Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials

Target product profile for a dengue pre-vaccination screening test

“…For each test, sensitivity appeared similar in samples from individuals with recent (<13 months) versus remote (3 to 4 years) virologically confirmed DENV infections. In general, dengue IgG RDTs were found to be more specific and less cross-reactive than ELISAs [13].…”

“…However, the disadvantages are that PRNT requires specialized The technical working group also considered selecting commercially available DENV IgG ELISAs that have performance characteristics close to this composite reference standard, but are widely available and can be performed in most laboratories. Sanofi Pasteur has published data showing that the Panbio Indirect and Euroimmun IgG ELISAs have the best performance profiles against the PRNT 90 , PRNT 50 , and NSI IgG as a serostatus reference standard [13]. The Euroimmun IgG ELISA exhibits a lower overall cross-reactivity to other flaviviruses, while the PanBio exhibits moderate levels of cross-reactivity to ZIKV and West Nile virus.…”

Optimising dengue pre-vaccination screening

“…In The Lancet Infectious Diseases , Carlos DiazGranados and colleagues evaluated five commercially available immunoassays—two IgG-based ELISAs (EUROIMMUN and Panbio) and three rapid diagnostic tests (RDTs; TELL ME FAST, SD BIOLINE, and OnSite)—for their potential to classify baseline dengue serostatus, using baseline samples from more than 3000 participants in the immunogenicity subsets of the phase 3 CYD14 and CYD15 efficacy trials. 7 All immunoassays exhibited high specificity (>98% for all immunoassays apart from SD BIOLINE RDT), but variable sensitivities, with higher sensitivities observed for the ELISAs (EUROIMMUN 89·2% [95% CI 87·9–90·3] and Panbio 92·5 [91·4 to 93·5]) than the RDTs (TELL ME FAST 52·5% [50·6 to 54·4], SD BIOLINE 71·1% [69·3 to 72·8], and OnSite 47·6% [45·7 to 49·5]). 7 These results are encouraging, and consistent with an earlier evaluation of various ELISA against RDTs, in which sensitivities for RDTs were found to generally be lower than those of the ELISAs (≥90%).…”

“… 7 All immunoassays exhibited high specificity (>98% for all immunoassays apart from SD BIOLINE RDT), but variable sensitivities, with higher sensitivities observed for the ELISAs (EUROIMMUN 89·2% [95% CI 87·9–90·3] and Panbio 92·5 [91·4 to 93·5]) than the RDTs (TELL ME FAST 52·5% [50·6 to 54·4], SD BIOLINE 71·1% [69·3 to 72·8], and OnSite 47·6% [45·7 to 49·5]). 7 These results are encouraging, and consistent with an earlier evaluation of various ELISA against RDTs, in which sensitivities for RDTs were found to generally be lower than those of the ELISAs (≥90%). 8 , 9 Those studies also found that sensitivity for the assays evaluated by DiazGranados and colleagues appeared similar in samples from individuals with recent (<13 months) versus remote (3–4 years) virologically confirmed dengue.…”

“…DiazGranados and colleagues also re-evaluated CYD-TDV vaccine efficacy in participants identified as dengue seropositive by the five immunoassays. 7 Vaccine efficacy against symptomatic virologically confirmed dengue in immunoassay-positive participants was high across all five immunoassays (from 82·8% [95% CI 66·9–91·1] by SD BIOLINE RDT to 89·7% [64·6–97·0] by OnSite RDT), as was vaccine efficacy against hospitalised virologically confirmed dengue (from 72·8% [38·9–87·9] by EUROIMMUN ELISA to 92·4% [37·8–99·1] by TELL ME FAST RDT), underpinning the public health usefulness of the first licensed dengue vaccine. Vaccine efficacy against severe virologically confirmed dengue was similarly high, but lacked precision owing to very few severe virologically confirmed dengue cases over the follow-up.…”