Diagnostic accuracy of rapid one-step PCR assays for detection of herpes simplex virus-1 and -2 in cerebrospinal fluid: a systematic review and meta-analysis.

BACKGROUND

Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management.

OBJECTIVES

Summarize the diagnostic accuracy of commercial rapid sample-to-answer PCR assays (results in <90 minutes, without a separate nucleic acid extraction step) for HSV1/2 detection in CSF.

DATA SOURCES: Four databases (MEDLINE, EMBASE, Scopus, and CENTRAL) and five conference abstract datasets from January 2012 to March 2022.

STUDY ELIGIBILITY CRITERIA: Eligible diagnostic accuracy studies provided sufficient data for the construction of a standard diagnostic accuracy two-by-two table.

PARTICIPANTS

Patients with suspected meningitis and/or encephalitis.

TESTS: FilmArray Meningitis-Encephalitis Panel and Simplexa HSV 1&2 Direct Kit PCR.

REFERENCE STANDARD: Real-time PCR assay.

ASSESSMENT OF RISK OF BIAS: Two investigators independently extracted data, rated risk of bias, and assessed quality using QUADAS-2. METHODS OF DATA SYNTHESIS: Accuracy estimates were pooled using Bayesian random effects models.

RESULTS

Thirty-one studies were included (27 FilmArray; 4 Simplexa), comprising 9924 samples, with 95 HSV-1 and 247 HSV-2 infections. Pooled FilmArray sensitivities were 84.3% (95% credible interval, 72.3-93.0) and 92.9% (95% credible interval (CrI), 82.0-98.5) for HSV-1 and HSV-2, respectively; specificities were 99.8% (95% CrI, 99.6-99.9) and 99.9% (95% CrI, 99.9-100). Pooled Simplexa sensitivities were 97.1% (95% CrI, 88.1-99.6) and 97.9% (95% CrI, 89.6-99.9), respectively; specificities were 98.9% (95% CrI, 96.8-99.7) and 98.9% (95% CrI, 97.1-99.7). Pooled FilmArray sensitivities favoured industry-sponsored studies by 10.0 and 13.0 percentage points for HSV-1 and HSV-2, respectively. Incomplete reporting frequently led to unclear risk of bias. Several FilmArray studies did not fully report true negative data leading to their exclusion.

CONCLUSIONS

Our results suggest Simplexa is accurate for HSV1/2 detection in CSF. Moderate FilmArray sensitivity for HSV-1 suggests additional testing and/or repeat CSF sampling is required for suspected HSV encephalitis when the HSV-1 result is negative. Low prevalence of HSV-1 infections limited summary estimates' precision. Underreporting of covariates limited exploration of heterogeneity.