BMJ: Monkeypox spreads "in large numbers" before symptoms appear or are detected

A UK study published today in the British Medical Journal found evidence of "massive" transmission of monkeypox before symptoms appear or are detected (known as presymptomatic transmission).

Transmission is detected four days before symptoms appear, and researchers estimate that more than half (53%) of transmission occurs in the pre-symptom phase, meaning many infections cannot be prevented
by requiring individuals to isolate after discovering their symptoms.

In a related editorial, the researchers said that if the findings are supported by other studies, presymptomatic transmission "will have important implications for global infection control.
"

Since the international outbreak of monkeypox in May 2022, more than 70,000 cases have been recorded globally, with just over 3,500 cases in the UK
.

Although the number of cases is now declining, it is still important to understand the "dynamics of transmission" of the virus – for example, how it spreads from one person to another and how quickly symptoms appear – which can help inform
policy decisions and future interventions.

While previous studies of pox viruses have not ruled out transmission before symptoms appear, this work represents the first evidence
to support this.

To explore this further, researchers from the UK Health Security Agency set out to analyse the dynamics
of the monkeypox outbreak in the UK.

Their findings are based on routine surveillance and contact tracing data
from 2746 individuals who tested positive for monkeypox virus in the UK between 6 May and 1 August 2022.
Their average age is 38, and 95 percent identify as gay
, bisexual, or men who have sex with men.

The two main measures of interest to the researchers were continuous interval (the time from the onset of symptoms in a patient with a primary case to the onset of symptoms in a secondary contact patient) and latency (the time from exposure to the onset of symptoms).

To estimate this, they linked information about these people's contacts and dates of symptom onset to their contacts through a contact tracing case questionnaire, which was then analyzed
using two statistical models.

These models are adjusted for several common biases in viral outbreaks, such as changes in infection rates over time, which would otherwise affect the results
.

The mean latency was estimated at 7.
6 days for one model and 7.
8 days for the other, while the mean sequence interval was estimated at 8 days for one model and 9.
5 days
for the other.

For both models, the median continuous interval was 0.
3 to 1.
7 days shorter than the median incubation period, indicating that a large amount of transmission
had occurred before symptoms appeared or detected.

Individual-level patient data analysis collected from a more detailed set of patients appeared to confirm this explanation, with 10 of the 13 pairs of case contacts reporting presymptomatic transmission
.
4 days is the maximum time that
transmission can be detected before symptoms appear.

Based on these results, the researchers say it would take a 16- to 23-day quarantine period to detect 95 percent of potentially infected people
.

These are observational findings, and the researchers point out some limitations, such as relying on contact tracing to determine the correct contact pair of cases and self-reported data
on the date of symptom onset.
In addition, the findings are not necessarily directly applicable to other populations
with different modes of transmission.

Nevertheless, this is a large study that uses robust methods and adjusts for key biases in the data, providing greater confidence in the
conclusions.

The scientists say the findings have important implications for isolation and contact tracing policies, adding that backward contact tracing strategies (tracing who the disease is transmitted from) should take into account the pre-symptomatic period
of infection when trying to find contacts of confirmed cases.

In a related editorial, researchers from the United States, the United Kingdom and Nigeria argue that pre-exposure vaccination and vaccine equity
are urgently needed globally.

They explain that vaccination may be more cost-effective than managing the consequences of preventable infections, including hospitalization, loss of income during isolation, and long-term
complications.

However, they note that many of the public health measures that play a key role during monkeypox outbreaks in high-income countries remain absent
in much of Africa.

"As monkeypox outbreaks decline in Europe and North America, it is incumbent upon us to deploy effective virus control tools at the global level – not just in rich countries
," they wrote.
"These tools include studies to understand transmission dynamics in African settings and the inclusion of endemic countries in vaccine trials
.
"