Pandemics have literally plagued the world for millennia and will continue to do so due to the simple concept of evolution. Contemporary viruses reflect evolution ranging from the RNA world to the DNA-protein world. Viruses are the most abundant biological entities on earth and are present everywhere, from our environment to every living being in it. A virus has the ability to combine with another and form a completely new virus to which we have no defense. In layman’s terms, once we have found a vaccine to combat a particularly aggressive virus, it means we have found a cure for one specific strain of a virus only, and with each new one that emerges the race will start all over. Examples of diseases caused by viruses are chickenpox, AIDS, and flu.
Bacteria can also cause infectious diseases, but the majority of bacteria do not. Some bacteria are actually good for us such as the harmless bacterium that lives in our intestines and helps to digest food, provides nutrients, and destroys some disease-causing organisms. Bacterial diseases include cholera, leprosy, tuberculosis, plague, syphilis, and anthrax.
We look at some of the more severe pandemics ranging from the 2nd century to date to illustrate how our understanding of disease and means of combating it developed over time, but first we have to differentiate between a plague and the disease ‘plague’. The former refers to an epidemic disease that causes high mortality and can be caused by a virus or a bacterium. The Plague of Galen, for instance, was probably caused by a virus. The disease called ‘plague’, however, is caused by Yersinia pestis bacteria, and occurs in various forms, with the most common being bubonic, septicemic, and pneumonic, often also referred to as Black Death.
165-180 AD : Antonine Plague (Plague of Galen):
This plague broke out during the Age of the Antonines (138-192 AD) in 165 AD, at the height of the Roman power throughout the Mediterranean world, during the reign of Marcus Aurelius Antoninus. Marcus Aurelius was one of the most respected emperors in Roman history and known as the last of the ‘Five Good Emperors’. The plague lasted for 15 years until the end of his reign in 180 AD, but a second outbreak would occur in the period 251-266 AD, once again lasting 15 years.
The plague is believed to have originated in China shortly before the start of the pandemic in Rome and spread along the Silk Road and by trading ships heading for Rome. The Roman military came into contact with the disease during the siege of Seleucia and the returning troops spread the disease to Gaul (present France, Belgium, Luxemburg and parts of the Netherlands, Switzerland, Germany on the west bank of the Rhine, and the Po Valley, in present Italy).
Two legends surrounding the origins of this plague give insight into ancient people’s beliefs in terms of the origin of disease. In one story the disease was released in punishment for violating an oath to the gods not to pillage a city when a Roman general opened a closed tomb in Seleucia during the siege of the city. The second story is similar, but in this one a Roman soldier opened a golden casket in the temple of Apollo in Babylon, thereby angering the gods.
It is, however, also called the Plague of Galen which in turn honours the Greek physician Aelius Galenus, better known as Galen, who is considered one of the most accomplished of all medical researchers of antiquity. He influenced the development of various scientific disciplines such as anatomy, physiology, pathology, pharmacology, neurology, as well as philosophy and logic. Galen’s accurate description of the symptoms and effects of the disease have led modern scientists to believe that the cause of the pandemic was either smallpox or measles. It is estimated that 60-70 million people, a quarter to a third of the entire population of the Roman Empire, died of this disease, including co-emperor Lucius Verus and Marcus Aurelius himself, at the end of the first wave of the plague in 180 AD.
542 AD : The Plague of Justinian (The 1st plague pandemic)
The Plague of Justinian is in general regarded as the first recorded incident of the Bubonic Plague and had a devastating effect in its year-long reign of terror in the Byzantine and Sasanian Empires as well as the Mediterranean port cities, with an estimated death toll of 25 million people. The capital of the Byzantine Empire, the city of Constantinople (modern Istanbul), was the worst afflicted, resulting in the death of 40% of the city’s population. Researchers today, however, believe the total number of deaths to have been lower, but still extreme.
The Byzantine Empire was a continuation of the Roman Empire in the eastern provinces during Late Antiquity and the Middle Ages, and the Sasanian Empire (known as the Empire of Iranians) was the last kingdom of the Persian Empire. The plague was named after the Byzantine emperor, Justinian, who reigned from 527-565 AD.
At the time of the outbreak of the plague Justinian was in the process of rebuilding his kingdom to the former glory of ancient Rome, but the plague put a swift end to it and plunged the Mediterranean area back into the Dark Ages. It left the Byzantine military and economy destroyed, and with that also Justinian’s dreams.
The symptoms of the disease started with a mild fever, followed by swellings a couple of days later. Black blisters filled with pus were a sure sign of having contracted the disease. The Greek historian Procopius wrote that many people believed the disease to be caused by a malevolent spirit or demon, and they started barring doors and would not allow visitors and even family members to enter their homes in an attempt to prevent the demon from entering their homes and infecting them. Perhaps the first occurrence of voluntary lockdown? We do not know how many people might have been saved by these measures, but the plague nevertheless killed so many people that the city could not stay ahead with burying them all. In the end, they resorted to digging long trenches for mass burials. People took to wearing nametags on their wrists to ensure that should they die away from home or in the streets, their families might be notified of their death and take care of the burial.
The outbreak in Constantinople was thought to have been brought to the city by infected rats on grain ships arriving from Egypt – in particular, the fleas on these rats (although the actual vector was figured out centuries later). Six years earlier Procopius had reported an epidemic in the port of Pelusium, generally known as the gateway to Egypt. In 2010, researchers confirmed earlier speculation that the cause of the Justinian Plague was Yersinia pestis, a facultative anaerobic organism that can infect humans via the Oriental rat flea. Three main strains have subsequently been identified, with Yersinia pestis antiqua the strain responsible for the Justinian Plague. Although genetic studies of modern and ancient Yersinia pestis DNA suggest that the origin of the Justinian Plague was in Central Asia, the most root level existing strains of Yersinia pestis as a whole species are found in Qinghai, China.
1347-1352 AD – The Black Death (The 2nd plague pandemic)
The Black Death of October 1347 to c1352 was the worst catastrophe in recorded history – a deadly bubonic plague that ravaged communities across Europe and Asia, changing forever their social and economic fabric. Over the course of three to four years it reduced the population of Europe from an estimated 80 million to 30 million. Some communities were completely wiped out, with some others barely touched. Although the medieval people believed that the plague came from God, as with the Plague of Justinian, Yersinia pestis was once again the culprit, but this time a different strain, namely Yersinia pestis medievalis.
Prior to the arrival of the plague in Europe, there were rumours of a ‘Great Pestilence’ across the trade routes of the Near and Far East. When 12 Genoese galleys arrived at the Sicilian port of Messina in October 1347, the people gathered on the docks were met with a horrific scene. Many sailors aboard the ship were dead, and those still alive were gravely ill and covered in black boils that oozed blood and pus. The ‘death ships’ were hastily ordered out of the harbour, but it was too late.
Cities that managed to keep the plague beyond their borders were those that devised and implemented quarantine. The Venetian-controlled port city of Ragusa (today Dubrovnik, Croatia) was a pioneer in this regard by keeping arriving sailors in isolation until it was clear they were not carrying the disease—creating social distancing that relied on isolation to slow the spread of the disease. The sailors were initially held on their ships for 30 days (a ‘trentino’), a period that was later increased to 40 days, or a quarantine—the origin of the term “quarantine” and a practice still used today.
The plague, however, was not responsible for all the deaths that occurred during this period. In German-speaking countries, France along the Rhine, and the Holy Roman Emperor, Jews were accused of spreading the Black Death by poisoning food and water sources. Entire communities of men, women, and babies were massacred for their supposed crimes. No such massacres arose in the British Isles, neither is there any clear evidence for such violence in Italy (except Sicily), nor are any recorded in the Middle East. During this period many Jews relocated to Poland where they were welcomed with open arms.
For centuries after this second wave in Europe ended, the epidemic continued to strike every ten years or so, with the last major outbreak the Great Plague of London in 1665-1666.
1894 CE: 3rd Plague pandemic
The third plague pandemic opened the era of great discoveries such as identification of the Yersinia pestis bacterium, of transmission vectors, and the first effective treatments. For the first time it became possible to control a disease which had spread throughout the world mainly because of progress in maritime transport.
The outbreak began in China’s Yunnan province and spread to Hong Kong in 1894, but research indicates this plague may have come from two different sources. The first one was, as with the Black Death, primarily bubonic and similarly spread through the ocean-going trade through the transporting of infected persons, rats, and fleas in the cargoes. The second was a more virulent strain and primarily pneumonic in character, with a strong person-to-person transmission. The latter strain was largely confined to Asia.
Prior to having reached the city of Hong Kong, an outbreak in Guangzhou, a neighbouring city of Hong Kong, was reported in January 1894. In March the same year scientists and doctors in Hong Kong became aware of the outbreak in China and by the end of April the government in Hong Kong requested the consular surgeon for Canton to report the disease. The first case in Hong Kong was identified in a patient at the Government Civil Hospital on 8 May 1894.
From China the plague was carried by ships to Japan, Singapore, Taiwan and the Indian sub-continent and over the next few years it spread to many cities around the world such as Bombay, Singapore, Alexandria, Buenos Aires, Rio de Janeiro, Honolulu, San Francisco, and Sidney. It reached Europe in October 1896 when two sailors from Bombay died of plague on ships docked in London on the Thames. Summaries of case reports from North America, South America, Africa, and Asia improved our present understanding of the historical epidemiology and distribution of plague. It was during this period that scientists identified the role of rats and rat-fleas in the spread of the disease. Other documented sources in Europe indicate human-to-human transmission of the plague. The low infection rate of humans in Europe could be the result effective public health intervention methods such as isolation of patients and contacts, prohibition of gatherings, and improved hygiene.
The 3rd pandemic had a particularly hard impact on Colonial India with 12,5 million people dead over a thirty-year period. In 1897 the British in India developed a vaccine against bubonic plague and began a mass vaccination campaign.
Although there is no mention of plague outbreaks in Europe after 1950, it has, however, never been fully eradicated as up to 3 000 cases are reported to the World Health Organization (WHO) every year. Most of these occur in Africa, Asia and South America and are most prevalent in the Democratic Republic of the Congo, Madagascar, and Peru.
1918 CE: The Spanish Influenza
The Spanish Flu pandemic of 1918 is still considered to have been the deadliest pandemic in history to date and also the one which is used as yardstick for the current Coronavirus outbreak – not only in preventative measures, but also in what should NOT be done. It infected an estimated 500 million people worldwide (approximately one third of the world’s population at the time), and an estimated 20-50 million of those infected, died. Similar to the current COVID-19 pandemic, there were no effective drugs or vaccines to treat this particularly virulent flu strain at the time. Instead, citizens were ordered to wear masks and schools, theatres, and businesses shut down. This was the correct decision, but (and in this lies what should not be done!) too late.
The Spanish flu broke out during the last year of World War I (1914-1918). At this time Spain was a neutral country with a free media that covered the outbreak from the start, first reporting on it in Madrid in late May 1918. Meanwhile, Allied countries and the Central Powers had wartime censors who covered up news of the flu to keep morale high and in so doing allowed the flu to spread like a veld fire out of control with the continuous move of army forces from country to country and back home. Because Spanish news sources were the only ones reporting the flu, many believed it to have originated there, whereas the Spanish referred to it as the French Flu as they believed it to have had its origins there.
Today, it appears that the Spanish might have been correct in this assumption, as the major UK troop staging and hospital camp in Étaples in France has been theorized by virologist John Oxford as being at the centre of the Spanish flu. (Oxford is a leading expert on influenza, including bird flu and the 1918 Spanish Influenza, as well as HIV/AIDS.) His study found that in late 1916 the Étaples camp was hit by the onset of a new disease with high mortality that caused symptoms similar to the flu – and, as mentioned, this news was censored, which allowed the virus to spread unchecked. According to Oxford, a similar outbreak occurred in March 1917 at army barracks in Aldershot (England) – once again censored. Military pathologists later recognized these early outbreaks as the same disease as the 1918 flu.
The overcrowded camp and hospital was an ideal site for the spreading of a respiratory virus. The hospital treated thousands of victims of chemical attacks, and other casualties of war, and 100,000 soldiers passed through the camp every day. It also was home to a piggery, and poultry was regularly brought in for food supplies from surrounding villages. Oxford and his team postulated that a significant precursor virus, harboured in birds, mutated and then migrated to pigs kept near the front. In further confirmation of this, a report published in 2016 in the Journal of the Chinese Medical Association found evidence that the 1918 virus had been circulating in the European armies for months and possibly years before the 1918 pandemic.
In 2005, researchers announced that they had successfully determined the gene sequence of the 1918 influenza virus. The virus was recovered from the body of a flu victim buried in the permafrost of Alaska, as well as from samples of American soldiers who fell ill at the time. Two years later, monkeys infected with the virus were found to exhibit the symptoms observed during the pandemic. Studies suggest that the monkeys died when their immune systems overreacted to the virus, a so-called “cytokine storm.” Scientists now believe that a similar immune system overreaction contributed to high death rates among otherwise healthy young adults in 1918.
Today scientists know more about how to isolate and handle large numbers of ill and dying patients, and physicians can prescribe antibiotics, not available in 1918, to combat secondary bacterial infections. To such commonsense practices as social distancing and hand-washing, contemporary medicine can add the creation of vaccinations and anti-viral drugs.
For the foreseeable future, viral epidemics will remain a regular feature of human life. As a society, we can only hope that we have learned the great 1918 pandemic’s lessons sufficiently well to quell the current COVID-19 challenge.
What have we learned?
The need for transparency (Prevention is better than cure!): History has taught us that it is easier to stop something from happening in the first place than to repair the damage after it has happened. Although preventative measures such as the wearing of masks, social distancing, quarantine and disinfecting surfaces are of the utmost importance, the need for transparency is even greater. If knowledge about the outbreak of the misnamed Spanish Flu was not suppressed by wartime censorship, the spread thereof might have been curbed and millions of lives spared. Similarly, the outbreak of COVID-19 is also the result of a lack of transparency by officials in Wuhan who ignored and suppressed initial warnings. The result in both was that it quickly ran out of control.
Quarantine: An order from the archives of Dubrovnik, the earlier Adriatic port city of Ragusa, reads that the city’s Major Council passed a law on 27 July 1377 which stipulates that ‘those who come from plague-infested areas shall not enter [Ragusa] or its district unless they spend a month on the islet of Mrkan or in the town of Cavtat, for the purpose of disinfection.’ This is the earliest surviving record of the passing of legislation requiring mandatory quarantine of incoming ships and trade caravans to screen for infection. As noted earlier, this 30-day period was known in Italian as a trentino, but officials had the authority to impose longer or shorter stays. Quarantine comes from the Italian word quarantino which means a 40-day period. It is surmised that a 40-day period might have been prescribed because of the religious significance of the number 40 to medieval Christians. There are 146 references in the Bible to the number 40, but it should also be borne in mind that the number 40 also features in Sumerian mythology up to Judaism, Hinduism, Buddhism, and several other current religions of the world.
Social distancing and disinfecting of surfaces: As early as 1348 (during the Black Plague), city officials put emergency public health measures in place that foreshadowed today’s best practices of social distancing and disinfecting of surfaces. According to Jane Crawshaw, a senior lecturer in early modern European history at the Oxford Brookes University, “They knew that you had to be very careful with goods that are being traded, because the disease could be spread on objects and surfaces, and that you tried your best to limit person-to-person contact.” Included with this is also the prohibition of large gatherings, shutting down of schools, businesses, theaters, etc.
Wearing masks: The Spanish Influenza taught the value of masks. It would have been equally effective during the 3rd plague pandemic, had they known the plague turned from bubonic to pneumonic.
We have also learned that all pandemics of the past had a severe negative impact on the economy worldwide, which in the aftermath of these pandemics affected the quality of life of all those who survived. Why is it then that so many people during the current COVID-19 pandemic do not adhere to the simplest preventative measurements – the washing of hands, wearing of masks, and maintaining social distance?
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 RNA = ribonucleic acid, a nucleic acid present in all living cells
 DNA = deoxyribonucleic acid, a self-replicating material which is present in nearly all living cells as the main constituent of chromosomes. It is the carrier of genetic information.
 Although Y. pestis was identified during the third plague pandemic , not all scientists initially agreed on this until as recently as 2010, when consensus was finally reached on the issue.
 Yersinia Pestis was named after the Hong Kong-based doctor, Elexandre Yersin, who identified the bacillus Yersinia pestis as the cause of plague.