Transmission and infection of H5N1 from infected avian sources to humans has been a concern since the first documented case of human infection in 1997, [1] due to the global spread of H5N1 that constitutes a pandemic threat.
Infected birds pass on H5N1 through 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 southeast and east Asia, where humans, pigs, and poultry live in close quarters. In these conditions a virus is more likely to mutate into a form that more easily infects humans. A few isolated cases of suspected human to human transmission exist, [2] with the latest such case in June 2006 (among members of a family in Sumatra). [3] No pandemic strain of H5N1 has yet been found.
H5N1 vaccines for chickens exist and are sometimes used, although there are many difficulties, and it's difficult to decide whether it helps more or hurts more. H5N1 pre-pandemic vaccines exist in quantities sufficient to inoculate a few million people [4] and might be useful for priming to "boost the immune response to a different H5N1 vaccine tailor-made years later to thwart an emerging pandemic". [5] H5N1 pandemic vaccines and technologies to rapidly create them are in the H5N1 clinical trials stage but can not be verified as useful until after there exists a pandemic strain.
Avian flu virus can last indefinitely at a temperature dozens of degrees below freezing, as is found in the northernmost areas that migratory birds frequent.[ citation needed ]
Heat kills H5N1 (i.e. inactivates the virus).
Influenza A viruses can survive:
While cooking poultry to 70 °C (158 °F) kills the H5N1 virus, it is recommended to cook meat to 74 °C (165 °F) to kill all foodborne pathogens. [7]
Inactivation of the virus also occurs under the following conditions:
Ordinary levels of chlorine in tap water kill H5N1 in public water systems. [10]
To kill avian flu viruses, [11]
(the) World Health Organization recommends that environmental surfaces be cleaned by the following:
- Disinfectants such as sodium hypochlorite, 1% in-use dilution, 5% solution to be diluted 1:5 in clean water, for materials contaminated with blood and body fluids
- Bleaching powder seven grams per liter with 70% available chlorine for toilets and bathrooms
- 70% alcohol for smooth surfaces, tabletops, and other surfaces where bleach cannot be used
H5N1 "can remain infectious in municipal landfills for almost 2 years. [...] The two factors that most reduced influenza survival times were elevated temperature and acidic or alkaline pH." [12]
According to Avian Influenza by Timm C. Harder and Ortrud Werner:
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.
There have been a number of farming practices that have changed in response to outbreaks of the H5N1 virus, including:
For example, after nearly two years of using mainly culling to control the virus, the Vietnamese government in 2005 adopted a combination of mass poultry vaccination, disinfecting, culling, information campaigns and bans on live poultry in cities. [20]
The majority of H5N1 flu 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 infected or suspected to be infected.[ citation needed ]
Dr. Robert G. Webster et al. write
Webster speculates that substandard vaccines may be preventing the expression of the disease in the birds but not stopping them from carrying or transmitting the virus through feces, or the virus from mutating. [22]
In order to protect their poultry from death from H5N1, China reportedly made a vaccine based on reverse genetics produced with H5N1 antigens, that Dr Wendy Barclay, a virologist at the University of Reading believes have generated up to six variations of H5N1. [23]
According to the United Nations FAO, wild water fowl likely plays 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. A newly mutated virus could circulate within the domestic and possibly resident bird populations until highly pathogenic avian influenza (HPAI) arises. This new virus is pathogenic to poultry and possibly to the wild birds that it arose from.[ citation needed ]
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.[ citation needed ]
The AI virus has adapted to the environment in ways such as using water for survival and to spread, and creating a reservoir (ducks) strictly tied to water. The water in turn influences movement, social behavior 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. Most research is needed concerning HPAI viruses in wild birds. [24] For example, small birds like sparrows and starlings can be infected with deadly H5N1 strains and they can carry the virus from chicken house to chicken house causing massive epidemics among the chickens. [25] However, pigeons do not present a risk as they neither catch nor carry the virus. [26] [27] [28]
The WHO believes that another influenza pandemic is as likely to occur at any time since 1968, when the last century's third of three pandemics took place. [29] The WHO describes a series of six phases, starting with the inter-pandemic period, where there are no new influenza virus subtypes detected in humans, and progressing numerically to the pandemic period, where there is efficient and sustained human-to-human transmission of the virus in the general population. [30] At the present moment, we are at phase 3 on the scale, meaning a new influenza virus subtype is causing disease in humans, but is not yet spreading efficiently and sustainably among humans. [29]
So far, H5N1 infections in humans are attributed to bird-to-human transmission of the virus in most cases. Until May 2006, the WHO estimate of the number of human to human transmission had been "two or three cases". On May 24, 2006, Dr. Julie L. Gerberding, director of the United States Centers for Disease Control and Prevention in Atlanta, estimated that there had been "at least three." On May 30, Maria Cheng, a WHO spokeswoman, said there were "probably about half a dozen," but that no one "has got a solid number." [31] A few isolated cases of suspected human to human transmission exist. [2] with the latest such case in June 2006 (among members of a family in Sumatra). [3] No pandemic strain of H5N1 has yet been found. [32]
Notwithstanding possible mutation of the virus, the probability of a "humanized" form of H5N1 emerging through genetic recombination in the body of a human co-infected with H5N1 and another influenza virus type (a process called reassortment) could be reduced by widespread seasonal influenza vaccination in the general population. It is not clear at this point whether vaccine production and immunization could be stepped up sufficiently to meet this demand.[ citation needed ]
If an outbreak of pandemic flu does occur, its spread might be slowed by increasing hygiene in aircraft, and by examining airline cabin air filters for presence of H5N1 virus.[ citation needed ]
The American Centers for Disease Control and Prevention advises travelers to areas of Asia where outbreaks of H5N1 have occurred to avoid poultry farms and animals in live food markets. [33] Travelers should also avoid surfaces that appear to be contaminated by feces from any kind of animal, especially poultry.
There are several H5N1 vaccines for 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. Daniel R. 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." [34] 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. [35] 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 drugs could prevent the evolution of a pandemic flu virus. [36]
The human incubation period of avian influenza A (H5N1) is 2 to 17 days. [37] 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. [38] For highly pathogenic H5N1 avian influenza in a human, "the time from the onset to presentation (median, 4 days) or to death (median, 9 to 10 days) has remained unchanged from 2003 through 2006." [39]
Influenza (flu) |
---|
Avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Usually other differences also exist. There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1.
Human flu symptoms usually 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 influenza in a human appears to be far worse, killing over 50% of humans reported infected with the virus, although it is unknown how many cases (with milder symptoms) go unreported. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. [40]
As of February 2008, the "median age of patients with influenza A (H5N1) virus infection is approximately 18 years [...] The overall case fatality proportion is 61% [...] Handling of sick or dead poultry during the week before the onset of illness is the most commonly recognized risk factor [...] The primary pathologic process that causes death is fulminant viral pneumonia." [39]
There have been studies of the levels of cytokines in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha (TNFα), a protein that 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. [41] The inflammatory cascade triggered by H5N1 has been called a 'cytokine storm' by some, because of what seems to be a positive feedback process of damage to the body resulting from immune system stimulation. H5N1 type flu virus induces higher levels of cytokines than the more common flu virus types such as H1N1. [42] Other important mechanisms also exist "in the acquisition of virulence in avian influenza viruses" according to the CDC. [43]
The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia is currently believed to be responsible for the enhanced proinflammatory cytokine response. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus.[ citation needed ]
In short, this one amino acid difference in the NS1 protein produced by the NS RNA molecule of the H5N1 virus is believed to be largely responsible for an increased pathogenicity (on top of the already increased pathogenicity of its hemagglutinin type which allows it to grow in organs other than lungs) that can manifest itself by causing a cytokine storm in a patient's body, often causing pneumonia and death.[ citation needed ]
Neuraminidase inhibitors are a class of drugs that includes zanamivir and oseltamivir, the latter being licensed for prophylaxis treatment in the United Kingdom. Oseltamivir inhibits the influenza virus from spreading inside the user's body. [36] It is marketed by Roche as 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 August 2005, Roche agreed to donate three million courses of Tamiflu 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 licenses for life-saving drugs.
A second class of drugs, which include amantadine and rimantadine, target the M2 protein, but have become ineffective against most strains of H5N1, due to their use in poultry in China in the 1990s, which created resistant strains. [44] However, recent data suggest that some strains of H5N1 are susceptible to the older drugs, which are inexpensive and widely available. [45]
Research indicates that therapy to block one cytokine to lessen a cytokine storm in a patient may not be clinically beneficial. [46]
From the first laboratory-confirmed case through November 21, 2016, the number of confirmed human cases of H5N1 reported to WHO stands at 856, with 452 fatalities, [47] reflecting a 53% fatality rate.
The global case fatality ratio looks only to the official tally of cases confirmed by the WHO. It takes no account of other cases, such as those appearing in press reports. Nor does it reflect any estimate of the global extent of mild, asymptomatic, [48] or other cases which are undiagnosed, unreported by national governments to the WHO, or for any reason cannot be confirmed by the WHO. While the WHO's case count is clearly the most authoritative, these unavoidable limitations result in an unknown number of cases being omitted from it.
Researchers from the US Environmental Protection Agency (EPA), the University of Georgia (Athens, GA) and US Department of Agriculture (USDA) found that the maintenance of a free chlorine residual of 0.52 to 1.08 milligrams per liter (mg/L) was sufficient to inactivate the virus by greater than three orders of magnitude within an exposure time of one minute, according to the study. They noted that EPA specifications for public water supplies that the free chlorine residual values be 6 to 8 mg/L per minute would be "more than sufficient" to inactivate H5N1 in the water environment.
Influenza A virus (IAV) is a pathogen that causes the flu in birds and some mammals, including humans. It is an RNA virus whose subtypes have been isolated from wild birds. Occasionally, it is transmitted from wild to domestic birds, and this may cause severe disease, outbreaks, or human influenza pandemics.
Avian influenza, also known as avian flu, is a bird flu caused by the influenza A virus, which can infect people. It is similar to other types of animal flu in that it is caused by a virus strain that has adapted to a specific host. The type with the greatest risk is highly pathogenic avian influenza (HPAI).
Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type A of subtype H5N1, is the highly pathogenic causative agent of H5N1 flu, commonly known as avian influenza. It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic and panzootic, killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Many references to "bird flu" and H5N1 in the popular media refer to this strain.
Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As of 2009, identified SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3.
An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The most recent, the 2009 swine flu pandemic, resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.
The global spread of H5N1 influenza in birds is considered a significant pandemic threat. While other H5N1 influenza strains are known, they are significantly different on a genetic level from a recent, highly pathogenic, emergent strain of H5N1, which was able to achieve hitherto unprecedented global spread in 2008. The H5N1 strain is a fast-mutating, highly pathogenic avian influenza virus (HPAI) found in multiple bird species. It is both epizootic and panzootic. Unless otherwise indicated, "H5N1" in this timeline refers to the recent highly pathogenic strain of H5N1.
H5 N2 is a subtype of the species Influenzavirus A. The subtype infects a wide variety of birds, including chickens, ducks, turkeys, falcons, and ostriches. Affected birds usually do not appear ill, and the disease is often mild as avian influenza viral subtypes go. Some variants of the subtype are much more pathogenic than others, and outbreaks of "high-path" H5N2 result in the culling of thousands of birds in poultry farms from time to time. It appears that people who work with birds can be infected by the virus, but suffer hardly any noticeable health effects. Even people exposed to the highly pathogenic H5N2 variety that killed ostrich chicks in South Africa only seem to have developed conjunctivitis, or a perhaps a mild respiratory illness. There is no evidence of human-to-human spread of H5N2. On November 12, 2005 it was reported that a falcon was found to have H5N2.
Influenza A virus subtype H7N7 (A/H7N7) is a subtype of Influenza A virus, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains (HPAI) and low pathogenic strains (LPAI) exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies. This unusual zoonotic potential represents a pandemic threat.
H5N1 genetic structure is the molecular structure of the H5N1 virus's RNA.
The global spread of H5N1 in birds is considered a significant pandemic threat.
The global spread of H5N1 in birds is considered a significant pandemic threat.
The global spread of H5N1 in birds is considered a significant pandemic threat.
Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province in Southeast China.
The Goose Guangdong virus refers to the strain A/Goose/Guangdong/1/96 (Gs/Gd)-like H5N1 HPAI viruses. It is a strain of the Influenzavirus A subtype H5N1 virus that was first detected in a goose in Guangdong in 1996. It is an HPAI virus, meaning that it can kill a very high percentage of chickens in a flock in mere days. It is believed to be the immediate precursor of the current dominant strain of HPAI A(H5N1) that evolved from 1999 to 2002 creating the Z genotype that is spreading globally and is epizootic and panzootic, killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread.
Human mortality from H5N1 or the human fatality ratio from H5N1 or the case-fatality rate of H5N1 is the ratio of the number of confirmed human deaths resulting from confirmed cases of transmission and infection of H5N1 to the number of those confirmed cases. For example, if there are 100 confirmed cases of humans infected with H5N1 and 10 die, then there is a 10% human fatality ratio. H5N1 flu is a concern due to the global spread of H5N1 that constitutes a pandemic threat. The majority of H5N1 flu cases have been reported in southeast and east Asia. The case-fatality rate is central to pandemic planning. Estimates of case-fatality (CF) rates for past influenza pandemics have ranged from to 2-3% for the 1918 pandemic to about 0.6% for the 1957 pandemic to 0.2% for the 1968 pandemic. As of 2008, the official World Health Organization estimate for the case-fatality rate for the outbreak of H5N1 avian influenza was approximately 60%. Public health officials in Ontario, Canada argue that the true case-fatality rate could be lower, pointing to studies suggesting it could be 14-33%, and warned that it was unlikely to be as low as the 0.1–0.4% rate that was built into many pandemic plans.
The global spread of H5N1 in birds is considered a significant pandemic threat.
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.
The pandemic H1N1/09 virus is a swine origin influenza A virus subtype H1N1 strain that was responsible for the 2009 swine flu pandemic. This strain is often called swine flu by the public media. For other names, see the Nomenclature section below.
Influenza A virus subtype H7N9 (A/H7N9) is a bird flu strain of the species Influenza virus A. Avian influenza A H7 viruses normally circulate amongst avian populations with some variants known to occasionally infect humans. An H7N9 virus was first reported to have infected humans in March 2013, in China. Cases continued to be reported throughout April and then dropped to only a few cases during the summer months. At the closing of the year, 144 cases had been reported of which 46 had died. It is known that influenza tends to strike during the winter months, and the second wave, which began in October, was fanned by a surge in poultry production timed for Lunar New Year feasts that began at the end of January. January 2014 brought a spike in reports of illness with 96 confirmed reports of disease and 19 deaths. As of April 11, 2014, the outbreak's overall total was 419, including 7 in Hong Kong, and the unofficial number of deaths was 127.
Cats with avian influenza exhibit symptoms that can result in death. They are one of the few species that can get avian influenza. The specific virus that they get is H5N1, which is a subtype of avian influenza. In order to get the virus, cats need to be in contact with waterfowl, poultry, or uncooked poultry that are infected. Two of the main organs that the virus affects are the lungs and liver.