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Magill's Medical Guide 4th rev. ed. Avian Influenza Also Known As: Bird flu, avian flu Anatomy or System Affected: Blood, blood vessels, circulatory system, gastrointestinal system, heart, intestines, kidneys, lungs, muscles, musculoskeletal system, nerves, nervous system, nose, reproductive system, respiratory system, stomach, throat, urinary system Specialties and Related Fields: Biochemistry, epidemiology, immunology, pathology, virology Definition: Avian influenza is caused by several virus strains that attack birds; occasionally, a strain develops the ability to attack humans, sometimes triggering an epidemic. There is concern that the H5N1 strain could mutate into a form that is highly contagious among humans and result in a pandemic. Key Terms antibody: a specific protein made by an organism in response to one kind of antigen; the antibody attaches to that antigen and deactivates the cell, virus, or chemical to which the antigen is attached, thus protecting the organism antigen: foreign material that stimulates the host organism to produce antibodies specific to that material epidemic: the spread of a disease through a population or region epidemiology: the study of the mechanisms by which diseases spread within and among populations and regions mutation: a change in the instructions, either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), of a cell or virus that sometimes changes the characteristics of the cell or virus pandemic: a disease that spreads around the world pathogenic: causing disease reassortment: one means of recombination among viruses; it occurs when two strains are present in the same host, where they may exchange genes to form viruses with new capabilities RNA virus: a virus that uses RNA as its genetic material, or ultimate instructions for its characteristics vaccine: an antigen from a virus or other disease-causing entity that is artificially prepared in a structure not capable of causing disease but which will stimulate the production of antibodies, thus bringing about immunity to the original disease Causes and Symptoms A group of RNA viruses causes influenza in birds. Most such viruses do not attack humans, although human influenza viruses were probably derived from bird influenza viruses. On the rare occasion that a bird flu strain achieves the ability to enter and reproduce in human cells, the human is unlikely to have effective defenses and the viral attack is likely to be severe. If the virus strain combines its ability to reproduce in humans and its highly pathogenic nature with the ability to transfer from human host to human host, then it is particularly dangerous. The most deadly human influenza pandemics in history probably began this way. At the turn of the twenty-first century, public health officials were concerned that the avian influenza virus strain H5N1 might undergo such a transformation and initiate such a pandemic. Influenza virus strains are named for two of their surface proteins, hemagglutinin (with fifteen or sixteen known types) and neuraminidase (with nine known types). Each different protein is assigned a number, so that H5 in H5N1 refers to the hemagglutinin which was assigned the number five. Similarly, N1 refers to the neuraminidase assigned the number one. Hemagglutinins are responsible for attachment of the virus to host cells and entry into those cells. After production of new viruses in the cell, neuraminidases are used by the new viruses to break out of the cell. Influenza viruses are notorious for their ability to change their surface antigens and thereby escape host defenses, which are dependent on recognition of those antigens. The H5 and N1, surface proteins that characterize the virus, are also the antigens targeted by host defenses. Both are displayed on the surface of the membranelike coat that surrounds the virus. The hemagglutinin (H5) is the primary target for cell defenses. If an organism has been exposed to a given hemagglutinin, then it will quickly produce antibodies that attach to that hemagglutinin, blocking the site that is normally used to attach to the organism's cells. The virus is rendered harmless if it cannot attach to and enter a cell. If this is the organism's first exposure to the specific hemagglutinin, however, then the response will not be as rapid. The host's immune system will begin making antibodies against the new antigen, but they are made too slowly during this first exposure, and illness results. Most humans have had no exposure to H5 antigens and so are unprotected against H5N1. Symptoms of avian influenza in humans include the familiar set generally caused by flu viruses. Those symptoms—fever, loss of appetite, clogged sinuses, runny nose, muscle aches, and so forth—pass in three to five days with most influenza strains, and the victim recovers. With H5N1, however, other host systems—such as the circulatory, nervous, reproductive, and gastrointestinal systems—often become involved. In more than 50 percent of human cases reported, death occurs, sometimes within a day of the onset of symptoms. Treatment and Therapy The major medical solutions to avian flu infection are medications and vaccination. Antiviral medications were difficult to develop, and few effective drugs are available. Many of the drugs prescribed for viral infections are actually used to combat secondary infections by bacteria attempting to take advantage of the host's weakened condition. Vaccine development against influenza viruses is also problematic. The vaccines target antigens on the surface of the viruses, and the viruses mutate and change their surface antigens so frequently that new vaccines must be developed almost every year to defend against the new strains of influenza. Given these difficulties and the fact that most influenza victims recover in three to five days without treatment, drugs and vaccines against influenza have not been a high priority compared to those against more deadly diseases such as smallpox. Periodically, however, a particularly pathogenic influenza strain has developed, and effective treatment would have saved many lives. Because the H5N1 strain is feared for its potential to be one of those strains, scientists have sought to develop both drugs and vaccines against this virus. Four medications that act against flu viruses are available, but the virus has quickly developed resistance to the older pair, amantadine and rimantadine. The H5N1 virus populations in Vietnam and other Southeast Asian countries are already resistant to these drugs. In those countries, the virus has been present in poultry, and occasionally in humans, a bit longer than elsewhere. Two newer drugs, oseltamivir (Tamiflu) and zanamivir (Relenza), are expected to be effective, but they have not yet been tested sufficiently against the H5N1 virus strain. Progress in vaccine development has been encouraging, but no proven vaccine is available. Even when a vaccine becomes ready for use, production of enough to meet the needs of a pandemic would be challenging. Stockpiling a vaccine in anticipation of a pandemic is possible, but the exact antigen against which it must be directed cannot be known until the virus is in the process of initiating the pandemic. Each year, experts predict the most likely antigens for an approaching flu season, and vaccines are produced in advance against those antigens. Should an influenza virus employ an antigen not anticipated by the experts, then the stockpiled vaccines would be worthless. Vaccine production technology is also improving, but the improvements have not been fully implemented. In the standard technique, the antigenic virus to be used in the vaccine is grown in fertilized eggs—an expensive, slow, and inefficient method. Tissue culture techniques, in which the antigenic virus is grown in cells in artificial media, promise dramatic improvement in vaccine preparation once they are fully integrated into the production system. Perspective and Prospects The history of influenza can be traced much further back in time than the understanding of its cause. Reports describing epidemics and pandemics in which the victims showed symptoms of influenza go back to the early 1500's at least, but the first isolation of an influenza virus did not occur until 1933. The worst flu pandemic occurred in 1918-1919 (the Spanish flu), when twenty million to one hundred million people died of influenza. It was one of the deadliest diseases in history. Two more recent flu pandemics, the Asian flu (1957) and the Hong Kong flu (1968), were seriously disruptive, but not as deadly. All these pandemics were caused by influenza type A viruses, the type to which strain H5N1 and the other avian influenza viruses belong. The concern over avian influenza type A H5N1 began in 1997 in Hong Kong, where poultry and humans came under attack. Three events associated with these infections captured the attention of epidemiologists, because together they suggested H5N1's potential as the agent of an influenza pandemic. First, transmission occurred from poultry to humans. Second, H5N1 proved to be highly pathogenic, as six of the eighteen infected humans died. Third, there was some indication of human-to-human transfer of the virus. If the virus maintained its pathogenic nature and its ability to move from poultry to humans, and if it added the ability to transfer efficiently from one human to another, it would almost certainly initiate another deadly pandemic. Between 1997 and 2006, a number of human cases of avian influenza type A were documented in a number of countries. Not all were the result of the feared H5N1 strain, but the other strains bear watching as well. Between 2004 and 2006, there were two hundred confirmed cases of human infection with H5N1, most in Southeast Asia (Vietnam, Cambodia, Indonesia, Thailand) but also in Egypt, Iraq, Azerbaijan, and Turkey. No H5N1 infections were documented in North America, but avian influenza virus type A H7N2 caused illness in New York, and H7N3 attacked poultry workers in Canada. No North American infection resulted in a human fatality. None of these infections involved extensive or sustained human-to-human transmission, though a few restricted transfers between humans may have occurred. Most of the human infections were transferred from infected domestic poultry. Some may have been contracted from wild waterfowl (ducks and geese). Human health is not the only concern regarding the H5N1 strain; there are agricultural and economic concerns as well. Poultry flocks can be destroyed by the virus. There were several poultry outbreaks around the world before 2006, in which an estimated 150 million barnyard birds either died as victims of the virus or were culled to remove the infection focus and prevent further spread of the virus. Although the governments involved often compensated individuals for their culled animals, the compensation was usually well below market value. This practice encourages farmers to hide infections that occur in their flocks, which slows discovery of potential outbreaks and gives the virus a headstart that it does not need. In addition, several governments were suspected of hiding avian flu outbreaks until they were impossible to conceal, in an attempt to protect their countries' economic interests. The role played by wild birds is an important piece of this puzzle as well. Wild birds, especially waterfowl, act as the reservoir for H5N1. The birds maintain the virus between epidemics. Waterfowl are known to carry the virus, release virus in their feces and oral secretions, and are usually not sickened by the virus infection. These characteristics of the reservoir indicate how easily a pandemic could start from a mutant virus in the reservoir. In Hong Kong in 2002-2003 and again in China in 2005, large numbers of wild birds were killed by the virus, emphasizing the virus's tendency to mutate. Experts believe that it may take only a few mutations for the virus to gain the ability to transfer between humans. If they are right, then the waterfowl reservoir is always just a step away from creating a pandemic virus strain. Given their mobility, especially during migration, wild birds also appear to be good candidates for spreading the virus among countries and continents. However, investigations suggest that, while wild bird migration might play a role in viral geographic expansion, it is probably secondary to the role played by commercial poultry exchanges. Avian influenza virus type A H5N1 has demonstrated its ability to transfer from wild birds to domestic poultry (and perhaps to humans), to decimate domestic poultry flocks, to be transferred from poultry to humans, and to be highly pathogenic for humans. It has not demonstrated the ability to pass freely from one human to another. If it were to add this last ability to its arsenal, it would be a candidate to initiate a pandemic as deadly as the influenza pandemics of the past. The change required to introduce this ability to the H5N1 virus is not thought to be elaborate. A few simple mutations in the viral RNA might suffice. Epidemiologists have one special concern, the potential for the virus to use pigs for reassortment of its genes. In developing countries, pigs often share living space with chickens and other poultry. Humans often live adjacent to the animals or even share their living space. These associations are troubling because pigs host both human and bird flu viruses, and the intimate association of the three species presents the two viral strains with the opportunity to invade the same pig. Together in the same host, they would be expected to exchange RNA strands. Some reassortments might produce a virus with the capability to transfer from human to human. There was no evidence that such a transformation has occurred. However, the possibility is real and the defenses (antiviral drugs and vaccination) are not in place and fully functional, so the concern is understandable. Some investigators suggest, however, that the concern has been overblown. They point out that no H5 influenza strain has ever caused a pandemic and that successful pandemic-causing influenza strains attach to receptors in the upper parts of the human respiratory tract, while the receptors to which H5N1 viruses attach are in the lower reaches. Some skeptics also argue that if H5N1 went through the changes necessary to achieve efficient transfer among humans, it would invariably lose pathogenic potency in the process, thus minimizing its pandemic potential. Governments and public health officials are between the proverbial rock and hard place. They would be criticized if they prepared for a threat that did not materialize, but more tragic results would occur if they failed to prepare and a pandemic broke out. Criticism for a perceived lack of preparation is already widespread. While another pandemic is probably inevitable, no one can know when it will materialize or what specific disease organism will be the cause, so there is no easy answer to their conundrum. For the long-term struggle against avian influenza, however, disease patterns in animal populations might be very helpful in predicting which threats have the potential to cause human pandemics and in otherwise understanding the viruses. This possibility calls for close coordination among students of wildlife, veterinary, and human disease. That coordination will not solve all the mysteries of influenza outbreaks but should aid in understanding them, and the influenza viruses will not be controlled until they are more thoroughly understood. Carl W. Hoagstrom, Ph.D. See AlsoEpidemiology; Immunization and vaccination; Influenza; Viral infections; Zoonoses. Further Information Clark, Larry, and Jeffrey Hall. "Avian Influenza in Wild Birds: Status as Reservoirs, and Risks to Humans and Agriculture." In Current Topics in Avian Disease Research: Understanding Endemic and Invasive Diseases, edited by Rosemary K. Barraclough. Washington, D.C.: American Ornithologists' Union, 2006. A nice outline of the problem. Also considers human health, agricultural concerns, and the potential effect on wild bird populations. Davis, Mike. The Monster at Our Door: The Global Threat of Avian Flu. New York: The New Press, 2005. A good discussion of the problem from the "sky-is-falling-and-nobody-is-doing-anything" perspective. Green, Jeffrey. The Bird Flu Pandemic. New York: Thomas Dunne Books, 2006. A balanced presentation of the potential for such an event with suggestions for appropriate individual responses. Sfakianos, Jeffrey N. Avian Flu. New York: Chelsea House, 2006. A good discussion of the biology of flu viruses. A balanced presentation of the bird flu problem. Siegel, Marc. Bird Flu: Everything You Need to Know About the Next Pandemic. Hoboken, N.J.: John Wiley & Sons, 2006. A good discussion of the problem from the perspective that "the sky-is-falling" theorists are overreacting. Wehrwein, Peter, ed. "Bird Flu: Don't Fly into a Panic." Harvard Health Letter 31, 8 (June, 2006): 1-3. A concise, balanced description of the problem and protective steps that an individual can take. |
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