Monkeypox (mpox) causes similar symptoms to smallpox, including fever, headaches, and lesions, and yet historically, humans only ever caught the virus from small mammals, like monkeys or rodents, not other humans.
Now, a study led by epidemiologist Áine O'Toole from the University of Edinburgh has found evidence of "sustained human transmission" outside the African countries with known mpox viral reservoirs.
The findings present a "fundamental shift" in how experts understand the spread of this virus, O'Toole and colleagues say. They also highlight the need for new public messaging around outbreak management and control.
Mpox was first identified by scientists in the 1950s when a curious illness struck a group of research monkeys in Denmark.
Later, in the 1970s, the first human case was officially reported in an infant in the Democratic Republic of the Congo.
For many decades, human-to-human transmission was a rare event. Most with human mpox were catching the virus from various mammals in central, east, and west Africa (although the original source of the virus remains unknown).
When researchers sequenced the genomes of those first global mpox cases, they identified a lineage of the virus called clade IIb, which is very rarely fatal, though the severity is much worse for those with weakened immune systems.
This globally distributed lineage looked different to other endemic strains in Africa, and now, researchers have shown that that could be due to human-to-human transmission.
Nearly all the mutations identified in clade IIb lineage are characteristic of a exposire to a human enzyme with an antiviral role.
This immune enzyme, called APOBEC3, acts on the DNA of the monkeypox virus and tends to cause an irreversible mutation that changes the sequence of base pairs in the viral genome in a predictable way.
With each human the virus encounters, more of these mutations accumulate.
This doesn't necessarily mean the virus is mutating to spread among humans more easily, although that is still a possibility. Instead, it could just be that the human body is leaving its neutral signature on the virus.
Either way, the mutations are rapidly accumulating, suggesting quite a lot of spread. O'Toole and colleagues predict that the human immune system has been confronting this particular lineage of mpox virus for about seven years.
Although some human mpox cases still come from animals, researchers conclude that "most cases since 2016 are likely the result of human-to-human transmission" – and that this transmission "continues unabated".
There may be places enduring current monkeypox epidemics that have not yet been recognized, and these could be seeding other outbreaks elsewhere in the world via travel.
"It is critical that global public health affords [mpox virus] cases in countries that are historically considered to have endemic reservoir species equal attention and concern to those elsewhere," the authors write.
"Surveillance needs to be global if [the mpox virus] is to be eliminated from the human population and then prevented from re-emerging."
The study was published in Science.