Monkeypox, now officially called mpox, was first identified in 1958 when captive monkeys at a research facility in Copenhagen, Denmark, broke out in pustular skin lesions. Despite the name, the virus didn’t originate in monkeys. Its true natural home is among small rodents and squirrels in the tropical rainforests of West and Central Africa, where it has circulated for centuries or longer before scientists gave it a name.
The 1958 Discovery in Danish Lab Monkeys
The story begins not in Africa but in a European laboratory. In 1958, crab-eating macaques that had been shipped from Singapore to an animal research facility in Copenhagen developed a nonfatal outbreak of pox-like skin lesions. Researchers isolated a previously unknown virus from the animals’ pustules by incubating samples in eggs. They called it “monkeypox virus” simply because monkeys were the first animals they found it in.
Those lab monkeys were never the virus’s natural host. They were incidental carriers, likely exposed somewhere along their transport chain. It took another 12 years before anyone realized the virus could also infect people.
The First Human Case in 1970
Monkeypox was recognized as a human disease in 1970 in the Democratic Republic of the Congo (DRC). The vast majority of documented human cases in the decades that followed occurred in the DRC as well, with over 1,000 cases reported per year across multiple provinces by the 2010s. For most of its history as a known human pathogen, mpox remained confined to rural, forested parts of Central and West Africa, spreading sporadically from animals to people and only rarely between humans.
The Real Hosts: African Rodents and Squirrels
The name “monkeypox” always was misleading. Monkeys, apes, and other primates can catch the virus, but they’re secondary hosts, not the source. The virus’s true reservoir almost certainly lives among small mammals native to African rainforests.
Researchers have detected the virus in a surprisingly wide range of wild animals: Gambian pouched rats, shrews, several species of squirrel, and various other rodents. The virus has been fully isolated and its genome sequenced from Thomas’s rope squirrel, a small tree-dwelling rodent found in the forests of the DRC, and from sooty mangabey monkeys in Côte d’Ivoire. A 2023 study comparing the geographic ranges of candidate species concluded that Thomas’s rope squirrel is the single most probable reservoir host, based on how closely its habitat overlaps with the areas where the virus circulates. Three other arboreal rodents and squirrels ranked close behind.
People in endemic regions typically catch the virus through hunting, trapping, or butchering wild animals. Direct contact with an infected animal’s skin lesions, bodily fluids, or waste can transmit it, as can bites and scratches.
Two Clades, Two Geographic Regions
Mpox virus comes in two major genetic lineages, called Clade I and Clade II, each rooted in a different part of Africa.
Clade I has historically circulated in Central Africa, particularly the DRC and surrounding countries. It was long considered the more dangerous strain, though recent data with better medical care show mortality rates of 2.5% or lower for the original Clade Ia, and less than 0.5% for the newer subclade Ib. Most deaths occur in people with weakened immune systems, including malnourished children.
Clade II circulates in West Africa. Clade IIa, the older West African lineage, has a mortality rate around 1% based on limited data, with no deaths recorded among travel-associated cases outside Africa. Clade IIb, the strain responsible for the 2022 global outbreak, has a mortality rate below 0.1%.
The 2022 Global Outbreak
For decades, mpox cases outside Africa were rare and almost always tied to travel from endemic regions. That changed dramatically in May 2022, when the United Kingdom recorded the first case of what became a worldwide outbreak. Within weeks, cases appeared across Europe, the Americas, and beyond. Denmark’s first case was linked to someone returning from the Canary Islands. The United Arab Emirates identified its first case in a traveler arriving from West Africa.
The 2022 outbreak was driven by Clade IIb and spread primarily through close skin-to-skin contact, including sexual contact. It marked the first time mpox had sustained widespread human-to-human transmission outside of Africa. More than 90,000 cases were eventually confirmed across dozens of countries.
Clade Ib and the 2024 Eastern Africa Surge
A newer chapter began in late 2023, when the eastern DRC reported a sharp rise in cases caused by a previously unrecognized strain called Clade Ib. This was notable for several reasons. Historically, Clade I outbreaks were small, rural, and driven by animal-to-human spillover with limited spread between people. Clade Ib broke that pattern, spreading primarily through sexual contact and sustaining ongoing human-to-human transmission.
By early 2025, Clade Ib had spread to countries that had never before reported mpox, including Kenya, Burundi, Rwanda, Uganda, Tanzania, Malawi, South Sudan, and Zambia. In Kenya’s outbreak, about 63% of confirmed cases were linked to sexual transmission, while roughly 10% spread through nonsexual household contact. Nearly all patients developed a generalized body rash, and about 69% had genital lesions. Meanwhile, a separate Clade II outbreak emerged in West Africa in 2025, with cases in Sierra Leone, Liberia, and neighboring countries linked to a summer uptick in U.S. cases.
A Relative of Smallpox
Mpox virus belongs to the Orthopoxvirus genus, the same family that includes variola (the virus behind smallpox), cowpox, and vaccinia (used in smallpox vaccines). All of these are large, double-stranded DNA viruses that produce skin lesions. The family connection is why smallpox vaccines offer some cross-protection against mpox. Unlike smallpox, which infected only humans, mpox virus has a broad host range, jumping between rodents, primates, and people.
Why It’s Now Called Mpox
In November 2022, the World Health Organization officially recommended replacing “monkeypox” with “mpox.” The original name, assigned in 1970, predated the WHO’s 2015 guidelines on disease naming, which call for avoiding geographic or animal references that could trigger stigma or harm to wildlife. During the 2022 outbreak, racist and stigmatizing language tied to the disease name was widely reported online and in communities. The new name was chosen for scientific appropriateness, ease of pronunciation across languages, and the absence of zoological or geographic references. Both terms will be used during a transition period, but mpox is now the standard in medical and public health communications.