Evaluation of rapid diagnostic tests and conventional enzyme-linked immunosorbent assays to determine prior dengue infection.

Background: In September 2018, the World Health Organization recommended that prevaccination screening be used with the tetravalent dengue vaccine (CYD-TDV), to ensure that only individuals with evidence of prior dengue infection (PDI) are vaccinated. Dengue rapid diagnostic tests (RDTs) would offer a potential solution for prevaccination screening at the point-of-care, but data on performance of available RDTs for identifying PDI are limited. We determined the suitability of four dengue RDTs and two conventional enzyme-linked immunosorbent assays (ELISAs) to identify PDI and evaluated cross-reactivity with co-circulating flaviviruses. Methods: Specificity was assessed using 534 dengue-negative [determined by 50% plaque reduction neutralization test (PRNT50)] serum samples from USA (n = 229) and dengue-endemic regions (n = 305). Sensitivity was assessed using 270 samples from recent (n = 90) or remote (n = 90) virologically confirmed prior dengue cases, and dengue PRNT50-positive samples (n = 90). Cross-reactivity was assessed in dengue-seronegative samples that were seropositive for yellow fever (n = 57), Japanese encephalitis (n = 37), West Nile (n = 59) or Zika (n = 41). Results: Dengue IgG RDTs and the Panbio ELISA exhibited favourable specificities (99-100%), higher than the Focus ELISA (95%). The RDTs had variable sensitivities (40-70%) that were lower than those of the ELISAs (>= 90%). Cross-reactivity to other flaviviruses was low with RDTs (<= 7%), but more significant with ELISAs (up to 51% for West Nile and 34% for Zika). No cross-reactivity to any of the four closely related flaviviruses was observed with the CTK Biotech RDT. For each SeroTest, sensitivity appeared similar in samples from individuals with recent (<13 months) vs remote (3-4 years) virologically confirmed PDI. Conclusions: In general, dengue IgG RDTs were found to be more specific and less cross-reactive than the ELISAs, but the latter were more sensitive for identifying PDI cases. Currently available RDTs could be temporizing tools for rapid and safe prevaccination screening until improved RDTs with increased sensitivity become available.