Avian Influenza Essay Example

Avian Influenza Essay Example Avian Influenza Paper Avian Influenza Paper Essay Topic: The Wild Duck Avian Influenza Introduction Bird flu in most cases begins with discomfort of lower respiratory ways and in unusual casesfrom upper respiratory air-ways. Elevated viral titer is isolated from pharynx but not from nose. Initial symptoms of the H5N1 influenza are: high grade fever, mild cold, cough and shortness of breath. Practically all patients develop viral pneumonia complicating to secondary bacterial infection, mild to severe respiratory distress, diarrhea, vomiting and abdominal pain. Conjunctivitis is entity. Sometimes gastrointestinal disorder develops earlier than respiratory symptoms. 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. Early chronology: 1929 Last evidence (serologic) of circulation in humans of a swine-like influenza virus 1930 Isolation of an influenza virus from swine 1933 First isolation of an influenza virus from humans Until 1995, only three of the 15 influenza hemagglutinins 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) and from Hong Kong. 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 waterbirds 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 animal s such as seals, whales, pigs, horses, and turkeys. Extensive analysis of the viruss genetic structure, or nucleic acid sequences, supports the hypotheses that mammalian influenza viruses, including those infecting man, may well originate in aquatic birds. (Suarez DL, Spackman E, Senne DA, 2003) Subtypes of influenza A, the various strains of these avian viruses can be classified as either highly pathogenic or as of low pathogenicity, based on their genetic features and the severity of illness they cause in birds. There are currently 27 potential forms of the three subtypes of avian influenza viruses differentiated by variations in the neuraminidase surface antigen. Thus, H5, H7, and H9 avian influenza viruses, so named for their hemagglutinin surface antigen, can each be matched with nine possible neuraminidase surface antigens, N1, N2, N3, etc. Thus, there could be H5N1 through H5N9, H7N1 through H7N9, and H9N1 through H9N9 strains. H9 viruses appear to be of low pathogenicity, while H5 and H7 viruses can be highly pathogenic for birds. However, low pathogenic forms of these viruses seem to be the cause of most outbreaks among poultry causing only mild or imperceptible illness and low mortality rates. Nonetheless, both H5 and H7 can develop high levels of pathogenicity in which case mortality rates in poultry flocks can reach 100%. The natural history of avian influenza viruses is characterized by spread through infected nasal, respiratory and fecal material, and a reservoir state in healthy birds. (Pascal James Imperato, 2005) www.springerlink.com/index/H6427776HH34G857.pdf Pathogenesis The pathogenesis of avian influenza A (H5N1) virus in humans has not been clearly explained. Apoptosis might also play a vital part. Apoptosis has been observed in alveolar epithelial cells, which is the major target cell type for the viral replication. Many apoptotic leukocytes were observed in the lungs of patients who died on day 6 of illness. Apoptosis may play a major role in the pathogenesis of influenza (H5N1) virus in humans by destroying alveolar epithelial cells. This pathogenesis causes pneumonia and destroys leukocytes, leading to leucopenia, which is an outstanding clinical feature of influenza (H5N1) virus in humans. Whether observed apoptotic cells were a directly related to viral replication or outcome of an over activation of the immune system needs further studies. (Uiprasertkul M, 2007) www.cdc.gov/EID/content/13/5/708.htm Infected birds were the major source of the H5N1 influenza virus among humans in Asia. Mainly humans became infected by eating infected birds, by poor hygiene procedures when cooking infected birds, or by close contact with infected poultry. (Reina J, 2002). Certain birds, particularly water birds, act as hosts for influenza viruses by carrying the virus in their intestines and shedding it. Infected birds shed virus in saliva, nasal secretions, and feces. Susceptible birds can become infected with avian influenza virus when they have contact with contaminated nasal, respiratory, or fecal material from infected birds. Fecal-to-oral transmission is the most common mode of spread among birds. Most often, the wild birds that are the hosts for the virus do not get sick, but they can spread influenza to other birds. (CDC, 2006) www.cdc.gov/flu/avian/gen-info/spread.htm At present spread of the H5N1 influenza from human to human by air born route has not been registered, but enduring monitoring for identification mutation and adaptation of H5N1 influenza virus to human is needed. Most studies performed in avian viral strains elucidates that virulence is a polygenic phenomenon. However, hemagglutinin and neuraminidase and the genes codifying these substances (genes 4 and 6) play a vital role in viral pathogenesis. (Gu J, Xie Z, Gao Z, Liu J, Korteweg C, Ye J, Lau LT, Lu J, Gao Z, Zhang B, McNutt MA, Lu M, Anderson VM, Gong E, Yu AC, Lipkin WI, 2007). Avian strains can be classified as virulent or avirulent according to the capability of hemagglutinin to be triggered by endoproteases of the respiratory tract merely or by proteases from other tissues. This ability is based on the ever going mutations that lead to the substitution of the normal amino acids at the point of hemagglutinin hydrolysis by the other basic amino acids that determine the amplifi cation of the spectrum of hydrolysis and activation. Neuraminidase contributes in the acquisition of virulence through its ability to attach to plasminogen and by escalating the concentration of activating proteases. Adaptation to the host, by recognition of the cell receptor, is an additional factor determining the virulence and interspecies spread of avian strains. (Reina J, 2002) Transmission to mammals Influenza A viruses from aquatic birds grow poorly in human cells, and vice versa. 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 geneti c 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 breakdown of hemagglutinin into two smaller units is required for virus infectivity. (Suarez DL, Spackman E, Senne DA, 2003). Shifts in the composition of the hemagglutinin (H) or neuraminidase (N), another glycoprotein, of influenza virus were observed in the 1933, 1957, 1968, and 1977 epidemics: 1933: H1N1 1957: H2N2 (Asian flu) 1968: H3N2 (Hong Kong flu) 1977: reappearance of H1N1, called the Russian flu The reappearance in 1977 of the Russian flu, a virus first isolated in 1933, raises the uneasy possibility that a return of the 1918-19 influenza epidemics with its devastation of human life is possible and perhaps likely. 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 viruss 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 HA 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. Conclusion Three major hypotheses have been put forth to explain antigenic shifts. First, as described above, 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. H owever, 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. (Gu J, Xie Z, Gao Z, Liu J, Korteweg C, Ye J, Lau LT, Lu J, Gao Z, Zhang B, McNutt MA, Lu M, Anderson VM, Gong E, Yu AC, Lipkin WI, 2007) 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? 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. References: CDC. Spread of Avian Influenza Viruses among Birds; Journal of Environmental Health, Vol. 68, 2006.www.cdc.gov/flu/avian/gen-info/spread.htm 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. Gu J, Xie Z, Gao Z, Liu J, Korteweg C, Ye J, Lau LT, Lu J, Gao Z, Zhang B, McNutt MA, Lu M, Anderson VM, Gong E, Yu AC, Lipkin WI. H5N1 infection of the respiratory tract and beyond: a molecular pathology study; Lancet Sep 29; 370(9593):1106-8, 2007 Pascal James Imperato. The Growing Challenge of Avian Influenza; Journal of Community Health, Vol. 30, 2005. www.springerlink.com/index/H6427776HH34G857.pdf 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. Reina J. Factors affecting the virulence and pathogenicity of avian and human viral strains (influenza virus type A)] Enferm Infecc Microbiol Clin; 20(7):346-53 (ISSN: 0213-005X) Hospital Universitario Son Dureta, Palma de Mallorca, Espaà ±a, 2002 direct.bl.uk/research/48/44/RN119578176.html Suarez DL, Spackman E, Senne DA. Update on molecular epidemiology of H1, H5, and H7 influenza virus infections in poultry in North America; Avian Dis. 2003; 47(3 Suppl): 888-97 ncbi.nlm.nih.gov/sites/entrez 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. Uiprasertkul M. Apoptosis and Pathogenesis of Avian Influenza A (H5N1) Virus in Humans Emerg Infect Dis; 13(5):708-12 (ISSN: 1080-6040) Mahidol University, Bangkok, Thailand.2007 www.cdc.gov/EID/content/13/5/708.htm