Changing epidemiology of Powassan encephalitis in North America suggests the emergence of the deer tick virus subtype

Keywords::

• deer tick virus
• encephalitis
• flavivirus
• Ixodes scapularis
• Powassan virus

In 1958, a 5-year-old boy from Powassan, Ontario, Canada, died from a severe form of encephalitis. A virus was isolated from brain tissue and named after the hometown where the child resided [1]. Since its original description, fewer than 100 cases of Powassan virus encephalitis have been reported in North America; in addition, at least 17 cases have been reported from the Primorski Krai region of Russia.

Classification of Powassan virus

Powassan virus is a member of the mammalian tick-borne encephalitis flaviviruses group [2] and is the only tick-borne transmitted arbovirus occurring in North America, with Minnesota, Wisconsin and New York State having the highest number of reported cases in recent years [101]. Powassan virus encompasses two closely related lineages: the Powassan virus prototype and the deer tick virus (DTV) lineage. These two lineages share 84% nucleotide sequence identity and 94% amino acid sequence identity, and can only be accurately differentiated by genetic sequence analysis [3]. Some researchers refer to DTV as lineage II, others as lineage I, which has created confusion within the scientific community. Thus, in this paper we will use the terms Powassan virus prototype and DTV, when the exact lineages are known.

Vectors & zoonotic reservoirs

Evidence of infection with Powassan virus has been found in at least 38 species of mammals including small- and medium-sized wild animals (rodents, woodchucks, skunks) and domestic animals (dogs, cats) [4]. Powassan virus prototype has been isolated from three tick species: Ixodes cookei, I. marxi and I. spinipalpus, whereas DTV has been exclusively detected in I. scapularis ticks [5], except once when it was recovered from Dermacentor andersoni ticks [3]. Powassan virus prototype is maintained in an enzootic cycle that involves mainly I. cookei as the tick vector and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis) as the principal reservoir hosts [6]. DTV is believed to be maintained between I. scapularis and the white footed mouse (Peromyscus leucopus) [7].

Epidemiology & clinical disease

Powassan virus is a rare cause of encephalitis and aseptic meningitis. In 2010, the rate of neuroinvasive disease secondary to Powassan virus infection was <0.01 per 100,000 habitants in the USA. Although this incidence was not different from that for St. Louis encephalitis virus and eastern equine encephalitis virus in the same year, it was lower than that for California serogroup viruses (including La Crosse virus) and West Nile virus, 0.02 and 0.2 per 100,000 habitants, respectively [8]. Most Powassan virus infections are thought to be asymptomatic. This assumption is based, in part, on seroprevalence data in humans which according to early studies ranges from 0.7% in New York State to 3% in Ontario, Canada [4]. Whether these values accurately reflect current seroprevalence rates is unknown. It is also unclear if seropositivity in asymptomatic individuals is an accurate indication of a past Powassan virus infection.

Children and the elderly are the most commonly affected with neuroinvasive Powassan virus infection and typically present 1–4 weeks after a tick bite with fever, generalized weakness and lethargy which may be associated with seizures and confusion. Within a few days, the illness can progress to coma and respiratory failure. White blood cell counts, platelet counts and liver function tests are usually within the normal range. As is the case with other causes of viral encephalitis, cerebrospinal fluid (CSF) typically reveals a lymphocytic pleocytosis with a mildly elevated protein level; however, a neutrophilic predominance in CSF has been observed in a few cases. Brain imaging findings are non-specific and include mainly grey matter abnormalities and acute ischemic changes, most commonly appreciated by magnetic resonance imaging [9]. Acute infection can be diagnosed based on the detection of a fourfold change in titers of Powassan virus-specific neutralizing antibodies in serum, detection of Powassan virus-specific IgM in CSF or direct detection of the virus by culture or by nucleic acid testing in blood, CSF or brain tissue [102].

Changing epidemiology may be related to the DTV strain of Powassan virus

Recent epidemiological data indicate an increase in the incidence of Powassan virus infections in North America, especially in certain Lyme disease endemic areas. During the first 40 years after its discovery (1958–1998), 27 cases of Powassan virus encephalitis were reported (average, 0.7 cases per year). None of the cases, however, was reported from Wisconsin or Minnesota, two North Central states that are highly endemic for Lyme disease; the vector for Lyme disease in this region is I. scapularis. From 1999 to 2007, 17 cases were reported (average, 1.9 cases per year), 17.6% of which were from Wisconsin or Minnesota. From 2008 to 2012, 39 cases (average, 7.8 cases per year) were reported from the USA, and 32 (82%) of these cases were from Wisconsin or Minnesota [101]. DTV has been detected in I. scapularis ticks from both Wisconsin and Minnesota [5].

The epidemiology of Powassan virus infections in New York State specifically has also been changing in a pattern consistent with the emergence of cases in counties in which Lyme disease is highly endemic. Of the 14 cases of Powassan virus encephalitis identified in New York State from 2004 through 2012, 10 patients (72%) were from three counties located in the Lower Hudson Valley, a highly endemic region for Lyme disease [9]. In comparison, of the nine cases of Powassan virus encephalitis diagnosed in New York State before 2004, none occurred in patients from this region [10].

One could argue that the increasing number of cases in the USA is in part due to better recognition of the disease, as accurate diagnostic tests became more available in the early 2000s. However, this would not explain why the majority of recently diagnosed cases have been from Lyme disease endemic areas.

Until 2001, DTV was not known to cause human infection [3]. However, the recent changes in the epidemiology of recognized neuroinvasive Powassan virus infections suggest that DTV is playing an increasingly important role [9]. There are three reported cases of genetic sequencing confirmed DTV encephalitis in the medical literature, one from Ontario, Canada [3,11] and two from New York State, both from the Lower Hudson Valley [12,13]. One additional case of DTV encephalitis has been documented in Minnesota from 2008 [14]. DTV has been detected in I. scapularis ticks from the Lower Hudson Valley with infection rates of up to 6% in adult ticks [5,15], whereas the prototype Powassan virus lineage has never been detected in I. scapularis ticks [7,16–18]. In a recent field, investigation conducted between 2007 and 2012 and involving more than 6100 I. scapularis ticks and 189 additional ticks from 6 other species collected throughout the Lower Hudson Valley, DTV was detected exclusively in I. scapularis ticks, whereas prototype Powassan virus was not found in any tick tested including the 99 I. cookei ticks evaluated [5]. This study also demonstrated that the prevalence of DTV infection in I. scapularis ticks was not uniform across the Lyme disease endemic areas studied, implying that the risk of DTV infection following an I. scapularis tick bite is dependent on where the tick was encountered, with a very low risk likely in many geographic areas currently.

Public health implications & prevention

Most tick bites in Lyme disease endemic areas in the USA are from I. scapularis ticks, far exceeding the frequency of I. cookei tick bites. Thus, people living in areas where I. scapularis ticks are infected with DTV are at risk for DTV infections, including neuroinvasive disease. In addition, DTV virus appears to be much more rapidly transmitted after tick attachment than other I. scapularis-transmitted infections. Experimentally, the duration of tick attachment required for transmission of DTV by I. scapularis in mammals has been estimated to be only 15 min [18]. Thus, although removal of infected I. scapularis ticks within 36 h typically results in minimal risk of Lyme disease, this might not be true for DTV virus infections.

Fatality rates in small case series of patients with Powassan virus encephalitis have been in the range of 10–36% [9,17]. A high proportion of patients who survive an episode of Powassan virus encephalitis are left with severe neurological sequelae [9,17], not infrequently requiring mechanical ventilation, gastric feeding tube placement and specialized care in long-term facilities. There is no vaccine or effective therapy for Powassan virus encephalitis. The aforementioned study of 14 cases of Powassan virus encephalitis from New York State raised the question of whether systemic corticosteroids might be beneficial in reducing mortality [9], an observation that may warrant further investigation.

Recommendations to potentially reduce the risk of Powassan virus encephalitis include the application of rigorous environmental control measures to decrease tick abundance and to limit the presence of wild mammals nesting near homes. Standard tick bite prevention strategies such as the use of insect repellents on exposed skin, reducing the amount of exposed skin by wearing appropriate clothing, bathing within 2 h of tick exposure and frequent tick checks are likely to be helpful.

Despite being discovered more than 50 years ago, many of the biological, epidemiological and clinical aspects of Powassan virus encephalitis remain to be defined. Evidence suggests the emergence of the DTV subtype as a cause of human infections associated with exposure to I. scapularis ticks.

Financial & competing interests disclosure

GP Wormser discloses research grants from CDC, NIH, Immunetics, Inc., BioRad, DiaSorin, Inc. and BioMerieux; equity in Abbott; expert witness in malpractice cases involving Lyme borreliosis; unpaid board member American Lyme Disease Foundation; expert witness regarding Lyme disease in a disciplinary action for the Missouri Board of Registration for the Healing Arts; consultant to Baxter regarding Lyme vaccines. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.