Transmission and infection of H5N1
Encyclopedia
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, pig
s, 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, with the latest such case in June 2006 (among members of a family in Sumatra). 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 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". 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.
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.
Inactivation of the virus also occurs under the following conditions:
Ordinary levels of chlorine
in tap water kill H5N1 in public water systems.
To kill avian flu viruses, the "World Health Organization recommends that environmental surfaces be cleaned by the following:
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."
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.
For example, after nearly two years of using mainly culling to control the virus, the Vietnam
ese government in 2005 adopted a combination of mass poultry vaccination, disinfecting, culling, information campaigns and bans on live poultry in cities.
(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.
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.
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.
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 duck
s. 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. 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.
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. 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.
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.
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." A few isolated cases of suspected human to human transmission exist. with the latest such case in June 2006 (among members of a family in Sumatra). No pandemic strain of H5N1 has yet been found.
There is also concern, although no definitive proof, that other animals — particularly cats — 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, and dogs will need to continue.
tic 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 . 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." 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 . 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 drug
s could prevent the evolution of a pandemic flu virus.
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.
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 cytokine
s 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 . 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 Other important mechanisms also exist "in the acquisition of virulence in avian influenza viruses
" according to the CDC.
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
.
, 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.. However, recent data suggest that some strains of H5N1 are susceptible to the older drugs, which are inexpensive and widely available.
Research indicates that therapy to block one cytokine to lessen a cytokine storm in a patient may not be clinically beneficial.
For possible later updates by the WHO, see http://www.who.int/csr/disease/avian_influenza/country/en/
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, 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.
Global spread of H5N1
The global spread of highly pathogenic H5N1 influenza in birds is considered a significant pandemic threat.While other H5N1 influenza strains are known, they are significantly different from a current, highly pathogenic H5N1 strain on a genetic level, making the global spread of this new strain...
that constitutes a pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
threat.
Infected birds pass on H5N1 through their saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
, nasal secretions
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
, and feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. 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
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
and east Asia
East Asia
East Asia or Eastern Asia is a subregion of Asia that can be defined in either geographical or cultural terms...
, where humans, pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s, and poultry live in close quarters. In these conditions a virus is more likely to mutate
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
into a form that more easily infects humans. A few isolated cases of suspected human to human transmission exist, with the latest such case in June 2006 (among members of a family in Sumatra). 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 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". H5N1 pandemic vaccines and technologies to rapidly create them are in the H5N1 clinical trials
H5N1 clinical trials
H5N1 clinical trials are clinical trials concerning H5N1 vaccines. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans.-Current status of H5N1 candidate vaccines:...
stage but can not be verified as useful until after there exists a pandemic strain.
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
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.
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)
- AcidAcidAn acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
ic pHPHIn chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
conditions - Presence of oxidizing agentOxidizing agentAn oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...
s such as sodium dodecyl sulfateSodium dodecyl sulfateSodium dodecyl sulfate , sodium laurilsulfate or sodium lauryl sulfate is an organic compound with the formula CH311OSO3Na). It is an anionic surfactant used in many cleaning and hygiene products...
, lipid solventSolventA solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...
s, and B-propiolactone - Exposure to disinfectants: formalin, iodineIodineIodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
compounds
Ordinary levels of chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
in tap water kill H5N1 in public water systems.
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"
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."
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. 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. Some LP strains such as certain Asian H9N2 lineages, adapted to efficient replication in poultry, may cause more prominent signs and also significant mortality. 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.
The current method of prevention in animal populations is to destroy infected animals, as well as animals suspected of being infected. In southeast Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, 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:- vaccinatingVaccinationVaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
poultry against bird flu - vaccinating poultry workers against human fluHuman fluHuman flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
- limiting travel in areas where H5N1 is found
- increasing farm hygiene
- reducing contact between livestockLivestockLivestock refers to one or more domesticated animals raised in an agricultural setting to produce commodities such as food, fiber and labor. The term "livestock" as used in this article does not include poultry or farmed fish; however the inclusion of these, especially poultry, within the meaning...
and wild birds - reducing open-air wet markets
- limiting workers contact with cock fightingCockfightA cockfight is a blood sport between two roosters , held in a ring called a cockpit. Cockfighting is now illegal throughout all states in the United States, Brazil, Australia and in most of Europe. It is still legal in several U.S. territories....
- reducing purchases of live fowl
- improving veterinary vaccineVaccineA vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
availability and cost.
For example, after nearly two years of using mainly culling to control the virus, the Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
ese government in 2005 adopted a combination of mass poultry vaccination, disinfecting, culling, information campaigns and bans on live poultry in cities.
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 NationsUnited Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...
(UN) World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) has expressed concern that not all countries are reporting outbreaks as completely as they should. China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
, for example, is known to have initially denied past outbreaks of severe acute respiratory syndrome
Severe acute respiratory syndrome
Severe Acute Respiratory Syndrome is a respiratory disease in humans which is caused by the SARS coronavirus . Between November 2002 and July 2003 an outbreak of SARS in Hong Kong nearly became a pandemic, with 8,422 cases and 916 deaths worldwide according to the WHO...
(SARS) and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, although there have been some signs of improvement regarding its openness, particularly with regard to H5N1.
Use of vaccines
Dr. Robert G. 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."
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.
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.
Transmission
Fão
Fão is a town in Esposende Municipality in Portugal....
, 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 duck
Duck
Duck is the common name for a large number of species in the Anatidae family of birds, which also includes swans and geese. The ducks are divided among several subfamilies in the Anatidae family; they do not represent a monophyletic group but a form taxon, since swans and geese are not considered...
s. 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
Qinghai Lake
Qinghai Lake , is a saline lake situated in the province of Qinghai, and is the largest lake in China. The names Qinghai and Kokonor both mean "Blue/Teal Sea/Lake" in Chinese and Mongolian. It is located about west of the provincial capital of Xining at 3,205 m above sea level in a depression...
-China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, 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
Mongolia
Mongolia is a landlocked country in East and Central Asia. It is bordered by Russia to the north and China to the south, east and west. Although Mongolia does not share a border with Kazakhstan, its western-most point is only from Kazakhstan's eastern tip. Ulan Bator, the capital and largest...
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. 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.
Human to human transmission
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
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. 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.
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.
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
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
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." A few isolated cases of suspected human to human transmission exist. with the latest such case in June 2006 (among members of a family in Sumatra). No pandemic strain of H5N1 has yet been found.
There is also concern, although no definitive proof, that other animals — particularly cats — 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, and dogs will need to continue.
Prevention
Notwithstanding possible mutation of the virus, the probability of a "humanized" form of H5N1 emerging through geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
tic recombination in the body of a human co-infected with H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
and another influenza virus type (a process called reassortment
Reassortment
Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...
) could be reduced by widespread seasonal influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
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
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
.
The American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
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 . 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." 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 . Vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
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 drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s could prevent the evolution of a pandemic flu virus.
Symptoms
The human incubation period of avian influenza A (H5N1) is 2 to 17 days. 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. 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."- See also PneumoniaPneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
Avian influenza HA bind alpha 2-3 sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic 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
Human flu
Human flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
symptoms usually include
fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....
, muscle aches
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
and, in severe cases, severe breathing problems and pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
followed rapidly by a coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
without developing respiratory or flu-like symptoms.
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 cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha (TNFα), a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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 . The inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
cascade triggered by H5N1 has been called a 'cytokine storm
Cytokine storm
A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
' by some, because of what seems to be a positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...
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 Other important mechanisms also exist "in the acquisition of virulence in avian influenza viruses
Influenzavirus A
Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
" according to the CDC.
The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in poultry
Poultry
Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...
and waterfowl
Waterfowl
Waterfowl are certain wildfowl of the order Anseriformes, especially members of the family Anatidae, which includes ducks, geese, and swans....
in Southeast Asia is currently believed to be responsible for the enhanced proinflammatory cytokine response. H5N1 NS1 is characterized by a single amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
change at position 92. By changing the amino acid from glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
to aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
, researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity
Pathogenicity
Pathogenicity is the ability of a pathogen to produce an infectious disease in an organism.It is often used interchangeably with the term "virulence", although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by...
of the H5N1 influenza virus.
In short, this one amino acid difference in the NS1 protein produced by the NS RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
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
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.
Treatment
Neuraminidase inhibitors are a class of drugs that includes zanamivir and oseltamivirOseltamivir
Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
, the latter being licensed for prophylaxis treatment in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
. Oseltamivir inhibits the influenza virus from spreading inside the user's body . It is marketed by Roche
Hoffmann-La Roche
F. Hoffmann-La Roche Ltd. is a Swiss global health-care company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange....
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
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
and rimantadine
Rimantadine
Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug...
, 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.. However, recent data suggest that some strains of H5N1 are susceptible to the older drugs, which are inexpensive and widely available.
Research indicates that therapy to block one cytokine to lessen a cytokine storm in a patient may not be clinically beneficial.
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, reflecting a 63.27% fatality rate.For possible later updates by the WHO, see http://www.who.int/csr/disease/avian_influenza/country/en/
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, 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.