Transmission and infection of H5N1

Transmission and infection of H5N1

Transmission and infection of H5N1 from infected avian sources to humans is a concern 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, [cite news
title=Seven Indonesian Bird Flu Cases Linked to Patients
date=May 23 2006
] with the latest such case in June 2006 (among members of a family in Sumatra). [cite web
title=WHO confirms human transmission< in Indonesian bird flu cluster
] 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 [cite web
title=HHS has enough H5N1 vaccine for 4 million people
date=July 5 2006
] 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". [cite web
title=Study supports concept of 2-stage H5N1 vaccination
date= October 13 2006
] 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 in birds

According to "Avian Influenza" by Timm C. Harder and Ortrud Werner::Following an incubation period of usually a few days (but rarely up to 21 days), depending upon the characteristics of the isolate, the dose of inoculum, the species, and age of the bird, the clinical presentation of avian influenza in birds is variable and symptoms are fairly unspecific. [cite journal
title=Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003
author=A.R. Elbers, G. Kock and A. Bouma
journal=Avian Pathol
] Therefore, a diagnosis solely based on the clinical presentation is impossible. The symptoms following infection with low pathogenic AIV may be as discrete as ruffled feathers, transient reductions in egg production or weight loss combined with a slight respiratory disease. [cite journal
author=I. Capua and F. Mutinelli
title=Low pathogenicity (LPAI) and highly pathogenic (HPAI) avian influenza in turkeys and chicken
journal=A Colour Atlas and Text on Avian Influenza
] Some LP strains such as certain Asian H9N2 lineages, adapted to efficient replication in poultry, may cause more prominent signs and also significant mortality. [cite journal
author=S. Bano S, K. Naeem K, S.A. Malik
title=Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in chicken
journal=Avian Dis
volume=47, Suppl
] [cite journal
author=C Li, K Yu, G TiaG, D Yu, L Liu, B Jing, J Ping, H. Chen
title=Evolution of H9N2 influenza viruses from domestic poultry in Mainland China
] In its highly pathogenic form, the illness in chickens and turkeys is characterised by a sudden onset of severe symptoms and a mortality that can approach 100% within 48 hours. [cite journal
author=D.E. Swayne, D.L. Suarez
title=Highly pathogenic avian influenza
journal=Rev Sci Tech
] [cite web
title=Avian Influenza
author=Timm C. Harder and Ortrud Werner
publisher=Influenza Report
] 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.

Poultry farming practices

There have been a number of farming practices that have changed in response to outbreaks of the H5N1 virus, including:

* vaccinating poultry against bird flu
* vaccinating poultry workers against human flu
* limiting travel in areas where H5N1 is found
* increasing farm hygiene
* reducing contact between livestock and wild birds
* reducing open-air wet markets
* limiting workers contact with cock fighting
* reducing purchases of live fowl
* improving veterinary vaccine availability and cost. [cite web
publisher=Council on Foreign Relations
title=The Threat of Global Pandemics
date=June 16 2005

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. [cite news
title=Vietnam to unveil advanced plan to fight bird flu
date=April 28 2006

Dealing with outbreaks

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 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 initially denied past outbreaks of severe acute respiratory syndrome (SARS) and HIV, although there have been some signs of improvement regarding its openness, particularly with regard to H5N1.

Use of vaccines

Dr. Robert Webster "et al" write

:Transmission of highly pathogenic H5N1 from domestic poultry back to migratory waterfowl in western China has increased the geographic spread. The spread of H5N1 and its likely reintroduction to domestic poultry increase the need for good agricultural vaccines. In fact, the root cause of the continuing H5N1 pandemic threat may be the way the pathogenicity of H5N1 viruses is masked by cocirculating influenza viruses or bad agricultural vaccines." [cite journal
title=H5N1 Outbreaks and Enzootic Influenza
author=Robert G. Webster "et al"
journal=Emerging Infectious Diseases
month=January | year=2006

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. [cite news
title=Expert: Bad vaccines may trigger China bird flu
date=December 30 2005

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. [cite web
title=Bird flu vaccine no silver bullet
date=February 22 2006


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.

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 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. [cite web
title=Wild birds and Avian Influenza
] For example, small birds like sparrows, starlings and pigeons 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. [cite web
title=Small birds must be kept out of poultry farms
date=December 12 2006
work=World Poultry

Avian flu in humans

Human to human transmission

The WHO believes that another influenza pandemic is as likely to occur as any time since 1968, when the last century's third of three pandemics took place. [ [ Current WHO phase of pandemic alert] ] 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. [ [ WHO Global Influenza Preparedness Plan] ] 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. [ [ Current WHO phase of pandemic alert] ]

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." [cite news| url=
title=Human Flu Transfers May Exceed Reports | publisher=New York Times | date=June 4 2006 | author=Donald G. McNeil Jr.
] A few isolated cases of suspected human to human transmission exist. [cite news
title=Seven Indonesian Bird Flu Cases Linked to Patients
date=May 23 2006
] with the latest such case in June 2006 (among members of a family in Sumatra). [cite web
title=WHO confirms human transmission< in Indonesian bird flu cluster
] No pandemic strain of H5N1 has yet been found. [cite news|url=|title=Avian influenza – situation in Indonesia – update 17|publisher=WHO|date=June 6 2006]

There is also concern, although no definitive proof, that other animals &mdash; particularly cats &mdash; may be able to act as a bridge between birds and humans. So far several cats have been confirmed to have died from H5N1 and the fact that cats have regular close contact with both birds and humans means monitoring of H5N1 in cats will need to continue.


Not withstanding 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.

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.

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 [cite web
date=March 24, 2005
title=Interim Guidance about Avian Influenza A (H5N1) for U.S. Citizens Living Abroad
publisher=U.S. Centers for Disease Control and Prevention
work=Travel Notices
author=National Center for Infectious Diseases, Division of Global Migration and Quarantine
] . 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. 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." [cite news
title=Bird flu vaccine won't precede pandemic
author=Jennifer Schultz
publisher=United Press International
date=November 28 2005
] 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 [Promising research into vaccines includes:
* cite journal
title=Avian Influenza: 'Pandemic Vaccine' Appears to Protect Only at High Doses
author=Martin Enserink
date=August 12 2005

* cite news
title=GlaxoSmithKline Initiates Human Trial Programme With Two H5N1 Pandemic Flu Vaccines
date=March 30 2006

* cite news
title=Murtha eager to speed vaccine
date=January 28 2006
A promising new bird flu vaccine developed by University of Pittsburgh researchers could provide better protection and be made more quickly than other experimental vaccines.
] . 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. cite web
title=Oseltamivir (Tamiflu)
publisher=National Institutes of Health
date=January 13 2000
Revised on January 10 2001.]

Environmental survival

Avian flu virus can last indefinitely at a temperature dozens of degrees below freezing, as is found in the northern most areas that migratory birds frequent.

Heat kills H5N1 (i.e. inactivates the virus).

Influenza A viruses can survive:
* Over 30 days at 0°C (32.0°F) (over one month at freezing temperature)
* 6 days at 37°C (98.6°F) (one week at human body temperature)
* decades in permanently frozen lakes
* on hard non-porous surface such as plastic or stainless steel for 24-48 hours
* on clothes, paper and tissues for 8-12 hours [cite web
title=The prevention and treatment of viral respiratory disorders

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. [ [ CIDRAP] article "Germany finds H5N1 in frozen duck meat" published September 10, 2007 ]

Inactivation of the virus also occurs under the following conditions:
* 30 minutes 60°C (140.0°F) (half hour at a temperature that causes first and second degree burns in humans in ten seconds [cite web
title=Hot Water Burn & Scalding Graph
] )
* Acidic pH conditions
* Presence of oxidizing agents such as sodium dodecyl sulfate, lipid solvents, and B-propiolactone
* Exposure to disinfectants: formalin, iodine compounds [cite web
title=Avian flu biofacts

Ordinary levels of chlorine in tap water kill H5N1 in public water systems. [ [ Water tech on line] article "Study: Chlorination inactivates avian flu strain" published September 10, 2007 says "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."]

To kill avian flu viruses, the "World Health Organization recommends that environmental surfaces be cleaned by the following:
*Disinfectants such as sodium hypochloride, 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" [ This quote is from page 28 of [ The Johns Hopkins University - The Impact of Pandemic Influenza on Public Health] Use [] to find more like this about H5N1 and [] about other subjects]


The human incubation period of avian influenza A (H5N1) is 2 to 17 daysFull text article online: cite journal
title=Avian Influenza A (H5N1) Infection in Humans
author=The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5
journal=New England Journal of Medicine
date=September 29 2005
] . 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. [cite web
title=Bird Flu: Public Health Implications for India
author=T Jacob John
date=November 12 2005
publisher=Economic and Political Weekly
] 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." [ New England Journal of Medicine] article "Update on Avian Influenza A (H5N1) Virus Infection in Humans" published January 17, 2008]

:"See also Pneumonia."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. [cite journal
journal=New England Journal of Medicine
author=Menno D. de Jong "et al"
date=February 17 2005
title=Fatal Avian Influenza A (H5N1) in a Child Presenting with Diarrhea Followed by Coma

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."

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 [cite journal
title=Influenza: The world is teetering on the edge of a pandemic that could kill a large fraction of the human population
author=Robert G. Webster and Elizabeth Jane Walker
journal=American Scientist
] . 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 [cite journal
title=Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells
author=M. C. Chan et al
journal=Respiratory Research
] Other important mechanisms also exist "in the acquisition of virulence in avian influenza viruses" according to the CDC. [cite journal
title=Novel Avian Influenza H7N3 Strain Outbreak, British Columbia
author=Martin Hirst, Caroline R. Astell, Malachi Griffith, Shaun M. Coughlin, Michelle Moksa, Thomas Zeng "et al"
month=December | year=2004
journal=Emerg Infect Dis

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.

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.


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 . 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. [cite news
title=Bird Flu Drug Rendered Useless: Chinese Chickens Given Medication Made for Humans
author=Alan Sipress
publisher=Washington Post
date=June 18 2005
] . However, recent data suggest that some strains of H5N1 are susceptible to the older drugs, which are inexpensive and widely available. [cite news
title=WHO sees role for older antivirals in some H5N1 cases
date=May 22 2006

Research indicates that therapy to block one cytokine to lessen a cytokine storm in a patient may not be clinically beneficial. [ [ CIDRAP] article "Study: Inhibiting cytokine response might not reverse H5N1 infections" published July 16, 2007]

Mortality rate

From the first laboratory-confirmed case through March 18, 2008, the number confirmed human cases of H5N1 reported to WHO stands at 373, with 236 fatalities [ [ Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO] ] , reflecting a 63.27% fatality rate.

For possible later updates by the WHO, see]

The global case fatality ratio looks only to the official tally [The tally may be obtained by clicking a link to the most current date shown by the UN on the WHO's web page entitled Epidemic and Pandemic Alert and Response (EPR)] 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 [ Options For Influenza Control VI (Conference, Toronto Canada, June 18, 2007) Even those who were in close contact with both infected birds and infected people showed no sign of ever having been infected, Dr. Dejpichai and colleagues found. The study is consistent with findings in Hong Kong, China, and Cambodia, which showed viral seroprevalence of no more than 10% among poultry workers and people living in villages where H5N1 outbreaks occurred, she said. But it contradicts a population-based study in Vietnam, published last year, that concluded that mild cases of the virus were likely to be common. (see Mild Avian Flu Transmission May Be Common) ] , 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.

Notes and references

ee also

*Fujian flu
*Severe acute respiratory syndrome

Further reading

* cite web
title=Avian Influenza (Bird Flu): Agricultural and Wildlife Considerations

* cite web
publisher=American Family Physician
title=Avian Influenza: Preparing for a Pandemic

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