Recognize the ability of Flavivirus cross-reactivity and raise awareness of Powassan virus.

Powassan virus (POWV) is a tick-borne virus that can cause severe encephalitis. Since 2012 there have less than 300 cases of Powassan encephalitis, 24 of which were fatal. It is part of the Flavivirus genus, which includes West Nile (WNV), Dengue, Yellow Fever, and Zika Virus. Having similar genomic structure, they can potentially cross-react with one another, causing false positive antibody levels and an incorrect diagnosis. As the number of Powassan cases rises, medical professionals and the public should be more mindful of its existence.

Literature review was completed by querying the National Library of Medicine for “Powassan cross-reactivity” and “Flavivirus cross-reactivity”. We also performed a retrospective patient chart review identifying all patients diagnosed with either POWV or WNV within the past 5 years.

No publications have reported cross-reactivity between Powassan virus and other flaviviruses, but there has been evidence to suggest this occurring in vitro. During the past five years, six patients have been diagnosed with either Powassan or West Nile Virus encephalitis. Two patients with a definitive diagnosis of POWV encephalitis also had positive West Nile IgM. Of the four patients with WNV encephalitis, two had positive WNV IgG and IgM along with a negative POWV test. However, the other two tested positive for WNV IgM and negative confirmatory testing without POWV testing.

While cross-reactivity is known between some flaviviruses, there is no report of Powassan virus cross-reactivity. Our retrospective patient analysis showed the diagnostic uncertainty medical professionals may stumble upon if other viruses are not tested. Due to the rise of Powassan encephalitis, our work demonstrates the importance of co-testing for POWV, WNV, or other Flaviviruses that may be endemic a particular region.