October 18, 2005
Last reviewed and revised on January 8, 2009
By Anthony L. Komaroff, M.D.
Harvard Medical School
The year 2005 will be remembered for a series of natural catastrophes the tsunami in Asia, hurricanes Katrina and Rita and the earthquake in Kashmir. Each of these tragic events killed or injured large numbers of people, made many more homeless, and did enormous economic damage. Recently, many people also heard for the first time about a new potential natural catastrophe: a worldwide pandemic of bird (or avian) flu. While no one can predict with confidence whether such a pandemic will occur, there is little disagreement among the experts that such a pandemic, should it come, would have terrible effects. Indeed, in our judgment, a pandemic of bird flu has the potential to be the largest threat to the public health of the United States, and the world, in the next decade.
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What is Bird Flu?
Flu is the short name for influenza, a disease caused by the influenza viruses. These viruses can infect humans, birds, pigs and other animals. Generally, each strain of the virus infects just one species, and does not leap to other species. For example, most strains that infect birds are contagious among birds but have a hard time spreading to humans.
Bird flu strains of the influenza virus spread among birds. The strains typically cause serious disease in birds. Wild, migratory birds can carry the virus over long distances to birds in other parts of the world. Only occasionally have strains of bird flu developed the ability to infect humans.
Each type of flu virus has genes that determine which animal species it can infect, and genes that determine how serious the illness it causes will be. The genes of flu viruses mutate easily, and when several different flu viruses infect the same animal, the viruses can "swap" genes, leading to new types of flu virus that are capable of producing more or less serious disease, and of being more or less contagious.
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How Serious and Contagious Is It?
The unusual occasions when bird flu viruses are transmitted to humans occur when humans live in close contact with birds, such as farmers raising chickens. When humans become infected by a bird flu virus, they typically become very sick. Indeed, even for healthy young adults, the disease can be fatal.
In 1997, there was an outbreak of bird flu in Hong Kong. The type of bird flu virus involved is called H5N1, based on two chemicals in the virus's protein coat. The 1997 outbreak of H5N1 flu involved large numbers of birds, including domestic poultry, and a few humans. That outbreak was stopped by killing virtually all commercial poultry being raised in Hong Kong. This was devastating to the local agricultural economy, but may have prevented worldwide epidemics.
However, there have been recurrent outbreaks of bird flu since 1997. More than 200 million birds worldwide have died or been killed, including the bulk of the commercial poultry industry of several nations. More than 100 humans have been infected with the H5N1 virus, all in Asia, and most of them have died. While a few of these cases may have involved transmission of the virus from one sick person to another person in close contact with the sick person, most of the cases have involved the virus being passed from birds to humans in close contact with the birds.
So, the bad news about this virus is that it is lethal: a majority of people infected have died. The good news is that the virus is extremely hard to transmit from animal to human, and even harder to transmit from one person to another. Thus, the current H5N1 virus could not cause a worldwide pandemic, or even a local epidemic, among humans.
The reason doctors are worried is that the H5N1 virus could change and become very contagious. In fact, most human flu viruses are very contagious: Humans easily pass the typical human flu viruses to other humans. In summary, the bird flu viruses cause serious disease but are not contagious, while the human flu viruses typically cause less serious disease but are very contagious.
Doctors are concerned that the H5N1 virus, or another bird flu virus, could undergo genetic changes that suddenly allow it to easily infect humans, while preserving the genes that cause it to produce serious disease in humans. Because the normal flu viruses are so contagious, epidemics of the virus tend to spread all over the world the kind of epidemic called a pandemic. There were three flu pandemics in the 20th century.
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The 20th Century Pandemics
By far the worst pandemic in the 20th century occurred in 1918. Studies of the bird flu virus that caused the pandemic of 1918, reported in October 2005, show that this virus has genes that are very similar to those of the H5N1 virus. The 1918 virus made a genetic change that allowed it to infect humans, and doctors are worried that the current, very similar, H5N1 virus also could jump to humans.
There is some evidence that the pandemic of 1918 started near Boston, Massachusetts. In September 1918, the camp hospital at Fort Devens outside Boston, which was built to house 1,200 soldiers, was suddenly overflowing with 6,000. The 6,000 soldiers had been healthy and fit young men who began to feel ill and within 12 to 24 hours were choking to death, their lungs filled with fluid.
Shortly after the outbreak at Fort Devens, 250 people a day were dying in Boston. The epidemic spread to New York City. Within a few weeks, 21,000 children in New York were orphaned. Within a few months, the flu epidemic spread across the entire globe. In less than a year, nearly one billion people were infected, worldwide, and between 20 million to 40 million died, as many or more as have died from AIDS in the past 25 years. About 3% of all people infected by the 1918 virus died, including many young and healthy individuals.
The pandemics of 1957 and 1968 were less severe than the 1918 pandemic. Fewer people were made ill or killed by the 1957 and 1968 viruses than by the 1918 virus. However, many more were killed than in a typical annual influenza epidemic.
The cost to society of these milder pandemics was considerable. The 1968 pandemic killed about one million people worldwide, a small fraction of the 20 million to 40 million killed in 1918. Yet the 1968 pandemic cost the U.S. economy between $70 billion and $167 billion, a figure not very different from the cost of the war in Iraq or the cost of rebuilding after hurricanes Katrina and Rita. Therefore, the cost to the U.S. and world economies of the 1918 pandemic, which killed 20 to 40 times more people than the 1968 pandemic, must have been enormous.
Finally, doctors are concerned because the 1918 virus killed about 3% of the people that it infected. In contrast, the current H5N1 virus has killed over 50% of the people it has infected. While the H5N1 virus may never mutate in such a way as to produce a pandemic, it is not hard to understand why doctors are worried.
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What Can Be Done?
The Public Health System Response
Preventing a pandemic of bird flu depends on public health systems in countries around the world. That means that the United States is critically dependent on the public health systems in many relatively poor countries in Asia.
The World Health Organization, an arm of the United Nations, is working with the U.S. Centers for Disease Control and Prevention and similar public health agencies around the world to assist the affected Asian countries. Health authorities are making extra efforts to detect any infected birds and to kill birds exposed to the virus. People who are in close contact with the birds, such as farmers, are being closely monitored. If they develop a flu-like illness, they are placed in medical observation and isolated from other people.
This kind of aggressive public health campaign halted the SARS epidemic in 2003. The window of opportunity in halting any epidemic is to identify and isolate people with the virus before they are capable of spreading it to others.
With the SARS virus, that window of opportunity is six days. With the typical flu virus, it is just two days. And the typical flu virus is much more contagious than the SARS virus.
The challenge to public health systems particularly in poor, developing nations is enormous. Consider Indonesia, for example, a country of about 250 million people that is composed of 6,000 islands. In the past few years, the H5N1 virus has been carried by wild birds to Indonesia. This is particularly worrisome, because of the size of the country and the close contact of humans and animals. Consider two animals: pigs and chickens.
Pigs are often described as the perfect "mixing vessel" in which a new lethal and contagious flu virus could develop. Pigs are easily infected by both avian and human flu viruses. It is estimated that up to half of the pigs in Indonesia are infected with the H5N1 virus; many also carry human flu viruses. As for chickens, in Indonesia there are 30 million farms containing 1.3 billion chickens.
What if there was an outbreak of avian flu on one of those farms, transmitted originally to humans by pigs or chickens, and now being spread among humans? Imagine the kind of public health system that it would take to spot that outbreak, and to quarantine the people on the farms before they traveled elsewhere, carrying the new virus with them. Then consider Indonesia, a country of 250 million people where the average person earns $3,500 a year and imagine the kind of public health system that Indonesia can afford to have.
In the past eight weeks, in Jakarta (a city of 20 million) there have been several family clusters of H5N1 flu, often fatal. It is not yet clear whether all of the infected people had close contact with animals.
Studies conducted in the past few years have found that one drug used to treat the regular flu virus, oseltamivir (Tamiflu), appears to kill the H5N1 virus in a test tube. Other drugs used against the regular flu virus have been less successful. A remarkable new technology called RNA interference, discovered by basic research, also has been effective in a test tube. However, treatments that work in a test tube do not always work in people. Since there has been no outbreak of human disease from H5N1 virus involving large numbers of people, it is impossible to say how effective various possible treatments would be. Even if oseltamivir proves to be effective, the current supply of the drug is too small to be able to offer much help against a pandemic.
Vaccines against the H5N1 virus were tested in 2005, and shown to effectively alert the immune system to attack the virus, a necessary condition if a vaccine is to be effective. But, as with drug treatments, until there is an outbreak of human disease with this virus, we will not know how effective the vaccine will be. Also, as with drug treatments, the world does not currently have the capacity to produce enough of this promising but unproven vaccine to deal with a pandemic of H5N1 virus should it come in the next couple of years.
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Reason for Encouragement
While there is plenty of reason for concern about a new pandemic of bird flu, the picture is not entirely bleak. If a new pandemic does develop from the H5N1 or a similarly lethal bird flu virus, it will not necessarily produce disease as severe as was seen in the 1918 pandemic. It all depends on luck: on which genes the new virus changes or acquires.
Also, the technologies available to scientists and doctors for diagnosis, treatment and immunization today are vastly superior to the technologies available in the 20th century pandemics. Even as recently as 1968, it was impossible to determine the structure of the virus's genes. Today, that can be done very rapidly, and versions of the virus can be created and tested (in high security facilities to prevent accidental escape). This allows doctors to identify which genes, and changes in those genes, are responsible for causing severe disease or contagiousness. It also allows them to test potential treatments and to develop vaccines more rapidly.
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Anthony L. Komaroff, M.D., is professor of medicine and editor-in-chief of Harvard Health Publications at Harvard Medical School. Dr. Komaroff also is senior physician and was formerly director of the Division of General Medicine at Brigham and Women's Hospital. Dr. Komaroff has served on various advisory committees to the federal government, and is an elected Fellow of the American Association for the Advancement of Science.