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Powassan virus is a subtype of the flavivirus group that is transmitted by the ixodid tick from various wild animal reservoirs such as white-footed mouse, red squirrel, and groundhog.
It is a single-stranded, positive-sense RNA virus with two recognized lineages: POWV (Lineage I) and Deer Tick Virus DTV (Lineage II). Both Lineages are phylogenetically distinct, however their clinical course is indistinguishable.
Geographic distribution of both lineages I and II (POWV and DTV) overlaps in the northeastern regions of the United States, with more data needed to map its distribution in Midwestern states.
We performed a chart review to discuss the clinical characteristics and outcomes of Powassan virus infection cases as we noticed an increased number of cases at our institution.
After IRB number 5697 approval, we performed a retrospective analysis of patients diagnosed with Powassan virus infection at our institution from January 1, 2012, through December 31, 2019. The diagnosis of Powassan virus infection was established according to the CDC Arboviral Disease Case Definition.
Suspected cases for powassan viral infection were screened using Polyvalent Microsphere Immunofluorescence Assay and later confirmed using one of the CDC approved diagnostic methods.
1. Isolation of powassan from, or detection of specific viral antigen or nucleic acid in blood serum, cerebrospinal fluid (CSF). 2. Change in powassan specific quantitative antibody titers in serum samples More than fourfold. 3. Detection of powassan virus specific IgM in serum with confirmatory neutralizing antibodies in the same or a later serum specimen. 4. Powassan specific IgM antibodies in CSF and a negative result for other arboviruses IgM antibodies in the same sample.
Evaluation of different serological diagnostic methods for tick-borne encephalitis virus: enzyme-linked immunosorbent, immunofluorescence, and neutralization assay.
All confirmatory methods were designed to specifically detect POWV (lineage I) in our cohort population.
The following data were obtained from the inpatient and outpatient medical records: demographics, relevant comorbidities, symptom onset, date of diagnosis, clinical characteristics, radiographic features, preliminary diagnosis by primary team before confirmation of final diagnosis, diagnostic testing, treatment, and outcome.
Twenty-two patients tested positive for Powassan Polyvalent antibodies via Microsphere Immunofluorescence Assay (MIA) in our institution lab. Five out of twenty-two patients were confirmed for Powassan virus infection. Three of these five patients had positive IgM in serum and Cerebrospinal Fluid (CSF) specimens simultaneously and the remaining two had POWV specific IgM with neutralizing antibodies. Of the remaining seventeen cases, four cases had a negative confirmatory test, eight cases did not have a confirmatory test or final diagnosis, and five cases were discharged with an alternative diagnosis, including paraneoplastic syndrome, viral encephalitis, and Lyme encephalitis.
Our study cohort was comprised of all males, predominantly Caucasian, with a mean age of 47 years old. The most common comorbidity was hypertension (80%). All patients presented in the summer (July 2/5, 40%) and fall (November 3/5, 60%). All five cases were diagnosed within the last 5 years, and mostly in 2019 2/5 (40%). The most frequent symptoms on initial presentation were fever 3/5 (60%), headache 2/5 (40%), and altered mental status 2/5 (40%). Of note, all five subjects had a documented fever while hospitalized or prior to transfer to our institution. 2/5 (40%) of patients developed seizures during hospitalization. Additionally, one patient (20%) was found to have co-infection of Lyme. Most patients were on average diagnosed two weeks after the onset of symptoms. CSF results predominately showed a lymphocytic infiltrate (71%) with a mean glucose of 70 mg/dL and mean protein of 92 mg/dL (Table 1). Radiographic imaging showed no specific pattern for diagnosis but showed cerebellar and basal ganglia hyperintensity and meningeal enhancement (Fig. 1).
Table 1Clinical characteristics of hospitalized Powassan patients.
Patients diagnosed with Powassan encephalitis were treated with steroids 2/5 (40%), plasma exchange 1/5 (20%), and intravenous immunoglobulins 1/5 (20%). Almost half of patients had residual weakness on discharge 2/5 (40%) and one patient died 1/5 (20%). Three patients required respiratory support with mechanical ventilation, with an average time of six days on ventilator.
We describe one of the largest clinical series of Powassan virus encephalitis in the capital district of New York state. All five cases were residents of counties that were not considered endemic previously.
As reported in the literature and we experienced in our cohort population, most of tick feeding and transmission of powassan virus occurs between Spring and the Fall, but it can extend into winter months if average temperatures are higher than freezing temperatures. Hence the importance of high clinical suspicion of unexplained neurological manifestations year round.
There are two case series from the northeast area previously published. We compared the clinical characteristics and outcomes of our study cohort with prior published cohorts from New York and New England states.
Like our patients, patients initially presented with fever, headache, and developed altered mental status during the hospitalization. A tick bite was reported in less than half of cases (36-50%) as it is possible that a tick bite may go unnoticed.
CSF findings were similar to our cohort, as a majority of previous cohorts had a lymphocytosis, high protein, and normal glucose levels. Less than half (13% to 40%) cases were treated with corticosteroids. The majority of cases developed or were discharged with residual weakness in more than 50% of the cases. Also, in hospital mortality was less common, seen in 7% to 25% of previous cases.
In comparison to the previously published largest epidemiological series (N=99) from the United states, including Midwestern and northeastern states between 2006-2016, we found similar clinical and radiographic presentation to our cohort. However, cases of Powassan virus infection were diagnosed throughout the year with peak detection was in May and June months, in our study cases were detected between July to November. Similar to our study, the mortality rate was around 11/99 (11%).
In this current series, we found that twenty-two cases were initially found to have positive screening tests, however only nine had a positive confirmatory test performed. Five were confirmed positive and four patients had false positive screening tests. This point emphasizes that all screened cases of Powassan virus infection should have confirmatory tests performed in the appropriate clinical settings. There is no known vaccine or effective treatment available for this viral infection and the primary focus should be on minimizing exposure to ticks.
Our analysis has several limitations. First, this is a single center retrospective study with a small sample size. Second, there might be referral bias, as our institution is a tertiary care center. Third, our diagnostic studies were specifically utilized to detect POWV. We might have missed cases of DTV related infection; however, these two lineages have no clinical differences. Lastly, only nine patients had confirmatory tests performed, which may suggest this sample of five cases might be an underestimation of cases.
In summary, clinicians in the capital district of New York should have high index of suspicion in patients presenting with unexplained neurological manifestations during summer to fall months.
Funding
None.
Declaration of Competing Interest
All authors have disclosed that they do not have any potential conflicts of interest.
Acknowledgment
All authors contributed to the writing and inception of this manuscript and had access to the data. Dr. Chopra is the guarantor of the article and takes responsibility for the integrity of the work, from inception to published article. Ms. Jain, and Drs. Austin, Dawani and Al-Tarbsheh helped with the data collection.
References
Hermance ME
Thangamani S
Powassan Virus: an emerging arbovirus of public health concern in North America.
Evaluation of different serological diagnostic methods for tick-borne encephalitis virus: enzyme-linked immunosorbent, immunofluorescence, and neutralization assay.
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