TY - JOUR
T1 - The diagnosis of mucormycosis by PCR in patients at risk
T2 - a systematic review and meta-analysis
AU - Brown, Lottie
AU - Tschiderer, Lena
AU - Alanio, Alexandre
AU - Barnes, Rosemary A.
AU - Chen, Sharon C.A.
AU - Cogliati, Massimo
AU - Cruciani, Mario
AU - Donnelly, J. Peter
AU - Hagen, Ferry
AU - Halliday, Catriona
AU - Klingspor, Lena
AU - Lagrou, Katrien
AU - Melchers, Willem
AU - Millon, Laurence
AU - Morio, Florent
AU - Salvador, Elena
AU - Stroffolini, Giacomo
AU - Ruhnke, Markus
AU - Toepfer, Stephanie
AU - van Dijk, Karin
AU - Borman, Andrew M.
AU - Buitrago, María José
AU - Gorton, Rebecca
AU - Löffller, Jürgen
AU - Rautemaa-Richardson, Riina
AU - Sendid, Boualem
AU - Willeit, Peter
AU - White, P. Lewis
AU - Lackner, Michaela
N1 - Publisher Copyright:
© 2025
PY - 2025/3
Y1 - 2025/3
N2 - Background: This systematic review and meta-analysis aimed to examine the performance of polymerase chain reaction (PCR) assays for diagnosing mucormycosis. Methods: A standardised search was conducted from conception to December 3rd 2024 using PubMed, Embase, Global Health, and Cochrane library. Original studies that used PCR-based methods on any human specimen to diagnose mucormycosis were analysed for eligibility. Using a bivariate meta-analysis, the diagnostic performance of PCR was examined against the European Organisation for Research and Treatment of Cancer–Mycoses Study Group Education and Research Consortium 2020 (EORTC-MSGERC) definitions of proven and probable invasive mould disease, which was modified to include all patients at risk of mucormycosis. The study protocol was registered on the PROSPERO database (CRD42023478667). Findings: Of 4855 articles, a total of 30 met inclusion criteria, including 5920 PCR reactions on 5147 non-duplicate specimens from 819 cases of proven/probable mucormycosis and 4266 patients who did not meet the EORTC-MSGERC 2020 criteria. According to specimen type, sensitivity of PCR varied (p < 0.001) whereas specificity was similar (p = 0.662). Bronchoalveolar lavage fluid offered the highest sensitivity of 97.5% (95% CI 83.7–99.7%), specificity of 95.8% (95% CI 89.6–98.4%), positive likelihood ratio (LR+) of 23.5, and negative likelihood ratio (LR−) of 0.03. Tissue provided sensitivity of 86.4% (95% CI 78.9–91.5%), specificity of 90.6% (95% CI 78.1–96.3%), LR+ of 9.2, and LR− of 0.15. Blood provided reduced sensitivity of 81.6% (95% CI 70.1–89.4%), specificity of 95.5% (95% CI 87.4–98.5%), DOR of 95, LR+ of 18.3, and LR− of 0.19. Formalin-fixed paraffin-embedded specimens yielded the lowest sensitivity of 73.0% (95% CI 61.0–82.3%), highest specificity of 96.4% (CI 95% 87.5–99.0%), LR+ of 20.2, and LR− of 0.28. The covariates best explaining heterogeneity of the overall analysis were specimen type, study design (cohort versus case-control) and disease prevalence while patient population (COVID-19 versus other) and PCR (conventional versus quantitative) had less impact on heterogeneity. Interpretation: This meta-analysis confirms the high performance of PCR for diagnosing mucormycosis and supports the instatement of PCR detection of free-DNA in blood, BALF and tissue into future updated definitions and diagnostic guidelines for mucormycosis. Funding: None.
AB - Background: This systematic review and meta-analysis aimed to examine the performance of polymerase chain reaction (PCR) assays for diagnosing mucormycosis. Methods: A standardised search was conducted from conception to December 3rd 2024 using PubMed, Embase, Global Health, and Cochrane library. Original studies that used PCR-based methods on any human specimen to diagnose mucormycosis were analysed for eligibility. Using a bivariate meta-analysis, the diagnostic performance of PCR was examined against the European Organisation for Research and Treatment of Cancer–Mycoses Study Group Education and Research Consortium 2020 (EORTC-MSGERC) definitions of proven and probable invasive mould disease, which was modified to include all patients at risk of mucormycosis. The study protocol was registered on the PROSPERO database (CRD42023478667). Findings: Of 4855 articles, a total of 30 met inclusion criteria, including 5920 PCR reactions on 5147 non-duplicate specimens from 819 cases of proven/probable mucormycosis and 4266 patients who did not meet the EORTC-MSGERC 2020 criteria. According to specimen type, sensitivity of PCR varied (p < 0.001) whereas specificity was similar (p = 0.662). Bronchoalveolar lavage fluid offered the highest sensitivity of 97.5% (95% CI 83.7–99.7%), specificity of 95.8% (95% CI 89.6–98.4%), positive likelihood ratio (LR+) of 23.5, and negative likelihood ratio (LR−) of 0.03. Tissue provided sensitivity of 86.4% (95% CI 78.9–91.5%), specificity of 90.6% (95% CI 78.1–96.3%), LR+ of 9.2, and LR− of 0.15. Blood provided reduced sensitivity of 81.6% (95% CI 70.1–89.4%), specificity of 95.5% (95% CI 87.4–98.5%), DOR of 95, LR+ of 18.3, and LR− of 0.19. Formalin-fixed paraffin-embedded specimens yielded the lowest sensitivity of 73.0% (95% CI 61.0–82.3%), highest specificity of 96.4% (CI 95% 87.5–99.0%), LR+ of 20.2, and LR− of 0.28. The covariates best explaining heterogeneity of the overall analysis were specimen type, study design (cohort versus case-control) and disease prevalence while patient population (COVID-19 versus other) and PCR (conventional versus quantitative) had less impact on heterogeneity. Interpretation: This meta-analysis confirms the high performance of PCR for diagnosing mucormycosis and supports the instatement of PCR detection of free-DNA in blood, BALF and tissue into future updated definitions and diagnostic guidelines for mucormycosis. Funding: None.
KW - Diagnosis
KW - Fungal
KW - Mucorales
KW - Mucormycosis
KW - PCR
UR - https://www.scopus.com/pages/publications/85218231964
U2 - 10.1016/j.eclinm.2025.103115
DO - 10.1016/j.eclinm.2025.103115
M3 - Article
AN - SCOPUS:85218231964
SN - 2589-5370
VL - 81
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 103115
ER -