The Mystery of Monkeypox’s Global Spread

Initial genomic sequencing suggests the virus hasn’t mutated to become more transmissible. So what explains its unprecedented rise across the world?
monkeypox virus
Photograph: CDC/Reuters

When Moritz Kraemer first heard about the new monkeypox outbreak spreading through the UK, Europe, and the US, it was not through conventional scientific channels, or from the UK Health Security Agency (UKHSA), but via Twitter. As each suspected case was reported, and infectious disease experts shared their theories in real time, Kraemer—an epidemiologist at the University of Oxford who specializes in modeling the spread of infectious diseases—became increasingly concerned.

“We realized that this outbreak was unusual in its geographic expansion, with some clusters not linked to travel,” he says. In the past, when monkeypox cropped up in Europe or North America, cases could be readily traced back to countries where the virus circulates. Not this time. To keep up with how the virus was spreading, Kraemer together with John Brownstein and colleagues at Global.health, swiftly created the Monkeypox Tracker, which collates information on confirmed and suspected cases. It is this tool that neatly visualizes all that is unusual about the new outbreak.

Although monkeypox is endemic in West and Central Africa, it is not known for being especially transmissible. It was first found in monkeys in 1958, but rodents and other small mammals are thought to be the main animal host, and the virus is most commonly transmitted through close contact between these creatures and humans, causing people to come down with a fever, as well as a telltale bumpy rash.

It can also be spread between humans—either through respiratory droplets or the body fluids of an infected person—but this tends to be less common, as monkeypox is not contagious until a person is displaying symptoms, by which point they’re more likely to be convalescing and avoiding contact with others. Mateo Prochazka, an epidemiologist at the UKHSA, says some of the longest transmission chains documented for the virus are only six successive person-to-person infections.

But as the Monkeypox Tracker illustrates, clusters of cases are suddenly appearing around the globe without clear links back to endemic countries. To date, the UK has the most confirmed cases at 57, along with clusters in Portugal and Spain, but cases have also emerged as far away as Canada and Australia.

So what is going on? Some scientists initially speculated that a new, more transmissible form of monkeypox might have emerged, but now the first viral genomic sequences from the outbreak are being published and appear to suggest otherwise. Last Friday, scientists at the Institute of Tropical Medicine in Antwerp, Belgium, published a sequence isolated from a 30-year-old patient that suggests the monkeypox currently in circulation is similar to that seen in an outbreak in 2018. Another sequence from a Portuguese patient also appears similar to the forms of the virus detected in 2018.

“If virus genomes from this outbreak are very similar to earlier ones, we’d feel more confident that there hasn’t been some evolution-driven jump in transmissibility,” says Jo Walker, a researcher at the Yale School of Public Health.

It seems more likely that this outbreak has stemmed from a flare in cases within parts of Africa, combined with a spike in air travel following the end of pandemic restrictions, and waning immunity against orthopoxviruses—the viral family that contains monkeypox, cowpox, smallpox, and others—across large swathes of the planet. Jamie Lloyd-Smith, a University of California, Los Angeles professor who has been studying monkeypox for more than a decade, says immunity against this family of viruses has been declining in humans ever since smallpox was eradicated in 1980.

“Eradicating smallpox stands as one of the greatest public health accomplishments of all time,” he says. “But a natural consequence of eradicating the one orthopoxvirus that circulated widely among humans, and then stopping the vaccination program that led to eradication, is that generations of people have no immune experience with any orthopoxvirus. There is no question that this makes life easier for monkeypox. It’s like a big pile of fuel that has never seen a spark.”

But this still doesn’t answer the prevailing question of why now? Studies show that monkeypox has been on the rise for several years in Nigeria, the Democratic Republic of the Congo (DRC), and other African nations, but the precise tipping point that has led to a much wider outbreak today remains a mystery. Scientists hope that further genetic sequencing and contact tracing will shed more light on exactly when and how the outbreak began.

“The two trends of declining immunity and growing air travel don’t explain why this is happening now and not a few years ago, or a few years in the future,” says Walker. “Maybe a random series of mutations in the last few months set this all off. Or maybe our luck ran out, and it took until now for a monkeypox case to make its way to a major population center, get on an airplane, and kickstart an outbreak without hitting a dead end.”

There is also the enigma of how exactly the virus is being passed from person to person. The UKHSA has suggested that the transmission routes could be sexual, based on data showing that a proportion of the confirmed cases are men who have sex with men, presenting with painful genital ulcers. However this has never been described before with monkeypox, and other scientists have cautioned against drawing such conclusions at this early stage of the outbreak, due to the potential stigma of characterizing an expanding outbreak as being fueled by sexual promiscuity.

“I don’t like to speculate because I do not think it is helpful and may fuel misinformation,” says Boghuma Titanji, a researcher at Emory University who has studied past monkeypox outbreaks. “Sexual transmission is always a possible mode of spread for any pathogen which spreads by close physical contact.” However, as new cases emerge and viruses are isolated and sequenced, it will become more possible to piece together transmission networks, Titanji says, and it may give us additional clues as to exactly how the virus spreads.

But while the news of an infectious disease that appears to be spreading around the world has prompted concern in the wake of Covid-19, there is far less reason to be fearful. Monkeypox is far less transmissible, with a reproduction number—the average number of people who will catch the virus from one infected person—of somewhere between one and two. In comparison, the Omicron variant of Covid-19 has a reproduction number above seven.

And while monkeypox can be lethal—the Congo Basin strain kills up to 10 percent of those infected—genomic sequences seem to indicate that the new outbreak involves the West African strain, which has a lower estimated fatality rate of 1 percent. So far, no patients are known to have become severely ill, and there are two vaccines already available in Europe and North America that prevent disease even if used up to four days after a person has been exposed.

Plus responses have been swift. The UK is already deploying ring vaccination strategies—vaccinating close contacts of those infected with monkeypox—while the UKHSA has issued a statement saying that those people should also self-isolate for 21 days and work from home. Last Friday, Belgium became the first country to introduce a mandatory 21-day quarantine for all monkeypox patients.

Titanji says countries can follow a playbook of strategies that have been successfully used by Cameroon, Nigeria, Gabon, and the DRC to contain monkeypox outbreaks in recent years. “We know from previous outbreaks that early contact tracing, testing, and isolation of positive cases is effective in interrupting transmission chains,” she says.

Right now the world is particularly well placed to implement such measures, which have been fine-tuned over the past two years. Genomic sequencing centers used to analyze Covid-19 samples have been quickly redeployed to sequence monkeypox, while Bill Hanage, an epidemiologist at the Harvard TH Chan School of Public Health, says he is using the novel viral surveillance technique of waste-water sampling—that is, looking for traces of the virus shed in sewage—as one method to understand just how widespread the outbreak is.

Scientists do not expect the latest outbreak to develop into a serious epidemic, but many argue that it serves as a warning sign for a group of viruses that have long been neglected by public health authorities and scientific journals. Hanage points out that the World Health Organization’s poxvirus team amounts to just a handful of staff, while Titanji says that when researchers in Cameroon tried to publish a paper based on a 2018 outbreak, their attempts were rejected.

She feels that while the current outbreak is containable, it illustrates how vital it is to keep monitoring for future monkeypox virus strains that may evolve to become more transmissible and capable of causing a major crisis.

“There is still a lot we can learn about this virus,” she says. “Every new outbreak presents an opportunity for us to do just that, and be better prepared the next time around.”

Updated 5-25-2022 7:30 am ET: This story was amended to include all of the creators of the Monkeypox Tracker. Previously the names of John Brownstein and Global.health were omitted.