Powassan virus presents a clinical challenge because there is no standard diagnostic protocol and most cases are only diagnosed after a patient goes through an extensive workup for other infectious diseases. Additionally, serologic testing is not widely available and only state health departments and the CDC can perform Powassan-specific IgM antibody testing utilizing enzyme-linked immunosorbent assay and immunofluorescence antibody (Fatmi et al. 2017). However, Powassan virus is generally diagnosed by a compatible clinical syndrome plus 1 of the following: virus isolation, detection of IgM antibodies by ELISA with a confirmatory plaque neutralization test (which measures the ability of patient serum to reduce virus infectivity in an experimental setting), detection of IgM in the CSF with negative results for other causes of encephalitis, or documented 4-fold rise in antibody titer (CDC 2015).
Fatmi et al. 2017 (“Powassan Virus—A New Reemerging Tick-Borne Disease”): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732952/
CDC 2015 (“Arboviral Diseases, Neuroinvasive and Non-neuroinvasive
2015 Case Definition”): https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/