Friday, October 16, 2020

Disease Post: Plague

OK, I am going to try for this post. I hope you are ready for a long one.

The plague is my very favorite infectious disease. It is so interesting and the history of it is devastating and fascinating. And what better way to celebrate the month of Halloween than talking about the Black Death? I mean, have you seen plague doctor outfits? They are terrifying (and I LOVE them). And yes, I do have a plague doctor costume, thanks for asking. 

It also helps me be a crazy rat lady since rat fleas (and/or other rodent fleas) are the primary carriers of plague. My rats do not have plague or fleas though, don't worry.

Plague of Marseilles- costumes for plague doctors. Credit- Wellcome Collection and Attribution 4.0 International

Plague is caused by a bacterium called Yersinia pestis. Y. pestis is a gram-negative (does not have peptidoglycan in its cell walls) rod or coccobacillus (round rod). It is a facultative anaerobe, which means that it "prefers" to have oxygen, but can survive without it by switching to fermentation for energy. This makes them fairly resilient little bugs.
Plague plush from Giant Microbes.
Historically, the plague has caused massive amounts of devastation worldwide and is still present all over the world. I will include a brief history later. 
Yersinia pestis is a zoonotic disease, meaning humans get it from animals and/or insects. In this case, the carriers are fleas.
Plague infographic from the WHO

How is it spread?
The infectious dose (or how many bacteria are needed to establish an infection) is not known, but is suspected to be quite low.
There are three different forms of plague: pneumonic (respiratory), septicemic, and (the famous) bubonic.
Let's start with bubonic plague and septicemic plague because they are similar. People get these by being bitten by an infected flea or by contact with contaminated animal tissue and/or fluid (like skinning or handling a plague-infected animal). Bubonic plague can turn into septicemic plague as the bacteria infiltrates the body and, therefore, the blood stream. And it can become pneumonic plague, too, if the bacteria spread to the lungs. Bubonic and septicemic forms do not spread from person to person.

Pneumonic plague can develop as mentioned above, or can be caught directly through respiratory droplets in the air. If a sick person or animal is coughing (or even just breathing), they release infectious bacteria into the air in tiny respiratory droplets. These can be inhaled by another person or animal, establishing an infection in the lungs. This form can be transmitted person-to-person, but usually requires close contact. You can find more detailed information about transmission from the CDC.

Image from the CDC

As I mentioned above, there are three forms which will present with different symptoms, though all three will present with a fever, chills, weakness, and (often) headaches. Vomiting, diarrhea, and abdominal pain are seen in some cases, too.

Bubonic plague has an incubation time of seven days or less from infection until the time a person shows symptoms. This form is characterized by the presence of one or more bubos. A bubo is a lymph node that  becomes inflamed, swelling enough to be visible. These are usually located in the neck, armpit, and/or groin. The bubos are tender and painful. From here, the infection can start to infect the bloodstream to develop into septicemic and/or pneumonic plague. Without treatment, estimated death rates are between 50%-70%.

Septicemic plague is the infection of the blood. It is not generally the initial infection that is established, but there are many records of people getting the plague this way. Once the bacteria is in the blood stream it can get just about anywhere. The CDC also notes that people may bleed into the skin or other organs and tissues will start to die and possibly develop gangrene (and turn black=the Black Death). One of my text books (Medical Microbiology by Murray et al.) estimates that 75% of people who have or develop septicemic plague die without treatment.

Pneumonic plague is generally the most worrisome. The incubation is shorter, generally 2-3 days. After the initial symptoms, patients will develop respiratory symptoms within a day or so. According to the CDC, the respiratory symptoms include: shortness of breath, cough, chest pain, and possibly bloody mucous. This is the only form of plague that can spread person-to-person and it is highly infectious. Most sources estimate that the death rate of pneumonic plague is 90% or more if not treated quickly (within 18-24 hours, according to the WHO).
Prevention and Treatment:
The good news is that plague is easily treated with a few common antibiotics! However, it needs to be caught as early as possible, especially for pneumonic plague. People do die even with treatment, especially if treatment is too late.

But plague, if there are no bubos, looks like lots of other illnesses. Diagnosis is helped if your doctor knows you have been exposed to fleas or wild rodents, especially in endemic areas (meaning it is "native" to those areas, like much of Asia, Africa--especially Madagascar, and the Southwest United States). 
Your pets can also become infected by the same means people can and your pets can spread it to you. Flea control is important and it is best to avoid wild rodents, especially ones that appear ill or have died. Wear gloves while handling dead animals that may be infected.

There is not great prevention besides that. There was a vaccine available in the United States, but not anymore. It did not protect against pneumonic plague. I'm sure there are groups working toward a vaccine, but no one knows if/when one will be available.
The plague of Florence, 1348; a scene from Boccaccio's Decameron. Etching by L. Sabatelli the elder after G. Boccaccio. Credit: the Wellcome Collection and Attribution 4.0 International

The plague has been around for centuries. It was also used in early biological warfare (bodies of plague victims catapulted into cities or enemy camps). Italian Gabriele de'Mussi gave an account of the Black Death origin in 1346: the Mongol army hurled plague-infected cadavers into the city of Caffa. This transmitted plague to the inhabitants, and those who fled took the plague with them towards Europe. This is explained by Mark Wheelis in his paper Biological warfare at the 1346 Siege of Caffa. Ultimately, it is suspected that the Black Death originated somewhere in Asia, though theories of exactly where differ.

There are three main plague pandemics (Perry et al). The first was in the early middle ages (the Plague of Justinian from 541 CE until the mid-700s) and is one of the earliest records we have of the plague. It is suspected to have originated in China and spread to Egypt and then to Constantinople. At the peak of the first pandemic, it is suspected to have killed 10,000 people per day and killed about 40% of citizens. A bit later, in 588 CE, there was another wave that spread it through the Mediterranean and about 100 million people died.

The second pandemic was the one most people are familiar with, from the 14th century to the 19th century. What is known as the Black Death started in this time period. The plague spread from China or somewhere in Asia along the Silk Road, infecting Asia, Europe, and Africa. China lost about half of its population, Europe lost a third to a half of its population, and Africa lost about an eighth of its population. For the record, people at the time did not call the plague the "Black Death," that is a more modern term. They called it the "great pestilence" or the "great mortality" mostly.

The third pandemic was in the 19th and 20th centuries. A wave began in China in 1855 which spread through China, to India, killing more than 12 million people in the two countries. From there, the plague traveled to Russia, causing a large outbreak in Siberia in 1910. It was during this pandemic, in the late 1800s, that the plague bacterium was identified and isolated. Alexandre Yersin is credited with the discovery and the bacteria was eventually named after him.
Part of the fear of plague has to do with its potential as a bioterrorism agent. This is part of what keeps this on the select agent list in the United States.

As mentioned above, cadavers of plague victims were intentionally thrown into the city of Caffa, causing an outbreak and causing the disease to spread. This is not the only time that this was done in the history of warfare.

I remember learning about this in history and in my biodefense class. This sentence sums it up fairly well, though it does not go into all the cruel experiments that the Japanese performed on the Chinese. "In World War II, the Japanese military experimented with plague in human subjects at their clandestine biological research facilities in Manchuria, and on several occasions dropped Y. pestis-infested fleas from low-flying planes on Chinese civilian populations, causing limited outbreaks of bubonic plague and initiating cycles of infection in rats" (Dennis, David T. Plague as a Biological Weapon).

The end-goal with Y. pestis as a biological weapon was to successfully aerosolize it, to cause pneumonic plague. I have in my old class notes that "aerosol release of Y. pestis would be odorless, colorless, and likely to be unnoticed until the first victims fell ill," but I have not been able to locate a source yet, so take it with a grain of salt. 
It was estimated by a committee of experts that "intentional release of 50 kg of aerosolized Y. pestis over a city of 5 million would... cause 150,000 cases of pneumonic plague and 36,000 deaths...[and] without adequate precautions, an initial outbreak of pneumonic plague involving 50% of a population could result in infection of 90% of the rest of the population in 20–30 days and could cause a case fatality ratio of 60–70%" (Dennis, David T. Plague as a Biological Weapon).

About the bacteria:
I was always interested in the bacteria itself and its interactions with flea and animal hosts. That isn't talked about much because people are concerned with the diseases of people. The flea is initially infected by taking blood from an infected host. I won't get into technical details, but so you know, it does affect the flea by blocking digestion until the flea regurgitates the bacteria when they bite another host. The blocked gut of the flea will eventually kill it. Animal carriers are often symptomatic and can also die of the plague.

There are some genes that the bacteria has that they can switch between based on which host it is in to help it adapt to either the temperature and environment (like pH) of the flea versus animal hosts

The bacteria switches between gene expressions based on the host and the host temperatures. Generally, the bacteria grows best at lower temperatures but can switch gene expression to help them survive and grow at normal human temperatures.

Fun Facts:
The plague doctor mask had the beak which was to be stuffed with flowers, spices, and/or herbs--anything that smelled nice because the belief was that disease traveled through bad smells or miasma.

The plague doctor outfit did actually afford them protection, but not because of the potpourri in the mask. The mask protected their faces from respiratory droplets. They also covered themselves from head to toe in mostly leather, which fleas could not bite through.

Books and Media:
There are several books and such concerning the plague that are great.

For educational purposes, The Black Death: The World's Most Devastating Plague by Dorsey Armstrong from Great Courses is amazing. It goes into details of spread and impacts of the plague (during and after) on society, art, economics, and more. You can get it through Great Courses or through Audible. 
This Podcast Will Kill You did a two-part episode on the plague that is very good.

The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time by John Kelly is said to be good. I have not read it yet, but I would like to.

The Black Death by Philip Ziegler sounds great, but is another one that I have not read.

Journal of the Plague Year by Daniel Defoe. Arguably, this account is not entirely credible as the author wrote it 57 years after the fact. But he did experience the plague and it is considered to be an accurate account of the time. It was good either way.

Year of Wonders by Geraldine Brooks. This is a historical fiction novel, but it is based on a real town in England that isolated themselves when they found that the plague had reached them. A friend gifted this book to me years ago and it was enjoyable.

The Plague by Albert Camus. I am embarrassed to admit that I have not read this book yet, though I want to, obviously.
Crow Boy by Philip Caveney is a fictional story about a modern boy in Edinburgh who travels back in time to 1645, during a plague outbreak. I enjoyed this one, even though the plague doctor was fake and kind of evil.

This is a silly video that will get the original song stuck in your head forever, but it's funny. We watched it at some point during my Masters program: Black Death (Hollaback Girl) aka Fleas on Rats.

There are so many more books that I have not yet read. If anyone has a particularly good suggestion, please drop it in the comments. And if you know of anything about plague doctors, I definitely need to know!

I hope you enjoyed my plague post. If you made it this far, thanks for reading!
Perry, Robert D and Fetherston, Jaqueline D. Yersinia pestis--etiologic agent of plague. 1997.
Medical Microbiology sixth edition by Patrick R. Murray, Ken S. Rosenthal, and Michael A. Pfaller
Armstrong, Dorsey. The Black Death: The World's Most Devastating Plague. 2016. Great Courses.
Dennis, David T. Plague as a Biological Weapon. 2009.