UN Chronicle | THE BIRD FLU: ARE WE READY FOR A PANDEMIC?

THE BIRD FLU
ARE WE READY FOR A PANDEMIC?
By Jane Lloyd

Article

After dying of avian flu or being culled, chicken carcasses are burned at a farm in Long An province, near Ho Chi Minh City, Viet Nam. © FAO photo

“Every country we know, and every population, is at risk for pandemic influenza”, according to Dr. David Heymann, Assistant Director-General of the World Health Organization (WHO), at a special event on avian influenza (or bird flu) at UN Headquarters in New York on 3 November 2005. Experts from around the world discussed the threat that it poses to the global community, including strategies to combat the virus, with emphasis on UN involvement. “For a pandemic to start”, he said, “there had to be three conditions: that the virus has to be new to humans; it has to cause illness or death; and it has to spread easily from human to human. This virus has not yet reached that third necessity.”

The avian influenza virus (H5N1) can change and be transmitted between humans in two ways, Dr. Heymann said. First is through an “adaptive mutation process”, which takes place when a mutation of the virus conducive for human to human transmission occurs during the H5N1 reproduction process. Considering that the virus is, as described by WHO, “sloppy, capricious and promiscuous” and that the rate of reproduction is some 100,000 copies per hour, with each copy reproducing itself at the same rate, this type of mutation is not outside the realms of possibility.

The second and most likely way is through “re-assortment or recombination”, which happens when a person is infected simultaneously with both human and avian influenza viruses that find themselves in the same cell. Mutation occurs when both viruses reproduce and, “through an accident in their activities, combine genetic material and end up with a virus that can transmit easily from human to human from the human virus, but maintains its ability to cause serious illness from the animal virus”, said Dr. Heymann. Although it’s not possible to predict whether H5N1 will mutate to allow human transmission, he cautioned that “this virus, as influenza viruses are, is very unstable, it’s gradually changing”. So far, three pandemics have occurred when an avian influenza virus mutated or re-assorted with a human virus: in 1918, 1957 and 1968. The 1918 pandemic resulted in the deaths of 40 million people, comprising mostly 20- to 40-year-old healthy adults, with a mortality rate of just 2 per cent; the 1957 and 1968 pandemics caused the deaths of 4.5 million people.

H5N1 was first discovered in birds in 1996. In early 2004, hundreds of thousands of domestic poultry died in more than 10 Asian countries; in July 2005, the virus was found in China and Mongolia in wild migratory birds that are largely asymptomatic to the disease. The first identified case of human infection occurred in Hong Kong in 1997 when 18 people fell ill with H5N1, one third of them died. Human infections have since been reported in Cambodia, Indonesia and Viet Nam. To date, there are 122 people known to have been infected with the virus, of which 62 have died. Louise Fresco, Assistant Director-General of the Food and Agriculture Organization of the United Nations (FAO), said that the spread of avian flu into wild birds has resulted in the emergence of a “Eurasian epidemic”. This started when the infected birds from China and Mongolia arrived in the Western Siberian lowlands and met with wild migratory birds. The unique ability of H5N1 to persist in cold water “means that there is a continuous source of infection and allows the redistribution of this cold-tolerant virus into other birds and moving along different migratory pathways”, she said.

In a world linked by global travel, if the virus mutates to allow for human to human transmission, the result could be catastrophic. The Severe Acute Respiratory Syndrome (SARS) epidemic killed some 800 people, with an economic cost estimated at $30 billion. So far, avian influenza has cost the Asian poultry sector approximately $10 billion; its potential socio-economic impact has brought about the collaboration of many parties, including UN agencies, Member States, development banks, humanitarian agencies and private entities. “In a time when viruses start to cross boundaries, it’s important also that humankind starts to cross boundaries and that we come together in cultural, political and scientific matters”, Ms. Fresco said. The international community must “share virus strains and information on isolation as soon as possible”, she added.

WHO experts advised that although there had been some promising developments in the field of H5N1 vaccine research, there is no vaccine yet that they were comfort-able would be safe and effective in the event of a human pandemic. As influenza viruses are constantly changing, a vaccine developed too far ahead of the emergence of a pandemic may only offer partial protection. It is hoped that Tamiflu, the antiviral drug currently being used, would prove useful; however, to be effective it must be administered shortly after the patient starts showing symptoms. Tamiflu reduces the impact of infection and can also be used as a prophylactic to protect people exposed to infection.

The crossover of avian influenza has resulted in a unique collaboration between the World Organization for Animal Health (OIE), FAO and WHO, whose regional networks in the affected areas conduct research into the nature and spread of the virus, as well as provide technical assistance, such as diagnostics, vaccination and training. FAO and OIE are responsible for leading the United Nations campaign to eradicate H5N1 in animals. In April 2005, they launched the New Worldwide Avian Influenza Network, designed to improve their laboratories’ collaboration in researching H5N1 in animals, while the WHO laboratories research the virus in humans.

In September 2005, Dr. David Nabarro was appointed by Secretary-General Kofi Annan as the UN System Coordinator for Avian and Human Influenza, responsible for ensuring that the UN system makes an effective and coordinated contribution to the global effort to control the epidemic. The campaign against the spread of H5N1 is “very much an information management challenge”, Dr. Nabarro said. The UN strategy to combat avian influenza is two-pronged: to control its spread in animals and simultaneously prepare for a pandemic.

“FAO believes that eliminating avian influenza among poultry can delay or prevent the transformation of the H5N1 virus into a form that could create a human pandemic”, Ms. Fresco said. Although avian influenza in domestic birds “can be brought under control if the tools are available”, it would be impossible to do the same with its spread in wild birds, she added. Emphasis would go to tracking the migratory routes of birds and monitoring any subsequent spread of the disease.

FAO faces a considerable challenge, according to Ms. Fresco, considering that “the world poultry population now stands at a staggering 18 billion birds—three for every human on this earth”—and the fact that the poultry industry had enjoyed an average annual growth rate of 5 per cent over the last few decades and the magnitude of the task at hand became clearer. FAO estimates that if all countries at risk of H5N1 infection are actually affected, approximately $425 million will be needed over the next two years to combat the disease; so far, it has secured $30 million.

FAO has devised a three-step strategy to eliminate the H5N1 in poultry. The first is to implement bio-security measures at both farm and market levels, in order to change the way of life in Asia, where humans and animals mix freely in backyard farms, and animal slaughter takes place usually on the farm or in the marketplace. Such measures should also be taken in large-scale chicken farms, where poultry concentration heightens the risk of H5N1 spread. Ms. Fresco illustrated the risk, saying that “78 per cent of the global duck and geese population are encountered in China and Viet Nam, on what is less than 0.5 per cent of the world’s terrestrial surface”. She also said that “this incredible concentration of over 1 billion birds in a humid ecosystem has led to the possibility for the virus to circulate and create exposure to humans and domestic poultry”.

The second step is to improve H5N1 surveillance and detection, but this faces several challenges: one is ensuring that local authorities charged with surveillance in their area have the ability to perform effective field and laboratory work. In the last 18 months, FAO has conducted approximately 120 technical workshops and trained some 3,500 individuals from all over the world. Another challenge is the perceived shame countries feel when reporting an outbreak of avian influenza. This was illustrated in mid-2005 when doctors, bewildered over how the H5N1 virus had suddenly became immune to the human antiviral medicine amantadine, discovered that Chinese farmers had been using the drug to vaccinate its chickens.

To improve surveillance and detection of avian flu, FAO needs to ensure compensation to farmers who had their livestock culled due to H5N1 infection. Otherwise, these farmers may be tempted not to report cases, according to Ms. Fresco, as “those who are most affected in their livelihoods are poor countries and poor communities”. Munir Akram of Pakistan, President of the UN Economic and Social Council that hosted the November special event on avian influenza, called for donors and financial institutions to consider setting up a fund to compensate farmers for losses incurred in culling infected bird stock.

The third and final step involves utilizing effective culling and vaccination methods in instances when the disease is detected. Although vaccinations have proven to be highly effective against the spread of avian influenza, Ms. Fresco said that more research is required to look at “ways to administer the vaccine in another way than we do today”, as injections are “difficult to manage at farm level in some areas”. Individual countries are also playing a part in controlling the spread of the avian flu. For example, Thailand now requires passports for fighting cocks, in order to track their movement throughout the country, even though a nationwide ban on cock fighting is already in place. These birds undergo mandatory testing for H5N1 every two months, and the results are entered in their passports.

WHO has formulated a five-step plan to monitor human cases of H5N1 infection and ensure global preparedness in the event of a human influenza pandemic:

Reduce the risk of the emergence of a pandemic by reducing the opportunities for H5N1 to mutate. One way to do this is to vaccinate people who are at risk of H5N1 exposure. Dr. Heymann said that if a person is protected against the human influenza virus and “the H5N1 virus enters that person, it will not be able to recombine or re-assort with that virus and pick up human transmittability”. The ability of the influenza viruses to mutate in this way is illustrated in the Chinese province of Guandong, which has a long history of human and poultry cohabitation and has been dubbed “the birthplace of the flu”, where it is believed at least two of the last three influenza pandemics originated.

Ensure that countries have preparedness plans in place. WHO has provided guidance, outlining what countries should do in the event of a human influenza pandemic; to date, over 40 countries have developed sound pandemic plans.

Improve the speed and sensitivity of surveillance of H5N1 in humans. Dr. Heymann stressed that “we need capacity to do field investigations when humans become infected”. However, there are problems with implement-ing this plan. Some people, because of their religious or cultural beliefs, do not allow autopsies on loved ones who are thought to have died of avian influenza, and thus removing an important diagnostic tool for WHO. Also, limited country infrastructure can hamper the speed and sensitivity of H5N1 surveillance. For example, scientists from Phnom Penh in Cambodia had to wait until WHO had shipped dry ice from Bangkok, Thailand, before they could send tissue samples of a suspected H5N1 case to Paris for analysis.

Ensure that everyone knows what to do in cases of avian influenza. Dr. Heymann said that communication between WHO and the international community is “important at the time that the world is gearing up in case there is a pandemic”, and also during a pandemic, “so that people would understand how they can protect themselves and how they can best deal with the situation”.

Put additional resources into vaccine development, as vaccination is the surest way of preventing and controlling a pandemic once it starts, according to Dr. Heymann. The global production capacity of flu vaccines stands at 300 million doses per year, but this is not enough, he said. There is no financial incentive for manufacturers to mass produce these vaccines if there is a pandemic, as profit margins per vaccine are so low. Several countries like Australia have advance contracts in place with vaccine manufacturers that will take effect if there is a pandemic.

Another problem facing WHO is the amount of time it takes to develop a vaccine, Dr. Heymann stressed, saying that “the lead time between the emergence of a virus and the production of vaccine must be as short as possible in order to minimize the pandemic’s impact”. Vaccine production methods involve using fertilized chicken eggs to breed the virus from which key proteins or antigens are then extracted; however, this is a long and complicated process and takes a minimum of six to nine months. In the absence of a vaccine, there is a “great potential in Tamiflu and it is being stockpiled”, Dr. Heymann said. Based on current trends, it would take its Swiss pharmaceutical manufacturer, Roche, about a decade to produce enough Tamiflu to cover 20 per cent of the global population. WHO recommends that Governments preparing for a pandemic stock up enough of the drug for at least 25 per cent of their population. Currently, there is a global shortage and in October 2005 Roche announced record share prices due to increased demand for Tamiflu.

A pandemic would “cause many, many people to be ill, lose work and not be able to function properly in a society that depends on human interaction”, Dr. Heymann said. As it has the potential to impact on many facets of a country’s operations, formulation of a pandemic preparedness plans often involve the collaboration of different government agencies. FAO and WHO are the two main UN bodies providing guidance to Governments on these plans. If required, the United Nations will dispatch a task team of experts to assist in a country’s response. The United Nations Development Programme will provide assistance on how to support national processes and advice on risk assessment and management. If the risk of a pandemic is imminent, the UN Humanitarian Coordinator, along with inter-agency humanitarian teams within the country, will be poised for action. The Office of the UN High Commissioner for Refugees, the United Nations Population Fund and the United Nations Children’s Fund will ensure that focus groups are adequately provided to respond to the pandemic.

Avian influenza “underlines the extent to which we have all become interdependent in a globalized world”, said Jan Eliasson, President of the sixtieth General Assembly. “Suddenly overstretched, underfunded, ill-equipped and understaffed, health services in some of the poorest countries in the world are no longer just the concern of those countries, or of donor agencies with an altruistic mission, they must be a concern for all our people”.

The virus H5N1 is considered to be highly pathogenic. Avian and human influenzas belong to the “A strain” virus that includes the common human viruses known as H1N1, H2N2 and H3N2, which reproduce themselves in animals and human cells, and attack the respiratory system. Those infected with H5N1 start showing varying symptoms within 48 hours, such as fever, coughing, muscle ache, diarrhoea, vomiting and abdominal pain. Lung failure is listed as the leading cause of death for half of the known human fatalities. People risk H5N1 infection when they come in contact with a sick bird’s nasal secretion, saliva or faeces. If avian influenza becomes pandemic, it is expected that it would pick up human transmission mechanisms, such as through coughing, sneezing and kissing.

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