There could be significant monkeypox transmission before symptoms appear, making it tougher to get infected people into timely quarantine, according to an observational study.

An analysis of contact-tracing data from the U.K. Health Security Agency (UKHSA) showed that transmission was spotted up to a maximum of 4 days before symptom onset, and that 53% of transmission occurred in this pre-symptomatic phase, reported Thomas Ward, of UKHSA in London, and colleagues.

“An isolation period of 16 to 23 days would be required to detect 95% of people with a potential infection,” they stated in The BMJ.

After adjustments for right truncation and epidemic phase bias, the group found that the average incubation period was estimated to be 7.8 days, while the average serial interval (the time from symptom onset in the primary case patient to symptom onset in the secondary contact) was 9.5 days.

“The median serial interval was estimated to be shorter than the incubation period, which indicates considerably greater pre-symptomatic transmission than previously thought, and was validated by analysis of individual level data,” wrote Ward and coauthors.

The findings from the modeling study indicate that many infections cannot be prevented by asking individuals to isolate after they notice their symptoms, and that “pre-symptomatic transmission … would have important implications for infection control globally,” Esther Freeman, MD, PhD, of Massachusetts General Hospital in Boston, and colleagues pointed out in an accompanying editorial.

Freeman’s group noted that postexposure vaccination of contacts found only through symptomatic people could be inadequate, so the U.K. and the U.S. are on the right track by shifting the monkey vaccine “from exclusively postexposure prophylaxis to include pre-exposure prophylaxis for some high-risk groups.”

Ward’s group looked at serial interval along with incubation period, or the time from exposure to onset of symptoms, in 2,746 individuals in the U.K from May to August 2022. Time to doubling of cases was 9.07 days (95% credible interval 7.08-12.63) on May 6, when the first case of monkeypox was reported in the U.K., while on August 1 the halving time of cases was 29 days (95% CI 23.44-38.02).

Participants all had PCR-confirmed monkeypox virus, their average age was 38 years, and 95% reported being gay, bisexual, or men who have sex with men.

The researchers found that 10 of 13 linked patients had documented pre-symptomatic transmission.

Among respondents (median age 37) to case questionnaires, “53% had a history of a sexually transmitted infection over the past year, and 31% had at least 10 or more sexual partners in the past three months,” Ward and colleagues said. That contrasted with “the Democratic Republic of the Congo, where in 2016 the median age was 10 years and by 2020 only 42% of cases were older than 5 years. This is indicative of changes in the primary routes of transmission for the monkeypox virus in the 2022 epidemic.”

Regarding their finding that 53% of transmissions took place in the pre-symptomatic phase, the authors cautioned that “since serial intervals depend on the incubation period this finding is an approximation of the proportion of infections due to pre-symptomatic transmission.” Other study limitations included the use of “contact tracing to identify the correct case-contact pairs and the self-reported data on date of symptom onset,” they noted in a press release. They also warned that the data may not necessarily be directly applicable to other populations with different transmission patterns.

Freeman’s group highlighted that lack of equitable access to vaccines to control monkeypox is a serious concern, and it’s even more of an issue if pre-symptomatic transmission is occurring. “In the U.S. … Black people account for 50% of monkeypox infections but received only 12% of the vaccines,” they wrote.

“From a health system perspective, vaccination is likely to be more cost effective than managing the consequences of preventable infections, including hospital admissions, loss of income during isolation, and long-term complications,” they said.

Freeman and colleagues also emphasized that the monkeypox outbreak may be waning in Europe and North America, but “we have a responsibility to deploy effective tools for viral control on a global level — not just in wealthy nations. These tools include research into understanding transmission dynamics in African settings and the inclusion of endemic countries in vaccine trials.”

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