Scientists zero in on origins of monkeypox outbreak

Scientists zero in on origins of monkeypox outbreak

When the first cases of monkeypox were identified in early May, European health officials were stumped. 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 now becoming clearer. Genetic analysis suggests that although the monkeypox virus spreads rapidly outdoors, it has been silently circulating among people for years.

Health officials have already identified two versions of monkeypox among US patients, suggesting at least two separate chains of transmission. Researchers in several countries have found cases without a known source of infection, indicating undetected community spread. And a research team argued last month that monkeypox had already crossed the threshold of sustainable human-to-human transmission.

Genetic information currently available indicated that, at some point in recent years, the virus enhanced its spread between people, said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.

“Genomic patterns 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. That carries the risk of monkeypox spreading from infected people to animals, likely rodents, in countries outside of Africa, which has struggled with the problem for decades. The virus can persist in infected animals, sporadically causing new infections in people.

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

As of Wednesday, the United States had identified 156 cases in 23 states and the District of Columbia. The global number has surpassed 3,400 confirmed cases and another 3,500 cases are being tested, tripling the numbers 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 which were in the Democratic Republic of the Congo.

Monkeypox is a large double-stranded DNA virus, about seven times larger than the coronavirus. DNA-based viruses can correct their own mistakes when they replicate their genetic material. They can collect only one or two mutations per year compared to 20 to 30 mutations for an RNA virus like coronavirus.

But the monkeypox virus appears to have accumulated an unexpectedly high number of mutations — nearly 50 compared to a version that circulated in 2018, according to preliminary analyses.

Of the 47 mutations identified in one analysis, 42 bear the distinctive 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 like 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 that monkeypox may have switched to people as hosts at that time, Dr Bedford said.

It is not clear how the mutations could change the virus. Of the 48 mutations identified in Britain, 21 can affect how the disease spreads, its severity and its response to a treatment called tecovirimat, according to the UK Health Security Agency.

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

Since then, scientists have been analyzing sequences from about 50 monkeypox cases, according to Dr. Ifedayo Adetifa, director of the Nigerian Center for Disease Control. But without the specialized equipment or expertise needed for rapid analysis, scientists have not yet completed their work, he said.

Although the researchers have received several requests for data from outside Nigeria, Dr. Adetifa said they would wait to publish their work to avoid being outdone by teams with more resources and taking credit.

“I am in favor of sharing open data 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 poxviruses and increased the odds that monkeypox will become a successful human pathogen.

In West Africa, the incidence of monkeypox has increased at least 20-fold since 1986. In general, in African countries, Dr. Adetifa said, “we suspect that some go unreported because there has been relatively low and perhaps a low perceived risk of monkeypox. Nigeria is stepping up its monkeypox surveillance, and the number of cases may rise as more people become aware of 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 mistaken for chickenpox. Many men in the current outbreak have lesions on their genitals, but these can be confused with sexually transmitted infections such as syphilis, gonorrhea and chlamydia.

Researchers in Italy and Germany have reported finding monkeypox DNA in semen, but it’s not clear whether the virus spreads that way or is simply present in semen and vaginal secretions.

Spread among young men with genital ulcers has been seen at least once before. In 2017, Nigeria recorded 228 suspected cases of monkeypox and confirmed 60. The virus spread mainly among young men who had genital ulcers.

Britain’s experience indicates how complicated it can be to trace contacts of a virus that can 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 get the names of less than a third of the 78 reported sexual contacts.

Many cases in Africa can be 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 smaller spaces, more viruses may jump to human hosts. Monkeypox is more likely to jump from rodents to people. There are about 2,000 rodent species worldwide, making up 40 percent of all mammal species. The African rope squirrel is a prime candidate as the primary reservoir for monkeypox, but there are other contenders, including striped mice and dormouse, giant rats, rusty-nosed rats, and brush-tailed porcupines.

In a 2003 outbreak in the United States, a shipment of Gambian 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 series of cases ended.

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

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