By Megan Molteni
The explosive trajectory of monkeypox to nearly 90 countries since the current outbreak was detected in the United Kingdom in mid-May has caught many governments off-guard, and created confusion about how monkeypox spreads from person to person.
In some ways, the virus is acting differently than it has in the past. For decades, researchers in West and Central Africa, where the virus is endemic, have observed that outbreaks there tend to be self-limiting. A single case or small cluster would pop up occasionally, caused by hunting and handling infected animals or being bitten by one, but those spillover events rarely kicked off long chains of transmission within communities.
As researchers rush to understand exactly what is different about this global outbreak, they’re finding that for the most part, monkeypox is still the same it’s always been. The mechanisms of how it moves from host to host remain unchanged. What’s different is the environment and the social networks monkeypox now finds itself in.
“This virus didn’t get a makeover,” said Peter Chin-Hong, an infectious disease physician at the University of California, San Francisco. “The transmission we’re seeing is completely consistent with what we’ve known about monkeypox, just in a new context.”
For the last three months, public health officials have anxiously tracked the relentless spread of monkeypox around the globe. The outbreak has now seen nearly 30,000 cases recorded, and 9,500 of those cases have been found in the U.S. Last week, the Biden administration declared monkeypox a public health emergency.
Since May, it has been spreading primarily among men who have sex with men, or MSM, and especially among men who have multiple sex partners or who have anonymous sex. Public health officials have not yet seen evidence that it has broken out of those networks into the wider population.
Still, an outbreak of this scale is giving scientists many more opportunities than ever before to study transmission in granular detail. And they are uncovering clues that raise new questions about how monkeypox spreads.
STAT spoke to several infectious disease experts to better understand what scientists know and don’t know at this point about monkeypox transmission, who’s most at risk, and how to avoid infection.
Monkeypox has spent most of its evolutionary history living inside Central and Western Africa’s small mammals — squirrels, rats, mice, and the true reservoir host, which remains unknown. It didn’t evolve to be good at infecting humans. So catching it requires getting a hefty dose of the virus, what scientists call a “high inoculum.”
There are three ways you can be exposed to sufficient amounts of the virus to become infected: direct skin-to-skin contact with the lesions caused by the virus, touching contaminated objects, and close contact with respiratory secretions like saliva from a person with lesions in their mouth or throat. What’s clear from the epidemiological evidence so far is that the current monkeypox epidemic is being driven overwhelmingly by the first of these — in particular, close intimate contact between sexual partners.
What’s less clear is whether urine, feces, blood, semen, or vaginal fluids can spread the virus, the extent to which people without symptoms can infect others, and how much of a role inhaled respiratory particles are playing in transmission.
But many experts emphasized that while for most people the risk of contracting monkeypox right now is very low, public health officials should be taking this disease more seriously. “We will not be able to control this epidemic until we have an effective vaccine available that we can use widely, and we are far from that,” José Luis Blanco, an infectious disease researcher at the Hospital Clinic de Barcelona, told STAT via email. “This is not an MSM infection, it is an infection that has started affecting MSM but can affect all of us.”
Skin-to-skin contact
Monkeypox has a thing for skin. Animal studies have shown that the virus has a preference for finding its way to skin and oral tissues, even when it’s injected into an animal’s muscles or sprayed into its nasal passages. Once there, it sets up shop, making lots of copies of itself, and these viral factories become the sites of lesions.
That’s why the dominant way to catch and spread monkeypox is by prolonged contact with an infected person who has the lesions, which can resemble small, pus-filled pimples, but are much more painful.
“Infection requires exposure to a high inoculum and nowhere is there more virus than in a lesion,” said Chin-Hong. A lesion is like a transit hub for monkeypox — from there it can go into the bloodstream to another place in the body or catch a ride into another host.
Brief contact — a handshake or fist bump — is unlikely to provide the virus with enough time to unload ample inoculum to induce a new infection. What’s likely required is hours of repeated touching, cuddling, or vigorous rubbing — especially any contact that might cause small abrasions in the skin to open up and make it easier for monkeypox to enter.
Is monkeypox a sexually transmitted disease?
Yes, and, also, no. It’s not so black and white.
Monkeypox can transmit in more ways than one, including through sexual contact. And in this outbreak, sexual contact is the primary means by which the virus is getting around.
Among 5,982 global cases for which there exists transmission data, 91% could be attributed to a sexual encounter, according to a World Health Orgaization report published this week. “Up until this point in time, the 2022 multi-country monkeypox outbreak has been overwhelmingly concentrated in MSM networks,” WHO officials wrote.
But within a sexual encounter, multiple mechanisms for transmissions are possible — contact with lesions, exchange of bodily fluids, inhalation of respiratory droplets — and disentangling them is difficult. True sexually transmitted diseases like chlamydia and syphilis require the kind of close intimate exchanges that only happen during sex. And the data on that for monkeypox remains mixed.
Last month, researchers and public health agencies in Germany reported 349 monkeypox cases for which there was available information about the likely mode of transmission — all 349 were men, and all of them had recently had sexual or other intimate contact with other men.
Unpublished contact-tracing data from the German research group found that people with monkeypox only infected others with whom they had sexual contact; other people who were considered close contacts — housemates and coworkers, for example — did not contract the disease.
In another study, published in the New England Journal of Medicine, researchers in London pored over medical records for about 500 cases of monkeypox in 16 countries during the first three months of this outbreak. They found that in 95% of cases, the person was most likely exposed through sexual contact with someone who was already infected. More than 70% of patients had lesions around their genitals, anus, or inside their mouths, sometimes only a single sore. And in the 32 cases where semen samples had been taken, the virus was present in 29.
This study is the largest to show that monkeypox is present in semen, and that it can present primarily as genital lesions without fever, widespread rash, and other typical symptoms.
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“Taken together, this makes a strong case for the likelihood of sexual transmission in the traditional sense,” Chloe Orkin, a professor of HIV Medicine at Queen Mary University of London who led the study, told STAT via email. “Sexual closeness — skin-to-skin contact with infected lesions — is the main driver.”
While Orkin’s group did not test to see if the monkeypox virus they found in semen was capable of infecting cells, another group in Italy did. In a case study published in The Lancet Infectious Diseases, the researchers found living, infectious virus in semen from one monkeypox patient for up to 19 days after his symptoms began.
This strengthens the argument that semen may be a potential conveyor of disease. But scientists stressed to STAT that the finding needs to be confirmed in other people. The patient described in the Lancet study was a man with HIV, and researchers want to be sure the discovery is not related to differences in the way the immune systems of people with HIV handle clearing the monkeypox virus from their bodies.
Still, evidence is mounting that semen requires a closer look as a potential transmission route for the virus.
A research team at the Hospital Clinic de Barcelona found high viral loads in the semen of seven out of nine monkeypox patients. The researchers also detected the virus in urine, feces, and blood — samples that have rarely been investigated for monkeypox — in a majority of 12 patients tested. “I would be very surprised if the virus is not infectious in some samples with high viral loads,” Miguel J. Martínez, an associate professor of microbiology who helped lead the study, told STAT via email. “There is a wide distribution of the virus in bodily fluids at least in the acute phase of the illness, and I think this is contributing to spread of the disease.”
More research will be required to understand exactly how much virus can survive in semen and other bodily fluids and for how long, to better inform prevention strategies.
Currently, U.K. public health authorities are recommending that people who’ve been infected with monkeypox use condoms for eight weeks after symptoms resolve. In the U.S., no official guidance has been issued, leaving physicians largely on their own for how to counsel patients.
“It’s a tough thing, because the data about viral shedding in the semen is notable but nobody really understands yet what it means for transmission,” said Chin-Hong. Instead, he’s been focusing on helping his patients reduce risks in other ways. The easiest and most effective thing men who have sex with men can do, said Chin-Hong, is limit their number of sexual partners. Like forming a Covid pod with close family or friends, keeping a more closed sexual network reduces the opportunities the virus has to spread.
“The data shows that the majority of cases in the U.S. are from people who are not just sexually active but active with lots of partners,” he said. “And that’s just playing monkeypox roulette.”
Clues that the virus could efficiently transmit sexually were apparent before this year. Starting in 2017, Nigeria began experiencing a large monkeypox outbreak that began taking off when the virus started to spread among men who have sex with men — warning signs that experts there say went unheeded.
Genetic sequencing of monkeypox genomes circulating in the current epidemic have revealed a surprising number of mutations compared with the virus circulating in Africa in 2017 and 2018. But researchers are still debating whether these changes indicate the virus has evolved to be more transmissible, or whether it simply found exactly the right kind of intimate and heavily connected social networks to ride.
WHO
Touching contaminated objects
When someone is actively infected with monkeypox, their surroundings can quickly become contaminated. Lesions, respiratory secretions, and body fluids can all leave the virus on surfaces and especially porous materials like the fabrics used in clothing and bed linens. According to guidance from the Centers for Disease Control and Prevention, the virus has been known to survive up to 15 days in the home of an infected person.
A team of researchers from Germany recently reported that they had recovered high levels of monkeypox from many hospital room surfaces, including samples they were later able to culture in living cells. But no secondary infections were found to be linked to contact with these surfaces.
Epidemiological data from this outbreak lends further evidence that the virus doesn’t spread well through this route. Only about 0.2% of people have caught the virus through contact with contaminated material, according to a recent report from the WHO.
Studies of monkeypox outbreaks in Africa in the 1980s and 1990s also found the risk of catching monkeypox from someone you’re living with to be rather low. Household attack rates there tended to hover between 3% and 11%.
Can monkeypox spread through the air?
Recent concerns over airborne transmission arose after a preprint study of hospitalized monkeypox patients in the U.K. found widespread contamination throughout their rooms, including in 5 out of 15 air samples. When they collected air during a bed linen change in one patient’s room, three out of the four samples came back positive, and the researchers were able to grow the virus from two of those samples inside cells — meaning the virus was likely infectious. The finding “highlights the importance of suitable respiratory protection equipment when performing activities that may re-aerosolise infectious material,” the researchers wrote.
This report is preliminary, and not yet peer-reviewed. But it is consistent with an incident from 2018 in which a health care worker in the U.K. caught monkeypox from a patient, possibly from inhaling virus disturbed when bedsheets were changed.
The ensuing investigation found that transmission most likely occurred when the worker was changing the patient’s bed sheets, before a diagnosis of monkeypox had been made and airborne precautions had been taken. The healthcare worker developed facial lesions as well as flu-like symptoms.
So far, the current monkeypox outbreak has not produced evidence of airborne transmission, and contact-tracing studies conducted in Europe have found infectious air to be an unlikely source of significant spread. One study by a group of researchers in Spain found that out of 153 people with known exposures, only 21 developed monkeypox, and of those,13 were household contacts. In all those cases, the exposure occurred before the patients had received their diagnosis. Once patients were diagnosed and self-isolated at home, no secondary cases appeared. A report from the UK’s National Health Service released last week also found very limited household transmission.
“If anyone was going to get infected by shared air, it would be household contacts,” said Chin-Hong. “That’s a compelling piece of data that shows even in these enriched household environments, the virus is not transmitting efficiently.”
The situation is different from Covid-19, which leading health authorities initially believed to be spread through close contact with droplets of infectious mucus and saliva released through coughing and sneezing. Evidence later emerged showing that inhalation of much smaller airborne particles drives transmission. As a result, variants of SARS-CoV-2 have much higher rates of household infections, ranging from 19% for the original strain to 43% for Omicron.
SARS-CoV-2 is a respiratory virus, setting up self-replicating shops in nose, throat, and lung tissues. And when people breathe and talk, it catches a ride on the invisible particles of goo that form as their secretion-covered airways open and close. Researchers have found that SARS-CoV-2 congregates in these smallest of particles, known as aerosols, which can stay afloat in the air for hours.
Those kinds of experiments have not yet been performed with monkeypox. But a study performed at three sexual health clinics in Spain found that in 188 patients, swabs taken from the nose and throat contained viral loads three orders of magnitude lower than swabs taken from skin lesions.
“Our study strengthens the evidence for skin-to-skin contact during sex as the dominant mechanism of transmission of monkeypox,” the authors wrote. At this point, the weight of the evidence suggests that the monkeypox virus can exist as an aerosol — either as a respiratory particle or as a fomite that’s been resuspended — but that inhaling these aerosols is not a major factor driving the epidemic.
Can asymptomatic people spread the disease?
After the outbreak began, researchers in Belgium went back and retrospectively tested 224 samples from male patients who had visited a sexual health clinic during the month of May. In a preprint study, they detected monkeypox in anal or rectal swabs taken from three men. None of them reported any symptoms in the weeks before and after the sample was taken.
“This is different to what has previously been understood about monkeypox,” said Orkin. The virus prefers replicating in skin tissues, so it’s unusual for someone to be infected without developing at least some lesions.
Whether or not such asymptomatic patients are capable of passing on monkeypox to others is still an open question. Without lesions, it’s unlikely an individual could generate enough viral inoculum to be contagious. According to the Belgian study, none of the contacts of the three asymptomatic individuals ever developed monkeypox. But this is a very new result and it will require much closer study to better understand the phenomenon and the potential risks.
The important thing about this study and the others that found monkeypox in unexpected places like blood and semen, said Chin-Hong, is that it highlights the need for physicians to rethink the way they diagnose the disease. The standard practice for testing for monkeypox is to swab a patient’s skin and any visible lesions. “That’s prehistoric,” he said. “We need explicit guidance about swabbing different sites — that’s going to be really important for keeping infected people from spreading this.”
The Statnews
