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Five pandemics that marked the human history

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Living in today’s reality, facing the everyday challenges of a pandemic, the world is brought into a new era, brimming with problems and controversies. However, this is not the first time that humanity faces a pandemic. Epidemics and pandemics have existed since the very early years of humanity, dating back to 1350 BC for epidemics and 1346 AD for pandemics. Although the world should have been more prepared by now, we still seem helpless and vulnerable in front of these challenges. Here, we will review some of the deadliest pandemics that have deeply marked the history of humanity.

The Justinian Plague

One of the most ancient pandemics that led to the death of 15 to 100 million people was the Plague of Justinian, dating back to 541 AD. It takes its name from the ruler of the Byzantine Empire, Justinian, who allegedly contracted the plague and recovered from it. This plague is believed to originate in Central Asia, after which it expanded to West Asia and Europe. Although the plague began to recede after a year, it returned periodically, affecting the Byzantine Empire and the Mediterranean area heavily on the medical, economic and political levels. This pandemic occurred at a most crucial time in history, during the transition from the Ancient World to the Middle Ages and has been reported to have caused irreparable damage on trade and commercial exchanges. According to historical records, the Justinian Plague was the result of Yersinia pestis, the bacteria which was believed to be transmitted via rats and fleas. Symptoms involved headaches, chills, fever and muscle weakness. Although it would be easy to treat with antibiotics today, back then it was impossible to be treated,  which led to its spreading throughout the body, causing organ failure and death.

The Black Death

The Black Death (also known as the Pestilence, the Great Mortality, Black Plague, Great Plague or Great Bubonic Plague) was a Bubonic plague pandemic that afflicted North Africa and Eurasia from 1346 to 1353. It was caused by the bacterium Yersinia pestis, which was carried by fleas on the black rats that travelled on slave ships. This was one of the most fatal pandemics in human history and resulted in the death of 75-200 million people. It wiped out 50 to 60% of the European population and reduced the world population  by ca.  350–375  million to 475 million in the 14th century. These numbers are however not surprising when we consider the hygiene conditions and public health at those times. Clean water was considered a luxury and was available mostly only to the royal families. In addition, hygiene and sanitation were extremely poor and the majority of the population used to live in big groups, in dark, filthy and humid houses. Medication at this time did not exist and only conservative methods were available, most of which were based on superstitions. Some of the “treatment” of the time included: bloodletting, where there was withdrawal of blood from veins as a way to reduce “hot” blood; rubbing onions, herbs, a chopped up snake or a chopped up pigeon over the infection; drinking vinegar, eating crushed minerals or even drinking arsenic and mercury.

The Third Cholera Pandemic

The Third Cholera Pandemic dates back to 1846, bursting out in India and spreading across the whole world until it subsided in 1860. It has been responsible for over 1-2 million deaths. It is considered one of the worst pandemics of the XIX century, peaking in 1853-54 in Great Britain, where it took the lives of 23,000 civilians. Vibrio cholera, the bacterium, which was responsible for this pandemic causes dehydration, diarrhea, low blood pressure and muscle cramps. It is easily treated today with hydration and in worst cases with antibiotic treatment. Thanks to the British Physician John Snow, who discovered the source of contamination in the water system in London, the pandemic was finally contained.

The 1918 Influenza Pandemic

At the end of World War I, when Europe was ravaged by the horrors of the war, the deadliest influenza pandemic emerged. The Spanish flu, also known as the 1918 influenza pandemic, led to the death of 25 to 50 Million people. Its name is a misnomer and created a false impression of Spain as the epicenter of the pandemic. The earliest reported case was actually in Kansas and it was caused by an H1N1 virus infection. Symptoms of the disease were that of a typical flu: chills, fever and fatigue but in the worst cases the patient's skin was turning blue and their lungs were filling with fluid that caused them to suffocate. One year after its emergence, one third of the world’s population was infected by the virus. Until today, it is not clear why it had such a high mortality rate in the younger population; some reports claim that the Spanish flu triggered a cytokine “storm”, a sudden increase in the body’s immune cells, which led to severe health issues. Some other reports suggest that the high mortality rates were due to the malnourishment and poor hygiene measures in overcrowded hospitals. Interestingly, a study dating back in 2008 by Yu et al reports that survivors of the influenza, born in the times of the pandemic or earlier, were still immune to the virus after almost one century! Infection back in 1918 offered a long-lived immunity to the population that managed to survive.

The HIV Pandemic

One of the most long-lasting epidemics-pandemics is the one caused by HIV (the Human Immunodeficiency Virus), dating back to 1981. It is referring to a viral infection that suppresses the immunological responses, leaving the organism vulnerable to infections.  While it is believed that HIV first originated around 1920 in Congo, when it crossed species from chimpanzees to humans, it was not until 1982 that the CDC of the United States of America formally introduced a name for the infections as “AIDS” (acquired immune deficiency syndrome).  Since then, it is estimated that over 75 million people have been infected, of which 32 million died and the rest are living with the disease. Diagnosis of HIV infection is very difficult since in most cases patients are asymptomatic. However, general symptoms usually include fever, muscle aches, fatigue, sore throat, chills and swollen lymph nodes. Despite how challenging it is to create antiviral drugs, the medical community has made a lot of progress in creating antiretroviral medications. These medications aim to suppress the virus and slow its progression in the human body and demonstrate encouraging results in patients with HIV. Studies have shown that the life expectancy of an HIV positive person is similar to that of an HIV negative one. Many patients positive for HIV managed to survive and are characterized as “long-term survivors”, even before the HIV medications were launched on the market.

In conclusion, it is definitely not new for humanity to face a pandemic. All pandemics led to consequences in the human history that, in some cases, led to economic and political crises and in some others, led to the death of a substantial part of the population. The good news is that for the majority of them, the scientific community already has a vaccine and a treatment. However, for some of them treatment still remains undiscovered. We should without a doubt consider the following question: Is COVID-19 one of the worst pandemics that the world has had to face so far?


Written by Evrydiki Asimaki; Edited by Jie Shi. Featured image: NGC/Design.


Huremović et al., Psychiatry of Pandemics (2019)
Piret et al., Frontiers in Microbiology (2020)
Hughes et al., The Origin and Prevention of Pandemics (2010)
Tognotti et al., Emerging Infectious Diseases, (2013)
Glatter & Finkelman, The American Journal of Medicine (2021)
Saunders-Hastings et al., Pathogens (2016)
Yu et al., Nature (2008) Nature 455, 532–536 (2008)

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