Aetiology
Infection in humans is caused by the zoonotic Macacine herpesvirus 1 (MHV-1), previously known as Cercopithecine herpesvirus 1.[14] The virus is commonly called the B virus, but is also known as herpes B, monkey B virus, herpesvirus simiae, and herpesvirus B. The virus is a member of the Alphaherpesvirus family (genus: Simplexvirus) and is closely related to the human herpes simplex virus (HSV). It is a large (approximately 160-180 nm), double-stranded DNA virus surrounded by an icosapentahedral capsid and a lipid-protein envelope.
The natural hosts for B virus are species of macaque monkeys (e.g., rhesus macaques, pig-tailed macaques, cynomolgus monkeys), a genus of Old World monkeys. Non-macaque monkeys (all New World monkeys and all other Old World monkeys) pose no risk for B virus infection. One noteworthy exception involves monkeys from other genera that have been housed together with macaques. One study described an outbreak of B virus infection in DeBrazza's monkeys (same family but distinct genus from macaques). Eight monkeys had been housed with lion-tailed macaques, but were separated by concrete walls. The means of transmission was not identified. All 8 monkeys were B virus positive by polymerase chain reaction (PCR) and serology; all of the animals developed symptoms consistent with herpesvirus infection, 3 of the 8 animals died.[15] Another study described B virus infection in a colony of brown capuchin monkeys that had been housed together with macaques.[16] B virus can cause fatal infections in capuchin monkeys, but in this instance 7 apparently healthy monkeys were confirmed by both serology and PCR to be asymptomatically infected with B virus. For non-macaque species that have had no contact with macaques, however, there is no risk of B virus exposure.
One species of macaque, the Barbary macaque (Macaca sylvanus), is native to North Africa (Algeria and Morocco) and Europe (Gibraltar), where it was introduced. The other 15 species of macaque are found in Asia. However, rhesus macaques are the most common non-human primates used in research around the world and thus are widely geographically disseminated via the research industry. Rhesus macaques now exist in free-living colonies introduced in the US and possibly other countries.[17] Macaques roam freely in a large number of temples, parks, and other settings in southern Asia, most notably in Indonesia, Nepal, and India. These monkeys have religious significance to Hindu worshippers and have adapted readily to living among humans. In recent years, some temples have been made into popular tourist attractions called monkey forests, where macaques are the main attraction. Local photographers make their living by coaxing macaques to climb onto visitors for souvenir pictures. The monkeys also frequent shopping areas, where tourists may be tempted to feed, pet, or tease the monkeys.
The virus may be present in body fluids or tissues (e.g., saliva, faeces, urine, or nervous tissue) of infected monkeys; it may also be found in cell cultures from infected monkeys.[3] There is a higher prevalence of shedding of B virus in infected primates that are stressed, breeding, immunosuppressed, or unwell.[4] Monkeys become infected via exposure of mucosa or broken skin to oral or genital secretions from other infected monkeys, or due to bites from other infected monkeys. Most infected monkeys are asymptomatic or have only mild symptoms; however, in some cases a disease similar to human HSV infection is seen (e.g., vesicular lesions on the tongue and lips, and sometimes on the skin).[1][3]
Of all the herpes simplex viruses identified in non-human primates, only B virus is known to be pathogenic for humans.[2] Infection in humans is usually caused by the bite or scratch from an infected macaque monkey, a percutaneous injury contaminated with macaque body fluids, or from mucosal contact with infected body fluid or tissue.[3]
Human infections have resulted from bites or injuries resulting in injection of B virus-containing body secretions from a macaque monkey, but also from mucous membranes or non-intact skin exposure to fluid without associated injury. Human infections have also resulted from injuries associated with laboratory exposure to B virus-infected cell lines, necropsy materials from macaque monkeys, sharp objects contaminated by macaque body fluids or tissues, and contact of non-intact skin with lesions from a B virus-infected person.[4][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Two cases of B virus infection were possibly associated with aerosols. Only one case of human-to-human transmission has been documented.[Figure caption and citation for the preceding image starts]: Rhesus monkey (Macaca mulatta)CDC/Dr Roger Broderson [Citation ends].
Pathophysiology
Following initial infection, the B virus replicates at the site of inoculation and then spreads along the peripheral nervous system to the spinal cord and brain. The virus can spread from cell to cell without contacting the extracellular environment. It can also spread between nerve ganglia by axonal transport.[2][36] The incubation period from confirmed exposure to onset of clinical symptoms ranges from a few days to 5 weeks, but symptoms generally appear between 1 to 3 weeks post-exposure.[2][4]
The virus rapidly enters the peripheral nervous system during the early stages of disease;[37] some patients develop initial tingling, itching, pain, or numbness at the site of infection. A vesicular rash may also develop at the site of infection. There have also been reports of lymphadenopathy close to the site of infection.[4]
Initial systemic symptoms are generally flu-like (e.g., fever, muscle aches, fatigue, or headache). Neurological symptoms (e.g., meningismus, confusion, diplopia, dysphagia, dizziness, dysarthria, cranial nerve palsies, or ataxia) usually develop as infection progresses to the central nervous system (CNS).[4] CNS symptoms may be gradual or abrupt in onset.[4] If the virus reaches the brainstem, the usual outcome is death.[37] Brainstem encephalomyelitis develops in the terminal stages of infection.
Based on the characteristics of other alphaherpesviruses, B virus is presumed to persist in the peripheral nervous system (usually the nerve ganglia) for the lifetime of the host. In at least two instances, symptomatic B virus infection has presented in a manner suggestive of recurrent disease.[18][38] The virus has not been found to be present at detectable levels in the blood or serum of infected hosts, but has been identified in other sites such as the buccal mucosa, saliva, genital fluids, or cerebrospinal fluid.
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