Asymptomatic mpox infections among men who have sex with men (MSM) may be far more common than previously recognized and could be playing a role in ongoing transmission, according to a study published last week in Nature Communications. Researchers estimate that actual infections may outnumber diagnosed cases by 33 to one.
The findings challenge the assumption that most mpox cases are spread by people with symptoms.
1% had asymptomatic mpox
For the study, researchers led by teams at the University of California (UC) at Berkeley and Kaiser Permanente Southern California tested for mpox in MSM in Los Angeles during routine sexually transmitted infection (STI) screening from May to November 2024. Then they monitored the same group of MSM for clinically diagnosed mpox.
Among nearly 8,000 eligible participants, only 15 laboratory-confirmed mpox cases were identified through standard clinical testing. But when the team tested for mpox DNA in 1,190 specimens collected from the routine STI tests, they found infections in six men who never presented with mpox symptoms or received an mpox diagnosis.
“We used the specimens from routine testing for other sexually transmitted diseases to test for mpox and found roughly 1% of men had asymptomatic infections without knowing it,” lead study author Joseph A. Lewnard, PhD, associate professor of epidemiology at the UC Berkeley School of Public Health, said in a news release. “From the testing, we estimated that only about one in every 33 infections gets diagnosed,” meaning infections exceeded reported cases by a 33-fold margin.
Undiagnosed cases may drive 31% to 44% of spread
These cryptic infections likely contribute to under-the-radar mpox spread. The authors estimate that undiagnosed infections may account for at least 31% to 44% of all transmission events and, under “realistic modelling assumptions,” potentially much more.
The findings run counter to current guidance from the Centers for Disease Control and Prevention, which has advised that people with symptoms primarily drive mpox spread, despite a lack of connection to a symptomatic partner.
“We have not known how mpox is transmitted, and why the cases seem to have very few connections to other cases,” senior study author and Kaiser Permanente scientist Sara Y. Tartof, PhD, MPH, said in the news release. “These findings help resolve a fundamental question in the epidemiology of mpox by suggesting that infected people pose a risk of transmitting the disease to others even in the absence of clinical symptoms.”
Vaccination may reduce disease severity
The researchers also found that pre-exposure immunization with the Jynneos vaccine was associated with 72% effectiveness against diagnosed mpox. The finding that previously vaccinated men accounted for five of the six subclinical infections identified through routine STI testing suggests that vaccination may help protect against mpox by reducing disease severity, which aligns with previous research.
“Unvaccinated people face risk of severe disease if they are exposed to mpox,” Lewnard said. “And our findings suggest this risk is greater than we previously understood.”
