Chapter VIII. Questions and Answers About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus

Avian Influenza

How is avian influenza detected in humans?

Avian influenza cannot be diagnosed by symptoms alone, so a laboratory test is required. Avian influenza is usually diagnosed by collecting a swab from the nose or throat during the first few days of illness. This swab is then sent to a laboratory, where they will either look for avian influenza virus using a molecular test, or they will try to grow the virus. Growing avian influenza viruses should only be done in laboratories with high levels of protection. If it is late in the illness, it may be difficult to find an avian influenza virus directly using these methods. If this is the case, it may still be possible to diagnose avian influenza by looking for evidence of the body's response to the virus. This is not always an option because it requires two blood specimens (one taken during the first few days of illness and another taken some weeks later), and it can take several weeks to verify the results.

What are the implications of avian influenza to human health?

Two main risks for human health from avian influenza are

1) the risk of direct infection when the virus passes from the infected bird to humans, sometimes resulting in severe disease; and

2) the risk that the virus, if given enough opportunities,will change into a form that is highly infectious for humans and spreads easily from person to person.

How is avian influenza in humans treated?

Studies done in laboratories suggest that the preblockedion medicines approved for human influenza viruses should work in treating avian influenza infection in humans. However, influenza viruses can become resistant to these drugs, so these medications may not always work. Additional studies are needed to determine the effectiveness of these medicines.

Does seasonal influenza vaccine protect against avian influenza infection in people?

No. Seasonal influenza vaccine does not provide protection against avian influenza.

Should I wear a surgical mask to prevent exposure to avian influenza?

Currently, wearing a mask is not recommended for routine use (e.g., in public) for preventing influenza exposure. In the United States, disposable surgical and procedure masks have been widely used in health-care settings to prevent exposure to respiratory infections, but the masks have not been used commonly in community settings, such as schools, businesses, and public gatherings.

Can I get avian influenza from eating or preparing poultry or eggs?

You cannot get avian influenza from properly handled and cooked poultry and eggs.
There currently is no scientific evidence that people have been infected with bird flu by eating safely handled and properly cooked poultry or eggs.

Most cases of avian influenza infection in humans have resulted from direct or close contact with infected poultry or surfaces contaminated with secretions and excretions from infected birds. Even if poultry and eggs were to be contaminated with the virus, proper cooking would kill it. In fact, recent studies have shown that the cooking methods that are already recommended by the U.S. Department of Agriculture (USDA) and the Food and Drug Administration (FDA) for poultry and eggs to prevent other infections will destroy influenza viruses as well.

So to stay safe, the advice is the same for protecting against any infection from poultry:

• Wash your hands with soap and warm water for at least 20 seconds before and after handling raw poultry and eggs.
• Clean cutting boards and other utensils with soap and hot water to keep raw poultry from contaminating other foods.
• Use a food thermometer to make sure you cook poultry to a temperature of at least 165 degrees Fahrenheit Consumers may wish to cook poultry to a higher temperature for personal preference.
• Cook eggs until whites and yolks are firm.

The U.S. government carefully controls domestic and imported food products, and in 2004 issued a ban on importation of poultry from countries affected by avian influenza viruses, including the H5N1 strain. This ban still is in place. For more information, see Embargo of Birds from Specified Countries.

We have a small flock of chickens. Is it safe to keep them?

Yes. In the United States there is no need at present to remove a flock of chickens because of concerns regarding avian influenza. The U.S. Department of Agriculture monitors potential infection of poultry and poultry products by avian influenza viruses and other infectious disease agents.

For additional information about avian influenza visit pandemicflu.gov.

Avian Influenza A (H5N1)

What is the avian influenza A (H5N1) virus that has been reported in Africa, Asia, Europe, and the Near East?

Influenza A (H5N1) virus , also called "H5N1 virus", is an influenza A virus subtype that occurs mainly in birds, is highly contagious among birds, and can be deadly to them.

Outbreaks of avian influenza H5N1 occurred among poultry in eight countries in Asia (Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Vietnam) during late 2003 and early 2004. At that time, more than 100 million birds in the affected countries either died from the disease or were killed in order to try to control the outbreaks. By March 2004, the outbreak was reported to be under control.

Beginning in June 2004, however, new outbreaks of influenza H5N1 among poultry and wild birds were reported in Asia. Since that time, the virus has spread geographically. Reports of H5N1 infection in wild birds in Europe began in mid-2005. In early 2006, influenza A H5N1 infection in wild birds and poultry were reported in Africa and the Near East.

Human cases of influenza A (H5N1) infection have been reported in Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey, and Vietnam. For the most current information about avian influenza and cumulative case numbers, see the World Health Organization Avian Influenza website.

What are the risks to humans from the current H5N1 outbreak?

H5N1 virus does not usually infect people, but more than 200 human cases have been reported. Most of these cases have occurred from direct or close contact with infected poultry or contaminated surfaces; however, a few cases of human-to-human spread of H5N1 virus have occurred.

So far, spread of H5N1 virus from person to person has been rare and has not continued beyond one person. Nonetheless, because all influenza viruses have the ability to change, scientists are concerned that H5N1 virus one day could be able to infect humans and spread easily from one person to another. Because these viruses do not commonly infect humans, there is little or no immune protection against them in the human population.

If H5N1 virus were to gain the capacity to spread easily from person to person, an influenza pandemic (worldwide outbreak of disease) could begin. No one can predict when a pandemic might occur. However, experts from around the world are watching the H5N1 situation in Asia and Europe very closely and are preparing for the possibility that the virus may begin to spread more easily from person to person.

How is infection with H5N1 virus in humans treated?

Most H5N1 viruses that have caused human illness and death appear to be resistant to amantadine and rimantadine, two antiviral medications commonly used for treatment of patients with influenza. Two other antiviral medications, oseltamivir and zanamavir, would probably work to treat influenza caused by H5N1 virus, but additional studies are needed to demonstrate their current and ongoing effectiveness.

Is there a vaccine to protect humans from H5N1 virus?

There currently is no commercially available vaccine to protect humans against the H5N1 virus that is being detected in Asia and Europe. However, vaccine development efforts are taking place. Research studies to test a vaccine that will protect humans against H5N1 virus began in April 2005, and a series of clinical trials is under way. For more information about the H5N1 vaccine development process, visit the National Institutes of Health website.

Updated June 30

What does CDC recommend regarding H5N1 virus?

In February 2004, CDC provided U.S. public health departments with recommendations for enhanced surveillance ('detection') of H5N1 influenza in the country. Follow-up messages, distributed via the Health Alert Network, were sent to the health departments on August 12, 2004, February 4, 2005, and June 7, 2006; all three notices reminded public health departments about recommendations for detecting (domestic surveillance), diagnosing, and preventing the spread of H5N1 virus. The notices also recommended measures for laboratory testing for H5N1 virus. To read these notices, visit Health Updates on Avian Influenza.

Does CDC recommend travel restrictions to areas with known H5N1 outbreaks?

CDC does not recommend any travel restrictions to affected countries at this time. However, CDC currently advises that travelers to countries with known outbreaks of H5N1 influenza avoid poultry farms, contact with animals in live food markets, and any surfaces that appear to be contaminated with feces from poultry or other animals. For more information, visit Travelers' Health.

Is there a risk in handling feather products that come from countries experiencing outbreaks of avian influenza A (H5N1)?

The U.S. government has determined that there is a risk to handling feather products from countries experiencing outbreaks of H5N1 influenza.

There is currently a ban on the importation of birds and bird products from H5N1-affected countries in Africa, Asia, and Europe. The regulation states that no person may import or attempt to import any birds (Class Aves), whether dead or alive, or any products derived from birds (including hatching eggs), from the specied countries (see Embargo of Birds from Specified Countries). This prohibition does not apply to any person who imports or attempts to import products derived from birds if, as determined by federal officials, such products have been properly processed to render them noninfectious so that they pose no risk of transmitting or carrying H5Nl and which comply with the U.S. Department of Agriculture (USDA) requirements. Therefore, feathers from these countries are banned unless they have been processed to render them noninfectious.Additional information about the import ban is available on the USDA website.

Is there a risk to importing pet birds that come from countries experiencing outbreaks of avian influenza A (H5N1)?

The U.S. government has determined that there is a risk to importing pet birds from countries experiencing outbreaks of H5N1 influenza. CDC and USDA have both taken action to ban the importation of birds from areas where H5N1 has been documented. There is currently a ban on the importation of birds and bird products from H5N1-affected countries in Africa, Asia, and Europe. The regulation states that no person may import or attempt to import any birds (Class Aves), whether dead or alive, or any products derived from birds (including hatching eggs), from the specified countries (see Embargo of Birds from Specified Countries).

Can a person become infected with avian influenza A (H5N1) virus by cleaning a bird feeder?

There is no evidence of H5N1 having caused disease in birds or people in the United States. At the present time, there is no risk of becoming infected with H5N1 virus from bird feeders. Generally, perching birds (Passeriformes) are the predominate type of birds at feeders. While there are documented cases of H5N1 causing death in some Passeriformes (e.g., house sparrow, Eurasian tree-sparrow, house finch), in both free-ranging and experimental settings, none occurred in the U.S. and most of the wild birds that are traditionally associated with avian influenza viruses are waterfowl and shore birds.

Influenza Pandemic Preparedness

What changes are needed for H5N1 or another avian influenza virus to cause a pandemic?

Three conditions must be met for a pandemic to start: 1) a new influenza virus subtype must emerge for which there is little or no human immunity; 2) it must infect humans and causes illness; and 3) it must spread easily and sustainably (continue without interruption) among humans. The H5N1 virus in Asia and Europe meets the first two conditions: it is a new virus for humans (H5N1 viruses have never circulated widely among people), and it has infected more than 190 humans, killing over half of them.

However, the third condition, the establishment of efficient and sustained human-to-human transmission of the virus, has not occurred. For this to take place, the H5N1 virus would need to improve its transmissibility among humans. This could occur either by 'reassortment' or adaptive mutation.

Reassortment occurs when genetic material is exchanged between human and avian viruses during co-infection (infection with both viruses at the same time) of a human or another mammal. The result could be a fully transmissible pandemic virus-that is, a virus that can spread easily and directly between humans. A more gradual process is adaptive mutation, where the capability of a virus to bind to human cells increases during infections of humans.

What is CDC doing to prepare for a possible H5N1 influenza pandemic?

CDC is taking part in a number of pandemic prevention and preparedness activities, including the following:

• Providing leadership to the National Pandemic Influenza Preparedness and Response Task Force, created in May 2005 by the Secretary of the U.S. Department of Health and Human Services.
• Working with the Association of Public Health Laboratories on training workshops for state laboratories on the use of special laboratory (molecular) techniques to identify H5 viruses.
• Working with the Council of State and Territorial Epidemiologists and others to help states with their pandemic planning efforts.
• Working with other agencies, such as the Department of Defense and the Veterans Administration, on antiviral stockpile issues.
• Working with the World Health Organization (WHO) to investigate influenza H5N1 among people (e.g., in Vietnam) and to provide help in laboratory diagnostics and training to local authorities.
• Performing laboratory testing of H5N1 viruses.
• Starting a $5.5 million initiative to improve influenza surveillance in Asia.
• Holding or taking part in training sessions to improve local capacities to conduct surveillance for possible human cases of H5N1 and to detect influenza A H5 viruses by using laboratory techniques.
• Developing and distributing reagent kits to detect the currently circulating influenza A H5N1 viruses.
• CDC has developed and is distributing the first FDA approved test for the detection of the H5 viruses that first emerged in Asia in 2003.

CDC also is working closely with WHO and the National Institutes of Health on safety testing of vaccine candidates and development of additional vaccine virus seed candidates for influenza A (H5N1) and other subtypes of influenza A viruses. Avian Influenza Infection in Animals

What animals can be infected with avian influenza A (H5N1) viruses?

In addition to humans and birds, we know that pigs, tigers, leopards, ferrets, and domestic cats can be infected with avian influenza A (H5N1) viruses. In addition, in early March 2006, Germany reported H5N1 infection in a stone marten (a weasel-like mammal). The avian influenza A (H5N1) virus that emerged in Asia in 2003 is evolving and it's possible that other mammals may be susceptible to infection as well. CDC is working closely with domestic and international partners to continually monitor this situation and will provide additional information to the public as it becomes available.

Can domestic cats be infected with avian influenza viruses?

While domestic cats are not usually susceptible to influenza type A infection, it is known that they can become infected and die (both experimentally and naturally) with avian influenza A (H5N1) viruses and, in a laboratory/research setting can spread the virus to other cats. It is not known whether domestic cats can spread the virus to other domestic cats under natural conditions.

How do cats become infected with avian influenza A (H5N1) viruses?

All of the cases of influenza A (H5N1) infection in domestic cats reported to date have been associated with H5N1 outbreaks among domestic poultry or wild birds and are thought to have occurred by the cat eating raw infected birds.

How commonly have cats been infected with avian influenza A (H5N1) viruses?

During the avian influenza A (H5N1) outbreak that occurred from 2003 to 2004 in Asia, there were only several unofficial reports of fatal infections in domestic cats. Studies carried out in the Netherlands and published in 2004 showed that housecats could be infected with avian influenza A (H5N1) and could spread the virus to other housecats. In these experiments, the cats became sick after direct inoculation of virus isolated from a fatal human case, and following the feeding of infected raw chicken. In February 2006, Germany reported that a domestic cat had died from influenza A (H5N1) infection. That cat lived in the northern island of Ruegen, where more than 100 wild birds are believed to have died of the disease. The cat probably got sick by eating an infected bird.

What about infection in large cats, like tigers?

Large cats kept in captivity have been diagnosed with avian influenza as well. In December 2003, two tigers and two leopards that were fed fresh chicken carcasses from a local slaughterhouse died at a zoo in Thailand. An investigation identified avian influenza A (H5N1) in tissue samples. In February and March 2004, the virus was detected in a clouded leopard and white tiger, respectively, both of which died in a zoo near Bangkok . In October 2004, 147 of 441 captive tigers in a zoo in Thailand died or were euthanatized as a result of infection after being fed fresh chicken carcasses. The cats are thought to have gotten sick from eating infected raw meat. Results of a subsequent investigation suggested that at least some tiger-to-tiger transmission occurred in that facility.

Can cats spread H5N1 to people?

There is no evidence to date that cats can spread H5N1 to humans. No cases of avian influenza in humans have been linked to exposure to sick cats, and no outbreaks among populations of cats have been reported. All of the influenza A (H5N1) infections in cats reported to date appear to have been associated with outbreaks in domestic or wild birds and acquired through ingestion of raw meat from an infected bird.

What is the risk to humans or other species from cats infected with avian influenza H5N1 virus?

There is no evidence to date that cats can spread H5N1 to humans. No cases of avian influenza in humans have been linked to exposure to sick cats, and no outbreaks among populations of cats have been reported. All of the influenza A (H5N1) infections in cats reported to date appear to have been associated with outbreaks in domestic or wild birds and acquired through ingestion of raw infected meat.

What is the current risk that a cat in the United States will become infected with influenza A (H5N1)?

As long as there is no influenza A (H5N1) in the United States, there is no risk of a U.S. cat becoming infected with this disease. The virus circulating in Asia, Europe and Africa has not yet entered the United States. CDC is working closely with domestic and international partners to continually monitor this situation and will provide additional information to the public as it becomes available.

If avian influenza A (H5N1) is identified in the United States, how can I protect my cat?

As long as there is no H5N1 influenza in the United States, at this time there is no risk of a U.S. cat becoming infected with this disease. In Europe, however, where H5N1 has been reported in wild birds, poultry, several cats, and a stone marten (a member of the weasel family), the European Center for Disease Prevention and Control has issued preliminary recommendations for cat owners living in H5N1-affected areas. Additionally, the Food and Agriculture Organization has produced guidance for areas where H5N1 HPAI has been diagnosed or is suspected in poultry or wild birds.

Where can I find out more information about avian influenza infection in cats?

For more information about avian influenza in cats, see Avian influenza Frequently asked questions (from the American Veterinary Medical Association) and H5N1 in Cats (from the Food and Agriculture Organization of the United Nations).

Cans dogs be infected with avian influenza?

While dogs are not usually susceptible to avian influenza viruses, the avian influenza A (H5N1) virus that emerged in Asia in 2003 has been documented to infect other carnivore species (e.g. cats, tigers, leopards, stone martens). This has raised concern that this strain of avian influenza A (H5N1) virus may be capable of infecting dogs. An unpublished study carried out in 2005 by the National Institute of Animal Health in Bangkok indicated that dogs could be infected with the virus, but no associated disease was detected. This limited information is not enough to determine definitively whether dogs are susceptible to the virus. CDC is coordinating with USDA, veterinary associations, and other partners domestically and internationally on this issue and will provide additional information to the public as it becomes available.

How would dogs be infected with avian influenza A (H5N1)?

There is not enough information available about avian influenza A (H5N1) infection in dogs to know how infection would occur. Affected domestic cats in Europe appear to have become infected by feeding upon raw infected poultry or wild birds. If dogs are susceptible to avian influenza A (H5N1), infection may be by the same route.

What is the current risk that a dog in the United States will become infected with avian influenza A (H5N1)?

As long as there is no influenza A (H5N1) in the United States, there is no risk of a U.S. dog becoming infected with this disease. The virus circulating in Asia, Europe and Africa has not yet entered the United States. CDC is working closely with domestic and international partners to continually monitor this situation and will provide additional information to the public as it becomes available.

B.World Health Organization: Frequently Asked Questions

What is avian influenza?

Avian influenza, or "bird flu", is a contagious disease of animals caused by viruses that normally infect only birds and, less commonly, pigs. Avian influenza viruses are highly species-specific, but have, on rare occasions, crossed the species barrier to infect humans.

In domestic poultry, infection with avian influenza viruses causes two main forms of disease, distinguished by low and high extremes of virulence. The so-called "low pathogenic" form commonly causes only mild symptoms (ruffled feathers, a drop in egg production) and may easily go undetected. The highly pathogenic form is far more dramatic. It spreads very rapidly through poultry flocks, causes disease affecting multiple internal organs, and has a mortality that can approach 100%, often within 48 hours.

Which viruses cause highly pathogenic disease?

Influenza A viruses¹ have 16 H subtypes and 9 N subtypes ². Only viruses of the H5 and H7 subtypes are known to cause the highly pathogenic form of the disease. However, not all viruses of the H5 and H7 subtypes are highly pathogenic and not all will cause severe disease in poultry.

On present understanding, H5 and H7 viruses are introduced to poultry flocks in their low pathogenic form. When allowed to circulate in poultry populations, the viruses can mutate, usually within a few months, into the highly pathogenic form. This is why the presence of an H5 or H7 virus in poultry is always cause for concern, even when the initial signs of infection are mild.

Do migratory birds spread highly pathogenic avian influenza viruses?

The role of migratory birds in the spread of highly pathogenic avian influenza is not fully understood. Wild waterfowl are considered the natural reservoir of all influenza A viruses. They have probably carried influenza viruses, with no apparent harm, for centuries. They are known to carry viruses of the H5 and H7 subtypes, but usually in the low pathogenic form. Considerable circumstantial evidence suggests that migratory birds can introduce low pathogenic H5 and H7 viruses to poultry flocks, which then mutate to the highly pathogenic form.

In the past, highly pathogenic viruses have been isolated from migratory birds on very rare occasions involving a few birds, usually found dead within the flight range of a poultry outbreak. This finding long suggested that wild waterfowl are not agents for the onward transmission of these viruses.

Recent events make it likely that some migratory birds are now directly spreading the H5N1 virus in its highly pathogenic form. Further spread to new areas is expected.

What is special about the current outbreaks in poultry?

The current outbreaks of highly pathogenic avian influenza, which began in South-East Asia in mid-2003, are the largest and most severe on record. Never before in the history of this disease have so many countries been simultaneously affected, resulting in the loss of so many birds.

The causative agent, the H5N1 virus, has proved to be especially tenacious. Despite the death or destruction of an estimated 150 million birds, the virus is now considered endemic in many parts of Indonesia and Viet Nam and in some parts of Cambodia, China, Thailand, and possibly also the Lao People's Democratic Republic. Control of the disease in poultry is expected to take several years.

The H5N1 virus is also of particular concern for human health, as explained below.

Which countries have been affected by outbreaks in poultry?

From mid-December 2003 through early February 2004, poultry outbreaks caused by the H5N1 virus were reported in eight Asian nations (listed in order of reporting): the Republic of Korea, Viet Nam, Japan, Thailand, Cambodia, Lao People's Democratic Republic, Indonesia, and China. Most of these countries had never before experienced an outbreak of highly pathogenic avian influenza in their histories.

In early August 2004, Malaysia reported its first outbreak of H5N1 in poultry, becoming the ninth Asian nation affected. Russia reported its first H5N1 outbreak in poultry in late July 2005, followed by reports of disease in adjacent parts of Kazakhstan in early August. Deaths of wild birds from highly pathogenic H5N1 were reported in both countries. Almost simultaneously, Mongolia reported the detection of H5N1 in dead migratory birds. In October 2005, H5N1 was confirmed in poultry in Turkey and Romania. Outbreaks in wild and domestic birds are under investigation elsewhere.

Japan, the Republic of Korea, and Malaysia have announced control of their poultry outbreaks and are now considered free of the disease. In the other affected areas, outbreaks are continuing with varying degrees of severity.

What are the implications for human health?

The widespread persistence of H5N1 in poultry populations poses two main risks for human health.

The first is the risk of direct infection when the virus passes from poultry to humans, resulting in very severe disease. Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 has caused the largest number of cases of severe disease and death in humans. Unlike normal seasonal influenza, where infection causes only mild respiratory symptoms in most people, the disease caused by H5N1 follows an unusually aggressive clinical course, with rapid deterioration and high fatality. Primary viral pneumonia and multi-organ failure are common. In the present outbreak, more than half of those infected with the virus have died. Most cases have occurred in previously healthy children and young adults. A second risk, of even greater concern, is that the virus - if given enough opportunities - will change into a form that is highly infectious for humans and spreads easily from person to person. Such a change could mark the start of a global outbreak (a pandemic).

Where have human cases occurred?

In the current outbreak, laboratory-confirmed human cases have been reported in four countries: Cambodia, Indonesia, Thailand, and Viet Nam.

Hong Kong has experienced two outbreaks in the past. In 1997, in the first recorded instance of human infection with H5N1, the virus infected 18 people and killed 6 of them. In early 2003, the virus caused two infections, with one death, in a Hong Kong family with a recent travel history to southern China.

How do people become infected?

Direct contact with infected poultry, or surfaces and objects contaminated by their faeces, is presently considered the main route of human infection. To date, most human cases have occurred in rural or periurban areas where many households keep small poultry flocks, which often roam freely, sometimes entering homes or sharing outdoor areas where children play. As infected birds shed large quantities of virus in their faeces, opportunities for exposure to infected droppings or to environments contaminated by the virus are abundant under such conditions. Moreover, because many households in Asia depend on poultry for income and food, many families sell or slaughter and consume birds when signs of illness appear in a flock, and this practice has proved difficult to change. Exposure is considered most likely during slaughter, defeathering, butchering, and preparation of poultry for cooking.

Is it safe to eat poultry and poultry products?

Yes, though certain precautions should be followed in countries currently experiencing outbreaks. In areas free of the disease, poultry and poultry products can be prepared and consumed as usual (following good hygienic practices and proper cooking), with no fear of acquiring infection with the H5N1 virus.

In areas experiencing outbreaks, poultry and poultry products can also be safely consumed provided these items are properly cooked and properly handled during food preparation. The H5N1 virus is sensitive to heat. Normal temperatures used for cooking (70oC in all parts of the food) will kill the virus. Consumers need to be sure that all parts of the poultry are fully cooked (no 'pink' parts) and that eggs, too, are properly cooked (no 'runny' yolks).

Consumers should also be aware of the risk of cross-contamination. Juices from raw poultry and poultry products should never be allowed, during food preparation, to touch or mix with items eaten raw. When handling raw poultry or raw poultry products, persons involved in food preparation should wash their hands thoroughly and clean and disinfect surfaces in contact with the poultry products Soap and hot water are sufficient for this purpose.

In areas experiencing outbreaks in poultry, raw eggs should not be used in foods that will not be further heat-treated as, for example by cooking or baking.

Avian influenza is not transmitted through cooked food. To date, no evidence indicates that anyone has become infected following the consumption of properly cooked poultry or poultry products, even when these foods were contaminated with the H5N1 virus.

Does the virus spread easily from birds to humans?

No. Though more than 100 human cases have occurred in the current outbreak, this is a small number compared with the huge number of birds affected and the numerous associated opportunities for human exposure, especially in areas where backyard flocks are common. It is not presently understood why some people, and not others, become infected following similar exposures.

What about the pandemic risk?

A pandemic can start when three conditions have been met: a new influenza virus subtype emerges; it infects humans, causing serious illness; and it spreads easily and sustainably among humans. The H5N1 virus amply meets the first two conditions: it is a new virus for humans (H5N1 viruses have never circulated widely among people), and it has infected more than 100 humans, killing over half of them. No one will have immunity should an H5N1-like pandemic virus emerge.

All prerequisites for the start of a pandemic have therefore been met save one: the establishment of efficient and sustained human-to-human transmission of the virus. The risk that the H5N1 virus will acquire this ability will persist as long as opportunities for human infections occur. These opportunities, in turn, will persist as long as the virus continues to circulate in birds, and this situation could endure for some years to come.

What changes are needed for H5N1 to become a pandemic virus?

The virus can improve its transmissibility among humans via two principal mechanisms. The first is a 'reassortment' event, in which genetic material is exchanged between human and avian viruses during co-infection of a human or pig. Reassortment could result in a fully transmissible pandemic virus, announced by a sudden surge of cases with explosive spread.

The second mechanism is a more gradual process of adaptive mutation, whereby the capability of the virus to bind to human cells increases during subsequent infections of humans. Adaptive mutation, expressed initially as small clusters of human cases with some evidence of human-to-human transmission, would probably give the world some time to take defensive action.

What is the significance of limited human-to-human transmission?

Though rare, instances of limited human-to-human transmission of H5N1 and other avian influenza viruses have occurred in association with outbreaks in poultry and should not be a cause for alarm. In no instance has the virus spread beyond a first generation of close contacts or caused illness in the general community. Data from these incidents suggest that transmission requires very close contact with an ill person. Such incidents must be thoroughly investigated but - provided the investigation indicates that transmission from person to person is very limited - such incidents will not change the WHO overall assessment of the pandemic risk. There have been a number of instances of avian influenza infection occurring among close family members. It is often impossible to determine if human-to-human transmission has occurred since the family members are exposed to the same animal and environmental sources as well as to one another.

How serious is the current pandemic risk?

The risk of pandemic influenza is serious. With the H5N1 virus now firmly entrenched in large parts of Asia, the risk that more human cases will occur will persist. Each additional human case gives the virus an opportunity to improve its transmissibility in humans, and thus develop into a pandemic strain. The recent spread of the virus to poultry and wild birds in new areas further broadens opportunities for human cases to occur. While neither the timing nor the severity of the next pandemic can be predicted, the probability that a pandemic will occur has increased.

Are there any other causes for concern?

Yes. Several.

1. Domestic ducks can now excrete large quantities of highly pathogenic virus without showing signs of illness, and are now acting as a 'silent' reservoir of the virus, perpetuating transmission to other birds. This adds yet another layer of complexity to control efforts and removes the warning signal for humans to avoid risky behaviours.

2. When compared with H5N1 viruses from 1997 and early 2004, H5N1 viruses now circulating are more lethal to experimentally infected mice and to ferrets (a mammalian model) and survive longer in the environment.

3. H5N1 appears to have expanded its host range, infecting and killing mammalian species previously considered resistant to infection with avian influenza viruses.

4. The behaviour of the virus in its natural reservoir, wild waterfowl, may be changing. The spring 2005 die-off of upwards of 6,000 migratory birds at a nature reserve in central China, caused by highly pathogenic H5N1, was highly unusual and probably unprecedented. In the past, only two large die-offs in migratory birds, caused by highly pathogenic viruses, are known to have occurred: in South Africa in 1961 (H5N3) and in Hong Kong in the winter of 2002-2003 (H5N1).

Why are pandemics such dreaded events?

Influenza pandemics are remarkable events that can rapidly infect virtually all countries. Once international spread begins, pandemics are considered unstoppable, caused as they are by a virus that spreads very rapidly by coughing or sneezing. The fact that infected people can shed virus before symptoms appear adds to the risk of international spread via asymptomatic air travellers.

The severity of disease and the number of deaths caused by a pandemic virus vary greatly, and cannot be known prior to the emergence of the virus. During past pandemics, attack rates reached 25-35% of the total population. Under the best circumstances, assuming that the new virus causes mild disease, the world could still experience an estimated 2 million to 7.4 million deaths (projected from data obtained during the 1957 pandemic). Projections for a more virulent virus are much higher. The 1918 pandemic, which was exceptional, killed at least 40 million people. In the USA, the mortality rate during that pandemic was around 2.5%.

Pandemics can cause large surges in the numbers of people requiring or seeking medical or hospital treatment, temporarily overwhelming health services. High rates of worker absenteeism can also interrupt other essential services, such as law enforcement, transportation, and communications. Because populations will be fully susceptible to an H5N1-like virus, rates of illness could peak fairly rapidly within a given community. This means that local social and economic disruptions may be temporary. They may, however, be amplified in today's closely interrelated and interdependent systems of trade and commerce. Based on past experience, a second wave of global spread should be anticipated within a year.

As all countries are likely to experience emergency conditions during a pandemic, opportunities for inter-country assistance, as seen during natural disasters or localized disease outbreaks, may be curtailed once international spread has begun and governments focus on protecting domestic populations.

What are the most important warning signals that a pandemic is about to start?

The most important warning signal comes when clusters of patients with clinical symptoms of influenza, closely related in time and place, are detected, as this suggests human-to-human transmission is taking place. For similar reasons, the detection of cases in health workers caring for H5N1 patients would suggest human-to-human transmission. Detection of such events should be followed by immediate field investigation of every possible case to confirm the diagnosis, identify the source, and determine whether human-to-human transmission is occurring.

Studies of viruses, conducted by specialized WHO reference laboratories, can corroborate field investigations by spotting genetic and other changes in the virus indicative of an improved ability to infect humans. This is why WHO repeatedly asks affected countries to share viruses with the international research community.

What is the status of vaccine development and production?

Vaccines effective against a pandemic virus are not yet available. Vaccines are produced each year for seasonal influenza but will not protect against pandemic influenza. Although a vaccine against the H5N1 virus is under development in several countries, no vaccine is ready for commercial production and no vaccines are expected to be widely available until several months after the start of a pandemic.

Some clinical trials are now under way to test whether experimental vaccines will be fully protective and to determine whether different formulations can economize on the amount of antigen required, thus boosting production capacity. Because the vaccine needs to closely match the pandemic virus, large-scale commercial production will not start until the new virus has emerged and a pandemic has been declared. Current global production capacity falls far short of the demand expected during a pandemic.

What drugs are available for treatment?

Two drugs (in the neuraminidase inhibitors class), oseltamivir (commercially known as Tamiflu) and zanamivir (commercially known as Relenza) can reduce the severity and duration of illness caused by seasonal influenza. The efficacy of the neuraminidase inhibitors depends, among others, on their early administration ( within 48 hours after symptom onset). For cases of human infection with H5N1, the drugs may improve prospects of survival, if administered early, but clinical data are limited. The H5N1 virus is expected to be susceptible to the neuraminidase inhibitors. Antiviral resistance to neuraminidase inhibitors has been clinically negligible so far but is likely to be detected during widespread use during a pandemic.

An older class of antiviral drugs, the M2 inhibitors amantadine and rimantadine, could potentially be used against pandemic influenza, but resistance to these drugs can develop rapidly and this could significantly limit their effectiveness against pandemic influenza. Some currently circulating H5N1 strains are fully resistant to these the M2 inhibitors. However, should a new virus emerge through reassortment, the M2 inhibitors might be effective.

For the neuraminidase inhibitors, the main constraints - which are substantial - involve limited production capacity and a price that is prohibitively high for many countries. At present manufacturing capacity, which has recently quadrupled, it will take a decade to produce enough oseltamivir to treat 20% of the world's population. The manufacturing process for oseltamivir is complex and time-consuming, and is not easily transferred to other facilities.

So far, most fatal pneumonia seen in cases of H5N1 infection has resulted from the effects of the virus, and cannot be treated with antibiotics. Nonetheless, since influenza is often complicated by secondary bacterial infection of the lungs, antibiotics could be life-saving in the case of late-onset pneumonia. WHO regards it as prudent for countries to ensure adequate supplies of antibiotics in advance.

Can a pandemic be prevented?

No one knows with certainty. The best way to prevent a pandemic would be to eliminate the virus from birds, but it has become increasingly doubtful if this can be achieved within the near future.

Following a donation by industry, WHO will have a stockpile of antiviral medications, sufficient for 3 million treatment courses, by early 2006. Recent studies, based on mathematical modelling, suggest that these drugs could be used prophylactically near the start of a pandemic to reduce the risk that a fully transmissible virus will emerge or at least to delay its international spread, thus gaining time to augment vaccine supplies.

The success of this strategy, which has never been tested, depends on several assumptions about the early behaviour of a pandemic virus, which cannot be known in advance. Success also depends on excellent surveillance and logistics capacity in the initially affected areas, combined with an ability to enforce movement restrictions in and out of the affected area. To increase the likelihood that early intervention using the WHO rapid-intervention stockpile of antiviral drugs will be successful, surveillance in affected countries needs to improve, particularly concerning the capacity to detect clusters of cases closely related in time and place.

What strategic actions are recommended by WHO?

In August 2005, WHO sent all countries a document outlining recommended strategic actions for responding to the avian influenza pandemic threat. Recommended actions aim to strengthen national preparedness, reduce opportunities for a pandemic virus to emerge, improve the early warning system, delay initial international spread, and accelerate vaccine development.

Is the world adequately prepared?

No. Despite an advance warning that has lasted almost two years, the world is ill-prepared to defend itself during a pandemic. WHO has urged all countries to develop preparedness plans, but only around 40 have done so. WHO has further urged countries with adequate resources to stockpile antiviral drugs nationally for use at the start of a pandemic. Around 30 countries are purchasing large quantities of these drugs, but the manufacturer has no capacity to fill these orders immediately. On present trends, most developing countries will have no access to vaccines and antiviral drugs throughout the duration of a pandemic.

Conclusion

The flu pandemic of 1918 provides us history of how horrible a flu virus can be. Projections are that the current strain of avian flu may turn in to a pandemic.A strength to help reduce that riks are current technological abilities to create a vaccine, in addition to the current preparation. The risks of spreading the disease is also a result of technology making the world a smaller place through air travel.

It is critical for healthcare practitioners to obtain as much information as possible regarding this virus and to keep updated on its progress.The information on the WHO and CDC websites provide a great resource for professional to stay up-to-date.

Bibliography

"Spanish flu." Wikipedia, The Free Encyclopedia. 13 Oct 2006, 04:17 UTC. Wikimedia Foundation, Inc. 15 Oct 2006 http://en.wikipedia.org/w/index.php?title=Spanish_flu&oldid=81149603.