Mpox

Introduction

Mpox is a zoonotic orthopoxvirus infection with two major strains (clades): Central African (clade I, more virulent) and West African (clade II, less virulent).

Epidemiology and transmission (1, 2)

The World Health Organization has labeled mpox a Public Health Emergency of International Concern (PHEIC). In the 2022 mpox PHEIC, most cases were linked to clade IIb infections and carried a mortality rate < 0.1%.

In 2024, the WHO once again declared mpox a PHEIC but linked to clade I, which is associated with higher transmissibility and a case fatality rate up to 2.5% globally, with greater risk in susceptible groups, such as children.

In endemic Central and West African regions, primary transmission is zoonotic through contact with infected rodents or contaminated animal carcasses. Human-to-human transmission can occur via respiratory droplets, direct skin or mucosal contact, and fomites such as contaminated bedding, towels, and clothing. (3)

During the 2022 PHEIC, key features of mpox included localized lesions often in genital, oral, and periorificial sites with less severe systemic symptoms. Significant transmission through sexual contact, especially in men who have sex with men (MSM), was identified. Mpox clade IIb continues to circulate globally in low levels.

Severe disease risk is highest in infants, pregnant individuals, malnourished patients, and those with immunocompromise, including advanced HIV infection. Maternal-fetal transmission is reported with all subtypes of mpox.

Clinical features (4)

The prodromal phase lasts up to 5 days and is characterized by fever, chills, headache, myalgia, back pain, sore throat, profound malaise, and tender lymphadenopathy, which is a key distinguishing feature from varicella.

The exanthem historically appears 1–3 days after fever as discrete 2–5-mm erythematous macules, first on the face in >90% of cases, then on the dorsal hands and feet (including palms and soles), trunk, and mucosae (oral, genital, conjunctival). In cases of sexually transmitted mpox, lesions are more commonly localized to the anogenital sites, oral mucosae, and/or periorificial face and may be accompanied by proctitis.

Lesions evolve synchronously in each involved area through papular, vesicular, and pseudo-pustular stages, then crusting and desquamation, with all lesions on a given body site at the same developmental stage.

“Mpox pustules” are firm and deep-seated and do not easily express pus. These are suggestive of mpox, as they are rare in other infectious diseases.

A 2022 study found that most cases had <10 lesions localizing to the anogenital area (73%), trunk / arms / legs (55%), face (25%), or palms / soles (10%). (5)

Complications (4)

Dermal necrosis may occur in severe cases, progressing to small-area skin ulcers, developing secondary bacterial infection, and healing with permanent scarring. Other cutaneous complications include mpox whitlows on the fingers or pox-like depressed scars.

Serious systemic complications include keratitis and ocular infections which risk blindness, neurologic complications such as encephalitis and myelitis, myopericarditis, and pneumonia.

Diagnosis (6)

• Mpox is diagnosed through PCR of swabs taken from the surface, roof, or exudate of lesions, or from oropharyngeal mucosa, with additional sequencing for clade identification when indicated.

• Additional confirmatory tests include electron microscopy or viral culture, though they are rarely required.

Patient management and treatment

Most immunocompetent mpox patients will have self-limited disease that resolves over 2-4 weeks and can be managed with supportive care.

For severe disease or high-risk patients (children, pregnant, immunocompromised, extensive mucosal or ocular involvement), antiviral therapy is recommended, with tecovirimat as first-line where available, and cidofovir or brincidofovir as alternatives.

Isolation is recommended until all lesions have crusted, scabs have fallen off, and new intact epithelium has formed, as patients remain contagious throughout lesion evolution. Close contacts should be monitored for symptoms for 21 days after their last exposure, with prompt testing and isolation if rash or prodrome develop.

Prevention (7, 8)

Two vaccines may be used to prevent mpox, including JYNNEOS for the prevention of mpox and smallpox, and ACAM2000, a second-generation vaccine that contains a live vaccinia virus and is indicated for the prevention of smallpox.

Because ACAM2000 is a live virus vaccine, important contraindications and precautions must be considered including immunodeficiency or immunosuppression, history or presence of eczema / atopic dermatitis and other skin conditions resulting in a compromised skin barrier due to risk of eczema vaccinatum, cardiac disease, ocular disease treated with topical steroids, infants < 12 months of age, and pregnancy. Household contacts may also be at risk of vaccine-related infection in those receiving ACAM2000 if the vaccinated individual cannot isolate from household contacts who meet any of these criteria.

The mpox vaccine can be given as post-exposure prophylaxis and is most effective within 4 days of exposure.

For more resources, visit our Mpox Resource Center.