There have been various well-known pandemics in history. The Athenian "plague" (430 BC) at the time of the Peloponnesian War (431-404 BC) was described by the Greek historian Thucydides, but the precise aetiology of this epidemic is uncertain. The profusion of different hypotheses (Ebola, Rickettsia prowazekii, ergotism, epidemic recurrent fever, smallpox, Bacillus anthracis, Yersinia pestis, arbovirosis, robovirosis, a variant of "Spanish" flu, etc. ) shows that, in the absence of essential data, a correct diagnosis after the event is a hopeless task.

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In 542 AD, at the time of the Roman emperor Justinian, an epidemic occurred in Pelusium, in Egypt, a seaport at the mouth of the eastern branch of the Nile delta. The epidemic subsequently struck Turkey and Europe (Justinian plague). The consequences and terrors were described by the Byzantine historian Procopius, secretary to Belisarius, one of the most important generals under Emperor Justinian. The epidemic ended about 767.

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At the beginning of the Middle Ages, following the fall of the Roman Empire, the European population figures declined. The birth rate, which was high because of the lack of reliable contraception, fell below the mortality rate. Because the climate was fairly cold, the harvests were poor. Many people died from hunger and malnutrition. Wars and internal violence as a result of conflicts between kings and princes seeking power brought with them many victims. In the absence of a labour force, the large landowners found it difficult to have their lands worked. They decided to tie the farmers to their estates. From the 7th century, the climate began to warm up. The fields produced more grain. From 800 to 900 AD, the political situation started to become somewhat more peaceful. There were fewer wars. More stable government by European monarchs appeared. The church promulgated "God’s truce" and "God’s peace". In these circumstances, the population numbers increased so that there was an increased need for food. Abandoned fields were taken back into use. Forests, heaths and peat moors were reclaimed. Land was won back from the sea by building dikes. Technical innovations made it possible to increase the yield per square metre. The rural population grew. Because of overpopulation there was migration to the cities, which then flourished. An end to the good times came around 1300. It was no longer possible to increase the average of farmland and the yield could no longer be increased with the resources existing at the time. Large international wars (e.g. the Hundred Years’ War) in which the tactics of trade embargoes were used held Europe in an iron grip. There were a number of consecutive very wet years, as a result of which the whole of Europe was transformed into a great quagmire for several years and harvests failed. It is against this background that the Black Death must be viewed. It was not until about 1450 that the European population returned to the numbers that existed in the year 200 AD.

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In 1346 there were cases of plague in Astrakhan, situated at the mouth of the Volga (north of the Caspian Sea). Afterwards, spread occurred via the River Don to the Sea of Azov and subsequently to the shores of the Black Sea. In 1347 there were Genoese traders in the city of Caffa (now Feodosiya), in the south of the Crimean peninsula in the Black Sea. It was the terminus of the northern branch of the Trans-Asiatic silk route. The city was besieged by Janiberg, leader of the Kipchak Tartars, in whose camp an epidemic of plague broke out. The Tartars catapulted bodies of their own comrades who died of the disease over the walls of the city. To what extent this contributed to the spread of plague is open to question. Anyway, the plague appeared in Caffa city. Twelve Genoese ships withdrew with cases of plague on board. Their crews went ashore at various places in Constantinople, Cyprus, Messina (Sicily), Southern France and Italy, after which a major epidemic broke out in December 1347. [The Italian writer Giovanni Boccaccio, in his famous book "Decameron", described the flight of 10 Florentines from the plague in 1348]. In June 1348 the plague reached Paris. In December it arrived in England. In May 1349 a ship with a cargo of wool sailed from London to Bergen in Norway. A few days later it was found drifting with the crew dead off the Norwegian coast. The cargo was brought on land and by the end of 1349 the plague had spread throughout the whole of the country. In 1351 the plague came to Poland. The Black Death in the 14^th century wiped out approximately a quarter of the population of Western Europe. Together with the other terrors of the 14^th century (e.g. the Hundred Years’ War between England and France, 1339-1453), this meant that the European population declined from 73 million to 45 million. These terrors were also partly the cause of the French Peasants’ Revolt, the Jacquerie, in 1358. The term "quarantine" stems from 1370, when seafarers arriving in the Republic of Ragusa in Southern Italy were isolated for 40 days (quaranti giorni). In 1423, a lazaretto (quarantine station) was brought into use off the coast of Venice on the island of Lazarro. This system was subsequently applied in Dubrovnik, Croatia, and later it became the model for the rest of Europe. According to legend, Mr Roch was a young nobleman who had survived the plague in Montpellier, France. After having fled the city, he returned to look after the sick because of his religious conviction. However he died in prison, possibly in 1327, which is prior to the beginning of the great plague epidemic in Europe. St Rochus is often viewed as the patron saint of the sick.

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Plague also raged from the 15^th to the 17^th century in Europe. The Great Plague of London in 1665 totalled 70,000 deaths. The epidemic was possibly stopped by the Great Fire of London in 1666, but according to English demographic data ("Bill of Mortality"), mortality had already declined before the Great Fire. [Anecdote: in 1665 the Englishman Robert Hooke published his book "Micrography", in which the first description of microscopic structures appeared. However, it was to take more than 200 years before the organism responsible for plague was demonstrated]. Subsequently other smaller outbreaks happened (Marseilles in 1720, Egypt in 1834). The decline of the plague has been associated with the reduction in the number of black rats and their replacement by brown rats which have less close contact with humans.

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In 1860, a new epidemic arose in Yunnan, China, which later spread, first to the town of Pakhoi and then to Canton (Guangzhou), before subsequently travelling downstream and reaching Hong Kong in 1894. It was then that the organism was isolated. From this port there was further spread via ships’ rats (e.g. to San Francisco 1903, Auckland, Bangkok, Manila, Rangoon, Saigon, Batavia, Tokyo, Sydney, Cape Town, Buenos Aires, Mauritius and Glasgow), which caused huge mortality, especially in India. Between 1898 and 1918, 8 to 12.5 million people died in India. The epidemic was brought to a halt in the first half of the twentieth century. In North China there was also a major epidemic. This resulted from the intensified hunting of marmots (Marmota bobak sibirica or Arctomys bobac; "tarabagan"). These mammals had a valuable pelt and were also very susceptible to plague. The local Mongols knew the risk of this only too well and shot the animals instead of catching them. They also always avoided touching sick or dead animals. When the price of pelts quadrupled in 1910, there was a large influx of inexperienced amateur Chinese who hunted without precautions in search of rapid profits. The hunters also often kept warm together in underground shelters, which was ideal for transmission. Pneumonic plague broke out in Hailar and spread along the railway line to Harbin and afterwards to Vladivostok.

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In the Second World War, Japanese Imperial Army's Unit 731 killed thousands of Chinese and Russians held prisoner in Japanese-occupied Manchuria, in experiments to develop chemical and biological weapons. Japanese doctors tested the use of plague, among others. Infected Pulex irritans fleas were cultured and released in a few Chinese towns, resulting in small epidemics of bubonic plague.