This episode is brought to you by Complexly Calendars, because we made a calendar themed around the number pi and you can get it for a limited time a complexlycalendars.com. Stick around til the end to learn more. 

This episode was filmed on September 27th, 2022. If major new developments happen, we will update them in the video description and make new videos as necessary. 

With everything the Covid pandemic has put us though, news of the circulating disease, commonly known as monkeypox, has weary folks thinking, "Not another pandemic." But monkeypox is not a pandemic.

In July of 2022, the World Health Organization declared it a Public Health Emergency of International Concern, which is a different designation. It shares this honour with COVID-19, which is a pandemic, but also polio, which is not. 

Unlike SARS-CoV-2, which was a brand new coronavirus in 2019, monkeypox is nothing new. It was first identified in humans decades ago in 1970. It had rarely been recorded outside of sporadic cases in central and west Africa where it has been endemic for decades. 

But as of summer of 2022, it's been found in over a hundred other countries including the United States, Canada, Australia, and parts of Europe. And in fact, there is now some evidence that our current outbreak has been slowly burning since 2017 when Nigeria saw its first cases of human monkeypox in almost 40 years. And that's not for sure yet, but the case is strong so we're going to treat it as somewhere between 'likely' and 'yeah this is a thing'. 

And the current situation is different in a lot of ways from disease outbreaks in the past. It's different from Covid, it's different from other diseases with disproportionate impacts in LBGTQ+ communities, and it's different from previous endemic human monkeypox outbreaks. Stop thinking about it like it's the same as anything else! 

Now before diving into some of the differences, a few basics upfront. 

Human monkeypox virus belongs to the genus orthopoxvirus, which also includes smallpox. Like smallpox, it is a large DNA-based virus that infects skin tissue.

Smallpox only affected humans allowing us to eradicate it with worldwide vaccination. Monkeypox on the other hand is carried by humans and animals, so it's harder to pin down.

Over the last few decades, there have been two major strains of the virus that researchers have identified, currently referred to as Clade I and Clade II, where a clade is a general term for a taxonomic group. These were renamed after having been initially named after the parts of Africa where they originated, so as not to worsen the geographic stigma associated with the current outbreak. 

In fact, we should note, that the term monkeypox itself is on the way out. Partly because of the association with racist slurs about black people. Scientists also argue that as a name it's simply inaccurate.

The virus was initially discovered in 1958 in a group of monkeys used for research, not in Africa but in Denmark. But even though it was discovered in primates, it's been known to infect all kinds of creatures. Squirrels, hedgehogs, and mice. And it's unclear which animal it first appeared in. 

Some researchers are using the rather clunky hMPXV for the human monkeypox virus as a placeholder. They're urging the international committee that names viruses to make a speedy decision on a new name. But for the purposes of the episode, we're going to call it human monkeypox despite the term's flaws.

And if you're betting on where we'll end up, the smart money might be on 'human monkeypox virus' or 'human simian orthopoxvirus' becoming the official name. I don't make the rules. I'm totally calling my shot though. I think 'human simian orthopoxvirus'. 

Now the first main difference between previous outbreaks and the current outbreak is how humans contract the disease. Reported cases in humans previously came from direct contact with infected animals, known as zoonotic transmission. We're going to call that zoonotic monkeypox for the rest of the video.

For instance, in 2003 a suspected 47 individuals in the US caught it from infected prairie dogs purchased from pet shops. Rarely, infected pregnant people could transmit it to their child during gestation and birth. But, in recent years, humans have been catching it from other humans, also known as human-to-human transmission, which we will be calling human monkeypox. 

This isn't 100% new, as it's been seen in endemic versions of the virus in the Democratic Republic of the Congo. 

But right now, and since 2017, sexual activity has been in the mix as a driver of the virus's spread. Note that human monkeypox is NOT classified as a sexually transmitted infection. As far as we know, close contact during sex just presents it with a good opportunity. So we should be cautious abut comparisons to HIV despite the similarities in communities affected, more on that in a moment. 

Researchers are currently working to determine whether people can catch it through genital excretions but there is currently no evidence for transmission via these fluids. Instead, sexual contact with an infected individual increases someone's skin-to-skin exposure to the virus, which is the main way it spreads. Handling contaminated bedding and clothes is another potential way to catch it.

It's also possible that prolonged face-to-face exposure to respiratory droplets during sex can spread human monkeypox though it's not airborne the way measles is.

Another main difference between the current human monkeypox outbreak and other disease outbreaks is the visibility of the inequity between wealthy and poor nations. Even though human monkeypox is not new, this new outbreak has reignited a conversation about wealthy nations ignoring diseases until they become a direct threat. Because people outside of the endemic region have started to pay attention for a change. But those in Sub-Saharan Africa are pointing out that they had been sending out an SOS for decades and the only difference is that other countries are finally taking notice. 

Unfortunately, taking notice has also meant that there's well-placed concern about the hoarding of resources, including vaccines by wealthier nations. The hope is that nations would distribute vaccines based on populations at highest risk and not based on who can pay for them. Already, however, wealthy nations like the US and UK seem to be snapping up supplies. 

The third difference is the more attention researchers have paid, the more they've realized that the virus itself has defied their expectations for how it should work. That means human monkeypox had been more pervasive and widespread than they thought. 

As we mentioned, this virus stores its genome in DNA like most organisms, not RNA like many viruses. Including the one that causes Covid-19. Usually, DNA viruses mutate 100 times slower than RNA viruses do. One of the main reasons for that is the enzyme that most RNA viruses use to replicate can't proofread its work for mistakes. Something DNA viruses can do.

So a pox virus would be expected to mutate once or twice per year. Genomic analysis of virus samples collected from various sites between 2018 and 2022, including one published in the journal Nature Medicine in June, reveal something surprising. The human monkeypox virus changed faster than expected over those years.

Somehow between 2018 and 2022, Clade II of the human monkeypox virus, the one that spurred the Nigerian outbreak, acquired over 50 mutations. That's around 6-12 times more than the typical mutation rate for this type of virus. It's changed enough for the World Health Organization to determine that the currently circulating flavour is a third distinct strain, called Clade IIb, while older versions now belong to Clade IIa.

The specific changes between these variants suggest that human immune defences may have helped inadvertently speed up mutations. A host's immune arsenal includes enzymes that edit a virus's genome while it tries to replicate which can disable it. But sometimes, those edits don't disable a virus. Instead of preventing a virus from churning out more copies of itself, the edits themselves get copied and make it into the viral offspring. 

However these mutations came to be, they seem to affect the shape of a specific protein on the surface of the virus that helps it infect host cells. It's possible that a tweak in it's machinery might be helping it infect and spread more easily, though it remains unclear how much more easily, if at all. 

Those 50 mutations then had to reach the right place at the right time. Well, the wrong place at the wrong time. The change from zoonotic to human-to-human transmission probably occurred in time to spur the start of the present outbreak in Nigeria in 2017. 

We don't know much about how that outbreak started but even back then the first patient in 2017 probably got it from a member of their household, not from interaction with wildlife. So already human transmission, not zoonotic.

Further shifts in human behaviour, in addition to the suite of mutations, probably converged to spur further spread until just the right social situations occurred in 2022 to allow things to take off. Covid-19 lockdowns, event cancellations, and just people staying home and taking fewer risks probably slowed monkeypox too. And getting back out there post-lockdown has had the opposite effect. 

Not only has its genome changed, the newest variant of human monkeypox seems to have different symptoms from the classic manifestation of zoonotic monkeypox. With zoonotic transmission, systemic symptoms like fever and feeling generally bad tend to occur before the lesions. Several hundreds of these pox then typically appear on multiple parts of the body. This usually includes the face, arms, legs, and sometimes the palms of the hands, the soles of the feet, and genitalia. 

With more recent cases of human monkeypox, patients aren't necessarily experiencing general malaise before lesions pop up. And instead of hundreds of lesions several of those who have been diagnosed during the outbreak have just one or a few lesions. 

An analysis of cases in central London published by the British Medical Journal in July of 2022 also notes that patients who contract this version can experience penile swelling and rectal pain. Along with other experts, the authors of this case study point out that these different symptoms should be added to public health messaging to reduce transmission. 

The ubiquity of this disease seems like a big difference between previous outbreaks and this one, but researchers are realizing that there could have been more transmission in non-endemic countries than was ever reported over the years. It's also clear that silent human-to-human transmission within and outside of endemic regions went under-reported prior to 2017. And it's also possible that cases of human monkeypox were misdiagnosed as sexually transmitted infections because the symptoms didn't match the old zoonotic version.

Waning smallpox immunity is another thing that's changed over the years. The proteins on the surface of the two viruses are shaped similarly enough that immune memory to smallpox can offer protection against monkeypox. That's why the two currently available vaccines against human monkeypox in the US are also approved for smallpox. 

In 2019, a group of epidemiologists and pharmaceutical consultants met in London to discuss the increasing threat of monkeypox. And in 2020, they published a report of their meeting in the journal Vaccine. In it, the authors explain that the proliferation of human monkeypox seems to be an unintended consequence of the successful eradication of smallpox. 

Starting in the 1950s, routine vaccination was implemented worldwide in a concerted effort to wipe out smallpox altogether. That routine vaccination stopped in the 70s when the effort proved successful. There was no more smallpox. It's one greatest triumphs of humanity ever. Over time, immunity among the global population has dropped as the vaccinated population has gotten old and died.

Yet another potential change that triggered this outbreak is urbanization and deforestation which have increased human contact with forest animals.

And this is just an abridged list of the complex convergence of changes that set the stage for this public health emergency of international concern. Researchers are still working to tease out the relevant factors 

And that brings us to the next way that human monkeypox differs from COVID-19: the community it most affects. It's crystal clear that COVID-19 is everywhere and can infect anyone in its vicinity if given the opportunity. When human monkeypox was thought to be almost exclusively transmitted from animals to humans, it didn't seem to disproportionately affect people of specific genders or sexual orientations, though it did affect younger patients. 

But some of the messaging around the 2022 human monkeypox outbreak suggests that it's a so-called "gay disease". You will no doubt have heard that human monkeypox is disproportionately affecting the community of men who have sex with men, or MSM which is the term used in public health research. 

I'm actually going to hang a big asterisk on this point. The 2017 Nigerian outbreak, in other words probably this one, has also been pinned to risky sexual behaviour. That's not moralizing about who or what you're doing, it's intended to be a value-neutral description of behaviours more likely to transmit disease like having multiple partners, having sex with sex workers, and this is the key part, not using barrier protection. 

Here in the US, we can see this is affecting the MSM community and if you're following English-language media that's the impression you're going to get. What we really know is that the spread of human monkeypox is tied to these risky behaviours. Though being an MSM can make the list, it's certainly not the only thing. 

To be clear, there is no such thing as a "gay disease". Advocates have noted disturbing parallels to the gross mishandling of HIV and AIDS in the 80s and 90s when systemic discrimination and homophobia lead to the neglect and stigmatization of the entire gay community. That's one reason LBGTQ+ folks are at the forefront of working to dismantle the stigma around diseases that circulate in those communities. They've also been behind the push to disseminate information, vaccination, and services for the current outbreak.  

As for the virus itself, the human monkeypox virus is no HIV. As of September 23, 2022, 23 human monkeypox virus deaths have been reported worldwide all year. By contrast, in 2021 there were over half a million deaths from HIV-related causes worldwide.

This time around some governments are making a concerted effort to talk frankly about sex in a way that they failed to do back then. Some public health agencies are issuing a lot more useful and specific guidelines for safe sex than they did in the 80s. This includes warning folks that spaces like sex clubs or parties where intimate sexual contact takes place are particularly likely to spread the disease. It also urges folks to be sure to change or clean clothes and gear between sexual partners and after use. 

And it explains that while condoms may protect someone's anus, penis, vagina, or mouth from infection, they can't prevent skin-to-skin exposure to other body parts and that's how this disease is transmitted.

With all of that said, some advocates are concerned that they are witnessing a gravely inadequate response that brings up worrying parallels to what they saw in the AIDS pandemic. Even in wealthy nations, they say, responses like vaccine distribution have been bafflingly slow. 

In the end, experts say that this is no more a "gay disease" than an "African disease". Ultimately, it seems likely that the aforementioned series of factors converged inadvertently to trigger this outbreak that has been concentrated among people who practice high-risk behaviours, in some cases overlapping with MSM.

But officials have made clear that the virus can spread readily in any densely connected sexual networks. It does infect women and people of other genders and orientations. And it can most definitely pass to other members of the household or other close contacts with no sexual activity whatsoever. Again, a virus that is taking advantage of sex to spread is not ipso facto an STI.

Officials have also noted that the high rate of reported infections among MSM could be partly due to this community having a tendency to be proactive about sexual health and seek testing more often than other communities. But again, this is just one element in a complex disease landscape and the role that increased surveillance among MSM plays in the number of recorded cases is still unclear.

So there you have it. In many ways, it serves us to treat every disease differently. So in that way, this is not Covid or HIV all over again. The mistakes of the past still loom, though, as something that must be avoided. Researchers, officials, and community advocates continue to iron out the details like diagnostic tools and surveillance, effective and equitable distribution of resources, and epidemiological questions.

The good news is, as of September 23rd, it appears to be working! The World Health Organization reports that there has been a 22% drop in reported cases in North America and Europe in the past week. With over 62,000 cases worldwide, and most in those two regions, this is an encouraging downward trend.

But like we know from Covid, trends that go down can go up again. So in the meantime, it's a good idea to stay vigilant about human monkeypox, but it is at least slightly reassuring that it is not the same as previous disease outbreaks and the public health outreach appears to be working. 

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