Henipavirus hendraense: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Henipavirus hendraense

Agent type

Virus

Taxonomy

Family

Paramyxoviridae

Genus

Henipavirus

Species

Henipavirus hendraense

Synonym or cross-reference

Hendra henipavirus, HeV, or Hendra virus, was originally named equine morbillivirus and was first isolated in 1994 in Hendra, Australia^{Footnote 1Footnote 2}.

Characteristics

Brief description

HeV has a single-stranded, antisense, RNA genome that is approximately 18.2 kbp in length^{Footnote 1}. The genome has six genes that encode: nucleoprotein, phosphoprotein, matrix protein, fusion glycoprotein, attachment glycoprotein, and RNA-dependent RNA polymerase^{Footnote 1}. HeV is encapsulated by a membrane glycoprotein and being pleomorphic, can range in size from 40 to 600 nm^{Footnote 2}. HeV observed by electron microscopy has a herringbone nucleocapsid structure, and the surface projections on its viral envelope have a double-fringed appearance^{Footnote 2}.

Properties

HeV causes the formation of multinucleated syncytia in some infected cell types such as bronchiolar epithelium and endothelial cells^{Footnote 2Footnote 3}. HeV attachment protein uses receptors found in neurons, smooth muscle and arterial endothelial cells^{Footnote 4Footnote 5}. The HeV glycoprotein lacks hemagglutinin and neuraminidase activity^{Footnote 4}.

Section II – Hazard identification

Pathogenicity and toxicity

HeV causes severe and often fatal neurologic and/or respiratory disease in humans and horses. Symptoms in humans include fever, cough, fatigue, myalgia, headache, and vertigo^{Footnote 6}. The disease can progress to encephalitis (drowsiness, seizures, ataxia), which can be fatal^{Footnote 6Footnote 7Footnote 8}. Characteristics of HeV infection include generalized vasculitis and parenchymal cell infection in multiple organs (e.g., lung, kidney, CNS)^{Footnote 8}. There have been 7 cases of human disease caused by Hendra virus since it was discovered in 1994^{Footnote 6}. Four cases were fatal (57% mortality rate), and three patients recovered without relapse^{Footnote 6}. One of the patients had a fatal relapse manifested as acute encephalitis^{Footnote 6Footnote 7}.

Horses often show signs of acute respiratory illness and/or neurological illness; however, there have been reports of horses that seroconverted without any clinical signs of illness^{Footnote 4}. Symptoms of HeV infection include fever, rapid shallow breathing, ataxia, facial swelling, depression, frothing of saliva, and nasal discharge^{Footnote 2Footnote 9Footnote 10}. The disease progresses rapidly, often causing death 2-3 days after symptoms appear^{Footnote 2Footnote 9}. Some horses were found dead and had appeared normal the previous day^{Footnote 10}. HeV causes pneumonia and vasculitis in a wide range of tissues (e.g., lung, brain, lymphoid tissues, and kidney)^{Footnote 2Footnote 3}. The mortality rate in horses is estimated to be 75-80%^{Footnote 11}.

Dogs are rarely infected in nature, and show no overt clinical signs of infection^{Footnote 12}.

Epidemiology

Hendra virus is maintained in pteropid bat populations in Queensland and New South Wales, Australia^{Footnote 1Footnote 13Footnote 14}. There have been 52 separate incidents of human and equine disease caused by HeV in Australia from 1994 to 2015. In most outbreaks, only 1-2 animals were effected, however there is a 75-80% mortality rate in horses^{Footnote 6Footnote 7Footnote 11}. In total, 84 horses have died of HeV infection^{Footnote 15}. There have only been 7 human cases since 1994; 4 of which were fatal, with no human cases reported since 2009^{Footnote 13}. To date, there have been no reported cases in children^{Footnote 6}.

Proximity to flying fox roosts is a risk factor for HeV infection in horses^{Footnote 16}. Horses residing within 7 km of a flying-fox roost have a higher risk of HeV infection^{Footnote 16}. Reproduction and physiological stress are predisposing factors for HeV infection in flying foxes^{Footnote 17}.

Host range

Natural host(s)

Pteropid fruit bats, such as the flying fox, are the primary hosts. Horses, humans, and dogs (rarely) are intermediate hosts^{Footnote 6Footnote 12Footnote 18}.

Other host(s)

Experimentally infected hosts include ferrets, hamsters, African green monkeys, pigs, guinea pigs, and cats^{Footnote 19Footnote 20 Footnote 21Footnote 22Footnote 23Footnote 24Footnote 25}.

Infectious dose

Unknown.

Incubation period

This is 5 to 21 days in humans and 4 to 16 days in horses^{Footnote 3Footnote 6}. HeV is shed primarily in the urine of flying foxes, but is also found in nasal and oral secretions and feces^{Footnote 26Footnote 27}. Horses can shed HeV in nasal secretions 2 days post-exposure, prior to onset of symptoms^{Footnote 28}. No HeV shedding has been found in patients or horses in the post acute infection phase^{Footnote 29Footnote 30}.

Communicability

HeV transmission can occur between flying fox and flying foxes, flying fox and horses, horse and horses, and horse and humans. In flying fox populations, HeV is primarily transmitted via direct contact with infected flying foxes and HeV containing urine^{Footnote 31}. HeV is transmitted from flying foxes to horses via oro-nasal contact with flying fox urine or ingestion of material (e.g., grass or water) contaminated with urine^{Footnote 1Footnote 13}. Transplacental transmission has also been suggested based on experimental infection^{Footnote 17}. Horse to horse transmission is infrequent and appears to mainly occur via direct contact with a horse in the late stages of disease, when high levels of virus are shed; or via cross-contamination mediated by humans in contact with infected horses^{Footnote 13Footnote 29Footnote 32}. Horse to human transmission occurs via inhalation of infectious aerosols and exposure of non-intact skin to secretions from infected horses^{Footnote 6}. The infection rate for humans exposed to potentially infectious material from horses is approximately 10%^{Footnote 33}.

Section III – Dissemination

Reservoir

Flying foxes, also known as pteropid fruit bats, of genus Pteropus^{Footnote 14}. P. alecto is the major reservoir; but HeV has also been found in P. poliocephalus, P. scapulatus, and P. conspicillatus^{Footnote 27Footnote 34}.

Zoonosis

HeV is transmitted from horses to humans.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Ribavirin and chloroquine have antiviral activity in vitro, but have shown no clinical benefit^{Footnote 22Footnote 35Footnote 36}. 4′- azidocytidine (R1479) shows antiviral activity against HeV in vitro^{Footnote 37}, and LJ001 inhibited other enveloped single stranded RNA viruses in vitro^{Footnote 38}. HeV-specific monoclonal antibody (m102.4) has shown promising results against HeV infection in vivo^{Footnote 39 Footnote 40}.

Susceptibility to disinfectants

0.5% bleach solution is effective at inactivating viral hemorrhagic fever viruses that are also Security Sensitive Biological Agents (SSBAs)^{Footnote 41}.

Physical inactivation

HeV in phosphate buffered saline containing 0.5% Tween-20 and 0.5% Triton-X100 with heat inactivation at 56°C for 30 min^{Footnote 42}.

Survival outside host

HeV is sensitive to pH, temperature, and desiccation. Ideal conditions are a low pH and temperate environment^{Footnote 43}. Survival time outside the host ranges from hours to more than 4 days, and is highly dependent on environmental conditions^{Footnote 43Footnote 44}.

Section V – First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms. Diagnostic tests include viral culture, electron microscopy, and reverse-transcriptase PCR^{Footnote 4Footnote 6}. Nasopharyngeal aspirates or swabs, urine, blood, and cerebrospinal fluid can be analysed using reverse-transcriptase PCR assays^{Footnote 3Footnote 28Footnote 42Footnote 45}.

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

Treatment is largely supportive, through intravenous hydration and mechanical ventilation when indicated^{Footnote 4}.

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

Equivac^® HeV Vaccine for Horses (Zoetis Australia Pty Ltd) has been used in Australia since 2012^{Footnote 46Footnote 47}. Since HeV transmission to humans has only occurred via infected horses, this measure is expected to reduce risk of HeV transmission to people^{Footnote 3}. There is currently no licensed vaccine available for humans.

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

Prophylaxis

There is currently no licensed or readily available prophylactic treatment. A human monoclonal antibody (m102.4) is undergoing human clinical trials and has been administered to humans exposed to HeV under emergency use protocol^{Footnote 35Footnote 48Footnote 49}.

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

Of the 7 human cases of HeV infection reported to date, four occurred in veterinary workers who had close contact with secretions from infected horses and/or performed autopsies on infected horses^{Footnote 6}.

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

Sources/specimens

Hendra virus has been isolated from nasopharyngeal aspirates or swabs, urine, blood, faeces, cerebrospinal fluid, and various tissues from infected humans and animals (e.g., lung, kidney, lymph nodes)^{Footnote 2Footnote 3Footnote 26Footnote 29}.

Primary hazards

Primary hazards include direct contact with infected tissue or body fluids from infected individuals and animals, and inhalation of aerosolized infectious material^{Footnote 6}.

Special hazards

HeV-infected horses can be asymptomatic^{Footnote 4}; equine health care workers should take precautions to prevent exposure when HeV is suspected.

Section VII – Exposure controls/personal protection

Risk group classification

HeV is considered to be a Risk Group 4 (RG4) human pathogen and a RG4 animal pathogen^{Footnote 50Footnote 51}. HeV is a Security Sensitive Biological Agent (SSBA) and a non-indigenous animal pathogen under CFIA authority^{Footnote 51Footnote 52}.

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS are required 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 4 requirements for personal protective equipment and clothing outlined in the CBS to be followed. The use of a positive-pressure suit or use of a Class III biological safety cabinet (BSC) line is required for all work with RG4 pathogens.

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 regulated materials are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects to be strictly limited. Open wounds, cuts, scratches, and grazes are to be covered with waterproof dressings. Additional precautions must be considered with work involving animal activities.

Section VIII – Handling and storage

Spills

The spill area must be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. Spills of potentially contaminated material must be covered with absorbent paper-based material (e.g., paper towels), liberally covered with an effective disinfectant (e.g., 1% sodium hypochlorite), and left to soak for an appropriate amount of time (e.g., 10 minutes) before being wiped up. Following the removal of the initial material, the disinfection process must be repeated. Individuals performing this task must wear PPE, including particulate respirators (e.g., N95 or higher). Disposable gloves, impermeable gowns and protective eye wear are to be removed immediately after completion of the process, placed in an autoclave bag, and decontaminated prior to disposal (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated materials, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 4 requirements for storage outlined in the CBS are to be followed. Pathogens, toxins, and other regulated materials to be stored inside the containment zone.

Inventory of Risk Group 4 (RG4) pathogens in long-term storage to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated materials
• a means to allow 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 HeV require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada. HeV is a non-indigenous animal pathogen in Canada; therefore, its importation requires an import permit, issued by the Canadian Food Inspection Agency.

The following is a non-exhaustive list of applicable designations, regulations, or legislations for controlled activities with HeV:

• 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
• Immediately notifiable disease (animal)
• The Australia Group - List of human and animal pathogens and toxins for export control

Last file update

November, 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.

Copyright ^© Public Health Agency of Canada, 2023, Canada

References