When the first cases of monkeypox were identified in early May, European health authorities were at a loss. The virus was not known to spread easily among people, let alone infect dozens – and soon hundreds – of young men.
The origins of the outbreak are now becoming increasingly clear. Genetic analysis suggests that while the monkeypox virus spreads rapidly outdoors, it has been silently circulating in humans for years.
Health officials have already identified two versions of monkeypox in American patients, suggesting at least two separate chains of transmission. Researchers in several countries have found cases with no known source of infection, indicating undetected community spread. And a research team argued last month that monkeypox had already crossed a threshold of sustained human-to-human transmission.
The genetic information available so far specified that the virus has been able to spread better between people at some point in recent years, said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.
“Genomic patterns suggest this happened around 2018,” said Dr. Bedford.
Once the virus has adapted to accept humans as hosts, monkeypox outbreaks could become more frequent and more difficult to contain. That poses a risk that monkeypox could spread from infected humans to animals — most likely rodents — in countries outside Africa that have been struggling with the problem for decades. The virus can persist in infected animals and sporadically cause new infections in humans.
“We can also extrapolate this to animals, which can transmit the disease in wildlife and to humans,” said Sagan Friant, an anthropologist at Pennsylvania State University who has been studying human-animal relationships in Nigeria for about 15 years.
The longer it takes to contain the virus, the higher the chances it will find a permanent new home in humans or animals, said Dr. Friant.
As of Wednesday, the United States had identified 156 cases in 23 states and the District of Columbia. The global toll has surpassed 3,400 confirmed cases and another 3,500 cases are being evaluated, triple the figure from two weeks ago.
In Africa, eight countries had reported more than 1,500 suspected cases and 72 deaths as of June 10, most of them in the Democratic Republic of the Congo.
Monkeypox is a large double-stranded DNA virus about seven times the size of the coronavirus. DNA-based viruses can correct their own mistakes when replicating their genetic material. They may only collect one or two mutations a year, compared to 20 to 30 mutations for an RNA virus like the coronavirus.
But the monkeypox virus appears to have accumulated an unexpectedly high number of mutations — almost 50 compared to a version circulated in 2018, according to preliminary analyses.
Of the 47 mutations identified in an analysis, 42 carry the unique signature of an enzyme called Apobec3. This enzyme, first discovered by researchers studying HIV, is what’s called a host defense factor — an immune system weapon that animals and humans use to disarm viruses like monkeypox.
The enzyme essentially forces viruses to make mistakes when trying to replicate, causing them to self-destruct. Mice only carry one version of this enzyme, while humans have seven. The rapid accumulation of mutations characteristic of the enzyme since 2018 suggests monkeypox may have switched to human hosts around this time, said Dr. Bedford.
It’s unclear how the mutations could alter the virus. Of 48 mutations identified in the UK, 21 can affect the spread of the disease, its severity and its response to a treatment called tecovirimat, according to the UK Health Security Agency.
But since mutations introduced by the enzyme Apobec3 are designed to harm the virus, their quantity alone isn’t of concern, said Michael Malim, a virologist at King’s College London who discovered Apobec3 in 2002. The effect of the mutations is “rather debilitating,” he said. Comparing the current version of the virus with samples from recent years could help understand its evolution, but that information is scarce to sequence material.
Since then, scientists there have analyzed the sequences of about 50 cases of monkeypox, according to Dr. Ifedayo Adetifa, Director of the Nigeria Center for Disease Control. But without the specialized equipment or expertise needed for rapid analysis, the scientists would not have completed their work, he said.
Although the researchers have made multiple requests for the data from outside Nigeria, Dr. Adetifa that they would wait to publish their work to prevent teams with more resources from outperforming them and gaining recognition.
What you should know about Monkeypox virus
What is monkeypox? Monkeypox is a virus endemic to parts of central and west Africa. It is similar to smallpox but less severe. It was discovered in 1958 after outbreaks in monkeys kept for research, according to the Centers for Disease Control and Prevention.
“I’m all for open data sharing and all that,” he said. “The question is who benefits?”
Some experts have warned for years that the eradication of smallpox in 1980 left the world vulnerable to the broader family of smallpoxviruses and increased the likelihood of monkeypox becoming a successful human pathogen.
In West Africa, the incidence of monkeypox has increased at least twenty-fold since 1986. In African countries in general, said Dr. Adetifa, “we suspect some under-reporting because there is relatively low awareness and perhaps low perceived risk of monkeypox.” Nigeria is stepping up its surveillance of monkeypox, and case numbers could rise as more people become aware of the virus, he added added.
Although monkeypox has a distinctive rash that appears on the palms and soles of the feet, it is often confused with chickenpox. Many men in the current outbreak have lesions on their genitals, but these can be mistaken for sexually transmitted infections such as syphilis, gonorrhea and chlamydia.
Researchers in Italy and Germany have reported finding monkeypox DNA in semen, but it’s unclear whether the virus spreads this way or is only present in semen and vaginal secretions.
Spread among young men with genital ulcers has been observed at least once before. In 2017, Nigeria recorded 228 suspected cases of monkeypox and 60 confirmed. The virus spread mainly among young men with genital ulcers.
The UK’s experience shows how complicated it can be to trace contacts of a virus that may be transmitted sexually, particularly in cases where infected people have had multiple anonymous partners. In an initial analysis of a subset of cases, officials said they were able to get names for fewer than a third of the 78 sexual contacts reported.
Many cases in Africa have been traced to contact with wildlife or the use of animal products in medicinal or cultural practices.
As deforestation and urbanization push humans and animals closer together, more viruses could make the leap to human hosts. Monkeypox is most likely to spread from rodents to humans. There are about 2,000 species of rodents worldwide, accounting for 40 percent of all mammal species. The African rope squirrel is a leading candidate as the main reservoir for monkeypox, but there are other contenders, including striped mice and dormouse, giant opossums, rust-nosed rats, and porcupines.
In a 2003 outbreak in the United States, a shipment of Gambian opossums imported from Africa transmitted monkeypox to prairie dogs, which then infected 71 Americans. But officials found no signs of the virus in animals in the United States after the spate of cases ended.
There is no guarantee that luck will last this time. “These spillovers from other species and what that means and what the trajectory is — it’s very unpredictable,” said Dr. Malim. “And it’s becoming more common.”