The History of Pandemics: Flu versus Man

“Everybody knows that pestilences have a way of recurring in the world; yet somehow we find it hard to believe in ones that crash down on our heads from a blue sky… A pestilence isn’t a thing made to man’s measure; therefore we tell ourselves that pestilence is a mere bogy of the mind, a bad dream that will pass away.”

(Albert Camus, La Peste)

We are in the midst of a pandemic.  This is no bad dream; this is our terrible reality.  The World Health Organisation (WHO) declared COVID-19 a pandemic on 11 March 2020.  As of early May, over 3.8 million cases had been reported worldwide with around 265,000 deaths.  SARS-CoV-2 had crept up on us and we were strangely slow to react, most disbelieving that such a thing could occur in our lifetime (despite the Spanish Flu of only last century).  This is not the first time, and so one wonders: is there a lesson we are supposed to be learning, that we simply are not?  It certainly seems that way. 

What has become clear is that there once was a subconscious (as well as financial, granted) purpose in our creation of technology that would enable us to communicate with each other across extreme distances.  Terrestrial borders may have shut at the start of the year in order to inhibit the further spread of COVID-19, but the information highway that is the internet 

(do people still use that expression?) remains very much open for the most part of the globe.  Was there a blueprint from which we strove to bring into existence such a connection, a genetically inherited warning that we might all have to be alone at some point, learned in our DNA by the lengthy sojourns indoors during plague outbreaks and other pandemics in history?  Whatever it was – thank goodness.

Indeed, as we grapple to put the pieces of our society back together after complete lockdown and a reiteration of complete lockdown – and so on – it is worth considering for a moment that history of our species’ survival during other pandemics in bygone ages.

From the Greek, pan (or ‘all’) and demos (or ‘people’), pandemic has become a word that rightly invokes fear each time it strikes.  Generally zoonotic in transmission, particularly in the case of influenzas, they pretty much all began with the domestication of animals. 

The Plague of Cyprian afflicted the Roman Empire between 249 and 262, one hypothesis from the few sources available suggesting that it was an influenza pandemic.  Nonetheless, this is unsubstantiated.  The Plague of Justinian, from 541 to 750, is recorded as the first outbreak of the Bubonic plague, while the Black Death (or Bubonic plague), from 1331 to 1353, was the first of a series of European plague epidemics which stretched to the 18th Century.  Between 1361 and 1480, the disease returned every 2 to 5 years in England alone.  The word “quarantine” comes from 14th Century Venice.  Latin for “forty”, it was appropriated to describe the forty days of enforced quarantine of those on incoming ships to the floating city. 

Hippocrates himself – the “Father of medicine” and he who taught us, “Let food be thy medicine” – mentions the “Cough of Perinthus” in 412 BC, an upper respiratory tract epidemic.  Nonetheless, the first record of an influenza pandemic occurred in 1580 and since then influenza outbreaks have happened every 10 to 30 years.  Mention of these is not to instill fear – remember, this was not coronavirus – but the recurrence of diseases which affect vast swathes of the human species don’t go quietly into the night… 

The BBC recently reported on June Almeida, the woman who discovered the first coronavirus.  A pioneer in viral imaging, Dr Almeida first identified a coronavirus in 1964 by aggregating viruses with antibodies for better imaging.  This took place in a laboratory at St. Thomas’ Hospital, London – the very hospital that treated our Prime Minister Boris Johnson when he needed oxygen support while battling COVID-19.  Her findings, on the strain B814, were published in 1965 in the British Medical Journal.

Of course, the most direct historic comparison to be made with COVID-19 is with the Spanish Flu outbreak of 1918-1920 (strange how we’re making such a link pretty much precisely a century later…).  During those few years, 500 million people globally became infected – even in the remote regions of the Arctic and the Pacific Islands – and up to 100 million are thought to have died.  What was unusual about the Spanish Flu was the high mortality rate of young adults, whereas if we look at COVID-19 the vulnerable category has been the “norm” for influenzas: the elderly and infants.

When considering mortality rates from pandemics, population growth does to some extent have to be assessed.  In 1900, there were 1.6 billion people on the planet.  In 2011, that figure had inflated to 6.8 billion.  As of March 2020, in the midst of the coronavirus’ peak, it was estimated there were 7.8 billion of us.  As much as it is a question of over-procreation, it is also a case of longevity: through medical advances in the main, but also through the adoption of a healthier way of living for many.

Since 2005, scientists had been warning that a global influenza outbreak was imminent, with a predicted 20% infection rate of the worldwide population.  Happily, as this article is being written the stats are nowhere near that – and that, no doubt, is due to the speedy implementation of lockdown measures worldwide.

The Flu Vaccine

To understand how the flu vaccine works, it is first necessary to understand how the human body works.  Our immune system is divided into two parts, the innate and the adaptive.  Our innate immune system protects us from pathogens, while our adaptive immune system learns from any infection we do pick up and remembers how to act in the event of any future similar infection.  Innate immune system responses include sweating and internalised inflammation occurring at the red and white blood cell level.  Our adaptive immune system then kicks in, our white (or B&T) cells storing information on the infection and directing phagocytes, mast cells, and natural killer cells to engage.

The respiratory system is more than just our lungs.  Including the nose, pharynx, epiglottis, trachea, and bronchi, in addition to the lungs, one can also term the ribcage, diaphragm, and intercostal muscles as part of this system, as they assist the pumping in and out of air into and from the chest.  The respiratory system overall then can be divided into the upper and lower respiratory tracts, where the dividing line is thought to be the larynx or windpipe.  Of course, problems beyond localised infection – upper or lower – bridge that divide: when a common cold becomes bronchitis; or when the flu becomes pneumonia. 

COVID-19 has been found in both the upper and lower respiratory tracts.

The development of a flu vaccine as known today began in the 1930s.  New versions of influenza vaccines are developed twice a year, due to the rapid changeability of the virus through antigenic drift (a very slight mutation that alters the strain).  If vaccinated against one strain, it seems that a better immunity is developed against any new strain that might be contracted.  Each vaccine comes in both an inactive and a live weakened form, and antibodies take approximately two weeks post-innoculation to form. 

It is recommended that the vaccine be received annually, particularly those in high risk groups (children between 2 and 5 years old, pregnant women, those with a history of other illnesses, the elderly, and those who work in healthcare).  Only healthcare workers should receive the live weakened form of vaccine from these high risks groups.

The vaccine is normally grown in fertilized chicken eggs, but is still recommended for those with egg allergies.  Since 2012, there have been methods of production explored using VLP (Virus-Like Particles) that bypass the need for eggs (with insect cells and certain plants, for instance) and it is hoped these might even afford a broader range of protection.  The strains normally used are from H1N1, H3N2, and a B influenza, determined by the WHO as to what might worst affect the population in the coming winter season.  Side effects of the vaccine include a fever, fatigue, and muscular aches and pains.  If an allergic reaction does occur, then the flu vaccine is not recommended to be repeated. 

A “universal” influenza vaccine and a DNA-based vaccine continue to be attempted to develop apace and – as has been widely publicized since the novel coronavirus struck worldwide this year – development of a COVID-19 vaccine has been desperately underway ever since lockdown.  It is hoped success will precede the coming winter season and any possibility of pandemic return.

Influenza A

The influenza A type virus is a negative-sense, single-stranded and segmented RNA virus.  Fowl are natural asymptomatic carriers of these viruses, whether the birds are domestic or wild.  Humanised A type flu results in symptoms such as fever, a cough and/or sore throat, muscle aches and pains, and also conjunctivitis.  In severe cases, breathing problems and even pneumonia result.

The subtypes of influenza A type flu are multiple and classified according to the quantity of haemagglutinin (H/HA) and neuraminidase (N/NA) in the virus. 

HA is a protein that causes red blood cells to agglutinate (or clump), while NA is an enzyme that separates glycosidic bonds in monosaccharide sialic acid (or neuraminic acid).  HA, of which there are 16 known subtypes, mediates the binding of the virus particles (or virion) with target cells and the entry of that viral genome into them.  NA, of which there are 9 known subtypes, is part of the process of release in non-productive attachment sites in mucus and progeny virions from infected cells and it is these that are the target of antiviral drugs, given their simultaneous antigen characteristic in binding with antibodies in immune responses.

Only H1, H2, and H3, together with N1 and N2 are commonly found in humans.  H1N1, H1N2, and H3N2 are those currently circulating the width and breath of Mankind’s reaches.  Researchers in Taiwan examined sequences from 1918’s Spanish Flu pandemic, establishing that it was the only influenza virus entirely derived from avian strains, while virologist Jeffery Taubenberger went further and declared Spanish Flu to be the “mother of all pandemics” that have since descended from it.

Jennifer Nuzzo co-authored the research paper, ‘Preparedness for a High-Impact Respiratory Pathogen Pandemic’ months before the first reported case of COVID-19.  During the early days of isolation – in addition to promoting the quarantine time to establish better, heart-healthy diets and develop an exercise regimen and general self-care routine (i.e. preventative measures for the future) – she took the opposite stance to Taubenberger, due to the questionable veracity of record-keeping from such a long time ago, together with lack of modern healthcare and IVs, antibiotics, or ventilators at the turn of the 20th Century; though she admitted the societal impacts were of mirror-like quality. 

Scientists have established an antibody that targets HA.  F16 was discovered in 2011 and is the only known antibody to be effective against all known subtypes of the influenza A type virus.  However, the virus is known to evolve, raising the very real concern over resistant strains developing if antiviral drugs are overemployed in the fight against seasonal flu (H1N1 and H1N2).

Influenza B, on the other hand, is much slower to mutate than type A.  Known to affect both humans and seals, it is of particular concern for school-aged children and adolescents.

Boccaccio’s Decameron and culture’s impact on medicine

The Black Death held a reign of terror over Europe between 1348 to 1350, necessitating a prolonged period of self-isolation indoors.  During that time, what was termed “narrative prophylaxis” became popular, physicians suggesting that one’s frame of mind played a large part in fighting off succumbing to the contagion.

Indeed, recreation and psychological distraction were the order of the day, each and every day of the 14th Century lockdown.  “Happiness” was the idealised state of being in which to exist in order to stay safe.  Thinking about the plague was thought to be a potential catalyst for infection: distraction was crucial.  So it was that, in years to follow, medical texts quite literally stated that “literary pursuits” – those journeys for the mind – should be undertaken as a prescription for maintaining the desired mental balance.  Boccaccio’s Decameron was the catalyst text for this advocacy, and it has been the trending text of 2020’s lockdown, too.

“Narrative prophylaxis” can be described not just as reading, but storytelling – a return to oral and aural performance and reception.  Similar to our own current fear of further contagion, 14th Century concerns over repeated outbreaks meant that open-air spaces were preferred for group readings and performances for more than a small handful of people.  Is this our next stage, then?  Our actors and musicians have kept their occupation alive and thriving over the internet this long period of self-isolation (despite the fears early on about financial ruin for self-employed people): are open-air theatres the next step on the path back to normalcy?

In the 15th century, narrative prophylaxis was adapted to include song.  We might no longer be living in a time when biblical inspiration taught “the transformative powers of music and word”, but we can learn by example now, certainly.  Today we find parallel in the ability to switch on the radio or click a playlist on Spotify, but perhaps the link between the spoken word and performative interpretation is best summed up by Patrick Stewart’s recitation of Shakespeare’s sonnets begun at the start of the lockdown.  The Bard himself, after all, wrote his great tragedy King Lear while in isolation during an outbreak of plague in the 17th Century and its infamous search for an escape from suffering has been all too poignant…

 

Cleanliness and Hand Sanitisers Like Gold Dust

“Catch it, kill it, bin it!”  The slogan of 2020 when it came to coughing and sneezing; the refrain of the year in which COVID-19 swept the world and stole so many and so much from us.  Given that we’ve now suffered through a major coronavirus every decade of the 21st Century, it is an understatement to say that the need for a coronavirus vaccine is absolutely crucial.  Until then, however, hand-hygiene is the first line of defense – even after social distancing measures loosen.

The Happy Birthday song has never been sung as much as it has this year: the perfect length for the vital 20-second thorough wash of hands with warm water and antibacterial soap, the internet has been – ahem – awash with humorous videos of people in the responsibly cleansing act.  When soap and water weren’t available, we were told to opt for hand sanitisers instead.  Indeed, it wasn’t loo roll that flew off the shelves first: it was hand sanitisers (as well as liquid soaps, closely followed by the humbly traditional yet no less effective soap bar).  Now, FirstHand sanitisers are available, too.

There are two types of hand sanitisers generally on the market: alcohol-based and the less effective alcohol-free versions.  Alcohol-based sanitisers contain between 60% and 95% alcohol (whether isopropyl alcohol or ethanol (ethyl alcohol) or n-propanol).  Essentially, the alcohol attacks the protein casing of the virus, killing it, whereas an alcohol-free sanitiser only limits its multiplication.  They should be rubbed into all parts of the hands for 20-seconds just like soap and water shing.

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