gösterilmekle birlikte, yeni nesil immünomodülatör ilaçların kullanıma girmesiyle, özellikle hematolojik malignitelerde, organ transplant alıcılarında, infl amatuvar bağ dokusu hastalıklarında yüksek P.jirovecii pozitifl ikleri bildirilmiştir [3][4][5]9,11 .…”

“…Bununla birlikte AIDS dışı immünosüp-resif hastalarda gözlenen PCP'de parazit yükünün çoğu zaman düşük olması, mikroskopik tanının duyarlılığını azaltmaktadır 4,7 . Günümüzde bu sorun PCR temelli yöntemlerin kullanıma girmesiyle önemli ölçüde aşılmış durumdadır 2,8 . Ancak klinik örneklerde P.jirovecii'nin veya DNA'sının saptanması mutlaka enfeksiyon anlamına gelmemektedir.…”

Diagnosis of Pneumocystis jirovecii Pneumonia in Immunocompromised Patients by Real-Time PCR: a 4-Year Prospective Study

“…However, microscopic diagnosis is difficult and requires specific skills, particularly when fungal burdens are low, and thus may be falsely negative. Various PCR targets and methods have been developed (10)(11)(12), and quantitative real-time PCR (qPCR) has progressively supplanted conventional PCR. Quantitative PCR is usually used to exclude PCP diagnosis because its negative predictive value (NPV) is nearly 100% (13).…”