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The Avian Flu

by Canice Nolan

What is the flu?

Influenza, more commonly known as flu, is caused by a virus which enters the body of birds, humans and other mammals by attacking their airways. The flu virus is remarkably simple and uses two elegant "keys" to get past the body defenses to infect cells and organs and reprogram their DNA systems to replicate itself. The first of these is hemagglutinin and the second is neuraminidase. There are fifteen variants of the first and nine of the second; for ease of discussion, scientists number these H1-H15 and N1-N9.

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It is important to differentiate at least three types of flu:

Normal seasonal flu, bad enough in itself, kills about 38,000 people in the US each year alone - most of them elderly or otherwise vulnerable. Its virus mutates sufficiently slowly that almost all of the population have been exposed to it to some extent and have some degree of immunity to it. The slow mutation rate is also useful in preparing vaccines against it. Each year the WHO selects the most likely candidate virus for the following season, distributing it to vaccine manufacturers and giving them many months to develop and produce vaccines in advance of the flu season.

Avian influenza, also called bird flu, also exists in many variants, and while these are not normally infectious in humans, they can infect other animals such as pigs. The current version of avian flu circulating in Southeast Asia is labeled H5N1. This is a relatively recent form, and because of its novelty human immune systems have never been exposed to anything like it. As a result, we will likely be defenseless against it should it ever become infectious in humans. The current strain of H5N1 seems to have a very low degree of human infectivity. Of the very few people known to have been infected (only about 130 in Southeast Asia), about half died.

One of most notable responses to reports of avian influenza at European borders was a drop in poultry consumption - even though the virus is heat-sensitive and is destroyed at normal cooking temperatures. This underlines the importance of clear and effective risk-communication in matters of food safety. As long as normal precautions are taken during the handling and cooking of poultry, the meat is safe to eat - not just safe from H5N1 but also from the other microbial pathogens that may be found in poultry.

Pandemic flu, the third type of flu, does not currently exist and at present there is a low risk that it will occur at all. However, because of the impact of a pandemic if it were to arrive, the risk is being taken seriously by public health officials and politicians alike.

What is the impact of a flu pandemic?

We have no prior experience with a worldwide avian influenza pandemic and it is difficult and probably meaningless to try to estimate the cost of one.

Estimating the impact of a human pandemic is more an art than a science. Evidence to date suggests that H5N1 induces a "cytokine-storm" overreaction in the immune systems of infected humans, flooding their lungs. This likely means that, unlike seasonal flu, it could disproportionately impact young adults. Using various models with various assumptions on how transmissible and how virulent a pandemic flu virus is, WHO estimates that up to 150 million deaths might occur worldwide.

It has been argued that, because of improvements in healthcare, this number is on the high side. But when put against the vastly increased world population and its mobility, the factors tend to cancel out. In addition, in many parts of the world the healthcare available in a pandemic today may not be much better than that of 1918, once essential services are swamped by demand. It is important to note how uncertain all these predictions are, however.

As with the deaths, the economic costs are all but impossible to predict. Again, building on experience with SARS and knowing that the global economy of today is very much based on just-in-time transactions, the disruptions to trade, even of raw supplies, will be immense - costing up to $1.5 trillion - particularly if the pandemic strikes in younger people. Again this is just a number full of uncertainty. The basic message is that the costs will be immense and that the investment needed to mitigate a pandemic (see below) is not disproportionate.

What is the risk of a pandemic?

With ten human pandemics in the last 300 years and three in the last 100 years (the most recent of which occurred more than 30 years ago), there seems to be a certain inevitability about a pandemic occurring in the not-too-distant future. Most experts now say "when" rather than "if" in conjunction with the outbreak of a pandemic. We cannot predict with certainty the source of the pandemic, but the most likely present candidate to trigger one is the H5N1 strain of avian influenza virus that was first detected in birds in Southeast Asia in the mid-1990s and is slowly spreading across the globe, possibly by commercial trade in captive birds as well as by migratory birds. It has spread to the eastern borders of the European Community.

This virus, quite virulent as avian flu viruses go, is now endemic in wild birds in Southeast Asia. It has been reported to infect and cause death in cats - even tigers - pigs and humans. However, to trigger a pandemic, several things have to fall into place. The first of these is that the H5N1 strain will have to mutate to a strain that can easily infect humans and be transmissible from human to human. This could arise through normal genetic drift, but it could also arise through a recombination event, i.e. when the avian flu infects a human or animal that is already infected with the normal seasonal flu and the genetic codes of the two strains are shuffled in the host, a deadly new strain may form that can infect and be passed among humans directly.

As the disease is endemic in Southeast Asia, there are now an untold number of H5N1 virus particles there that can mutate, so the risk of a dangerous mutation occurring is greater than before the outbreak started when H5N1 numbers were low. This is the reason that the best prevention against such an occurrence is to tackle the disease at its source in Southeast Asia.

How can we reduce the risk of a human pandemic?

The easiest way to reduce the risk is to reduce exposure, and the risks can be reduced on the avian side as well as on the human side. The smaller the numbers of infections, the smaller the risks of transmission and the smaller the risks of a spontaneous mutation arising.

As far as birds go, there are several options:

First, by reducing the exposure of domestic birds to possibly infected wild birds, the chances of those domestic birds getting infected is greatly diminished. It is striking that of all the cases reported in Southeast Asia, none has taken place in large commercial poultry facilities. This is because the bio-security measures put in place by those operations is very effective. In Southeast Asia, the practice of most smallholder bird producers is to allow the birds to roam freely among humans and other livestock (including pigs). Often, after the harvest, they are allowed onto rice fields which migratory waterfowl have already contaminated with droppings - a rich source of H5N1 virus. When H5N1 was first reported in Russia, European poultry farmers in several countries were advised to bring their free-range hens indoors to avoid such contacts.

A second option is to reduce the number of infected birds. The standard response to the detection of an infection is to cull all birds in a flock and to impose a quarantine in the locality. This is costly in terms of animal welfare as well as in economic terms, particularly for peasant farmers. Without proper incentives, this can act as a barrier to early reporting.

Third, there is the option of vaccinating poultry against avian influenza. If undertaken in a serious manner with a good strategy, vaccination can be a very useful tool in containing an outbreak of an infectious disease. But apart from the economics (cost of vaccine versus profit from selling a hen) and the numbers involved (billions of poultry in Southeast Asia), it is a fact of life that vaccination will protect a bird from dying but the bird could still shed the virus. Therefore, for the vaccination to be effective, a good vaccination strategy is needed, preferably using a DIVA (Differentiating between Infected and Vaccinated Animals) strategy and an effective post-vaccination strategy which includes surveillance for the disease. Many countries, however, would not accept vaccination as a reason to unblock trade from countries utilizing this tool. At the macro level, the likelihood of trade blocks can also act as a disincentive to early reporting.

Fourth, reducing the possibility of avian influenza mixing with human influenza makes good sense. Separating flocks of poultry from domestic pigs is easy in commercial operations but at present impossible in many smallholdings in Southeast Asia. Preventing people suffering from human flu from coming into contact with infected birds also makes sense, and can be done in commercial settings more easily than in smallholdings. This, incidentally, is one of several reasons why it makes sense to promote vaccination against seasonal flu - the vaccination will not help against avian flu but it should reduce the risks of recombination events taking place.

It is a challenge to provide incentives to people and countries to report early, as soon as avian flu is suspected in a flock. Some thought should be - and is being - given to compensating farmers and even countries for reporting outbreaks.

Most people now agree that avian flu should be tackled at its source in Southeast Asia. It has long been known that early response by affected countries is a key to managing an outbreak before it gets out-of-hand. This requires a capacity to detect and willingness by affected countries to report early. This is improving of late but progress is still needed in this area.

How can we reduce the impact of a human pandemic flu?

Planning for functional preparedness and response is crucial. A plan alone is not sufficient, as we saw in the wake of Hurricane Katrina.

We need to improve the capacity in countries concerned to detect, report, and act quickly on outbreaks of avian flu in birds and humans. To do this requires a well-structured control mechanism, a good infrastructure, and coordination between veterinary and public health services. We need to fight the disease at its source and that means being able to act and to get supplies to remote areas without delay.

As soon as sustained human-to-human transmission is confirmed and a pandemic is declared by the WHO, the virus needs to be isolated and provided to vaccine manufacturers to start production of vaccines. It is likely that production of regular vaccines such as those for seasonal flu and childhood diseases will fall rapidly as production is switched to producing a pandemic vaccine. A vaccine will take months to produce and worldwide production capacity of vaccines is far short of the needs for a pandemic vaccine. This is another reason why promotion of seasonal vaccination should be stimulated: It keeps production capacity up. Most of the world's production capacity is in Europe and many questions have been asked about how a vaccine would be distributed equitably in the event of a pandemic. Answers, like vaccine stocks, are in short supply. Apart from country-to-country distribution, there are also equitability questions at a national level. It is likely, but not guaranteed, that countries will decide that first responders and those responsible for essential services will receive priority. These are political decisions to be made nationally. During the months of vaccine production, approvals will need to be obtained from governments that the vaccines may be used there. In Europe and the US, discussions are already taking place about speeding up the normal regulatory process for such approvals. In the US, manufacturers are already citing its strict liability laws as a barrier to vaccine production. Huge investments are being made to move away from the old egg-based vaccine production to cell-based methods, but these will take years to bear fruit.

However, in the months before the first stocks of vaccine become available, the pandemic will be spreading around the world. Mathematical models indicate that closing borders and limiting flights will only slow down the spread, not eliminate it. In any case, international flights are essential if business is to continue providing products and services to people. Governments and businesses will also try to limit opportunities for people to congregate. Many can work from home, but essential services and manufacturing still need a physical presence at work. These people need transport. They can be provided with masks (while they are still available), they can be educated to wash their hands and so on, but people will still become infected.

Infected people can be physically isolated (although it is likely that they will be infectious long before they show symptoms) and treated with antivirals. The main antiviral that has been shown to be effective against the current strain of avian H5N1 is osteltamavir (Tamiflu). It is only effective if given within 48 hours of infection and its effectiveness against the mutated strain that will eventually trigger a pandemic is unknown. It is in short supply and governments around the world are queuing up to purchase stocks. The cost is prohibitive for many countries.

Who is doing what?

At the national level, governments around the world are drafting preparedness plans for use at national down to local levels. Currently in Europe, 49 out of 52 governments have completed plans, and the US published its plan in early November. These should be based on international guidelines (of the WHO, FAO, and OIE) where possible and tailored for national needs. It is the European Commission's view that there should be country-ownership of these plans if they are to work.

At the international level, the commission fully supports the work of the three most involved international organizations - the WHO, the FAO, and the OIE. Indeed, these organizations have been working on avian flu for decades and on a possible pandemic for many years. Much has already been done to provide advice and support to affected regions. Much more could be done, but it is often the case that the technical experts are limited by resources.

To this end we can only commend the organization by the US of a meeting of the International Partnership for (or is it against?) Avian and Pandemic Influenza last September. This effectively raised the political profile of this topic around the world. It was followed by International Ministerial meetings in Canada, Europe, and Asia.

Early in November, it was the subject of a major meeting in Geneva, convened by the WHO, FAO, OIE, and the World Bank. This meeting brought many sectors together at a high level to discuss global and national response strategies against avian flu and action plans as well as country needs assessments and financing gaps. It will be followed by a ministerial donors pledging conference in Beijing in mid-January 2006, co-sponsored by the Government of China, the European Commission, and the World Bank. The international donors' community will be invited to pledge support to national action plans of least developed countries affected or at risk of Avian Influenza. The principle of aid effectiveness requiring donors' harmonization and alignment (Paris Declaration - OECD-DAC) was recognized in Geneva. The Beijing conference will further examine the possibility of establishing common joint financing mechanisms.

The author, Canice Nolan, is first counselor and head of the Food Safety, Health, and Consumer Affairs Section at the Delegation of the European Commission in Washington DC.


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