Origin of Monkeypox outbreak becomes clearer to scientists

When the first cases of monkey pox were identified in early May, European health officials were stunned. The virus was not known to spread easily among humans, let alone infect dozens — and soon hundreds — of young men.

The origin of the outbreak is now becoming clearer. Genetic analysis suggests that although the monkeypox virus spreads rapidly in the open, it has been quietly circulating among humans for years.

Health officials have already identified two versions of monkeypox in U.S. patients, suggesting at least two separate chains of transmission. Researchers in several countries have found cases with no known source of infection, indicating undetected spread in the community. And a research team argued last month that monkeypox had already crossed a threshold for sustained person-to-person transmission.

The genetic information available so far indicated that at some point in recent years, the virus was better able to spread between humans, 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 host humans, monkeypox outbreaks could become more frequent and more difficult to contain. That poses the risk that monkeypox could pass from infected humans to animals — most likely rodents — in countries outside Africa, which have struggled with that problem for decades. The virus can persist in infected animals and occasionally cause new infections in humans.

“We can also give this back to animals that can spread the disease to wildlife and back to humans,” said Sagan Friant, an anthropologist at Pennsylvania State University who has studied human-animal interactions in Nigeria for about 15 years.

The longer it takes to contain the virus, the more likely it will find a permanent new home in humans or animals, said Dr. friant.

By Wednesday, the United States had identified 156 cases in 23 states and the District of Columbia. The global number has passed 3,400 confirmed cases and an additional 3,500 cases are under evaluation, tripling the number two weeks ago.

In Africa, as of June 10, eight countries had reported more than 1,500 suspected cases and 72 deaths, most of them in the Democratic Republic of 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 they replicate their genetic material. They can only collect one or two mutations per 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 — nearly 50 compared to a version circulating in 2018, according to preliminary analyses.

Of the 47 mutations identified in one analysis, 42 bear the clear signature of an enzyme called Apobec3. First discovered by researchers studying HIV, this enzyme is a so-called host defense factor — an immune system weapon that animals and humans use to disarm viruses such as monkeypox.

The enzyme essentially forces viruses to make mistakes when they try to replicate, causing them to self-destruct. Mice carry only one version of this enzyme, while humans have seven. The rapid accumulation of mutations, characteristic of the enzyme since 2018, suggests monkeypox may have transitioned to humans as hosts around that time, said Dr. bedford.

It is unclear how the mutations could alter the virus. Of the 48 mutations identified in Britain, 21 may affect how the disease spreads, its severity and how well it responds to a treatment called tecovirimat, according to the UK Health Security Agency.

But because mutations introduced by the enzyme Apobec3 are meant to harm the virus, their amount alone isn’t a cause for concern, said Michael Malim, a virologist at King’s College London who discovered Apobec3 in 2002. The effect of the mutations is “probably debilitating,” he said. Comparing the current version of the virus with samples from recent years can help understand how it evolved, but that information is scarce. Nigeria only had the ability to sequence genetic material in 2017.

Since then, scientists there have analyzed the sequences of about 50 monkeypox cases, 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 have not yet completed their work, he said.

Although the researchers have made several requests for the data from outside Nigeria, Dr. Adetifa that they would wait to publish their work to prevent teams with more resources from beating them and getting credit.

“I’m all for open data sharing and stuff,” he said. “The question is, who benefits?”

For years, some experts have warned that the smallpox eradication in 1980 left the world vulnerable to the broader family of smallpox viruses and increased the chances of monkeypox developing into a successful human pathogen.

In West Africa, the incidence of monkey pox has increased at least twentyfold since 1986. In African countries in general, said Dr. Adetifa, “we suspect some underreporting because there has been relatively low awareness and perhaps a low perceived risk of monkey pox.” Nigeria is stepping up its surveillance of monkey pox and the number of cases may increase as more people become aware of the virus, he added.

Although monkeypox has a distinctive rash that appears on the palms and soles, it is often confused with chickenpox. Many men in the current outbreak have lesions on their genitals, but those can be mistaken for sexually transmitted diseases such as syphilis, gonorrhea and chlamydia.

Researchers in Italy and Germany have reported finding monkey pox DNA in semen, but it’s unclear whether the virus spreads that way or is only present in semen and vaginal secretions.

The spread among young men with genital ulcers has been observed at least once before. In 2017, Nigeria registered 228 suspected monkey pox cases and confirmed 60. The virus spread mainly among young men with genital ulcers.

Britain’s experience shows how complicated it can be to trace contacts of a potentially sexually transmitted virus, especially in cases where infected people have had multiple anonymous partners. In an initial analysis of a subset of cases, officials said they could get names for less than a third of the 78 sexual contacts reported.

Many cases in Africa can be traced back to contact with wildlife or the use of animal products for medicinal or cultural practices.

As deforestation and urbanization bring people and animals closer together, more viruses may make the leap to human hosts. Monkeypox most likely jumps at people from rodents. There are about 2000 species of rodents worldwide, which make up 40 percent of all mammal species. The African rope weekhorn is a leading candidate as the primary reservoir for monkeypox, but there are other contenders, including striped mice and dormice, giant possums, rusty-nosed rats, and brush-tailed porcupines.

In a 2003 outbreak in the United States, a shipment of pouched Gambian rats imported from Africa transmitted monkeypox to prairie dogs, which subsequently infected 71 Americans. But officials found no signs of the virus in animals in the United States after the wave 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.”

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