Herpes B Virus Non-human primates Agent Information Sheet

Boston University
Research Occupational Health Program (ROHP)
617-358-7647

Agent

The primary infectious agent from non-human primates is Herpes B virus, or Cercopithecine herpesvirus 1 (CHV-1). CHV-1 belongs to the subfamily Alphaherpesvirinae, genus Simplex virus, and is closely related to herpes simplex virus-1 and -2. CHV-1 is the only non-human primate herpesvirus that has been shown to infect humans.

Disease/Infection

B virus infection can result in a fatal encephalomyelitis

Pathogenicity

In humans, B virus disease in humans is extremely rare, but often fatal.

The mortality rate is over 80% in untreated individuals, and neurological sequelae are common in those who survive. 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.

Biosafety Information

Risk Group/BSL
Risk Group 2
Biosafety Level 2

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.

Host Range/Reservoir
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).

Symptoms
Infection presents as a localized vesicular eruption near the site of inoculation is accompanied by fever, myalgia, headache, and/or nausea. The vesicular eruption is clinically and pathologically similar to that caused by herpes simplex virus. 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. Symptoms of clinical disease generally develop between 5 and 45 days of exposure, they are generally variable and inconsistent.

Incubation Period
Reported range is 2 days to 5 weeks, although most cases fall into a range of 5 to 21 days.

Viability                                                                                                                                                                                                                                                                                                                      Herpes B virus is presumed to survive on dry surfaces for 3 to 6 hours.  Herpes B virus is susceptible to fresh 0.25% hypochlorite solution, povidone-iodine, and chlorhexidine.

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. 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. All infectivity of CHV-1 is lost after storage in tissue culture media at 40°C for 2 weeks.

Information for Lab Workers

Laboratory PPE

Laboratory coat, gloves, eye protection or face shield must be worn when in contact with infectious materials, additional PPE can be recommended based on risk assessment.  The correct use of gloves, masks, and protective coats, gowns, aprons, or overalls is recommended for all personnel while working with non-human primates, especially macaques and other Old World species; this is inclusive for all persons entering animal rooms where non-human primates are housed.

Containment

Research should be conducted using Biosafety Level 2 practices, equipment, and facility design. Gloves and gowns should be worn when handling infected laboratory animals and when there is the likelihood of direct skin contact with infectious materials.  The correct use of gloves, masks, and protective coats, gowns, aprons, or overalls is recommended for all personnel while working with non-human primates, especially macaques and other Old World species; this is inclusive for all persons entering animal rooms where non-human primates are housed.Animal studies may be performed at ABSL-3. BSL-4 facilities are recommended for the propagation of viruses obtained from diagnostic samples or stocks. Experimental infections of macaques as well as small animal models with B virus are recommended to be restricted to ABSL-4 containment. BSL-3 practices are recommended for handling diagnostic materials with possible B virus. BSL-2 practices and facilities are suitable for all activities involving the use or manipulation of tissues, cells, blood, or serum from macaques with appropriate personal protective equipment.  BSL-2 practices, containment equipment, and facilities are recommended for activities using clinical materials and diagnostic quantities of infectious cultures.

In Case of Exposure/Disease

• For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…):
  • Medical Campus: call or have a coworker call the Control Center at 617-414–4144.
  • Charles River Campus: call or have a coworker call campus security at 617-353-2121.
    You will be referred to or transported to the appropriate health care location by the emergency response team.
• For lab exposures (needle sticks, bite, cut, scratch, splash, etc…) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7 hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
• Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
• Provide the wallet-size agent ID card to the physician.

Vaccination

There currently is no vaccine available for Herpes B

Information for First Responders/Medical Personnel

Public Health Issues

Person to person transmission is rare and has been reported in one case from intimate contact with vesicular lesions. Therefore, body fluids should be considered potentially infectious. Oral and genital secretions from persons who have been exposed to herpes B virus should be considered potentially infectious to others and proper barrier precautions should be used. If the incubation period for herpes B virus (generally 5 weeks in untreated persons) has passed and the person is asymptomatic and/or serologies are persistently negative (at least 12 weeks after exposure in patients given antiviral prophylaxis), then the likelihood of infection and virus transmission is exceedingly low. In patients with proven infection, private room should be used, with contact precautions along hand hygiene.

Diagnosis/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. Acute and covalence serum testing is available. MRI, CT and EEG of the brain can also be used to detect the neurological signs of CHV-1 infection.

First Aid/Post Exposure Prophylaxis

Perform one of the following actions:

For post exposure prophylaxis, 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. All macaques regardless of their origin should be considered potentially infected. Animals with no detectable antibody are not necessarily B virus-free. Macaques should be handled with strict barrier precaution protocols and injuries should be tended immediately according to the recommendations of the B Virus Working Group led by NIH and CDC.

Prophylaxis is started as soon as possible after exposure (within hours), but only after wound cleaning has been completed. 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. Three orally administered agents are currently available for post exposure prophylaxis of CHV-1 infection: acyclovir, valacyclovir, and famciclovir. The drug of choice is valacyclovir 1gram for 14 days.

Treatment

Intravenous antiviral therapy with acyclovir or ganciclovir is recommended until symptoms resolve and two cultures over 2 week period are negative. Treatment may be followed by long term suppressive therapy with oral antivirals.

References

CDC (Centers for Disease Control and Prevention). 1987. Guidelines for the Prevention of Herpesvirus simiae (B Virus) Infection in Monkey Handlers. Morbidity and Mortality Weekly Report (MMWR) 36 (41): 680-682, 687-689; October 23, 1987.

Cohen, Jeffrey I., et al. Recommendations for Prevention of and Therapy for Exposure to B Virus (Cercopithecinec Herpesvirus 1). Clinical Infectious Diseases 2002; 35:1191-1203.

CME Resource. Zoonotic Diseases. Prevention and Nursing Care. January 2001, Vol 73, No.2.

Holmes, et. al. Guidelines for the Prevention and Treatment of B-virus Infections in Exposed Persons. Clinical Infectious Diseases 1995; 20:421-439.

Cercopithecine herpesvirus 1 (B Virus) infection resulting from ocular exposure. NOISE, May 1999. Publication No. 99-100.   http://www.cdc.gov/niosh/docs/99-100/ Reviewed 11/27/02. Revised: 6/19/07, 7/08

Biosafety in Microbiological and Biomedical Laboratories 6^th edition

Mandell, G. L., J. E. Bennett, et al. (2010). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Philadelphia, PA, Churchill Livingstone/Elsevier.

“People at High Risk for Infection for Herpes B Virus.” Centers for Disease Control and Prevention, 31 Jan. 2019, www.cdc.gov/herpesbvirus/infection.html.

Revised: 7/18/23