Macacine alphaherpesvirus 1

Background

• Also known as macacine herpesvirus 1, macacine alphaherpesvirus 1, cercopithecine herpesvirus 1, CHV-1), herpes B virus, monkey B virus, herpesvirus simiae and herpesvirus B

History

• First described in 19331, named 'B' for the first patient's initial

Microbiology

• Double-stranded DNA virus
• Alphaherpesvirus, in the same family as HSV

Epidemiology

• 50 documented cases worldwide, in people who handle macaques or their lab samples

Pathophysiology

• Virus replicates locally at the site of inoculation, then spreads from peripheral nerves to spinal cord to brainstem to brain

Clinical Manifestations

• Typically via bite or scratch of macaque monkey
  • Asymptomatic or similar presentation to HSV in the monkey
  • Seroprevalence reaches 100% in some populations of macaques
• Incubation period 5 to 21 days (range 2 days to 5 weeks)
• Three clinical forms:
  • Flu-like illness followed by CNS symptoms
  • Local symptoms (itching, tingling, numbness, or pain) at the inoculation site, with or without vesicular rash and regional lymphadenopathy
  • Peripheral or central nervous system symptoms, with meningismus, vomiting, confusion, cranial nerve palsies
  • There has been a single case of reactivation 10 years after last macaque exposure2
• Eventually progresses to global encephalitis, seizures, paralysis, and respiratory failure
• Mortality 70-80% if untreated

Diagnosis

• Serology, with acute and convalescent (3 to 6 weeks) titres, looking for a 4-fold rise
  • Seroconversion may be delayed if on acyclovir, so should be repeated at 12 weeks
  • Done at NML or sent out to Georgia State University
• Viral culture is possible but not done routinely
• PCR is available for swab, tissue, blood, and CSF
  • Sent out to Georgia State University
  • In autopsy, send right and left trigeminal ganglia or the sacral dorsal root ganglia

Management

Initial management

• Local wound irrigation, flushing for 15 minutes
• Assess risk:
  • Source of exposure: must be a macaque, as there are no other known hosts. Captive macaques have up to 100% seropositivity, depending on age.
  • First aid: risk decreases with flushing for 15 minutes
  • Type of wound: risk is higher with deeper wounds (e.g. bites) and larger area, as well as with high-risk areas (head, neck, or torso)
• Consider sending wound swab and baseline serology
  • CDC recommends against routine swabbing
  • Contact the lab, especially if you will be sending PCR

Treatment of diagnosed infection

• Acyclovir 12.5 to 15 mg/kg IV q8h
• Alternative: ganciclovir 5 mg/kg IV q12h
• Duration at least 2 weeks and until resolution of symptoms and 2 negative cultures

Postexposure prophylaxis

• Recommended for everyone with skin or mucosal exposure to a captive macaque, and there was inadequate cleaning (deep puncture bites are assumed to not be adequately cleaned)
  • Should be started within hours
  • First-line treatment: valacyclovir 1 g po tid
  • Alternatives: acyclovir 800 mg po 5 times daily, or famciclovir 500 mg po 5 times daily
  • Continue for 2 weeks (some recommend up to 5 weeks, the longest known incubation period)