Thursday, November 03, 2022

BMJ: Transmission Dynamics of Monkeypox in the United Kingdom: Contact Tracing Study


Monkeypox Virus Credit CDC PHIL


A little over two years ago - after repeated exported cases of Monkeypox turned up in the UK, Israel, and Singapore - the Bulletin of the World Health Organization carried a report called Modelling human-to-human transmission of monkeypox, where the authors reassuringly stated:

Monkeypox is not considered contagious during its incubation period and asymptomatic monkeypox infection has not been documented.

Of course, `has not been documented' isn't quite the same thing as `never happens'.

Particularly when you are talking about a poorly investigated disease like Monkeypox. Earlier this summer, after the dramatic surge of Monkeypox reported in the MSM community, a statement from the CDC left the possibility of asymptomatic transmission on the table. 

Unknown/Still learning: Contact with people who are infected with monkeypox but have no symptoms (We think people with symptoms are most likely associated with spread, but some people may have very mild illness and not know they are infected).

Six weeks ago, in Annals Int. Med.: Detection of Monkeypox Virus in Asymptomatic Men Who Have Sex With Men (MSM), we saw a report from the Bichat-Claude Bernard Hospital in Paris that documented the detection - via PCR-tested anal swabs from 200 asymptomatic MSM visiting a clinic - of the Monkeypox virus in 6.5% (n=13) of the tests.

While two of these 13 eventually reported symptoms, this data suggested that asymptomatic carriage of the virus is not only possible, it may even be fairly common. 

Yesterday the BMJ published a study (and an accompanying editorial) that provides additional (statistical) evidence suggesting that asymptomatic - or pre-symptomatic - transmission of Monkeypox likely occurs with considerable frequency.  Their summary: 

What is already known on this topic
Monkeypox was first detected in 1970 in the Democratic Republic of the Congo

The incubation period and serial interval have been estimated from observational studies

Since the international outbreak of monkeypox in May 2022 a study estimated a mean incubation period of 8.5 days; however, the sample size was small (n=18)

What this study adds

This study found evidence of pre-symptomatic transmission of monkeypox, using contact tracing data and adjustments for interval censoring, right truncation, and epidemic phase bias

The maximum time that transmission was detected before symptoms manifested for infected individuals who could be linked through reliable personal identifiable information was four days

While those who are statistically challenged (like myself) will find it tough sledding, the full open-access is available for your perusal. I've only posted some excerpts from the Abstract and the implications of their findings.  Follow the link to read it in its entirety.

Transmission dynamics of monkeypox in the United Kingdom: contact tracing study
BMJ 2022; 379 doi: (Published 02 November 2022)
To analyse the transmission dynamics of the monkeypox outbreak in the UK, declared a Public Health Emergency of International Concern in July 2022.
Contact tracing study, linking data on case-contact pairs and on probable exposure dates.
Case questionnaires from the UK Health Security Agency (UKHSA), United Kingdom.
2746 people with polymerase chain reaction confirmed monkeypox virus in the UK between 6 May and 1 August 2022.

We found that shorter serial intervals are more common than short incubation periods for monkeypox, which suggests considerable pre-symptomatic transmission. This has also been observed for other viral infections1112 and is a consequence of transmission during the pre-symptomatic period. Previous research has not found evidence of transmission and substantial shedding of monkeypox virus before symptom onset, which is reflected in guidance from WHO and the European Centre for Disease Prevention and Control.2333 

Assuming statistical independence between the serial interval and incubation period, we found that 53% (95% credible interval 43% to 62%) of transmission occurs in the pre-symptomatic phase. However, since serial intervals depend on the incubation period this finding is an approximation of the proportion of infections due to pre-symptomatic transmission. This finding is consistent with the proportion of pre-symptomatic transmission among the subset of case-contact pairs where transmission can be identified relative to the date of symptom onset after exposure. Data for both the serial interval and the incubation period are similarly distributed across the monkeypox outbreak in the UK, so temporal changes in reporting should affect both distributions comparably (see supplementary material C).

(Continue . . . )

You'll find an accompanying editorial that urges "Pre-exposure vaccination and vaccine equity are urgently needed worldwide", at: The dynamics of monkeypox transmission (BMJ 2022;379:o2504). 

An assessment on the study's design by Dr Boghuma Kabisen Titanji, Assistant Professor of Medicine, Emory University (Atlanta), is posted on the Science Media Centre's website.

While these findings are less surprising today than they would have been 6 months ago, they remind us that science is a journey of discovery, and of the importance of changing public health tactics when new data appears.