Mediscene

Why I’m scared about an Influenza Pandemic

Dr. Sanjaya Senanayake, an Infectious Diseases Physician looks at the 20th century history of Influenza

There has been a lot in the news recently about influenza in Sri Lanka. Given the hype, particularly in 2009 when swine flu emerged, you may wonder what all the fuss is about. Isn't influenza just a matter of enduring a sore throat and achy muscles for a few days? Well, it can be that but it can also be a lot more, especially for certain groups.

The reason that influenza generates such apprehension in clinicians and public health officials lies in its biology but can be better illustrated and appreciated through its history. And we need look no further than the 20th century to see what influenza can do when unleashed in all its fury.

The 1918 Influenza Pandemic

Back in 1918, mankind didn’t need infections or other natural disasters to eliminate each other. No, we were doing quite a decent job ourselves through a little event called World War 1. Estimates suggest that around 16 million people died during that horrific period from 1914-1918. But an infection came along in the last year of World War 1 that was so fearsome in its transmissibility and its virulence that it wiped out 50-100 million lives – three to six times more than the total deaths from World War 1. In addition, while World War 1 took more than four years to reach its grisly target, this new infection only took one year to eliminate its victims. The infection? It was the first influenza pandemic of the 20th century, commonly known as “Spanish flu”.

2009: Passengers wear protective masks at Mexico City's international Airport fearing the spread of Swine Flu. (Pic courtesy Daily Mail.com)

It would be worth exploring the origin of the term, “Spanish flu”, at this point. Any Spaniards reading this may be a bit miffed that their country has been named in association with the most devastating infection outbreak in modern times – and they’d be justified. The implication that Spain was central to Spanish flu is wrong – the infection didn’t start in Spain nor was Spain the most heavily affected country. The term “Spanish flu” was an accident of war. Most of Europe during World War 1 had heavily censored media.

This is understandable since a government would not want its misfortunes being widely publicised in case their enemies saw an opportunity of which they could take advantage. So the two warring sides did not widely report cases of influenza occurring in their respective countries. Spain, however, was neutral in World War 1 and therefore had an unrestricted media which freely reported its cases of influenza. The price of being the country with the most prominent reporting of influenza cases was having the infection named after it – and the term “Spanish flu” has stuck ever since.

The Spanish flu pandemic was truly awful. It could not be accused of discrimination since it was brutally efficient in dispatching people of various races from different countries to the afterlife. While millions of Europeans and Americans were dying from Spanish flu, whole communities of Polynesians and Eskimos were being wiped out, some never to be seen again. South Asia was also affected with millions of deaths being reported in India.

But for many, the most frightening feature of the 1918 influenza pandemic was the age group that suffered. These days, yearly influenza outbreaks tend to most severely affect the extremes of age – the very young and the very old. People accept that the old and the very young are more susceptible to death from various agents due to their frailty and helplessness. But the striking feature of the 1918 flu pandemic was that it killed young, healthy people who normally never succumbed to influenza. To think that young people in the prime of their life could be cut down so sudden was a great shock to many. And remember – millions of healthy young men were already dying in the battlefields of World War 1 at the same time. One wonders how the people of the time mentally coped with such tragedy – they would have felt like Job being plagued by one misfortune after another without respite.

Certainly, media reports of the day provide an insight into the opinion of one particular nation towards the overwhelming 1918 pandemic. Their attitude to the outbreak was at best paranoid, and at its most extreme, almost supernatural. Was it a primitive, developing nation who thought this way? No, it was the United States – one of the most highly industrialized nations of that time. The theories that abounded in parts of the US were that pandemic influenza was biological warfare being waged by the Germans. People in Boston reported that a mysterious German ship was sighted and that a strange cloud was released over the harbour. Others pointed the finger at the German pharmaceutical company Bayer who produced aspirin.

Some people believed that the German company had inoculated aspirin tablets with influenza to promote spreading of the infection! Interestingly though, aspirin may have contributed to deaths during the influenza pandemic; however, this wasn’t due to a diabolical plot emanating from some faceless malevolent organisation. If aspirin is given for a fever, typically to a child with a viral illness, it can lead to a fatal reaction called Reye’s syndrome – that’s why aspirin is barred from being used in modern times for childhood fevers. And back in 1918, aspirin was widely used to control fever and pain. Furthermore, large doses of aspirin can cause fatal inflammation of the lungs. So there are a couple of ways in which aspirin could have knocked off someone with influenza back in 1918.

When people say “Hell on Earth”, it is a phrase that is often used flippantly in situations where less morbid terms would be more appropriate. But during the time of the Spanish flu, “Hell on Earth” would have been a most apt description. For a start, the economic and destructive effects of World War 1 would have made a number of towns and cities grim and grey places in which to live. Then add the influenza pandemic to the equation to complete the doom and gloom.

There are descriptions from that time of bodies piling up in city mortuaries, presumably filling the air with the stench of decaying flesh as mortuary attendants struggled to dispose of the crescendo of corpses. The streets were deserted – people were afraid to go out. Schools were cancelled while cafes and cinemas were empty. Often the only people visible were groups of authorities policing the streets in masks, their hidden faces giving the impression of an army of ghosts. The atmosphere arising from this social desolation, especially for young children, must have been terrifying.

Bird Flu (H5N1)

Following 1918, there were two more influenza pandemics in 1957 and 1968, known as the Asian flu and Hong Kong flu respectively. Although both spread widely, infecting millions, they were mild in terms of lethality compared to their 1918 predecessor – the Asian flu was responsible for around two million deaths while the Hong Kong flu generated half a million fatalities – much less than the 50-100 million deaths from the 1918 pandemic. After the 1968 pandemic, it was quiet on the influenza pandemic front for almost thirty years. Then in 1997, the first case of H5N1, known as bird flu or avian influenza, appeared in Hong Kong. For a brief moment in time, health authorities contemplated the possibility of a pandemic pogrom that could rival 1918 in all its horror. The medical term for such events is “brown underwear time”.

Why such concern about the emergence of bird flu? What makes an influenza virus a pandemic strain? The answer to both questions lies in two letters of the alphabet.

When you read about influenza, you’ll see the virus described in terms of “H” and “N”. The “H” stands for haemagglutinin and the “N” for neuraminidase. Both are proteins found on the influenza virus that are intimately involved in its ability to spread between cells. There are sixteen haemagglutinin genes and nine neuraminidase genes. The various combinations of the H’s and N’s determine what we call the influenza virus. For example, the 1918 pandemic was due to H1N1, the 1957 pandemic to H2N2 and the 1968 pandemic to H3N2. What do you immediately notice about these three strains of influenza?

The obvious feature is that each pandemic was due to a new combination of H and N – and this is central to understanding how a pandemic can be so deadly. As we all know, influenza occurs every year – in temperate climates, it is an accepted part of winter. But we don’t have a devastating influenza pandemic every year, do we? That is because the strains of circulating influenza are largely unchanged from year to year – nowadays they tend to be H1N1, H3N2 and influenza B. Our immune systems have therefore become accustomed to them. But the reason that we still get influenza cases every year is that these influenza strains (H1N1, H3N2 and influenza B) develop minor variations in their structure. These minor variations are enough to make us susceptible to influenza every year but not varied enough to make large numbers of us desperately ill.

Returning to 1997, the reason that a case of H5N1 in Hong Kong so alarmed health authorities was that it was a new combination of H’s and N’s in humans. As discussed earlier, there are about sixteen H’s and nine N’s with the potential for a multitude of combinations; however, many of these combinations are restricted to the animal population and are never seen in humans. H5N1 was one of those combinations known to be associated with birds – it was not regarded as a human pathogen. In other words, the human immune system was not used to it and therefore could not cope with it if it were ever exposed. Thus, the advent of a human case of H5N1 influenza was an egregious epidemic of pandemic proportions which could have made the 1918 experience seem like a picnic. Thankfully, a H5N1 pandemic never eventuated in 1997 although six of the eighteen cases died.

Having said that, the H5N1 story didn’t end there. After a hiatus of six years, cases of H5N1 bird flu suddenly re-emerged in 2003 and have continued to appear with unerring regularity in many parts of the world, especially Asia and Africa. The only positive aspect about H5N1 bird flu is that human-to-human transmission is exquisitely rare - the vast majority of human cases have been acquired directly from birds. If the H5N1 virus ever mutates sufficiently to be freely transmitted between people, then we’ll have a full-blown pandemic on our hands. The death rate from H5N1 bird flu in people is over 50%. And while that sounds scary as an absolute figure, remember that the death rate from the apocalyptic 1918 pandemic was only about 2.5% i.e. twenty-five times less! Presumably the H5N1 virus would lose some of its lethality in its efforts to become transmissible between people but even if it maintains a semblance of its current death rate, it will still be far more deadly than the horror that was 1918.

We’re certainly better equipped to deal with an influenza pandemic today compared to 1918: there are vaccines, antibiotics and more advanced medical care. But you now can understand why the prospect of an influenza pandemic keeps this Infectious Diseases Physician awake at night – along with restless children, leg cramps and an enlarging prostate.

(Sanjaya Senanayake is an Associate Professor of Medicine at the Australian National University)

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