New study suggests monkeypox outbreak may be fueled in part by pre-symptomatic transmission

A new British study suggests people who are infected with monkeypox may be able to transmit the virus to others before they develop noticeable symptoms of the disease — and that this type of transmission could account for a sizable portion of infections in the current international outbreak.

Experts who reviewed the new analysis, published Wednesday in the journal BMJ, praised the rigor of the work, but warned that it cannot be considered the final answer on whether pre-symptomatic transmission occurs and if it does, to what degree it happens. More and different types of studies are needed to flesh out this question, they said.

“There is still more work needed to understand pre-symptomatic and asymptomatic infections and what that might mean for future policies and management of the monkeypox outbreak,” Nachi Arunachalam, the monkeypox incident director at the United Kingdom’s Health Security Agency, said in a statement.

The lead author of the paper, Tom Ward, is the UKHSA’s head of infectious diseases modeling; the other authors are also staff of the agency. Arunachalam is not an author on the paper.

The researchers used data from 2,746 people infected with monkeypox in the U.K. from May 6 to Aug. 1 to try to come up with estimates of the incubation period and the serial interval for the current outbreak. The incubation period is the time from infection to the development of symptoms; the serial interval is the average time from one person’s symptom onset to when the next person infected begins to show illness.

The former was estimated to be, on average, 7.6 days while the latter was estimated to be eight days — though both estimates had ranges that overlapped.

Using this information, the researchers looked at the question of whether some transmission could be happening before symptom onset occurred. It has been widely assumed that some transmission has occurred from people who were not exhibiting symptoms, based on anecdotal reports.

But in this study, the authors concluded as many as 53% of transmission events could have occurred before the person transmitting the virus developed symptoms.

“The median serial interval was estimated to be shorter than the incubation period, which indicates considerably greater pre-symptomatic transmission than previously thought,” they wrote.

There is already evidence of pushback on the 53% figure.

“It’s an important piece of the transmission jigsaw, but personally I want to see it joined up with other pieces from other types of studies before we say asymptomatic or pre-symptomatic transmission is known to account for a substantial proportion of transmission in the … outbreak affecting mostly gay, bisexual and men who have sex with men (GBMSM) in the UK,” Jake Dunning, a senior research fellow in emerging and high consequence infectious diseases at the University of Oxford’s Pandemic Sciences Institute, said in a statement.

Caitlin Rivers, an infectious diseases epidemiologist at Johns Hopkins Bloomberg School of Public Health, said it’s known that people with monkeypox are most infectious when they have the telltale lesions. But at that point, they may be less likely to have sex or other types of physical contact with others.

Paradoxically, though people may be emitting less virus in the earlier stage of their infection, when they have very mild or no discernible symptoms — a time called the prodrome — they may at that time be more likely to have contact that could lead to transmission, Rivers said.

“That could explain maybe a surprisingly high proportion of transmission happening during the prodromal period,” she said.

Esther Freeman, lead author of an editorial on the study, cautioned that it can be extremely difficult to get a clear picture of when symptom onset occurred. A person could feel tired but put it down to a bad night’s sleep, only realizing a day or two later when a rash develops that he or she had been incubating the virus.

“Anytime there’s self-reported symptom data it requires the person to have noticed the symptoms,” Freeman, director of global health dermatology at Massachusetts General Hospital and Harvard Medical School, told STAT in an interview. “When you think about what pre-symptomatic transmission is, that’s not the same for person A as it is for person B.”

Rivers agreed, saying with self-reported data “there’s always a bit of squishiness there.”

Freeman said whether pre-symptomatic transmission accounts for 53% or some smaller portion of onward spread, the fact that it likely occurs points to a need for vaccination policies to focus on protecting people before they have been exposed.

“Specifically, post-exposure or ‘ring’ vaccination of contacts identified only through individuals with symptoms, could be inadequate,” she and her co-authors wrote.

Freeman said the finding underscores the need for international discussions about vaccine equity. “If you look at the big picture of where this virus traditionally has been endemic, there is still zero access to vaccine,” Freeman said.

“We know that there could be some pre-symptomatic or pre-people-noticing-their-symptoms transmission, and really the way to handle this is to not wait till people know they’ve been exposed to be vaccinated but to have pre-exposure vaccination.”

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