H5N1
Encyclopedia : H : H5 : H5N : H5N1
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| WHO pandemic phases 1. Low risk 2. New virus 3. Self limiting 4. Person to person 5. Epidemic exists 6. Pandemic exists |
A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or simply "bird flu", and is endemic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) of Asian lineage is spreading globally. It is epizootic (an epidemic in nonhumans) and panzootic (a disease affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of other birds in an attempt to control its spread. Most references in the media to "bird flu" and to H5N1 are about this specific strain.
This was reprinted in 2005:
HPAI A(H5N1) is an avian disease, and there is no evidence of efficient human-to-human transmission or of airborne transmission of HPAI A(H5N1) to humans. In almost all cases, those infected with H5N1 have had extensive physical contact with infected birds. However, around 50% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from H5N1 flu, and H5N1 has the potential to mutate or reassort into a strain capable of efficient human-to-human transmission. In 2003, world-renowned virologist Robert Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist calling for adequate resources to fight what he sees as a major world threat to possibly billions of lives.
Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large host reservoir, and its significant ongoing mutations, the H5N1 virus is the world's largest current pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic.
Genetics
- redirect
This e-book is under constant revision and is an excellent guide to Avian Influenza It has also been called "Asian lineage HPAI A(H5N1)".
Terminology
H5N1 isolates are named as in this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):- A stands for the species of influenza (A, B or C).
- chicken is the species the isolate was found in
- Nakorn-Patom/Thailand is the place this specific virus was isolated
- CU-K2/04 is the identifier distinguishing it from other isolates at the place of the specimen it was isolated from with 04 representing the year 2004
- H5 stands for the fifth of several known types of the protein hemagglutinin.
- N1 stands for the first of several known types of the protein neuraminidase.
As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent, and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The current strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other current strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally a highly pathogenic avian virus is not highly pathogenic to either humans or non-poultry birds. This current deadly strain of H5N1 is unusual in being deadly to so many species.
Genetic structure and related subtypes
H5N1 is a subtype of the species Influenza A virus of the Influenzavirus A genus of the Orthomyxoviridae family. It is a virus, a type of microscopic intracellular parasite that infects cells in biological organisms. Like all other influenza A subtypes, the H5N1 subtype is an RNA virus. It has a segmented genome of eight negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA, M and NS.
HA codes for hemagglutinin, an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells.
The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1.
Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:
- H1N1, which caused "Spanish Flu" and currently causes seasonal human flu
- H2N2, which caused "Asian Flu"
- H3N2, which caused "Hong Kong Flu" and currently causes seasonal human flu
- H5N1, the world's major current pandemic threat
- H7N7, which has unusual zoonotic potential and killed one person
- H1N2, which is currently endemic in humans and pigs and causes seasonal human flu
- H9N2, which has infected three people
- H7N2, which has infected two people
- H7N3, which has infected two people
- H10N7, which has infected two people
Properties of H5N1
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Infectivity
| Highly pathogenic H5N1 | |
|---|---|
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| → Countries with poultry or wild birds killed by H5N1. | |
| → Countries with humans, poultry and wild birds killed by H5N1. | |
H5N1 is easily transmissible between birds facilitating a potential global spread of H5N1. While H5N1 undergoes specific mutations and reassorting creating variations which infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to what are known as α2,3 galactose receptors, which populate the avian respiratory tract from the nose to the lungs. These receptors are virtually absent in humans, occurring only in and around the alveoli, structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.
H5N1 is mainly spread by domestic poultry, both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without themselves becoming sick.
Virulence
H5N1 has mutated into a variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift, H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all currently belonging to genotype Z of avian influenza virus H5N1, now the dominant genotype.
Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus
H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002 new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.
Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1 that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997.
Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations are occurring within this genotype that are increasing their pathogenicity.
Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.
Transmission and host range
Infected birds transmit H5N1 through their saliva, nasal secretions, feces and blood. Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C ( 32.0 °F) (over one month at freezing temperature) or 6 days at 37 °C ( 98.6 °F) (one week at human body temperature) so at ordinary temperatures it lasts in the environment for weeks. In arctic temperatures, it doesn't degrade at all.
Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.
In October 2004, researchers discovered that H5N1 is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading the highly pathogenic strain of H5N1 to chickens, crows, pigeons, and other birds, and the virus was increasing its ability to infect mammals as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic.
"Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability".
The New York Times, in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important".
High mutation rate
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of the influenza genome facilitates genetic recombination by segment reassortment in hosts who are infected with two different influenza viruses at the same time. H5N1 viruses can reassort genes with other strains that co-infect a host organism, such as a pig, bird, or human, and mutate into a form that can pass easily among humans. This is one of many possible paths to a pandemic.
The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types.
H3N2 ("swine flu") is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2, which is now resistant to the standard antiviral drugs amantadine and rimantadine. The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2.
Both the H2N2 and H3N2 pandemic strains contained avian flu virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source".
This e-book is under constant revision and is an excellent guide to Avian Influenza
Humans and H5N1
The earliest infections of humans by H5N1 coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population. This panzootic (a disease affecting animals of many species, especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory.
| Country | Report dates | [ edit ] Total | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2003 | 2004 | 2005 | 2006 | ||||||||||||
| cases | deaths | cases | deaths | cases | deaths | cases | deaths | cases | deaths | ||||||
| 8 | 5 | 63% | 8 | 5 | 63% | ||||||||||
| 4 | 4 | 100% | 2 | 2 | 100% | 6 | 6 | 100% | |||||||
| People's Republic of China | 8 | 5 | 63% | 11 | 7 | 64% | 19 | 12 | 63% | ||||||
| 1 | 0 | 0% | 1 | 0 | 0% | ||||||||||
| 14 | 6 | 43% | 14 | 6 | 43% | ||||||||||
| 17 | 11 | 65% | 36 | 30 | 83% | 53 | 41 | 77% | |||||||
| 2 | 2 | 100% | 2 | 2 | 100% | ||||||||||
| 17 | 12 | 71% | 5 | 2 | 40% | 22 | 14 | 64% | |||||||
| 12 | 4 | 33% | 12 | 4 | 33% | ||||||||||
| 3 | 3 | 100% | 29 | 20 | 69% | 61 | 19 | 31% | 93 | 42 | 45% | ||||
| Total | 3 | 3 | 100% | 46 | 32 | 70% | 95 | 41 | 43% | 86 | 56 | 65% | 230 | 132 | 57% |
| Source World Health Organization (WHO) : [Communicable Disease Surveillance & Response (CSR)]. | |||||||||||||||
Symptoms in humans
- Further information: Pneumonia
Humans who catch a humanized Influenza A virus (in other words a human flu virus of type A) usually have symptoms that include fever, cough, sore throat, muscle aches, conjunctivitis and, in severe cases, severe breathing problems and pneumonia that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's immune system and if the victim has been exposed to the strain before, and is therefore partially immune. No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu.
Highly pathogenic H5N1 avian flu in a human is far worse, killing 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms.
Treatment and prevention for humans
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- Further information: Flu research
However, WHO expert Hassan al-Bushra has said:
- "Even now, we remain unsure about Tamiflu's real effectiveness. As for a vaccine, work cannot start on it until the emergence of a new virus, and we predict it would take six to nine months to develop it. For the moment, we cannot by any means count on a potential vaccine to prevent the spread of a contagious influenza virus, whose various precedents in the past 90 years have been highly pathogenic".
There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide 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 H5N1 pandemic so there can be no pandemic vaccine".
Animal and lab studies suggest that Relenza (Zanamivir), which is in the same class of drugs as Tamiflu, may also be effective against H5N1, in a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals" (Leneva 2001).[Influenza Report] However another paper, de Jong 2005, suggested that Zazamivir might not provide protection in humans from the current avian strain of H5N1 if "systemic involvement of influenza infection is suspected - as has recently been suggested by some reports on avian H5N1 influenza in humans." While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can currently be manufactured in quantities that would be meaningful once efficient human transmission starts. [CIDRAP]
Preparations for pandemic
"The United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Department of State, the U.S. Department of Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government".
Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness".
Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention, the World Health Organization, the European Commission, and others.
There has been a huge impact of H5N1 on human society; especially the financial, political, social and personal responses to both actual and predicted deaths in birds, humans, and other animals.
Billions of U.S. dollars are being raised and spent to research H5N1 and prepare for a potential avian flu pandemic. Over ten billion dollars have been lost and over two hundred million birds have been killed to try to contain H5N1.
This, like everything else, is subject to political spin; wherein every interest group picks and chooses among the facts to support their favorite cause resulting in a distortion of the overall picture, the motivations of the people involved and the believability of the predictions.
People have reacted by buying less chicken causing poultry sales and prices to fall. Many individuals have stockpiled supplies for a possible flu pandemic.
From Wikipedia, the Free Encyclopedia. Original article here. Support Wikipedia by contributing or donating.Impact on human society
See also
Sources and notes
Further reading
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