Pathogen Safety Data Sheets: Infectious Substances – Cercopithecinae herpes virus 1 (CHV-1)

Pathogen Safety Data Sheet - Infectious Substances

Section I - Infectious Agent

Name: Cercopithecinae herpes virus 1 (CHV-1).

Synonym or Cross Reference: Herpes simiae virus, herpesvirus simiae, B virus, herpes B virus, herpes B, monkey B virus, W virus, monkey herpes infection, simian herpesvirus B infection, and B virus infection (1-12).

Characteristics: CHV-1 belongs to the subfamily Alphaherpesvirinae, genus Simplexvirus, and is closely related to herpes simplex virus-1 and -2 (3, 10). CHV-1 is the only non-human primate herpesvirus that has been shown to infect humans (2, 3, 7, 10).

CHV-1 is an enveloped icosapentahedral virion, measuring approximately 160 to 180 nm in diameter, and has a double-stranded DNA genome (2, 3).

Section II - Hazard Identification

Pathogenicity/Toxicity: After a brief incubation period, a localised vesicular eruption near the site of inoculation is accompanied by fever, myalgia, headache, and/or nausea (6, 7). The vesicular eruption is clinically and pathologically similar to that caused by herpes simplex virus (6, 7). Neurological symptoms follow 3 to 7 days later, including meningismus, nausea, vomiting, persistent headache, confusion, diplopia, dysphagia, dizziness, dysarthria, cranial nerve palsies, and ataxia (6).

Virus spread to the central nervous system is an ominous sign, since, even with antiviral therapy and supportive care, most patients die. Deaths are often attributed to respiratory failure associated with ascending paralysis (3).

The mortality rate is over 70% in untreated individuals, and neurological sequelae are common in those who survive (3, 4, 7, 10).

Epidemiology: Human infection with CHV-1 is rare, and around 40 to 50 cases have been described worldwide (3, 5, 6, 10). The first human case of CHV-1 was reported in a laboratory researcher in 1932, who was bitten on the finger by an apparently healthy rhesus macaque and died of progressive encephalomyelitis 15 days later (3, 9, 11).

Host Range: Humans, monkeys of the genus Macaca, including the stumptail macaque (M. artoides), pig-tailed macaque (M. nemestrina), Japanese macaque (M. fuscata), bonnet macaque (M. radiate), and Taiwan macaque (M. cyclopis) (1-3, 7-12).

Experimental hosts include rabbits, dogs, mice and guinea pigs (2).

Infectious Dose: Unknown.

Modes of Transmission: Humans are infected in most cases by monkey bites, but transmission has also occurred following direct inoculation of the eye or respiratory tract with the bodily fluids of CHV-1 infected monkeys (1, 2, 5-7, 10). Direct contamination of a pre-existing wound with CHV-1 infected monkey saliva is a less common mode of transmission (2). Indirect contact, such as injury from a contaminated fomite (e.g. needlestick injury, cuts from broken tissue culture bottles containing infected monkey cells, or cage scratch), has also resulted in human infection (2, 3).

Incubation Period: Reported range is 2 days to 5 weeks, although most cases fall into a range of 5 to 21 days (3, 6, 7).

Communicability: Person-to-person transmission from intimate contact with vesicular lesions has been documented in a single case (1-3, 5, 7, 10).

Section III - Dissemination

Reservoir: The rhesus macaque (M. mulatta) and the long-tailed macaque (M. fascicularis) are the main natural reservoirs (1, 3, 5).

Zoonosis: Yes, through direct or indirect contact with the bodily fluids of CHV-1 infected monkeys (1, 3, 5, 7, 10).

Vectors: None.

Section IV – Stability and Viability

Drug Susceptibility: CHV-1 is susceptible to the antiviral drugs acyclovir, valacyclovir, and famciclovir (6).

Susceptibility to Disinfectants: CHV-1 is susceptible to fresh 0.25% hypochlorite solution, povidone-iodine, and chlorhexidine (4, 6).

Physical Inactivation: Like all other enveloped viruses, it is likely that exposure to ultraviolet light and heat (56°C for at least 30 minutes) will inactivate CHV-1 (2).

Survival Outside Host: Storage of CHV-1 in tissue culture medium (pH 7.2, 4°C) was shown to result in a slight loss in viability after 8 weeks (12). A single episode of freezing at either -20°C or -72°C resulted in an initial loss of 2 logs of infectivity of tissue culture medium stored specimens (12). All infectivity of CHV-1 is lost after storage in tissue culture media at 40°C for 2 weeks (12).

Section V – First Aid / Medical

Surveillance: Methods of detection of CHV-1 in suspected cases include viral culture of the agent from swab specimens, cerebrospinal fluid, and punch-biopsied material from possible sites of infection (bites and scratch wounds), PCR, ELISA, Western blot and PCR-microplate hybridisation assay (1, 2, 6, 8). Due to significant cross-reactivity with herpes simplex virus -1 and -2, serological testing is of human sera is of limited diagnostic merit (13). MRI, CT and EEG of the brain can also be used to detect the neurological signs of CHV-1 infection (6).

Note: All diagnostic methods are not necessarily available in all countries.

First Aid/Treatment: All bites and scratches should be immediately cleaned with soap or detergent for at least 20 minutes, and eyes and mucous membranes should be vigorously rinsed with sterile saline (1, 3, 4, 7). In addition to soap or detergent, povidone-iodine and chlorhexidine are recommended (4, 6). The time spent scrubbing or soaking the wound (15 to 20 minutes) is much more important for limiting/preventing transmission, than the type of solution used (4). Antiviral therapy is administered if the individual is thought to be at risk (3, 4, 6).

Immunization: None.

Prophylaxis: Yes, individuals thought to be at high risk for infection following a bite, laceration, or puncture wound when working with infected neural tissue are administered antivirals (4, 6). Prophylaxis is started as soon as possible after exposure (within hours), but only after wound cleaning has been completed (6). Three orally administered agents are currently available for postexposure prophylaxis of CHV-1 infection: acyclovir, valacyclovir, and famciclovir. The drug of choice is valacyclovir (6).

Section VI - Laboratory Hazards

Laboratory-Acquired Infections: Virtually all known CHV-1 infections were laboratory acquired and of approximately 40 to 50 cases reported worldwide only 26 have been well documented (6). Of those 26, the majority were contracted from the bite of a CHV-1 infected monkey (6).

Sources/Specimens: Blood, saliva, conjunctival fluid, or urogenital secretions of infected macaques (4-6). Central nervous system tissues and cerebrospinal fluid of monkeys are also potentially infectious (6).

Primary Hazards: Bite or scratches from CHV-1 infected monkeys, exposure of broken skin or mucous membranes to infected secretions of monkeys, needlestick or sharps injuries when handling infected samples (2, 5-7, 10).

Special Hazards: Cell culture and autopsy materials derived from infected monkeys can present a potential hazard (2). Exposure to virus from the natural aerosols that surround monkeys is a possibility but is considered to be of unknown or low risk (4).

Section VII – Exposure Controls / Personal Protection

Risk Group Classification: Risk Group 4.

Containment Requirements: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and cultures.

Protective Clothing: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes (14).

Other Precautions: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. 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 should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings (14). Additional precautions should be considered with work involving animal activities.

Section VIII - Handling and Storage

Spills: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectants, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (14).

Disposal: Decontaminate all materials for disposal from the containment laboratory by steam sterilisation, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes (14).

Storage: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory (14).

Section IX – Regulatory and other Information

Regulatory Information: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

Updated: August 2010.

Prepared by: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©

Public Health Agency of Canada, 2010

Canada

References:

  1. Acha, P. N., & Szyfres, B. (2003). Zoonoses and Communicable Diseases Common to Man and Animals (3rd ed., ). Washington, D.C.: Pan American Health Organization.
  2. Weigler, B. J. (1992). Biology of B virus in macaque and human hosts: A review. Clinical Infectious Diseases, 14(2), 555-567.
  3. Huff, J. L., & Barry, P. A. (2003). B-virus (Cercopithecine herpesvirus 1) infection in humans and macaques: Potential for zoonotic disease. Emerging Infectious Diseases, 9(2), 246-250.
  4. Holmes, G. P., Chapman, L. E., Stewart, J. A., Straus, S. E., Hilliard, J. K., Davenport, D. S., Kalter, S. S., Brown, D., Adams, S. R., Anderson, D. C., Balk, M., Broderson, J. R., Brown, B., Brown, N. A., Dillehay, D., Else, J., Freeman, D., Freifeld, A., & Heberling, R. L. (1995). Guidelines for the prevention and treatment of B-virus infections in exposed persons. Clinical Infectious Diseases, 20(2), 421-439.
  5. Cercopithecine herpesvirus 1 (B virus) infection resulting from ocular exposure. (2001). Applied Occupational and Environmental Hygiene, 16(1), 32-34.
  6. Cohen, J. I., Davenport, D. S., Stewart, J. A., Deitchman, S., Hilliard, J. K., & Chapman, L. E. (2002). Recommendations for prevention of and therapy for exposure to B virus (cercopithecine Herpesvirus 1). Clinical Infectious Diseases, 35(10), 1191-1203.
  7. Hudnall, S.D., and Stanberry, L.R. (2006). Human Herpesvirus Infections. In R. L. Guerrant (Ed.), Tropical Infectious Diseases: Principles, Pathogens, and Practice. (Elsevier Churchill Livingston ed., pp. 609-620) Philadelphia, PA.
  8. Oya, C., Ochiai, Y., Taniuchi, Y., Takano, T., Ueda, F., Yoshikawa, Y., & Hondo, R. (2004). Specific Detection and Identification of Herpes B Virus by a PCR-Microplate Hybridization Assay. Journal of Clinical Microbiology, 42(5), 1869-1874.
  9. . Gay, F. P., & Holden, M. (1933). The herpes encephalitis problem, II. J. Infect. Dis., 53, 287-303.
  10. krauss, H., Weber, A., Enders, B., Isenberg, H. D., Schiefer, H. D., Slenczka, W., Graevenitz, A. V., & Zaher, H. (2003). Viral zoonoses. Zoonoses: Infectious Diseases Transmissible from Animals to Humans (pp. 1-173, 146-149). Washington, D.C.: ASM Press pp.
  11. Sabin, A. B., & Wright, A. M. (1934). Acute ascending myelitis following a monkey bite, with isolation of a virus capable of reproducing the disease. J. Exp. Med., 59(2), 115-136.
  12. Krech, U., & Lewis L.J. (1954). Propagation of B-virus in tissue cultures. Proc. Soc. Exp. Biol., 87(1), 174-178.
  13. Balachandran, N., Oba, D. E., & Hutt-Fletcher, L. M. (1987). Antigenic cross-reactions among herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus. Journal of Virology, 61(4), 1125-1135.
  14. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.
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