Maeki et al.
Analysis of cross-reactivity among flaviviruses using sera of patients with dengue showed the importance of neutralization tests with paired serum samples for the correct interpretations of serological test results for dengue
J Infect Chemother. Published online January 25, 2023. doi:10.1016/j.jiac.2023.01.015

Upon infection with a flavivirus like the TBE virus (TBEV), West Nile virus (WNV), Yellow fever virus, (YFV), Zika virus (ZIKV), Japanese encephalitis virus (JEV) or Dengue virus (DENV), cross-reactive antibodies are produced by the host in addition to specific antibodies. These antigenic relationships between flaviviruses can make the diagnostic difficult when serological assays are used.

A Japanese team has collected 16 sera from patients with dengue and have tested these sera for i) IgM against ZIKV, WNV, JEV and TBE virus using ELISA; ii) for TBE virus IgG antibodies using ELISA; and iii) for neutralizing antibodies against ZIKV, WNV, JEV and TBE virus. Among the 16 sera from Dengue patients’ samples tested using ELISA, seven were IgM-positive against at least one other flavivirus (one cross-reactive positive for TBE virus) and nine were IgG-positive for TBE virus. Neutralizing antibody titers against ZIKV, WNV and TBE virus were one-fourth or lower than those against DENV in the samples.

In summary, these results show that neutralization assays with paired samples are important for the differentiation between flavivirus infections. In addition, it is important to know i) which flavivirus is endemic in a region of residence and/or of travel of the patient, ii) symptoms caused by the endemic flaviviruses, and iii) vaccination history of the patient.

Various articles dealing with the topic of cross-reactivity among flaviviruses have recently been published and some of them are shown below:

Vilibic-Cavlek et al.
Cross-reactive antibodies in tick-borne encephalitis: case report and literature review
Antibodies. 2022;11(4):72. doi:10.3390/antib11040072

Könenkamp et al.
Antibody ratios against NS1 antigens of tick-borne encephalitis and West Nile viruses support differential flavivirus serology in dogs
Transbound Emerg Dis. 2022;69(5):e2789-e2799. doi:10.1111/tbed.14630

Da Silva et al.
Serological cross-reactivity in zoonotic flaviviral infections of medical importance
Antibodies. 2023;12(1):18. doi:10.3390/antib12010018

Čabanova et al.
Co-circulation of West Nile, Usutu, and tick-borne encephalitis viruses in the same area: A great challenge for diagnostic and blood and organ safety
Viruses. 2023;15(2):366. doi:10.3390/v15020366

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