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Strengths and limitations of molecular diagnostics for Pneumocystis jirovecii pneumonia
Lottie Brown1, Alexandre Alanio2, Mario Cruciani3
1Institute of Infection and Immunity, St George's Hospital and St George's University, London, UK.
Introduction:
While Pneumocystis pneumonia (PcP) remains a major AIDS-defining disease, the majority of cases of PcP now present in the HIV-negative cohort, causing significant mortality. PcP PCR diagnosis is not novel, and the optimal route of diagnosis remains unclear, with an imperfect reference method and complexity in result interpretation for alternative tests.
Areas Covered:
This extensive review utilizing a literature search underpinning a recent systematic review/meta-analysis discusses the technical and clinical performance of PcP PCR, the added benefits of PCR testing, future aspects/considerations, and how PCR may be best used in clinical algorithms to provide a probability of PcP.
Expert Opinion:
Given the current imperfect reference test for PcP, an alternative would be beneficial. Concerns over PcP PCR generating false positive results are valid but can be resolved by using positivity thresholds that drive specificity. Unfortunately, the extensive range of PCR assays complicates the provision of a PCR reference method. Combination testing incorporating PCR and B-D-Glucan, along with clinical and host risk factors, is key to understanding the individual probability of PcP. It is critical that access to PcP PCR testing is improved through technical and logistical development. Conversely, syndromic approaches including PcP need to be fully evaluated.
Insights
Pneumocystis pneumonia (PcP) diagnosis in HIV-negative individuals is challenging. This review explores PCR testing for PcP, emphasizing combination testing and improved access for better clinical probability assessment.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Diagnostic Microbiology
Background:
- Pneumocystis pneumonia (PcP) is a significant cause of mortality, predominantly in HIV-negative individuals.
- Current diagnostic methods for PcP have limitations, including an imperfect reference standard and complex interpretation of alternative tests.
Purpose of the Study:
- To review the technical and clinical performance of Pneumocystis pneumonia Polymerase Chain Reaction (PcP PCR) testing.
- To discuss the potential benefits and future considerations for PcP PCR in clinical algorithms.
- To explore strategies for improving the diagnostic probability of PcP.
Main Methods:
- Literature search and synthesis of data from a recent systematic review and meta-analysis.
- Analysis of technical and clinical performance data for PcP PCR assays.
- Evaluation of combination testing strategies including PCR, B-D-Glucan, and clinical factors.
Main Results:
- Concerns regarding false positive PcP PCR results can be mitigated by using appropriate positivity thresholds.
- A wide variety of PCR assays complicates the establishment of a universal PCR reference method.
- Combination testing integrating PcP PCR, B-D-Glucan, and clinical/host risk factors is crucial for determining PcP probability.
Conclusions:
- Improved access to PcP PCR testing through technical and logistical advancements is critical.
- Syndromic management approaches for PcP require further comprehensive evaluation.
- Optimizing PcP diagnosis necessitates a multi-faceted approach combining molecular testing, biomarkers, and clinical assessment.
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