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Two distinct monkeypox variants found in U.S., adding to outbreak’s mystery

Differences in the genetic sequences of U.S. monkeypox cases complicate the picture of the outbreak's origin.
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At least two genetically distinct monkeypox variants are circulating in the U.S., according to new sequencing data from the Centers for Disease Control and Prevention.

Although the CDC hasn’t sequenced all 22 confirmed U.S. cases yet, two of them were found to be genetically similar to a 2021 infection in a Texas man who traveled to Nigeria. Both are in people who recently traveled to Africa — a woman from Virginia and man from Florida.

The rest of the sequenced U.S. cases resemble the genetic codes of the cases in Europe, and a 2021 infection in a Maryland resident who traveled to Nigeria.

"While they’re similar to each other, their genetic analysis shows that they’re not linked to each other," Jennifer McQuiston, deputy director of the CDC’s High Consequence Pathogens and Pathology division, said of the two variants at a Friday press briefing.

McQuiston and other disease experts said this new information suggests the U.S. cases stem from two outbreaks instead of one, complicating our understanding of their origins.

"It’s likely that within the last couple of years, there have been at least two different instances where monkeypox virus spilled over to people in Nigeria from the animal that maintains it and that that virus likely began to spread through person-to-person close contact, possibly intimate or sexual contact," McQuiston said.

That possibility, in turn, raises questions about how long monkeypox has been circulating outside Africa and how transmissible the virus is.

“This is like tuning in to a new television series and we don’t know what episode we’ve landed on,” Anne Rimoin, an epidemiology professor at UCLA Fielding School of Public Health, said. “We’re now just starting to get some of the origin story.”

Was monkeypox spreading undetected?

Nearly 900 monkeypox cases have been reported outside Africa since early May, according to, a group that gathers infectious disease data. Before that, the largest outbreak in the Western Hemisphere was 47 U.S. cases in 2003. Those people were infected by pet prairie dogs; no human-to-human transmission was documented.

Experts are weighing various possible explanations for the quick growth of the current outbreaks. It could be that a few events simply gave the virus a chance to spread. Or, monkeypox may have evolved to get better at human-to-human transmission. A third hypothesis is that the virus may have been spreading undetected for some time.

WHO Director-General Tedros Adhanom Ghebreyesus suggested this week that the third option is likely.

"We might be seeing [the variants] now because we’re looking so hard," Andrew Read, a professor at Pennsylvania State University who studies the evolution of infectious diseases, said.

But McQuiston said a previous large-scale outbreak would not have been missed.

"It’s certainly possible that there could have been monkeypox cases in the United States that went under the radar previously, but not to any great degree," she said.

'Lots of genes to play with'

As for the idea that the virus has become more transmissible, Read pointed to the fact that monkeypox seems to be spreading more efficiently among close contacts than scientists had observed in the past.

Monkeypox is a DNA virus, which does not mutate as fast as RNA viruses like the coronavirus. But Read pointed out that DNA viruses have long genomes: Moneypox's genome is seven times larger than that of the coronavirus.

"The fact that it’s got lots of genes to play with means all manner of things can happen," he said.

Stephen Morse, an epidemiology professor at Columbia University, said it's worth investigating whether one variant spreads more easily than the other.

"If a particular variant were capable of more cycles of human-to-human transmission, that would be important to know," he said.

But Rimoin said it's too soon to know whether monkeypox has evolved in any meaningful way.

The size of this outbreak, she said, "doesn’t necessarily mean that the virus in and of itself has changed."

More transmission makes the virus harder to contain

Experts are optimistic that the U.S. outbreak can still be contained, though they're concerned about ongoing transmission.

"I worry a lot about if it becomes very common in humans," Read said. "The potential to become more common and more transmissible through time, as we’ve had with Covid, would be very, very unfortunate."

The more widespread cases become, the harder they are to contain, but that "doesn’t mean that it’s impossible," Rimoin said.

Experts know how to stop monkeypox transmission: Test people with symptoms, isolate infected patients and vaccinate their close contacts.

"I don’t think that the fact that there’s two [variants] circulating now is going to complicate control measures," Read said. "Let's just stop the evolution by getting rid of these things now."