Causative Agent

DNA Herpesvirus. There are more than 35 herpesviruses of NHPs, most of which are not zoonotic. This disease has been described as one of the most feared infections of non-human primate handlers. First reported case of encephalitis caused by B virus in monkey handler was in 1932. Called B virus after the initials W.B. of the first patient. 23 additional cases described through 1973. Four cases including first known person to person transmission occurred in Pensacola, FL in 1987. Most of these cases resulted in encephalitis and 20 resulted in fatalities. In 1988, two confirmed cases occurred. Both were identified early and clinical signs were averted by administration of Acyclovir.

Reservoir and Incidence

The virus is enzootic in rhesus, cyno and other Asiatic monkeys of macaque genus. Baboons, Chimpanzees, and African Greens have also shown positive titers. Young monkeys can be infected by adult carriers as soon as they lose maternal antibody. One study found that 80 percent of adult monkeys in a closed colony had been infected. The virus has been isolated from trigeminal and lumbosacral ganglia in clinically normal sero-positive rhesus and cyno’s.

Transmission

Transmission of the virus is basically by direct contact. Transmission to man is thought to occur via bites, scratches, aerosols, or improper handling of contaminated monkey tissues. Virus has been isolated from saliva, blood, urine, feces, and kidney tissue cultures of infected monkeys. Most cases have occurred in people exposed to monkeys or monkey tissues. One case occurred by common use of an over-the-counter antibiotic ointment passing the virus from an infected individual to another person. An additional case occurred by self inoculation of a needle, after the needle had been use for blood collection. The virus has been isolated from animals that had no visible lesions. AN INFECTED MONKEY SHOULD BE CONSIDERED INFECTED FOR LIFE.

Disease in Non-human Primates

The animal may be completely asymptomatic. The virus may cause mild cold sore type lesions of mucous membranes, dorsum of the tongue, lips or face; similar to those caused by Herpes simplex in man. These usually heal spontaneously in 7 to 14 days. There may be mild conjunctivitis and nasal discharge are present. In some animals the disease may be severe and cause considerable discomfort as well as neurological signs and symptoms. The virus remains latent and may reactivate spontaneously or in ties of stress resulting in virus shedding. An animal should be considered to be infected for life. AN INFECTED ANIMAL CAN APPEAR NORMAL!

Disease in Humans

The disease has been characterized by a variety of symptoms which generally occur within a month of exposure. Symptoms have included vesicular skin lesions at or near the site of inoculation, localized neurological symptoms, ascending paralysis, and ultimately encephalitis. Death usually occurs three to 21 days after the appearance of clinical signs. A unique feature of the Pensacola cases was the occurrence of mild disease in two of four patients. Both of these received Acyclovir early in the course of the disease. They became culture negative and lesions resolved during therapy.

Since there is a high percentage of infection in monkeys yet relatively few human cases, risk of acquiring infection appears to be low. Possible reasons for this apparently low rate of transmission may include:

• Infrequent virus shedding by macaques.
• Cross reactive immunity stimulated by Herpes simplex infection or Herpes zoster (chicken pox).
• Undetected asymptomatic infection in man. The frequency of this has not yet been adequately assessed but antibody titers have been found in some monkey handlers showing no signs of disease.

In a retrospective study of 95 banked sera from monkey handlers at NIH, three percent were found to be sero-positive, with no history of a bite. NIH is currently conducting a prospective study of monkey handlers to determine incidence of antibody specific for Herpes B.

Diagnosis

Diagnosis is by histology, virus culture, and serology.

Treatment

Anti viral therapy with Acyclovir (9-[2-hydroxyethoxymethyl] guanine), both in vivo and in vitro efficacy against B-virus has been demonstrated. Hyperimmune human B-virus globulin or vaccine is not currently available. These are from the guidelines established by the B-Virus Working Group, June 1987:

• Macaques should be used for research only when clearly indicated.
• B virus – free animals should be used whenever possible and maintained under conditions to assure maintenance of this status.
• Direct handling of macaques should be minimized and appropriate restraint methods employed (i.e., squeeze cages, chemical restraint, pole and collar etc.).
• Protective clothing should be worn when working with macaques or macaque tissues (long sleeves, gloves, mask, goggles).
• Cages and equipment should be maintained free of sharp edges that could cause injuries.
• Access to areas where macaques are housed should be limited.
• Routine screening of animals for B virus is NOT recommended.
• Animals with lesions should be quarantined until lesions have healed.
• Education and training of personnel should be assured.
• An occupational medical service should be available.
  • Employee serum samples collected and banked annually.
  • All bite or scratch wounds should be immediately and thoroughly scrubbed with soap and water (or Modified Dakin’s solution: buffered sodium hypochlorite 0.5 percent) Refer for medical treatment if necessary.
  • All bite or scratch wounds should be reported, documented, and followed up for one month.

If you get bitten or scratched by a non-human primate or are working in non-human primate areas:

You need to follow the procedure that the Center for Comparative Medicine has developed in conjunction with EHS.