What's up with the recent monkeypox cases? Why are we seeing a monkeypox outbreak now just as COVID-19 vigilance is winding down? Why didn't we see more monkeypox outbreaks 10 or 20 years ago? 

Tl;dr: Waning smallpox immunity has allowed monkeypox to spread steadily since the 1990s. The disease recently returned to Nigeria, just as Nigeria started getting a lot more tourism. People are traveling more post-pandemic. Most Nigerian vacationers go home to their families, but this Nigerian vacationer went to, or at least knows people who went to, a couple of huge pride raves.

This virus has boring, known genetics. So, unless we start offering a program of smallpox vaccination in Africa, this is probably the first of a series of monkeypox outbreaks. But it's not the start of a pandemic.

First, we are starting to get data falsifying the hypothesis that this is a new, more infectious variant. Dr. Grant McFadden, director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University, was reported by NBC as describing the early draft of the outbreak monkeypox virus's genetics as looking pretty run-of-the-mill.

This is reassuring, but it doesn't explain why we're seeing such a big monkeypox outbreak now, or why we've seen a quiet but persistent drumbeat of non-African cases in the last few years.

So let's consider how it is that conditions have become conducive to monkeypox jumping from Africa to other continents. Monkeypox as we known it transmits relatively slowly, has been studied for decades, and the USA has an 85 million dose stockpile of 85% effective vaccine and some possible antiviral treatments.

Bunge et al. (2022) discuss the epidemiology of monkeypox. Their paper was well-timed, published just a couple months before our current multi-continent outbreak. I'll be referring to it frequently here.

Waning vaccination

Ah, the good old days. Back in 1967, 80% of the population in every country was vaccinated against smallpox, and consequently against monkeypox as well. However, maintaining such a mass vaccination campaign is expensive, and the vaccine causes smallpox in very rare cases. The producer of smallpox vaccine stopped production in 1982, shortly after the disease was declared eradicated. For all these reasons, very few people, relatively speaking, have received smallpox vaccine since then.

Smallpox vaccine efficacy also declines starting about 3-5 years after the jab.

Here's Bunge on waning population immunity:

Using statistical modeling, Nguyen and colleagues estimated that in 2016, the year before the outbreak in Nigeria began, only 10.1% of the population was vaccinated, and the population immunity, which takes into account waning individual-level immunity, was 2.6%, down from 65.6% in 1970. By 2018, the vaccinated population had decreased to 9.3% and the estimated population immunity had declined to 2.2%. In our review of the literature, we found that unvaccinated individuals accounted for approximately 80–96% of monkeypox cases.

Bunge references a couple of studies that find that:

• "the majority of cases (approximately 80–96%) occurred in unvaccinated individuals"
• "in a study of confirmed and suspected cases in the CAR, 19.2% (5/26) had a smallpox vaccination scar"

This shouldn't be reassuring at all, given that individual-level immunity was around 2.6% in 2016 and the vaccinated population is around 10%. If I had to guess how 19.2% of cases in the CAR had a vaccination scar when only around 10.1% of the Nigerian population is vaccinated, I'd guess that it's caused by differences in national vaccination rates and, possibly, a larger number of cases among older people; I haven't looked into this.

Waning vaccination isn't bad on its own. Absent an accident or bioterrorism, we are at zero risk of getting smallpox anymore. But monkeypox, unlike smallpox, has animal reservoires, and it was only a matter of time before it re-emerged...

Disease re-emergence and spread

Once monkeypox started to sneak back out of the jungle and into African communities, it was able to spread steadily, increasing both in terms of the number of annual cases and the number of countries where it's endemic. Since monkeypox transmits relatively slowly, we don't see the explosive spikes and crashes of cases, as we saw in COVID-19. Instead, we see steady growth in case numbers year over year.

Over the last 10 years, monkeypox re-emerged in Nigeria "after a 40 year hiatus." They reported 3 cases from 1970-2017, and then got hammered with 228 suspected cases (or 181 "confirmed and probable cases" according to Bunge) in September 2017. Since then, monkeypox has persisted in Nigeria.

Both clades have been increasing steadily over time throughout the African countries where it is endemic. Some of the case discovery is due to better reporting as opposed to real increases in cases, but after 2008, the DRC, which is the main reporter for the Congo Basin clade, had stable reporting.

So we have a progressively more vulnerable population, with the disease becoming ever more common in central and west Africa year by year.

Increased tourism

Patient zero in this outbreak was a UK resident returning from a trip to Nigeria. To infect Europe, the virus had to take a vacation of its own. The more tourism we have in countries where the virus is endemic, the more chances the virus has to hitch a ride to the EU, Asia, Australia, and the Americas.

Our outbreak's brand of monkeypox, the West African clade, is endemic in Nigeria, Benin, Cote d'Ivoire, Liberia, Sierra Leone, and Cameroon. Tourism is low or data unavailable in most of these countries, but Nigeria has been experiencing a tourism explosion from 2006 at least through 2016, and Cameroon's has been increasing more recently.

As we know, monkeypox is also becoming more and more common in these regions. These two trends combined are giving the virus more chances to mix with the tourist population and spread to other continents.

Is Nigerian tourism really booming? The US state department recommends against traveling in Nigeria, and some bad stuff has gone down in Nigeria over the last 10 years. The tourism data in these charts is patchy, and we don't have post-pandemic data. Nigeria is one of the most corrupt countries in the world. Can we trust this data on their international arrivals or tourist spending? It's hard to know for sure, but it tracks with what we're seeing right now.

You might have heard that there's a deadlier monkeypox out there, the Congo Basin clade. It's endemic in Gabon, Republic of the Congo, Democratic Republic of the Congo, Central African Republic, and South Sudan, but tourism in this region is about 0.1% of that in West Africa. If tourism is important for generating viral outbreaks in Europe or the Americas, then the West African clade is probably the one to worry about.

Once the virus makes it to Europe, it's easy for it to spread around as EU members like to visit each other's countries for their vacations. 83% of inbound arrivals in the EU are from other EU countries. And we are in a time where many people are excited to go on vacations they've been unable to take for the last few years, although tourism still seems somewhat lower than at this time in 2019.

So people are probably traveling to Nigeria more than they did over the last two years, and Europeans are also traveling between each others’ nations more often, giving the disease more of a chance to spread from Africa to Europe and circulate within Europe.

Random chance

We've seen individual monkeypox cases, and one 47-person outbreak in the USA in 2003 linked to prairie dogs. They'd been housed next to 800 small imported Ghanian mammals - "rope squirrels, tree squirrels, African giant pouched rats, brush-tailed porcupines, dormice, and striped mice." I could show you a picture of a person with monkeypox pustules, but instead I'll show you Magawa, the landmine-sniffing pouched rat who does not have monkeypox:

All our previous outbreaks apparently infected boring responsible people who have to stay home to take their prairie dogs for a walk or whatever. Fortunately, such people make up a large proportion of the world's population. This time, it seems we got unlucky. with a disease that happened to hit a group of people having a whole lot more fun, making it easy to transmit the virus to each other.

I think this outbreak is well-explained by waning vaccination causing increased viral spread in Africa, along with increased African and European tourism giving more chances for the virus to cause an outbreak. Sometimes, we'll get lucky, and other times, people will go to a rave with monkeypox.

When we add in the early data that seems to show boring known genetics for the virus causing the outbreak, plus the confidence of epidemiologists in being able to carry off ring vaccination to contain the outbreak, I think we do not have to worry about a monkeypox pandemic.

At the same time, we're only going to see more monkeypox outbreaks in the future as the disease continues to spread in Africa. This is going to be an intermittent and incrementally growing problem, and the people of the industrialized world may want to figure out how to support Africa better in driving monkeypox back down.

For forecasting, some of the most important questions are:

• Will the current monkeypox outbreak be declared eradicated by the WHO by October 1, 2022?
  • My prediction: 75% yes.
• Will at least one peer-reviewed publication with evidence that the current outbreak was started by a faster-transmitting virus be published in 2022?
  • My prediction: 90% no.
• Will a second monkeypox outbreak infecting more than 100 people occur by May 24, 2027?
  • My prediction: 70% no.