The origin of the monkeypox outbreak becomes clearer to scientists

When the first cases of monkeypox were identified in early May, European health officials were baffled. The virus was not known to spread easily between people, let alone infect dozens – and soon hundreds – of young men.

The origins of the outbreak are becoming clearer. Genetic analysis suggests that although the monkeypox virus is spreading rapidly outdoors, it has been quietly circulating in people for years.

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

The genetic information available so far indicated that, at some point in recent years, the virus has improved in spreading among people, said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

‘Genomic models would suggest this occurred around 2018,’ said Dr Bedford.

If the virus has adapted to include people as hosts, monkeypox outbreaks could become more frequent and more difficult to contain. This carries the risk that monkeypox could overflow from infected people in animals – most likely rodents – in countries outside of Africa, which has struggled with this problem for decades. The virus can persist in infected animals, sporadically triggering new infections in people.

“We can also pass it on to animals that can spread the disease within wildlife and return 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 is to find a new permanent home in people or animals, Dr. Friant said.

As of Wednesday, the United States had identified 156 cases in 23 states and the District of Columbia. The global toll has exceeded 3,400 confirmed cases and another 3,500 cases are being evaluated, tripling the numbers compared to two weeks ago.

In Africa, eight countries had reported over 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 they replicate their genetic material. They can only harvest one or two mutations per year compared to 20-30 mutations in an RNA virus such as the coronavirus.

But the monkeypox virus appears to have amassed an unexpectedly high number of mutations, nearly 50 compared to a version circulating in 2018, according to preliminary analyzes.

Of the 47 mutations identified in one analysis, 42 carry the distinct signature of an enzyme called Apobec3. This enzyme, first discovered by researchers studying HIV, is a so-called host defense factor, a weapon of the immune system that animals and people use to disarm viruses such as monkeypox.

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

It is not clear how mutations can change the virus. Of the 48 mutations identified in Britain, 21 can affect how the disease spreads, its severity and how well it responds to a treatment called tecovirimat, according to the UK’s Health Safety Agency.

But because the mutations introduced by the Apobec3 enzyme are meant to damage the virus, their quantity alone is not of concern, said Michael Malim, a virologist at King’s College London who discovered Apobec3 in 2002. It is more likely that the effect of the mutations is debilitating, “He said. Comparing the current version of the virus with samples from recent years could help understand how it evolved, but this information is scarce. Nigeria has not had the ability to sequence genetic material until to 2017.

Since then, scientists have analyzed sequences of about 50 monkeypox cases, according to Dr Ifedayo Adetifa, director of Nigeria’s Center for Disease Control. But without the specialized equipment or experience needed for quick analysis, the scientists haven’t finished their work yet, he said.

Although the researchers responded to several requests for data from outside Nigeria, Dr Adetifa said she would wait to publish her work to prevent more resourceful teams from getting past them and grabbing credit.

“I’m all about sharing open data and everything in between,” he said. “The question is, who benefits from it?”

Some experts have warned for years that the eradication of smallpox in the 1980s left the world vulnerable to the wider poxvirus family and increased the odds of monkeypox to evolve into a successful human pathogen.

In West Africa, the incidence of monkeypox has increased at least twenty times since 1986. In African countries in general, Dr Adetifa said, “we suspect there has been underreporting because there has been relatively low awareness and possibly a low perceived risk of monkeypox. ” Nigeria is stepping up surveillance of monkeypox and the number of cases could increase as more people learn about the virus, he added.

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

Researchers in Italy and Germany have reported finding monkeypox DNA in sperm, but it is unclear whether the virus spreads this way or is simply present in sperm and vaginal secretions.

Spread among young people with genital ulcers has been observed at least once previously. In 2017, Nigeria recorded 228 suspected cases of monkeypox and confirmed 60. The virus has spread mainly among young people with genital ulcers.

Britain’s experience indicates how complicated it can be to trace the contacts of a virus that could be sexually transmitted, especially 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 obtain names for less than a third of the 78 reported sexual contacts.

Many cases in Africa have been traced back to contact with wild animals or the use of animal products for medicinal or cultural practices.

As deforestation and urbanization push people and animals into closer quarters, more viruses could make the leap to human hosts. Monkeypox is very likely to jump to people from rodents. There are approximately 2,000 rodent species worldwide, which make up 40 percent of all mammalian species. The African squirrel is a prime candidate as a primary reservoir for monkeypox, but there are other contenders, including striped mice and dormice, giant pouch rats, rusty-nosed rats, and brush-tailed porcupines.

In a 2003 outbreak in the United States, a shipment of Gambian pouch rats 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 once the case series ended.

There is no guarantee that luck will hold up this time around. “These spillovers from other species, and what that means and what the trajectory is – it’s very unpredictable,” said Dr Malim. “And it’s happening more and more.”

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