Powassan Virus

Introduction

The two lineages of Powassan virus (POWV) are the causative agents for Powassan neuroinvasive disease. A POWV Lineage 1 was initially isolated in 1958 in Powassan, Ontario, Canada, from the brain of a young boy who died of encephalitis. This virus bears some serological relationship to the Far Eastern tickborne encephalitis virus (TBEV-FE), formerly known as Russian spring–summer encephalitis (RSSE) virus. Both are members of the TBEV complex but are distinct species. Tickborne encephalitic flaviviruses appear to have evolved from nonencephalitic viruses that migrated eastward and northeastward from Africa into Asia and southern Pacific islands. They then migrated northward to Far East Asia before spreading westward across Eurasia into Western Europe over the last 2000–4000 years. Only the Powassan virus is known to have made its way to North America.

POWV is found primarily in Canada and the United States and, to a far lesser extent, in Russia. It is the only pathogenic tickborne flavivirus that is known to infect humans in North America. Antibodies to POWV have also been detected in Mexico. On the Eastern Seaboard, POWV is found from Virginia to Nova Scotia and inland in New York, Pennsylvania, and Quebec. In the interior of the United States, it has been reported in the North Central states (Michigan, Wisconsin, and Minnesota) and western and Pacific coast states (Colorado, New Mexico, and California). It is also found across Canada (Ontario, Quebec, Alberta, and British Columbia) and in other very cold regions, such as Alaska and Siberia. In Siberia, voles host the virus, while in New Mexico, infection occurs in pinion mice and deer mice. The pinion mice have a higher prevalence rate than is seen in deer mice.

In addition to expanding its geographical range over time, prevalence of POWV is increasing in both its tick vectors and vertebrate hosts. Infections typically occur from May to September and are often associated with known tick exposure. Between 1999 and 2005, the average yearly number of human POWV cases was 1.3 in the United States, compared to 0.7 cases per year during the 40 preceding years. Furthermore, from 1958 to 1998, 27 cases were reported, while from 1999 to 2016, there were 98 known cases, reflecting an increase of 671% over 18 years. Similarly, the numbers of infected deer are increasing. Significantly, infected snowshoe hares, wild murine rodents, and horses have displayed neurological disease manifestations.

POWV is a rarely reported cause of encephalitis in the United States. In the northeastern part of the country, POWV Lineage II is transmitted to humans by Ixodes scapularis ticks. POWV is serologically indistinguishable from deer tick virus (DTV) and both POWV and DTV use the same tick vector. In addition, they have an 84% nucleoside sequence identity. It has thus been suggested that they represent different lineages of the same encephalitis virus.

History

Since its discovery in 1958, over 100 human cases of Powassan virus encephalitis have been reported in North America. Although the first reported discovery of POWV in humans occurred in Canada, later studies found the virus in a tick pool collected in 1952 in Colorado, in the western United States. POWV was first isolated in Russia in 1972 from Haemaphysalis longicornis ticks and, in 1978, from the blood of a healthy woman following a tick bite. At that time, the examination of sera from Russia detected an antibody against TBEV in 69.2% of the tested encephalitis patients ( n = 117), an antibody against POWV in 4.3% of the patients, and antibodies against both viruses in 4.3% of the encephalitis patients. Subsequent seroepidemiological studies and viral isolations revealed that POWV is present in ticks, rodents, and humans. Comparative analysis of the complete viral genome sequences determined that a 2006 Russian strain of POWV from an infected human was 99.8% similar to the strain isolated in Canada in 1958. As many as 3.2% of the people living in the northern Ontario region of Canada are seropositive, despite low numbers of reported cases of POWV-associated encephalitis, indicating that POWV is not usually infectious to humans or that infection is rarely pathogenic. POWV-associated disease may also be misdiagnosed. Reported disease incidence is increasing, whether due to increased numbers of people infected by one of the POWV lineages or increased surveillance and detection. From 2006 through 2016, 99 cases of this viral disease were reported from 12 states in the United States. Of these, 89 cases were neuroinvasive. The states with the highest disease incidence were Minnesota (0.468 cases per 100,000 population), Wisconsin (0.333), Maine (0.226), and Massachusetts (0.197). Of concern, the highest numbers of cases were reported in 2011 ( n = 16), 2013 ( n = 15), and 2016 ( n = 22).

POWV Lineage I are present in the Great Lakes region of North America, but more recently, cases of POWV Lineage II have been reported in the northeastern part of the United States. Lineage II was first isolated from I. scapularis ticks in 1997. The recent increase in human cases of Powassan encephalitis may be due, at least partially, to the emergence of this lineage in new areas, especially in the Hudson Valley of New York State. Hudson Valley reported 14 Powassan encephalitis cases from 2004 to 2012 and 4 more cases in 2013, accounting for 72% of the patients with POWV encephalitis. I. scapularis are responsible for more than 75% of the human tick bites in this region, while no bites were attributable to Ixodes cookei , strongly suggesting that most of the encephalitis cases in that area are due to POWV Lineage II, rather than to Lineage I. Lineage II, but not Lineage I, viruses were only found in I. scapularis and up to 6% of the tested adult ticks were infected by POWV Lineage II. A study of Pennsylvania ticks from 2013 to 2015 found that 66.9% were adult I. scapularis ( n = 2973 ticks) and that the statewide POWV infection rate was 0.05%. Studies in New York and Connecticut have detected Lineage II virus in 3% of the tested ticks. In contrast, as many as 55% of the ticks were positive for Borrelia burgdorferi , the spirochete that is the causative agent of Lyme disease. Additionally, the reported prevalence of POWV-infected deer in Connecticut, Vermont, and Maine has increased from less than 25% before 1996 up to 80%–90% in 2005–09. This increase in the infection rate of deer was accompanied by a similar increase in Powassan encephalitis in humans of the region. Deer from Connecticut tend to have more exposure to Lineage II virus than animals from Vermont or Maine, which may be related to having greater more I. scapularis ticks, which are more prevalent in southern, than northern, New England.