Transmission and infection of H5N1

The transmission and infection of H5N1 is a concern due to the global spread of H5N1that constitutes a pandemicthreat. This article is about the transmission of the H5N1virus, infection by that virus, the resulting symptoms of that infection (having or coming down with influenzaor more specifically avian fluor even more specifically H5N1 flu which can include pneumonia), and the medical response including treatment.

Infected birds pass on H5N1through their saliva, nasal secretions, and feces. Other birds may pick up the virus through direct contact with these excretions or when they have contact with surfaces contaminated with this material. Because migratory birds are among the carriers of the H5N1 virus it may spread to all parts of the world. Past outbreaks of avian flu have often originated in crowded conditions in southeastand east Asia, where humans, pigs, and poultry live in close quarters. In these conditions a virus can mutateinto a form that more easily infects humans.

The majority of H5N1flu cases have been reported in southeast and east Asia. Once an outbreak is detected, local authorities often order a mass slaughter of birds or animals affected. If this is done promptly, an outbreak of avian flu may be prevented. However, the United Nations(UN) World Health Organization(WHO) has expressed concern that not all countries are reporting outbreaks as completely as they should. China, for example, is known to have officially denied past outbreaks of severe acute respiratory syndrome(SARS) and HIV.

H5N1infections in humans are generally caused by bird to human transmission of the virus. A few isolated cases of suspected human to human transmission exist, but there is no proof either way in those cases.

Transmission by wild birds (waterfowl)

According to the United NationsFAO:

Looking at the epidemiological data currently available, there is no denying the fact that wild water fowl most likely play a role in the avian influenza cycle and could be the initial source for AI viruses, which may be passed on through contact with resident water fowl or domestic poultry, particularly domestic ducks. The virus undergoing mutations could circulate within the domestic and possibly resident bird populations until HPAI arises. This new virus is pathogenic to poultry and possibly to the wild birds that it arose from. Wild birds found to have been infected with HPAI were either sick or dead. This could possibly affect the ability of these birds to carry HPAI for long distances. However, the findings in Qinghai Lake-China, suggest that H5N1 viruses could possibly be transmitted between migratory birds. Additionally, the new outbreaks of HPAI in poultry and wild birds in Russia, Kazakhstan, Western China and Mongolia may indicate that migratory birds probably act as carriers for the transport of HPAI over longer distances. Short distance transmission between farms, villages or contaminated local water bodies is likewise a distinct possibility. The AI virus has adapted to the environment in ways such as: 1) the use of water for survival and to spread 2) has evolved in a reservoir (ducks) strictly tied to water. The water in turn influences movement, social behaviour and migration patterns of water bird species. It is therefore of great importance to know the ecological strategy of influenza virus as well, in order to fully understand this disease and to control outbreaks when they occur. There remains a body of data and analysis missing on the collection and detection of HPAI viruses in wild birds. Finding HPAI viruses in wild birds may be a rare event, but if the contact with susceptible species occurs it can cause an outbreak at the local level or in distant areas. ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_FAO_wildbirds]}

Prevention

The current method of prevention in animal populations is to destroy infected animals, as well as animals suspected of being infected. In southeast Asia, millions of domestic birds have been slaughtered to prevent the spread of the virus.

The probability of a "humanized" form of H5N1 emerging through geneticrecombination in the body of a human co-infected with H5N1and another influenza virus type (a process called reassortment) could be reduced by influenzavaccinationof those at risk for infection by H5N1. It is not clear at this point whether vaccine production and immunization could be stepped up sufficiently to meet this demand.

If an outbreak of pandemicflu does occur, its spread might be slowed by increasing hygiene in aircraft, and by examining airline cabin air filters for presence of H5N1virus.

The AmericanCenters for Disease Control and Preventionadvises travelers to areas of Asia where outbreaks of H5N1 have occurred to avoid poultry farms and animals in live food markets ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_CDCtravel]}. Travelers should also avoid surfaces that appear to be contaminated by feces from any kind of animal, especially poultry.

There are several H5N1vaccinesfor several of the avian H5N1 varieties. H5N1 continually mutates rendering them, so far for humans, of little use. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1pandemicso there can be no pandemic vaccine." ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_Schultz]} However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_Enserink]}. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

It is not likely that use of antiviral drugscould prevent the evolution of a pandemic flu virus ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_tamifluNIH]}.

Environmental survival

Heat kills H5N1:

• Over 30 days at 0ºC ( 32.0ºF) (over one month at freezing temperature)
• 6 days at 37ºC ( 98.6ºF) (one week at human body temperature)
• 30 minutes 60ºC (140.0ºF) (half hour at a tempertature that causes second and third degree burns in humans in five seconds)

Influenza A viruses can survive for over 30 days at 0ºC (32.0ºF). H5N1 can survive in the environment for 6 days at 37ºC (98.6ºF). Inactivation of the virus occurs under the following conditions:

• Temperatures of 56ºC (132.8ºF) for 3 hours or 60ºC (140ºF) or more for 30 minutes (running a high fever helps kill avian flu viruses)
• Acidic pH conditions
• Presence of oxidizing agents such as sodium dodecyl sulfate, lipid solvents, and B-propiolactone
• Exposure to disinfectants: formalin, iodine compounds [1][2][3]

Incubation

The incubation period of avian influenza A (H5N1) is 2 to 17 days^{[{{fullurl:Template:FULLPAGENAME}}#endnote_NEJM29September2005]}. Once infected, the virus can spread by cell-to-cell contact, bypassing receptors. So even if a strain is very hard to initially catch, once infected, it spreads rapidly within a body.^{[{{fullurl:Template:FULLPAGENAME}}#endnote_epw_india]}

Symptoms

See also Pneumonia.

Since H5N1 is an influenza virus, symptomssimilar to those of the common flu, such as fever, cough, sore throat, and sore muscles, can develop in infected humans. However, in more severe cases, pneumoniaand respiratory failurecan develop and eventually cause death. Patients with H5N1 avian influenza have rarely had conjunctivitis^[9], unlike human cases of infection by the H7 virus. Severe infection from H5N1 caused multiple lung infections (including pus, fever, cough), lung scar tissue, fluid in the space surrounding the lungs, enlarged lymph nodes and cavities forming in the lung tissue.

There have been studies of the levels of cytokinesin humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor alpha(TNF?), a proteinthat is associated with tissue destruction at sites of infection and increased production of other cytokines. Flu virus-induced increases in the level of cytokines is also associated with flu symptoms including fever, chills, vomiting and headache. Tissue damage associated with pathogenic flu virus infection can ultimately result in death ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_cytokine1]}. The inflammatorycascade triggered by H5N1 has been called a 'cytokine storm' by some, because of what seems to be a positive feedbackprocess of damage to the body resulting from immune systemstimulation. H5N1 type flu virus induces higher levels of cytokines than the more common flu virus types such as H1N1 ^{[{{fullurl:Template:FULLPAGENAME}}#endnote_cytokine2]}.

Treatment

Neuraminidase inhibitors are a class of drugs that includes zanamivirand oseltamivir, the latter being licensed for prophylaxistreatment in the United Kingdom. Oseltamivir inhibits the influenza virus from spreading inside the user's body ^[8]. It is marketed by Rocheas Tamiflu. This drug has become a focus for some governments and organizations trying to be seen as making preparations for a possible H5N1 pandemic. In August2005, Roche agreed to donate three million courses of Tamiflu to the World Health Organization, to be deployed by the WHO to contain a pandemic in its region of origin. Although Tamiflu is patented, international law gives governments wide freedom to issue compulsory licensesfor life-saving drugs.

A second class of drugs, which include amantadineand rimantadine, target the M2 protein, but are ineffective against H5N1. Unlike zanamivir and oseltamivir, these drugs are inexpensive and widely available and the WHO had initially planned to use them in efforts to combat an H5N1pandemic. However, the potential of these drugs was considerably lessened when it was discovered that farmers in China has been administering amantadine to poultry with government encouragement and support since the early 1990s, against international livestock regulations; the result has been that the strain of the virus now circulating in South East Asia is largely resistant to these medications and hence significantly more dangerous to humans^{[{{fullurl:Template:FULLPAGENAME}}#endnote_resistance]}.

Sources

1. ^ UN FAO - ANIMAL HEALTH SPECIAL REPORT - Wild birds and Avian Influenza
2. ^  Interim Guidance about Avian Influenza A (H5N1) for U.S. Citizens Living Abroadfrom the U.S. Centers for Disease Control and Prevention. Initial release, March 24, 2005. Updated on November 18, 2005.
3. ^  Bird flu vaccine won't precede pandemicby Jennifer Schultz for United Press International(November 282005).
4. ^  Promising research into vaccines includes 1)"Avian Influenza: 'Pandemic Vaccine' Appears to Protect Only at High Doses" by Martin Enserink in Science, volume 309, page 996, 12 August2005DOI:10.1126/science.309.5737.996b 2) Science DailyGlaxoSmithKline in London announced Thursday that it would begin clinical trials of its H5N1 vaccine in April. 3) Tribune-ReviewA promising new bird flu vaccine developed by University of Pittsburgh researchers could provide better protection and be made more quickly than other experimental vaccines.
5. ^ ^{{qif

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|else=a}}  Oseltamivir (Tamiflu) informationfrom United States National Institutes of Health. Webpage content initially developed on January 13, 2000 and revised on January 10, 2001.

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|else=a}}  Full text article online: "Avian Influenza A (H5N1) Infection in Humans" by  The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5 in New England Journal of Medicine (29 September2005) Volume 353 pages 1374-1385. 

1. ^  Bird Flu: Public Health Implications for India
2. ^ Influenza: The world is teetering on the edge of a pandemic that could kill a large fraction of the human populationby Robert G. Webster and Elizabeth Jane Walker in American Scientist 2003Volume 91 Page 122.
3. ^  Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cellsby M. C. Chan et al in Respiratory Research 2005Volume 6 page 135.
4. ^  Influenza virus replicationin Medical Microbiology, 4th edition edited by Samuel Baron. 1996Chapter 58. ISBN 0963117211.
5. ^ Bird Flu Drug Rendered Useless: Chinese Chickens Given Medication Made for HumansBy Alan Sipress in the Washington Post Saturday, June 182005.

Further reading

• WHO Avian influenza resource (updated)
• CDC Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus

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It uses material from the http://en.wikipedia.org/wiki/Transmission+and+infection+of+H5N1 Wikipedia article Transmission and infection of H5N1.