Simon Doubleday February 6, 2020

The Plague (and Us)

Q&A with Prof. Monica Green 

In February 2020, Prof. Monica Green kindly invited students in my “Black Death” special topics class at Hofstra University to raise questions relating to recent scientific work on historical plague pandemics, and its relationship with current international public health concerns including coronavirus…. She answered these questions in compelling detail:  

 

QUESTION A: How plausible is that that we could experience another *large-scale* outbreak of Yersinia Pestis? Could the bacteria mutate into a form that we will not be equipped to face?

Okay, two separate questions here: possibility of a repeat Black Death; and possibility of mutation(s) that modern science couldn’t handle.

UNDER CURRENT CONDITIONS a repeat of the BD is unlikely. Plague is currently found on all continents save Antarctica, and almost all strains are lethal to humans as were the strains involved in the BD. BUT we know where those foci are and are more or less vigilant in monitoring them. Remember the incident with the Phish concert this past summer? No? That’s because the danger was well enough contained that there was not a single human case of plague. Sure, a bunch of prairie dog colonies died off. But we know that because of the surveillance systems. Ditto in China and Mongolia this past summer and fall. In all, there were only five human cases; two fatalities (the couple on the Mongolia-Russia border in June/July). The places where public health infrastructure is poorly funded (Madagascar, Democratic Republic of Congo, and Peru) are the places where we get more regular human outbreaks. Even there, however, the provision of antibiotics will control an outbreak. I live in Arizona and we have plague here. But I don’t lose sleep at night (or at least, not b/c of plague), b/c I know those surveillance systems are in place.

As I said, under current conditions, plague is one of the better controlled major infectious diseases. In fact, it’s not considered “major” at all anymore. EXCEPT that, with climate change, all bets are off. Plague is really a cold weather disease. [Update on this point: plague has most certainly adapted from being a cold-weather disease to existing quite comfortably in equatorial regions. But the common denominator of most foci (long-term reservoirs where plague persists, and not just short-term areas it temporarily invades in epidemics) is that it persists at high altitudes. That was a major revelation for me when I realized that. There are exceptions: e.g. Vietnam. But from what I’ve seen (and this is where my scientific knowledge begins to fail me), most of the strains persisting in “tropical” areas have undergone considerable genetic change. All the East African strains (which I discussed in my *Afriques* essay) have acquired a huge number of distinctive SNPs in comparison with strains that have stayed in local marmot populations in Inner Asia].

Plague  originated in the steppe of Eurasia, probably in the late Neolithic, and has done most of its worst work there. Even today, it thrives in high elevation areas (mountains of Uganda and Madagascar, Peru, Colorado, New Mexico, Arizona, California, etc.). BUT look at how late we had outbreaks in Mongolia! November this year!! So Y. pestis may be keeping its same preferences for cool temperatures. But if the hibernating animals that normally host it have their diurnal/annual cycles disrupted by climate change, then that means our surveillance strategies will have to change, too. And they will likely become more expensive. And they will likely, at times, fail. A massive pandemic like the BD? Unlikely. But more little flareups that keep us busy putting them out? Very likely.

(2) Possibility of MUTATIONS: mutations are just evolution-in-action. And that’s on-going all the time. HOWEVER, Yersinia pestis, over the long haul, is one of the most slowly evolving organisms known to modern science. That’s what’s been stunning because of the palaeogenetic (aDNA) work: how very close the modern strains of plague are to what’s been retrieved from historical gravesites. There are a few strains that have wacky, off-the-charts levels of change. But it’s not clear that those are more lethal. In fact, we need to look at the lack of mutation as the scary factor. Y. pestis has developed such an exquisite mechanism of harm that most “innovations” die out. Biologists call this “purifying selection.” Which is pretty scary when you think about it. (A P.S. to this: for some reason, the idea got circulated a number of years ago that pathogens evolve toward “symbiosis” with their hosts. If they kill off their hosts too efficiently, then they die off, too. Well, Y. pestis never got that memo.)

QUESTION 2. Has the recent scientific work yet clarified the nature of the catalyst or turning point that saw plague originally affecting animals and then move to affecting humans at such a high rate?

A: first of all, although we use the term “zoonosis” pretty commonly now in talking about infectious diseases, the idea that diseases move from animals to humans covers a couple of different scenarios. There are diseases that come from animals and then *stay* in humans, being perpetuated by human-to-human transmission. That was likely the case with smallpox and measles, and is probably the case with the newest human disease, the nCoV2019 coronavirus. The other scenario is what we have with Y. pestis: a disease that’s constantly moving from animals to humans. Pneumonic plague is human-to-human transmission, but that usually burns out very quickly, precisely because humans aren’t “carriers”–that is, there are no asymptomatic individuals who harbor the disease for a long time. And since pneumonic plague is nearly 100% lethal without antibiotic therapy, there will not be long chains of transmission. So, the first answer to the question is that what we’re looking for is LOTS of circumstances that would allow what is in essence a rodent disease to repeatedly get transmitted to human populations. So, let’s follow the rodents.

Now that we’ve clarified that what we’re looking for is multiple events, then we can break down stages in Y. pestis‘s evolution and the history of enzootic, epizootic, epidemic, and pandemic events. A good summary of what we know about the stages in the evolution of Y. pestis virulence is this piece that came out early last year. The crazy thing about Y. pestis (and by that I mean, “crazy scary”) is that it’s a triple-threat killer: it will kill you if it gets directly into your bloodstream (septicemic plague, caused, for example, if you cut yourself while skinning an animal you hunted & killed); if it gets into your lungs from droplets coughed by someone or something else that’s already sick (primary pneumonic plague); or if it gets into you via a flea or tick bite (bubonic plague). (For some reason, mosquitoes, which are so effective in transmitting other diseases, don’t seem to play a role in plague. Something to be grateful for!) Plague can also get into your body if you eat the undercooked or raw meat of an animal infected with plague. This is the great under-researched area of plague studies. Presumably, once you consume it, the bacterium propagates in your bloodstream the same way as in septicemic plague. So, my point is that in understanding the evolution of Y. pestis virulence, we need to look at all those “entry mechanisms” differently. And indeed, they all seem to have different genes involved.

Our immediate question is: why is this important historically? Well, it’s clear that pneumonic transmission was acquired before bubonic (flea-borne) transmission. The latter only seems to have happened in the Bronze Age. But it’s clear that humans were being infected by plague even before bubonic capability was acquired; this finding was first made by Rasmussen et al. in 2015) But (you’ll recall) I’ve already said that pneumonic plague infections (which this earliest Late Neolithic/early Bronze Age strain was clearly capable of) only produces short chains of transmission, b/c it kills people too quickly. So, how was it transmitted across long distances, which is clearly what was happening given the range of places across the Eurasian steppe where these strains have been found? The most recent suggestion: horses! This is an unpublished study, whose findings were only floated in a newsletter a few months ago. But if this is right, it would be ingenious. Horses are one of the few domesticated animals that are believed to be largely unaffected by plague. Is it because fleas don’t like horses? Or is it because horses (or more specifically, the horses we now have in the world, which are only a tiny sliver of the diversity of lineages that once existed) were the original “carriers” of plague, and it only became a rodent disease thereafter? These are open questions. But the timing and the geographic distances across which plague is moving 5-6000 years ago clearly indicates that we’ve got some ‘splaining to do.

So, that’s the “deep” story on plague’s emergence. Now we can fast-forward to “The Age of Pandemics.” (There are actually some other Bronze Age stories that it would be interesting to tell about plague’s history, but there’s not enough data on that.) So, plague’s been around, and been “plaguing” humans, for at least 7000 years. Whether it’s been causing isolated outbreaks or more sizeable epidemics in the Bronze Age, we don’t know yet. By the time we get to the Justinianic Plague (hereafter, JP) in the 6th cent. CE, however, we’re looking at a different ecology into which plague might insert itself. CITIES! Normally, plague persists in the wilderness: in rodent burrows in vast deserts or very high mountain pastures. So what causes this normally isolated organism to get urbanized? SPILLOVER EVENTS! This gets us back to our enzootic-epizootic-epidemic-pandemic cycles. Bruce Campbell, who wrote an interesting book about the climate-plague connection in 2016 (The Great Transition, Cambridge UP) presses the argument (already proposed for some time by scientists) that plague outbreaks are closely linked to climate transitions. This only applies to bubonic-capable strains, but since those are clearly the ones involved in the historic pandemics, that’s all we need to pay attention to. The math is simple: more rain -> more food for rodents. More food -> more breeding. More rodents -> more fleas parasitizing rodents. Less rain -> less food. Less food -> fewer rodents. Fewer rodents -> more fleas parasitizing the rodents that survive. More intense flea coverage -> more opportunity for disease transmission. More disease transmission -> greater likelihood that disease in rural rodent populations will spill over into rodents that live near humans. Those commensal rodents (a great word to have in your vocabulary, by the way) then are key in spreading the disease in human communities. So plague outbreaks actually have a lot of bit players, and you need all of them playing their roles–and doing it at the right time and in the right climatic circumstances–for the whole drama of a pandemic to come together. But that’s what happened, at least twice: in the 6th cent CE (JP) and in the 14th cent (BD). In both cases, I think long-distance grain shipping plays the biggest role. But that remains to be documented in detail.

QUESTION C: Quarantining is a controversial strategy in the US, in the face of coronavirus. Is there any evidence of collective quarantining in the context of the Black Death, and is it likely to have been effective?

A: First of all, let’s make sure everybody understands the terminology. There’s quarantine; there’s isolation; and there’s cordons sanitaires (public health do-not-pass blockades). Quarantine comes from the Italian word for “40” (quaranta): 40 days. (It was probably originally just 30 days, but who’s counting?) This was a practice of barring entry to people who *appeared* to be healthy and making them wait out the 30/40 days to make sure they didn’t become sick in that time. In other words, it’s not therapy (treatment for someone who’s already sick) or prophylaxis (prevention of sickness, or at least not out of concern for the person being quarantined). “Isolation” is when you segregate off someone who’s already sick, to keep them from passing the disease to others and to allow their caregivers to provide care in a safe environment. A cordon sanitaire prevents the movement of people under pain of punishment. (Historically, that might include death.) The lines between all these aren’t strict in practice; the issue really is the motive for separation/segregation, and that’s not always clear in every situation. So, to the question: does quarantine work? The answer is YES and NO. Yes, if you physically separate the ill from the not-ill, you cut off the opportunity for transmission. Full stop. Infectious diseases need the opportunity to infect. If you interrupt transmission, then you’ve stopped the disease. But that’s the question: have you really stopped ALL MODES of transmission? If plague is spread throughout a city by rats scurrying through sewers underground, what good does it do to bar the movement of *people* on the streets above? In Wuhan, it was already clear that attempts to stop people’s movement out of the city were ineffective because so many people had already left before the orders were implemented. In short, what might work in principle doesn’t always work in practice. For the early history of quarantine in late medieval Europe, this is the best book: Zlata Blažina-Tomić and Vesna Blažina. Expelling the Plague: The Health Office and the Implementation of Quarantine in Dubrovnik, 1377–1533 (Montreal: McGill-Queen’s University Press, 2015).