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Bird Flu
(Avian Flu, Avian Influenza)

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

 

This fact sheet provides general information about bird flu and information about one type of bird flu, called avian influenza A (H5N1) that is infecting birds in Asia and has infected some humans.

What is avian influenza (bird flu)?

Bird flu is an infection caused by avian (bird) influenza (flu) viruses . These flu viruses occur naturally among birds. Wild birds worldwide carry the viruses in their intestines, but usually do not get sick from them. However, bird flu is very contagious among birds and can make some domesticated birds, including chickens, ducks, and turkeys, very sick and kill them.

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.

How does avian influenza spread among birds?

Infected birds shed influenza virus in their saliva, nasal secretions, and feces. Susceptible birds become infected when they have contact with contaminated excretions or with surfaces that are contaminated with excretions or secretions. 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.

Do bird flu viruses infect humans?

Bird flu viruses do not usually infect humans, but more than 100 confirmed cases of human infection with bird flu viruses have occurred since 1997. The World Health Organization (WHO) maintains situation updates and cumulative reports of human cases of avian influenza A (H5N1). Please visit these and previous WHO situation updates and cumulative reports for additional information.

How do people become infected with avian influenza viruses?

Most cases of avian influenza infection in humans have resulted from direct or close contact with infected poultry (e.g., domesticated chicken, ducks, and turkeys) or surfaces contaminated with secretions and excretions from infected birds. The spread of avian influenza viruses from an ill person to another person has been reported very rarely, and transmission has not been observed to continue beyond one person. During an outbreak of avian influenza among poultry, there is a possible risk to people who have direct or close contact with infected birds or with surfaces that have been contaminated with secretions and excretions from infected birds.

What are the symptoms of avian influenza in humans?

Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms (fever, cough, sore throat , and muscle aches) to eye infections, pneumonia , severe respiratory diseases (such as acute respiratory distress syndrome), and other severe and life-threatening complications. The symptoms of avian influenza may depend on which specific virus subtype and strain caused the infection.

How is avian influenza detected in humans?

A laboratory test is needed to confirm avian influenza in humans.

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 prescription 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 the current seasonal influenza vaccine protect me from avian influenza?

No. Influenza vaccine for the 2005-06 season 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.

Is there a risk for becoming infected with avian influenza by eating poultry?

There is no evidence that properly cooked poultry or eggs can be a source of infection for avian influenza viruses. For more information about avian influenza and food safety issues, visit the World Health Organization website .

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, http://www.cdc.gov/flu/avian/outbreaks/embargo.htm .

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.

What precautions can be taken to reduce the risk for infection from wild birds in the United States?

As a general rule, the public should observe wildlife, including wild birds, from a distance. This protects you from possible exposure to pathogens and minimizes disturbance to the animal. Avoid touching wildlife. If there is contact with wildlife do not rub eyes, eat, drink, or smoke before washing hands with soap and water. Do not pick up diseased or dead wildlife. Contact your state, tribal, or federal natural resource agency if a sick or dead animal is found.

What precautions can hunters take to reduce the risk for infection when hunting birds in the United States?

Hunters should follow routine precautions when handling game, including wild birds. The National Wildlife Health Center recommends that hunters:

  • Do not handle or eat sick game.
  • Wear rubber or disposable latex gloves while handling and cleaning game, wash hands with soap and water (or with alcohol-based hand products if the hands are not visibly soiled), and thoroughly clean knives, equipment and surfaces that come in contact with game.
  • Do not eat, drink, or smoke while handling animals.
  • Cook all game thoroughly.

Avian Influenza A (H5N1)

What is the avian influenza A (H5N1) virus that has been reported 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 have been 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 and Romania and among wild migratory birds in Croatia .

Human cases of influenza A (H5N1) infection have been reported in Cambodia, China, Indonesia, Thailand, Turkey, and Vietnam. For the most current information about avian influenza and cumulative case numbers, see the World Health Organization website at http://www.who.int/csr/disease/avian_influenza/en/.

What are the risks to humans from the current H5N1 outbreak in Asia and Europe?

H5N1 virus does not usually infect people, but more than 140 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 does H5N1 virus differ from seasonal influenza viruses that infect humans?

Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 virus has caused the largest number of reported cases of severe disease and death in humans. In the current situation in Asia, more than half of the people 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.

Unlike seasonal influenza, in which infection usually causes only mild respiratory symptoms in most people, H5N1 infection may follow an unusually aggressive clinical course, with rapid deterioration and high fatality. Primary viral pneumonia and multi-organ failure have been common among people who have become ill with H5N1 influenza.

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 .

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, and February 4, 2005; both alerts reminded public health departments about recommendations for detecting (domestic surveillance), diagnosing, and preventing the spread of H5N1 virus. The alerts also recommended measures for laboratory testing for H5N1 virus. To read the alerts, 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 update.

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 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 following countries: Cambodia, Indonesia, Japan, Laos, Kazakhstan, Malaysia, People's Republic of China, Romania, Russia, South Korea, Thailand, Turkey, Ukraine, and Vietnam (current as of December 29, 2005) . 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 Asia. 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 following countries: Cambodia, Indonesia, Japan, Laos, Kazakhstan, Malaysia, Peoples' Republic of China, Romania, Russia, South Korea, Thailand, Turkey, Ukraine, and Vietnam. (current as of December 29, 2005) .

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, the risk of becoming infected with H5N1 virus from bird feeders is low. 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, 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; 2) it must infect humans and causes serious illness; and 3) it must spread easily and sustainedly (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 100 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 pig. The result could be a fully transmissible pandemic virus-that is, a virus that can spread easily and directly to 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 flu pandemic?

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

  • 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) and Vietnamese Ministry of Health to investigate influenza H5N1 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 reagents kits to detect the currently circulating influenza A H5N1 viruses.

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.

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Avian influenza (" bird flu") - Fact sheet

February 2006

THE DISEASE IN BIRDS

Avian influenza is an infectious disease of birds caused by type A strains of the influenza virus. The disease occurs worldwide. While all birds are thought to be susceptible to infection with avian influenza viruses, many wild bird species carry these viruses with no apparent signs of harm.

Other bird species, including domestic poultry, develop disease when infected with avian influenza viruses. In poultry, the viruses cause two distinctly different forms of disease – one common and mild, the other rare and highly lethal. In the mild form, signs of illness may be expressed only as ruffled feathers, reduced egg production, or mild effects on the respiratory system. Outbreaks can be so mild they escape detection unless regular testing for viruses is in place.

In contrast, the second and far less common highly pathogenic form is difficult to miss. First identified in Italy in 1878, highly pathogenic avian influenza is characterized by sudden onset of severe disease, rapid contagion, and a mortality rate that can approach 100% within 48 hours. In this form of the disease, the virus not only affects the respiratory tract, as in the mild form, but also invades multiple organs and tissues. The resulting massive internal haemorrhaging has earned it the lay name of “chicken Ebola”.

All 16 HA (haemagluttinin) and 9 NA (neuraminidase) subtypes of influenza viruses are known to infect wild waterfowl, thus providing an extensive reservoir of influenza viruses perpetually circulating in bird populations. In wild birds, routine testing will nearly always find some influenza viruses. The vast majority of these viruses cause no harm.

To date, all outbreaks of the highly pathogenic form of avian influenza have been caused by viruses of the H5 and H7 subtypes. Highly pathogenic viruses possess a tell-tale genetic “trade mark” or signature – a distinctive set of basic amino acids in the cleavage site of the HA – that distinguishes them from all other avian influenza viruses and is associated with their exceptional virulence.

Not all virus strains of the H5 and H7 subtypes are highly pathogenic, but most are thought to have the potential to become so. Recent research has shown that H5 and H7 viruses of low pathogenicity can, after circulation for sometimes short periods in a poultry population, mutate into highly pathogenic viruses. Considerable circumstantial evidence has long suggested that wild waterfowl introduce avian influenza viruses, in their low pathogenic form, to poultry flocks, but do not carry or directly spread highly pathogenic viruses. This role may, however, have changed very recently: at least some species of migratory waterfowl are now thought to be carrying the H5N1 virus in its highly pathogenic form and introducing it to new geographical areas located along their flight routes.

Apart from being highly contagious among poultry, avian influenza viruses are readily transmitted from farm to farm by the movement of live birds, people (especially when shoes and other clothing are contaminated), and contaminated vehicles, equipment, feed, and cages. Highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low. For example, the highly pathogenic H5N1 virus can survive in bird faeces for at least 35 days at low temperature (4oC). At a much higher temperature (37oC), H5N1 viruses have been shown to survive, in faecal samples, for six days.

For highly pathogenic disease, the most important control measures are rapid culling of all infected or exposed birds, proper disposal of carcasses, the quarantining and rigorous disinfection of farms, and the implementation of strict sanitary, or “biosecurity”, measures. Restrictions on the movement of live poultry, both within and between countries, are another important control measure. The logistics of recommended control measures are most straightforward when applied to large commercial farms, where birds are housed indoors, usually under strictly controlled sanitary conditions, in large numbers. Control is far more difficult under poultry production systems in which most birds are raised in small backyard flocks scattered throughout rural or periurban areas.

When culling – the first line of defence for containing outbreaks – fails or proves impracticable, vaccination of poultry in a high-risk area can be used as a supplementary emergency measure, provided quality-assured vaccines are used and recommendations from the World Organisation for Animal Health (OIE) are strictly followed. The use of poor quality vaccines or vaccines that poorly match the circulating virus strain may accelerate mutation of the virus. Poor quality animal vaccines may also pose a risk for human health, as they may allow infected birds to shed virus while still appearing to be disease-free.

Apart from being difficult to control, outbreaks in backyard flocks are associated with a heightened risk of human exposure and infection. These birds usually roam freely as they scavenge for food and often mingle with wild birds or share water sources with them. Such situations create abundant opportunities for human exposure to the virus, especially when birds enter households or are brought into households during adverse weather, or when they share areas where children play or sleep. Poverty exacerbates the problem: in situations where a prime source of food and income cannot be wasted, households frequently consume poultry when deaths or signs of illness appear in flocks. This practice carries a high risk of exposure to the virus during slaughtering, defeathering, butchering, and preparation of poultry meat for cooking, but has proved difficult to change. Moreover, as deaths of birds in backyard flocks are common, especially under adverse weather conditions, owners may not interpret deaths or signs of illness in a flock as a signal of avian influenza and a reason to alert the authorities. This tendency may help explain why outbreaks in some rural areas have smouldered undetected for months. The frequent absence of compensation to farmers for destroyed birds further works against the spontaneous reporting of outbreaks and may encourage owners to hide their birds during culling operations.

THE ROLE OF MIGRATORY BIRDS

During 2005, an additional and significant source of international spread of the virus in birds became apparent for the first time, but remains poorly understood. Scientists are increasingly convinced that at least some migratory waterfowl are now carrying the H5N1 virus in its highly pathogenic form, sometimes over long distances, and introducing the virus to poultry flocks in areas that lie along their migratory routes. Should this new role of migratory birds be scientifically confirmed, it will mark a change in a long-standing stable relationship between the H5N1 virus and its natural wild-bird reservoir.

Evidence supporting this altered role began to emerge in mid-2005 and has since been strengthened. The die-off of more than 6000 migratory birds, infected with the highly pathogenic H5N1 virus, that began at the Qinghai Lake nature reserve in central China in late April 2005, was highly unusual and probably unprecedented. Prior to that event, wild bird deaths from highly pathogenic avian influenza viruses were rare, usually occurring as isolated cases found within the flight distance of a poultry outbreak. Scientific studies comparing viruses from different outbreaks in birds have found that viruses from the most recently affected countries, all of which lie along migratory routes, are almost identical to viruses recovered from dead migratory birds at Qinghai Lake. Viruses from Turkey's first two human cases, which were fatal, were also virtually identical to viruses from Qinghai Lake.

COUNTRIES AFFECTED BY OUTBREAKS IN BIRDS

The outbreaks of highly pathogenic H5N1 avian influenza that began in south-east Asia in mid-2003 and have now spread to a few parts of Europe, are the largest and most severe on record. To date, nine Asian countries have reported outbreaks (listed in order of reporting): the Republic of Korea, Viet Nam, Japan, Thailand, Cambodia, the Lao People's Democratic Republic, Indonesia, China, and Malaysia. Of these, Japan, the Republic of Korea, and Malaysia have controlled their outbreaks and are now considered free of the disease. Elsewhere in Asia, the virus has become endemic in several of the initially affected countries.

In late July 2005, the virus spread geographically beyond its original focus in Asia to affect poultry and wild birds in the Russian Federation and adjacent parts of Kazakhstan. Almost simultaneously, Mongolia reported detection of the highly pathogenic virus in wild birds. In October 2005, the virus was reported in Turkey, Romania, and Croatia. In early December 2005, Ukraine reported its first outbreak in domestic birds. Most of these newer outbreaks were detected and reported quickly. Further spread of the virus along the migratory routes of wild waterfowl is, however, anticipated. Moreover, bird migration is a recurring event. Countries that lie along the flight pathways of birds migrating from central Asia may face a persistent risk of introduction or re-introduction of the virus to domestic poultry flocks.

Prior to the present situation, outbreaks of highly pathogenic avian influenza in poultry were considered rare. Excluding the current outbreaks caused by the H5N1 virus, only 24 outbreaks of highly pathogenic avian influenza have been recorded worldwide since 1959. Of these, 14 occurred in the past decade. The majority have shown limited geographical spread, a few remained confined to a single farm or flock, and only one spread internationally. All of the larger outbreaks were costly for the agricultural sector and difficult to control.

THE DISEASE IN HUMANS
History and epidemiology.

Influenza viruses are normally highly species-specific, meaning that viruses that infect an individual species (humans, certain species of birds, pigs, horses, and seals) stay “true” to that species, and only rarely spill over to cause infection in other species. Since 1959, instances of human infection with an avian influenza virus have been documented on only 10 occasions. Of the hundreds of strains of avian influenza A viruses, only four are known to have caused human infections: H5N1, H7N3, H7N7, and H9N2. In general, human infection with these viruses has resulted in mild symptoms and very little severe illness, with one notable exception: the highly pathogenic H5N1 virus.

Of all influenza viruses that circulate in birds, the H5N1 virus is of greatest present concern for human health for two main reasons. First, the H5N1 virus has caused by far the greatest number of human cases of very severe disease and the greatest number of deaths. It has crossed the species barrier to infect humans on at least three occasions in recent years: in Hong Kong in 1997 (18 cases with six deaths), in Hong Kong in 2003 (two cases with one death) and in the current outbreaks that began in December 2003 and were first recognized in January 2004.

A second implication for human health, of far greater concern, is the risk that the H5N1 virus – if given enough opportunities – will develop the characteristics it needs to start another influenza pandemic. The virus has met all prerequisites for the start of a pandemic save one: an ability to spread efficiently and sustainably among humans. While H5N1 is presently the virus of greatest concern, the possibility that other avian influenza viruses, known to infect humans, might cause a pandemic cannot be ruled out.

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, if detected sufficiently early.

During the first documented outbreak of human infections with H5N1, which occurred in Hong Kong in 1997, the 18 human cases coincided with an outbreak of highly pathogenic avian influenza, caused by a virtually identical virus, in poultry farms and live markets. Extensive studies of the human cases determined that direct contact with diseased poultry was the source of infection. Studies carried out in family members and social contacts of patients, health workers engaged in their care, and poultry cullers found very limited, if any, evidence of spread of the virus from one person to another. Human infections ceased following the rapid destruction – within three days – of Hong Kong's entire poultry population, estimated at around 1.5 million birds. Some experts believe that that drastic action may have averted an influenza pandemic.

All evidence to date indicates that close contact with dead or sick birds is the principal source of human infection with the H5N1 virus. Especially risky behaviours identified include the slaughtering, defeathering, butchering and preparation for consumption of infected birds. In a few cases, exposure to chicken faeces when children played in an area frequented by free-ranging poultry is thought to have been the source of infection. Swimming in water bodies where the carcasses of dead infected birds have been discarded or which may have been contaminated by faeces from infected ducks or other birds might be another source of exposure. In some cases, investigations have been unable to identify a plausible exposure source, suggesting that some as yet unknown environmental factor, involving contamination with the virus, may be implicated in a small number of cases. Some explanations that have been put forward include a possible role of peri-domestic birds, such as pigeons, or the use of untreated bird faeces as fertilizer. At present, H5N1 avian influenza remains largely a disease of birds. The species barrier is significant: the virus does not easily cross from birds to infect humans. Despite the infection of tens of millions of poultry over large geographical areas since mid-2003, fewer than 200 human cases have been laboratory confirmed. For unknown reasons, most cases have occurred in rural and periurban households where small flocks of poultry are kept. Again for unknown reasons, very few cases have been detected in presumed high-risk groups, such as commercial poultry workers, workers at live poultry markets, cullers, veterinarians, and health staff caring for patients without adequate protective equipment. Also lacking is an explanation for the puzzling concentration of cases in previously healthy children and young adults. Research is urgently needed to better define the exposure circumstances, behaviours, and possible genetic or immunological factors that might enhance the likelihood of human infection.

Assessment of possible cases

Investigations of all the most recently confirmed human cases, in China, Indonesia, and Turkey, have identified direct contact with infected birds as the most likely source of exposure. When assessing possible cases, the level of clinical suspicion should be heightened for persons showing influenza-like illness, especially with fever and symptoms in the lower respiratory tract, who have a history of close contact with birds in an area where confirmed outbreaks of highly pathogenic H5N1 avian influenza are occurring. Exposure to an environment that may have been contaminated by faeces from infected birds is a second, though less common, source of human infection. To date, not all human cases have arisen from exposure to dead or visibly ill domestic birds. Research published in 2005 has shown that domestic ducks can excrete large quantities of highly pathogenic virus without showing signs of illness. A history of poultry consumption in an affected country is not a risk factor, provided the food was thoroughly cooked and the person was not involved in food preparation. As no efficient human-to-human transmission of the virus is known to be occurring anywhere, simply travelling to a country with ongoing outbreaks in poultry or sporadic human cases does not place a traveller at enhanced risk of infection, provided the person did not visit live or “wet” poultry markets, farms, or other environments where exposure to diseased birds may have occurred.

Clinical features 1

In many patients, the disease caused by the H5N1 virus follows an unusually aggressive clinical course, with rapid deterioration and high fatality. Like most emerging disease, H5N1 influenza in humans is poorly understood. Clinical data from cases in 1997 and the current outbreak are beginning to provide a picture of the clinical features of disease, but much remains to be learned. Moreover, the current picture could change given the propensity of this virus to mutate rapidly and unpredictably.

The incubation period for H5N1 avian influenza may be longer than that for normal seasonal influenza, which is around two to three days. Current data for H5N1 infection indicate an incubation period ranging from two to eight days and possibly as long as 17 days. However, the possibility of multiple exposure to the virus makes it difficult to define the incubation period precisely. WHO currently recommends that an incubation period of seven days be used for field investigations and the monitoring of patient contacts.

Initial symptoms include a high fever, usually with a temperature higher than 38oC, and influenza-like symptoms. Diarrhoea, vomiting, abdominal pain, chest pain, and bleeding from the nose and gums have also been reported as early symptoms in some patients. Watery diarrhoea without blood appears to be more common in H5N1 avian influenza than in normal seasonal influenza. The spectrum of clinical symptoms may, however, be broader, and not all confirmed patients have presented with respiratory symptoms. In two patients from southern Viet Nam, the clinical diagnosis was acute encephalitis; neither patient had respiratory symptoms at presentation. In another case, from Thailand, the patient presented with fever and diarrhoea, but no respiratory symptoms. All three patients had a recent history of direct exposure to infected poultry.

One feature seen in many patients is the development of manifestations in the lower respiratory tract early in the illness. Many patients have symptoms in the lower respiratory tract when they first seek treatment. On present evidence, difficulty in breathing develops around five days following the first symptoms. Respiratory distress, a hoarse voice, and a crackling sound when inhaling are commonly seen. Sputum production is variable and sometimes bloody. Most recently, blood-tinted respiratory secretions have been observed in Turkey. Almost all patients develop pneumonia. During the Hong Kong outbreak, all severely ill patients had primary viral pneumonia, which did not respond to antibiotics. Limited data on patients in the current outbreak indicate the presence of a primary viral pneumonia in H5N1, usually without microbiological evidence of bacterial supra-infection at presentation. Turkish clinicians have also reported pneumonia as a consistent feature in severe cases; as elsewhere, these patients did not respond to treatment with antibiotics.

In patients infected with the H5N1 virus, clinical deterioration is rapid. In Thailand, the time between onset of illness to the development of acute respiratory distress was around six days, with a range of four to 13 days. In severe cases in Turkey, clinicians have observed respiratory failure three to five days after symptom onset. Another common feature is multiorgan dysfunction. Common laboratory abnormalities, include leukopenia (mainly lymphopenia), mild-to-moderate thrombocytopenia, elevated aminotransferases, and with some instances of disseminated intravascular coagulation.

Limited evidence suggests that some antiviral drugs, notably oseltamivir (commercially known as Tamiflu), can reduce the duration of viral replication and improve prospects of survival, provided they are administered within 48 hours following symptom onset. However, prior to the outbreak in Turkey, most patients have been detected and treated late in the course of illness. For this reason, clinical data on the effectiveness of oseltamivir are limited. Moreover, oseltamivir and other antiviral drugs were developed for the treatment and prophylaxis of seasonal influenza, which is a less severe disease associated with less prolonged viral replication. Recommendations on the optimum dose and duration of treatment for H5N1 avian influenza, also in children, need to undergo urgent review, and this is being undertaken by WHO.

In suspected cases, oseltamivir should be prescribed as soon as possible (ideally, within 48 hours following symptom onset) to maximize its therapeutic benefits. However, given the significant mortality currently associated with H5N1 infection and evidence of prolonged viral replication in this disease, administration of the drug should also be considered in patients presenting later in the course of illness.

Currently recommended doses of oseltamivir for the treatment of influenza are contained in the product information at the manufacturer's web site. The recommended dose of oseltamivir for the treatment of influenza, in adults and adolescents 13 years of age and older, is 150 mg per day, given as 75 mg twice a day for five days. Oseltamivir is not indicated for the treatment of children younger than one year of age.

As the duration of viral replication may be prolonged in cases of H5N1 infection, clinicians should consider increasing the duration of treatment to seven to ten days in patients who are not showing a clinical response. In cases of severe infection with the H5N1 virus, clinicians may need to consider increasing the recommended daily dose or the duration of treatment, keeping in mind that doses above 300 mg per day are associated with increased side effects. For all treated patients, consideration should be given to taking serial clinical samples for later assay to monitor changes in viral load, to assess drug susceptibility, and to assess drug levels. These samples should be taken only in the presence of appropriate measures for infection control.

In severely ill H5N1 patients or in H5N1 patients with severe gastrointestinal symptoms, drug absorption may be impaired. This possibility should be considered when managing these patients.

COUNTRIES WITH HUMAN CASES IN THE CURRENT OUTBREAK

To date, human cases have been reported in six countries, most of which are in Asia: Cambodia, China, Indonesia, Thailand, Turkey, and Viet Nam. The first patients in the current outbreak, which were reported from Viet Nam, developed symptoms in December 2003 but were not confirmed as H5N1 infection until 11 January 2004. Thailand reported its first cases on 23 January 2004. The first case in Cambodia was reported on 2 February 2005. The next country to report cases was Indonesia, which confirmed its first infection on 21 July. China's first two cases were reported on 16 November 2005. Confirmation of the first cases in Turkey came on 5 January 2006, followed by the first reported case in Iraq on 30 January 2006. All human cases have coincided with outbreaks of highly pathogenic H5N1 avian influenza in poultry. To date, Viet Nam has been the most severely affected country, with more than 90 cases.

Altogether, more than half of the laboratory-confirmed cases have been fatal. H5N1 avian influenza in humans is still a rare disease, but a severe one that must be closely watched and studied, particularly because of the potential of this virus to evolve in ways that could start a pandemic.

 

 


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