Modes of Transmission and Clinical Manifestations of Monkeypox Virus

The recent re-emergence of Monkeypox in nonendemic countries poses a significant public health concern. ¹ In fact, as of June 8, 2022, the Centers for Disease Control and Prevention (CDC) has reported 1200 confirmed cases across 29 countries including the United States and Canada. ²

Monkeypox is a double-stranded DNA virus, that belongs to the Orthopoxvirus genus in the Poxviridae family. ¹ Among the different types of orthopoxvirus, four species are pathogenic for humans: monkeypox virus, variola major virus (smallpox virus, eradicated in 1980 by vaccination program), variola minor virus and cowpox. ³ Two genetic clades of monkeypox virus have been determined through genomic sequencing: Central African (Congo Basin clade), thought to cause more severe illness, and documented human-to-human transmission, ³ West African, thought to cause mild illness, and no human-to-human transmission. ³

Given the zoonotic nature of the disease, ¹ modes of transmission include animal-to-human and human-to-human. ¹ Though the natural reservoir of monkeypox virus has yet to be elucidated, several animals including squirrels, rats and monkeys are thought to transmit disease to humans by direct contact with blood, fluids and epidermal/mucosal lesions. ³ Human-to-human transmission may occur by direct contact (bodily fluids, respiratory secretions, skin lesions, contaminated surfaces), respiratory droplets (during prolonged contact), and in-utero. ^1,2

The incubation period varies between 6 to 13 days and can go up to 21 days ¹ . It usually presents with a non-specific prodrome which may go unnoticed ⁴ or can present as fever, myalgia, back pain, asthenia, headaches, and lymphadenopathy. ^1,5 The skin eruption usually appears 1 to 3 days after the prodromal phase, first involving the oral mucosa. Then, it spreads centrifugally to the face, followed by the extremities, including the palms and soles. ⁵ The number of skin lesions varies from a few to thousands. ⁵ They are characterized as firm, range from 2 to 10 mm in size, and progress through different phases: macules, papules, vesicles, and pustules. ⁵ Up to 7 days after the formation of pustules, crusts form and desquamate over several weeks, after which patients are no longer considered infectious. ⁵

The cornea and conjunctiva can also be affected and lead to keratitis. ¹ Atypical presentations have been reported during the recent outbreaks, including genital, perianal lesions and proctitis. ⁴ Complications related to monkeypox may include pneumonia, encephalitis, sepsis, and permanent loss of vision by corneal scarring. ^1,5

While most patients have mild, self-limiting symptoms, some may develop severe disease and could benefit from pharmacological treatment. ¹ Tecovirimat is an antiviral initially used for smallpox, that has recently been approved for treatment of monkeypox. ¹ In addition, two vaccines are currently available for prevention: ACAM2000 (approved in 2007 for smallpox) and MVA-BN (approved in 2019 for smallpox and monkeypox), although their supply is still limited. ⁴

The global outbreaks of monkeypox virus have been increasing at an alarming rate. This resurgence may be attributed to the waning population immunity since discontinuing smallpox vaccination after its eradication. Clinicians should have a high index of suspicion upon examining individuals with characteristic skin lesions in order to promptly identify an ongoing infection and prevent transmission, and morbidity.