Preparing for Plagues and Pandemics

Here I explore how recurring plagues in human history, stimulated efforts to be more prepared for them in the future.

Key Plagues and Pandemics

I first looked at the key plagues and pandemics to see what people were learning from their regular experience with these events which must have disrupted society much like COVID-19 is changing our life in the early 2020’s.  Yes, humans survived all of them, however millions of individuals and their DNA did not survive these, dramatically effecting evolution, especially regarding how our bodies fight against these deadly agents.

Six devastating plagues are noted elsewhere (1):

1. The Plague of Justinian, 541–542 AD, with recurrences until 750 (2).
2. The Black Death, 1331–1353 AD, with European history from 1347–1353 AD (3).
3. The Italian Plague, 1629–1631 AD (4).
4. The Great Plague of London, 1665–1666 AD (5).
5. The Great Plague of Marseilles, 1720–1722 AD (6).
6. The Third Plague Pandemic, 1855–1960 AD (7).

Another source (8) mentions the five deadliest pandemics of history.

1. The Pelopennesian War Pestilence also known as Plague of Athens, 430-426 BC, the oldest recorded pandemic (9)
2. The Antonine Plague also known as the Plague of Galen, 165-150 AD, a small pox or measles pandemic (10)
3. The Plague of Justinian, see above
4. The Black Death, see above
5. The Spanish Flu, 1918-1919 AD, an H1N1 Flu (11)

A detailed list of all known epidemics and pandemics is provided in Wikipedia.  Also before reading the rest of my post below, check out this infographic:

How Did We Come to Understand Pandemics?

What did people learn from these pandemics?  The following will attempt to address this question, but will not get into understandings about the virology and pathology gained as the result of these events.  Instead my focus is more on the public health learnings – what needs to be done to minimize the risk of the spread and fatality from pandemics.  I divide this section into seven learnings:

• During the Pelopennesian War Pestilence of the 5th Century BC
• During the Antonine Plague of the 2nd Century
• During the Plague of Justinian
• Between 6th and 14th Century
• About the Importance of Quarantine
• About the Importance of a Public Health Infrastructure
• About the Cause of Pandemics

During the Pelopennesian War Pestilence of 5th Century BC.  Fear during this pandemic made people violate every rule of religion and law because people felt they already had a death sentence (9).  This fear was probably the result of the lack of understanding of how to protect themselves from the disease.  People noticed that tending to the sick increased their risk of death as indicated by their avoidance of caretaking, and immunity was also noted in the fact that those who had had the disease were the caretakers of the sick. (9).

During the Antonine Plague of 2nd Century. Marcus Aurelius noted that pestilence was less deadly than falsehood and lack of understanding.  Aurelius died of the disease associated with this plague and yet asked his subjects to be more concerned for the others dying around them. (10)

During Plague of Justinian from 6th to 8th Century.  Some contemporaries of this Plague properly reasoned that rats were the vectors of the plague, a fact lost in later outbreaks when such knowledge could have led to efforts to rid cities of rats (2).  It wasn’t until the 19th century that this vector of the plague was again identified (2) (7).

Between 8th and 14th Century.  I am not clear about why recurrences of the plague after the 8th century were not significant until the Black Death of the 14th century (2).  Could someone have understood that better sanitation and efforts to reduce the number of rats was the best way to minimize the threat of plague?  Was the weather or some other environmental characteristic limiting the populations of rats reducing the risk of pandemic? Or did the remaining human populations have some new genetic-based immunity until a Yersinia pestis strain developed that overcame that immunity in the 14th century?  Clearly some people, probably clerics of the church during the dark and middle ages, understood how to reduce the risk of plague, but I think it more likely that it was environmental factors effecting rat and flea populations, in combination with strengthened genetic-based immunity gained from centuries of exposure to plague and the associated selection for populations with these genetic-based immunities.

About the Importance of Quarantine.  It was during the Black Death of the 14th century that quarantine was clearly recognized as a means of controlling the spread of the disease (2).  The tie between the infected and transmission to newly infected individuals caused the Venetians to banish the infected to islands in a nearby lagoon during the Italian Plague of 1629-1631 (1).  During the Great Plague of London of 1665-1666 victims were quarantined in homes marked with a red cross (1).   Also ship quarantines were used during this plague for any ships coming to London, and voyagers that came to shore from these ships were required to remain in quarantine for another 40 days (5).  The Great Plague of London also saw people escaping from the city to get away from the people who were infected, certainly the beginning of physical distancing (i.e., ‘social distancing’) (5).

About the Importance of a Public Health Infrastructure.  Following the Plague of 1580 in Marseilles, the city council started a sanitation board which monitored external threats, built public sanitation infrastructure, and took other steps to slow the progress of future plagues (6).  The Marseilles Sanitation Board created a quarantine system that inspected incoming ships giving them a “bill of health”, quarantine islands for ships from cities with plague activity were given a minimum of 18 days of isolation for ships with the least likelihood of infection, while crews expected of being infected were sent to a different site and had 50-60 days of isolation (6).   In fact, Marseilles city leaders understood the threat of the ship that brought the plague to that city in 1720 because they attempted to quarantine that ship and its crew (1).  An Act of the Parlement of Aix during the Great Plague of Marseilles established the death penalty for communication outside of Marseilles, and a plague wall was built with guard posts to stop such communication (6). Still the disease spread through Marseilles because it was rats with carrier fleas that spread the disease, and the rats could not be contained even with plague walls built to stop the contagion.  Prior to the Plague of Marseilles, the city leaders also created the first hospital of Marseilles with accredited doctors, and provided information to the public about credible doctors (6).  However, shortly after breakout of the disease in 1720  hospitals were overwhelmed (6) – many involved at that time must have first understood the importance of hospital system capacity during pandemics.  The leaders of Marseille in the 16th century clearly knew the important role government played in slowing and addressing pandemics.

About the Cause of Pandemics. At the time of the Great Plague of London, now considered part of the Second Plague Pandemic which started with the Black Death, the cause of plague was still not understood, being blamed on “pestilential effluviums” or pestilent emanations from the earth, weather, livestock sickness, and increases in moles, frogs, mice or flies (5).  In the 18th century Edward Gibbon noted that the Antonine Plague had less impact than the political trends at that time, and later in the 19th century Michael Rostovtzeff pointed out that economic trends were key to the spread of the Antonine Plague.  Much of this thinking was from recognition that the spread resulted from military movements (10).

Then in 1894 the causative bacteria of the bubonic plague, Yersinia pestis was discovered by a Hong Kong doctor named Alexandre Yersin after whom the genus was named (1) (7). A controlled test of a vaccine developed by Waldemar Haffkine demonstrated significant protection against the bubonic plague in 1897 (7).  Shortly after this in 1898, Paul-Louis Simond discovered that the infection was transmitted by flea bites (2) (7).

Francis Aidan Gasquet attributed the same agent causing the Third Plague Pandemic for the Black Death in 1908, and subsequently other plagues in history were similarly attributed (2).  It wasn’t until 2010 when definitive proof was provided that Y. pestis caused the Black Death by demonstrating Y. pestis RNA and DNA in tooth sockets found in skeletons from mass graves in Europe were archaeologically proven to be associated with the Black Death (2).  Similarly Y. pestis was found in the DNA of teeth from individuals found in burial pits associated with the Great Plague of London (5).

Research concerning the Spanish Flu have pointed to the importance of animals as the source of the original infection, with the swine being the expected agent of the Spanish Flu, with avian species serving as the source for the swine infection (11).  Sophisticated DNA studies have suggested that the current SARS-CoV2 is originally from the RaTG13 virus found in bats (12).

Important learnings from past plagues.

In summary what was learned from pandemics that killed millions since our historians started recording them?

1. Honest communication about the facts associated with reducing risk of the spread of disease is critical to the success of efforts to limit pandemics.
2. Quarantine is essential to slowing the spread of pandemics.
3. Physical distancing (also called social distancing) reduces the spread of disease.
4. Understanding the mechanism of diseases that cause pandemics helps slow the progress of pandemics, treat victims, and even reduce the threat of pandemics ever getting established.
5. The spread of disease needs to be closely monitored.
6. Health systems need to be prepared with excess capacity.
7. A public health infrastructure is necessary to ensure the above are being addressed.

Next blog will be about how the anthrax terrorist attacks of 2001 stimulated pandemic-related, also called emerging infectious disease research, based on my personal experience at Virginia Tech.  This will be a story involving a discussion of important research funding programs, efforts to build out safe research facilities both large and small, and planning for pandemic stockpiles.

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REFERENCES

1. Andrews, Evan. “6 Devastating Plagues.” HISTORY. Accessed March 18, 2020. https://www.history.com/news/6-devastating-plagues.
2. “Plague of Justinian.” In Wikipedia, March 17, 2020. https://en.wikipedia.org/w/index.php?title=Plague_of_Justinian&oldid=945985107.
3. “Black Death.” In Wikipedia, March 18, 2020. https://en.wikipedia.org/w/index.php?title=Black_Death&oldid=946228338.
4. “1629–1631 Italian Plague.” In Wikipedia, March 17, 2020. https://en.wikipedia.org/w/index.php?title=1629%E2%80%931631_Italian_plague&oldid=946077139.
5. “Great Plague of London.” In Wikipedia, March 16, 2020. https://en.wikipedia.org/w/index.php?title=Great_Plague_of_London&oldid=945803116.
6. “Great Plague of Marseille.” In Wikipedia, March 18, 2020. https://en.wikipedia.org/w/index.php?title=Great_Plague_of_Marseille&oldid=946209780.
7. “Third Plague Pandemic.” In Wikipedia, March 18, 2020. https://en.wikipedia.org/w/index.php?title=Third_plague_pandemic&oldid=946200158.
8. “5 Deadliest Pandemics in History – Neatorama.” Accessed March 18, 2020. https://www.neatorama.com/2009/04/27/5-deadliest-pandemics-in-history/.
9. “Plague of Athens.” In Wikipedia, February 29, 2020. https://en.wikipedia.org/w/index.php?title=Plague_of_Athens&oldid=943242562.
10. “Antonine Plague.” In Wikipedia, March 17, 2020. https://en.wikipedia.org/w/index.php?title=Antonine_Plague&oldid=946068433.
11. “Spanish Flu.” In Wikipedia, March 19, 2020. https://en.wikipedia.org/w/index.php?title=Spanish_flu&oldid=946245134
12. Andersen, Kristian G., Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes, and Robert F. Garry. “The Proximal Origin of SARS-CoV-2.” Nature Medicine, March 17, 2020, 1–3. https://doi.org/10.1038/s41591-020-0820-9.