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Since monkeypox sickened thousands of people worldwide this spring, two big questions have arisen: Why is a virus that never managed to spread beyond a few cases outside of Africa suddenly causing such a large, global outbreak? And why are the vast majority of those affected men who have sex with men (MSM)?
A long history of work on sexually transmitted infections and early studies of the current outbreak suggest the answers may be connected: The virus may have found its way into highly interconnected sexual networks within the MSM community, where it spread to a can spread in ways that the general population cannot.
An epidemiological modeling study published in preprint last week by researchers at the London School of Hygiene & Tropical Medicine (LSHTM) supports this idea. It suggests that the outbreak will continue to grow rapidly unless the spread is contained. It also has implications for how to protect those most at risk and limit the spread, while suggesting the risk to the general population remains low.
But there are still many uncertainties and communication is strained because of the risk of stigmatizing MSM – and because it is difficult to communicate openly about sexual behaviour. “I think we need to talk more about sex,” says Gregg Gonsalves, an epidemiologist and former HIV activist at the Yale School of Public Health. “Everyone has been very clear about stigma and has said it over and over again. The point is, you need to continue to address the risk of infection in our community.”
Since the beginning of May, more than 2,000 cases of monkeypox have been reported in more than 30 countries where the virus does not normally occur. (Outbreaks are more common in at least a dozen countries in west and central Africa where the virus has animal reservoirs. More than 60 cases and one death have been confirmed there this year.)
The vast majority of cases in the current outbreak have involved MSM. For example, researchers at the UK Health Security Agency (UKHSA) asked patients to fill out questionnaires. Of 152 who did, 151 said they were MSM, the team wrote in a technical briefing released June 10; the remaining patient refused to answer. Other countries have seen similar patterns.
This could of course be a distorted picture. “MSM have better relationships with doctors than straight men,” says Lilith Whittles, an infectious disease modeler at Imperial College London, which could mean they’re more likely to report monkeypox symptoms and get tested for the virus. “I don’t know if we’re necessarily looking enough at heterosexual social media to conclude that this isn’t a broader problem,” says Boghuma Titanji, a virologist at Emory University who works at a sexual health clinic.
However, most researchers say such “detection bias” is unlikely to explain the striking pattern. Although some monkeypox patients have mild infections that can be missed or misdiagnosed, others have very distinctive skin rashes and excruciating pain that require hospitalization for pain management. If many people outside of the MSM community had monkeypox, more would have shown up in the statistics by now.
Ashleigh Tuite, an infectious disease epidemiologist at the University of Toronto, says she “understands the reluctance” to focus on MSM given the risk of stigma that could exacerbate discrimination result in those affected delaying their search for medical care. “But based on the data we have and based on the contact tracing that has been done, it’s very clear that this is an MSM-related outbreak at this point,” she says. “Anyone can get monkeypox, but we see disease activity mainly in” MSM, confirms Demetre Daskalakis, HIV prevention specialist at the US Centers for Disease Control and Prevention.
Sexual encounters clearly play a role in transmission. Of the 152 people in the UKHSA dataset, 82 were invited to additional interviews focused on their sexual health. Of the 45 participants, 44% reported having had more than 10 sexual partners in the past 3 months and 44% reported group sex during the incubation period. What is less clear is how the virus is transmitted. Researchers have found viral DNA and even infectious viruses in some patients’ semen, but they’re not sure if this is important for transmission; Skin-to-skin contact may suffice. (Other sexually transmitted infections, including herpes and scabies, also spread primarily this way.)
For those who study how pathogens spread through social and sexual networks, the pattern comes as no great surprise. In the 1970s and ’80s, researchers trying to understand the spread of STDs like gonorrhea were stumped, says LSHTM epidemiologist Adam Kucharski: Survey data showed that the average number of people’s sexual partners was too small to know the maintain transmission. But the averages masked the fact that while many people have fewer sexual partners, some have many. This helps drive transmission because if infected, they are more likely to infect others as well.
Sexual networks among MSM are no different in nature from those of other groups, Whittles points out, but a core group of people are much more closely connected than people outside the MSM community. They change partners more often and have more than one partner at the same time. “These things happen in all sexual networks, it’s just a matter of scale,” says Whittles. And in a densely connected network, the virus is less likely to hit a dead end.
“It’s entirely possible that this epidemic is raging among a subset of people just because that subset is networked differently than everyone else,” says Keletso Makofane, a social networking epidemiologist at the FXB Center for Health and Human Rights at Harvard University. Along with colleagues, Makofane hopes to start a study in New York City in August to better understand how the disease spreads. “The idea is to get a sense of how many people are reporting symptoms consistent with monkeypox and how they are related,” he says.
The LSHTM study, published June 13 on medRxiv, used UK data on sexual partnership patterns to model the spread of monkeypox among MSM and outside this group. Since it is not yet clear how contagious the virus is, the researchers modeled scenarios with different risk levels. Without effective interventions or behavioral changes, a large and sustained outbreak with more than 10,000 cases in MSM worldwide is “very likely,” they write. “In contrast, sustained transmission in the non-MSM population is unlikely in all scenarios considered.”
Because the model is based on UK data, the results may not apply elsewhere in the world, says first author Akira Endo. And other factors may have exacerbated the outbreak. Monkeypox may have mutated in a way that makes it easier to transmit, and the proportion of the population who have received the smallpox vaccine — which also provides some protection against monkeypox — has been declining since smallpox vaccination was abandoned worldwide starting in the 1970s. But the modeling shows that “we don’t necessarily need it [those factors] to explain the observed patterns,” says Endo.
Such conclusions put epidemiologists in an awkward position, and some have refused to speak to them Science for fear of stigmatizing MSM. Endo says he understands this and agrees that the results could be easily misconstrued. “Now I also understand that there’s a risk going the other way — that information won’t reach those who need it most before it’s too late,” he says.
Whittles agrees, calling the findings “practical information in terms of where it’s spreading. It’s a morally neutral thing,” she says. “Knowing what is happening is power, even if that knowledge is imperfect and will change,” adds Daskalakis.
The virus could still find other networks with similar characteristics. Daskalakis recalls an outbreak of methicillin resistance in the US staphylococci aureus in the 2000s that started in the MSM community but later spread to gyms, among athletes, and in prisons. Monkeypox could also spread among sex workers and their clients, Tuite says.
How quickly the virus will spread in the coming months depends on control efforts. National health authorities in Europe, Canada and the United States have issued guidance on how to reduce the risk of infection, and dating apps have alerted users to the risk of monkeypox and its symptoms, which can change contact patterns. Raising awareness among healthcare workers could also have an impact, Whittles says: faster diagnoses mean patients isolate their infection sooner, reducing onward transmission. “So there are a few different ways that behavior can change, even if it’s not about people having less sex,” she says. And the The model did not take into account that infected individuals developed immunity. That means “we may see a slowdown in the outbreak sooner than we can imagine,” Endo says.
Many countries are also preparing to launch vaccination campaigns. Vaccination of people with many sexual partners may be the most efficient approach. In the Canadian province of Quebec, the vaccine is already being offered to MSM who have had two or more sexual partners in the previous 14 days. It’s important to warn this community and do it right, says Gonsalves. “We should say: It’s not about who you are. It’s about what you do. And we won’t stigmatize it. But be aware that if you fit this profile, you are at greater risk.”
