British researchers have identified evidence of “considerable” transmission of monkeypox in the few days before symptoms of the virus emerge.
If replicated, the finding would upend received wisdom about how the virus spreads. It could help explain how monkeypox, which causes sometimes excruciatingly painful lesions, got so out of control this year, while also refining efforts to combat it.
US Centers for Disease Control and Prevention (CDC) guidance on monkeypox currently indicates that people “can spread it to others from the time symptoms start until the rash has fully healed”. While the CDC states that to date “there is no evidence that monkeypox spreads from people with no symptoms”, the agency is monitoring for new information.
Researchers from the UK Health Security Agency (UKHSA) published such new information in the BMJ, the British Medical Association journal, on Wednesday.
“It’s an important and potentially controversial paper,” said Dr Esther E Freeman, director of Global Health Dermatology at Harvard Medical School and a co-author of an accompanying editorial.
“It provides evidence that there may be presymptomatic transmission of monkeypox going on. But like any modeling paper, it still needs to be reproduced and validated using other real-world data.”
A relative of smallpox, monkeypox was first identified in humans in 1970 and is endemic to 11 African nations. During an unprecedented global outbreak first identified in the UK in May, the virus has largely been transmitted through sexual contact between men.
Globally, 77,174 people have been found to have monkeypox in 109 countries, including 28,442 in the US, according to the CDC. Global and US cases have been declining steadily since peaking in August, probably driven down by vaccination, sexual behavioral change and acquired immunity.
The authors of the new study examined routine surveillance data collected by UKHSA on 2,746 people diagnosed with monkeypox in Britain between 6 May and 1 August, in particular 650 who completed questionnaires. Of the 1,213 overall cohort members about whom there was such information, 95% were men who reported sex with men.
According to the accompanying editorial, the study authors made “appropriate statistical adjustments” to the data in their analysis. Specifically, they used mathematical models to control for various factors that might introduce bias, such changing UK infection rates.
The investigators analyzed questionnaire data regarding 54 members of the cohort to estimate the monkeypox incubation period – the time from infection to symptom onset. They further looked at data on 79 individuals to estimate the so-called serial interval, the period between one person’s first symptoms and the symptom onset of a person to whom they probably passed the virus.
Depending on the mathematical models used, the median serial interval was 0.3 to 1.7 days shorter than the median incubation period, which was typically about a week. This suggested that a “substantial” proportion of cases – an estimated 53% –transmitted presymptomatically.
Validation of this finding came from an analysis of 13 pairs of people between whom monkeypox was probably transmitted. Ten of these cases suggested presymptomatic transmission, occurring a maximum of four days before symptom onset.
Such findings, the authors write, suggest that efforts to trace the close contacts of people with monkeypox should not remain restricted to contacts dating back to the day symptoms began.
The investigators suggest that while monkeypox viral load might be relatively low during the presymptomatic period, “specific types of high intensity interactions” such as sexual contact might effectively overcome this obstacle and facilitate transmission.
People might also transmit the virus when they first have symptoms but before they become aware of them.
If presymptomatic transmission is indeed a major driver of the monkeypox outbreak, this calls into question the impact of public health policies compelling people to isolate while symptomatic, the study authors write. Some infectious disease experts have suggested that isolation policies might have a limited curbing effect on a virus that does not typically spread through casual contact.
Dr Boghuma Titanji, an infectious disease specialist at Emory University in Atlanta, called the study “very well done” and said it “makes a very strong argument that there is some presymptomatic transmission”.
Noting that infections that can pass silently like this are harder to control, Titanji said the study’s main finding “throws a curveball into modeling what the outbreak will look like in coming months”.
The study is limited by the fact that it depended on potentially unreliable recollections of sexual contacts and the timing of symptoms.
A French study released in a pre-print in July and published in October raised the specter of monkeypox transmitting without any symptoms. Among anal swabs taken from 200 men who have sex with men who had no monkeypox signs, 13 tested positive for the virus. At least two ultimately developed symptoms.
In a statement, Dr Nachi Arunachalam, UKHSA monkeypox incident director, said “there is still more work needed to understand presymptomatic and asymptomatic infections and what that might mean for future policies and management of the monkeypox outbreak”.
