Monkeypox Likely Circulated for Years Before Outbreak, Scientists Say

“You have a virus that was able to establish itself in a dense social and sexual network and transmit efficiently because there’s no immunity,” said Anne Rimoin, professor of epidemiology at the University of California, Los Angeles.

A gradual decline of herd immunity against the closely related smallpox virus gave monkeypox more possibilities to jump from its natural animal hosts, infection-disease experts say. And one day, years ago, it infected someone who was part of a network with close physical contact between members—maybe a gay man with multiple sexual partners, or a sex worker—allowing it to spread sustainably among humans for the first time, these experts theorize.

That spread likely continued for years, undetected, until someone—or some people—with the virus traveled to large international events in Europe in May. Some attendees caught the virus and brought it back to their home countries, setting in motion the global outbreak that has now infected more than 29,000 people.

In the 1970s, many countries stopped routine vaccination against smallpox. A long-running campaign to eradicate one of the world’s deadliest diseases had the added benefit of preventing human infections of monkeypox, a closely related, though less severe, virus.

Starting in 1970, sporadic cases of monkeypox sprang up, mainly in people who lived in small villages in the rainforests of Central and West Africa, in close proximity to some animal populations—such as tree squirrels and other rodents—known to harbor monkeypox. Between 1970 and 1979, the World Health Organization recorded 45 cases. The majority were young children who had been infected by an animal. The virus spread to a close family member on four occasions, but went no further.

As the proportion of unvaccinated people increased, so too did the frequency of monkeypox. A 2010 study, published in the Proceedings of the National Academy of Sciences, found that in one of the most affected regions in Congo, the rate of monkeypox was 20 times higher between 2005 and 2007 than during the 1980s, a period when the WHO conducted widespread testing for the virus.

Almost all cases were in younger people who had been born after mass vaccination ended in 1980. UCLA’s Dr. Rimoin, who led the study, at the time urged governments to tackle the rise of monkeypox in central Africa, while the disease’s geographic range was still limited.

As population immunity declined, the virus was still held back by its limited ability to spread between people. Monkeypox requires close contact to spread. Typically, that means direct contact with the skin lesions caused by the virus, although it can also spread through shared personal items like bed linens or respiratory droplets from prolonged face-to-face contact. African researchers believe that, for most of the last five decades, monkeypox outbreaks quickly fizzled out, with a person catching the virus from an animal and then maybe spreading it to a few people they lived with. Before this year, the longest known chain of transmission—meaning the number of successive person-to-person infections—for monkeypox was just nine people, according to the WHO.

Now, though, virologists and infectious-disease experts say that at some point in the past few years, the virus jumped from an animal to a person and then kept spreading.

Genomic analysis of samples from the current outbreak suggests that the virus has been spreading among people for years, according to Geoffrey Smith, professor of pathology at the University of Cambridge and an expert in poxviruses. The pattern of mutations, he says, is consistent with genetic blips that would have been introduced by a human protein that interferes with viral replication.

So far, there is no evidence that those mutations have led to the virus becoming more transmissible, or brought about any other new properties such as drug resistance or increased severity, said Prof. Smith.

It isn’t known precisely when that sustained human-to-human transmission began. The number of genetic mutations linked to the human protein suggests that the current outbreak can be traced to an animal-to-human infection that took place around April 2016, according to researchers at the University of Edinburgh.

Dimie Ogoina, an infectious-disease doctor in Nigeria, said he suspected that sexual contact had become an important route of transmission for monkeypox when the virus suddenly resurfaced in that country in 2017, after nearly four decades without a case.

An early clue, he said, came from a husband and wife. The husband had a rash that was most prominent in his genitals. The wife later developed a single lesion in her genital area, but had no other symptoms. The couple had two children at home under the age of 10, neither of whom caught the virus.

Dr. Ogoina, who has treated a few dozen cases since 2017, said he could link the virus with sexual contact in the majority of patients that he has seen. However, when he shared this observation with colleagues at a conference in 2019, some were skeptical, as it didn’t fit with how monkeypox had spread in the past.

“It’s a roll of the dice as to whether or not it’s going to end up in a dense network,” said Dr. Rimoin. She said it is likely that the virus was already circulating among men who have sex of men and that some of them traveled to large gatherings in the Canary Islands and Belgium that took place in May. Those events were linked to multiple cases that were later identified in various European countries including the U.K., Spain and Portugal.

Although the virus is circulating predominantly through sexual networks of gay and bisexual men, that isn’t its only mode of spread. A small number of women and children have also caught the virus by, for example, catching it from someone they live with.

“This is something that was wholly predictable if monkeypox got itself into the right population for spread,” said Dr. Rimoin. “Now we have to wake up and get to work.”

Write to Denise Roland at denise.roland@wsj.com