With recent outbreaks of the Monkeypox virus in Europe and the United States, interest in Monkeypox prevention and treatment has increased. Similar to Variola, the causative agent of smallpox, the Monkeypox virus belongs to the genus Orthopoxvirus. It is a large, complex, double-stranded DNA virus that can infect homo sapiens as well as non-human primates. In fact, it can infect a wide variety of mammalian species. Current evidence points to rodents as key reservoir hosts. Transmission occurs via saliva/respiratory excretions or contact with lesion exudate or crust material, either via contact with infected animals or person-to-person transmission. The secondary attack rate among unvaccinated contacts within households is about 9%, so it is much less transmissible than smallpox. Wearing a face mask and avoiding close contact can reduce the risk of transmission.
The incubation period is about 2 weeks (~7-17 days) and an initial febrile prodrome is followed by generalized headache and fatigue. A key distinguishing feature of monkeypox, when compared to smallpox and varicella-zoster, is the presence of lymphadenopathy in most patients (but not all). Fever usually declines up to 3 days after rash onset with subsequent development of lesions as first macular, then papular, then vesicular, and pustular. About 40% of patients develop complications such as bacterial skin infections, respiratory disorders, gastrointestinal disorders, and keratitis. The overall mortality rate is about 10%, up to 15% in unvaccinated children.
There are 2 distinct phylogenetic clades of Monkeypox viruses: the West Africa clade and the Congo Basin clade. The West Africa clade, endemic in West Africa, generally exhibits a less severe illness with a mortality rate of about 3-4%. The Congo Basin clade, which occurs in Central Africa, exhibits a more severe illness with a mortality rate of about 10-11%. Nextstrain.org is now tracking reported Monkeypox genome data. The recent outbreaks in Europe and the United States seem to be based on the West African clade.
The 2022 ACIP Guidelines for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses was recently published. There are currently 2 orthopoxvirus vaccines available: ACAM2000, which is a live replication-competent vaccinia virus, and Jynneos, which is a replication-deficient modified vaccinia Ankara.
CDC recommends preexposure vaccination for persons at risk for occupational exposure to orthopoxviruses, persons who administer ACAM2000 or care for patients with infection with replication-competent viruses.
ACAM2000 is approved for anyone over the age of 1 year, in the absence of contraindications, and Jynneos is approved for persons over the age of 18 years. While Jynneos is recommended as an alternative to ACAM2000, it's important to keep in mind contraindications to receipt of ACAM2000.
Full guideline text can be found here:
Treatment options for orthopoxviruses are limited. Acyclovir, ganciclovir, foscarnet, and HIV NRTIs and NNRTIs are inactive in vitro. Entecavir has in vitro activity, but there's limited evidence for its use for poxviruses. Cidofovir has in vitro activity and established animal data but it's limited to its severe toxicity profile with many black box warnings. Tecovirimat and brincidofovir are oral options that have recently been approved via FDA's Animal Rule for the treatment of smallpox and may be used for the treatment of monkeypox.
The choice between brincidofovir (dosed twice daily for 14 days) and tecovirimat (dosed once weekly for 2 doses) is based on many factors including tolerability, adherence, potential risks of carcinogenecity, teratogenecity, and infertility. Overall, tecovirimat seems to have an advantage over brincidofovir due to its apparently better safety profile (based on very limited evidence, primarily driven by animal studies).
More information can be found here:
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