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In recent months, there have been increasing reports of the spread of avian influenza (so-called "bird flu") in Asia and potentially into Eastern Europe. At least 121 human cases and 62 deaths have been reported. These developments have raised concerns that the avian virus -- which so far has not been efficiently transmitted from human to human -- might mutate and become much more transmissible. This could lead to a worldwide pandemic with potentially devastating health consequences. The purpose of this white paper is to provide background on influenza and influenza pandemics, describe what is known about avian influenza and its potential to adapt to humans, and outline briefly what can be done to mitigate a possible pandemic.
Influenza Pandemics
Two criteria must be met for an influenza pandemic to occur. First, a new strain of influenza A virus to which the vast majority of the population lacks immunity must appear; and second, the new virus must be able to easily infect and be transmitted by humans.
During the past century, there were three influenza pandemics, 1918-1919, 1957-58, and 1968-69, which caused approximately 500,000, 70,000, and 34,000 U.S. deaths, respectively. The chief determinant of immunity to influenza is a surface protein of the virus, the hemagglutinin or H protein. Only three varieties of hemagglutinins have circulated in humans, H1, H2, and H3. In recent years both H1 and H3 viruses have circulated so most people have some underlying immunity to these viruses. However, there are 13 other known hemagglutinins in nature. These hemagglutinins have their "reservoir " in birds, primarily wild waterfowl. If any of them become part of viruses that are adapted to human hosts, they could cause pandemics.
Avian Influenza
The influenza A (H5N1) virus, the so called avian or bird flu, raises concerns because humans lack natural immunity to it. The H5 virus caused an epidemic among chickens in 1997 in Hong Kong. At that time, approximately 18 persons who had contact with poultry developed a severe respiratory illness, and six died. There was no evidence of person-to-person spread among cases. Since that time, the virus has been spreading extensively in Southeast Asia among chickens and aquatic birds, is now affecting the former Soviet Union and Eastern Europe, and has mutated to become much more virulent in birds. Further, the virus seems to be able to infect mammals including large cats. It is known to have infected approximately 121 persons in Vietnam, Thailand, Cambodia, and Indonesia, leading to 62 deaths. The vast majority of human cases can be traced to exposure to birds. However, there is some limited evidence of person-to-person spread in families, but this transmission seems to require prolonged intimate contact. There is no evidence of efficient transmission of avian influenza viruses from person-to-person, as occurs with human-adapted influenza viruses.
The H5 virus has infected patients of all ages. In contrast to annual influenza epidemics, which disproportionately cause deaths among the elderly and those with underlying conditions that put them at high risk of complications from influenza, many of the deaths from avian influenza have occurred in children and younger adults.
Avian influenza can adapt to humans in two ways. First, the avian viruses can infect humans or animals at the same time these hosts are infected by human-adapted influenza viruses. This concomitant infection by the two different sources of influenza virus could lead to an exchange of genes, whereby the surface of the new virus has an H5 protein but many of the other genes are from human-adapted viruses. Alternatively, the avian viruses, as they spread in birds and other species, can mutate to the point that they can easily infect humans.
What are the chances of a pandemic?
Ed Marcuse, a former Chairman of the National Vaccine Advisory Committee, has stated "The pandemic clock is ticking. We just don't know what time it is." Experts are certain there will be future pandemics of influenza. However, it is not clear whether the pandemic will occur this year, next year, or 10 or more years from now. In addition, it is not known whether the next pandemic will be caused by an H5 virus or by a virus with some other new hemagglutinin. Nevertheless, given the potential devastating consequences of pandemic influenza, it is worth increasing our preparedness to mitigate its burdens.
What can be done to reduce the threat and consequences of an influenza pandemic?
Three categories of intervention are possible: 1) vaccines, 2) anti-viral drugs, and 3) measures to limit spread in the population, such as isolation of cases, shutting schools, etc. Each of these will be discussed briefly.
- Influenza vaccines are the optimal means of preventing influenza. Current influenza vaccines usually protect about 70-90 percent of healthy adults who are vaccinated each year. The effectiveness of vaccines in preventing illness is lower in elderly populations but vaccines are more efficacious in preventing complications of influenza, including death, in this population. Influenza vaccines are reformulated annually because human-adapted influenza viruses tend to mutate.
At the present time, the government has approximately 2 million doses of avian influenza vaccine, assuming that the quantity of protein needed to protect against this virus is the same as the quantity of H proteins in standard annual influenza vaccines. Approximately 20 million more doses have been ordered.
There are several barriers to preventing avian influenza by vaccination that will need to be overcome. First, preliminary studies suggest that the quantity of H5 protein needed in each dose to induce a successful immune response may be four or more times that in standard vaccines. Second, two doses may be needed. Third, the H5 viruses have been mutating. It's unclear whether vaccine produced today will cover potential future strains that are spreading in people. Fourth, normally, it takes about 4-6 months to produce an influenza vaccine. Thus, comprehensive surveillance of influenza, particularly in Asia, is needed to have as much lead time as possible. Most experts assume that there is not likely to be sufficient quantities of vaccine early in a pandemic to make a difference, but since most pandemics have multiple waves, vaccines may be extremely helpful later.
- Antiviral drugs. There are two categories of drugs that can treat or prevent influenza, neuraminidase inhibitors (e.g., oseltamivir) and adamantanes. Only the neuraminidase inhibitors appear to be effective against the H5 viruses currently in circulation. At this time the government has purchased 2.3 million treatment courses of oseltamivir and plans to purchase an additional 20 million courses. Expert committees have recommended that a high priority be placed on the use of such drugs for both treatment and prevention in the event of a pandemic. Highest priorities are likely to go to hospitalized patients and persons providing critical societal support, such as health care workers.
- Population-based measures. Other strategies to minimize transmission of influenza may include isolating infected patients, eliminating large gatherings of people such as sporting events, shutting down other places where people congregate such as schools and places of employment, and use of "respiratory etiquette" including covering the mouth while coughing, frequent hand washing, and wearing face masks. Quarantine of potentially exposed persons has been mentioned but would be very difficult to enforce during a pandemic. Quarantine and isolation are of particularly limited practicality for influenza due to the short incubation period (1-4 days) and ability of an infected individual to transmit virus prior to developing symptoms of illness (up to 24 hours before symptoms).
Personal health advice
Get vaccinated with current influenza vaccines. Influenza vaccines are currently recommended for about 190 million Americans annually. The strains of influenza that are most likely to circulate this coming winter are the ones in the present vaccine, not avian influenza. Getting your flu shot will protect against current influenza strains.
Don't stockpile. Questions have been asked about whether individuals should stockpile anti-viral drugs. This is not being recommended. First, the quantities needed for effective prevention would be excessive. Drugs might need to be taken for months and there are side effects to the drugs. While the course of treatment once infection occurs does not require as much of the drug, one runs the risk of using the drugs for non-influenza illness since many other infectious agents can mimic influenza. Use of the drugs in persons with respiratory illnesses may result in not having medications when they are really needed for influenza.
For individuals eager to acquire such agents, however, the following pros and cons should be considered:
Pros-
- the anti-viral drug may prevent infection or ameliorate illness,
- individual acquisition will lessen dependency on governmental sources, which will be insufficient to meet the needs of all persons requiring treatment or prophylaxis if a severe pandemic occurs,
- drugs may be unavailable from any source when needed.
Cons-
- the drugs may be ineffective and are likely to be expensive,
- the optimal dose is not known, they have adverse reactions and for prophylaxis (prevention) they may have to be taken for many weeks (or even months?),
- it may be difficult to determine when to take them (unclear when exposures will have occurred, many illnesses may have similar symptoms as flu),
- individual use will undermine carefully considered national policy establishing those most at risk, in that:
- such use will diminish community supplies,
- stockpiles will be disproportionately available to the wealthiest citizens not those most at risk,
- there is currently no pandemic occurring, and
- personal stockpiling may result in shortages for use in seasonal influenza infections (the current season of what is most likely to be influenza that is non-avian is about to begin).
The most important personal health measure is to continue to watch for new alerts and recommendations. The CDC and other agencies will be making further recommendations. States and communities and Emory are engaged in pandemic planning efforts, which will need to be enhanced.
We will keep you informed with new information as it becomes available and are happy to try and answer any questions you might have.
The Internet websites below offer more information about avian influenza and pandemics.
http://www.who.int/csr/disease/avian_influenza/en/
http://www.hhs.gov/nvpo/pandemics/index.html
http://www.cdc.gov/flu/avian/gen-info/spread.htm
http://www.cdc.gov/flu/avian/gen-info/vaccines.htm
http://www.cdc.gov/flu/avian/gen-info/avian-influenza.htm
This information provided courtesy of the Office of the Executive Vice president for Health Affairs, Woodruff Health Sciences Center.
Special credit to infectious disease experts Drs. Walt Orenstein, James Hughes, David Stephens and Jeff Koplan.
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