‘Substantial’ pre-symptomatic monkeypox spread found

There is now more evidence for pre-symptomatic transmission of monkeypox virus. A study published recently in BMJ, which involves a larger cohort, found that pre-symptomatic transmission had taken place as long as four days before symptoms manifested. The researchers have estimated that 53% of monkeypox virus transmission have occurred during the pre-symptomatic phase. 

Pre-symptomatic transmission of monkeypox virus will mean that many infections cannot be prevented by simply isolating people showing symptoms. Also, the effectiveness of contact tracing and subsequent quarantine will not be sufficient to break the transmission chain since by the time all the contacts have been traced, they might have already spread the virus to other people. “Pre-symptomatic transmission has implications for vaccination strategies and the feasibility of disease elimination,” Dr. Boghuma K. Titanji, a physician-scientist at Emory University in Atlanta, said in a tweet.

Previously, two smaller studies — published in the  Annals of Internal Medicine and  Nature Medicine — had found evidence of such transmission before symptoms showed up. “The smaller studies are more what one would call a signal. They were too small to be considered solid evidence of this phenomenon. [This] paper is really compelling with a much more robust sample size,” she tweeted. 

Detailed study

The contact tracing study of 2,746 individuals who tested positive for the monkeypox virus in the U.K. between May 6 and August 1, 2022 has linked data on case-contact pairs and on probable exposure dates together with modelling to determine pre-symptomatic transmission.  

The researchers first set out to find the mean incubation period and mean serial interval using two models. Serial interval is the time from illness onset in the primary case to illness onset in the secondary case. They found the mean incubation period to be 7.6 days in one model and 7.8 days in the other, and the mean serial interval to be 8 days in one model and 9.5 days in the other.

The most important finding was that the median serial interval was 0.3-1.7 days shorter than the median incubation period. This provides crucial evidence that considerable transmission was happening even before symptoms showed up.

In a cohort of 13 case-contact patient pairs with detailed individual-level patient data — symptom onset date in the primary case, date of exposure in contacts, serial interval, and the incubation period — 10 out of 13 linked patients had documented pre-symptomatic transmission.

According to the researchers, pre-symptomatic transmission can take place in “specific types of high intensity interactions such as sexual contacts where lower pre-symptomatic viral loads are infectious”.

In endemic countries in Africa, people were infected with monkeypox virus by coming in contact with infected animals. Human-to-human transmission occurred only occasionally and was largely restricted to household contacts. Human-to-human transmission prolonging over a few generations were rare, if not absent. But the virus spread outside Africa this year has primarily been due to human-to-human spread and the transmission during prolonged sexual contact among men who have sex with men, has led to clear instances of pre-symptomatic spread of the virus.

The study has a few limitations. The study relied on self-reported data such as the symptom onset date, which is the date patients noticed they had an infection. Also, the study relied entirely on contact tracing to identify case-contact pairs. The study has assumed the linked pair to be genuine transmission events and had no way of directly ascertaining the direction of transmission. The study has assumed that transmission follows the direction of symptom onset dates. Though likely to be true in most cases, the possibility of some overestimation of the serial interval cannot be ruled out.

“The overestimation in turn will bias the data away from pre-symptomatic transmission, which further supports the evidence of pre-symptomatic transmission,” they write.

A linked editorial has cautioned that “post-exposure or ring vaccination of contacts identified only through individuals with symptoms could be inadequate”. But the U.S. and the U.K. had already shifted from exclusively post-exposure prophylaxis to include pre-exposure prophylaxis for some high-risk groups. 

The editorial also underlines the importance of making vaccines accessible and equitable. Even in the U.S., while the black people account for 50% of infections, only 12% of the vaccines were administered to this vulnerable group. In the case of Nigeria, where monkeypox is endemic, vaccines are simply not unavailable currently. The same is the case in other endemic countries in Africa. Not only vaccines, even PCR testing remains unavailable in much of Africa, it says.