Adapting Rapid Diagnostic Tests to Detect Historical Dengue Virus Infections

Fernando Echegaray, Peter Laing, Samantha Hernandez, Sully Marquez, Amanda Harris, Ian Laing, Adam Chambers, Neil McLennan, Victor A. Sugiharto, Hua Wei Chen, Sandra Vivero Villagran, Abigail Collingwood, Magelda Montoya, Fausto Bustos Carrillo, Mark P. Simons, Philip J. Cooper, Andrea Lopez, Gabriel Trueba, Joseph Eisenberg, Shuenn Jue WuWilliam Messer, Eva Harris, Josefina Coloma, Leah C. Katzelnick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The only licensed dengue vaccine, Dengvaxia®, increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity. The World Health Organization has recommended using rapid diagnostic tests (RDT) to determine history of prior DENV infection and suitability for vaccination. Dengue experts recommend that these assays be highly specific (≥98%) to avoid erroneously vaccinating individuals without prior DENV infection, as well as be sensitive enough (≥95%) to detect individuals with a single prior DENV infection. We evaluated one existing and two newly developed anti-flavivirus RDTs using samples collected >6 months post-infection from individuals in non-endemic and DENV and ZIKV endemic areas. We first evaluated the IgG component of the SD BIOLINE Dengue IgG/IgM RDT, which was developed to assist in confirming acute/recent DENV infections (n=93 samples). When evaluated following the manufacturer’s instructions, the SD BIOLINE Dengue RDT had 100% specificity for both non-endemic and endemic samples but low sensitivity for detecting DENV seropositivity (0% non-endemic, 41% endemic). Sensitivity increased (53% non-endemic, 98% endemic) when tests were allowed to run beyond manufacturer recommendations (0.5 up to 3 hours), but specificity decreased in endemic samples (36%). When tests were evaluated using a quantitative reader, optimal specificity could be achieved (≥98%) while still retaining sensitivity at earlier timepoints in non-endemic (44-88%) and endemic samples (31-55%). We next evaluated novel dengue and Zika RDTs developed by Excivion to detect prior DENV or ZIKV infections and reduce cross-flavivirus reactivity (n=207 samples). When evaluated visually, the Excivion Dengue RDT had sensitivity and specificity values of 79%, but when evaluated with a quantitative reader, optimal specificity could be achieved (≥98%) while still maintaining moderate sensitivity (48-75%). The Excivion Zika RDT had high specificity (>98%) and sensitivity (>93%) when evaluated quantitatively, suggesting it may be used alongside dengue RDTs to minimize misclassification due to cross-reactivity. Our findings demonstrate the potential of RDTs to be used for dengue pre-vaccination screening to reduce vaccine-induced priming for severe dengue and show how assay design adaptations as well quantitative evaluation can further improve RDTs for this purpose.

Original languageEnglish
Article number703887
JournalFrontiers in Immunology
StatePublished - 23 Jul 2021
Externally publishedYes


  • Zika
  • dengue
  • dengue vaccine
  • pre-vaccination screening
  • rapid diagnostic test


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