Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection: A systematic review and meta-analysis

Background: Chikungunya virus (CHIKV) causes febrile illnesses and has always been misdiagnosed as other viral infections, such as dengue and Zika; thus, a laboratory test is needed. Serological tests are commonly used to diagnose CHIKV infection, but their accuracy is questionable due to varying degrees of reported sensitivities and specificities. Herein, we conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of serological tests currently available for CHIKV. Methodology and principal findings: A literature search was performed in PubMed, CINAHL Complete, and Scopus databases from the 1st December 2020 until 22nd April 2021. Studies reporting sensitivity and specificity of serological tests against CHIKV that used whole blood, serum, or plasma were included. QUADAS-2 tool was used to assess the risk of bias and applicability, while R software was used for statistical analyses. Conclusion: Based on our meta-analysis, antigen or antibody-based serological tests can be used to diagnose CHIKV reliably, depending on the time of sample collection. The antigen detection tests serve as a good diagnostic test for samples collected during the acute phase (≤7 days post symptom onset) of CHIKV infection. Likewise, IgM and IgG detection tests can be used for samples collected in the convalescent phase (>7 days post symptom onset). In correlation to the clinical presentation of the patients, the combination of the IgM and IgG tests can differentiate recent and past infections. Author summary: Chikungunya virus (CHIKV) causes non-specific symptoms such as fever, and the infection is sometimes misinterpreted as other viral infections, such as dengue and Zika. Although serological tests are commonly used to diagnose CHIKV infection, the reliability of these tests is questionable due to their highly variable performance. A systematic review and meta-analysis were performed to determine the diagnostic accuracy of these serological tests. As the analytes (antigen and antibodies) are present in the patient’s sample at different time points of CHIKV infection, we analysed the diagnostic performance of serological tests detecting CHIKV antigen, IgM, and IgG antibodies. Our meta-analysis showed that antigen or antibody-based serological tests could reliably be used to diagnose CHIKV, depending on the time of sample collection. Antigen detection test serves as a good diagnostic test for samples collected within the acute phase (1 to 7 days) of CHIKV infections. On the other hand, the IgM and IgG tests can be used for convalescent-phase (>7 days of symptom onset) samples, differentiating recent and past CHIKV infections. Although IgM antibodies start to develop as early as 2 to 4 days of CHIKV infection, our result showed that the IgM detection tests for acute-phase samples exhibited low accuracy. Thus, the IgM detection test is not recommended for samples collected