Hantaan orthohantavirus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Hantaan orthohantavirus

Agent type

Virus

Taxonomy

Family

Hantaviridae

Genus

Orthohantavirus

Species

Hantaan orthohantavirus

Synonym or cross-reference

Old world Hantavirus, Hantaan orthohantavirus (HTNV)^{Footnote 1Footnote 2}, hemorrhagic fever with renal syndrome (HFRS), Korean hemorrhagic fever, epidemic hemorrhagic fever^{Footnote 3}.

Characteristics

Brief description

HTNV have a monopartite, trisegmented, negative-sense RNA genome^{Footnote 1Footnote 4}. Large, medium, and small genome segments are approximately 6.5 kb, 3.6 kb, and 1.7 kb, respectively^{Footnote 5}. The virus is pleomorphic, enveloped and measures approximately 100nm in diameter^{Footnote 1Footnote 4}.

Properties

HFRS is primarily found in Asia and Europe^{Footnote 3Footnote 6Footnote 7}. Species of the genus Orthohantavirus that cause HFRS include Puumala orthohantavirus and Seoul orthohantavirus, which typically cause a mild form of disease, and Dobrava-Belgrade orthohantavirus and HTNV, which can cause severe disease^{Footnote 6}.

Section II – Hazard identification

Pathogenicity and toxicity

HFRS caused by HTNV can present as mild to severe in patients with a mortality rate of less than 1% or 5-15%, respectively^{Footnote 8}. The disease is classically divided into 4 phases, although mild cases do not display the full spectrum of clinical manifestations^{Footnote 8}. Phase 1: the febrile phase lasts 3–7 days and patients show symptoms such as high fever, chills, thirst, headache, blurred vision, malaise, and anorexia, followed by abdominal pain, gastrointestinal symptoms, flushing of the face/neck, conjunctival injection, and an erythematous rash^{Footnote 6Footnote 9}. Increased capillary permeability is generalized and typically results in retroperitoneal edema and back pain^{Footnote 9}. Hemorrhage (e.g., petechiae, epistaxis) may occur late in the febrile phase^{Footnote 9}. Phase 2: the hypotensive phase lasts from 4-24 hours^{Footnote 8}, and is characterized by defervescence to a low-grade fever, nausea, vomiting, decrease in urine volume, and sudden onset of hypotension, which may progress to shock^{Footnote 9}. Phase 3: the oliguric phase lasts 2-14 days and blood pressure may return to normal or become high, urinary output falls dramatically, and severe hemorrhage (e.g., hemoptysis, gastrointestinal bleeding, hematuria) may occur^{Footnote 8Footnote 9Footnote 10}. Phase 4: the polyuric phase leads to convalescence^{Footnote 11Footnote 12Footnote 13}. Cases caused by European variants of HTNV are often milder than those caused by Asian variants^{Footnote 12}. In the Republic of Korea, 30% of patients show mild clinical symptoms without hemorrhagic manifestations, 50% show a moderate form of the disease, and 20% have the severe form of the disease^{Footnote 12}.

Although rodents, such as the striped field mouse (Apodemus agrarius) are reservoirs, there are no reported signs of clinical symptoms in animals^{Footnote 14Footnote 15}.

Epidemiology

HTNV is maintained in the rodent population in Korea, China, Malaysia, and eastern Russia^{Footnote 3Footnote 7Footnote 15Footnote 16}. HTNV was originally found in Korea and occurs mainly in rural areas^{Footnote 7Footnote 15}. Approximately 30,000 HFRS cases occur worldwide each year, and more than 90% of these occur in China^{Footnote 17Footnote 18}. Vaccination programs were implemented in Korea in 1990, and in China in 2008^{Footnote 18}. Since vaccination campaign implementation, HFRS cases in China have dropped significantly^{Footnote 18}. Cases follow a seasonal distribution pattern, with the majority of cases occurring with increased agricultural activity or increase in rainfall^{Footnote 19}.

Host range

Natural host(s)

Humans, and several species of rodents, including A. grarius^{Footnote 16Footnote 20}.

Other host(s)

Closely related serotypes of Hantaan virus have been found at low levels in bat populations^{Footnote 21}.

Infectious dose

Unknown.

Incubation period

Typically 2 to 4 weeks, however it can range from a few days to 42 days^{Footnote 9Footnote 12}.

Communicability

HTNV is primarily transmitted through inhalation of aerosolized droplets of urine, respiratory secretions, and/or saliva of infected rodents, or by inhalation of aerosolized particles of feces from infected rodents^{Footnote 4}. Secondary spread of infection does not occur^{Footnote 4Footnote 22}; however, there has been a single recorded case of vertical transmission^{Footnote 12}. Transmission through rodent bites, ingestion of contaminated food or water, and direct contact of cutaneous injuries or mucous membranes with the infectious virus may be possible; however, this has not been confirmed^{Footnote 23Footnote 24}.

Intraspecific transmission of HTNV has been demonstrated experimentally in A. agrarius^{Footnote 15}.

Section III – Dissemination

Reservoir

Rodent populations, mainly the striped field mouse (Apodemus agrarius); bats are a possible reservoir^{Footnote 2Footnote 21Footnote 25}.

Zoonosis

HTNV is transmitted from rodents to humans^{Footnote 19Footnote 24}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Clinical studies with HFRS patients in China and Korea found that ribavirin treatment reduced patient morbidity and mortality^{Footnote 9Footnote 26Footnote 27}.

Susceptibility to disinfectants

Unknown for HTNV. Other Orthohantavirus species have been shown to be susceptible to 1% solution of sodium hypochlorite, 1-5% Clidox^® (chlorine dioxide), 1-5% Dettol^® (parachlorometaxylenol), 1-5% Halamid-d^® (sodium-p-toluene-sulfonchloramide), 1-5% peracetic acid, or Virkon^® with a 10 minute contact time^{Footnote 28}. Inactivation was also achieved using absolute methanol with a 10 minute contact time and 70% ethanol with a 30 minute contact time^{Footnote 28}.

Physical inactivation

Unknown for HTNV. Other Orthohantavirus species are inactivated by heat (15 minutes at 56ºC for viruses in cell culture medium, and 2 hours at 56°C for dried viruses)^{Footnote 29}.

Survival outside host

Under wet conditions at 20ºC and 4ºC, HTNV remained infectious for 9 days and 96 days, respectively^{Footnote 30}. Dried HTNV was infectious for less than 24 hours at room temperature^{Footnote 30}. Other Orthohantavirus species can survive for 12-15 days in contaminated beddings, 5-11 days at room temperature in cell culture supernatants, and 18 days at 4ºC in cell culture supernatants^{Footnote 29}.

Section V – First aid/medical

Surveillance

Surveillance is done through the monitoring of clinical symptoms. Diagnosis is based mainly on serological tests to detect Hantavirus specific IgM, IgG, and neutralizing antibodies against the N protein or glycoproteins. Many different serological methods can be used, including immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), hemagglutination-inhibition assay, and complement fixation tests^{Footnote 4Footnote 7}. HTNV RNA in clinical samples such as blood, serum, or tissues may also be detected using reverse transcriptase PCR (RT-PCR) and sequencing^{Footnote 4Footnote 7Footnote 23}.

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.

First aid/treatment

Treatment is supportive to ensure the patient does not become dehydrated, with careful monitoring of the renal system^{Footnote 8Footnote 12Footnote 31}. Clinical studies with HFRS patients in China and Korea found that ribavirin treatment reduced patient morbidity and mortality^{Footnote 9}.

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 Canadian Biosafety Handbook.

Immunization

Hantavax^® (Green Cross Corporation, Yongin, ROK) is an inactivated HTNV vaccine that became available commercially in Korea in 1990^{Footnote 32}, but provides limited long-lasting protection^{Footnote 33Footnote 34}. In China, bivalent inactivated vaccines against HTNV were approved by the Pharmacopoeia of China in 2005^{Footnote 18}. There are no vaccines against HTNV approved for use in Canada, the United States, or Europe.

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

Prophylaxis

None.

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

Section VI – Laboratory hazard

Laboratory-acquired infections

A total of 226 cases (no deaths) of HTNV infection have been reported in laboratory settings, with the majority coinciding with initial isolation of HTNV and study in infected rodents^{Footnote 35Footnote 36}.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Infected bedding, fomites, urine, respiratory secretions, and feces^{Footnote 1Footnote 36}.

Primary hazards

Inhalation of airborne or aerosolized infectious material^{Footnote 1Footnote 36}.

Special hazards

Working with laboratory animals (exposure to animal excreta, fresh necroscopy material, and animal bedding)^{Footnote 24}, and performing laboratory operations that may create aerosols (e.g., centrifugation, vortex-mixing)^{Footnote 37}.

Section VII – Exposure controls/personal protection

Risk group classification

Hantaan orthohantavirus is a Risk Group (RG) 3 Human Pathogen, a Risk Group 3 Animal Pathogen, and a Security Sensitive Biological Agent (SSBA)^{Footnote 38}.

Containment requirements

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

Note: 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 Canadian Biosafety Standard 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. Due to the high risk of inhalation of infected materials, respirators to be used when working with cages.

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

For Containment Level 3: 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.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, 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 (Canadian Biosafety Handbook).

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 (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 3 requirements for storage outlined in the Canadian Biosafety Standard 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.

SSBA: 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 RG4 pathogens, and SSBA toxins 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 HTNV require a Human Pathogens 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 Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

2022

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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