Evaluating the performance of common reference laboratory tests for acute dengue diagnosis: a systematic review and meta-analysis of RT-PCR, NS1 ELISA, and IgM ELISA.

BackgroundDengue fever is listed among the top ten global health threats by WHO. Prompt identification of dengue virus can guide clinical management and outbreak response, yet laboratory diagnosis is complex, costly, and lacks consensus on performance evaluation. This systematic review aims to provide reliable diagnostic accuracy estimates in order to inform global guidance and evaluate novel rapid diagnostic tests.MethodsIn this systematic review and meta-analysis, we searched nine literature databases on Feb 16, 2021, for reports on five common reference tests for dengue infection: NS1 ELISA, IgM ELISA, IgG ELISA, RT-PCR, and viral neutralisation test. Articles were included if they reported primary data from more than five participants to complete 2×2 tables comparing one of these tests (on human serum) with any comparator. Diagnostic accuracy was estimated using Bayesian random-effect meta-analysis, which does not require a gold-standard comparator. Risk of bias was assessed using QUADAS-2. This review is registered with PROSPERO (CRD42022341552).FindingsData were extracted from 161 articles, allowing analysis of multiple timeframes for three tests of interest. Pooled sensitivities of RT-PCR (0-4 days after symptom onset), NS1 ELISA (0-4 days), and IgM ELISA (1-7 days) were 95% (95% credible interval 77-99), 90% (68-98), and 71% (57-84), respectively. The corresponding pooled estimates of specificity were 89% (60-98), 93% (71-99), and 91% (82-95). A subanalysis of only studies at low risk of bias demonstrated similar estimates.InterpretationIgM ELISA shows poor diagnostic accuracy early in the symptom course. NS1 ELISA shows similar diagnostic accuracy to RT-PCR, which has important implications for global public health policy, given its relatively low cost and accessibility.FundingNone.