Diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus infection-systematic review and meta-analysis.

OBJECTIVES: We aimed to assess diagnostic test accuracy of antigenaemia assay for PCR-proven cytomegalovirus (CMV) infection.

METHODS: We systematically searched studies that provide data both on sensitivity and specificity of the CMV antigenaemia assay using the PCR as the reference standard. Adults, children, infants, individuals who were immunocompromised for any reason, symptomatic patients and asymptomatic individuals were all included. A hierarchical summary receiver operating characteristics model was used for diagnostic meta-analysis. Study quality was assessed by Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies. Protocol registration identification is CRD42016035892.

RESULTS: We identified 75 eligible articles including 9058 CMV PCR-positive individuals and 22 232 PCR-negative individuals. The diagnostic odds ratio for positive antigenaemia was 30 (95% CI 24-38, I2  = 28%) and the area under the hierarchical summary receiver operating characteristic curve was 0.86 (95% CI 0.83-0.88). The summary estimates of sensitivity and specificity were 0.65 (95% CI 0.59-0.70) and 0.94 (95% CI 0.93-0.95), respectively. The positive likelihood ratio of 10.9 (95% CI 8.5-14.0) suggested that a positive result from the antigenaemia assay greatly increased the probability of PCR-proven CMV infection, but a negative likelihood ratio of 0.38 (95% CI 0.32-0.44) indicated that a negative result led to a small decrease in the probability of PCR-proven CMV infection. Sensitivity and subgroup analyses replicated these results.

CONCLUSIONS: The antigenaemia assay overlooked 35% of PCR-proven CMV infections; hence, a negative result of an antigenaemia assay could not rule out a CMV infection.