Avian influenza "Bird Flu" The Facts & Guidelines

Avian influenza "Bird Flu"

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

Bird flu viruses do not usually infect humans, but dozens cases of human infection with bird flu viruses have occurred since 1997. It is believed that most cases of bird flu infection in humans has been a result of contact with infected poultry or contaminated surfaces.

Why all the recent attention?

An especially virulent strain of the bird flu has spread from Asia to Europe. The virus, known as H5N1, can infect humans as well as birds. Health officials throughout the world are taking the threat of an outbreak of this virus over an extensive geographical area seriously and pressure is on to develop effective containment measures and treatments.

The number of human cases involving H5N1 has been small. However the potential for the virus to change into a more serious threat to humans is real. That’s why we has created this booklet to generate awareness and provide suggestions addressing fundamental health issues, particularly in the workplace and for first responders.

Avian Flu Protection

The Occupational Safety and Health Administration (OSHA) has published personal protection guidelines on its Web site regarding bird flu. The document, entitled “Guidance for Protecting Workers against Avian Flu,” provides background information on the disease and offers recommendations for employees or individuals who could potentially be exposed to the disease.

According to OSHA’s guidelines, “Exposure to infected poultry and their feces or dust contaminated with feces has been associated with human infection; however this is a rare occurrence.” OSHA advises that everyone who has been in close contact with infected animals wash their hands frequently. Proper hand washing consists of washing with soap and water for a minimum of 15 to 20 seconds.

Further guidelines are given for those involved in the culling, transporting or disposal of infected birds. OSHA advises the use of protective clothing and gloves capable of being disinfected or disposed, goggles, boots or protective foot covers that can be disinfected or disposed, and respiratory protection. The minimum form of respiratory protection OSHA recommends is an N95, N99 or N100 disposable respirator. It’s also recommended that anyone involved in handling infected birds receive the current season’s influenza vaccine.

Symptoms of bird flu in humans have ranged from typical flu-like symptoms such as fever, cough, sore throat and muscle aches, to eye infections, pneumonia, severe respiratory diseases and other severe and life-threatening complications. Prescription medicines approved for human flu viruses may work to prevent bird flu infection in humans, but flu viruses have shown an ability to develop resistance to drugs. There are currently no vaccines to protect humans against the Asian virus, but efforts are being made to develop them. Research studies to test just such a vaccine began in April of 2005.

Handling & Eating Poultry

Contrary to popular opinion, bird flu cannot be contracted by humans by eating cooked chicken and eggs. Chickens that are cooked at 56 degrees Celsius for three hours or at 60 degrees Celsius for 30 minutes are safe. In fact, the only way people can get the disease is if they come in close contact with the secretions of the infected animals. This makes people who raise chickens and those who work in farms or deliver chickens more at risk. People who prepare chickens and eggs may also be infected provided that the virus is fresh enough to infect them. This often occurs to people who cook food for families in the farms. If you are one of the many turning your nose at poultry due to the threat of bird flu, you may be interested to know there are measures you can take in order to continue to eat your favorite foods. There have been contradictory reports on whether the virus has been spread from the consumption of undercooked poultry, but you should err on the side of safety in this regard to avoid becoming infected.

Interestingly enough, many of the bird flu precautions are the same precautions you should already be taking to avoid bacteria such as salmonella. A little common sense and good hygiene will go a long way in preventing infection.

The first and most obvious tip is – DO NOT EAT RAW POULTRY! You should fully cook all meat you ingest. How do you tell if the meat is fully cooked? It should not retain any pink color, the juice should run clear, and the meat should reach a temperature of at least 70 to 75 degrees Celsius or roughly 165 degrees Fahrenheit. While freezing will not kill the disease, heat will - but only at sufficient temperatures. Therefore, you should be sure to thoroughly cook all poultry.

Other tips from the World Health Organization (WHO) include a few more of the basics. You should not handle raw meat without washing your hands thoroughly before and after (with antibacterial soap, preferably); you should take special care not to cross contaminate cooked food and raw meat by allowing the two to come in contact, using the same knife or other utensils, or handling food without properly washing your hands; and do not place cooked food back on the same plate or dish it was on when it was raw. Each of these is basic information that applies to, not only poultry, but all meat.

Also, thoroughly wash all surfaces and dishes that come in contact with raw meat (with antibacterial cleanser or soap). You should also avoid using raw or undercooked eggs in food preparation and cook eggs thoroughly (they suggest cooking until yolks are no longer runny).

In handling meat, you should also remember that the bird flu virus is not killed by freezing; therefore, all precautions should also be taken in handling frozen poultry as though it had just come from the market. With these simple steps, you can feel comfortable ingesting poultry, free from worry about bird flu.

Migratory Birds & Birds As Pets

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 smoldered 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.

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.

Advice To Travelers

Avoid contact with high-risk environments in affected countries

Travelers to areas affected by avian influenza in birds are not considered to be at elevated risk of infection unless direct and un-protected exposure to infected birds (including feathers, feces and under-cooked meat and egg products) occurs.

World Health Organization (WHO) continues to recommend that travelers to affected areas should avoid contact with live animal markets and poultry farms, and any free-ranging or caged poultry. Large amounts of the virus are known to be excreted in the droppings from infected birds. Populations in affected countries are advised to avoid contact with dead migratory birds or wild birds showing signs of disease.

Direct contact with infected poultry, or surfaces and objects contaminated by their droppings, is considered the main route of human infection. Exposure risk is considered highest during slaughter, defeathering, butchering, and preparation of poultry for cooking. There is no evidence that properly cooked poultry or poultry products can be a source of infection.

Travelers should contact their local health providers or national health authorities for supplementary information.

Children, School & Bird Flu

Classrooms can be a breeding ground for viruses One of the most important preventative measures that can be done to prevent a child from contacting colds, seasonal flu and the avian bird flu virus is the practice of good hand washing skills. Children do not hand the same hygiene practices as most adults and while at school tend to share desks, tables, toys, cups, plates and utensils. Many times children pick their runny noses or simply wipe their nose with their arms or shirts, which then could come into contact with other children. That's why it is so crucial to wash these organisms off to prevent their spread."

Studies have shown that 40 percent to 60 percent of people don't wash their hands after using the restroom. And those who do wash their hands often don't know the proper technique.

"Most people who do wash their hands do so much too quickly," In order to be effective, hands should be washed with soap from 20 to 25 seconds. The three keys are soap, friction and water. "If we could get the world to embrace hand washing, we would have much less illness."

Hands should be washed after playtime that includes close contact with other children; before and after eating; after a child uses a restroom or when helping a child to use the bathroom; after changing a diaper; after a nose blowing; coughing or sneezing into hands; after handling animals and pets; and before going to a vehicle on the way home.

These simple precautions can limit the spread of bird flu to other people. It is important to keep your child home from school if they feel under the weather or are exhibiting signs of illness to avoid carrying germs to school.

Child Pandemic Defense Kit™

Your children may be exposed to many flu viruses in a school classroom throughout the season. The items in this kit if properly used can go a long way towards defending your children from exposure from many of those viruses as well as the possibility of an avian bird flu virus outbreak. You may want to purchase additional items from our store to add to this kit, but we added the basic items such as respiratory protection, Pocket tissues, individually packaged soap toweletes and a nylon storage bag with cord lock.

The Child Pandemic Defense Kit™ can be easily stored in a School locker, child's classroom cubby, and may even be carried in a backpack to assure your child will have immediate access. Caution should be the rule when providing a repirator mask or other protective items contained in these kits to a child as these items will be of no use if not properly worn or instructions for use are not followed. A phyician should be consulted Prior to purchasing a respirator mask for a child. Please read all instructions provided with masks and practice them with your children. Children using respirator masks should always be under the direct supervision of an adult.

The Science of an Outbreak

The Science is present for a pandemic outbreak

Scientists are certain another pandemic will strike at some point -- they just don't know whether the current bird flu virus will be the spark. Their worries are heightened because the bird flu is mutating in a manner similar to the virus that caused the 1918 Spanish flu, which killed more than 40 million worldwide.

For now, people can contract the bird flu -- which has killed more than 100 people but has not yet reached the United States (As of the printing of this booklet) -- only through contact with an infected bird. But experts fear the longer the virus circulates, the greater the odds it will mutate or combine with a different virus to create a new strain easily passed among humans. Because people would have no immunity, such a strain could spark a global pandemic that could kill tens of millions

Experts say the bird flu virus could arrive in the United States in coming months. It likely would show up first in Alaska, in birds that migrated from Asia, but could spread through the rest of North America as birds migrate southward this fall.

A pandemic could swiftly overwhelm health providers and disrupt everything from transportation systems to schools. Experts estimate that up to 30 percent of the population could contract the virus. The potential is very real; the science is there."

History of the bird flu virus

During the 20th century, influenza pandemics caused millions of deaths, social disruption and profound economic losses worldwide. Influenza experts agree that another pandemic is likely to happen but are unable to say when. The specific characteristics of a future pandemic virus cannot be predicted. Nobody knows how pathogenic a new virus would be, and which age groups it would affect. The impact of improved nutrition and health care needs to be weighed against the effect of increased international travel or simultaneous health threats. The level of preparedness will also influence the economic and medical impact of the disease and the final death toll. However, even in one of the more conservative scenarios, it has been calculated that the world will face up to several 100 million outpatient visits, more than 25 million hospital admissions and several million deaths globally, within a very short period.

Consequences of an influenza pandemic

In the past, new strains have generated pandemics causing high death rates and great social disruption. In the 20th century, the greatest influenza pandemic occurred in 1918 -1919 and caused an estimated 40–50 million deaths world wide. Although health care has improved in the last decades, epidemiological models from the Centers for Disease Control and Prevention, Atlanta, USA project that today a pandemic is likely to result in 2 to 7.4 million deaths globally. In high income countries alone, accounting for 15% of the world’s population, models project a demand for 134–233 million outpatient visits and 1.5–5.2 million hospital admissions. However, the impact of the next pandemic is likely to be the greatest in low income countries because of different population characteristics and the already strained health care resources.

The Outbreak

Influenza pandemic

An influenza pandemic occurs when a new influenza virus appears against which the human population has no immunity, resulting in several, simultaneous epidemics worldwide with enormous numbers of deaths and illness. With the increase in global transport and communications, as well as urbanization and overcrowded conditions, epidemics due the new influenza virus are likely to quickly take hold around the world.

A new influenza virus: how it could cause a pandemic Annual outbreaks of influenza are due to minor changes in the surface proteins of the viruses that enable the viruses to evade the immunity humans have developed after previous infections with the viruses or in response to vaccinations. When a major change in either one or both of their surface proteins occurs spontaneously, no one will have partial or full immunity against infection because it is a completely new virus. If this new virus also has the capacity to spread from person-to-person, then a pandemic will occur.

Outbreaks of influenza in animals, especially when happening simultaneously with annual outbreaks in humans, increase the chances of a pandemic, through the merging of animal and human influenza viruses. During the last few years, the world has faced several threats with pandemic potential, making the occurrence of the next pandemic just a matter of time.

If an influenza pandemic appears, we could expect the following:

• Given the high level of global traffic, the pandemic virus may spread rapidly, leaving little or no time to prepare.
• Vaccines, antiviral agents and antibiotics to treat secondary infections will be in short supply and will be unequally distributed. It will take several months before any vaccine becomes available.
• Medical facilities will be overwhelmed.
• Widespread illness may result in sudden and potentially significant shortages of personnel to provide essential community services.

The effect of influenza on individual communities will be relatively prolonged when compared to other natural disasters, as it is expected that outbreaks will reoccur.

Symptoms & Treatment

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. Diarrhea, vomiting, abdominal pain, chest pain, and bleeding from the nose and gums have also been reported as early symptoms in some patients. Watery diarrhea 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 diarrhea, 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.

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.

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 the World Health Organization (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.

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.

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, the World Health Organization (WHO) will have a stockpile of antiviral medications, sufficient for 3 million treatment courses, by early 2006. Recent studies, based on mathematical modeling, 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 behavior 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 World Health Organization (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.

Countries affected by the outbreak 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 behaviors identified include the slaughtering, defeathering, butchering and preparation for consumption of infected birds. In a few cases, exposure to chicken feces 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 feces 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 feces 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, behaviors, 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 feces 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 traveling to a country with ongoing outbreaks in poultry or sporadic human cases does not place a traveler 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.

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.

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. 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.

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 feces, 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 feces, 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 behaviors. • 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 behavior 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 travelers.

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 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.

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.

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.

Things You Need To Know About Pandemic Influenza

Pandemic influenza is different from avian influenza. Avian influenza refers to a large group of different influenza viruses that primarily affect birds. On rare occasions, these bird viruses can infect other species, including pigs and humans. The vast majority of avian influenza viruses do not infect humans. An influenza pandemic happens when a new subtype emerges that has not previously circulated in humans.

For this reason, avian H5N1 is a strain with pandemic potential, since it might ultimately adapt into a strain that is contagious among humans. Once this adaptation occurs, it will no longer be a bird virus--it will be a human influenza virus. Influenza pandemics are caused by new influenza viruses that have adapted to humans. Influenza pandemics are recurring events.

An influenza pandemic is a rare but recurrent event. Three pandemics occurred in the previous century: “Spanish influenza” in 1918, “Asian influenza” in 1957, and “Hong Kong influenza” in 1968. The 1918 pandemic killed an estimated 40–50 million people worldwide. That pandemic, which was exceptional, is considered one of the deadliest disease events in human history. Subsequent pandemics were much milder, with an estimated 2 million deaths in 1957 and 1 million deaths in 1968.

A pandemic occurs when a new influenza virus emerges and starts spreading as easily as normal influenza – by coughing and sneezing. Because the virus is new, the human immune system will have no pre-existing immunity. This makes it likely that people who contract pandemic influenza will experience more serious disease than that caused by normal influenza.

The World May Be On The Brink Of Another Pandemic

Health experts have been monitoring a new and extremely severe influenza virus – the H5N1 strain – for almost eight years. The H5N1 strain first infected humans in Hong Kong in 1997, causing 18 cases, including six deaths. Since mid-2003, this virus has caused the largest and most severe outbreaks in poultry on record. In December 2003, infections in people exposed to sick birds were identified. Since then, over 100 human cases have been laboratory confirmed in four Asian countries (Cambodia, Indonesia, Thailand, and Viet Nam), and more than half of these people have died. Most cases have occurred in previously healthy children and young adults. Fortunately, the virus does not jump easily from birds to humans or spread readily and sustainably among humans. Should H5N1 evolve to a form as contagious as normal influenza, a pandemic could begin.

All Countries Will Be Affected

Once a fully contagious virus emerges, its global spread is considered inevitable. Countries might, through measures such as border closures and travel restrictions, delay arrival of the virus, but cannot stop it. The pandemics of the previous century encircled the globe in 6 to 9 months, even when most international travel was by ship. Given the speed and volume of international air travel today, the virus could spread more rapidly, possibly reaching all continents in less than 3 months.

Widespread Illness Will Occur

Because most people will have no immunity to the pandemic virus, infection and illness rates are expected to be higher than during seasonal epidemics of normal influenza. Current projections for the next pandemic estimate that a substantial percentage of the world’s population will require some form of medical care. Few countries have the staff, facilities, equipment, and hospital beds needed to cope with large numbers of people who suddenly fall ill. Medical supplies will be inadequate.

Supplies of vaccines and antiviral drugs – the two most important medical interventions for reducing illness and deaths during a pandemic – will be inadequate in all countries at the start of a pandemic and for many months thereafter. Inadequate supplies of vaccines are of particular concern, as vaccines are considered the first line of defense for protecting populations. On present trends, many developing countries will have no access to vaccines throughout the duration of a pandemic. Large numbers of deaths will occur.

Historically, the number of deaths during a pandemic has varied greatly. Death rates are largely determined by four factors: the number of people who become infected, the virulence of the virus, the underlying characteristics and vulnerability of affected populations, and the effectiveness of preventive measures. Accurate predictions of mortality cannot be made before the pandemic virus emerges and begins to spread. All estimates of the number of deaths are purely speculative.

The World Health Organization (WHO) has used a relatively conservative estimate – from 2 million to 7.4 million deaths – because it provides a useful and plausible planning target. This estimate is based on the comparatively mild 1957 pandemic. Estimates based on a more virulent virus, closer to the one seen in 1918, have been made and are much higher. However, the 1918 pandemic was considered exceptional. Economic and social disruption will be great.

High rates of illness and worker absenteeism are expected, and these will contribute to social and economic disruption. Past pandemics have spread globally in two and sometimes three waves. Not all parts of the world or of a single country are expected to be severely affected at the same time. Social and economic disruptions could be temporary, but may be amplified in today’s closely interrelated and interdependent systems of trade and commerce. Social disruption may be greatest when rates of absenteeism impair essential services, such as power, transportation, and communications.

AvianFlu