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
Kamla Pillay MSc , Suzanne H Keddie PhD , Elizabeth Fitchett MPH , Cassandra Akinde MSc , Oliver Bärenbold PhD , Prof John Bradley PhD , Jane Falconer MA , Prof Ruth H Keogh PhD , Zhia Ning Lim MRes , Behrouz Nezafat Maldonado MSc , Laura Maynard-Smith MBBS , Ellen Sugrue MSc , Okuda Taylor MSc , Heidi Hopkins MD , Audrey Dubot-Pérès PhD
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引用次数: 0
Abstract
Background
Dengue 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.
Methods
In 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).
Findings
Data 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.
Interpretation
IgM 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.
期刊介绍:
The Lancet Microbe is a gold open access journal committed to publishing content relevant to clinical microbiologists worldwide, with a focus on studies that advance clinical understanding, challenge the status quo, and advocate change in health policy.