Strengths and limitations of molecular diagnostics for pneumonia.

Alexandre Alanio, Mario Cruciani, J Peter Donnelly, Juergen Loeffler, P Lewis White, Rosemary Barnes, Riina Rautemaa-Richardson, Lottie Brown

Journal: Expert review of molecular diagnostics 2024;24(10):899-911

PMID: 39552603

Abstract

INTRODUCTION

While 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.

Address: Institute of Infection and Immunity, St George's Hospital and St George's University, London, UK.; Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France.; FPCRI, Verona, Italy.; Department of Infection, Immunity and Biochemistry and School of Medicine, University of Cardiff, Cardiff, UK.; EAPCRI, Nijmegen, The Netherlands.; Medizinische Klinik II, Labor WÜ4i, Universitätsklinikum Würzburg, Würzburg, Germany.; Mycology Reference Centre Manchester and Department of Infectious Diseases, Manchester Academic Health Science Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust and Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Public Health Wales Mycology Reference laboratory and Cardiff University Centre for Trials Research, UHW, Cardiff, UK.

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