Transmission and infection of H5N1
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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, due to the
global spread of H5N1 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 ...
that constitutes a
pandemic A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic (epidemiology), endemic disease wi ...
threat. Infected birds pass on
H5N1 Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of typ ...
through their
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
, nasal secretions, and
feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
. 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 The points of the compass are a set of horizontal, radially arrayed compass directions (or azimuths) used in navigation and cartography. A compass rose is primarily composed of four cardinal directions—north, east, south, and west—each sepa ...
and
east Asia East Asia is the eastern region of Asia, which is defined in both geographical and ethno-cultural terms. The modern states of East Asia include China, Japan, Mongolia, North Korea, South Korea, and Taiwan. China, North Korea, South Korea and ...
, where humans,
pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus s ...
s, and poultry live in close quarters. In these conditions a virus is more likely to
mutate In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitos ...
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 are clinical trials concerning H5N1 vaccines, which are intended to provide immunization to influenza A virus subtype H5N1. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines m ...
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 northernmost 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) *
Acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
ic pH conditions * Presence of anti-microbial
surfactant Surfactants are chemical compounds that decrease the surface tension between two liquids, between a gas and a liquid, or interfacial tension between a liquid and a solid. Surfactants may act as detergents, wetting agents, emulsifiers, foaming ...
s such as
sodium dodecyl sulfate Sodium dodecyl sulfate (SDS) or sodium lauryl sulfate (SLS), sometimes written sodium laurilsulfate, is an organic compound with the formula . It is an anionic surfactant used in many cleaning and hygiene products. This compound is the sodium sal ...
and lipid
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
s * Exposure to
disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
s: B-propiolactone,
formalin Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section Fo ...
, and
iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
compounds Ordinary levels of
chlorine Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...
in tap water kill H5N1 in public water systems. To kill avian flu viruses, 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 Influenza A virus subtype H9N2 (A/H9N2) is a subtype of the species Influenza A virus ( bird flu virus). Since 1998 a total of 86 cases of human infection with H9N2 viruses have been reported. Infection in birds H9N2 is the most common subtype ...
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 (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
, 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 Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
poultry against
bird flu "Bird Flu" is an urumee melam-dance song by recording artist M.I.A. on her second studio album '' Kala'' (2007). It was released as a digital download in 2006 through XL Recordings under exclusive license to Interscope Records in the US. Cr ...
* vaccinating poultry workers against
human flu Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...
* limiting travel in areas where H5N1 is found * increasing farm hygiene * reducing contact between
livestock Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to animals ...
and wild birds * reducing open-air
wet markets A wet market (also called a public market or a traditional market) is a marketplace selling fresh foods such as meat, fish as food, fish, greengrocer, produce and other consumption-oriented shelf life, perishable goods in a non-supermarket sett ...
* limiting workers contact with
cock fighting A cockfight is a blood sport, held in a ring called a cockpit. The history of raising fowl for fighting goes back 6,000 years. The first documented use of the ''word'' gamecock, denoting use of the cock as to a "game", a sport, pastime or ente ...
* reducing purchases of live fowl * improving veterinary
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
availability and cost. For example, after nearly two years of using mainly culling to control the virus, the
Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making i ...
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 infected or suspected to be infected.


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

According to the United Nations
FAO The Food and Agriculture Organization of the United Nations (FAO)french: link=no, Organisation des Nations unies pour l'alimentation et l'agriculture; it, Organizzazione delle Nazioni Unite per l'Alimentazione e l'Agricoltura is an intern ...
, 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 is the common name for numerous species of waterfowl in the family Anatidae. Ducks are generally smaller and shorter-necked than swans and geese, which are members of the same family. Divided among several subfamilies, they are a form t ...
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 or Ch'inghai Lake, also known by other names, is the largest lake in China. Located in an endorheic basin in Qinghai Province, to which it gave its name, Qinghai Lake is classified as an alkaline salt lake. The lake has fluctuat ...
-
China China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
, 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; Mongolian script: , , ; lit. "Mongol Nation" or "State of Mongolia" () is a landlocked country in East Asia, bordered by Russia to the north and China to the south. It covers an area of , with a population of just 3.3 million, ...
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 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. However, pigeons do not present a risk as they neither catch nor carry the virus.


Avian flu in humans


Human to human transmission

The
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
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 The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
in
Atlanta Atlanta ( ) is the capital and most populous city of the U.S. state of Georgia. It is the seat of Fulton County, the most populous county in Georgia, but its territory falls in both Fulton and DeKalb counties. With a population of 498,715 ...
, 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.


Prevention

Notwithstanding possible mutation of the virus, the probability of a "humanized" form of H5N1 emerging through
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
tic recombination in the body of a human co-infected with
H5N1 Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of typ ...
and another influenza virus type (a process called
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 particula ...
) could be reduced by widespread seasonal
influenza 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 ...
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 A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
. The
American American(s) may refer to: * American, something of, from, or related to the United States of America, commonly known as the "United States" or "America" ** Americans, citizens and nationals of the United States of America ** American ancestry, pe ...
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.
Daniel R. Lucey Daniel R. Lucey is an American physician, researcher, senior scholar and adjunct professor of infectious diseases at Georgetown University, and a research associate in anthropology at the Smithsonian National Museum of Natural History, where he ...
, 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 A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
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 drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...
s could prevent the evolution of a pandemic flu virus. Revised on January 10, 2001.


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 Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.
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
Pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
.'' Avian influenza HA bind alpha 2-3
sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...
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 Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, an ...
symptoms usually include
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
,
cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three pha ...
,
sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include * viral infections * group A streptococcal infection (GAS) bacterial infection * pharyngitis (inflammation of the throat) * tonsi ...
, muscle aches,
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the conjunctiva, outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may ...
and, in severe cases, severe breathing problems and
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity ...
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 The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
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, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
followed rapidly by a
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
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 Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of
tumor necrosis factor-alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
(TNFα), a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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 A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Norma ...
' by some, because of what seems to be a
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the ...
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 Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, quails, a ...
and
waterfowl Anseriformes is an order of birds also known as waterfowl that comprises about 180 living species of birds in three families: Anhimidae (three species of screamers), Anseranatidae (the magpie goose), and Anatidae, the largest family, which in ...
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 acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
change at position 92. By changing the amino acid from
glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
to
aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
, researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the
pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
of the H5N1 influenza virus. In short, this one amino acid difference in the NS1 protein produced by the NS
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
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 is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
.


Treatment

Neuraminidase inhibitors are a class of drugs that includes
zanamivir Zanamivir is a medication used to treat and prevent influenza caused by influenza A and influenza B viruses. It is a neuraminidase inhibitor and was developed by the Australian biotech firm Biota Holdings. It was licensed to Glaxo in 1990 and ap ...
and
oseltamivir Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at hig ...
, the latter being licensed for
prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
treatment in the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...
. Oseltamivir inhibits the influenza virus from spreading inside the user's body. It is marketed by
Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX S ...
as ''
Tamiflu Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at hig ...
''. 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 A compulsory license provides that the owner of a patent or copyright licenses the use of their rights against payment either set by law or determined through some form of adjudication or arbitration. In essence, under a compulsory license, an ...
for life-saving drugs. A second class of drugs, which include
amantadine Amantadine, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to wid ...
and
rimantadine Rimantadine ( INN, sold under the trade name 'Flumadine'') 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 s ...
, 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 November 21, 2016, the number of confirmed human cases of H5N1 reported to WHO stands at 856, with 452 fatalities, 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,http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/5964 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) http://www.medpagetoday.com/InfectiousDisease/URItheFlu/tb/2450 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


See also

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Fujian flu : ''See Influenza for details about the illnesses and Influenza A virus subtype H5N1 and Influenza A virus subtype H3N2 for details about the causative agents.'' Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 ...
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Severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''seve ...


Further reading

* * * * * * {{DEFAULTSORT:Transmission And Infection Of H5n1 Epidemiology Influenza A virus subtype H5N1 Avian influenza