The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis

Lottie Brown; Lena Tschiderer; Alexandre Alanio; Rosemary A Barnes; Sharon C-A Chen; Massimo Cogliati; Mario Cruciani; J Peter Donnelly; Ferry Hagen; Catriona Halliday; Lena Klingspor; Katrien Lagrou; Willem Melchers; Laurence Millon; Florent Morio; Elena Salvador; Giacomo Stroffolini; Markus Ruhnke; Stephanie Toepfer; Karin van Dijk; Andrew M Borman; María José Buitrago; Rebecca Gorton; Jürgen Löffller; Riina Rautemaa-Richardson; Boualem Sendid; Peter Willeit; P Lewis White; Michaela Lackner

doi:10.1016/j.eclinm.2025.103115

The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis

Lottie Brown, Lena Tschiderer, Alexandre Alanio, Rosemary A Barnes, Sharon C-A Chen, Massimo Cogliati, Mario Cruciani, J Peter Donnelly, Ferry Hagen, Catriona Halliday, Lena Klingspor, Katrien Lagrou, Willem Melchers, Laurence Millon, Florent Morio, Elena Salvador, Giacomo Stroffolini, Markus Ruhnke, Stephanie Toepfer, Karin van DijkAndrew M Borman, María José Buitrago, Rebecca Gorton, Jürgen Löffller, Riina Rautemaa-Richardson, Boualem Sendid, Peter Willeit, P Lewis White, Michaela Lackner

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

Samenvatting

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.

Originele taal-2	Engels
Pagina's (van-tot)	103115
Tijdschrift	EClinicalMedicine
Volume	81
DOI's	https://doi.org/10.1016/j.eclinm.2025.103115
Status	Gepubliceerd - mrt. 2025

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10.1016/j.eclinm.2025.103115

Citeer dit

Brown, L., Tschiderer, L., Alanio, A., Barnes, R. A., Chen, S. C.-A., Cogliati, M., Cruciani, M., Donnelly, J. P., Hagen, F., Halliday, C., Klingspor, L., Lagrou, K., Melchers, W., Millon, L., Morio, F., Salvador, E., Stroffolini, G., Ruhnke, M., Toepfer, S., ... Lackner, M. (2025). The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis. EClinicalMedicine, 81, 103115. https://doi.org/10.1016/j.eclinm.2025.103115

@article{2264f9e8579447e4815a083c8c4d6146,

title = "The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis",

abstract = "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.",

author = "Lottie Brown and Lena Tschiderer and Alexandre Alanio and Barnes, {Rosemary A} and Chen, {Sharon C-A} and Massimo Cogliati and Mario Cruciani and Donnelly, {J Peter} and Ferry Hagen and Catriona Halliday and Lena Klingspor and Katrien Lagrou and Willem Melchers and Laurence Millon and Florent Morio and Elena Salvador and Giacomo Stroffolini and Markus Ruhnke and Stephanie Toepfer and {van Dijk}, Karin and Borman, {Andrew M} and Buitrago, {Mar{\'i}a Jos{\'e}} and Rebecca Gorton and J{\"u}rgen L{\"o}ffller and Riina Rautemaa-Richardson and Boualem Sendid and Peter Willeit and White, {P Lewis} and Michaela Lackner",

note = "Crown Copyright {\textcopyright} 2025 Published by Elsevier Ltd.",

year = "2025",

month = mar,

doi = "10.1016/j.eclinm.2025.103115",

language = "English",

volume = "81",

pages = "103115",

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Brown, L, Tschiderer, L, Alanio, A, Barnes, RA, Chen, SC-A, Cogliati, M, Cruciani, M, Donnelly, JP, Hagen, F, Halliday, C, Klingspor, L, Lagrou, K, Melchers, W, Millon, L, Morio, F, Salvador, E, Stroffolini, G, Ruhnke, M, Toepfer, S, van Dijk, K, Borman, AM, Buitrago, MJ, Gorton, R, Löffller, J, Rautemaa-Richardson, R, Sendid, B, Willeit, P, White, PL & Lackner, M 2025, 'The diagnosis of mucormycosis by PCR in patients at risk: a systematic review and meta-analysis', EClinicalMedicine, vol. 81, blz. 103115. https://doi.org/10.1016/j.eclinm.2025.103115

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

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.

U2 - 10.1016/j.eclinm.2025.103115

DO - 10.1016/j.eclinm.2025.103115

M3 - Article

C2 - 40083443

SN - 2589-5370

VL - 81

SP - 103115

JO - EClinicalMedicine

JF - EClinicalMedicine

ER -