The bird flu: are we ready for a pandemic?

"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."

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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 comfortable 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 implementing 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, under-funded, 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".

RELATED ARTICLE: Meeting on Avian and Human Pandemic Influenza

A global meeting, held in Geneva from 7 to 9 November 2005, discussed the urgent need of countries already affected by avian influenza and those most at risk for financial and other resources, as well as to identify and respond immediately to a human pandemic. Co-sponsored by WHO, FAO, the World Organisation for Animal Health and the World Bank, the meeting was attended by more than 600 delegates, including country representatives, donor partners and regional organizations, from over 100 countries. Key components of a global action plan were identified to control avian influenza in animals and limit the threat of a human influenza pandemic.

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RELATED ARTICLE: Influenza Pandemics: 'They are Natural Disasters'

"Pandemics of influenza are inevitable from time to time; like earthquakes or hurricanes, they are natural disasters", said Dr. Stephen Morse, Director of the Center for Public Health Preparedness at Columbia University's Mailman School of Public Health. These are not particularly comforting words when you consider the aftermath of Hurricane Katrina, a natural disaster that occurred in the world's wealthiest nation and, as acknowledged by United States President George Bush, "exposed serious problems in our response capability at all levels of Government".

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Dr. Morse told the UN Chronicle that the key to dealing with the threat of a pandemic is to be "systematically prepared". Although most Governments have a general outline of what would be required in the event of a pandemic, he said that "we're not there yet in terms of actually implementing them, and that's going to require political will and resources. If you have a pandemic, where many, many people are infected, even if the mortality rate is low, the infrastructure and the support systems of most societies are going to be very seriously compromised".

Health-care systems are in danger of being overwhelmed during a pandemic and Governments need to look at implementing procedures that address the medical needs of those infected, while at the same time "preventing them from passing it on to others", according to Dr. Morse. Once a country has a pandemic preparedness plan in place, it's important to test its feasibility. These simulations help people to learn to work together and "find the gaps in the plan so that they can improve their planning", he said. However, he acknowledged that if a pandemic were "to happen in the real world, things will be much messier and much less certain".

Dr. Morse believed that the SARS epidemic of 2003 gave the international community valuable experience working under the guidance of UN agencies like WHO and represented "a good example of some of the lessons we might have to learn on pandemic influenza". He welcomed the United Nations involvement, stating that avian influenza "is a global problem and therefore requires global resources and global solutions". He stressed that all countries needed to be prepared for the threat of avian flu, because if it turns pandemic it would be too late to prepare, as "the chicken would have already flown the coop".

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Vaccines, Antivirals and Other Interventions

** Contingency planning. Preparation will mitigate the direct medical and economic effects of an influenza pandemic by ensuring that adequate measures are taken and implemented before the outbreak. Preparing will also provide benefits now, as improvement in public health infrastructures can have immediate and lasting benefits and can mitigate the effects of other infectious disease epidemics.

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** Pandemic vaccine: A calculated bet on H5N1. Because the pandemic strain has not yet emerged, no vaccine is available yet. As a pandemic vaccine needs to be a close match to the actual virus, commercial production cannot begin prior to the emergence and characterization of the pandemic virus. WHO, through its network of specialized laboratories, has constantly monitored the evolution of the H5N1 since its initial human infection in 1997 in Hong Kong. These laboratories prepare the prototype vaccine strain provided to the industry as the "seed" for vaccine development. Several companies have begun work on a potential vaccine, using the WHO "seed" stock that is based on the H5N1 strain circulating in Viet Nam.

United States researchers in August 2005 announced preliminary results from an experimental pandemic vaccine that provoked a strong immune response in humans in a clinical trial. This development should cut the lead time needed to produce a vaccine to two to three months. The vaccine would only be effective if it is ultimately the H5N1 strain that provokes the pandemic and the strain has not significantly changed from that used to develop the vaccine. If the pandemic is caused by another avian influenza subtype, it is unlikely that the vaccine would offer much protection. Once the pandemic strain is identified, it would likely take at least six months to produce any significant quantities of the vaccine. WHO is urging the international community to find ways to increase manufacturing capacity and ensure that developing countries have access to an effective vaccine at an affordable price. Based on current trends, however, most developing countries will have no access to a vaccine during the first wave of a pandemic and perhaps throughout its duration.

** Antivirals: Buying time before the vaccine is available. There is currently only one class of antiviral that has been shown to be effective against all H5N1 human isolates from Asia: oseltamivir, known as Tamiflu, produced by Roche; and zanamivir, known as Relenza, which must be inhaled orally, by GlaxoSmithKline. In the event of a pandemic caused by an adopted version of H5N1, oseltamivir could potentially help slow its spread. WHO recommends that countries with the resources consider stockpiling antivirals. Roche has offered to provide WHO with an international stockpile of oseltamivir, which would treat people in greatest need at the site of an emerging pandemic in order to contain it. However, the strategy's success depends on several assumptions about the early behaviour of the pandemic virus and on the sensitive surveillance and logistics capacity in the initially affected areas, combined with an ability to regulate the movement of people in and out of the area.

** Non-medical health interventions: Other potential ways to stop the pandemic. At the start of a pandemic, all countries will face inadequate supplies of vaccines and antiviral drugs. Whether or not quarantine, isolation or travel recommendations will be useful depends largely on the characteristics of the virus, i.e. attack rate, virulence, age groups affected and modes of transmission.

** Social distancing: Reducing opportunities for exposure. This involves school and workplace closures, as well as avoiding mass gatherings at large conferences, public events and congregations, which may be necessary in helping to slow the pandemic's spread.

** Personal hygiene intervention measures. The role of personal hygiene may be important in reducing the spread of the disease during a pandemic. Populations should repeatedly be informed about the need for frequent hand-washing with soap and water, covering their mouth when coughing or sneezing, and careful disposal of used tissues. Mask-wearing may not have an appreciable impact on slowing transmission, but should be permitted as this is likely to occur spontaneously.

** Delaying the pandemic's arrival. Slowing the pandemic's arrival in other countries will be vital, as it would buy time to produce an effective vaccine and introduce other measures. Antivirals used intensively in an area where a pandemic is emerging, combined with other measures, such as quarantine and isolation, could help delay its spread. Countries will implement different measures while a vaccine is being produced. Although many of these measures will eventually fail, they may still have some public health impact in allowing time for countries to reinforce their response capacities and vaccinate certain target groups.

BY ERIKA REINHARDT

Source: WHO Handbook for Journalists: Influenza Pandemic

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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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RELATED ARTICLE: Videconference Series Explores Pandemic Containment

An interactive videoconference and discussion--"The Coming Avian Flu Pandemic: Its Scope and Consequences on a Global Society"--was held at Fairleigh Dickinson University (FDU) on 3 November 2005. It was the first collaborative event in a series between the United Nations Department of Public Information (DPI), FDU and the United Nations Association of the United States of America. The partnership seeks to develop a higher education outreach project, using videoconferencing as a communications and learning tool.

The panel focused on the some of the "practicalities" faced in the advent of an avian flu outbreak. It explored the uncertainties that have remained on the spread of the virus, including global preparedness, and discussed the need for a worldwide pandemic containment and eradication strategy. What emerged from the video-conference was a deeper understanding of the best practices in dealing with the pandemic and the necessity for knowledge-sharing among policy makers, universities and the public in order to prevent and contain the influenza virus.

Participants from the United Nations included, Richard Alderslade, Senior External Relations Officer, World Health Organization; moderator Ramu Damodaran, Chief of the Civil Society Service of the DPI Outreach Division; and Russell Taylor, editor of the UN Chronicle magazine, Educational Outreach Section. Ittiporn Boonpracong, Minister Counselor of the Permanent Mission of Thailand to the United Nations, was also a panellist, and Donald Zimmerman, Executive Director of the FDU Center for Healthcare Management Studies, served as host and facilitator. In addition to the audience at FDU, those at Western Michigan State University, Roger Williams University in Rhode Island, and World Vision International in California helped broaden the discussion through a question-and-answer session.

Fairleigh Dickinson University has been associated with the United Nations since 1945 and that relationship has deepened recently through partnerships with the Ambassador's Club at the United Nations and the UN Pathways Program. Each semester several ambassadors and diplomats visit FDU for lectures and discussions with students.

In 2002, FDU became one of only three universities in the United States to be associated with DPI as a non-governmental organization, bringing a wealth of programming and special access to the University's faculty and students. Future events will expand the interactive videoconference broadcasts from the United Nations via FDU to include colleges and universities nationwide and internationally.