Gone Viral

The Germs That Share Our Lives

By Frank Bowden

University of New South Wales Press Ltd

Copyright © 2011 Francis Joseph Bowden
All rights reserved.
ISBN: 978-1-74223-273-7

Contents

Author's note,
Introduction,
1 Under the influence,
2 A beautiful anachronism,
3 Life during wartime,
4 The pricking of my thumb,
5 Malcolm in the beginning,
6 The Semmelweis effect,
7 In the blood,
8 Severe and acute? That has to be bad!,
9 The pox under our noses,
10 Cultures that stink,
11 Like a blowtorch to the groin,
12 So common it can't be a disease,
13 Let's not talk about sex,
14 The Yellow Pages,
15 Sleepers, wake,
Glossary,
Acknowledgments,
Index to pathogens and diseases,

CHAPTER 1

Under the influence

Influenza A – an RNA virus that affects birds and mammals. Influenza A viruses are constantly changing. While humans who have been infected with one influenza strain in the past retain some degree of immunity to new strains, eventually a mutant appears that can overcome these defences and an influenza epidemic occurs. The word influenza is Italian for 'influence', and in medieval times the emergence of a flu epidemic was thought to be controlled by the stars – hence if someone was 'under the influence' it originally meant they had flu.

'I had a little bird/Its name was Enza/ I opened up the window/And in-flu-enza ...' (children's skipping rhyme, c. 1918)

One of the great advantages of being a well paid specialist on the staff of a public hospital rather than a ridiculously well paid visiting medical officer in private practice is that you are entitled to long service and study leave. After ten years without a break of any substance, I was tired, grumpy, sick of being on call to the hospital, fed up with working on the weekend, short with my colleagues and occasionally dismissive of my students. I knew that soon I would reach that lowest of low points for a doctor – when you start to see patients as enemy; when you complain about them in the tea room as though they had contrived their illnesses just to annoy you. My family had started giving me concerned looks across the dinner table, and even my dog was keeping her distance.

So it was with considerable anticipation that I began a three-month sabbatical on 27 April, 2009. I was determined to make the leave count – I promised myself that I would be sitting at my desk every morning ready to write by no later than nine and, in an uncharacteristic display of planning, I had even constructed a timetable for the next 12 weeks. On the first morning, unshaved, wearing Ugg boots, tracksuit pants and tee-shirt, I drove my wife to work, returned home to read the paper slowly over breakfast, had a long shower – safe for once from spousal admonitions about water conservation – and arrived at my desk only a few minutes after my self-imposed deadline. I quickly scanned the top stories on the ABC News website and one item caught my eye.

'Experts say the swine flu outbreak currently stoking fears of a global epidemic poses a greater risk to Australia, with the onset of winter bringing the peak of the flu cycle.' I checked the BBC site: 'Schools in the capital city of Mexico are closed due to an outbreak of a disease called swine flu'.

Now this was strange – we had been expecting the next influenza pandemic to be caused by a mutation in the avian influenza virus, the H5N1 strain that mainly affected birds, not the H1N1 virus that was associated with pigs. I rang my wife, who works in infection control, and asked her what was going on.

'I can't talk, I have to go into a meeting with the chief health officer in a minute. There's a bit of a flap on in here.'

There were five infectious diseases specialists in our unit at the time. Two were on duty, one was overseas working on a project, one was in the Kimberley on holidays, out of phone range and I was ... 'Oh no, you can't do this to me', I said out loud. I put down the phone and tried to concentrate on writing, without success. I turned on the radio and listened to the 10am bulletin. The top story was swine flu.

Influenza pandemics of the 20th century

There had been three influenza pandemics in the past 100 years – 1918, 1957 and 1968. The 1918 Spanish flu pandemic was the greatest natural disaster of the 20th century – estimates vary, but a minimum of 20 million and possibly up to 50 million people died, at least double the ten million who were killed on the battlefields of the First World War. In a world without antibiotics the secondary bacterial infections that followed the epidemic were often deadly, and there were no intensive care units (ICUs) to provide the care needed to allow patients time for their own immune system to win the fight against the pathogen. Around a third of the global population was infected with Spanish flu and more than 2.5 per cent of humanity died. The other pandemics were, by comparison, not in the same league: the Asian flu of 1957 is estimated to have caused around two million deaths worldwide, while the Hong Kong flu of 1968 is thought to have killed at most a million people.

I became intimately acquainted with Hong Kong flu as an eight year old; by nearly killing my father, the infection probably saved his life. I remember my father lying in the single bed in the spare room, the bedclothes pulled up over him as he shook his way through what I now know to be a rigour. When my mother had picked him up from the train station the previous night he had been completely well, but during the three-minute drive home he started complaining of chills and had started to shiver. By the time he had put his case down in the bedroom he could hardly talk because of the shaking. Hong Kong flu was on that evening's television news and on the front page of the day's Sun, so my mother had already made the diagnosis by the time our GP arrived the next morning. He gave my father an injection in his bottom – everyone received penicillin in those days, even though doctors knew that antibiotics didn't work against viruses. I remember my mother's concern and the hushed kitchen conversations with friends who had never seen my father stopped by anything and suggested that he needed to go to hospital. He coughed and spluttered for weeks after the worst was over and he always remembered the illness as one of the worst he had experienced. He had smoked more than 20 cigarettes a day since the war, but after he recovered he never smoked again. He died at the age of 81.

Then for 40 years it was all quiet on the influenza front. There was a false alarm for a swine flu pandemic in 1975, but virologists believed that the next pandemic was not a matter of if but when.

Drift, shift, replication and re-assortment

There are three types of influenza virus – A, B and C. Pandemics are always caused by influenza A. Infection with influenza B can be severe but is rarely fatal and infection with C is uncommon and usually mild. The viruses have two main proteins on their surface – haemagglutinin (H) and neuraminidase (N) which are responsible for their confusing nomenclature. There are 16 N and 9 N subtypes but only H1, H2 and H3 and N1 and N2 commonly cause human disease. The Spanish flu and the 2009 swine flu were H1N1, the Asian flu was H2N2 and the Hong Kong flu was H3N2. Bird (avian) influenza is H5N1.

To understand why pandemics occur we need to understand a little about the way influenza viruses reproduce and how our immune systems respond to them.

Viruses commandeer the protein-making machinery of the body's cells to generate tens of thousands of copies of themselves. Every time a flu virus replicates (or copies) itself there is the potential for an error (mutation) to occur, resulting over time in significant changes to the structure of the virus and altering the way the host's immune system 'sees' it. After a first encounter with a virus it takes days or weeks for the immune system to produce specific antibodies against it, but if the same virus is encountered in the future the body's reaction time is much faster and the antibodies can destroy the virus before it has time to invade the human cell, replicate and cause disease. However, if a virus has mutated, the antibodies are unable to recognise it, giving the virus time to invade, replicate and cause disease all over again.

Some viruses mutate very little during replication. The measles virus that we are exposed to in childhood will be almost identical to the one that we may be re-exposed to decades later, and so immunity is life-long. The influenza A virus, however, is notable for its sloppy proof-reading and at least one mutation occurs with every copy. Most of these mutations are minor but when enough of them have accumulated by successive passages through infected human hosts, the structure of the virus at the end of the flu season may be quite different from the one at its beginning. This is known as antigenic drift, which, as the word 'drift' implies, is a gradual process which allows the human immune system to almost keep pace with viral evolution; you might be susceptible to next year's strain, but you are likely to have a least partial immunity. Antigenic drift won't lead to a pandemic – for that you need a sudden and profound change in the viral structure to produce a virus that no one in the population has previously encountered and developed immunity to – this seismic phenomenon is called antigenic shift. (It is important to point out that susceptibility is not the same as virulence: it is possible, as we will see, to have a pandemic that infects hundreds of millions but kills very few.) A shift requires more than just a few typos while transcribing the viral genetic code – it requires viruses to have sex with each other. Now, viral sex may be a difficult image to visualise (or not, I suppose, for many of the internet generation) but it really happens. Higher-order organisms such as us combine half their genetic material with half that of a member of the opposite sex to increase the genetic diversity of their offspring. Lower-order organisms mainly reproduce by making identical copies of themselves, but occasionally they display the more mature behaviour of their superiors. Sex between consenting viruses is more accurately, if less evocatively, known as re-assortment. A human influenza strain can re-assort with a bird or a pig strain and the resulting hybrid may have properties that produce very severe disease in humans. The frequently cited doomsday scenario is a re-assortment of the bird flu virus H5N1 with a human influenza virus that allowed bird flu to be transmitted from human to human. The reason infectious diseases specialists worry so much about such an event is that the world's insatiable appetite for poultry has produced a chicken population explosion, particularly in Asia. With so many birds living in close proximity to humans, viral re-assortments are occurring all the time and the emergence of a deadly strain is considered inevitable.

The 2009 swine flu pandemic

All epidemics start quietly – their early stages are usually undetectable by the routine surveillance mechanisms that health departments have in place. By the time you know that something is going on, the infectious agent is well established in the population. The swine flu virus responsible for the 2009 pandemic was first detected in Mexico in April, in four-year-old Edgar Hernandez who recovered completely, but the virus would have been circulating in the community for weeks or even months prior to this. Within a few days of Edgar's highly publicised diagnosis dozens of other people across Mexico were reporting fevers, muscle aches, and coughs. As I read the news bulletins each morning over the next few weeks it became clear to me that an antigenic shift had occurred. By the time the virus causing their symptoms was identified as swine flu (H1N1) in the Centers for Disease Control laboratory in Atlanta, Georgia, thousands more had been infected. The new virus was very similar in composition to the 1918 Spanish flu, but it was not clear if it possessed the same virulence as its 20th century ancestor. The World Health Organization (WHO) had been preparing for this event for more than a decade and an elaborate influenza pandemic plan had been formulated.

By the end of April 2009, cases of swine flu had been reported in the United States, Europe, India, Pakistan, Bangladesh and New Zealand. On June 11 Margaret Chan, Director-General of the WHO, told a press conference in Geneva: 'We are all in this together, and we will all get through this, together'. She had just declared the beginning of the first influenza pandemic of the 21st century.

Influenza is an autumn and winter disease, so though the virus was circulating in the northern hemisphere it was not expected to take off there until later in the year. The European and US public health communities were, therefore, closely watching the behaviour of the epidemic when it reached Australia and New Zealand during our winter. As had been predicted, attempts to contain the virus proved futile in a world interconnected by modern air travel, although many jurisdictions, including some in Australia, attempted to create a cordon sanitaire, reasoning that slowing the tempo of the epidemic even by a small degree would buy some time to get local plans in place.

One of the planks of the pandemic plan is the use of antiviral prophylaxis – the administration of a drug to people who are exposed to the virus to prevent them from contracting the illness and to break the chain of transmission. The antiviral agents that work against influenza – zanamavir (trade name Relenza – an Australian discovery) and oseltamivir (Tamiflu) – do not have anything approaching the potency that antibiotics have against severe bacterial infections. The anti-flu drugs inhibit the neuraminidase enzyme of the virus (the 'N' of H1N1) and as they have no effect on human cells they are very safe. The original studies that led to their licensing showed that patients with influenza who received either agent were, on average, free of symptoms for about one day less than those who received a placebo – a real but only modest benefit. Their effectiveness against serious, life-threatening influenza has never been subjected to a randomised clinical trial. Each country has established a national stockpile of the drugs, which are dispensed to those most in need during a pandemic – initially health care workers on the frontline of health care delivery. The problem with their use in prophylaxis is that they only work while you are taking them – if you stop the drug and are then re-exposed to influenza you can still become infected. Antiviral prophylaxis is a little akin to a First World War soldier donning a gas mask in the trenches when the mustard gas has been released – you are protected only as long as you have the mask on. To be able to safely discard the mask, to continue the metaphor, you need a ceasefire and this can only be achieved with vaccination.

Mild for most, fatal for a few

Influenza can manifest in many ways, from trivial and short-lived symptoms, such as a few muscle aches and a bit of a headache, to the disease that we all know as the flu – in which the symptoms range from severe muscle aches, feeling dreadful, high temperature, chills and uncontrollable shaking, through to life-threatening pneumonia, respiratory and other organ failure, and death. Every year thousands of people around the world die from what is known as seasonal influenza – but those affected are usually the frail and elderly members of the population and those with pre-existing serious chronic illness. During the 1918 pandemic the sequence of completely well, to moribund, to dead could occur within 24 hours and the disease targeted the younger and otherwise well members of the population.

We soon discovered that the 2009 swine flu was a mild disease in most people. There were exceptions: a fortnight after contracting swine flu two doctors at my hospital developed a neurological condition called Guillain-Barré, which damages the peripheral nerves and produces muscle weakness. One continued to work until he found himself unable to get out of the chair in his consulting room; the other woke to find himself unable to move the muscles of his face.

Our hospital was busy, but because the majority of those who were sick with the flu could be managed at home. There was no need for me to rush back to work and help my colleagues man the pumps. The smaller number of critically ill patients required the skills of the intensive care doctors, not my humble services. My wife gave me daily updates and, while subtly mentioning the important role she was playing, made it clear that I would just be in the way. At least my dog was talking to me again.

By July it was apparent that the death rate overall was between 0.001 and 0.03 per cent of those infected – much lower than the 0.1 per cent of the 1968 pandemic. The attack rate would turn out to be relatively low too – antibody testing performed after the epidemic ended would show that somewhere between 10 and 20 per cent of the population had been infected. But while some of us were busy reassuring the population that this was no 1918 Spanish flu, the intensive care doctors had witnessed something new and frightening: an epidemic of viral pneumonia that affected pregnant women, children and the middle-aged. In Australia, a total of 722 patients with H1N1 were admitted to an intensive care unit and 103 of these died, including seven pregnant women and seven children. Many more would have died if not for the heroic measures instituted in some cases – the sickest patients were treated with extra-corporeal membrane oxygenation (ECMO). This is the equivalent of putting someone on cardiac bypass for open-heart surgery, but instead of stopping after three hours you continue until the patient's lungs have recovered – which could take days or even weeks. ECMO is an expensive treatment that carries with it considerable risk of complications and can only be performed in a few specialist centres. After the epidemic was over, I attended a conference where the director of a major urban ICU said that during the epidemic his unit had reached the upper limit of its ability to cope with critically ill patients. If the number of cases had been any greater, he believed, the unit would not have been able to provide adequate care for all who needed it. In that event, many older people with complications of the flu who would otherwise have received intensive care would have been denied it to allow younger people, pregnant women and other high-risk patients access to treatment.

(Continues...)Excerpted from Gone Viral by Frank Bowden. Copyright © 2011 Francis Joseph Bowden. Excerpted by permission of University of New South Wales Press Ltd.
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