Powassan virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Powassan virus

Agent type

Virus

Taxonomy

Family

Flaviviridae

Genus

Orthoflavivirus

Species

Orthoflavivirus powassanense

Synonym or cross-reference

POWV, POW, Powassan encephalitis virus, deer tick virus, flavivirus Powassan^{Footnote 1 Footnote 2 Footnote 3 Footnote 4}.

Characteristics

Brief description

Powassan virus (POWV) is a spherical, enveloped virus, about 50 nm in diameter^{Footnote 5}. The linear, single-stranded, positive sense RNA genome is 10.8 kb in length, encoding for 10 proteins and has a G+C content of 52-55%^{Footnote 5 Footnote 6}.

Properties

Ticks that spread POWV usually rely on a three-host lifecycle lasting 2-3 years^{Footnote 7}. The first hosts are small rodents infected by larvae, the second hosts are other smaller mammals or birds infected by nymphs, and the final hosts are larger mammals and humans infected by adult ticks. Unlike other tick-borne diseases, transmission of POWV to animal and human hosts are completed very quickly (within 15 minutes)^{Footnote 8}. POWV invade tick salivary glands rapidly and persist for at least 120 days. Tick saliva is quickly transferred to the bite site on a host, with the saliva containing anti-inflammatory and immunosuppressive properties to facilitate infection^{Footnote 7 Footnote 8}. Macrophages and fibroblasts are early targets of infection that release cytokines and establish a pro-inflammatory environment, thereby facilitating further infection in the host^{Footnote 9 Footnote 10}.

Like other flaviviruses, POWV enters the host cell through receptor-mediated endocytosis and releases viral RNA into the cytoplasm^{Footnote 5}. The genome is translated into viral proteins and the virus further replicates in the host cytoplasm. Assembled mature virions are released through exocytosis to infect other cells.

Two lineages of POWV are recognized, POWV and deer tick virus (DTV), with different animal-tick cycles. However, both lineages have the same clinical manifestations and similar genetic composition. They can only be distinguished by genetic sequencing and therefore are often referred to together as POWV^{Footnote 10 Footnote 11}.

Section II – Hazard identification

Pathogenicity and toxicity

Majority of initial symptoms after the incubation period include flu-like symptoms such as fever, sore throat, drowsiness, headaches, muscle weakness, nausea, and disorientation. Symptoms last 1-7 days and are typically self-limiting^{Footnote 5 Footnote 10}. A maculopapular rash on the trunk and chest have been reported, although uncommon^{Footnote 7}. POWV can cause rare but severe neuroinvasive disease in humans with infection of neurons and astrocytes^{Footnote 9 Footnote 10}. Weeks after the prodromal period, untreated infection could lead to encephalitis, meningoencephalitis, and aseptic meningitis. This is characterized by vomiting, fever, respiratory distress, seizures, and loss of coordination, appearing in over 89% of recent cases^{Footnote 10 Footnote 11}. Febrile seizures are commonly reported in children^{Footnote 5}. Cases of hemorrhagic encephalitis^{Footnote 12}, ophthalmoplegia^{Footnote 13}, nystagmus^{Footnote 14}, and polio-like illness^{Footnote 15} due to POWV encephalitis have been reported. Years after initial infection, severe long-term neurologic sequelae of paralysis, hemiplegia, memory loss appear in over 50% of survivors^{Footnote 5 Footnote 10}. Long-term complications which can appear after years of infection include paralysis, hemiplegia, memory loss, cognitive deficits, and muscle wasting^{Footnote 5}. Case-fatality rates are estimated to be 10-15% for patients with neuroinvasive disease.

Rabbits experimentally infected with POWV demonstrated encephalitis and meningitis^{Footnote 16}. Horses experimentally infected demonstrated encephalomyelitis and brain necrosis.

Epidemiology

POWV is the only type of tick-borne encephalitis (TBE) flaviviruses that is found in North America^{Footnote 17}. The first POWV case was reported from the brain autopsy of a young boy in Powassan, Ontario in 1958^{Footnote 18}. Most human cases of POWV in North America are now found around the Great Lakes, northeastern USA, and eastern Canada, but infected ticks have been found across numerous regions of USA and Canada, including New Mexico, Colorado, California, British Columbia, Calgary, and Atlantic Canada^{Footnote 19 Footnote 20}. One outbreak of POWV was reported in Maine and Vermont from 1999-2001 with four cases reporting POWV encephalitis^{Footnote 21}. POWV is also endemic in East Russia, most likely spreading from eastern Canada, and was first reported in 1972^{Footnote 22}.

The number of infections were low before the 2000s, with only 27 cases reported in North America until 1998^{Footnote 11}. However, POWV infections have been emerging recently in the US due to increased numbers and geographic range of tick vectors (due to warm weather, changing rainfall patterns, and deforestation), higher urbanization, and increased arbovirus awareness and surveillance^{Footnote 3 Footnote 11}. Between 2004 and 2023, there were 322 reported cases in USA^{Footnote 23 Footnote 24}. Conversely, in Canada and Russia, there are less reported cases, with 22 cases reported as of 2018 in Canada and 18 cases reported as of 2020 in Russia^{Footnote 11 Footnote 25 Footnote 26}. However, the number of reported infections in Canada and Russia are not increasing as rapidly as in the US; for instance, 16 out of 18 cases were registered in Russia between 1979-1989, and in Canada, the highest number of cases reported per year was four^{Footnote 22 Footnote 27}. However, seroprevalence studies suggest that POWV infections may often be asymptomatic, and testing only occurs after neuroinvasive disease manifests^{Footnote 11}. Seroprevalence of POWV in the general population or hospital patients is found to be between 0-4%, however, there can sometimes be cross-reactivity in serological studies between POWV antigens and those of other flaviviruses^{Footnote 5 Footnote 19}.

Most infections occur in the late spring to early fall, when ticks are most active in feeding^{Footnote 10}. POWV is preferably found in a transmission cycle between I. marxi ticks and squirrels and I. cookei and groundhogs, while DTV is mostly found between I. scapularis and mice^{Footnote 11}. I. scapularis is a more aggressive and a less host-specific tick species, increasing the danger of DTV over POWV.

Risk factors of POWV infection include living in forested areas, conducting outdoor activities around the time of high tick activity, and contact with wild animals^{Footnote 5}. Males have higher seroprevalence than females and older age was associated with death^{Footnote 28}. Patients receiving rituximab therapy or other B-cell depleting monoclonal antibodies have experienced severe or prolonged arboviral disease^{Footnote 29}.

Host range

Natural host(s)

Small to medium-sized mammals such as squirrels^{Footnote 30}, groundhogs, skunks^{Footnote 31}, opossums^{Footnote 32}, foxes, mice, porcupines^{Footnote 33}, hamsters^{Footnote 34}, guinea pigs, raccoons^{Footnote 35}, hares^{Footnote 36}, deer^{Footnote 37}, voles^{Footnote 7}, coyotes^{Footnote 38} and birds^{Footnote 32}. Humans are dead-end hosts^{Footnote 11}.

Other host(s)

Monkeys^{Footnote 39}, rabbits^{Footnote 16}, and horses have been infected experimentally.

Infectious dose

In an experimental study of DTV-infected mice, clinical signs of disease were seen in mice inoculated with 10¹ to 10⁵ focus-forming units (FFU) of DTV^{Footnote 40}. Other Flaviviruses, specifically West Nile Virus, has an ID₅₀ of 0.5 plaque-forming units (PFU) in mosquitoes, and 0.66 PFUs in young chickens^{Footnote 41}.

Incubation period

In natural infection, the incubation period ranges from 1-5 weeks following exposure^{Footnote 5 Footnote 10}. However, in experimentally infected mice, the incubation period has been shown to be as short as 5 days following exposure^{Footnote 40}.

Communicability

The main route of infection is injection via the bite of a tick that has been infected by feeding on infected hosts^{Footnote 7 Footnote 10}. Human-to-human transmission can occur through blood transfusion and organ transplantation^{Footnote 42 Footnote 43}.

In animals, the route of infection is also mainly via infected tick bite^{Footnote 7 Footnote 11}. In some vector species such as H. longicornis, transstadial transmission of POWV from adult ticks to larvae and transovarial transmission from adults to eggs have been observed^{Footnote 44}.

Section III – Dissemination

Reservoir

Ticks and small to medium-sized forest mammals maintain the POWV transmission cycle such as mice^{Footnote 45}, squirrels^{Footnote 10}, chipmunks, groundhogs, skunks, voles^{Footnote 20}, and shrews. POWV is mostly found between I. marxi ticks and squirrels and I. cookei and groundhogs, while DTV is mostly found in I. scapularis and mice^{Footnote 11}.

Zoonosis

Indirect zoonosis of virus transfer between reservoir animals and humans via tick vectors^{Footnote 3}.

Vectors

Mainly Ixodes spp. Ticks^{Footnote 10}. I. scapularis is the primary vector on the US East Coast and I. cookei is the primary vector in the US Midwest and Canada^{Footnote 7}. Other species in North America include I. marxi, I. spinipalpus, Dermacentor andersoni, Ambylomma Americanum, and Dermacentor variabilis^{Footnote 7 Footnote 10 Footnote 34 Footnote 46}. In Russia, POWV is found in Hemaphysalis longicornis as the primary vector, but has been found in H. neumanni, H. concinna, H. japonica, D. silvarum and I. persulcatus^{Footnote 47}.

Section IV – Stability and viability

Drug susceptibility/resistance

None.

Susceptibility to disinfectants

Unknown for POWV, however, for other flaviviruses, susceptible to 60-80% ethyl alcohol, 60-95% isopropyl alcohol, 200-5000 ppm chlorine, 2-8% formaldehyde, >2% glutaraldehyde, 7% stabilized hydrogen peroxide, 0.55% ortho-phthaldehyde, 75-150 ppm iodine, 12-2250 ppm peracetic acid, phenolics, and quaternary ammonium compounds^{Footnote 48 Footnote 49}.

Physical inactivation

Flaviviruses are inactivated by heating at 56^oC for 30 minutes, 60^oC for 3 minutes, 365 nm UV-A exposure for 40 minutes combined with 10 µg/mL of 4'-aminomethyl-trioxsalen^{Footnote 50}, 10 megarad of gamma ray radiation^{Footnote 51}.

Survival outside host

Unknown. Other flaviviruses, such as West Nile Virus, can survive up to 72 hours at 4^oC in a solution containing 30-150 ppt NaCl^{Footnote 52}, and can survive in blood for 5 days in platelets, 33 days in red blood cells, and 44 days in frozen plasma^{Footnote 53}.

Section V – First aid/medical

Surveillance

Monitor for symptoms^{Footnote 5}. Imaging methods (e.g., CT scans or MRI scans) are used at first sign of clinical manifestation to rule out other neurological conditions^{Footnote 7}. POWV is mainly identified in serum samples using methods such as immunofluorescence antibody assay^{Footnote 7}, enzyme-linked immunosorbent assay (ELISA), microsphere-based immunoassay, and plaque reduction neutralization tests to confirm cases^{Footnote 54}. However, results take several weeks to complete^{Footnote 5}. Nucleic acid amplification methods such as RT-PCR are able to detect POWV in blood serum or cerebrospinal fluid during the first few days of clinical presentation, but have to be confirmed using sequencing or mass spectrometry^{Footnote 5 Footnote 55}. Metagenomic sequencing performed on cerebrospinal fluid can also rapidly diagnose POWV^{Footnote 14}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

No treatment is available for POWV. Patients demonstrating symptoms receive supportive treatment such as respiratory support, intravenous fluids, and measures to reduce cerebral edema^{Footnote 11}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine currently available.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

No known post-exposure prophylaxis.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

None reported.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents.

Sources/specimens

Cerebrospinal fluid^{Footnote 14}, brain tissue, blood, urine^{Footnote 56}, and ticks^{Footnote 32}.

Primary hazards

Bites of an infected tick and autoinoculation with infectious material are the primary hazards associated with exposure to POWV^{Footnote 7 Footnote 10 Footnote 42 Footnote 43}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

POWV is a Risk group 3 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 4}. POWV is a Security Sensitive Biological Agent (SSBA).

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS are to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must considered with work involving animals or large scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 57 Footnote 58}.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access. Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and SSBA in long-term storage, to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows for the detection of a missing or stolen sample in a timely manner

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with POWV require a Human Pathogen and Toxins licence issued by the Public Health Agency of Canada.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National notifiable disease (human)

Note: As of 2023, POWV is a notifiable disease in Quebec, Alberta, Newfoundland and Labrador, and Nova Scotia^{Footnote 59 Footnote 60 Footnote 61 Footnote 62}. In Ontario, it is considered a disease of public health significance^{Footnote 63}. It is also a nationally notifiable condition in the USA^{Footnote 28}.

Last file update

December, 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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