Viruses are masters of interspecies navigation. Mutating rapidly and often grabbing the genetic material of other viruses, they can jump from animals to humans with a quick flick of their DNA. Sometimes, as in West Nile fever, the transfer occurs through an intermediate host such as a mosquito. But viruses can also make the leap directly.

Since the 1980s, the list of diseases that have hitchhiked directly from animals to people has grown rapidly — hantavirus, SARS, monkeypox and, most recently, avian influenza, commonly called bird flu. With the exception of HIV/AIDS, perhaps none of these illnesses has more potential to create widespread harm than bird flu does.

In people, bird flu usually begins much like conventional influenza, with fever, cough, sore throat and muscle aches, but bird flu can lead to life-threatening complications.

In early 2005, health officials increasingly warned of the potential for a major bird flu outbreak. The grimmest scenario would be a global epidemic to rival the flu pandemic of 1918 and 1919, which claimed at least 20 million lives worldwide.

Meanwhile, researchers continue to look at ways to prevent or blunt such an outbreak. In August 2005, the U.S. government announced plans to acquire millions of doses of an experimental vaccine, after tests showed its effectiveness. Initial tests showed the vaccine stimulated an immune response in healthy adults. Additional tests were to continue on children and in people older than 65.

Signs and symptoms

Bird flu viruses are complex, with a number of subtypes and strains that vary considerably from one another. In the broadest terms, however, the viruses are classified as having a low or high chance of causing disease (low or high pathogenicity).

Among birds, the effects of low pathogenic viruses are usually minor — ruffled feathers or reduced egg production. But highly pathogenic forms cause severe disease, including respiratory distress, and almost 100 percent mortality in susceptible species. In some cases, domestic birds may die the same day symptoms appear.

Scientists don't yet know just how these subtypes affect humans, but highly pathogenic viruses appear to cause the most serious problems — and the greatest number of deaths — in both people and animals.

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. Sometimes the only indication of the disease is a relatively mild eye infection (conjunctivitis). But more often, signs and symptoms of bird flu resemble those of conventional influenza, including:

• Cough
• Fever
• Sore throat
• Muscle aches

People with the most virulent type of bird flu virus — (A) H5N1 — may develop life-threatening complications, particularly viral pneumonia and acute respiratory distress, the most common cause of bird flu-related deaths.

Causes

Lying in bed with chills, a spiking fever and that run-over-by-a-truck feeling, you're not likely to care much about the habits and history of flu viruses. But epidemiologists do care — and with good reason.

Each winter, an average of 36,000 people die of influenza in the United States. 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 on both the small and the grand scale 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

All influenza viruses are divided into three types — A, B or C — depending on the virus structure. Type A is responsible for lethal influenza pandemics whereas type B causes smaller, localized outbreaks. Less common and more stable than other strains, type C has milder symptoms. Influenza B and C are usually found only in humans. But type A influenza infects both people and animals, including birds, pigs, horses, whales and seals.

Influenza A viruses are divided into subtypes based on two surface proteins:

• Hemagglutinin (HA)
• Neuraminidase (NA)

Fifteen distinct HA subtypes and nine NA subtypes exist, but they can combine to form a number of other subtypes, some of which normally are specific to a single species.

For example, subtypes H1N1, H1N2 and H1N3 usually cause influenza in humans, whereas H7N7 and H3N8 viruses cause disease in horses. 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 indiscriminately — that makes them so unpredictable and potentially deadly.

Faster than you can say antigenic

All living things change, but influenza A viruses change quickly, constantly and sometimes cataclysmically. This takes place in two ways:

• Antigenic drift. These are small, permanent, ongoing alterations in the genetic material of a virus. Because viruses aren't able to repair genetic errors that take place as they reproduce, new strains are continually replacing old ones. Once you have a particular strain of flu, you develop antibodies to it, but those antibodies won't protect you from new strains. In the same way, the flu vaccine you received last season won't ward off this year's bug.
• Antigenic shift. This occurs when influenza A subtypes from different species — a bird and a human, for example — trade and merge genes. The result is an entirely new strain, different from either of the parent viruses. Because no natural immunity to the new strain exists, it can spread quickly, causing widespread illness and death. And when one of the original subtypes is a human influenza virus, the new virus has the ability to spread easily from person to person and the potential to become a global epidemic.

How humans get bird flu

Migratory waterfowl, and ducks in particular, carry the viruses that cause bird flu. Often unaffected themselves, the host birds can spread the infection to susceptible species, especially domesticated chickens, turkeys and geese, resulting in severe epidemics that sicken and kill large numbers of birds — sometimes in a single day.

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 the Netherlands, Canada and throughout Asia. Most were traced to contact with infected poultry or surfaces contaminated by sick birds.

The genetic scrambling that occurs in antigenic shift explains how a disease that normally affects a bird or animal can suddenly turn up in humans. 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. They may also catch the disease the same way humans contract conventional flu — by inhaling the airborne virus. Bird flu spreads quickly and lethally within a flock and is inadvertently transported from farm to farm on tractors and other equipment, on cages, and on 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 often sold in crowded and unsanitary conditions, are hotbeds of infection and spread the disease into the wider community. Cock fighting, rampant throughout much of Asia, has also been implicated in the spread of bird flu — fighting roosters are often trucked long distances and smuggled across borders. 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 chicken or fighting rooster.

The ease of worldwide travel has the potential to spread bird flu around the globe, although that hasn't happened yet. Scientists don't think that migratory birds are carrying the virus from continent to continent because outbreaks haven't followed traditional flyways. Instead, outbreaks seem much more likely to spread locally through "wet markets," contaminated clothing and equipment, and smuggled birds.

(A) H5N1: Prelude to a pandemic?

Fifteen known subtypes of influenza A virus can affect birds. Although some strains are more deadly than others, even mild forms can quickly mutate into highly pathogenic types.

In the current epidemic, two influenza subtypes have proved especially dangerous — (A) H7N7, which sickened poultry workers in the Netherlands, and (A) H5N1, which has been responsible for the majority of human and avian deaths in Asia. Of these, (A) H5N1 is of particular concern for several reasons:

• Direct transmission. H5N1 became the first known bird flu strain to jump directly from birds to people when it surfaced in Hong Kong in 1997. It has since infected people in other Southeast Asian countries, including Vietnam and Thailand. Two other strains have caused illness in humans, but neither is as severe as H5N1.
• Virulence. The virus is especially lethal, killing close to 100 percent of susceptible birds and more than half of infected people. Birds who do survive can shed the virus for at least 10 days, greatly increasing the flu's spread.
• Rapid spread. Since 2003, hundreds of millions of birds have died, a loss that's ecologically and economically devastating. It's also alarming from a public health standpoint — widespread infections among birds may lead to more human disease.
• Genetic scrambling. (A) H5N1 mutates quickly and is notorious for grabbing large blocks of genetic code from viruses that infect other species, a process called reassortment. For that reason, it 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.

Risk factors

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 such transmission becomes more widespread, infected birds or material present the greatest hazard.

Even so, the pattern of human transmission remains mysterious. Young children seem especially vulnerable to the virus. Some scientists speculate they may simply be more likely to breathe infected dust or feces. On the other hand, tens of thousands of unprotected Asian workers involved in culling chickens haven't developed the disease. At this point, too few people have been infected to know all the possible risk factors for bird flu.

When to seek medical advice

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 were traveling and whether you visited any farms or open-air markets.

Doctors have rapid tests to identify the flu virus, but the tests can't distinguish between avian flu and other influenza A viruses. For that reason, specimens from anyone with a suspected case of bird flu would be sent to state health labs or the Centers for Disease Control and Prevention (CDC) for analysis.

Complications

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 rather than with air, leading to severe breathing difficulties.

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 preponderance of human genes. This could make the virus highly contagious and, with no 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 it's just a matter of time before avian viruses figure out a way to way to spread easily among people.

Treatment

In August 2005, the U.S. government said it would purchase millions of doses of an experimental bird flu vaccine from a French vaccine maker. The announcement came after the government said tests showed that the vaccine promoted an immune system response in healthy adults younger than age 65. The vaccine still needs to tested over several months in adults older than 65 and in children. And the U.S. Food and Drug would still need to approve use of the vaccine. The government would plan to use the vaccine if it is shown that bird flu can pass from person to person and if the disease were to reach the United States.

Right now, the primary treatment option is the flu drug oseltamivir (Tamiflu), a neuraminidase inhibitor that works by preventing the virus from escaping its host cell. It's not clear how effective Tamiflu will ultimately prove against (A) H5N1 — preliminary studies have shown that flu viruses may become resistant to it fairly quickly. What's more, the drug has to be taken within two days after the appearance of symptoms, something that may prove logistically difficult on a worldwide scale. Tamiflu also is expensive and in limited supply. How the drug would be allocated in the event of a widespread epidemic remains problematic.

Prevention

The international effort to prevent the spread of bird flu is multifaceted, focusing on the health of both birds and humans. Measures to help control the virus among domestic poultry include:

• Culling. Since 1997, when the first human cases of bird flu appeared, hundreds of millions of sick or exposed birds — primarily chickens — have been destroyed. In many cases, affected farms were also quarantined. Although some have questioned the wisdom of such wholesale slaughter as well as the methods used to cull birds — many are burned or buried alive — the WHO considers this approach the first-line defense against avian viruses.
• Surveillance programs. Some nations have instituted strict vaccination and surveillance programs for poultry farms and markets, taken steps to prevent bird smuggling, and put in place programs that quarantine new birds until they're proved healthy and that require poultry farmers to disinfect boots and tires.
• Banned birds. Many countries have banned or restricted the importation of birds and hatching eggs from regions with bird flu epidemics. In February 2004, the CDC banned the importation of poultry into the United States from most Asian nations.

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 colorful or dreadful, depending on your tolerance level, but no matter how you see them, they're often breeding grounds for disease.
• Wash your hands. One of the simplest ways to prevent infections of all kinds, hand washing is also one of the best. When you're traveling, alcohol-based hand sanitizers, which don't require the use of water, are an excellent choice. They're actually more effective than hand washing in killing bacteria and viruses that cause disease. Commercially prepared hand sanitizers contain ingredients that help prevent skin dryness. In fact, use of these products can result in less skin dryness and irritation than hand washing. Not all hand sanitizers are created equal, however. Some "waterless" hand sanitizers don't contain alcohol. Use only the alcohol-based products.
• 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 from bird flu, but it may help reduce the risk of simultaneous infection with bird and human flu viruses.

Preparing poultry

No human cases of bird flu have been linked to eating poultry, although in at least one instance, the H5N1 virus was found in a package of frozen duck. 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 an internal temperature of 180 F. Avoid eating raw or undercooked eggs or any products containing them, including mayonnaise, hollandaise sauce and homemade ice cream.