Bird flu has led to the deaths of hundreds of millions of wild and domestic birds and to a small number of human deaths. Right now, however, bird flu remains difficult for humans to contract. Most people who have developed symptoms have had close contact with sick birds, though in a few cases, bird flu has passed from one person to another.

Health officials are concerned that a major bird flu outbreak could occur in humans if the virus — H5N1 — mutates into a form that can spread more easily from person to person. The grimmest scenario would be a global outbreak to rival the flu pandemic of 1918 and 1919, which claimed millions of lives worldwide. For now, researchers are trying to develop a vaccine that would protect people in the event of a bird flu pandemic.

Although the exact incubation period for bird flu in humans isn't clear, illness seems to develop within one to five days of exposure to the virus.

Common signs and symptoms
Most often, signs and symptoms of bird flu resemble those of conventional influenza, including:

• Cough
• Fever
• Sore throat
• Muscle aches

A relatively mild eye infection (conjunctivitis) is sometimes the only indication of the disease.

Severe signs and symptoms
People with bird flu also may develop life-threatening complications, particularly:

• Viral pneumonia
• Acute respiratory distress — the most common cause of bird flu-related deaths

According to the Centers for Disease Control and Prevention (CDC), about 36,000 people die of influenza in the United States each winter. And three or four times every century, a flu pandemic sweeps the globe, claiming millions of lives. That the flu can cause so much misery is a result of its ability to change quickly and unexpectedly, to outwit "best guess" vaccines, and to take the immune system by storm.

The ABCs of influenza viruses
Influenza viruses are divided into three types (strains) of viruses — influenza A, B and C. Type A is responsible for the deadly influenza pandemics. Type B can lead to smaller, more localized outbreaks. Less common and more stable than other strains, type C has milder symptoms. Either types A or B can cause the flu that circulates almost every winter. Types B and C are usually found only in humans, whereas type A infects both people and animals, including birds, pigs, horses, whales and seals.

Numerous influenza A subtypes exist, and they can combine to form even more subtypes, some of which affect only certain animals. At least 15 flu subtypes affect birds, the most virulent of which is H5N1. Until recently, avian subtypes have rarely been found in humans or in animals other than pigs.

Type A influenza viruses are further divided into strains, which are constantly evolving. And it is exactly this — the ability of influenza viruses to change their genetic makeup and to swap genes — that makes them so unpredictable and potentially deadly.

How humans get bird flu
Avian viruses generally don't affect humans, but in 1997, an outbreak of bird flu in Hong Kong infected 18 people, six of whom died. Since then, human cases of bird flu have been reported in Asia, Europe and the Middle East. Most were traced to contact with infected poultry or surfaces contaminated by sick birds.

Often, flu viruses that cross the species barrier originate in areas where people live in close proximity to chickens and pigs. That's because pigs are susceptible to infection with both avian and human viruses and so are an ideal "mixing bowl" for genes.

But at least some bird flu viruses don't need a third party. Instead, they shuffle and rearrange their genetic material directly in humans. That seems to be the case in most instances of human-acquired bird flu. People become sick after direct contact with infected birds or bird-contaminated surfaces, not from contact with other animals.

Direct bird-to-human transmission works like this:

• Wild birds shed the virus. Infected migratory waterfowl, the natural carriers of bird flu viruses, shed the virus in their droppings, saliva and nasal secretions.
• The virus spreads to domesticated birds. Domestic poultry become infected from contact with these birds or with contaminated water, feed or soil. Bird flu spreads quickly within a domestic flock and is inadvertently transported from farm to farm on equipment, cages, and workers' shoes and clothing. Heat destroys the virus, but it can survive for extended periods in cool temperatures.
• Markets provide pathways to humans. Open-air markets, where eggs and birds are sold in crowded and unsanitary conditions, are hotbeds of infection and spread the disease into the wider community. At any point along the way, humans may pick up the virus through close contact with sick birds or contaminated surfaces. An ailing bird can shed the virus in its feathers as well as in droppings, and some people have contracted bird flu simply by touching an infected bird.

The ease of worldwide travel has the potential to spread bird flu around the globe. And migratory birds can carry the virus from continent to continent along flyways. Outbreaks may also spread locally through unsanitary markets, contaminated clothing and equipment, and smuggled birds.

Prelude to a pandemic?
H5N1 mutates quickly and is able to incorporate large blocks of genetic code from viruses that infect other species, a process called reassortment. For that reason, H5N1 has particular potential to combine with a human flu virus, creating a new viral strain that spreads rapidly from person to person. The emergence of such a virus would mark the beginning of a potentially devastating pandemic. The ability of H5N1 to evolve rapidly was demonstrated in October 2006 when a new strain, called H5N1 Fujian-like, appeared in China and spread quickly throughout much of Southeast Asia. The new strain is immune to the vaccines normally given to birds to prevent H5N1 infections.

The greatest risk factor for bird flu seems to be contact with sick birds or with surfaces contaminated by their feathers, saliva or droppings. The World Health Organization (WHO) has confirmed a handful of cases of limited human-to-human transmission of bird flu. But unless the virus begins to spread more easily among people, infected birds or associated material presents the greatest hazard.

The pattern of human transmission remains mysterious. Young children seem especially vulnerable to the virus, although some experts note that children are more likely to have contact with sick birds or to play on ground contaminated with droppings. What's more, people of all ages have contracted and died of bird flu. At this point, too few people have been infected to know all the possible risk factors for bird flu.

See your doctor immediately if you develop flu symptoms, including a fever, cough and body aches, and have recently traveled to a part of the world where bird flu occurs. Be sure to let your doctor know when and where you traveled and whether you visited any farms or open-air markets.

Doctors have rapid tests to identify the flu virus, but until recently, the tests couldn't distinguish between avian flu and other influenza A viruses. For that reason, specimens from anyone with a suspected case of bird flu were sent to state health labs or the Centers for Disease Control and Prevention (CDC) for analysis. However, in September 2007, researchers in Singapore announced a new rapid test that detects bird flu by taking a swab of your throat, then analyzing the collected droplets using a hand-held device. This test or similar ones may become commercially available in the future.

Most people with bird flu have signs and symptoms of conventional influenza. Some also develop life-threatening complications such as viral pneumonia and acute respiratory distress syndrome, which causes the air sacs in your lungs to fill with fluid, leading to severe breathing difficulties. More than half the people who have contracted bird flu have died.

But the greatest complication of bird flu is still hypothetical — the emergence of a new viral strain that spreads easily from person to person. If a person were simultaneously infected with human and bird flu viruses, the reassortment of genetic material could produce an entirely new subtype with a majority of human genes. This could make the virus highly contagious and, with little natural immunity among the world population, especially lethal.

So far this hasn't happened. A few cases of person-to-person transmission have occurred, but they were limited in scale. Still, some health officials fear that it's just a matter of time before avian viruses figure out a way to spread easily among people.

For now, the primary treatment option remains the flu drug oseltamivir (Tamiflu), which works by preventing the virus from multiplying. It's not clear how effective Tamiflu will prove against H5N1. Another antiviral flu drug, zanamivir (Relenza), may be an alternative. However, viruses may become resistant to both of these drugs.

These drugs must be taken within two days after the appearance of symptoms, something that may prove logistically difficult on a worldwide scale, even if there were enough to go around. Because they're in short supply, it's not entirely clear how flu drugs would be allocated if there were a widespread epidemic.

Bird flu vaccine
In April 2007, the Food and Drug Administration approved the first human vaccine to prevent infection with one strain of H5N1 bird flu virus. This new bird flu vaccine isn't available to the public, but the U.S. government is stockpiling it and will distribute it in the event of an outbreak. It's intended to help protect adults ages 18 to 64 and could be used early in such an outbreak to provide limited protection until another vaccine — designed to protect against the specific form of the virus causing the outbreak — is developed and produced.

When tested, the bird flu vaccine fully protected only about 45 percent of those vaccinated — about half the effectiveness rate of the seasonal influenza vaccine. However, it still may help reduce the severity of the disease and decrease the risk of hospitalization and death in those who aren't fully protected.

Researchers are also studying other vaccines. One such vaccine, not yet approved for humans, appears to be safe and even more effective than the currently approved vaccine. Research published in the June 2008 issue of the New England Journal of Medicine showed that up to 75 percent of those injected with the vaccine produced antibodies to multiple strains of the bird flu virus. And, because this vaccine can be created in cell culture instead of an egg, it could be produced more quickly than the already approved vaccine.

Recommendations for travelers
If you're traveling to Southeast Asia or to any region with bird flu outbreaks, consider these public health recommendations:

• Avoid domesticated birds. If possible, avoid rural areas, small farms and especially any close contact with domesticated fowl.
• Avoid open-air markets. These can be interesting places to visit, but they're often breeding grounds for disease.
• Wash your hands. This is one of the simplest and best ways to prevent infections of all kinds. When you're traveling, alcohol-based hand sanitizers containing at least 60 percent alcohol are an excellent choice. They are effective, easy to use, don't require water, and they're safe for children.
• Watch your kids. Keep a careful eye on young children, who are likely to put their hands in their mouths and who may not wash thoroughly.
• Steer clear of raw eggs. Because eggshells are often contaminated with bird droppings, avoid mayonnaise, hollandaise sauce, ice cream, and any other foods containing raw or undercooked eggs.
• Ask about a flu shot. Before traveling, ask your doctor about a flu shot. It won't protect you specifically from bird flu, but it may help reduce the risk of simultaneous infection with bird and human flu viruses.

Preparing poultry
Because heat destroys avian viruses, WHO officials don't consider cooked poultry a health threat. Even so, it's best to take precautions when handling and preparing poultry, which is often contaminated with salmonella or other harmful bacteria.

• Wash well. Carefully wash cutting boards, utensils and all surfaces that have come into contact with raw poultry in hot, soapy water. Wash your hands thoroughly before and after handling poultry and dry them with a disposable towel.
• Cook thoroughly. Cook chicken until the juices run clear, and it reaches a minimum internal temperature of 165 F (74 C).