The proportion of false positives IgM in the CYD-TDV vaccinated group (17.4%) was higher than in the control group (10.1%), particularly within the 2 months following vaccination. [...]it was necessary to review and redefine a reliable diagnostic testing algorithm in light of false dengue positives, which would be used by healthcare professionals to confirm suspected dengue cases in vaccinees and to evaluate the effectiveness of the CYD-TDV vaccine in the vaccinated populations. IgG ELISA test is usually not utilized for dengue diagnostic in endemic countries for DENV and other flaviviruses due to possible cross-reactivity. [...]a ≥4-fold dengue IgG ELISA value increase between acute and convalescent samples in the dengue-infected CYD-TDV group was observed in only 19.7% of cases compared to 35.5% of the control (placebo) group, ruling out such antibody rise as a viable diagnostic criterion . Negative NS1 ELISA results on acute samples should be tested by RT-PCR for DENV (Fig 1). [...]RT-PCR is generally more specific and sensitive than NS1 ELISA and determines the infecting viral serotype, which can inform vaccine developers of breakthrough infections by a specific serotype. [...]in order to address the sensitivity of the combination of IgM and NS1 ELISAs in a population in which the majority of individuals are seropositive for DENV and/or other flaviviruses (e.g., ZIKV, JEV, or YFV) and vaccinated with CYD-TDV, a prospective study is required. Since a large variability in the results of the diagnostics may occur between different kits and laboratories worldwide, future phase IV studies of CYD-TDV vaccine effectiveness should use the proposed combined diagnostic testing with the same validated and standardized kits/protocols and international guidelines when designing sentinel sites to ensure quality assurance and to enhance data sharing and comparability across regions .
Hunsperger, E. A., Duarte dos Santos, C. N., Vu, H. T. Q., Yoksan, S., & Deubel, V. (2017). Rapid and accurate interpretation of dengue diagnostics in the context of dengue vaccination implementation: Viewpoints and guidelines issued from an experts group consultation. PLOS Neglected Tropical Diseases, 11(9), e0005719. https://doi.org/10.1371/journal.pntd.0005719