Monkeypox: Origin, Transmission and Concern

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While we no longer worry as much about the severity of Covid, there are questions about whether the pandemic has left us more exposed to other serious illnesses. Massachusetts officials reported a rare case of a virus related to smallpox, called monkeypox, on Wednesday. A small number of cases has also been reported in the UK, Canada, Spain and Portugal. Bloomberg Intelligence senior pharmaceutical analyst Sam Fazeli spoke to Therese Raphael about what we know so far.

Monkeypox: Origin, Transmission and Concern

Therese Raphael: How is monkeypox related to smallpox and how is it transmitted?

Sam Fazeli: Monkeypox virus comes from the same family as smallpox — the orthopoxviruses. It’s the most common of its family infecting humans after smallpox was eradicated. It was not really thought of as a distinct infection until it was detected in a patient who was thought to have smallpox in Democratic Republic of the Congo in 1972. The disease that is caused by the virus is similar to smallpox, with early fever, headache and fatigue, followed by a rash two to four weeks later. Monkeypox has an incubation period of one to two weeks, similar to smallpox. The average case fatality rate of monkeypox in unvaccinated persons has been reported at as high as 10%-13%.

On transmission, the first thing to note is that monkeypox is a zoonotic infection, i.e. it goes from animals to humans, and it can infect a wide variety, but there is little detail on this. Human-to-human transmission of monkeypox is thought to be through saliva or respiratory droplets or contact with skin lesions, but it is not clear how efficient airborne transmission is. It is possible for the virus to be shed by infected individuals prior to them having skin lesions, suggesting that asymptomatic transmission can theoretically occur. While transmission is thought to be less efficient than for smallpox, there really haven’t been many epidemiological studies on this.

TR: There are two strains of the virus, one more serious than the other. What are we seeing so far?

SF: The Congo Basin monkeypox virus strain is more pathogenic than the West African strain, with higher morbidity as measured by lesion count and mortality, which for the former has been pegged at 10%–13% compared with 1% for the West African strain. So the good news is that, at least in the U.K., the cases so far appear to be of the West African strain.

TR: Does the fact that transmission is not airborne suggest we aren’t likely to see the kind of exponential growth in cases that we got used to with SARS-CoV-2? What sort of numbers would raise concerns about an outbreak?

SF: There can be transmission through respiratory droplets, though this has not been studied extensively enough to be sure how efficient it is. Remember that the problem with SARS-CoV-2 was that it was also transmitted by aerosol, which can hang around in a room for much longer than droplets, which tend to fall to the ground relatively quickly. But given its mortality rate, even of the less virulent West African strain, and the fact that many younger people born after the 70s do not have immunity to the virus, even low rates of transmission can have dramatic societal impact.

TR: Do existing vaccines protect against monkeypox? Are there antiviral treatments that work for those who become ill?

SF: We have both. Two vaccines are approved for smallpox, though one has actually been approved for monkeypox. Bavarian Nordic’s Jynneos has been approved by the US Food and Drug Administration and many other regulatory agencies for both smallpox and monkeypox, whereas Emergent BioSolutions Inc./Sanofi’s ACAM2000 is only approved for smallpox, though is also likely to work against monkeypox.

The biggest difference between the two vaccines is safety, with ACAM2000 carrying a black-boxed warning on its FDA label about the risk of myocarditis/pericarditis, which was seen at a high rate of 5.7 cases per 1,000 people. There are other side effects that could preclude its broad use.

There are also drugs. Chimerix’s Tembexa capsules and liquid formulation, which the company is in the process of selling to Emergent BioSolutions, was approved by the FDA in June 2021 for the treatment of smallpox infections. It has shown activity against monkeypox in animal models, but I am not aware of data in humans. SIGA’s Tpoxx capsules were approved in 2018 and a liquid formulation has been developed since.

TR: The fact that we’re seeing this emerge now — is that pure coincidence or does that suggest the pandemic has weakened immunity enough to allow something like this to seed?

SF: It has nothing to do with weakened immunity associated with the pandemic. You could say that about flu or the common cold virus or even Respiratory Syncytial Virus, but not this. What is likely going on is that the global level of immunity to orthopoxviruses has declined, as the last smallpox vaccination campaigns ended in the 1970s. As such, not only have a lot of people been born since and not been vaccinated with a smallpox vaccine, but also there is probably some decline in immunity against infection, even in those who did get a vaccine a long time ago.

TR: So should we be worried about monkeypox?

SF: I would say it depends on when and where you were born, which determines your vaccination status. There is clear data in non-human primates that shows those vaccinated with a smallpox vaccine were protected from a lethal dose of monkeypox. For those who are too young to have been vaccinated against smallpox, the risk is likely to be in the ranges noted above.

The biggest question is whether infections will spread or can they be quickly contained. One way is to use ring vaccination, that is, vaccinating individuals in areas where there has been a case detected — and certainly the people who have been at risk of contact with the infected individuals. As such, the transmission chain can be broken a lot easier than with SARS-CoV-2. Whether the virus has mutated in a way that increases its transmission is unknown.

It’s very early days and we have tools to help manage outbreaks. But we need to be very vigilant given the morbidity/mortality risk of the virus.

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