Sensitivity and Specificity of Polymerase Chain Reaction in Blood and Bronchoalveolar Lavage Samples for Mucormycosis: A Bayesian Diagnostic Test Accuracy Meta-Analysis.

Abstract

Background: The utility of polymerase chain reaction (PCR) for diagnosing mucormycosis is uncertain. We conducted a diagnostic test accuracy meta-analysis to determine the performance of Mucorales PCR.

Methods: We systematically reviewed PubMed, Embase, and Cochrane Central databases to identify studies reporting Mucorales PCR (blood or bronchoalveolar lavage fluid [BALF] samples) in at least 10 suspected mucormycosis cases. We pooled sensitivity and specificity using Bayesian (weak and two informative priors) and frequentist methods. Subgroup analyses included middle vs. high-income countries, risk factors (hematological diseases vs. others), study design, assay type (commercial vs. in-house), and testing protocol (serial testing vs. single-time PCR). We assessed the effect of the number of blood tests performed per participant on sensitivity using multivariable meta-regression.

Results: We identified 1524 citations, of which 36 studies (41 datasets, n = 6627 participants; 16,613 samples) were included. The pooled sensitivity and specificity (with 95% credible interval) by Bayesian weak priors (primary analysis) were 51% (34-67%) and 97% (95-98%) for blood; 64% (50-76%) and 97% (95-98%) for BALF samples. We found wide variation in sensitivity, with a 14% increment for every additional blood sample tested per patient. Studies from middle-income countries reported a significantly lower pooled sensitivity (31 vs. 68%) in blood samples and lower specificity in BALF (72 vs. 98%) than high-income countries. No other subgroups showed significant differences.

Conclusion: Mucorales PCR was highly specific but poorly sensitive in blood, and moderately sensitive with high specificity in BALF. Before routine implementation, further well-designed studies from diverse settings and underrepresented regions are needed.