Adapting Rapid Diagnostic Tests to Detect Historical Dengue Virus Infections.

Area of Science:

• Virology
• Immunology
• Diagnostic Assays

Background:

• The dengue vaccine Dengvaxia® poses a risk of severe dengue in seronegative individuals but is protective in seropositive individuals.
• The World Health Organization recommends rapid diagnostic tests (RDTs) to identify individuals with prior dengue virus (DENV) infection for vaccination suitability.
• Optimal RDTs require high specificity (≥98%) to prevent vaccinating seronegative individuals and high sensitivity (≥95%) to detect prior DENV infection.

Purpose of the Study:

• To evaluate the diagnostic performance of existing and novel anti-flavivirus RDTs for pre-vaccination screening of dengue virus (DENV) infection.
• To assess the impact of quantitative evaluation and assay adaptations on RDT sensitivity and specificity.
• To determine the suitability of RDTs for minimizing the risk of vaccine-induced severe dengue.

Main Methods:

• Evaluated the SD BIOLINE Dengue IgG/IgM RDT and two novel Excivion RDTs (dengue and Zika) using samples from individuals with known DENV/ZIKV exposure.
• Assessed RDT performance using both visual interpretation and quantitative reader evaluation.
• Determined RDT sensitivity and specificity according to manufacturer instructions and extended assay run times.

Main Results:

• The SD BIOLINE Dengue RDT showed 100% specificity but low sensitivity (0-41%) when used as directed; extended run times improved sensitivity but reduced specificity.
• Quantitative evaluation of the SD BIOLINE Dengue RDT achieved ≥98% specificity with improved sensitivity (44-88% non-endemic, 31-55% endemic).
• The Excivion Dengue RDT achieved ≥98% specificity with moderate sensitivity (48-75%) via quantitative evaluation. The Excivion Zika RDT demonstrated high specificity (>98%) and sensitivity (>93%) quantitatively.

Conclusions:

• Quantitative evaluation of RDTs can significantly enhance diagnostic accuracy for dengue pre-vaccination screening.
• Novel RDTs, like the Excivion Zika RDT, show promise in reducing cross-flavivirus reactivity and improving screening accuracy.
• Optimized RDTs are crucial for safe dengue vaccination strategies, preventing severe dengue by accurately identifying individuals with prior DENV infection.