PCR diagnostic platforms for non-Aspergillus mold infections: ready for routine implementation in the clinic?

ABSTRACT

Introduction

While Aspergillus spp. remain the predominant cause of invasive mold infections, non-Aspergillus molds, such as the Mucorales or Fusarium spp., account for an increasing proportion of cases. The diagnosis of non-Aspergillus invasive mold infections (NAIMI) is challenging because of the low sensitivity and delay of conventional microbiological tests. Therefore, there is a particular interest to develop molecular tools for their early detection in blood or other clinical samples.

Areas covered

This extensive review of the literature discusses the performance of Mucorales-specific PCR and other genus-specific or broad-range fungal PCR that can be used for the diagnosis of NAIMI in diverse clinical samples, with a focus on novel technologies.

Expert opinion

PCR currently represents the most promising approach, combining good sensitivity/specificity and ability to detect NAIMI in clinical samples before diagnosis by conventional cultures and histopathology. Several PCR assays have been designed for the detection of Mucorales in particular, but also Fusarium spp. or Scedosporium/Lomentospora spp. Some commercial Mucorales PCRs are now available. While efforts are still needed for standardized protocols and the development of more rapid and simpler techniques, PCR is on the way to becoming an essential test for the early diagnosis of mucormycosis and possibly other NAIMIs.

KEYWORDS:

• Mucormycosis
• fusariosis
• scedosporiosis
• metagenomics
• multiplex
• bronchoalveolar lavage

Article highlights

• PCR currently represents the most sensitive and specific tool for diagnosis of non-Aspergillus invasive mold infections (NAIMI) in non-invasive clinical samples (e.g. serum or plasma).

• PCR allows earlier detection of NAIMI compared to conventional diagnostic tools (culture or histopathology), which may have a favorable impact on prognosis.

• While some commercial PCR for NAIMI diagnosis are now available, efforts are still needed for the development of more standardized procedures and simpler (automated) tools for their widespread application in clinical routine.

Declaration of interest

F Lamoth reports research funding from Gilead Sciences, Merck, Sharp and Dohme (MSD), Pfizer, and Novartis, and honoraria for conferences or advisory boards from Gilead Sciences, MSD, Pfizer, Mundipharma, and Becton-Dickinson. All contracts were made with and fees paid to their institution (CHUV). DP Kontoyiannis reports honoraria and research support from Gilead Sciences and Astellas Pharma. He has further received consultant fees from Astellas Pharma, Merck, and Co, Knight, and Gilead Sciences, and is a member of the Data Review Committee of Cidara Therapeutics, AbbVie, Scynexis, and the Mycoses Study Group. DP Kontoyiannis also acknowledges support from the Robert C Hickey Endowment for Cancer Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.