Welcome to this influenza course at Lancaster University. The flu, needs little in the way of introduction. Most of you will have experienced it. And some of you may have had very severe attacks that have lasted a couple of weeks. We’ll be investigating the world of the influenza virus, looking at what it is, how we can treat it, or perhaps prevent it, where it comes from, and what might lie in wait for us in the future. The word influenza is Italian and is the origin of our English word “influence,” as well as the English medical term, influenza. In the Middle Ages, influenza was used in a medical context to describe how environmental conditions seemed to be associated with certain diseases.
So for instance, for those Renaissance Italians who had no idea about malaria parasites or plague bacteria, the disease of malaria was under the “influenza” of swamps and marshes. And plague was supposedly under the “influenza” of bad smells. The first use of the word to describe the disease we recognise today as the flu was in 1708 by Dr John Hugger and medical historians have traced several supposed influenza outbreaks in the 18th and 19th centuries. Now, this was a time when serious epidemic diseases, such as tuberculosis, typhoid, scarlet fever, diphtheria, and cholera, were features of daily life, and even in the richest countries.
So the public profile of influenza was fairly low, despite it causing the death of the second in line to the British throne, Queen Victoria’s grandson the Duke of Clarence in 1892. All that changed, though, in 1918. Just as the First World War was drawing to a close– which had been the biggest war the world had seen up to date, with around 8 million battlefield casualties and an equal number of civilian deaths– a particularly nasty strain of flu started to spread around the world. It killed so many people that the total numbers remain more or less a matter of guesswork– between about 20 million and 100 million deaths around the world.
Even the most conservative of those estimates would make that flu pandemic outbreak of 1918 deadlier than the First World War, and possibly even up to five times deadlier. 1918 was a flu pandemic, meaning an epidemic that spreads right across the planet, ignoring the usual seasonal winter rhythms. At the time, it was given the name Spanish flu. But it definitely didn’t originate there. The reason for this misnomer was that Spain was a neutral country in the First World War. And therefore, it had no reporting restrictions. However, the media of the combatant countries didn’t report the disease for fear of damaging morale and affecting the war effort. The real origin of the outbreak is unknown.
But the first fact that we have about the 1918 pandemic is that cases started to appear at allied military bases in the USA and France. The neighbouring civilian population were infected. And soon, the disease was in most major cities of continental Europe and North America. British troops returning home across the channel, especially after the war ended in November 1918, brought the disease back to the UK. And this was true for troops returning to many other parts of the world as well. There was no treatment for influenza in 1918 and little or no idea of its cause. Viruses in general had been discovered by Dimitri Ivanovsky in 1892. But in 1918, the medical profession initially went looking for a culprit elsewhere.
The candidate suggested at the time was a bacterium that was given the name haemophilus influenzae. Antibiotics hadn’t even been discovered in 1918 so although the public health authorities of the day wrongly suspected that this bacterium, haemophilus influenzae, was to blame, they were in any case in no position to do anything about it, even if they had been correct. Instead, the response was focused on public health measures, such as the wearing of face masks in the street and the prohibition of spitting in public. These may be fairly low-tech solutions, but in some cases, they can be quite effective.
And in some other videos, we’ll be looking at the epidemiology of influenza and seeing how even in today’s modern world of flu vaccines and anti-viral drugs, one of the most important factors in flu prevention is that kind of low-tech hygiene with respect to our coughs and sneezes. The 1918 pandemic appeared in two waves. And it was 1920 before the outbreak quietened down finally. Normally, what happens after a pandemic is that the flu strain responsible returns the following winter in a milder form and keeps doing so for some time. The pandemic flu, thereby, becomes what we call a seasonal flu. We assume that this happened from 1920 onwards, even though we have no clinical samples preserved from that period.
Nevertheless, we can be pretty confident about this theory since, when some victims of the 1918 pandemic in Alaska were exhumed and the flu viruses retrieved by molecular methods and sequenced, it was found that they were of the same general variety– the technical classification uses the term type and subtype– the same general variety as the first flu strains isolated in the laboratory in 1933. That variant is called type A subtype H1N1. The meaning of the letter and number designations for flu subtypes will be explained in a related video. So, we therefore have strong reason to believe that the H1N1 flu circulated seasonally from 1920 onwards, returning to the northern hemisphere every January and staying for a few months.
And then, the same process being repeated in the southern hemisphere winter six months later. This phenomenon of seasonal influenza continues today, although the strains of flu involved have changed quite a bit, as we’ll see. The reasons for this global oscillation are still rather unclear and are the subject of a very active area of research. It seems that the flu, whether heading south or north depending on the time of year, always originates somewhere around Southern China and Southeast Asia. 1947 was a particularly heavy year for seasonal flu. And every now and then, one of these heavy seasonal flu years will happen.
Perhaps, there at the end of the Second World War in 1945 had led to a re-establishment of global transport and trade links that had been disrupted since the outbreak of war in 1939, thus allowing the virus to spread more easily around the world. Or perhaps, the reason lay in the virus itself. And this reason– lying in the virus itself– is one of the core concepts in the study of influenza and is called antigenic drift. Viruses, like all infectious agents, are going to find themselves under attack from your immune system. And that means antibodies are produced against the virus.
And once bound by an antibody, a virus particle may be disrupted in its function and also could be targeted for destruction by other parts of your immune system. For some viruses, such as measles, this kind of immunity is lifelong. Nobody ever gets the measles twice. However, it’s a different story for influenza. The reason why you could potentially catch the flu every year is that the flu virus evolves very quickly. So if one rare variant of flu escapes destruction by your immune system and by the immune systems of other sufferers, then that variant will not be destroyed and will be the ancestor of next year’s strains.
And this means that the immunity you acquired against this year’s viruses might be of no use anymore. In years when seasonal influenza is particularly bad– such as 1947 and more recently in 1999 was also a very bad year– these are usually years when antigenic drift, as we call it of that sort, as particularly strong. So, we’ve come to the end of the short introduction. We’ve covered the catastrophic flu outbreak of 1918. And we’ve seen how it turned from pandemic flu into a seasonal flu, returning every winter for several decades, each time having undergone antigenic drift, allowing it to avoid the antibodies its human hosts made against the strains of the previous years.