Outbreaks of monkeypox infection have been reported in atypical areas and without travel links to endemic regions. While epidemiologic investigations are initiated and we learn more about these unusual clusters of infection, here’s what we know about monkeypox.

1. What is monkeypox?

Monkeypox virus is a member of the Orthopoxvirus genus in the family Poxviridae, which includes variola virus, the virus that causes smallpox and vaccinia virus, the virus used in one of the smallpox vaccines. Monkeypox is a zoonotic infection, but its wild animal reservoir is unknown.

There are two genetically distinct clades of monkeypox that vary epidemiologically and clinically. The Congo Basin strain is estimated to have a fatality rate of 10 percent. The West African strain (confirmed in the U.K. cases) has a fatality rate of about one percent.

2. Where did monkeypox come from?

Monkeypox was first identified in an outbreak of research monkeys (hence the name). The first human cases were reported in 1970 in the Democratic Republic of Congo, and since then, isolated outbreaks have occurred throughout central and West Africa. Few cases have been reported elsewhere and many have been associated with travel to Africa.

In 2003, dozens of suspected cases of monkeypox were reported to the United States CDC from six different states. Investigations revealed that all the cases had contact with newly acquired pet prairie dogs that had been imported from Africa. This outbreak was contained and no human-to-human spread of monkeypox was identified.

3. How does monkeypox spread?

Animal-to-human spread of monkeypox (i.e., spillover) occurs through a bite or scratch or contact with animal fluids such as in the preparation of wild game. Human-to-human spread occurs with contact with bodily fluids, including pus from lesions, and respiratory droplets. A patient is considered contagious from the onset of symptoms until lesions have healed, which may be a month or more.

While some current cases have occurred among people self-identifying as gay or bisexual, it is not clear if monkeypox is transmitted by sexual intercourse. It is possible that these clusters occurred due to prolonged close contact, exposure to lesion material, or contaminated clothing or bedding between individuals.

4. What are the clinical features of disease due to monkeypox infection?

Monkeypox has a rather long incubation period ranging from five to 21 days between infection and onset of symptoms. Early symptoms are nonspecific and include fever, fatigue, headache, and myalgia. Monkeypox infection also causes swelling of lymph nodes — a notable distinction from smallpox, though less clinically useful since smallpox has been eradicated.

This prodrome is followed by a progressive rash characterized by deep-seated and well-circumscribed lesions. The first lesions may be mucosal, commonly occurring on the tongue and in the mouth, followed by a macular rash on the face before spreading throughout the body. Over the course of a few weeks, lesions progress from macules to raised papules, they become vesicular then pustular, and ultimately crust and scab over before falling off.

Some of the cases described in 2022 have involved localized rashes in the genital and perianal region prompting confusion with common sexually transmitted infections. A high index of suspicion is warranted for anyone with a characteristic rash plus either travel history to an endemic area, close contact with someone with a similar appearing rash, or is a man who has sex with men.

All suspected cases should be reported to infection control personnel and healthcare workers caring for patients should follow standard contact and droplet precautions.

5. Is there a treatment or a vaccine for monkeypox?

There is no proven treatment for monkeypox infection, though a few antivirals have been tested. Cidofovir and brincidofovir have shown activity against poxviruses in in vitro and animal studies. Another drug, tecovirimat, is FDA-approved for treatment of smallpox.

A new vaccine called Jynneos was granted FDA approval in 2019 for the prevention of both smallpox and monkeypox, though real-world effectiveness is unknown. It is also thought that traditional smallpox vaccination with the closely related vaccinia virus is likely to provide some protection. Global smallpox vaccination programs ended in 1970’s with only rare, targeted vaccination of select individuals such as military personnel and researchers working with pox viruses since then. We learned from the 2003 outbreak in the U.S. that previous immunization with the smallpox vaccine was not completely protective. So, it’s not clear whether 50+ year old immunity would be sufficient.

While these monkeypox outbreaks do not pose a great threat to the general public, physicians should be on alert for its characteristic lesions, even in unusual body areas such as the genitals, and especially among men who have sex with men.