SOME OF THE WORLD’S WORST PANDEMICS

Pandemic. This is a word that’s become all too familiar in the last few years, thanks to the onset of the COVID-19 pandemic which has sent the world into a state of turmoil.

But in fact, pandemics have threatened mankind for time immemorial. In this blog article, Gael Martin, one of our PhD students at the Institute for Glycomics, discusses past and present pandemics, including some of the worst pandemics the world has ever seen.

Not only is this information interesting and educational, but it also further emphasises the great importance of research to control and eradicate disease.

Let’s begin…

What is a pandemic?

The word ‘pandemic’ originates from the Greek word pandēmos (from pan ‘all’ + dēmos ‘people’). A pandemic defines an epidemic of country, continent, or world proportions. The most widely understood meaning of the word refers to a pathogen (a micro-organism responsible for a disease) that circulates rapidly across a large area.

Why are pandemics such a global health concern?

In the event of a pandemic, human populations have either never, or rarely, been exposed to a pathogen (often a new strain of an already-circulating micro-organism). This lack of exposure means that the immune system is not prepared to respond to such an infection and will most likely not have enough time to produce antibodies in large enough quantities before severe symptoms appear.

In this instance, the disease is likely to progress through the population without obstacle. As a result, hospitals and health institutions that would usually be able to handle a limited number of patients, would be filled to capacity and unable to care for new incoming patients.

Adding to such circumstances are the difficulties that come with the treatment of such patients. Firstly, in early stages of transmission the disease is unlikely to be fully understood. This means that it is difficult to stop the progression throughout the population. Secondly, healthcare workers need to be protected so as not to get infected themselves. Often, extra precautions are necessary in early stages. Finally, since the disease is novel, treatment might not be available. This means that severe cases could be associated with severe outcomes, potentially even death.

What is thought to be the most fatal pandemic in recorded history?

Probably the most fatal pandemic recorded in history was the “Black Death” – also known as “The Plague”.

The Plague occurred between 1347 and 1351, most likely originating in China and Central Asia, and was first reported in Crimea (Ukraine/Russia). It then spread throughout the Mediterranean Sea through ports. The pathogen responsible for this disease was a bacterium called Yersinia pestis, which is now thought to have been first transmitted from rodents to humans from the bite of fleas.

Its name ‘The Black Death/Plague’ originated from one of the symptoms, being the blackening of lymph nodes and skin tissue once infected.

The Plague showed a combination of bubonic and pneumonic plague characteristics, with transmissibility through rodents, and from human to human via cough droplets, meaning that it was very easily transmissible. Once infected, the chances of survival were about 40%. Rough estimations place the total death toll to between 25 and 50 million people, or about 60% of the European population at the time.

In an attempt to control this pandemic, authorities in Italy started imposing restrictions on the general population and on boats traveling. These restrictions included social distancing, isolation for infected patients, and a 40-day isolation for sailors and merchants. This is where we get the term “quarantine”, which in Latin languages means “forty days”.

Despite these control methods, throughout the centuries there were many resurgences. The disease is still present to this day, but in localised outbreaks. The most recent one occurred in Madagascar. Nowadays, The Plague causes 1,000-3,000 deaths annually.

What are some of the most famous pandemics from the 20^th century?

• “Spanish Flu” – influenza pandemic

Perhaps one of the most memorable influenza pandemics in history was the “Spanish Flu”, which occurred mainly from February 1918 to April 1920, after first being reported in Kansas, USA, in March 1918. The pathogen responsible for the Spanish Flu was the influenza virus H1N1.

Since this was a disease described right as the war ended, it is difficult to establish a clear timeline and trace the origin. Modern research is also hindered by the fact that no tissue sample remains for analysis. Currently there are three theories as to the origin of the Spanish Flu. The three hypotheses place the origin either in Kansas USA, Europe, or China. There is evidence leaning towards all three hypotheses making them all valid potential options. Regardless of the country of origin, current phylogenetical analysis and evolutionary biology data shows that it is very likely that the virus has an avian (bird) origin.

So, you may ask, if it didn’t originate in Spain then why was it called the “Spanish Flu”?  Interestingly, due to Wartime censors, and in order to maintain morale, countries involved in World War I did not report on it. However, Spain reported freely on the outbreak that soldiers were experiencing, creating the false narrative that the outbreak originated in Spain.

Quite alarmingly, an estimated 500 million people were infected with the Spanish Flu and between 25 and 50 million deaths were reported. Proportionally, about one third of Europe died due to this pandemic. Economically, businesses suffered greatly. Long term studies have shown that educational attainment, physical disability, lower income rates, as well as birth defects rates, all increased during the 1920s.

The pandemic lasted for four distinct waves. The first wave happened during the end of WWI celebrations and reported numbers do not show exceedingly high numbers. However, the second wave was remarkably deadly and, as a result, a mask mandate was issued; quarantine, and social distancing rules were enforced. Throughout the third and fourth wave, numerous deaths were reported, although less than during the second wave.

Due to the devastation caused by the second wave, the virus caused a strong immune reaction in the surviving population and led to what is called “herd immunity”, where a large majority of the population is actively immunised against a pathogen. The decline of deaths during the third and fourth wave is also explained partly by the fact that only the generally fitter (those with a younger and stronger immune system) portion of the population survived the second. Rules were enforced and cases declined until the disease became a seasonal strain. To this day, and after mutating for a century, influenza is still a deadly seasonal virus.

• “Smallpox” or Variola

Smallpox has most likely been circulating for the last 3,500 years, if not more, as medical scriptures mention it in Egypt and China in as early as 1500 BCE and 1122 BCE respectively.

Smallpox is a disease caused by two viruses, Variola minor and Variola major. The origin of variola is unknown but could be as old as 16,000 years. It is probable that it originated from an African terrestrial rodent.

Smallpox is one of the deadliest diseases in history and has caused more than 300 million deaths since 1900.

Early attempts at eradicating the disease came in the form of inoculation of disease from other patients. In 1796, Edward Jenner was the first to introduce the idea of using Cowpox (a similar virus infecting cattle) as a source of immunity for Smallpox.

This allowed for safe antibody production against the variola virus. Proving its effectiveness, vaccination became a priority in most countries for the next century and half. By 1930, the majority of the Northern hemisphere was free of Smallpox. And by 1975 and 1977, the last naturally occurring cases of Smallpox were recorded in Bangladesh (Variola major) and Somalia (Variola minor) respectively.

Post-eradication, the last person to die from Smallpox was a British medical photographer in 1978. Following this incident, every sample of the virus contained in research laboratories was destroyed with the exception of two highly secure laboratories in the US and Russia.

Smallpox is the only human infectious disease to have ever been completely eradicated.  Although, with continuous vaccination efforts, polio, measles, mumps and rubella could be eradicated too. In fact, polio and measles were very close to being fully eradicated until recently.

• “Asian Flu” – influenza pandemic

“Asian Flu” was first reported in Guizhou in southern China and occurred between 1957 and 1958. The pathogen responsible for Asian Flu was influenza A subtype H2N2, a recombination of an avian H2N2 and a human influenza virus.

It was termed “Asian Flu” because it originated in China and rapidly spread to Hong-Kong, Singapore, and Taiwan.

Between one and four million deaths were reported worldwide from this pandemic. In the UK, for every 1,000 cases, 2 to 10 deaths were reported, and the World Health Organisation (WHO) estimates the case fatality rate to be close to 0.1%.

Since this was a novel strain of influenza, world populations had non-existent exposure and minimal immunity. This strain was, however, able to cause pneumonia without any secondary bacterial infection. The main factor contributing to the decline of this outbreak was the rapid development, production, and distribution of a vaccine, thanks to Dr Hilleman. This led to a clear improvement in healthcare. It is thought that this virus has infected as many people as the Spanish Flu, but thanks to the vaccine as well as antibiotics preventing opportunistic bacterial infections, less deaths were reported.

• “AIDS” pandemic

AIDS (Acquired Immune Deficiency Syndrome) is a late-stage HIV (human immunodeficiency virus) infection. This disease was first identified and described in 1983 at the Pasteur Institute, in France.

The first case reported and confirmed retroactively dates to 1959, in Kinshasa in the Democratic Republic of Congo. HIV is the pathogen responsible for AIDS. It is a lentivirus, and as such, attacks the immune system of humans.

There are two kinds of HIV, HIV-1, and HIV-2. Both types come from monkeys. We now know that HIV originated from sooty mangabey monkeys, was then passed on to chimpanzees, and later passed on to humans. The reason for this jump from monkey to human is thought to be poaching, hunting, and eating infected monkeys. The jump is thought to date back to the 1920s.

Since Kinshasa is close to many transportation paths, the disease spread from there and was brought back to Haiti in the 1960s. in the 1980s, the virus reached the US and first affected the gay community.

Initially, due to the nature of the virus, the gay community was blamed and was met with stigma and heavy discrimination. Once the disease started to reach many outside of this community, and doctors identified the origin, being a virus transmissible through bodily fluids, more attention was brought to the larger population. To date, 78 million people have been infected, and 38 million deaths have been reported.

Nowadays, we understand HIV/AIDS much more and thanks to the work of researchers, antivirals are available. There is still no perfect cure, however being diagnosed with an HIV infection is no longer a death sentence. Information campaigns and condom distribution play a major role in the disease spreading. Additionally, in most parts of Africa, newborns are given anti-HIV antibodies to prevent mother-infant transmission. Despite all of these efforts, AIDS is still a leading cause of death, and in 2019 alone, 1.7 million people were reported to be newly infected worldwide.

• “Hong Kong Flu” – influenza pandemic

The Hong Kong Flu pandemic occurred between 1968 and 1969. Caused by the virus influenza A subtype H3N2, it was first recorded in British Hong Kong. This virus is a descendant of the Asian Flu pandemic strain. This strain went through an antigenic shift, meaning one of the key surface proteins – haemagglutinin (H) – shifted form.

The Hong Kong Flu killed between one and four million people worldwide. The WHO estimates that the case-fatality rate of the Hong-Kong Flu is lower than 0.2%. This is partly because, being a descendant of the Asian Flu strain, the world population likely had pre-existing antibodies that were cross-reactive, although not much is known. Despite this, the pandemic still spread rapidly throughout the winter months of the Northern Hemisphere. Economically, a significant portion of the workforce was unable to work, hence causing an economic downfall.

Quick to act, Dr Hilleman and his team developed a vaccine and the distribution helped reduce hospital admissions. The second wave was responsible for about five times more cases than the first. This strain of influenza virus is still circulating to this day as a seasonal form. It is included in annual flu vaccines.

Pandemics of the 21^st century

• “Swine Flu” – influenza pandemic

The Swine Flu pandemic started in June 2009 and lasted until August 2010. It was first reported independently in the US in April 2009. Caused by the pathogen influenza A subtype H1N1, this virus is the result of a triple reassortment of bird (avian), pig (swine) and human, that infected Eurasian pigs and combined with the native pig influenza virus.

Between 700 million and 1.4 billion patients were infected with the 2009 Swine Flu and estimated deaths range from between 150,000 and 500,000 people, which is comparable to the annual flu death rate. Compared to the usual influenza epidemics, this strain disproportionally infected the young. This led numerous schools in the US to close temporarily or for students to stay home if symptoms were detected.

The WHO stated that containment was not an option and advised the world leaders to try to mitigate its impact on the population. Unlike any previous flu pandemic, antivirals acting specifically against flu had been developed and were available on the market (oseltamivir and zanamivir). These, combined with a swift vaccine distribution, led to a much lower death toll than before. Face masks were not made mandatory and were only recommended in the event of symptom occurrence. Several countries imposed quarantines on international travellers. This strain is now a recurrent seasonal strain and is included in the annual flu vaccine.

• “COVID-19 pandemic” – coronavirus pandemic

Requiring no formal introduction, the COVID-19 pandemic was first recorded in December 2019 when numerous patients showing pneumonia symptoms were reported in Wuhan, China. SARS-CoV-2 is the virus that causes COVID-19 (Coronavirus Disease 2019).

This virus is part of the already existing and well-established family of coronaviruses. This family has been reported to include strains such as the one responsible for the common cold; others are known for being much more dangerous, such as SARS and MERS.

In the wild, the natural reservoir for coronaviruses includes mainly bats, but also camels and pangolins, among others. Considering the genetic sequence of SARS-CoV-2, scientists have determined that there is no clear evidence of genetic manipulation or human intervention leading to its origin. All seems to point towards it being a natural evolution of coronaviruses circulating in bats.

One hypothesis is that the virus came from bats in the Wuhan animal market and jumped from one permissive species to the next (animals such as pangolins are permissive) and is likely to have infected workers.

As of September 2021, COVID-19 has infected more than 225 million people and is responsible for 4.7 million deaths worldwide. Despite the health and medical personnel worldwide working tirelessly, COVID-19 is still very much a threat. Access to several vaccines has drastically helped contain transmission of the disease.

Governments have decided to halt numerous international transactions and travel to limit transmission. As a consequence, the tourism industry has dramatically suffered. Social distancing and mask mandates were put in place in most countries. Despite these measures, millions suffered long lasting consequences or even death.

Thankfully, the vaccines offer significant protection against severe COVID-19 symptoms, and a vast majority of severe reported cases are in the unvaccinated population. If these drastic measures had not been put in place, it is likely that these numbers would be much higher. Nevertheless, lockdowns and other controlling actions have had a severe impact economically, and it is likely that this pandemic will have a long-lasting impact on our society.

How and what do scientists learn from pandemics?

Scientists learn constantly from ongoing health crises. For the general public, diseases worthy of attention are rare, but there are scientists all over the globe who work everyday recording, collecting, sequencing, and categorising viruses worldwide in order to predict, warn and prevent the next potential pandemic.

Despite this, the current COVID-19 pandemic has outlined the importance and the need for clear, transparent, and efficient scientific communication, especially in the early stages of disease transmission, within research institutions and countries. COVID-19 has also shown the world that scientists are capable of studying, understanding, and providing a vaccine against a disease in record time.

These pandemics have also helped us understand more about the way viruses and other pathogens progress through populations, as well as give a general understanding of population behaviour.

As a final note, it is important for us all to realise that we were not adequately prepared for such a pandemic. It is crucial that governments worldwide use the knowledge gained from this situation to implement robust pandemic preparedness programs for the future in order to save lives and at the same time maintain a functioning economic system.  

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