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  » Medical Topic Archive  »  Avian Influenza (Bird Flu)

Avian Influenza (Bird Flu)

Key Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus

Avian influenza in birds

Avian influenza is an infection caused by avian (bird) influenza (flu) viruses. These influenza viruses occur naturally among birds. Wild birds worldwide carry the viruses in their intestines, but usually do not get sick from them. However, avian influenza is very contagious among birds and can make some domesticated birds, including chickens, ducks, and turkeys, very sick and kill them.
Infected birds shed influenza virus in their saliva, nasal secretions, and feces. Susceptible birds become infected when they have contact with contaminated secretions or excretions or with surfaces that are contaminated with secretions or excretions from infected birds. Domesticated birds may become infected with avian influenza virus through direct contact with infected waterfowl or other infected poultry, or through contact with surfaces (such as dirt or cages) or materials (such as water or feed) that have been contaminated with the virus.
Infection with avian influenza viruses in domestic poultry causes two main forms of disease that are distinguished by low and high extremes of virulence. The “low pathogenic” form may go undetected and usually causes only mild symptoms (such as ruffled feathers and a drop in egg production). However, the highly pathogenic form spreads more rapidly through flocks of poultry. This form may cause disease that affects multiple internal organs and has a mortality rate that can reach 90-100% often within 48 hours.

Human infection with avian influenza viruses

There are many different subtypes of type A influenza viruses. These subtypes differ because of changes in certain proteins on the surface of the influenza A virus (hemagglutinin [HA] and neuraminidase [NA] proteins). There are 16 known HA subtypes and 9 known NA subtypes of influenza A viruses. Many different combinations of HA and NA proteins are possible. Each combination represents a different subtype. All known subtypes of influenza A viruses can be found in birds.
Usually, “avian influenza virus” refers to influenza A viruses found chiefly in birds, but infections with these viruses can occur in humans. The risk from avian influenza is generally low to most people, because the viruses do not usually infect humans. However, confirmed cases of human infection from several subtypes of avian influenza infection have been reported since 1997. Most cases of avian influenza infection in humans have resulted from contact with infected poultry (e.g., domesticated chicken, ducks, and turkeys) or surfaces contaminated with secretion/excretions from infected birds. The spread of avian influenza viruses from one ill person to another has been reported very rarely, and transmission has not been observed to continue beyond one person.
“Human influenza virus” usually refers to those subtypes that spread widely among humans. There are only three known A subtypes of influenza viruses (H1N1, H1N2, and H3N2) currently circulating among humans. It is likely that some genetic parts of current human influenza A viruses came from birds originally. Influenza A viruses are constantly changing, and they might adapt over time to infect and spread among humans.
During an outbreak of avian influenza among poultry, there is a possible risk to people who have contact with infected birds or surfaces that have been contaminated with secretions or excretions from infected birds.
Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections, pneumonia, severe respiratory diseases (such as acute respiratory distress), and other severe and life-threatening complications. The symptoms of avian influenza may depend on which virus caused the infection.
Studies done in laboratories suggest that some of the prescription medicines approved in the United States 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 demonstrate the effectiveness of these medicines.

Avian Influenza A (H5N1)

Avian influenza A (H5N1) in Asia and Europe
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. Since late June 2004, however, new outbreaks of influenza H5N1 among poultry were reported by several countries in Asia (Cambodia, China [Tibet], Indonesia, Kazakhstan, Malaysia, Mongolia, Russia [Siberia], Thailand, and Vietnam). It is believed that these outbreaks are ongoing. Influenza H5N1 infection also has been reported among poultry in Turkey Romania, and Ukraine. Outbreaks of influenza H5N1 have been reported among wild migratory birds in China, Croatia, Mongolia, and Romania.
As of January 7, 2006, human cases of influenza A (H5N1) infection have been reported in Cambodia, China, Indonesia, Thailand, Vietnam, and most recently, several cases in Turkey. A January 9, 2006 WHO Situation Report describes detection of the H5 subtype of avian influenza virus in samples from an additional 10 people in Turkey . These samples are undergoing further analysis to determine whether they contain the H5N1 strain. For the most current information about avian influenza and cumulative case numbers, see the World Health Organization (WHO) website at http://www.who.int/csr/disease/avian_influenza/en/ .

Human health risks during the H5N1 outbreak

H5N1 virus does not usually infect people, but more than 140 human cases have been reported by the World Health Organization since January 2004. Most of these cases have occurred as a result of people having direct or close contact with infected poultry or contaminated surfaces. So far, the spread of H5N1 virus from person-to-person has been rare and has not continued beyond one person.
Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 has caused the largest number of detected cases of severe disease and death in humans. In the current outbreaks in Asia and Europe , more than half of those infected with the virus have died. Most cases have occurred in previously healthy children and young adults. However, it is possible that the only cases currently being reported are those in the most severely ill people, and that the full range of illness caused by the H5N1 virus has not yet been defined.
So far, the spread of H5N1 virus from person to person has been limited 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. For more information about influenza pandemics, see http://www.cdc.gov/flu/pandemic/ and http://www.pandemicflu.gov .
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 and widely from person to person.

Treatment and vaccination for H5N1 virus in humans

The H5N1 virus that has caused human illness and death in Asia is resistant to amantadine and rimantadine, two antiviral medications commonly used for influenza. Two other antiviral medications, oseltamavir and zanamavir, would probably work to treat influenza caused by H5N1 virus, but additional studies still need to be done to demonstrate their effectiveness.
There currently is no commercially available vaccine to protect humans against H5N1 virus that is being seen in Asia and Europe. However, vaccine development efforts are taking place. Research studies to test a vaccine to protect humans against H5N1 virus began in April 2005, and a series of clinical trials is under way. For more information about H5N1 vaccine development process, visit the National Institutes of Health website.

Avian Influenza Infection in Humans

Although avian influenza A viruses usually do not infect humans, more than 100 confirmed cases of human infection with avian influenza viruses have been reported since 1997. For example, the World Health Organization (WHO) maintains situation updates and cumulative reports of human cases of avian influenza A (H5N1). Most cases of avian influenza infection in humans are thought to have resulted from direct contact with infected poultry or contaminated surfaces. However, there is still a lot to learn about how different subtypes and strains of avian influenza virus might affect humans. For example, it is not known how the distinction between low pathogenic and highly pathogenic strains might impact the health risk to humans. (For more information, see “Low Pathogenic versus Highly Pathogenic Avian Influenza Viruses” on the CDC Influenza Viruses Web page.
Because of concerns about the potential for more widespread infection in the human population, public health authorities closely monitor outbreaks of human illness associated with avian influenza. To date, human infections with avian influenza A viruses detected since 1997 have not resulted in sustained human-to-human transmission. However, because influenza A viruses have the potential to change and gain the ability to spread easily between people, monitoring for human infection and person-to-person transmission is important. (See Information about Influenza Pandemics for more information.)

Instances of Avian Influenza Infections in Humans

Confirmed instances of avian influenza viruses infecting humans since 1997 include:

° H5N1, Hong Kong, Special Administrative Region, 1997: Highly pathogenic avian influenza A (H5N1) infections occurred in both poultry and humans. This was the first time an avian influenza A virus transmission directly from birds to humans had been found. During this outbreak, 18 people were hospitalized and six of them died. To control the outbreak, authorities killed about 1.5 million chickens to remove the source of the virus. Scientists determined that the virus spread primarily from birds to humans, though rare person-to-person infection was noted.

° H9N2, China and Hong Kong, Special Administrative Region, 1999: Low pathogenic avian influenza A (H9N2) virus infection was confirmed in two children and resulted in uncomplicated influenza-like illness. Both patients recovered, and no additional cases were confirmed. The source is unknown, but the evidence suggested that poultry was the source of infection and the main mode of transmission was from bird to human. However, the possibility of person-to-person transmission could not be ruled out. Several additional human H9N2 infections were reported from China in 1998-99.

° H7N2, Virginia, 2002: Following an outbreak of H7N2 among poultry in the Shenandoah Valley poultry production area, one person was found to have serologic evidence of infection with H7N2.

° H5N1, China and Hong Kong, Special Administrative Region, 2003: Two cases of highly pathogenic avian influenza A (H5N1) infection occurred among members of a Hong Kong family that had traveled to China. One person recovered, the other died. How or where these two family members were infected was not determined. Another family member died of a respiratory illness in China, but no testing was done.

° H7N7, Netherlands, 2003: The Netherlands reported outbreaks of influenza A (H7N7) in poultry on several farms. Later, infections were reported among pigs and humans. In total, 89 people were confirmed to have H7N7 influenza virus infection associated with this poultry outbreak. These cases occurred mostly among poultry workers. H7N7-associated illness included 78 cases of conjunctivitis (eye infections) only; 5 cases of conjunctivitis and influenza-like illnesses with cough, fever, and muscle aches; 2 cases of influenza-like illness only; and 4 cases that were classified as “other.” There was one death among the 89 total cases. It occurred in a veterinarian who visited one of the affected farms and developed acute respiratory distress syndrome and complications related to H7N7 infection. The majority of these cases occurred as a result of direct contact with infected poultry; however, Dutch authorities reported three possible instances of transmission from poultry workers to family members. Since then, no other instances of H7N7 infection among humans have been reported.

° H9N2, Hong Kong, Special Administrative Region, 2003: Low pathogenic avian influenza A (H9N2) infection was confirmed in a child in Hong Kong. The child was hospitalized and recovered.

° H7N2, New York, 2003: In November 2003, a patient with serious underlying medical conditions was admitted to a hospital in New York with respiratory symptoms. One of the initial laboratory tests identified an influenza A virus that was thought to be H1N1. The patient recovered and went home after a few weeks. Subsequent confirmatory tests conducted in March 2004 showed that the patient had been infected with avian influenza A (H7N2) virus.

° H7N3 in Canada, 2004: In February 2004, human infections of highly pathogenic avian influenza A (H7N3) among poultry workers were associated with an H7N3 outbreak among poultry. The H7N3-associated, mild illnesses consisted of eye infections.

° H5N1, Thailand and Vietnam, 2004, and other outbreaks in Asia during 2004 and 2005: In January 2004, outbreaks of highly pathogenic influenza A (H5N1) in Asia were first reported by the World Health Organization. Visit the Avian Influenza section of the World Health Organization Web site for more information and updates.

Symptoms of Avian Influenza in Humans

The reported symptoms of avian influenza in humans have ranged from typical influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections (conjunctivitis), pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening complications.

Antiviral Agents for Influenza

Four different influenza antiviral drugs (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration (FDA) for the treatment of influenza; three are approved for prophylaxis. All four have activity against influenza A viruses. However, sometimes influenza strains can become resistant to these drugs, and therefore the drugs may not always be effective. For example, analyses of some of the 2004 H5N1 viruses isolated from poultry and humans in Asia have shown that the viruses are resistant to two of the medications (amantadine and rimantadine). Also, please note the January 14, 2006 CDC Health Alert Notice (HAN), in which CDC recommends that neither amantadine nor rimantadine be used for the treatment or prevention (prophylaxis) of influenza A in the United States for the remainder of the 2005-06 influenza season. Monitoring of avian influenza A viruses for resistance to influenza antiviral medications is ongoing.

Avian influenza frequently asked questions
revised 5 December 2005

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 subtypes2. 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 Vietnam.
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.
• 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.
• 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.
• H5N1 appears to have expanded its host range, infecting and killing mammalian species previously considered resistant to infection with avian influenza viruses.
• 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.
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1 Influenza viruses are grouped into three types, designated A, B, and C. Influenza A and B viruses are of concern for human health. Only influenza A viruses can cause pandemics.

2 The H subtypes are epidemiologically most important, as they govern the ability of the virus to bind to and enter cells, where multiplication of the virus then occurs. The N subtypes govern the release of newly formed virus from the cells

Further Information Links

Q. How can I find out more information?
Answer: The majority of information is available on websites throughout the world.

U.S. Government Agencies

PandemicFlu.gov

Avian Influenza Response
U.S. Agency for International Development (USAID)

Avian Influenza
U.S. Centers for Disease Control (CDC)

Avian Influenza (Bird Flu)
U.S. Department of Agriculture (USDA)

Animal and Plant Health Inspection Service (APHIS)
U.S. Department of Agriculture (USDA)

Avian Influenza Information
National Agricultural Library, U.S. Department of Agriculture

Avian Influenza
U.S. Department of Defense

National Vaccine Program Office
U.S. Department of Health and Human Services (HHS)

Avian Influenza
U.S.Department of State

Avian Flu
VOANews.com

Online Reading

Key Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus
U.S. Centers for Disease Control and Prevention (CDC), October 25, 2005

Pandemic Influenza Response and Preparedness Plan
The White House, November 1, 2005

H5N1 - Killer Flu
Video documentary from PBS

Pandemics and Pandemic Scares in the 20th Century
U.S. Department of Health and Human Services (HHS)

OIE-FAO International Conference on Avian Influenza
Paris, France 7 - 8 April 2005

Avian Influenza Trade Ban Status as of 2-23-05 APHIS/USDA

Avian Influenza: Multiple Strains Cause Different Effects Worldwide
Congressional Research Service (CRS) Updated May 14, 2004

Guidance For Protecting Workers Against Avian Flu
U.S. Department of Labor, Occupational Safety & Health Administration

Avian Influenza A (H5N1) in 10 Patients in Vietnam
New England Journal of Medicine, March 18, 2004

Biosecurity for the Birds APHIS/USDA

If you do not have access to the internet, visit your local library or an internet café. Sites such as the World Health Organization ( www.who.int ), the World Animal Health Organisation ( www.oie.int ) and the United States Centre for Disease Control (CDC) ( www.cdc.gov ) have links to many other sites around the world that provide information about avian influenza.

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