Avian Influenza Viruses - Essay Example

Name of writer appears here] [Course name appears here] [Professor’s name appears here] [Date appears here] Avian influenza Avian influenza viruses are shed in respiratory secretions and feces of birds. Infected ducks, for example, shed virus for at least 30 days. Influenza virus from the feces of waterfowl can be recovered from surface water. Avian species develop infection that ranges from asymptomatic to lethal. Avian influenza has caused major outbreaks in poultry farms. Influenza virus can undergo genetic mutations in hemagglutinin or neuraminidase (antigens on the surface of the virus) that can lead to epidemics. Much less commonly, a completely new hemagglutinin or neuraminidase emerges—with the new genetic material coming from animals. This genetic shift typically leads to pandemics. Until 1995, only three of the 15 influenza hem agglutinins that had been identified were known to cause infections in humans. Birds have all 15 identified hemagglutinins and nine neuraminidases. New influenza viruses often emerge from southern China, a region characterized by a large, densely settled human population and abundant pigs and ducks living in close proximity to humans. Until events in Hong Kong in 1997, scientists thought that avian influenza posed no direct threat to humans. In 1997, after causing influenza outbreaks on chicken farms, avian influenza (H5N1) spread to humans (Claas et al. 1998). Eighteen human cases were confirmed, six of them fatal. Infection was concentrated in children and young adults, unlike the pattern in most outbreaks where morbidity and death are most common in older adults. The virus recovered from humans was identical to that found in birds (Subbarao et al. 1998). Epidemiological studies suggested that there had been multiple independent introductions of the influenza virus into the human population from birds, but that very limited person-to-person spread occurred. At the time of the human cases, there were estimated to be 300–600 live bird markets in Hong Kong, where mixing of different avian species (ducks, chickens, pheasants, pigeons, wild birds) was possible. When the Hong Kong live bird markets were studied, 10% or more of birds were found to be shedding H5N1, in multiple avian species (geese, chickens, ducks). The birds (more than one million) were killed, and no additional human cases of H5N1 have been documented. In 1999, human infection with H9N2, another avian influenza strain widespread in Asia, was also documented for the first time in humans, at a time of enhanced surveillance (Peiris et al. 1999). The events in Hong Kong have led to heightened global surveillance for influenza in humans and animals. There was reason to be concerned about the events in Hong Kong, a densely populated city with extensive links to the rest of the world. In 1993, there were an estimated 41.4 million passenger movements (boat, train, car, airplane) to and from Hong Kong. In recent years, multiple large outbreaks of influenza have been documented on cruise ships (as well as on smaller boats, barges, and in other settings). In the summer of 1998, 40,000 tourists and tourism workers were affected during influenza A outbreaks in Alaska and the Yukon territories (CDC 1999). Many were initially infected during land travel, but transmission continued on cruise ships. Air-conditioned buses and other places with shared air may have been sites of transmission. A cruise ship with 1,500 or more passengers who dispersed widely after a trip potentially spread the influenza virus widely. Influenza typically occurs during the winter months in temperate regions. Increasingly, summertime outbreaks are being documented. Travel to tropical regions (where influenza transmission occurs year round) or to the opposite hemisphere may be the source of some infections. Creation of new habitats may be another reason. Influenza is transmitted most effectively where there is indoor crowding and low relative humidity (Schaffer et al. 1976). The creation of air-conditioned spaces where people congregate during hot weather may provide a good environment for influenza transmission. The influenza viruses that afflict humans are divided into three types: A, B, and C. Influenza A is responsible for the epidemics and infects not only man but also pigs, horses, seals, and a large variety of birds. Indeed, influenza A has been isolated worldwide from both domestic and wild birds, primarily water birds including ducks, geese, terns, and gulls and domesticated birds such as turkeys, chickens, quail, pheasants, geese, and ducks. Studies of wild ducks in Canada from 1975 to 1994 indicated that up to 20 percent of the juveniles were infected, and fecal samples from their lakeshore habitats contained the virus. These birds usually shed the virus from five to seven days (with a maximum of thirty days) after becoming infected even though they show no sign of the disease. Obviously, this virus and its hosts have adapted mutually over many centuries and created a reservoir that ensures perpetuation of the virus. Duck virus has been implicated in outbreaks of influenza in animals such as seals, whales, pigs, horses, and turkeys. Extensive analysis of the virus's genetic structure, or nucleic acid sequences, supports the hypotheses that mammalian influenza viruses, including those infecting man, may well originate in aquatic birds. Influenza A viruses from aquatic birds grow poorly in human cells, and viceversa. However, both avian and human influenza viruses can replicate in pigs. We have known that pigs are susceptible to influenza viruses that infect man ever since the veterinarian J. S. Koen first observed pigs with influenza symptoms closely resembling those of humans. Retrospective tests of human blood indicate that the swine virus isolated by Shope in 1928 was similar to the human virus and likely responsible for the human epidemic. Swine influenza still persists year-round and is the cause of most respiratory diseases in pigs. Interestingly, in 1976, swine influenza virus isolated from military recruits at Fort Dix was indistinguishable from virus isolates obtained from a man and a pig on a farm in Wisconsin. The examiners concluded that animals, especially aquatic birds and pigs, can be reservoirs of influenza virus. When such viruses or their components mix with human influenza virus, dramatic genetic shifts can follow, creating the potential of a new epidemic for humans. The influenza virus continually evolves by antigenic shift and drift. Early studies in this area by Robert Webster and Graeme Laver established the importance of monitoring influenza strains in order to predict future epidemics. Antigenic shifts are major changes in the structure of the influenza virus that determines its effect on immune responses. Of the viral proteins, the hemagglutinin (H), a major glycoprotein of the virus, plays a central role in infection, because, as mentioned at the beginning of this chapter, breakdown of hemagglutinin into two smaller units is required for virus infectivity (Claas, et al.1998). In March of 1997, part of influenza virus nucleic acid was isolated from a formalin-fixed lung tissue sample of a twenty-one-year-old Army private that died during the 1918-19 Spanish influenza pandemic. Since the first influenza viruses were not isolated until the 1930s, characterization of the 1918-19 strain relied on molecular definition of the virus's RNA. Chemical evidence indicated a novel H1N1 sequence of a viral strain that differed from all other subsequently characterized influenza strains and that the 1918 H A human sequence correlated best with swine influenza strains. Once the entire sequence is on hand, a virulent marker for the influenza virus associated with killing over 675,000 Americans from 1918 to 1919 may be uncovered and a vaccine planned that might abort the return of this virus form of influenza. When such antigenic shifts occur, the appearance of disease is predictable. Therefore, surveillance centers have been established all over the world where isolates of influenza are obtained and studied for alterations, primarily in the hemagglutinin. According to the evidence from these centers, isolates identified in late spring are excellent indicators of potential epidemics in the following winter. Both avian and human influenza viruses can replicate in pigs, and genetic reassortants or combinations between them can be demonstrated experimentally. A likely scenario for such an antigenic shift in nature occurs when the prevailing human strain of influenza A virus and an avian influenza virus concurrently infect a pig, which serves as a mixing vessel. Reassortants containing genes derived mainly from the human virus but with a hemagglutinin and polymerase gene from the avian source are able to infect humans and initiate a new pandemic. In rural Southeast Asia, the most densely populated area of the world; hundreds of millions of people live and work in close contact with domesticated pigs and ducks. This is the likely reason for influenza pandemics in China. Epidemics other than the 1918-19 catastrophes have generally killed 50,000 or fewer individuals, although within a year over one million people had been infected with these new strains. Three major hypotheses have been put forth to explain antigenic shifts. First, a new virus can come from a reassortant in which an avian influenza virus gene substitutes for one of the human influenza virus genes. The genome of human influenza group A contains eight RNA segments, and current wisdom is that the circulating influenza hemagglutinin in humans has been replaced with an avian hemagglutinin. A second explanation for antigenic shifts that yield new epidemic viruses is that strains from other mammals or birds become infectious for humans. Some believe that this is the cause of the Spanish influenza virus epidemic in 1918-19, with the transmission of swine influenza virus to humans. A third possibility is that newly emerging viruses have actually remained hidden and unchanged somewhere but suddenly come forth to cause an epidemic, as the Russian H1N1 virus once did. H1N1 first was isolated in 1933, then disappeared when replaced by the Asian H2N2 in 1957. However, twenty years later the virus reappeared in a strain isolated in northern China and subsequently spread to the rest of the world. This virus was identical in all its genes to one that caused human influenza epidemics in the 1950s. Where the virus was for twenty years is not known. Could it have been inactivated in a frozen state, preserved in an animal reservoir, or obscured in some other way? If this is so, will the Spanish influenza virus also return, and what will be the consequences for the human population? (Subbarao, et al, 1998). In addition to antigenic shift, which signifies major changes in existing viruses, antigenic drift permits slight alterations in viral structure. These follow pinpoint changes (mutations) in amino acids in various antigen domains that relate to immune pressure, leading to selection. For example, the hemagglutinin molecule gradually changes while undergoing antigenic drift. Such mutations allow the virus to escape from attack by antibodies generated during a previous bout of infection. Because these antibodies would ordinarily protect the host by removing the virus, this escape permits the related infection to remain in the population. With these difficulties of antigenic shift and, drift and animal reservoirs, it is not surprising that making an influenza vaccine as effective as those for smallpox, pohovirus, yellow fever, or measles is difficult to achieve. Another complication is that immunity to influenza virus is incomplete; that is, even in the presence of an immune response, influenza can still occur. Nevertheless, the challenge of developing vaccines based on surveillance studies has been met. A chemically treated, formalin-inactivated virus has been formulated in a vaccine that is 30 to 70 percent effective in increasing resistance to influenza virus. The vaccine decreases the frequency of influenza attacks or, at least, the severity of disease in most recipients, although protection is not absolute. In addition, the secondary bacterial infections that may accompany influenza are today treatable with potent antibacterial drugs previously unavailable. Nonetheless, of the plagues that visit humans, influenza is among those that require constant surveillance, because we can be certain that some form of influenza will continue to return. Reference: Centers for Disease Control and Prevention (CDC). 1999. Outbreak of influenza A infection among travelers—Alaska and the Yukon Territory, May—June 1999. Morbid Mortal Wkly Rep 48:545–546, 555. Claas, E. C. J., A. D. M. E. Osterhaus, R. van Beek, J. C. De Jong, G. F. Rimmelzwaan, D. A. Senne, S. Krauss, K. F. Shortridge, and R. G. Webster. 1998. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351:472–477. Schaffer, F. L., M. E. Soergel, and C. D. Straube. 1976. Survival of airborne influenza virus: effects of propagating host, relative humidity, and composition of spray fluids. Arch Virol 51:263–273. Subbarao, K., A. Klimov, J. Katz, H. Renery, W. Lim, H. Hall, M. Perdue, D. Swayne, C. Bender, J. Huang, M. Hemphill, T. Rowe, M. Shaw, X. Xu, K. Fukuda, and N. Cox. 1998. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279:393–396. Peiris, M., K. Y. Yuen, C. W. Leung, K. H. Chan, P. L. S. Ip, R. W. M. Lai, W. K. Orr, and K. F. Shortridge. 1999. Human infection with influenza H9N2. Lancet 354:916–917. Read More