A 74-year-old woman from the upper Midwest presented to the ED with acute onset ataxia and altered mentation. She has regular outdoor exposure in wooded areas, with known mosquito and tick exposures (Figure 1), and frequently feeds wild deer. A CBC on CSF demonstrated 127 cells with lymphocytic predominance. Microbiological workup and imaging were consistent with aseptic meningitis/encephalitis. Given the exposures, testing for arboviruses was performed. A Powassan virus IgM and Powassan virus PCR on blood were both positive.
The correct answer is ...
Powassan IgM testing should be performed on patients with >7 days of symptoms.
Powassan virus (POWV) is a single-stranded, positive-sense RNA virus and member of the Flavivirus genus, which includes West Nile virus (WNV), Zika virus, yellow fever virus, and dengue viruses. POWV is an emerging arboviral pathogen, transmitted by Ixodes sp. ticks (primarily I. scapularis, I. marxi, and I. cookei). Following infection, the incubation period for POWV can range from 1-4 weeks, with ~60% of infected individuals remaining asymptomatic or developing only mild, self-limiting symptoms, including headache, fever, arthralgia, and myalgia. Severe manifestations can occur, including development of neuroinvasive disease in approximately 30% of symptomatic patients, with long-term sequelae remaining in half of those individuals and an associated mortality rate of 10%–15%. Between 2012–2021, the CDC reported 202 cases, with 189 of these being neuroinvasive. Zero deaths have been reported from non-neuroinvasive cases, and 13% of neuroinvasive cases were fatal.
Risk factors for POWV infection include living and travel to Ixodes-endemic areas during the late spring, summer, and fall. While not specific to POWV, the Infectious Disease Society of America (IDSA) recommends that evaluation of co-infections with other tick-borne pathogens be performed in patients with Lyme disease for whom symptoms may suggest a co-infection.
Diagnosis of POWV infection can be established via serologic and/or real-time PCR (PCR) testing; however, appropriate test selection can be challenging and should be guided by the symptom timeline. Patients presenting with <7 days of symptoms are likely to be negative by serologic testing but may be positive by PCR on blood, urine, and/or CSF. The utility of PCR testing is limited to this narrow window due to the rapid decrease in viremia within approximately one week of symptom onset (Figure 2). However, POWV RNA can be detected for longer in urine compared to other sources, as has been documented for WNV and other flaviviruses. Importantly, a negative molecular result for POWV does not exclude the possibility of POWV infection, and serologic testing should be performed if POWV is suspected.
For patients with ≥7 days of symptoms, it is recommended that anti-POWV serologic testing be ordered. Available POWV serologic testing methods include IgM/IgG ELISAs, IgM capture (MAC) ELISAs, immunofluorescence assays (IFA), and plaque-reduction neutralization test (PRNT), the latter of which remains the reference method for arboviral antibody detection. Thus, confirmatory PRNT for samples positive by ELISA or IFA may be considered. IgM antibody levels become detectable after 7 days and may remain detectable for weeks to months. IgG antibody levels will become detectable within months and may remain detectable for decades.
Although targeted antiviral therapy is not available for POWV, accurate diagnosis of infection is important for discontinuation of unnecessary antimicrobial therapy, for prognostic information and allows us to continue to monitor the epidemiology of this virus.
Josh Shirley, Ph.D.
Fellow, Clinical Microbiology
Elitza Theel, Ph.D.
Consultant, Clinical Microbiology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science