What drives sustained growth of monkeypox cases

As of June 15, a total of 1,882 monkeypox cases have been lab-confirmed from more than 30 countries across the world. With 1,158 confirmed cases from 22 countries, Europe has reported the highest number of cases so far, according to the European Centre for Disease Prevention and Control. The U.S. has reported 83 cases across 19 States as of June 16.

While monkeypox has been endemic in about a dozen countries in Central and West Africa, the virus is not endemic in people. “Nearly all” monkeypox outbreaks in these countries have been due to the virus jumping across the species barrier from animals to humans.

Sustained human-to-human transmission in the endemic countries has been “rare”, Dr. Christian Happi from the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University, Nigeria and others write in a report posted in virological.org.

Outbreaks in the endemic countries in Africa have witnessed only a “limited” proportion of cases spread among humans, with sustained transmission observed only up to seven generations. And the basic reproduction number (R0) for monkeypox in the endemic countries has been less than one, even among populations that have not received smallpox vaccination. The basic reproduction number being less than one would mean that “outbreaks would fade out if without continuous introductions from animals”, Dr. Akira Endo from the London School of Hygiene & Tropical Medicine, London, tweeted.

In contrast, the current outbreak in the U.S., Europe, Middle East and Australia has shown a clear trend of sustained spread among people, particularly among men who have sex with men (MSM). Before this outbreak, there have been about 100 cases of monkeypox cases outside Africa, with the outbreak in the U.S in 2003 being the biggest with over 70 people infected by the virus. But all the 70 cases were due to exposure to imported animals with no human-to-human transmission reported back then. In the past, outside Africa, the virus had spread to just one healthcare worker and two household contacts, a far cry from the sustained human-to-human transmission now being reported. 

Modelling exercise

To explain the vastly different pattern of spread to a large number of people within a month after the first case was reported in the U.K. on May 7, Dr. Endo and others used a mathematical model based on sexual partnership data in the U.K., to explain the epidemiology of the current outbreak. The results of the modelling exercise have been posted in medRxiv preprint server; preprints are yet to be peer-reviewed.

Increased importation of the virus, undetected spread in the community, virus evolution, and increased susceptibility to monkeypox virus infection due to smallpox vaccination coming to an end a few decades ago could be possible reasons for the current outbreak outside Africa The researchers point out that most of these factors are “not strongly supported by external (if indirect) evidence” nor able to explain human spread predominantly among men who have sex with men (MSM) and not widespread in the general population in the community. 

The driver

The researchers found that a “small fraction of individuals who have disproportionately large numbers of partners” must be responsible for the sustained human-to-human transmission of the virus among men who have sex with men.

This is the largest outbreak predominantly among men who have sex with men. In Nigeria, higher prevalence and lesions in the genital area have been recorded in a recent outbreak.

“Our model suggests that the MSM population has possibly always been at risk of a sustained outbreak. The reason we haven’t seen an outbreak among MSM before might be that the virus had not reached this network given how few cases there were in total,” Dr. Endo tweeted.

The researchers explain this in more detail in the preprint when they say that monkeypox virus always had a “substantial transmission potential in the MSM” community even in the past but the small number of imported cases outside Africa likely resulted in the virus not spreading to this network resulting in large-scale transmission.

The researchers also modelled outbreaks that are sexually associated in both MSM and non-MSM populations. They considered varying assumptions for the risk of transmission between sexual partners in both these groups.

In contrast to a small fraction of MSM individuals who have a large number of partners thus increasing the virus spread to many people in the MSM community, the researchers found sustained spread in the non-MSM population “unlikely” due to less probability of a few individuals having multiple sex partners. But “10-10,000 additional cases may be observed if a substantial number of infections are introduced into the non-MSM sexual contact network,” they write. 

Seeding the outbreak

They note that a “very small number of sexually-associated transmissions” in the MSM community is sufficient to cause a large outbreak. In contrast, a large number of non-sexually-associated imported cases are needed for the virus to gain a foothold in the MSM community and then spread to large number of people through sexually-associated spread. And this may be the reason why the virus did not reach the MSM community in the past through imported non-sexual cases. They note that better surveillance in the endemic countries might be needed if the current outbreak outside Africa in the MSM community had come about from a few sexually-associated cases imported from the endemic countries.

“Without sufficient interventions, we may see continued growth in MSM. Monkeypox virus can infect anyone; the non-MSM population will also be affected if we fail to contain it. Tailored and non-stigmatising messaging/support for those at highest risk would be key to earliest containment,” Dr Endo tweeted. Targeted messaging is necessary for prevention and early detection of cases among MSM who have multiple partners, the authors write. 

• While monkeypox has been endemic in about a dozen countries in Central and West Africa, the virus is not endemic in people.
• Researchers found that a “small fraction of individuals who have disproportionately large numbers of partners” must be responsible for the sustained human-to-human transmission among men who have sex with men (MSM).
• The researchers found sustained spread in the non-MSM population “unlikely” due to less probability of a few individuals having multiple sex partners.

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