Macacine alphaherpesvirus 1: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Macacine alphaherpesvirus 1 (MaHV-1)

Agent type

Virus

Taxonomy

Family

Herpesviridae

Genus

Simplexvirus

Species

Macacine alphaherpesvirus 1

Synonym or cross-reference

Monkey B virus, BV ^{Footnote 1}, B-virus ^{Footnote 2Footnote 3}, Herpes virus B, simian immunodeficiency virus. Formerly Macacine herpesvirus, Herpesvirus simiae virus, or Cercopithecine herpesvirus 1 ^{Footnote 4Footnote 5Footnote 6}.

Characteristics

Brief description

MaHV-1 is a double-stranded DNA, enveloped, icosapentahedral virus. It measures approximately 160 to 180 nm in diameter^{Footnote 3Footnote 7}, and has a genome measuring approximately 147 kbp long^{Footnote 1}.

Properties

MaHV-1 has a biphasic lifecycle. Following clearance of primary infection, the virus remains latent in the host and may reactivate at a later time ^{Footnote 8}. Upon reactivation, the virus enters a lytic phase, in which viruses are actively produced. The virus is shed in saliva and/or genital secretions of infected hosts during periods of reactivation^{Footnote 8}.

Section II – Hazard identification

Pathogenicity and toxicity

MaHV-1 may present as a subclinical infection, or localised vesicular eruptions near the site of infection, accompanied by fever, myalgia, headache, and nausea^{Footnote 6Footnote 9}. Vesicular eruptions are clinically and pathologically similar to those caused by herpes simplex virus in humans^{Footnote 6Footnote 9}. Neurological symptoms follow within 3 to 7 days of symptom onset, and can include meningismus, nausea, vomiting, persistent headache, confusion, diplopia, dysphagia, dizziness, dysarthria, cranial nerve palsies, and ataxia^{Footnote 9}. The mortality rate in untreated individuals is 70-80%, and neurological sequelae are common in those who survive^{Footnote 3Footnote 6Footnote 10Footnote 11Footnote 12}.

Viral spread to the central nervous system increases the mortality rate to 80%, in treated and untreated individuals. Death is often attributed to respiratory failure associated with ascending paralysis^{Footnote 3}. Early detection and administration of antiviral drugs can reduce this rate to less than 20%^{Footnote 12}.

Epidemiology

Human infection with MaHV-1 in nature is rare. There have been about 50 cases reported worldwide, almost all involving laboratory staff^{Footnote 1Footnote 3Footnote 5Footnote 9Footnote 11}. The first human case of MaHV-1 was reported in 1932 in a laboratory researcher bitten by a seemingly healthy rhesus macaque. The researcher died of progressive encephalomyelitis 15 days later^{Footnote 3Footnote 13Footnote 14}.

There are no reported cases of zoonotic MaHV-1 infection following natural exposure to macaques, in high contact areas in Asia, where an estimated 72-92% are seropositive for MaHV-1-reactive antibodies^{Footnote 1Footnote 12}. MaHV-1 is enzootic in Asiatic monkeys of the genus Macaca (e.g., rhesus, cynomolgus)^{Footnote 10}.

Host range

Natural host(s)

Humans, monkeys of the genus Macaca, including rhesus monkeys (M. mulatta), cynomolgus monkeys (M. fascicularis), stump-tail (M. artoides), Japanese (M. fuscata), pig-tailed (M. nemestrina), bonnet (M. radiata), and Taiwan (M. cyclopis) macaques^{Footnote 3Footnote 4Footnote 6Footnote 7Footnote 11Footnote 13Footnote 14Footnote 15Footnote 16}.

Other host(s)

Rabbits, dogs, mice and guinea pigs have been experimentally infected^{Footnote 7}.

Infectious dose

Unknown.

Incubation period

Incubation period is approximately 2 to 35 days^{Footnote 3Footnote 9}. Most cases fall into the 5 to 21 day range.

Communicability

The most common infection route is direct inoculation with tissue or fluid from a monkey via monkey bite/scratch or cage scratch^{Footnote 7}. Laboratory acquired infections through injury from a contaminated fomite, such as needlestick and cuts from broken tissue culture bottles containing infected monkey cells, have also resulted in human infection^{Footnote 3Footnote 7}. Person-to-person transmission via intimate contact with vesicular lesions has been documented in a single case ^{Footnote 17}.

Section III – Dissemination

Reservoir

Two species of Macaques are the primary reservoirs of the virus: rhesus macaque (M. mulatta) and the cynomolgus macaque (M. fascicularis)^{Footnote 3Footnote 4Footnote 5}.

Zoonosis

MaHV-1 is transmitted from infected macaques to humans through direct contact (e.g., scratches or bites) or indirect contact, such as inoculation of the eyes or respiratory tract with the bodily fluids of infected monkeys^{Footnote 4Footnote 5Footnote 6Footnote 7Footnote 9Footnote 11}. Laboratory acquired infections also occur through injury from a contaminated fomite (e.g. needlestick injury, cuts from broken tissue culture bottles containing infected monkey cells, or cage scratch). Direct contamination of an injury site through MaHV-1 infected monkey saliva has also been reported^{Footnote 7}.

Human infections are rare in areas with high rates of direct contact with wild macaques^{Footnote 1Footnote 3Footnote 7Footnote 18}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Antiviral drugs, including acyclovir, valacyclovir, and famciclovir, may be used to treat MaHV-1 infections before onset of neurologic symptoms^{Footnote 9}.

Susceptibility to disinfectants

MaHV-1 is susceptible to 0.25% sodium hypochlorite, povidone-iodine, and chlorhexidine^{Footnote 9Footnote 10}. Most herpes viruses are also susceptible to quaternary ammonium compounds, ethanol and isopropanol ^{Footnote 19Footnote 20}.

Physical inactivation

Herpes viruses are inactivated by heat (56°C for at least 10 minutes), and pH less than 5 or greater than 11 ^{Footnote 21Footnote 22}.

Survival outside host

Storage of MaHV-1 in tissue culture medium was shown to result in no significant loss in viability after 8 weeks storage at 4°C^{Footnote 16}. A single episode of freeze/thaw at -20°C or -72°C resulted in an initial loss of 2 logs in infectivity titer of MaHV-1 in tissue culture medium, although no further loss was observed upon longer storage at freezing temperatures^{Footnote 16}. All infectivity of MaHV-1 is lost after storage in tissue culture media at 40°C for 2 weeks^{Footnote 16}.

Section V – First aid/medical

Surveillance

Viral culture for MaHV-1 prepared from swab specimens, cerebrospinal fluid, and punch-biopsied material can be analyzed using PCR, enzyme-linked immunosorbant assay (ELISA), Western blot and PCR-microplate hybridisation assay^{Footnote 4Footnote 7Footnote 9Footnote 15}. Magnetic resonance imaging (MRI), computerized tomography (CT) and electroencephalogram (EEG) brain scans can also be used to detect the neurological signs of MaHV-1 infection^{Footnote 9}.

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

All bites and scratches must be rapidly and thoroughly cleaned with detergent (e.g., povidone-iodine, chlorhexidine) for at least 20 minutes to inactivate and wash away virus present at the exposure site^{Footnote 9Footnote 10}. Eyes and mucous membranes must be vigorously rinsed with sterile saline^{Footnote 3Footnote 4Footnote 6Footnote 10}. Immediate and proper wound care is vital for limiting infection; however adhering to the 20 minutes cleaning timeframe is more important than the type of disinfectant used^{Footnote 10}. Prophylactic antiviral therapy is unnecessary in most cases, but can be administered after exposure if the individual is thought to be at high risk^{Footnote 3Footnote 9Footnote 10}.

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 is currently available.

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

Prophylaxis

Individuals thought to be at high risk for infection following a bite, laceration, or puncture wound when working with infected materials are administered antivirals. Three orally administered agents are currently available for post-exposure prophylaxis: acyclovir, valacyclovir, and famciclovir, with valacyclovir being the preferred drug^{Footnote 9}. Prophylaxis must be started as soon as possible after exposure and wound cleaning (i.e., within hours) due to the high neurovirulence^{Footnote 9}.

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

To date, almost all confirmed MaHV-1 infections were laboratory-acquired by persons working with captive monkeys; approximately 50 cases have been reported worldwide^{Footnote 9Footnote 18}. Most infections resulted from monkey bites and scratches, parenteral inoculation, cage scratch, and mucosal exposure to tissue or fluids from an infected monkey^{Footnote 9}.

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

Blood, saliva, conjunctival fluid, or urogenital secretions of infected macaques^{Footnote 5Footnote 9Footnote 10}. Central nervous system tissues and cerebrospinal fluid of monkeys are also potentially infectious.

Primary hazards

Bites or scratches from MaHV-1 infected monkeys, exposure of broken skin or mucous membranes to infected secretions of monkeys, needle stick or sharps injuries when handling infected samples^{Footnote 5Footnote 6Footnote 7Footnote 9Footnote 11}.

Special hazards

Cell culture and autopsy materials derived from infected monkeys can present a potential hazard^{Footnote 7}. Exposure to virus from the natural aerosols that surround monkeys is possible but is currently considered to be low risk ^{Footnote 23}.

Section VII – Exposure controls/personal protection

Risk group classification

Macacine alphaherpesvirus 1 is a Risk Group 4 (RG4) Human Pathogen and RG4 Animal Pathogen ^{Footnote 24Footnote 25}.

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 4 requirements for personal protective equipment and clothing outlined in the CBS are 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 are 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 is to be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. Spills of potentially contaminated material are to 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 is to 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 are to be stored inside the containment zone.

Inventory of RG4 pathogens in long-term storage to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated materials; and
• 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 MaHV-1 require a Human Pathogens and Toxins Licence issued by the Public Health Agency of Canada. MaHV-1 is a non-indigenous animal pathogen in Canada; therefore, importation of MaHV-1 requires an import permit, issued by the CFIA ^{Footnote 26}. 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

November, 2019

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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