Powassan Virus Encephalitis, Minnesota, USA

Powassan virus (POWV) is a rare tick-borne agent of encephalitis in North America. Historically, confirmed cases occurred mainly in the northeastern United States. Since 2008, confirmed cases in Minnesota and Wisconsin have increased. We report a fatal case of POWV encephalitis in Minnesota. POWV infection should be suspected in tick-exposed patients with viral encephalitis.

leukocytes), 5 erythrocytes, and 64 mg/dL of protein. The patient was given piperacillin/tazobactam and doxycycline.
The next day, she was less responsive and was transferred to Abbott Northwestern Hospital in Minneapolis. Shortly thereafter, she became unresponsive and labored breathing developed. Her temperature reached 102°F (38.9°C), and the following laboratory values were outside the reference range: leukocyte count (11.3 × 10 3 /mm 3 ), sodium level (131 mmol/L), erythrocyte sedimentation rate (49 mm/h), and protein level (2.3 mg/dL). Neurology and infectious disease specialists suspected viral encephalitis. Magnetic resonance imaging (MRI) was deferred because of the unknown composition of the aneurysm clip, and the patient underwent a computed tomography angiogram of the head and neck. Infarction, vasculitis, meningeal enhancement, and structural abnormalities were not found. Twenty-four-hour electroencephalogram monitoring and administration of ceftriaxone (2 g intravenously [IV] every 24 h), acyclovir (500 mg IV every 8 h), and doxycycline (100 mg IV every 12 h) were initiated.
Overnight, the patient became apneic and required intubation. Examination revealed absent deep tendon refl exes, ocular deviation, positive Babinski response, and bilateral fl accid paralysis of the extremities. Pupillary light and corneal refl exes remained intact. No independent respirations were initiated. Complement levels were within reference range. No evidence of seizure was shown on electroencephalogram, although epileptiform discharges were seen. Given the severity of encephalopathy, prophylactic levetiracetam was initiated.
Results of repeat screen for B. burgdorferi antibodies, smear for Ehrlichia spp., and blood and urine cultures were unremarkable. Brain MRI revealed nonspecifi c infl ammatory changes within the thalamus, midbrain, and cerebellum, with no evidence of meningeal irritation, temporal lobe abnormality, mass effect, acute infarct, or hydrocephalus ( Figure 1, panel A, Appendix, wwwnc.cdc. gov/EID/article/18/10/12-0621-F1.htm). Acyclovir was dis-continued. Routine bacterial culture of CSF was negative. Ceftriaxone and doxycycline were continued because acute Lyme disease, which rarely manifests in this manner, could not be ruled out by serologic testing alone.
The patient remained unresponsive with fl accid paralysis and arefl exia. Four days after the initial examination, repeat MRI showed substantial progression of signal abnormality in cerebral hemispheres, thalamus, and midbrain. Mass effect was evident with crowding of structures at the foramen magnum. Lateral and third ventricle dilation, consistent with acute hydrocephalus, was noted ( Figure 1, panel B). A repeat lumbar puncture was not performed, given clinical interpretation of illness, known imaging fi ndings, key pending results, and lack of indications for additional testing.  (5-7). Human infection has been documented in North America and Russia (8). Both prototypic (POWV) and deer tick virus (DTV) genotypes exist (6,9). In Canada and the northeastern United States, I. cookei ticks are the typical vectors for POWV. In Minnesota and Wisconsin, I. scapularis ticks are the typical vectors for DTV. Although I. cookei ticks are present in these states, they rarely attach to humans, and according to MDH data, all sequenced strains in Minnesota are of the DTV genotype. Transmission time from tick to host has been documented in mice as quickly as 15 minutes (10). The length of attachment time required for diseasecausing viremia in humans is unknown. Literature estimates vary, but <40 cases were documented during 1958-2000 (2,4,11,12). According to the Centers for Disease Control and Prevention and the health departments of Minnesota and Wisconsin, 33 US cases were reported during 2001-2010: 12 in New York, 9 in Wisconsin, 8 in Minnesota, 2 in Maine, and 1 each in Michigan and Virginia. In 2011, of 16 confi rmed cases in the United States, 11 occurred in Minnesota and 4 occurred in Wisconsin. Figure 2 illustrates the geographic distribution of human cases and infected ticks.
Patients with POWV infection typically exhibit encephalitis after an incubation period of 1-4 weeks. Fever and headache are common; the typical viral prodrome lasts 1-3 days. Mental status changes, cerebellar symptoms, and hemiplegia are also common and may be severe. Results of CSF testing and brain imaging are generally consistent with viral encephalitis. Reverse transcription PCR of CSF, serologic testing of CSF, and serologic testing of serum are the preferred diagnostic tests, but they are not widely available. Diagnostic testing for POWV should be referred to state and federal laboratories to ensure accuracy and standardization (4,8,9,(11)(12)(13) Pathogenesis is due to lymphocytic infi ltration of perivascular neuronal tissue with a predilection for gray matter, including thalamus, midbrain, and cerebellum (11). Supportive care is the only therapy. A European vaccine against the related tick-borne encephalitis virus is available, but although the viruses are antigenically similar, its effectiveness against POWV is unknown (12). Approximately 10% of the reported infections have been fatal, and an additional 50% have produced long-term neurologic sequelae, including hemiplegia and headaches (2,9,13).

Conclusions
POWV is causing an emerging and potentially severe tick-borne infection in Minnesota and Wisconsin. POWV infection should be suspected when tick-exposed patients exhibit viral encephalitis, especially those with cerebellar Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 10, October 2012 symptoms and/or thalamus/midbrain gray matter disease. Preventing tick attachment by using chemical prophylaxis and vigilance are essential in disease-endemic environments to prevent contraction of POWV infection.
Dr Birge practices hospital medicine at Bergan Mercy Medical Center in Omaha, Nebraska, USA. His research interests include hospital infections, cardiopulmonary resuscitation, and physical activity.
Dr Sonnesyn is an assistant clinical professor of medicine at the University of Minnesota. He is also a partner at Infectious Disease Consultants, P.A., and serves as hospital epidemiologist at Abbott Northwestern Hospital, Minneapolis.