Introduction:
Cercopithecine herpesvirus 1 is a zoonotic infection carried by most macaques (colloquially rhesus monkeys) without any sign of the disease. These nonhuman primates are used in biomedical research as they are genetically similar to humans. The infection with Cercopithecine herpesvirus 1 can cause fatal encephalomyelitis or severe neurologic impairment in humans. However, the incidence of this zoonotic virus in humans is extremely low.
Early initiation of antiretroviral therapy, according to the clinical signs and risk factors, can prevent severe disease or fatality. Only Cercopithecine herpesvirus 1 (B virus) is known to be pathogenic in humans of the thirty-five herpesvirus identified in non-human primates.
Around 40 zoonotic Cercopithecine herpesvirus 1 (B) infections have been identified. This number is comparatively low compared to the number of people who come in contact with these macaques.
How Was the Cercopithecine Herpesvirus 1 Discovered?
The first case of human Cercopithecine herpesvirus 1 infection was reported in 1932 when a researcher was bitten on the hand by a rhesus macaque (Macaca mulatta). Fifteen days later, he died of progressive encephalomyelitis. The samples obtained from the patient showed the same disease progression in rabbits.
The International Committee on the Taxonomy of Viruses named the virus Cercopithecine herpesvirus 1 derived from:
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Family: Herpesviridae.
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Subfamily: Alphaherpesvirinae.
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Genus: Simplex virus.
How Does Cercopithecine Herpesvirus 1 Affect Humans?
Most cases of this zoonotic infection have been related to direct contact with macaques, such as a scratch, bite, or mucosal contact with body fluid. Cases of human infection through indirect contact, such as injury from a needle puncture or cage scratch, have also been recorded. Only one case of human-to-human transfer has been recorded so far. The intubation period can range from a few days to several weeks, and the symptoms occur within one month of exposure. The development and progression of the disease depend on:
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The site of exposure.
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The amount of virus inoculated.
The general symptoms of the disease include:
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Fever.
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Muscle aches.
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Fatigue.
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Headache.
Other variable symptoms include:
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Lymphadenitis (inflammation of a lymph node).
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Lymphangitis (inflammation of a lymphatic vessel).
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Nausea and vomiting.
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Abdominal pain.
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Hiccups.
The virus may spread to the central nervous system and cause the following symptoms:
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Hyperesthesias (increased sensitivity to touch).
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Ataxia (lack of muscle coordination).
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Diplopia (double vision).
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Agitation (feeling of restlessness or anxiety).
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Ascending flaccid paralysis (progressive weakness and loss of muscle tone that starts in the legs and moves up the body).
The spread of the central nervous system is extremely dangerous and fatal, even if antiviral therapy and supportive care are given. Respiratory failure associated with ascending paralysis can often lead to death. The possibility of mild or asymptomatic infection has also been suggested.
In case of danger of exposure, the individuals should wear personal protective equipment (PPE) according to the level of exposure. This protection ensures that the virus does not enter the human host as most of their skin is covered. The exposed individual may take an antiviral medication directly after exposure, depending on the severity of the exposure. This is known as postexposure prophylaxis, which has proved to be effective in rabbits but did not show positive results in humans.
How Is the Cercopithecine Herpesvirus 1 Infection Detected?
Early diagnosis is extremely important in the case of Cercopithecine herpesvirus 1 infection to control the spread of human infection to the central nervous system. The extreme cross-reactivity of primate alphaherpesviruses has led to the development of diagnostic methods that can distinguish between herpes simplex virus (HSV) and Cercopithecine Herpesvirus 1 infection.
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Direct culture of this virus has been the most suitable method for the diagnosis of this infection. However, this method has a risk of exposure, and avoiding this risk requires a unique containment facility.
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Serologic methods can also be used to diagnose this virus. However, this method is used for retrospective analysis and not for therapeutic decisions that require rapid results.
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Polymerase chain reaction (PCR) methods have been recently implemented for the diagnosis of the virus. It allows direct demonstration of the virus without any risk of exposure to the virus.
What Is the Treatment of Cercopithecine Herpesvirus 1 Infection in Humans?
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An essential protocol that should be followed in case of viral exposure is thoroughly cleaning the wound or exposure site for at least fifteen minutes.
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The virus can enter the nerve endings within five minutes of exposure. Hence, it is necessary to clean the wound as early as possible to prevent infection.
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Sterile saline or running water should be used to clean the wound and wash away the virus.
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After the initial cleaning of the injury, immediate medical care should be provided. Antiviral therapy is successful if it is provided before the onset of neurological symptoms.
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The treatment should be performed under a physician trained to handle cases of Cercopithecine Herpesvirus 1 infection and exposure. Samples from the exposed person or the source animal are essential for serologic testing and virus culture.
Is There a Vaccine Available for Cercopithecine Herpesvirus 1 Infection?
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A vaccine against the infection caused by rhesus macaques was developed to reduce the transfer of the virus and reduce the prevalence of infection in the captive macaque community.
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In the 1960s, a formalin-inactivated vaccine was developed and tested in the Cercopithecine herpesvirus 1. This vaccine did produce an antibody response, but the antibody titers were low, and boosters every three months were required.
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The vaccinia and DNA vaccines have been developed that are likely to induce cellular immunity against Cercopithecine Herpesvirus 1 infection. As the clinical trials of herpes simplex virus (HSV) vaccines progress, the development of a vaccine against the macaques or humans at risk for exposure should be considered.
Conclusion:
Fatal human infection with Cercopithecine herpesvirus 1 is a constant problem as exposures occur commonly in humans while taking care of and using macaques in research programs. The death rate for Cercopithecine Herpesvirus 1 infection before the availability of antiviral therapy is more than 70 percent. Neurological problems are commonly recorded in patients who survive the infection.
Antiviral treatment may decrease the death rate, but early diagnosis and prompt therapy are essential in controlling the transmission of the virus in the central nervous system and limiting neurologic problems. In case of failure of exposure prevention, the time of injury or exposure decontamination procedures play an important role in determining the risk of this infection.
