The History of Pandemics
Pan·dem·ic /panˈdemik/ (of a disease) prevalent over a whole country or the world.
As humans have spread across the world, so have infectious diseases. Even in this modern era, outbreaks are nearly constant, though not every outbreak reaches pandemic level as COVID-19 has.
Today’s visualization outlines some of history’s most deadly pandemics, from the Antonine Plague to the current COVID-19 event.
A Timeline of Historical Pandemics
Disease and illnesses have plagued humanity since the earliest days, our mortal flaw. However, it was not until the marked shift to agrarian communities that the scale and spread of these diseases increased dramatically.
Widespread trade created new opportunities for human and animal interactions that sped up such epidemics. Malaria, tuberculosis, leprosy, influenza, smallpox, and others first appeared during these early years.
The more civilized humans became – with larger cities, more exotic trade routes, and increased contact with different populations of people, animals, and ecosystems – the more likely pandemics would occur.
Here are some of the major pandemics that have occurred over time:
|Name||Time period||Type / Pre-human host||Death toll|
|Antonine Plague||165-180||Believed to be either smallpox or measles||5M|
|Japanese smallpox epidemic||735-737||Variola major virus||1M|
|Plague of Justinian||541-542||Yersinia pestis bacteria / Rats, fleas||30-50M|
|Black Death||1347-1351||Yersinia pestis bacteria / Rats, fleas||200M|
|New World Smallpox Outbreak||1520 – onwards||Variola major virus||56M|
|Great Plague of London||1665||Yersinia pestis bacteria / Rats, fleas||100,000|
|Italian plague||1629-1631||Yersinia pestis bacteria / Rats, fleas||1M|
|Cholera Pandemics 1-6||1817-1923||V. cholerae bacteria||1M+|
|Third Plague||1885||Yersinia pestis bacteria / Rats, fleas||12M (China and India)|
|Yellow Fever||Late 1800s||Virus / Mosquitoes||100,000-150,000 (U.S.)|
|Russian Flu||1889-1890||Believed to be H2N2 (avian origin)||1M|
|Spanish Flu||1918-1919||H1N1 virus / Pigs||40-50M|
|Asian Flu||1957-1958||H2N2 virus||1.1M|
|Hong Kong Flu||1968-1970||H3N2 virus||1M|
|HIV/AIDS||1981-present||Virus / Chimpanzees||25-35M|
|Swine Flu||2009-2010||H1N1 virus / Pigs||200,000|
|SARS||2002-2003||Coronavirus / Bats, Civets||770|
|Ebola||2014-2016||Ebolavirus / Wild animals||11,000|
|MERS||2015-Present||Coronavirus / Bats, camels||850|
|COVID-19||2019-Present||Coronavirus – Unknown (possibly pangolins)||6.9M (Johns Hopkins University estimate as of March 1, 2023)|
Despite the persistence of disease and pandemics throughout history, there’s one consistent trend over time – a gradual reduction in the death rate. Healthcare improvements and understanding the factors that incubate pandemics have been powerful tools in mitigating their impact.
March 1, 2023 Update: Due to popular request, we’ve also visualized how the death tolls of each pandemic stack up as a share of total estimated global populations at the time.
Wrath of the Gods
In many ancient societies, people believed that spirits and gods inflicted disease and destruction upon those that deserved their wrath. This unscientific perception often led to disastrous responses that resulted in the deaths of thousands, if not millions.
In the case of Justinian’s plague, the Byzantine historian Procopius of Caesarea traced the origins of the plague (the Yersinia pestis bacteria) to China and northeast India, via land and sea trade routes to Egypt where it entered the Byzantine Empire through Mediterranean ports.
Despite his apparent knowledge of the role geography and trade played in this spread, Procopius laid blame for the outbreak on the Emperor Justinian, declaring him to be either a devil, or invoking God’s punishment for his evil ways. Some historians found that this event could have dashed Emperor Justinian’s efforts to reunite the Western and Eastern remnants of the Roman Empire, and marked the beginning of the Dark Ages.
Luckily, humanity’s understanding of the causes of disease has improved, and this is resulting in a drastic improvement in the response to modern pandemics, albeit slow and incomplete.
The practice of quarantine began during the 14th century, in an effort to protect coastal cities from plague epidemics. Cautious port authorities required ships arriving in Venice from infected ports to sit at anchor for 40 days before landing — the origin of the word quarantine from the Italian “quaranta giorni”, or 40 days.
One of the first instances of relying on geography and statistical analysis was in mid-19th century London, during a cholera outbreak. In 1854, Dr. John Snow came to the conclusion that cholera was spreading via tainted water and decided to display neighborhood mortality data directly on a map. This method revealed a cluster of cases around a specific pump from which people were drawing their water from.
While the interactions created through trade and urban life play a pivotal role, it is also the virulent nature of particular diseases that indicate the trajectory of a pandemic.
Scientists use a basic measure to track the infectiousness of a disease called the reproduction number — also known as R0 or “R naught.” This number tells us how many susceptible people, on average, each sick person will in turn infect.
Measles tops the list, being the most contagious with a R0 range of 12-18. This means a single person can infect, on average, 12 to 18 people in an unvaccinated population.
While measles may be the most virulent, vaccination efforts and herd immunity can curb its spread. The more people are immune to a disease, the less likely it is to proliferate, making vaccinations critical to prevent the resurgence of known and treatable diseases.
It’s hard to calculate and forecast the true impact of COVID-19, as the outbreak is still ongoing and researchers are still learning about this new form of coronavirus.
Urbanization and the Spread of Disease
We arrive at where we began, with rising global connections and interactions as a driving force behind pandemics. From small hunting and gathering tribes to the metropolis, humanity’s reliance on one another has also sparked opportunities for disease to spread.
Urbanization in the developing world is bringing more and more rural residents into denser neighborhoods, while population increases are putting greater pressure on the environment. At the same time, passenger air traffic nearly doubled in the past decade. These macro trends are having a profound impact on the spread of infectious disease.
As organizations and governments around the world ask for citizens to practice social distancing to help reduce the rate of infection, the digital world is allowing people to maintain connections and commerce like never before.
Editor’s Note: The COVID-19 pandemic is in its early stages and it is obviously impossible to predict its future impact. This post and infographic are meant to provide historical context, and we will continue to update it as time goes on to maintain its accuracy.
Update (March 1, 2023): We’ve adjusted the death toll for COVID-19, and will continue to update on a regular basis.
Visualizing How COVID-19 Antiviral Pills and Vaccines Work at the Cellular Level
Despite tackling the same disease, vaccines and antiviral pills work differently to combat COVID-19. We visualize how they work in the body.
Current Strategies to Tackle COVID-19
Since the pandemic started in 2020, a number of therapies have been developed to combat COVID-19.
The leading options for preventing infection include social distancing, mask-wearing, and vaccination. They are still recommended during the upsurge of the coronavirus’s latest mutation, the Omicron variant.
But in December 2021, The United States Food and Drug Administration (USDA) granted Emergency Use Authorization to two experimental pills for the treatment of new COVID-19 cases.
These medications, one made by Pfizer and the other by Merck & Co., hope to contribute to the fight against the coronavirus and its variants. Alongside vaccinations, they may help to curb extreme cases of COVID-19 by reducing the need for hospitalization.
Despite tackling the same disease, vaccines and pills work differently:
|Taken by injection||Taken by mouth|
|Used for prevention||Used for treatment only|
|Create an enhanced immune system by stimulating antibody production||Disrupt the assembly of new viral particles|
How a Vaccine Helps Prevent COVID-19
The main purpose of a vaccine is to prewarn the body of a potential COVID-19 infection by creating antibodies that target and destroy the coronavirus.
In order to do this, the immune system needs an antigen.
It’s difficult to do this risk-free since all antigens exist directly on a virus. Luckily, vaccines safely expose antigens to our immune systems without the dangerous parts of the virus.
In the case of COVID-19, the coronavirus’s antigen is the spike protein that covers its outer surface. Vaccines inject antigen-building instructions* and use our own cellular machinery to build the coronavirus antigen from scratch.
When exposed to the spike protein, the immune system begins to assemble antigen-specific antibodies. These antibodies wait for the opportunity to attack the real spike protein when a coronavirus enters the body. Since antibodies decrease over time, booster immunizations help to maintain a strong line of defense.
*While different vaccine technologies exist, they all do a similar thing: introduce an antigen and build a stronger immune system.
How COVID Antiviral Pills Work
Antiviral pills, unlike vaccines, are not a preventative strategy. Instead, they treat an infected individual experiencing symptoms from the virus.
These medications disrupt specific processes in the viral assembly line to choke the virus’s ability to replicate.
The Mechanism of Molnupiravir
RNA-dependent RNA Polymerase (RdRp) is a cellular component that works similar to a photocopying machine for the virus’s genetic instructions. An infected host cell is forced to produce RdRp, which starts generating more copies of the virus’s RNA.
Molnupiravir, developed by Merck & Co., is a polymerase inhibitor. It inserts itself into the viral instructions that RdRp is copying, jumbling the contents. The RdRp then produces junk.
The Mechanism of Nirmatrelvir + Ritonavir
A replicating virus makes proteins necessary for its survival in a large, clumped mass called a polyprotein. A cellular component called a protease cuts a virus’s polyprotein into smaller, workable pieces.
Pfizer’s antiviral medication is a protease inhibitor made of two pills:
- The first pill, nirmatrelvir, stops protease from cutting viral products into smaller pieces.
- The second pill, ritonavir, protects nirmatrelvir from destruction by the body and allows it to keep working.
With a faulty polymerase or a large, unusable polyprotein, antiviral medications make it difficult for the coronavirus to replicate. If treated early enough, they can lessen the virus’s impact on the body.
The Future of COVID Antiviral Pills and Medications
Antiviral medications seem to have a bright future ahead of them.
COVID-19 antivirals are based on early research done on coronaviruses from the 2002-04 SARS-CoV and the 2012 MERS-CoV outbreaks. Current breakthroughs in this technology may pave the way for better pharmaceuticals in the future.
One half of Pfizer’s medication, ritonavir, currently treats many other viruses including HIV/AIDS.
Gilead Science is currently developing oral derivatives of remdesivir, another polymerase inhibitor currently only offered to inpatients in the United States.
More coronavirus antivirals are currently in the pipeline, offering a glimpse of control on the looming presence of COVID-19.
Author’s Note: The medical information in this article is an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. Please talk to your doctor before undergoing any treatment for COVID-19. If you become sick and believe you may have symptoms of COVID-19, please follow the CDC guidelines.
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