Children and young adults were disproportionately affected in comparison to seasonal influenza, which causes severe disease mainly in the elderly, persons with chronic conditions and pregnant women. Three influenza pandemics occurred at intervals of several decades during the 20th century, the most severe of which was the so-called "Spanish Flu" caused by an A H1N1 virus , estimated to have caused 20—50 million deaths in — Milder pandemics occurred subsequently in — the "Asian Flu" caused by an A H2N2 virus and in the "Hong Kong Flu" caused by an A H3N2 virus , which were estimated to have caused 1—4 million deaths each.
With each pandemic, researchers, public health experts and international organizations have gained a better understanding of the complexity and dynamics of influenza pandemics. Justinian also got sick with the plague but survived. However, his empire gradually lost territory in the time after the plague struck. The Black Death traveled from Asia to Europe, leaving devastation in its wake.
Some estimates suggest that it wiped out over half of Europe's population. It was caused by a strain of the bacterium Yersinia pestis that is likely extinct today and was spread by fleas on infected rodents.
The bodies of victims were buried in mass graves. The plague changed the course of Europe's history. With so many dead, labor became harder to find, bringing about better pay for workers and the end of Europe's system of serfdom. Studies suggest that surviving workers had better access to meat and higher-quality bread.
The lack of cheap labor may also have contributed to technological innovation. The infection that caused the cocoliztli epidemic was a form of viral hemorrhagic fever that killed 15 million inhabitants of Mexico and Central America. Among a population already weakened by extreme drought, the disease proved to be utterly catastrophic. A recent study that examined DNA from the skeletons of victims found that they were infected with a subspecies of Salmonella known as S.
Enteric fever can cause high fever, dehydration and gastrointestinal problems and is still a major health threat today. The American Plagues are a cluster of Eurasian diseases brought to the Americas by European explorers.
These illnesses, including smallpox, contributed to the collapse of the Inca and Aztec civilizations. Another Spanish force led by Francisco Pizarro conquered the Incas in The Spanish took over the territories of both empires. In both cases, the Aztec and Incan armies had been ravaged by disease and were unable to withstand the Spanish forces. When people from Britain, France, Portugal and the Netherlands began exploring, conquering and settling the Western Hemisphere, they were helped by the fact that disease had vastly reduced the size of any indigenous groups that opposed them.
The plague started in April and spread rapidly through the hot summer months. Fleas from plague-infected rodents were one of the main causes of transmission. However, this was not the end of that city's suffering. On Sept. Historical records say that the Great Plague of Marseille started when a ship called "Grand-Saint-Antoine" docked in Marseille, France, carrying a cargo of goods from the eastern Mediterranean.
Although the ship was quarantined, plague still got into the city, likely through fleas on plague-infected rodents. Plague spread quickly and, over the next three years, as many as , people may have died in Marseille and surrounding areas. In plague-ravaged Moscow, the terror of quarantined citizens erupted into violence. Riots spread through the city and culminated in the murder of Archbishop Ambrosius, who was encouraging crowds not to gather for worship.
The empress of Russia, Catherine II also called Catherine the Great , was so desperate to contain the plague and restore public order that she issued a hasty decree ordering that all factories be moved from Moscow.
By the time the plague ended, as many as , people may have died. A pandemic is an epidemic that spreads globally. An emerging infection newly appears in a population or is spread in a new geographic area Morens et al. The zoonotic transmission of pathogens from animals to humans is a pivotal mechanism by which emerging infections have afflicted humans throughout history Wolfe et al.
The probability of cross-species transmission of pathogens was dramatically enhanced with increased interactions with animals through hunting, animal farming, trade of animal-based foods, wet markets or exotic pet trade Bengis et al. The process of cross-species transmission of pathogens involves 5 different stages Wolfe et al. The animal species that harbor the pathogen, the nature of human interaction with that animal and the frequency of these interactions likely modulate the risk of zoonotic transmission.
Furthermore, land use and climate changes are suggested to play important roles in the transmission of pathogens from wildlife to humans El-Sayed and Kamel, ; White and Razgour, There is thus a need to implement surveillance programs to rapidly detect the emergence of pathogens with a potential for zoonotic transmission at the animal-human interface. Climate changes also influence the transmission of pathogens e.
The emergence of vector-borne pathogens in non-endemic regions often results in explosive epidemics. Land use due to increasing human population also affects the distribution of disease-carrying vectors Kilpatrick and Randolph, Control of vector-borne zoonotic pathogens usually requires vector control to reverse the drivers of transmission. Furthermore, the spread of several infectious diseases e. These diseases show a wider spread as a result of the acquisition of drug resistance, tolerance of mosquito vector to insecticides, poor sanitation, land use and climate changes as well as increased in human mobility and travels Cutler et al.
Furthermore, outbreaks of cholera in regions where natural disasters occurred such as earthquakes and floods were also reported. Surveillance programs should be also implemented to control the spread of these pathogens from endemic to non-endemic regions.
Finally, infectious agents e. These weapons are based on natural microorganisms or microorganisms that are engineered to be more virulent, highly transmissible or resistant to therapy Narayanan et al.
The release of these biological weapons is intended to induce diseases in humans or even death. Therefore, governments should establish biowarfare, bioterrorism and biocrime preparedness plans to protect the population. In this paper, we review major pandemics that have afflicted humankind throughout history such as plague, cholera, influenza and coronavirus diseases, the way they were controlled in the past and how these diseases are managed today.
Infectious diseases still represent threats for human health as pathogens can spread rapidly through global trade and travels.
Global surveillance programs are thus needed to detect and identify pathogens spillover from animals to humans as well as to control water-borne pathogens and vector-borne diseases. Furthermore, effective non-pharmaceutical and pharmaceutical measures for the prevention and control of these infections are required to limit their dissemination in the human population. Plague is caused by the flea-borne bacteria Yersinia pestis that is responsible of at least three human plague pandemics, the plague of Justinian, the Black Death and the third plague Table 1 Zietz and Dunkelberg, Fleas acquire the bacteria by sucking blood from an infected rodent.
Bacteria quickly multiply and block the alimentary canal in the gut of the fleas Bacot and Martin, The fleas transmit the bacteria to new rodent hosts by regurgitating the clotted blood. Plague manifests in three forms, i.
The bubonic form is the most common and results from the bite of an infected flea. Clinical manifestations include flu-like symptoms such as fever, chills, headache, body pains, weakness, vomiting and nausea followed by painful swollen lymph nodes. The mortality rate is higher in patients with septicemic plague than in those with the bubonic form. Pneumonic plague occurs when the bacteria infects the lungs, either primarily by infectious respiratory droplets or secondarily as a complication of bubonic plague.
This form is characterized by a fulminating onset and is rapidly fatal when left untreated. Between and , the plague killed an estimated million people in the Roman Empire and especially in its capital, Constantinople. The highly developed structure of the Roman Empire facilitated the spread of the Justinian plague along its trade and military routes. The high mortality caused by the disease might have contributed to the weakening and eventually to the decline of the Byzantine Empire.
After this initial pandemic, intermittent plague outbreaks occurred every 8 to 12 years for two centuries and then disappeared for unknown reasons. The identification of the causative pathogen involved in the death of victims of past pandemics usually relies on ancient DNA techniques aimed to directly extract DNA from skeletal remains.
A great advance in paleomicrobiology techniques was the isolation of microbial DNA in dental pulp specimens Drancourt et al. Indeed, bacteria are trapped in the dental pulp early in the course of a bacteremia and can be isolated from preserved teeth of victims. Therefore, analysis of the dental pulp is more efficient than bones to accurately identify microbial DNA from rapidly fatal infections that occurred in the past.
Corpses of victims of the Justinian plague could be recovered in burial sites. Ancient DNA techniques from dental pulp samples identified Y. The second plague pandemic, the Black Death, originated in East Asia and swept across Central Asia into Europe through the land and sea trade routes of the medieval Silk Road Zietz and Dunkelberg, The second plague pandemic lasted in Europe until the early of the 19th century and killed million people. The lineages of Y.
It is suggested that the bacteria may have persisted in rodent reservoirs in Europe and periodically re-emerged in the human population Seifert et al. Another hypothesis could be that climate-driven outbreaks of Y. The bacteria suddenly disappeared from Europe and this could be possibly related to the extinction of local rodent reservoirs Spyrou et al. At that time, there was no effective treatment against plague. Initial institutional responses to disease control began during the Black Death Tognotti, A sanitary cordon was imposed by armed guards along transit routes and at access points to cities.
A separation between healthy and infected persons was accomplished in camps and then in permanent plague hospitals called lazarettos. Port cities were closed to ships arriving from plague-infected areas. Ships with suspicion of plague were put in quarantine, passengers and crew were isolated in lazarettos and vessels were thoroughly fumigated and retained for 40 days.
The Black Death decimated Medieval Europe and had major impacts on its socio-economic development, culture, art, religion and politics Bramanti et al. Based on genomic analysis of ancient and recent genomes, it was suggested that a wave of plague may have traveled from Europe to Asia after the Black Death, eventually setting in China and giving rise to the third plague pandemic Spyrou et al. The latter plague pandemic originated in the middle of the 19th century in the Yunnan region China , reached Canton and spread to Hong Kong Zietz and Dunkelberg, In , Alexandre Yersin discovered the bacteria, Y.
The pandemic then reached Japan, Singapore, Taiwan and India via ships. Over the following years, plague became endemic in many countries around the world Stenseth et al. Between and , the number of plague cases was estimated at 3, with fatalities worldwide, most of them occurring in Democratic Republic of the Congo, Madagascar and Peru Glatter and Finkelman, The basic reproduction number R o was estimated at 1.
The case fatality rate was as high as 8. Plague is seasonal in most endemic countries with a well-defined geographic distribution which corresponds to those of the vectors and rodent reservoirs Prentice and Rahalison, Nowadays, plague should be considered as a neglected human threat due to its rapid spread, its high fatality rate without early treatment and its capacity to disrupt social and healthcare systems Valles et al.
The genetic plasticity of Y. Surveillance and control programs of fleas and animals involved in the life cycle of Y. Individuals should protect themselves against flea bites in regions where plague is present. It is also recommended to avoid contact with infected body fluids and tissues as well as animal carcasses.
Public health interventions that can be put in place to prevent or limit plague outbreaks include the killing of fleas with insecticides and, if required, the control of infected rodents; the early isolation of patients, the rapid diagnostic and treatment of infected individuals with antibiotics; the detection and isolation of contacts and the administration of chemoprophylaxis to exposed individuals Prentice and Rahalison, Standard treatments against plague include streptomycin and doxycycline.
Alternative drugs consist of gentamicin and fluoroquinolones Butler, ; Yang, The WHO does not recommend vaccination except for health care workers and laboratory personnel who are highly exposed to the pathogen. Fifty years ago, a plague vaccine based on whole Y. This vaccine was effective against bubonic plague but not against the pneumonic form of the disease.
Furthermore, this vaccine was associated with a high reactogenicity. As highlighted in the Madagascar outbreak, Y. Furthermore, Y. Therefore, the development of a plague vaccine against the most deadly form of the disease is needed.
Cholera is an acute often fatal disease of the gastrointestinal tract caused by Vibrio cholerae Faruque et al. The bacteria colonizes the small intestine and produces the cholera toxin which is responsible for a rapid and massive loss of body fluids leading to dehydration, hypovolemic shock and death. Humans are infected through contaminated water used for drinking or preparing foods.
The infection is often mild or asymptomatic and bacteria are eliminated with feces in 1 or 2 weeks. Cholera was endemic in Asia until , when a first pandemic spread from India to several other regions of the world Table 1 Faruque et al. This pandemic emerged during a period of increasing globalization resulting from technological progress in transportation. Indeed, the advent of steamships and railways allowed a dramatic decrease in travel time and a rise in trade.
At that time, health prevention strategies were essentially the same than those implemented during the Black Death Tognotti, Infected persons were isolated in lazarettos. Port entry was forbidden for ships arriving from regions where cholera was present. Travelers who had contacts with infected persons or who came from a place where cholera was circulating were quarantined.
Thereafter, five additional major pandemics of cholera that originated from India and spread to other continents occurred during the 19th and 20th centuries Table 1 Faruque et al.
The second and sixth pandemics, and presumably the other ones, were caused by the O1 classical biotype of V. The second pandemic of cholera reached the British islands. During the cholera outbreak in Soho London , in , the physician John Snow used for the first time epidemiological methods to trace the source of the outbreak.
He described the time course of the outbreak and its geographical spread in the city. He identified the public pumps used for water supply in these areas and understood that water was the source of the contamination. He then proposed effective measures to prevent the transmission through the removal of pump handle in the city areas where the outbreak occurred Smith, The bacillus of cholera was isolated during the fifth pandemic that extensively affected South America by Robert Koch who also understood the importance of clean water in preventing its transmission.
The toxin responsible for the disease was only discovered in De, The seventh cholera pandemic is the most extensive in terms of geographic spread and duration Mutreja et al. It began in Indonesia in and became endemic in many regions of the world. Cholera epidemics usually ended because of a lack of favorable environmental conditions for the survival of vibrios.
The seventh cholera pandemic was caused by El Tor biotype strain of V. In late , the O serogroup caused a large cholera outbreak in Bangladesh and neighboring countries and raised the fear of a 8th cholera pandemic Albert et al. Cholera cannot be eradicated as it is a natural inhabitant of aquatic ecosystems. However, it is estimated that the global burden of cholera is higher due to underreporting.
Between and , the number of cases was shown to range between 1. Environmental and climate changes may increase the geographical distribution of cholera Chowdhury et al. The persistence of cholera is related to poor living conditions including shortage of safe drinking water, insufficient sanitation, crowded housing and the lack of efficient sewage systems. Re-emergence of the disease can also occur following natural disasters such as earthquakes that disrupt access to safe water supply.
Cholera outbreaks could be predicted based on real-time monitoring of oceanic regions, climate fluctuations and epidemiological surveillance program Chowdhury et al.
The disease could be prevented by implementation of public health measures to ensure adequate sanitation and safe water supply Somboonwit et al. The access to safe drinking water and sanitation are among the primary priorities of the Millenium Development Goals and the sustainable Development Goals Igere and Ekundayo, These vaccines should be used in areas with endemic cholera, cholera outbreaks and humanitarian crisis with high-risk of cholera in combination with other cholera prevention and control measures World Health Organization [WHO], Cholera is first identified based on clinical symptoms of severe acute watery diarrhea.
The disease is then confirmed by the detection of V. The majority of infected individuals can be treated by the administration of prompt oral rehydration solution. Severely dehydrated patients who are at risk of shock require rapid administration of intravenous fluids as well as antibiotics. First-line drug consists of doxycycline whereas alternative treatments include tetracycline, ciprofloxacin and azithromycin Hsueh and Waters, Influenza viruses belong to the Orthomyxoviridae family.
Influenza viruses are enveloped, negative-sense, single-stranded RNA viruses Wright and Webster, Their genome consists of 7 or 8 RNA segments encoding at least 10 structural and non-structural proteins. Structural proteins include a hemagglutinin HA , a neuraminidase NA , two matrix proteins and a nucleoprotein.
Influenza viruses can be distinguished in types A, B, C, and D. Influenza A and B are responsible for outbreaks in tropical regions and seasonal epidemics in temperate regions whereas influenza A viruses are the only ones with a pandemic potential Lofgren et al. Indeed, influenza A virus is endemic in a number of species including humans, birds and pigs Webster et al. Gene reassortments can thus occur between human and animal influenza A viruses and lead to a new virus subtype which can be pathogenic to humans Webster et al.
In a typical seasonal epidemics, influenza virus causes 3 to 5 million cases of severe illness and approximately , deaths worldwide Iuliano et al. Most typical seasonal influenza infections are asymptomatic or cause only mild or classical influenza illness characterized by 4 or 5 days of fever, cough, chills, headache, muscle pain, weakness and sometimes upper respiratory tract symptoms Zambon, Among the most severe complications is pneumonia which can be associated with secondary bacterial infection.
Annual influenza epidemics are sustained in the human population through mutations occurring especially in the HA and NA viral surface glycoproteins, the major targets for neutralizing antibodies.
Seasonal influenza virus results from frequent antigenic drifts every 2—5 years in response to selection pressure to evade human immunity Kim et al. Its genome contains segmented genes which may undergo reassortments in cells co-infected with two or more influenza viruses. Each influenza A virus has a gene encoding for 1 of 16 possible HAs and another gene encoding for 1 of 9 possible NAs that are involved in viral attachment and release, respectively Dugan et al.
Rarely, antigenic shift which results from reassortment between human and animal viruses leads to the emergence of a new virus subtype Webster et al. This antigenically distinct virus may have the ability to infect humans and achieve sustained human-to-human transmission and may cause a pandemic if the immunity in the human population is partial or lacking Webster et al.
The time in which influenza virus began to infect humans or cause a pandemic cannot be determined with accuracy but many historians agree that the first influenza pandemic could have likely occurred in Morens et al. The Russian flu that occurred between and was the first well-described pandemic Taubenberger et al. The virus spread rapidly as it took only 4 months to circumvent the planet Valleron et al. The pandemic virus reappeared every year for 3 years and caused an estimated 1 million deaths worldwide Table 1.
The median R o was estimated at 2. The case fatality rates ranged from 0. Attack rates were highest in individuals aged 1—60 years and lower in infants and seniors Valtat et al. In contrast, mortality rate showed a J-shape curve with highest rates in infants and people over 20 years of age Valtat et al.
Before its identification, the virus spread silently around the world and its region of origin could not be determined.
The — pandemic spread in at least 3 distinct waves within a 9 month interval. The first wave occurred during spring-summer and caused high morbidity and low mortality. Both the second and third waves in summer-fall and winter — caused high mortality.
The — influenza pandemic resulted in approximately million infections and 50 million deaths worldwide Johnson and Mueller, However, the — pandemic showed a W-shaped mortality curve with high case fatality rates in the very young and the elderly as well as in healthy young adults aged 20—40 years Morens and Taubenberger, This uncommon age distribution suggests that the severity of the — influenza pandemic was not primarily due to a hyper-virulent strain but was more likely related to host factors that prevent individuals to control the infection.
It is suggested that the influenza virus had an enhanced capacity to spread to and damage bronchial and bronchiolar epithelial cells that could allow bacteria to breach the mucociliary barrier leading to fatal bacterial pneumonia Morens and Fauci, The H1 hemagglutinin of the — pandemic virus was identified as a key virulence factor for mammalian and was associated with increased respiratory epithelial pathogenicity and elicitation of a strong pro-inflammatory response Qi et al.
Most deaths occurred from several days to weeks median 7—10 days after the onset of symptoms Shanks and Brundage, In large cities of Western world, health authorities implemented a series of containment strategies to prevent the spread of the disease including the closure of schools, churches and theaters and the suspension of public gatherings.
Physicians encouraged the practice of individual measures such as respiratory hygiene and social distancing. However, these measures were implemented too late and in an uncoordinated manner due to World War I. Travel restrictions and border controls were impossible to put in place. The movement of military troops and the poor living conditions of soldiers in the trench warfare in Europe facilitated the spread of the disease. Over the past century, descendants of the pandemic virus were the cause of almost all seasonal influenza A epidemics worldwide.
All influenza A viruses responsible for the , and pandemics Table 1 also derived from the founding virus by gene reassortments between human, avian and swine influenza viruses Morens et al. Figure 1. Timeline of influenza pandemics caused by the H1N1 virus and its descendants produced by reassortment of circulating strains with avian influenza viruses AIV and swine H1N1 viruses.
The reassortment of genes is shown in parenthesis. The re-emergence of H1N1 virus in is also shown as it co-circulated with the H3N2 virus before being replaced by the H1N1pdm Sustained transmission of the — pandemic virus started on December with recurrent waves occurring over several years Housworth and Langmuir, The morbidity was highest in children and the mortality was highest at the extremes of age.
Unfortunately the same year as his discovery went down as the worst year of the pandemic, in which 23, people died in Great Britain. Death Toll: 75 — million Cause: Bubonic Plague From to an outbreak of the Plague ravaged Europe, Africa, and Asia, with an estimated death toll between 75 and million people. Thought to have originated in Asia, the Plague most likely jumped continents via the fleas living on the rats that so frequently lived aboard merchant ships.
Ports being major urban centers at the time, were the perfect breeding ground for the rats and fleas, and thus the insidious bacterium flourished, devastating three continents in its wake. Death Toll: 25 million Cause: Bubonic Plague Thought to have killed perhaps half the population of Europe, the Plague of Justinian was an outbreak of the bubonic plague that afflicted the Byzantine Empire and Mediterranean port cities, killing up to 25 million people in its year long reign of terror.
This unknown disease was brought back to Rome by soldiers returning from Mesopotamia around AD; unknowingly, they had spread a disease which would end up killing over 5 million people and decimating the Roman army. What About Covid the Novel Coronavirus? Third Cholera Pandemic — Death Toll: 1 million Cause: Cholera Generally considered the most deadly of the seven cholera pandemics, the third major outbreak of Cholera in the 19th century lasted from to The Black Death Death Toll: 75 — million Cause: Bubonic Plague From to an outbreak of the Plague ravaged Europe, Africa, and Asia, with an estimated death toll between 75 and million people.
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