Avian flu - the ecology of an epidemic

| 1st December 2005
Bird flu has been raging through Asia for more than a decade. But it is only recently that most of us have started to pay attention to the story. Pat Thomas seperates fact from fiction and asks whether this is a random act of nature or yet another man-made disaster.

The words ‘bird flu’ strike terror into many hearts for many different reasons. As the story of Avian influenza H5N1 gains momentum, the panic induced by the possibility of a virulent strain of influenza that not only jumps national borders but might also jump species has galvanised several influential sectors of society into action.

Farmers, fearful for their economic survival, are slaughtering hundreds of millions of birds in order to control the virus. Doctors, seeing an opportunity to save humanity from a potential pandemic and get published at the same time, are busy studying this and other related viruses. Drug companies, spying an unprecedented opportunity for profit, are busy attempting to produce experimental vaccines and anti-viral medicines for both animals and humans. The media, hungry for a good scare story, have been able to generate a more or less daily flow of such tales. Politicians looking for political capital are talking about quarantines, closing borders and waging war on a microscopic enemy.

But think about it. After several years of intense analysis and debate, how much do you really know about H5N1? If you are like most people you have probably, at some point in the narrative, confused the actual bird disease with the theoretical human one. Like many people you may have been distracted from the process of examining the origins of the outbreak among poultry by predictions of the imminent annihilation of the human race. Yet it is only by examining the ecology of avian influenza that we can begin to understand where we are now and here the disease might be going in the future.

Avian influenza is a generic term for any number of influenzas that can arise in and infect birds. There are 16 known types of avian influenza of which type-A H5N1 is just one.

While it is widely assumed that the first outbreak of H5N1, more commonly known as ‘bird flu’, occurred in South Korea in December 2003, this unusually virulent virus has been with us for a long time. Retrospective data from the World Health Organisation shows that in the last 45 years or so, H5N1 has counted for four of the 21 known outbreaks of avian influenza in commercial poultry throughout the world. The first occurred in 1959 in Scottish chickens. It emerged again in 1991 in English turkeys, and then in 1997 and again in 2002 among chickens in Hong Kong.

In the last 10 years or so the virus has made gains in virulence and transmissibility among birds and once conventionally reared poultry become infected, outbreaks can be difficult to control and often cause major economic damage to poultry farmers in affected countries.

All you need is drugs

Worry about a human pandemic, coupled with acceptance of the idea that drugs will save us all, has allowed pharmaceutical companies to set the agenda for how we respond to the threat of bird flu. It could be argued, however, that this quick-fix solution is of greater benefit to the pharmaceutical industry than it is to most average people. Last year Roche’s profits were in the region of £144 million. This year, thanks to the antiviral Tamiflu, this figure is expected to soar to £500 million, and next year £1 billion.

In preparation for a potential pandemic caused by a human mutation of H5N1, governments throughout the world are stocking up on vaccines and anti-viral medicines. Off the back of a potential crisis, many governments have cynically promoted this year’s flu vaccine as a way to stop H5N1 mutating – without a shred of evidence that this is so. Indeed, as a general rule vaccines force rather than prevent viral mutations. Equally cynical was the recent PR campaign by Roche, which at the height of people’s fears over a potential human variant of H5N1, painted their antiviral Tamiflu as a near natural remedy derived from the Asian herb Star Anise, when in fact only a single constituent of the herb is used at the beginning of a 10-stage, year-long manufacturing process that results in a synthetic substance very different from the natural herb.

Step away from the hype and the truth is that Roche has developed a method for producing Tamiflu without using Star Anise, so stories about scarce supplies of Star Anise leading to Tamiflu shortages can only be viewed as an attempt to drive the price of the remedy up – and it’s worked. Last year Tamiflu was retailing at around £16 for 10 pills. Today on the open market people are paying £100 or more for the same five-day supply. While several pharmaceutical companies are now racing to develop a vaccine against H5N1, the likelihood is that the virus will have mutated significantly in the time between the development of the vaccine and any future outbreak, epidemic or pandemic, making a vaccine based on the virus’s current genetic incarnation useless.

Consider also the unintended consequences of vaccination. In 1976 in the US an outbreak of swine flu among soldiers at Fort Dix, New Jersey, was found to be related to the 1918 influenza strain. One soldier died and 50 million Americans were vaccinated against an epidemic that never happened. In the end the vaccine, which triggered Guillain-Barré syndrome, a neurological disorder similar to polio, killed more people (32 in all) than the flu itself.

Vaccinating entire flocks of birds against the current strain of avian flu has also been put forward as a solution. But given the poor effectiveness of the human flu vaccine, it is hard to see this as a viable alternative. It may even make things worse.

In poultry, as in people, a vaccine may prevent some animals from falling ill, but it can also foster a ‘silent epidemic’ where the birds still carry low numbers of the virus which can still replicate and mutate inside their bodies, often at an unprecedented rate, and with unpredictable consequences. Scientists reporting on Mexico’s experience of H5N1 in the Journal of Virology in 2004 say that these silent epidemics can easily force the evolution of new and more virulent strains of influenza that more easily jump from birds to people.

In the same way that antibiotics can force super resistant strains of bacteria, antivirals can also produce stronger, more virulent viruses. Studies show that the avian virus is now resistant to most antiviral medicines including the Tamiflu, which the UK government has recently purchased in great quantities. Even if resistance was not a problem, Tamiflu is of uncertain benefit. It must be taken within 24-48 hours of the appearance of symptoms and even then it is not a cure or a ‘temporary vaccine’ as some of the newspapers have called it. Summaries of scientific literature show that Tamiflu will only reduce the duration of the flu by an average 1.3 days. In some individuals it may reduce severity of symptoms but taking it over the long term, as many will be tempted to do, can reduce its overall effectiveness, has never been proven safe, and may have unintended and as yet unstudied interactions with other medications.

Another antiviral, GlaxoSmithKline’s Relenza, has not shown any resistant strains – yet – and reduces the duration and severity of flu to the same degree as Tamiflu. But as it is inhaled rather than coming in capsule form it is not for everyone (for instance the very young), and it can also cause severe breathing difficulties in people with asthma and/or chronic obstructive pulmonary disease (COPD).

If a pandemic does occur, and if it proves deadly, it will not be because our drugs were not strong enough, but because our immune systems were not. In this way things may have not changed very much from 1918. Only now it’s not world war, but the chemical warfare waged on our bodies by a constant barrage of toxic chemicals, poor quality food, and increasing levels of stress that makes us sitting ducks for the next pandemic.

While there is still time, while H5N1 remains a bird rather than a human epidemic, while tens of billions are being made available in preparation for a potential pandemic, a commitment to improving diets, lifestyles and living conditions of the population as a whole, and the most vulnerable in particular, and to improved education about hygiene and the nature of viruses, would be our best medicine. Terrifyingly, this has yet to be put on any government agenda.

Kentucky Fried Flu

There is good reason to believe, however, that it is not the virus, but the inhumane conditions in which the birds are reared that is most deadly. Rearing animals in crowded conditions, feeding them unnatural diets, and exposing them to unimaginable stress during their short lifetimes creates a breeding ground for illness, infection and eventually epidemics.

Such appalling conditions arise from our general apathy and inaction as regards the importance of animal welfare, but also from our evolving belief that cheap food in general and cheap chicken in particular is some kind of human birthright.

The average chicken you buy in the supermarket may be ‘British’ (a loose definition that can include a chicken that was grown and packaged in this country or one that was shipped in from somewhere else and packaged here), but the vast majority of chicken ‘products’ – nuggets, goujons, kievs, pizzas, pies, sandwiches, ready meals and airline, school, hospital and pub meals – are generally made from chicken imported from abroad. Likewise, the proliferation of fast food restaurants on British high streets rely on a steady supply of cheap imported chicken to sustain them.

Consumers, of course, rarely know where their chicken has come from. Before the outbreak, few knew that the Asian region affected by the spread of avian flu is home to around seven billion chickens, approximately 40 per cent of all the world’s poultry. After the US, Brazil, and the EU, Thailand is the fourth largest exporter of poultry in the world.

The amount of chicken imported from Thailand into the UK has grown considerably over the last few years. In 2000, more than 23,420 tonnes of prepared chicken was imported into the UK from Thailand. By 2003 and 2004, when avian influenza was in full swing, this figure had risen to 45,073 and 44,316 tonnes respectively. So even at the height of the outbreak it’s a fair bet that you have eaten Asian chicken in some form over the last year or two. To meet our increasing demand for cheap chicken Asian farmers (indeed poultry farmers everywhere), are encouraged to produce lots of birds quickly and cheaply. Inevitably corners – in hygiene and animal welfare – get cut.

While news reports have focused on heartbreaking stories of family farmers whose small flocks have been devastated by avian flu, this does not give a true picture of the Asian poultry business, which is home to many vast battery farms (indeed Tesco is the majority share owner in one of Thailand’s largest battery farms). One of these farms is rumoured to house as many as five million birds. Under these conditions a farmer is nothing more than an impotent guardian, unable to spot disease when it first emerges and unable to stop its spread once it takes hold.

Killing with kindness

Since mortality rates are high with H5N1, infected birds are generally destroyed, or ‘culled’, in order to prevent the spread of the disease within the flock and to neighbouring farms. To date, the current outbreak in Asia and the more remote corners of the EU has resulted in the culling of more than 100 million birds.

Culling, however, is a crude and ineffective method of disease control. When H5N1 first appeared in Hong Kong in 1997 some 40 million birds were culled. This did not stop the disease emerging more strongly than ever in 2002. Nor did it prevent it crossing national borders or infecting human beings.

Culling wild birds in the hope of stopping the international spread of the virus is an equally violent and futile act. In July 2004, the UN’s Food and Agriculture Organisation (FAO) cautioned that doing so was ineffective and ‘will not help to prevent or control avian influenza outbreaks’.

Wild birds are natural reservoirs for many types of virus and most of the time they are immune to illness. While local authorities panic at every dead duck found in a pond or lake, it is worth remembering that the spread of avian influenza through wild birds is limited by the simple fact that sick birds do not fly far, and dead birds don’t fly at all. It is hardly surprising then that, to date, there is no scientific evidence that wildlife spreads the disease to domestic or commercially reared birds, or that it is the major factor in the resurgence of the disease in Asia or of isolated outbreaks in countries such as Turkey, Greece and Romania.

Other proposed solutions such as hunting wild birds, some of which are listed as endangered, or cutting down trees to destroy roosting sites, are more likely to disperse wild birds into new areas, stress them further and make them more susceptible to avian influenza and/or other diseases.

Furthermore, the FAO has emphasised that wildfowl are also an important element of the biologically complex wetlands ecosystem, acting as herbivores, predators and prey, as well as facilitating plant dispersal. Killing them on a just-in-case basis would have profound ecological impacts.

Culture of death

The ‘culture of death’ that surrounds sick animals is not new. One needs only to look back as far as 2001 and the outbreak of foot and mouth disease in Britain to find significant examples of the tendency to wage war on nature every time our manipulation of it threatens the global economy.

Like avian flu, foot and mouth is caused by a virus. The characteristic
sores on the mouths, gums, teats and other parts of infected animals are little more than large cold sores. If they are well cared for, afflicted animals usually recover within a week or two, just like humans with the flu. Yet in 2001, rather than waiting for the animals to get better, millions of sheep and cows in the UK were culled in an effort to keep the disease under control. This slaughter occurred in spite of the fact that there was no threat to humans from the meat of infected animals.

The fact is that animals, like humans, get sick. For example, figures from the US Department of Agriculture show that since 1997 more than 16 outbreaks of H5 and H7 influenza have occurred among poultry in the US. From the birds’ perspective such outbreaks usually result in either no illness or mild illness and low levels of mortality. To date there has been no evidence that the virus is transmitted through the meat or eggs from infected birds.

When problems such as foot and mouth or avian flu arise, out-of proportion publicity about the risks to human health are often used to obscure more pressing issues such as the way these hard to control, but otherwise natural and cyclical occurrences threaten to expose the economic reality of intensive farming.

From a modern farmer’s perspective sick animals are unproductive animals. In farmed birds catching the flu is undesirable due to the way it temporarily slows down growth and reduces the number of eggs a bird will lay. The unspoken and unanswered question is: is it cheaper (or even more profitable given the carrot of government subsidies for culling) to kill them than to sit out a period of decreased productivity that naturally accompanies any period of illness?

Farmers argue that culling is kinder to the birds since up to 90 per cent of birds infected with avian flu will die anyway. If kindness and animal welfare were really on the top of farmers’ agendas, however, we would be looking seriously at the contribution of modern intensive farming practices to the emergence of highly pathogenic H5N1.

Should bird flu spread widely beyond Asia, its impact on human health may be much less destructive than feared (see page 21), but it will certainly devastate a multi-billion pound poultry industry. While it’s hard not to feel some sympathy for farmers, there is good reason to believe that when our animals get sick we are being hoist by our own petard.

What is the risk?

The most pressing concern about bird flu is that it will mutate into a variety that will easily infect humans. To date this has not happened; the people in Asia who have become ill or died from H5N1 have been infected with the bird virus, rather than a mutated human virus.

Most avian influenza viruses remain unique to their hosts and pose no threat to human health. However, under the right circumstances, some can ‘jump’ from animals to humans. In this respect H5N1 is not unique.

Of the 16 known types of avian influenza, three subtypes – H5, H7 and H9 – are known to be capable of crossing the species barrier. Since 1997 types H5N1, H7N2, H7N3, H7N7, and H9N2 have all caused small, confirmed outbreaks in humans throughout the world. The fact that a virus can cross the species barrier, however, does not mean that it is dangerous.

For instance, just because H5N1 is lethal in chickens doesn’t necessarily mean that it will be so in humans – the virus could just as easily mutate into a less virulent form as it can a more virulent one, and the direction of its mutation is difficult to predict. Likewise few humans live in the crowded conditions common to battery chickens and, for this reason, even if the virus were to jump species, it may not necessarily spread as quickly through the human population as it has with chickens.

While scientists suspect that H5N1 may have been spread between one mother and daughter in Thailand, this remains unconfirmed. To date there is no unequivocal evidence of person-to-person transmission. Instead, the handful of human cases can be traced back to direct contact with the faeces and blood of infected birds. Likewise there has been no evidence that the virus is transmitted through the meat or eggs of infected birds.

It is also worth remembering that since the 2002 outbreak of H5N1 there have been literally billions of interactions between chickens and humans. Yet, according to the FAO’s Technical Task Force on Avian influenza, the number of humans who have been infected with avian influenza over the last two years totals just 118, and these cases are largely confined to Vietnam, Thailand and Cambodia.

Nevertheless, viruses can mutate rapidly and many molecular virologists are concerned that it would take little more than a chance mutation to turn H5N1 into a deadly, easily transmissible human disaster. Such mutations, however, don’t occur out of context.

If a host becomes infected with two or more viruses simultaneously, these can easily swap genetic material and mutate into new and never-before seen strains. If one virus happens to be extremely communicable and the other extremely lethal, a mixing and matching of their genes could produce a lethal hybrid. If one virus is from an animal such as a bird or a pig, and the other is from a human, the result may be a virus that can easily infect humans. However, in a virus that is largely contained among birds, such as H5N1, the chance of swapping genetic material with an easily communicable human virus is very low.

Likewise for the virus to spread easily among humans it would have to produce specific symptoms, such as coughing and sneezing, and lodge itself in easily accessible major airways. The few autopsies performed on human victims of H5N1 have revealed that the virus lodges deep in the crevasses of the lung tissue, not in the major airways as would be the case in an infectious flu.

No one can predict when or if the virus will mutate into the ‘potential doomsday virus’ described in a recent edition of The Sunday Times, but clearly it is still more than a random mutation away.

How deadly is deadly?

Forecasts of how deadly the virus will be should the pandemic occur are prone to vast disparities. Consider the predictions for the UK. While a figure of around 50,000 deaths in the UK is widely quoted, eminent scientists such as Professor Hugh Pennington, president of the Society for General Microbiology, have suggested a figure of two million. Waving the shroud of the 1918 pandemic, a medical correspondent for the BBC recently put the figure at 11 million.

Early reports suggested that avian influenza killed about 90 per cent of its human victims. Available figures suggest a lower rate of around 50 per cent – among the 118 known cases of avian flu there have been 60 deaths. But even this figure may be misleading.

First of all, we simply don’t know how many people in the world have genuinely been infected with avian flu, nor do we know how many may have had mild or asymptomatic flu as was the case in a handful of Japanese workers. We don’t know how many people are naturally carrying antibodies to H5N1, though such studies as exist suggest that as many as 38 per cent of the population may already be immune.

Surveillance in many parts of Asia is far from comprehensive. Keeping track of people who have died is relatively simple, keeping track of those who carry the virus and either do not become infected or only have minor symptoms is much more difficult. In many poorer regions the combination of a lack of good roads and express mail systems, too few trained technicians and inadequate laboratory facilities makes it impossible to establish reliable data. In addition, establishing a true death rate depends on governments’ honesty in overcoming fears about losses from decreased tourism and trade, and reporting all known cases. This honesty cannot be taken for granted.

Secondly, it is worth remembering that to this day scientists cannot agree on how many people actually died in the 1918 pandemic. Estimates range from 20-100 million – an absurd margin of error. On the whole it is accepted that the 1918 pandemic had an average death rate of around two per cent of those infected – with mortality significantly higher among the poverty stricken and undernourished and lower among the healthiest people. The last two pandemics, in 1959 and 1967, killed one and two million respectively – a trend that is a far cry from the 50 per cent death rate predicted for a potential avian fl u pandemic.

Scientists are currently studying the 1918 pandemic in order to better understand the potential threat posed by H5N1. Unfortunately the 1918 virus was never isolated in its entirety so, in an act of Jurassic Park science, US researchers working with the military have spliced together incomplete pieces of the virus with those from another strain, and have created an entirely unique strain of human super-virus that they say will help them understand the structure, virulence and transmissibility of H5N1. However, It’s hard to see what this flashy genetic hocus pocus, akin to studying bananas in order to better understand tomatoes, will achieve.

Looking for links between the putative 1918 human virus and the current avian virus also distracts us from the fact that the unusual virulence of the 1918 virus had more to do with the fact that it evolved amid the unique mayhem of World War I. Crowded, unhygienic conditions – tens of thousands of troops stuffed into transport ships, trenches and military hospitals – favoured the mutation and spread of the highly virulent, easily transmissible virus.

Most of us are asking: ‘What if the experts are right?’ The other equally relevant question, ‘What if the experts are wrong?’, hasn’t attracted much serious attention. Can we say with any certainty that the pandemic is on its way? And if it is, can we say with any certainty that H5N1 will be the cause? All the available evidence suggests that we cannot. In the meantime, governments throughout the world are investing hundred of millions in drug stockpiles and waging an ongoing and totally ineffective war against nature – a war that ignores the value of the human immune system in fighting disease and which may, in the end, bring us closer to the pandemic we fear so much.

This article first appeared in the Ecologist December 2005