New research may change the narrative over how mpox, formerly known as monkeypox, has become a human problem. Researchers found evidence that strains of the virus have been circulating between humans since at least 2016, years before it caused a surprise global epidemic in 2022. Though reported cases of the viral disease have since slowed down considerably, the findings suggest that it will be even harder than expected to eradicate the disease completely.
We first became aware of monkeypox in the 1950s, when it caused an isolated outbreak among lab monkeys that had been transported from Africa to Denmark. In the 1970s, the first known human cases were documented. The monkeypox virus is a close relative of smallpox, and, much like the extinct virus, the infection tends to cause rashes and flu-like illness in its victims.
Monkeypox, now officially called mpox, has long been considered a zoonotic disease, one that primarily spreads from animals (likely rodents, not monkeys) to humans and is only rarely transmitted between people. But that perception changed in early 2022, when the virus began to cause widespread human-to-human outbreaks outside Africa.
These outbreaks spanned the globe, with over 90,000 cases in 115 countries documented since January 2022. The virus can spread through any kind of direct contact, but these cases have largely been transmitted sexually between gay and bisexual men. Fortunately, the strains that spread widely belonged to less fatal clades of the virus, though there have been at least 157 deaths attributed to the epidemic.
It’s still not clear exactly how mpox managed to break free of its known confines and spread worldwide. But a team of researchers at the University of Edinburgh and elsewhere say they’ve been able to figure out one of the important aspects behind its emergence: its recent evolutionary journey prior to 2022.
Like past studies, the researchers found that the earliest epidemic strains of monkeypox in 2022 belong to the same lineage of strains documented in 2018 that originated from Nigeria, one of the areas in Africa where zoonotic transmission of the disease is endemic. But these later strains have lots of genetic differences compared to the 2018 version. A possible explanation for this divergence is that, between those years, one or more of these strains rapidly mutated inside humans, and these mutations allowed the virus to adapt and spread more easily between people from then on.
According to the study authors, though, this scenario doesn’t make much sense, based on what we know about the evolution rate of other, similar viruses. The team identified that nearly all of these mutations affected how the virus would respond to an antiviral enzyme our cells produce called APOBEC3. They argue that these changes are actually the result of the virus gradually adapting to us, suggesting that sustained human transmission of mpox has been going on much longer than we knew. By using these APOBEC3-related mutations as a window to the past, the researchers now estimate that some strains of mpox have been spreading among humans since at least 2016.
“These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis,” the team wrote in their paper, published Thursday in Science.
The findings, assumed they’re validated by other research, shouldn’t just change our thinking about mpox’s past but its future as well, the authors say. There are other lineages of the virus still out there, so it’s possible that they could also be spreading or someday spread between humans. And though the current epidemic has substantially quieted down—thanks in part to vaccination and awareness campaigns in high-risk communities—it’s not gone.
Truly getting rid of mpox will require much more vigilance than is currently practiced, the authors say.
“It is critical that global public health affords MPXV cases in countries that are historically considered to have endemic reservoir species equal attention and concern to those elsewhere,” they wrote. “Surveillance needs to be global if MPXV is to be eliminated from the human population and then prevented from reemerging.”