Pandemic – from dinosaurs to Covid-19

Prof. RNDr. Aleš Macela, DrSc.
Prof. RNDr. Vanda Boštíková, Ph.D.

Introduction

The SARS-CoV-2 virus has triggered a pandemic that has caused nearly seven million deaths to date (see https://covid19.who.int/). Many people, after contracting the infection, still experience its effects in the form of post-covid syndrome, referred to as long covid. Thus, infection with SARS-CoV-2 has affected the physical and mental health of many people. Analysis of mortality during the Covid-19 pandemic has shown that the coexistence of non-infectious diseases with infection, or the confluence of multiple infections, is particularly dangerous for patients’ survival during SARS-CoV-2 infection. The term syndemia was chosen for such a situation. In addition, it has been shown that a pandemic may not always be associated with only one type of virus. The SARS-CoV-2 virus changed very rapidly, mutating at a rate of about 1 to 2 mutations per month during its spread in the population, so that within two years an omicron variant emerged that accumulated 30 mutations in its spike protein, completely changing its spatial conformation. In addition, omicron has ten mutations in the protein domain responsible for binding to the ACE2 receptor on host cells. It is the changes in the virus induced by the mutations that result in changes in the interactions between the host, i.e. human and the SARS-CoV-2 virus. These changes also condition the ability of the SARS-CoV-2 virus to reinfect a person who has already had Covid-19, allow resistance to antibodies produced after infection or vaccination, or change the rate of spread of the virus in a population. The latter is most crucial for the emergence of a pandemic. We have already introduced some terms such as pandemic, syndemic and infection. In order to have a fundamental understanding of epidemiological processes in a population that is exposed to a constant burden of different pathogens, it is necessary to explain the basic concepts in order to understand pandemic processes and the anti-epidemic measures taken to deal with them.

The term infection is derived from Latin or Greek. The word infection can be traced back to the initial verb facere (to make) and the prefix in (in), giving rise to the verb inficere, from which it is a short step to the word infectio, which means to infect or infest. Infection thus means the entry of pathogens into the body and their multiplication, often leading to disease. The term infection therefore refers only to a particular organism, a particular person. In contrast to the term infection, the term epidemic is derived from the Greek preposition epi- (over) and the noun demos (people) and refers to a sharp increase in the incidence of, most often, the same disease over a certain period of time and in a certain population. The term pandemic is derived from the Greek words pan- (all) and demos (people) and refers to an infectious disease causing an epidemic spreading across countries and continents. It is a very dangerous process, threatening millions of people with its consequences.

Infection

All living multicellular organisms, including humans, have been subject to coevolution with microorganisms from the beginning until today. And even pathogenic microorganisms that cause infectious diseases. Man is confronted with them from birth until old age, when infections are often the cause of his death. In prehistoric and early historic times, infections were believed to be divine punishment for wrongdoing or the result of supernatural forces directed at a particular person by shamans or witches. Also, the cure of disease was left to people who were believed to have some power over supernatural forces or to have extraordinary “secret” knowledge, such as healers. We encounter this phenomenon more than once in the twenty-first century, when, based on false information, people distrust conventional medicine and turn to alternative therapeutic practices.

Today, there is no doubt that infections are caused by pathogens, i.e. viruses, bacteria, fungi (most often fungi, which are a specific type of fungus) or parasites. Bacteria were first seen in 1676 by the naturalist Antoni van Leeuwenhoek (1632-1723) when he saw moving microscopic objects, which he called animacules, animals, under a microscope he had built himself. He didn’t call them bacteria until Christian Gottfried Ehrenberg (1795-1876) did so more than 150 years later, in 1838. He used the Greek word bacterion for microscopic rod-shaped objects, which is the word used for a rod. The connection between bacteria, or living microorganisms, and disease was understood in the mid-nineteenth century by Louis Pasteur (1822-1895), who advocated that bacteria do not arise spontaneously from inanimate matter. He thus denied Aristotle’s (384 BC – 322 BC) hypothesis of abiogenesis, according to which living organisms can arise, for example, from dirt and garbage (the theory of spontaneous generation).

Viruses were essentially discovered by the Russian botanist Dmitry Ivanovsky (1864-1920), who in 1892 demonstrated the transmission of tobacco mosaic disease by a solution prepared from diseased plants and filtered through a microbiological sieve through which bacteria do not pass. The infectious particles that cause tobacco mosaic disease were described six years later by Martinus Beijerinck (1851-1831). He called them contagium vivum fluidum (from the Latin for „infectious living fluid“). The word virus originally referred to a poison, later to a microbe, and finally to filterable infectious particles, i.e. viruses in today’s terms, which are so-called non-cellular organisms.

Moulds have been known since time immemorial because they formed a white or coloured fine coating on the surfaces of substrates and were unnoticeable. The term mould is a non-systematic term referring to phycomycetes, eruptive fungi and fungi imperfecta. Infectious diseases caused by moulds, called mycoses, are most commonly caused by yeasts or dermatophytes. They can occur anywhere on the body, but also in body cavities, e.g. in the case of sinusitis, but most often occur between the toes, on the feet, hands, armpits, ear or hair.

The parasitic way of life, i.e. the coexistence or symbiosis of two organisms, one of which, the parasite, uses the other, the host, is inherent in both prokaryotic, nucleusless microbes and eukaryotic microbes having a nucleus. Francesco Redi (1626-1697), probably the first physician-naturalist to challenge the theory of abiogenesis, is considered the father of parasitology. Nicolas Andry de Bois-Regard (1658-1742) then directly attributed the origin of disease to germs that entered the human body. Initially, they studied parasitic worms (tapeworms, Taenia saginata or Taenia hydatigena), and later unicellular organisms causing more or less serious diseases in humans. Diseases caused by unicellular parasites include, for example, malaria (caused by the unicellular parasitic protozoan Plasmodium falciparum), or trichomoniasis (Trichomonas vaginalis), leishmaniasis, one form of which is known as kala-azar (Leishmania donivani) or even toxoplasmosis (Toxoplasma gondii).

According to the duration and intensity of the course, infections are divided into acute and chronic, and acute infections can be further divided into superacute (fulminant) infections, which have a very rapid course with very dramatic symptoms. Acute infections take days to develop and take longer to resolve, whereas subacute infections take weeks or months to resolve. Chronic infections can then proceed either completely asymptomatically or with symptoms that may be persistent or progressively worsen. Chronic infections can last for many years in infected patients.

Some pathogens do not have the ability to move from person to person, so they do not spread freely in the population and cannot affect large numbers of people unless they come into direct contact with the source of infection. An example is tularemia, sometimes called rabbit disease. Its source is either a tick or an infected rodent or rabbit. Other pathogens, however, can be spread by droplets (aerosols) or dust from poorly maintained environmental hygiene from person to person and can cause an epidemic. Examples are influenza viruses, which in certain circumstances cause major or minor epidemics.

Epidemics

It is usually stated that the term epidemic comes from Homer’s Odyssey. The word epidemios, epidemeo, epidamos, and other variants of it denoted something native or endemic. The meaning of the word epidemic, with approximately the same meaning as we understand it now, comes from Hippocrates (460 BC – 370 BC) writing “On Epidemics.” Over the centuries, the form and meaning of the term epidemic have been further refined. Successive plague epidemics in the Middle Ages contributed to the definition of an epidemic as the spread of a single, well-defined disease. Today, according to the Centers for Disease Control and Prevention in Atlanta (CDC), an epidemic is defined as „the occurrence of more cases of disease, injury, or other health conditions than would be expected in a given area or among a specific group of people during a given period of time“. Cases are usually assumed to have a common cause or to be related in some way. Thus, an epidemic is not necessarily of infectious origin (according to the WHO, there is an obesity epidemic), but is usually used to refer to the spread of an infectious disease that is not necessarily transmissible from person to person (e.g. the West Nile epidemic, the causative agent of West Nile virus is transmitted by mosquitoes).

The source of epidemics caused by pathogenic microorganisms may not always be a microorganism with epidemic potential from the outset. Due to the high generational turnover of viral and bacterial pathogens, mutations occur that alter the relationship between the pathogen and its host by changing virulence or altering the ability to bind to the cells of the target organism. Similarly, a pathogen that is endemic to a particular area, occurs there permanently and is in recurrent contact with the host population living there may not cause serious health problems. However, if such a pathogen enters a so-called naive host population that has never encountered this type of pathogen, it can cause an epidemic with very serious health, social and economic consequences. An example is the entry of SARS-CoV-2 into the human population and its gradual transformation through a series of mutations. Another example would be the transmission of European viruses (smallpox, measles) and bacteria by Spanish colonisers to Central and South America. From the 1520s and then from the 1530s, epidemics of smallpox and measles, newly introduced diseases that the local population had never encountered before, decimated the Mexican Aztecs and Peruvian Incas. The German Jesuit missionary Joseph Stöcklein (1676-1733) commented: „Indians die easily. All they have to do, is to see and feel the Spaniards and they let their souls go straight away. There is another possibility, where a microorganism that is fairly harmless in a given host population may begin to spread freely and cause an epidemic by transferring to a new host.

A change of host or spread of the pathogen to new sites gives rise to so-called emerging or re-emerging infections (Figure 2). It is such infections that have epidemic potential, as the pathogen enters a naive host population. A simple classification has been developed that sorts emerging infections by origin, relative to the human population. These include “emerging infections” that have not previously been described in humans, such as HIV/AIDS, and “re-emerging infections,” meaning diseases that have spread to new locations or that are no longer controlled by previous treatments. The other two categories refer to infections whose agent has been artificially created, „deliberately emerging infectious diseases“ referring to agents created with the aim of terrorist or military exploitation, and finally „accidentally emerging infectious diseases“ caused by unintentional spread by humans. SARS-CoV-2, the agent of the Covid-19 pandemic, could fall into this category.

The epidemics that occurred at the beginning of this century largely meet the criteria for inclusion in one of the categories of emerging or re-emerging diseases. Here are a few examples:

• SARS (Acute Respiratory Failure Syndrome), a disease caused by a coronavirus designated SARS-CoV-1. The SARS epidemic (2002-2004) affected Hong Kong, Vietnam, Singapore, Canada, with nearly 8,000 cases registered and a mortality rate of 7%.
• MERS (Middle East Respiratory Syndrome Coronavirus), an epidemic caused by the MERS-CoV coronavirus from the Coronaviridae family, which is related to SARS-CoV-1. The virus itself has been known since 2012, but the epidemic did not occur until a year later.
• Ebola (Ebola haemorrhagic fever), is a viral disease of haemorrhagic fevers;  the causative agent is the Ebola filovirus. Since 1976, Ebola has been occurring in tens to hundreds of cases per year across a swath of Central African countries. Major Ebola epidemics occurred in Uganda in 2000-2001 and in the Central and West African belt of states from 2013 to the present.
• Zika (Zika fever), the first major epidemic caused by the Zika virus, was monitored in Micronesia, where 185 people fell ill in April-May 2007. The causative agent of the fever is the Zika virus of the Flaviviridae family, which is transmitted by Aedes aegypti mosquitoes, but there is reason to suspect that it is also transmitted through sexual contact. A very well-known and media-attractive epidemic took place in 2015 and 2016 in South America, with nearly 175,000  confirmed cases and more than half a million suspected cases.
• Parotitis epidemica (mumps), a disease caused by one of the paramyxoviruses, virus parotitidis. Between 2004 and 2005, 56,000  cases were reported in the UK, approximately 6,000 cases in the USA in 2006, and 16,350 cases in Macedonia in 2009. Then in 2010, mumps reappeared in New York, with a total of 3,500      cases recorded. In the Czech Republic, mild mumps epidemics occur in approximately two to five-year cycles.
• Morbilli (measles), the etiological agent of measles, is Morbillivirus of the family Paramyxoviridae. In 2015, measles emerged in Berlin (approximately 500 cases were reported) and in the United States and Canada. In the Czech Republic, several hundred cases occurred  annually between 2014 and 2020.

Epidemics caused by the spread of infectious diseases      have occurred throughout human history and in many cases have influenced that history. The free spread of a pathogenic micro     organism in a population, which becomes catastrophic, is referred to as a pandemic. It also gives rise to a relatively new form of disease or epidemic process, the syndemic.

Syndemia

Syndemia is a synergistic epidemic, so much for the definition. It is essentially the confluence of two or more diseases spreading epidemically in a population and worsening the prognosis of return to the original state. In the course of the Covid-19 pandemic, the term infodemia was coined to refer to the phenomenon of the spread of excessive amounts of false or inaccurate information about a health problem (e.g., virus, epidemic, pandemic, etc.). The result is a deterioration in the flow of relevant information about the disease itself and about the possibilities of its treatment and prophylaxis, as well as psychological pressure on the population suffering from an epidemic or pandemic [5].

A syndemic is a synergistic epidemic, so many definitions. It is essentially the confluence of two or more diseases spreading epidemically in a population and worsening the prognosis for a return to the original state. The term was first used in the 1990s by Merrill Singer (*1950) in the context of the epidemic spread of infection with HIV, the causative agent of AIDS. The name syndemia was prompted by recognition of the synergy of social relations across social class, race, gender and sexual orientation on the one hand, and the level of public health, epidemiological conditions or categories of disease transmission on the other. Later, the whole theory of the syndemic approach to disease, which resulted from the integration of biological, abiotic and social influences, was elaborated by Singer’s group. From this, they also derived the principles of an integrated approach to an individual’s disease and the spread of both infectious and non-infectious diseases in a population. An integrated approach to understanding the nature of a health problem should be more effective at the stage of disease diagnosis, treatment and recovery. The whole system resembles that of family physicians, but somewhat faces the limitations of the number of available physicians and the creation of large structured databases. These should include personal, family, work and social history, including pharmacological and toxicological history (abusive behaviour) and up-to-date information relating to the patient’s current state of health.

An integrated approach to the analysis of non-infectious and infectious diseases has been used to elucidate synergies in the development of a range of health problems. These include diet-related chronic diseases such as diabetes, atherosclerosis, hypertension and gout. Several studies have used a syndemic approach to analyse the relationship of socioeconomic and political factors with sexually transmitted diseases, including HIV/AIDS infection. The bio-psycho-social approach has been used to analyse in more detail the nature of tuberculosis, where stress plays a significant role. In addition, in the case of tuberculosis, there is a significant AIDS-TB syndemic where multidisciplinary approaches that consider mycobacterial infection and HIV infection together rather than as separate health problems will be more appropriate.

The ongoing Covid-19 pandemic has also been identified as a syndemic. A synergistic effect on the course of SARS-CoV-2 infection has been demonstrated with other infectious diseases (tuberculosis, Lyme disease or AIDS), non-infectious health problems (obesity, high blood pressure, diabetes), psychological problems (stress), as well as with the age of the patient. A number of comorbidities with fatal consequences for the patient have been identified during the pandemic. Thus, the syndemic becomes a very serious problem when an infectious agent with pandemic potential enters the population.

Pandemic

Large-scale epidemics or pandemics are part of the biological processes that have been taking place on this planet probably since the very beginning of life. They are essentially a parasitic mode of coexistence between two organisms. This mode of coexistence is visible and perceived when the existence or even extinction of a particular biological taxon is threatened. A pandemic may have been responsible for the widespread collapse of the dinosaurs.

More than a hundred hypotheses have been linked to the extinction of the dinosaurs. Many of these are hypotheses related to planetary fates, such as the impact of other celestial bodies, asteroids, on the Earth’s surface, with the subsequent side effects of triggering volcanic eruptions, changes in ocean levels and associated climate change. The movements of continents over the ages have also been taken into account. In the Lower Cretaceous geological period, the break-up of the continent of Gondwana begins and the separated parts start to move northwards. In the subsequent Upper Cretaceous period, both the break-up of Gondwana continues and the disintegrating parts begin to merge, forming new land bridges between the parts, the continents, and thus exchanging megafauna and microflora. It was the arrival of pathogenic microorganisms from other parts of the continent that may have caused the pandemic that resulted in the extinction of the flightless dinosaurs. Roy Lee Moodie (1880-1934), a geologist and palaeopathologist, stated that diseases may have been behind the end of the dinosaur era, but that they also disappeared with the demise of the dinosaurs. This idea was followed up in 1986 by Robert Thomas Bakker (*1945) with his book Dinosaur Heresies, where he argues that it was at the end of the Cretaceous that the dinosaur and mammal faunas of what was then East Asia and North America mixed, bringing with them viruses, bacteria and other pathogens that may have started a pandemic marking the end of the dinosaur era. Later, George Poinar, Jr. (*1936) and his group did indeed demonstrate the presence of parasitic trypanosomatids (phylum Euglenozoa) in a sand fly (Palaeomyia burmitis) preserved in Burmese amber dating to the Early Cretaceous period, and the presence of parasitic worms and protozoan cysts in a relatively well-preserved skeleton of an Iguanodon that lived in the Lower Cretaceous period, some 130 to 120 million years ago. Pathogenic microorganisms in an immune-naive population could have triggered a pandemic and contributed to the demise of these creatures.

The family Hominidae, to which the species Homo sapiens, i.e. man, belongs, is also living its era in symbiosis with pathogenic microorganisms. Along with the increasing number of individuals of a certain species, including humans, the probability of infectious outbreaks with epidemic or even pandemic potential is increasing. Every major civilization on this planet has encountered rapidly spreading diseases. Depending on their worldview, they have called them either epidemics or pandemics.

Perhaps historically, the first major epidemic that can be considered a pandemic, for the reasons mentioned above, struck the area of Megiddo in Canaan (now in northern Israel). Clay tablets found at el-Amarna in Upper Egypt, containing administrative correspondence, contain a text addressed to Pharaoh Amenhotep III stating that the aforementioned area was „consumed by death, pestilence and dust“.

The actual first recorded pandemic took place in 430 BC during the Peloponnesian War, when the city-state of Sparta was at war with the city-state of Athens. The epidemic first appeared in southern Ethiopia and, already a pandemic, spread to Egypt, Libya, Persia and Greece and was introduced via the port of Piraeus to Athens. It killed more than a third of the population, greatly weakening the Athenians and hastening their defeat by the Spartans. A very detailed account of this pandemic was left by Thucydides (460 BC – 399 BC) in his History of the Peloponnesian War. Thucydides described quite accurately several symptoms, which, however, correspond to many      infectious diseases. He added that Athenian physicians had not yet encountered such a disease. Several later authors have tried to identify the disease. John F. D. Shrewsbury (1898-1971) of Birmingham University and Denys L. Page (1908-1978) of Cambridge University both considered it to be measles. William MacArthur (1884-1964), a British military physician, later president of the Royal Society of Tropical Medicine and Hygiene, considered a pandemic spread of typhus caused by one of the rickettsias. Harold D. Evjen (1929-2016) spoke of glanders caused by the bacterium Burkholderia mallei. Robert J. Littman, for a change, speculated about smallpox (smallpox) in a 1969 article, and J. M. H. Hopper considered viral Lassa hemorrhagic fever in his 1992 article „An arenavirus and the plague of Athen”. DNA analyses performed so far have not provided a significant answer.

With the new millennium came the “plagues”. The first of these, the Antonine Plague, or Galen Plague, according to the Greek physician Aelius Galen (129 AD -216 AD), struck between 165 and 180 AD and affected the entire Roman Empire at the time, during the reign of Marcus Aurelius Antonius Augustus. Hence the name Antonine Plague. Ancient sources agree that the pandemic probably appeared during the Roman siege of the Mesopotamian city of Seleucia, near Baghdad, in the winter of 165. The spread continued westwards, probably with the movement of Roman legions, throughout the empire. Although Galen describes this pandemic in some detail, again, it is not possible to determine from his information what the disease was. Today, we conclude smallpox. The total number of victims of the Antonine plague is estimated at 5-10 million, which at the time was about 10 percent of the population of the empire.

The plague of Cyprian was a pandemic that struck the Roman Empire between 249 AD and 270 AD. It affected the entire Mediterranean region from Rome to Carthage. The epidemic probably spread as a result of Roman commercial and military activity. It took its name from the Carthaginian bishop Cyprian, who described the pandemic in his work De mortalitate. The cause of this pandemic is also unclear. It could have been smallpox, a flu pandemic or one of the bleeding fevers caused by filoviruses. Two Roman emperors were also victims of this pandemic: Gaius Valens Hostilianus Messius Quintus, known by the abbreviated name Hostilianus (230-251), and Marcus Aurelius Claudius, known as Claudius II Gothicus (214-270).

Between 541 and 544, during the reign of the Byzantine Emperor Justinian, the first major pandemic of bubonic or bubonic plague caused by the bacterium Yersinia pestis broke out. Its first pandemic wave, occurring between 541 and 544, had a disastrous impact on the population and the economy, as the empire was at the same time dealing with a conflict with Persia. The plague first appeared in Ethiopia and quickly spread to Egypt. Thanks to military activities during the Byzantine-Persian conflict, the epidemic spread throughout the Mediterranean, into Mesopotamia and in the opposite direction into Gaul and Ireland. In Constantinople alone, a third of the population died of the plague. The pandemic situation lasted for about three years, but after a brief interval of about eight years, the plague returned, and the epidemic recurred at intervals of about four years until 622. It is estimated that the Plague of Justinian was responsible for between 30 and 50 million deaths.

From today’s point of view, it is very significant that the educated people of the time in the 7^th century AD first made the connection between the movement of people and goods and the spread of plague, and the first primitive method of preventing the spread of plague by blocking the movement of people and goods in trade was devised and tested from our present point of view. The knowledge was based on the fact that most goods came by sea, and the plague spread inland from the ports. It was also known that the migration of people from cities affected by the pandemic to places previously free of the disease contributed to the spread of the plague. By the mid-fourteenth century, plague had virtually disappeared in Europe.

Leprosy, or Hansen’s disease, is another of a number of diseases that carry pandemic potential. It is a chronic infectious disease that primarily affects the skin, peripheral nerves, upper respiratory tract and sometimes the eyes. References to leprosy can be found in ancient Egyptian, Greek and Roman writings. However, the disease did not reach pandemic proportions until the Middle Ages, most notably in the eleventh century. In the Old Testament, leprosy was regarded as a divine punishment after committing one of the seven biblical sins (pride, covetousness, envy, wrath fornication, intemperance and sloth). In Buddhism, leprosy was considered karma, or the result of a cause. The term leprosy comes from the Latin word lepros, meaning defilement. The causative agent of leprosy is the bacterium Mycobacterium leprae, which was discovered by Gerhard Armauer Hansen (1841-1912) in 1873 while working in a leprosarium, a facility designed to isolate leprosy patients, in Bergen, Norway. At that time, Norway was suffering from a major leprosy epidemic. However, the bacterium was first named Mycobacterium leprae murium because in 1902 a disease of rodents (rats) resembling leprosy had appeared in Odessa in the Crimea and was not distinguishable microscopically and microbiologically from the causative agent of the disease by the technical possibilities available at that time. Cat leprosy was also described in 1962. Today, the prevailing view, supported by the polymerase chain reaction (PCR) method, is that these are two distinct microorganisms, Mycobacterium leprae (the causative agent of leprosy in humans) and Mycobacterium lepraemurium (the causative agent of feline leprosy). The views on the pandemic spread of leprosy are also interesting. One sees the demand for squirrel skins and meat, an item traded by the Vikings, as the cause of the spread, while the other speaks of the spread of leprosy as a result of religious pilgrimages.

In the fourteenth century, the plague returned to Europe again, on such a scale that it earned the name Black Death. Between 1347 and 1353, some 75-200 million people died of the plague. According to John Kelly’s description in The Great Mortality, the great outbreak was in the city of Sarai, on the Volga River between the Black and Caspian Seas. It was the capital of the Golden Horde, a Mongol-Tatar khanate. It was the starting point from where Khan Jani Beg led the Tatar army to conquer the port of Caffa, originally a Greek colony, later a Byzantine and Genoese fortress situated on the southern coast of the Crimea. During the siege of the city, a plague broke out in the Tartar army. The Tartars used the bodies of the dead as a biological weapon and catapulted them over the walls into the city. Genoese and merchants fleeing Crimea then carried the disease to Europe. In May 1347, one of the fleeing ships landed in Constantinople, and in October 1347, other ships, in many cases with dead sailors, found asylum in Messina, Sicily. The plague spread rapidly, and by November of that year, people were dying in Marseilles, where another ship from Caffa had landed. By 1348, virtually all of southern Europe, including the Balkans, was affected, but also the north, including England and Wales. The following year,

English ships spread the plague to Denmark and Sweden via the Norwegian port of Bergen. By the end of the first half of the 14^th century, the plague had spread through trade routes to the Near and Far East. The disease had reached Syria, Egypt, Persia, India and China. It should be added that the plague recurred almost regularly in England from then on until 1480. Smaller epidemics of plague continued to occur in Europe until the eighteenth century. The last major epidemic or pandemic of plague occurred between 1855 and 1904 in China and India, killing approximately 10 million people.

The causative agent of plague is the pathogenic bacterium Yersinia pestis, which was described almost simultaneously in 1894 by the Swiss-French physicist and bacteriologist Alexandre E. J. Yersin (1863-1943) and the Japanese bacteriologist Shibasaburo Kitasato (1853-1931). It is a zoonosis, i.e. a disease transmitted to humans by an animal. The tarbagan rodent, a species of marmot (Marmota sibirica), is reported to be the source of infection in the area of its original endemic distribution.