Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the
influenza A virus which can cause illness in
human
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, cultu ...
s and many other animal species.
A bird-adapted strain of H5N1, called HPAI A(H5N1) for highly pathogenic avian influenza virus of type A of subtype H5N1, is the highly
pathogen
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 ...
ic causative agent of
H5N1 flu, commonly known as
avian influenza
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds. ("bird flu"). It is
enzootic
Enzootic is the non-human equivalent of endemic and means, in a broad sense, "belonging to" or "native to", "characteristic of", or "prevalent in" a particular geography, race, field, area, or environment; native to an area or scope.
It also has ...
(maintained in the population) in many bird populations, especially in
Southeast Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainlan ...
. One strain of HPAI A(H5N1) is
spreading globally after first appearing in Asia. It is
epizootic
In epizoology, an epizootic (from Greek: ''epi-'' upon + ''zoon'' animal) is a disease event in a nonhuman animal population analogous to an epidemic in humans. An epizootic may be restricted to a specific locale (an "outbreak"), general (an "epi ...
(an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the
culling
In biology, culling is the process of segregating organisms from a group according to desired or undesired characteristics. In animal breeding, it is the process of removing or segregating animals from a breeding stock based on a specific tr ...
of hundreds of millions of others to stem its spread. Many references to "bird flu" and H5N1 in the popular media refer to this strain.
[ ]
This was reprinted in 2005:
According to the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
(WHO) and the
United Nations
The United Nations (UN) is an intergovernmental organization whose stated purposes are to maintain international peace and security, develop friendly relations among nations, achieve international cooperation, and be a centre for harmoniz ...
Food and Agriculture Organization
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 ...
, H5N1
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 ge ...
is gradually continuing to rise in endemic areas, but the avian influenza disease situation in
farmed birds is being held in check by vaccination, and there is "no evidence of sustained human-to-human transmission" of the virus. Eleven outbreaks of H5N1 were reported worldwide in June 2008, in five countries (China, Egypt, Indonesia, Pakistan and Vietnam) compared to 65 outbreaks in June 2006, and 55 in June 2007. The global HPAI situation significantly improved in the first half of 2008, but the FAO reports that imperfect
disease surveillance
Disease surveillance is an epidemiological practice by which the spread of disease is monitored in order to establish patterns of progression. The main role of disease surveillance is to predict, observe, and minimize the harm caused by outbreak ...
systems mean that occurrence of the virus remains underestimated and underreported. As of May 2020, the WHO reported a total of 861 confirmed human cases which resulted in the deaths of 455 people since 2003.
Several
H5N1 vaccine
A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.
Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the H5N1 epizootic is w ...
s have been developed and approved, and stockpiled by a number of countries, including the United States (in its
National Stockpile
National may refer to:
Common uses
* Nation or country
** Nationality – a ''national'' is a person who is subject to a nation, regardless of whether the person has full rights as a citizen
Places in the United States
* National, Maryland, c ...
), Britain, France, Canada, and Australia, for use in an emergency.
Research has shown that a highly contagious strain of H5N1, one that might allow airborne transmission between mammals, can be reached in only a few mutations, raising concerns about a
pandemic and
bioterrorism
Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, insects, fungi, and/or toxins, and may be in a naturally occurring or a human-modified form, in much the same ...
.
Overview
HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus. A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans has been characterized as inefficient. Still, around 60% of humans known to have been infected with the Asian strain of HPAI A(H5N1) have died from it, and H5N1 may
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 ...
or
reassort into a strain capable of efficient human-to-human transmission. In 2003, world-renowned virologist
Robert G. Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in ''
American Scientist''. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives.
On September 29, 2005,
David Nabarro
Sir David Nunes Nabarro (born 26 August 1949) is a Special Envoy on Covid-19 for the World Health Organization. He has made his career in the international civil service, working for either the Secretary-General of the United Nations or the Di ...
, the newly appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people.
Experts have identified key events (creating new
clades, infecting new species, spreading to new areas) marking the progression of an avian flu virus towards becoming pandemic, and many of those key events have occurred more rapidly than expected.
Due to the high lethality and
virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
of HPAI A(H5N1), its endemic presence, its increasingly large
host
A host is a person responsible for guests at an event or for providing hospitality during it.
Host may also refer to:
Places
* Host, Pennsylvania, a village in Berks County
People
*Jim Host (born 1937), American businessman
* Michel Host ...
reservoir, and its significant ongoing mutations, in 2006, the H5N1 virus has been regarded to be the world's largest pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential
influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the population. There have been six major influenza epidemics in the last ...
.
At least 12 companies and 17 governments are developing prepandemic
influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly one. Full-scale production of a
vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. that could prevent any illness at all from the strain would require at least three months after the virus's emergence to begin, but it is hoped that vaccine production could increase until one billion doses were produced by one year after the initial identification of the virus.
H5N1 may cause more than one
influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the population. There have been six major influenza epidemics in the last ...
, as it is expected to continue mutating in birds regardless of whether humans develop
herd immunity
Herd immunity (also called herd effect, community immunity, population immunity, or mass immunity) is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become im ...
to a future pandemic strain.
Influenza pandemics from its genetic offspring may include
influenza A virus subtypes other than H5N1. While genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the
Spanish flu
The 1918–1920 influenza pandemic, commonly known by the misnomer Spanish flu or as the Great Influenza epidemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case wa ...
pandemic,
planning for a future influenza pandemic is based on what can be done and there is no higher
Pandemic Severity Index level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad as the Spanish flu or worse; and for which ''all'' intervention measures are to be used.
Signs and symptoms
![H1N1 versus H5N1 pathology](https://upload.wikimedia.org/wikipedia/commons/b/b0/H1N1_versus_H5N1_pathology.png)
In general, humans who catch a humanized influenza A virus (a
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 ...
virus of type A) usually have symptoms that include
fever
Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
,
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 ph ...
,
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)
* to ...
,
muscle aches,
conjunctivitis
Conjunctivitis, also known as pink eye, is inflammation of the 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 occur. The ...
, and, in severe cases, 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 severi ...
that may be fatal.
The severity of the infection depends in large part on the state of the infected persons'
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 splint ...
s and whether they had been exposed to the strain before (in which case they would be partially immune). No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu.
The avian influenza
hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
binds alpha 2-3
sialic acid receptors, while human influenza hemagglutinins bind alpha 2-6 sialic acid receptors.
This means when the H5N1 strain infects humans, it will replicate in the lower respiratory tract, and consequently will cause
viral pneumonia
Viral pneumonia is a pneumonia caused by a virus. Pneumonia is an infection that causes inflammation in one or both of the lungs. The pulmonary alveoli fill with fluid or pus making it difficult to breathe. Pneumonia can be caused by bacteria, vir ...
.
There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1.
The reported
mortality rate
Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
of highly pathogenic H5N1 avian influenza in a human is high;
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 ...
data indicate 60% of cases classified as H5N1 resulted in death. However, there is some evidence the actual mortality rate of avian flu could be much lower, as there may be many people with milder symptoms who do not seek treatment and are not counted.
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 w ...
followed rapidly by a
coma without developing respiratory or flu-like symptoms.
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 ...
, a protein 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. Norm ...
' 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 th ...
process of damage to the body resulting from 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 splint ...
stimulation. H5N1 induces higher levels of cytokines than the more common flu virus types.
In birds
Clinical signs of H5N1 in birds range from mild—decrease in egg production, nasal discharge, coughing and sneezing—to severe, including loss of coordination, energy, and appetite; soft-shelled or misshapen eggs; purple discoloration of the wattles, head, eyelids, combs, and hocks; and diarrhea. Sometimes the first noticeable sign is sudden death.
Genetics
The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959, but that strain was very different from the highly pathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
from 1999 to 2002 creating the Z genotype. It has also been called "Asian lineage HPAI A(H5N1)".
Asian lineage HPAI A(H5N1) is divided into two antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
ic clades. "Clade 1 includes human and bird isolates from 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 ...
, Thailand
Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
, and Cambodia
Cambodia (; also Kampuchea ; km, កម្ពុជា, UNGEGN: ), officially the Kingdom of Cambodia, is a country located in the southern portion of the Indochinese Peninsula in Southeast Asia, spanning an area of , bordered by Thailan ...
and bird isolates from Laos and Malaysia
Malaysia ( ; ) is a country in Southeast Asia. The federation, federal constitutional monarchy consists of States and federal territories of Malaysia, thirteen states and three federal territories, separated by the South China Sea into two r ...
. Clade 2 viruses were first identified in bird isolates from China, Indonesia
Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania between the Indian and Pacific oceans. It consists of over 17,000 islands, including Sumatra, Java, Sulawesi, and parts of Borneo and New Guine ...
, Japan, and South Korea
South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its eas ...
before spreading westward to the Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabia (including the Arabian Peninsula and Bahrain), Asia Minor (Asian part of Turkey except Hatay Province), East Thrace (Europ ...
, Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...
, and Africa
Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections
Map
* Subclade 1, Indonesia
* Subclade 2, Europe, Middle East, and Africa (called EMA)
* Subclade 3, China"
A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia."
Terminology
H5N1 isolates are identified like this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):
* A stands for the genus of influenza ( A, B or C).
* chicken is the animal species the isolate was found in (note: human isolates lack this component term and are thus identified as human isolates by default)
* Nakorn-Patom/Thailand is the place this specific virus was isolated
* CU-K2 is the laboratory reference number that identifies it from other influenza viruses isolated at the same place and year
* 04 represents the year of isolation 2004
* H5 stands for the fifth of several known types of the protein hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
.
* N1 stands for the first of several known types of the protein neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glyc ...
.
Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/shoveler
The shovelers or shovellers are four species of dabbling ducks with long, broad spatula-shaped beaks:
* Red shoveler, ''Anas platalea''
* Cape shoveler, ''Anas smithii''
* Australasian shoveler, ''Anas rhynchotis''
* Northern shoveler, ''Anas c ...
/Egypt/03(H5N2).
As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
, and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds. This deadly strain of H5N1 is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus
''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ' ...
.
Genetic structure and related subtypes
H5N1 is a subtype of the species ''Influenza A virus'' of the genus
Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...
''Alphainfluenzavirus
'' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. Strains of all subtypes of influenza A virus have been isolated from wi ...
'' of the family '' Orthomyxoviridae''. Like all other influenza A subtypes, the H5N1 subtype is an RNA virus. It has a segmented genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
of eight negative sense, single-strands of 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 ...
, abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS.
HA codes for hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
, an antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
ic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase
Exo-α-sialidase (EC 3.2.1.18, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glyc ...
, an antigenic glycosylated enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells.
The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the ''H'' and ''N'' come from in ''H5N1''.
Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:
* H1N1
In virology, influenza A virus subtype H1N1 (A/H1N1) is a subtype of influenza A virus. Major outbreaks of H1N1 strains in humans include the Spanish flu, the 1977 Russian flu pandemic and the 2009 swine flu pandemic. It is an orthomyxoviru ...
, which caused the 1918 flu pandemic
The 1918–1920 influenza pandemic, commonly known by the misnomer Spanish flu or as the Great Influenza epidemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case was ...
("Spanish flu") and the 2009 flu pandemic
The 2009 swine flu pandemic, caused by the H1N1 influenza virus and declared by the World Health Organization (WHO) from June 2009 to August 2010, is the third recent flu pandemic involving the H1N1 virus (the first being the 1918–1920 Span ...
("swine flu
Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As ...
") and is causing seasonal 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 ...
* H2N2, which caused "Asian flu"
* H3N2
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
, which caused "Hong Kong flu" and causes seasonal human flu
* 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 type ...
, ("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 ...
"), which is noted for having a strain (Asian-lineage HPAI H5N1) that kills over half the humans it infects, infecting and killing species that were never known to suffer from influenza viruses before (e.g. cats), being unable to be stopped by culling all involved poultry—some think due to being endemic in wild birds, and causing billions of dollars to be spent in flu pandemic preparation and preventiveness
* H7N7
Influenza A virus subtype H7N7 (A/H7N7) is a subtype of Influenza A virus, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains (HPAI) and low pathogenic strains (LPAI) exist. H7N7 can infect humans, bir ...
, which has unusual zoonotic
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
potential and killed one person
* H1N2
Influenza A virus subtype H1N2 (A/H1N2) is a subtype of the species Influenza A virus (sometimes called bird flu virus). It is currently endemic in pig populations and is occasionally seen in humans.
The virus does not cause more severe illne ...
, which is endemic in humans and pigs and causes seasonal human flu
* 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 ...
, which has infected three people
* H7N2
Influenza A virus subtype H7N2 (A/H7N2) is a subtype of the species Influenza A virus. This subtype is one of several sometimes called bird flu virus. H7N2 is considered a low pathogenicity avian influenza (LPAI) virus. With this in mind, H5 & ...
, which has infected two people
* H7N3
Influenza A virus subtype H7N3 (A/H7N3) is a subtype of the species Influenza A virus (sometimes called bird flu virus).
In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004; flocks ...
, which has infected two people
* H10N7
Influenza A virus subtype H10N7 (A/H10N7) is a subtype of the species Influenza A virus (sometimes called bird flu virus). H10N7 was first reported in humans in Egypt in 2004. It caused illness in two one-year-old infants, and residents of Is ...
, which has infected two people
* H7N9
Influenza A virus subtype H7N9 (A/H7N9) is a bird flu strain of the species Influenza virus A (avian influenza virus or bird flu virus). Avian influenza A H7 viruses normally circulate amongst avian populations with some variants known to occ ...
, which as of Feb 2014 has infected 309 people, and lead to 70 deaths
Low pathogenic H5N1
Low pathogenic avian influenza H5N1 (LPAI H5N1) also called "North American" H5N1 commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain.
* 1966 – LPAI H5N1 A/Turkey/Ontario/6613/1966(H5N1) was detected in a flock of infected turkeys in Ontario, Canada
* 1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin.
* 1981 and 1985 – LPAI H5N1 was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time.
* 1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania.
* 1986 – LPAI H5N1 was detected in a wild mallard duck in Ohio.
* 2005 – LPAI H5N1 was detected in ducks in Manitoba, Canada.
* 2008 – LPAI H5N1 was detected in ducks in New Zealand.
* 2009 – LPAI H5N1 was detected in commercial poultry in British Columbia.
"In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health (OIE
The World Organisation for Animal Health (WOAH), formerly the (OIE), is an intergovernmental organization coordinating, supporting and promoting animal disease control.
Mission and status
The main objective of the WOAH is to control epizoo ...
) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets."
High mutation rate
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
facilitates genetic recombination by segment 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 particul ...
in hosts infected with two different strains of influenza viruses at the same time.[ A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic.
The ability of various influenza strains to show species-selectivity is largely due to variation in the ]hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
genes. Genetic mutation
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 replication, DNA or viral repl ...
s in the hemagglutinin gene that cause 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 a ...
substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types. This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.
Influenza A virus subtype H3N2
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
, which is now resistant to the standard antiviral drugs 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 wi ...
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 ...
. The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
.
Both the H2N2 and H3N2
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predomina ...
pandemic strains contained avian influenza
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds. virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source".
''This e-book is under constant revision and is an excellent guide to Avian Influenza''
Prevention
Vaccine
There are several H5N1 vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. s for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. 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
Georgetown University is a private university, private research university in the Georgetown (Washington, D.C.), Georgetown neighborhood of Washington, D.C. Founded by Bishop John Carroll (archbishop of Baltimore), John Carroll in 1789 as Georg ...
has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. ". 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.
Public health
"The United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...
is collaborating closely with eight international organizations, including the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
(WHO), the Food and Agriculture Organization of the United Nations
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 ...
(FAO), the World Organization for Animal Health
The World Organisation for Animal Health (WOAH), formerly the (OIE), is an intergovernmental organization coordinating, supporting and promoting animal disease control.
Mission and status
The main objective of the WOAH is to control epizoo ...
(OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development
The United States Agency for International Development (USAID) is an independent agency of the U.S. federal government that is primarily responsible for administering civilian foreign aid and development assistance. With a budget of over $27 ...
(USAID) and the U.S. Department of State
The United States Department of State (DOS), or State Department, is an executive department of the U.S. federal government responsible for the country's foreign policy and relations. Equivalent to the ministry of foreign affairs of other ...
, the U.S. Department of Health and Human Services (HHS), and Agriculture
Agriculture or farming is the practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled people t ...
(USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government".[
]
Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness".[
Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the ]USGS
The United States Geological Survey (USGS), formerly simply known as the Geological Survey, is a scientific agency of the United States government. The scientists of the USGS study the landscape of the United States, its natural resources, a ...
National Wildlife Health Center, the 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 ...
, the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
, the European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...
, and others.[
]
Treatment
There is no highly effective treatment for H5N1 flu, but 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 high ...
(commercially 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 ...
as Tamiflu), can sometimes inhibit the influenza virus from spreading inside the user's body. This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic. On April 20, 2006, Roche AG announced that a stockpile of three million treatment courses of 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 hi ...
are waiting at the disposal of the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
to be used in case of a flu pandemic; separately Roche donated two million courses to the WHO for use in developing nations
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreeme ...
that may be affected by such a pandemic but lack the ability to purchase large quantities of the drug.
However, WHO expert Hassan al-Bushra has said:
:"Even now, we remain unsure about Tamiflu's real effectiveness. As for a vaccine
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. , work cannot start on it until the emergence of a new virus, and we predict it would take six to nine months to develop it. For the moment, we cannot by any means count on a potential vaccine to prevent the spread of a contagious influenza virus, whose various precedents in the past 90 years have been highly pathogenic".[
]
Animal and lab studies suggest that Relenza (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 ...
), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. In a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals".[
] In addition, mice studies suggest the combination of zanamivir, celecoxib and mesalazine looks promising producing a 50% survival rate compared to no survival in the placebo arm. While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can be manufactured in quantities that would be meaningful once efficient human transmission starts. In September, 2006, a WHO scientist announced that studies had confirmed cases of H5N1 strains resistant to Tamiflu and Amantadine. Tamiflu-resistant strains have also appeared in the EU, which remain sensitive to Relenza.[
][
]
Epidemiology
The earliest infections of humans by H5N1 coincided with an epizootic
In epizoology, an epizootic (from Greek: ''epi-'' upon + ''zoon'' animal) is a disease event in a nonhuman animal population analogous to an epidemic in humans. An epizootic may be restricted to a specific locale (an "outbreak"), general (an "epi ...
(an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population in 1997. This panzootic A panzootic (from Greek παν all + ζόιον animal) is an epizootic (an outbreak of an infectious disease of animals) that spreads across a large region (for example a continent), or even worldwide. The equivalent in human populations is calle ...
(a disease affecting animals of many species, especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. However, the disease has continued to spread; outbreaks were reported in Asia again in 2003. On December 21, 2009, the WHO announced a total of 447 cases which resulted in the deaths of 263.
Contagiousness
H5N1 is easily transmissible between birds, facilitating a potential 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 ...
. While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type of galactose
Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
receptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around the alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit.
Uses in anatomy and zoology
* Pulmonary alveolus, an air sac in the lungs
** Alveolar cell or pneumocyte
** Alveolar duct
** Alveolar macrophage
* ...
, structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.[
][
]
H5N1 is mainly spread by domestic poultry
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, ...
, both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl
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 i ...
(wild 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 ...
s, geese
A goose ( : geese) is a bird of any of several waterfowl species in the family Anatidae. This group comprises the genera '' Anser'' (the grey geese and white geese) and ''Branta'' (the black geese). Some other birds, mostly related to the she ...
and swans) carry H5N1, often without becoming sick.[
][
] Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown.[
]
According to a report by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
, H5N1 may be spread indirectly. The report stated the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people.
Virulence
H5N1 has mutated
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 variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift
Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is ...
, H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all belong to genotype Z of avian influenza virus H5N1, now the dominant genotype.[
]
''Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin
In molecular biology, hemagglutinins (or ''haemagglutinin'' in British English) (from the Greek , 'blood' + Latin , 'glue') are receptor-binding membrane fusion glycoproteins produced by viruses in the '' Paramyxoviridae'' family. Hemagglutinins a ...
genes from various isolates of the virus''
H5N1 isolates found in Hong Kong
Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delta i ...
in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002, new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in 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 ...
s. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.
Genotype Z emerged in 2002 through 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 particul ...
from earlier highly pathogenic genotypes of H5N1[ that first infected birds in China in 1996, and first infected humans in ]Hong Kong
Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delta i ...
in 1997. Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations occurring within this genotype are increasing their pathogenicity. Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.
Transmission and host range
Infected birds transmit H5N1 through their saliva, nasal secretions, feces and blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
. Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at (over one month at freezing temperature) or 6 days at (one week at human body temperature); at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it does not degrade at all.
Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.
In October 2004, researchers discovered H5N1 is far more dangerous than was previously believed. 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 i ...
were revealed to be directly spreading this highly pathogenic strain to chicken
The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adu ...
s, crow
A crow is a bird of the genus '' Corvus'', or more broadly a synonym for all of ''Corvus''. Crows are generally black in colour. The word "crow" is used as part of the common name of many species. The related term "raven" is not pinned scientifica ...
s, pigeon
Columbidae () is a bird family consisting of doves and pigeons. It is the only family in the order Columbiformes. These are stout-bodied birds with short necks and short slender bills that in some species feature fleshy ceres. They primarily ...
s, and other birds, and the virus was increasing its ability to infect mammals, as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic.
"Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability."
''The New York Times'', in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important".
On September 29, 2007, researchers reported the H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells.
In May 2013, North Korea
North Korea, officially the Democratic People's Republic of Korea (DPRK), is a country in East Asia. It constitutes the northern half of the Korean Peninsula and shares borders with China and Russia to the north, at the Yalu (Amnok) and T ...
confirmed a H5N1 bird flu outbreak that forced authorities to kill over 160,000 ducks in Pyongyang
Pyongyang (, , ) is the capital and largest city of North Korea, where it is known as the "Capital of the Revolution". Pyongyang is located on the Taedong River about upstream from its mouth on the Yellow Sea. According to the 2008 populat ...
.
2021/2022 outbreaks in Europe/Atlantic flyway
Over the winter of 2021 and 2022 avian flu spread among the population of barnacle geese
The barnacle goose (''Branta leucopsis'') is a species of goose that belongs to the genus ''Branta'' of black geese, which contains species with largely black plumage, distinguishing them from the grey ''Anser'' species. Despite its superficial s ...
on the Solway Firth, UK, with estimates of up to a third of the Svalbard population being lost; pink-footed geese
The pink-footed goose (''Anser brachyrhynchus'') is a goose which breeds in eastern Greenland, Iceland and Svalbard. It is migratory, wintering in northwest Europe, especially Ireland, Great Britain, the Netherlands, and western Denmark. The na ...
were also affected there and it seems carried the virus to new sites in northern Scotland. The disease was confirmed in sandwich tern
The Sandwich tern (''Thalasseus sandvicensis'') is a tern in the family Laridae. It is very closely related to the lesser crested tern (''T. bengalensis''), Chinese crested tern (''T. bernsteini''), Cabot's tern (''T. acuflavidus''), and elega ...
s in South Africa in April 2022. In late spring 2022 avian flu outbreaks affected many species of wild bird in the United Kingdom, with heavy losses reported among seabirds returning to breed at colonies in the Northern Isles and Outer Hebrides, including great skua
The great skua (''Stercorarius skua''), sometimes known by the name bonxie in Britain, is a large seabird in the skua family Stercorariidae. It is roughly the size of a herring gull. It mainly eats fish caught at the sea surface or taken fr ...
s (bonxie) for which outbreaks had initially been reported in 2021 (Scotland hosts c. 60% of the world's breeding population) - the 2022 census on St Kilda showed a 64% decline on 2019 with 106 dead birds recorded so far (to 6 June), gannets
Gannets are seabirds comprising the genus ''Morus'' in the family Sulidae, closely related to boobies.
Gannets are large white birds with yellowish heads; black-tipped wings; and long bills. Northern gannets are the largest seabirds in the N ...
(1000+ birds reported dead at the Shetlands' Hermaness
Hermaness is the northernmost headland of Unst, the most northerly inhabited island of Shetland, Scotland. It consists of huge sea cliffs and moorland, making it an ideal habitat for a variety of birds. Hermaness was designated a national nature ...
colony alone, where there are around 26,000 breeding pairs), with many more gannets being reported dead at other colonies ( Troup Head, Bass Rock
The Bass Rock, or simply the Bass (), ( gd, Creag nam Bathais or gd, Am Bas) is an island in the outer part of the Firth of Forth in the east of Scotland. Approximately offshore, and north-east of North Berwick, it is a steep-sided volca ...
, and St Kilda); the range of species also seems to be expanding, with reports for many species of wildfowl, seabirds (auks, terns and gulls) and scavenging species (corvids and raptors).
Elsewhere in Europe the virus killed hundreds (574+) of Dalmatian pelican
The Dalmatian pelican (''Pelecanus crispus'') is the largest member of the pelican family, and perhaps the world's largest freshwater bird, although rivaled in weight and length by the largest swans. They are elegant soaring birds, with wingspa ...
s in Greece, and in Israel around 6000 common crane
The common crane (''Grus grus''), also known as the Eurasian crane, is a bird of the family Gruidae, the cranes. A medium-sized species, it is the only crane commonly found in Europe besides the demoiselle crane (''Grus virgo'') and the Siberian ...
s were found dead at Hula in December 2021. A report by Scientific Task Force on Avian Influenza and Wild Birds on: "H5N1 Highly Pathogenic Avian Influenza in poultry and wild birds: Winter of 2021/2022 with focus on mass mortality of wild birds in UK and Israel" summarises the situation up to 24 January 2022 and mentions that "H5N8 HPAI is still responsible for poultry and wild bird cases mainly in Asia, H5N1 has now in effect replaced this subtype in Africa and Eurasia in both poultry and wild birds".
2022 outbreaks in New World
In parallel to above reports, similar outbreaks noted from gannet
Gannets are seabirds comprising the genus ''Morus'' in the family Sulidae, closely related to boobies.
Gannets are large white birds with yellowish heads; black-tipped wings; and long bills. Northern gannets are the largest seabirds in the ...
colonies in Canada, with thousands of birds dead in June 2022, as well as common eider
The common eider (pronounced ) (''Somateria mollissima''), also called St. Cuthbert's duck or Cuddy's duck, is a large ( in body length) sea-duck that is distributed over the northern coasts of Europe, North America and eastern Siberia. It breed ...
s and great black-backed gull
The great black-backed gull (''Larus marinus'') is the largest member of the gull family. Described by the Cornell Lab of Ornithology as "the king of the Atlantic waterfront", it is a very aggressive hunter, pirate, and scavenger. It breeds on t ...
s. Prior to that there were reports of spread in wild birds in over 30 states in the US, including major mortalities in a double-crested cormorant
The double-crested cormorant (''Nannopterum auritum'') is a member of the cormorant family of water birds. It is found near rivers and lakes, and in coastal areas, and is widely distributed across North America, from the Aleutian Islands in Al ...
colony in Barrington, Illinois, the virus also spreading to scavengers including three bald eagles in Georgia.
H5N1 transmission studies in ferrets (2011)
Novel, contagious
Contagious may refer to:
* Contagious disease
Literature
* Contagious (magazine), a marketing publication
* ''Contagious'' (novel), a science fiction thriller novel by Scott Sigler
Music
Albums
*''Contagious'' (Peggy Scott-Adams album), 1997
* ...
strains of H5N1 were created by Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011. Three mutations were introduced into the H5N1 virus genome, and the virus was then passed from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times.[
] After these 10 passages the H5N1 virus had acquired the ability of transmission between ferrets via aerosols or respiratory droplets.
After Fouchier offered an article describing this work to the leading academic journal ''Science
Science is a systematic endeavor that Scientific method, builds and organizes knowledge in the form of Testability, testable explanations and predictions about the universe.
Science may be as old as the human species, and some of the earli ...
'', the US National Science Advisory Board for Biosecurity
The National Science Advisory Board for Biosecurity (NSABB) is a panel of experts that reports to the Secretary of the United States Department of Health and Human Services. It is tasked with recommending policies on such questions as how to preve ...
(NSABB) recommended against publication of the full details of the study, and the one submitted to Nature by Yoshihiro Kawaoka of the University of Wisconsin describing related work. However, after additional consultations at the World Health Organization and by the NSABB, the NSABB reversed its position and recommended publication of revised versions of the two papers. However, then the Dutch government
The politics of the Netherlands take place within the framework of a parliamentary representative democracy, a constitutional monarchy, and a decentralised unitary state.''Civil service systems in Western Europe'' edited by A. J. G. M. Bekk ...
declared that this type of manuscripts required Fouchier to apply for an export permit in the light of EU directive 428/2009 on dual use goods. After much controversy surrounding the publishing of his research, Fouchier complied (under formal protest) with Dutch government demands to obtain a special permit for submitting his manuscript, and his research appeared in a special issue of the journal ''Science'' devoted to H5N1. The papers by Fouchier and Kawaoka conclude that it is entirely possible that a natural chain of mutations could lead to an H5N1 virus acquiring the capability of airborne transmission between mammals, and that a H5N1 influenza pandemic would not be impossible.
In May 2013, it was reported that scientists at the Harbin Veterinary Research Institute Harbin Veterinary Research Institute (HVRI) is a Chinese biological research institute located in Harbin, China. It is under the supervision of the Chinese Academy of Agricultural Sciences (CAAS).
HVRI was created in 1948 and is the first veterinar ...
in Harbin, China, had created H5N1 strains which passed between guinea pigs
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the a ...
.
In response to Fouchier and Kawaoka's work, a number of scientists expressed concerns with the risks
In simple terms, risk is the possibility of something bad happening. Risk involves uncertainty about the effects/implications of an activity with respect to something that humans value (such as health, well-being, wealth, property or the environme ...
of creating novel potential pandemic pathogens, culminating in the formation of the Cambridge Working Group
Gain-of-function research (GoF research or GoFR) is medical research that genetically alters an organism in a way that may enhance the Function (biology), biological functions of gene products. This may include an altered pathogenesis, Transmissio ...
, a consensus statement calling for an assessment of the risks and benefits of such research.
Society and culture
H5N1 has had a significant effect on human
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, cultu ...
society
A society is a group of individuals involved in persistent social interaction, or a large social group sharing the same spatial or social territory, typically subject to the same political authority and dominant cultural expectations. Soci ...
, especially the financial, political
Politics (from , ) is the set of activities that are associated with making decisions in groups, or other forms of power relations among individuals, such as the distribution of resources or status. The branch of social science that stud ...
, social
Social organisms, including human(s), live collectively in interacting populations. This interaction is considered social whether they are aware of it or not, and whether the exchange is voluntary or not.
Etymology
The word "social" derives from ...
, and personal responses to both actual and predicted 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 ...
s in bird
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...
s, human
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, cultu ...
s, and other animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s. Billions of dollars are being raised and spent to research H5N1 and prepare for a potential avian influenza
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds. pandemic. Over $10 billion have been spent and over 200 million birds have been killed to try to contain H5N1.
People have reacted by buying less chicken, causing poultry sales and prices to fall. Many individuals have stockpiled supplies for a possible flu pandemic. International health officials and other experts have pointed out that many unknown questions still hover around the disease.[International Institute for Sustainable Development (IISD)](_blank)
''Scientific Seminar on Avian Influenza, the Environment and Migratory Birds on 10–11 April 2006'' published 14 April 2006.
Dr. David Nabarro
Sir David Nunes Nabarro (born 26 August 1949) is a Special Envoy on Covid-19 for the World Health Organization. He has made his career in the international civil service, working for either the Secretary-General of the United Nations or the Di ...
, Chief Avian Flu Coordinator for the United Nations, and former Chief of Crisis Response for the World Health Organization has described himself as "quite scared" about H5N1's potential impact on humans. Nabarro has been accused of being alarmist before, and on his first day in his role for the United Nations, he proclaimed the avian flu could kill 150 million people. In an interview with the International Herald Tribune, Nabarro compares avian flu to AIDS in Africa, warning that underestimations led to inappropriate focus for research and intervention.
In February 2020 an outbreak of H5N1 avian flu occurred in Shuangqing District
Shuangqing District () is one of three urban districts in Shaoyang City, Hunan province, China. The district is located in the northeast of the city proper and on the east shore of Zi River, it is bordered by Xinshao County to the north, Shaodon ...
of Shaoyang City, in the Hunan province. After poultry had become ill from the virus the city killed close to 18,000 chickens to prevent the spread of the illness. Hunan borders Hubei province
Hubei (; ; alternately Hupeh) is a landlocked province of the People's Republic of China, and is part of the Central China region. The name of the province means "north of the lake", referring to its position north of Dongting Lake. The prov ...
where Wuhan
Wuhan (, ; ; ) is the capital of Hubei Province in the People's Republic of China. It is the largest city in Hubei and the most populous city in Central China, with a population of over eleven million, the ninth-most populous Chinese city an ...
is located, the epicenter of the coronavirus pandemic
The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identifie ...
.
See also
* Antigenic shift
* Avian influenza virus
Avian influenza, known informally as avian flu or bird flu, is a variety of influenza caused by viruses adapted to birds.[Favipiravir
* ](_blank)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 ...
* 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 ...
* H7N9
Influenza A virus subtype H7N9 (A/H7N9) is a bird flu strain of the species Influenza virus A (avian influenza virus or bird flu virus). Avian influenza A H7 viruses normally circulate amongst avian populations with some variants known to occ ...
* Influenza research
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 ...
* Influenzavirus A
'' A virus'' (''IAV'') causes influenza in birds and some mammals, and is the only species of the genus ''Alphainfluenzavirus'' of the virus family ''Orthomyxoviridae''. Strains of all subtypes of influenza A virus have been isolated from wild ...
* International Conference on Emerging Infectious Diseases
* National Influenza Centers National Influenza Centers (also called National Influenza Centres) are institutions which are formally recognized as such by the World Health Organization (WHO).Swine influenza
Swine influenza is an infection caused by any of several types of swine influenza viruses. Swine influenza virus (SIV) or swine-origin influenza virus (S-OIV) refers to any strain of the influenza family of viruses that is endemic in pigs. As ...
* Zoonosis
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
Notes
References
Citations
Sources
* Analysis of the efficacy of an adjuvant-based inactivated pandemic H5N1 influenza virus vaccine. https://link.springer.com/article/10.1007%2Fs00705-019-04147-7 Ainur NurpeisovaEmail authorMarkhabat KassenovNurkuisa RametovKaissar TabynovGourapura J. RenukaradhyaYevgeniy VolginAltynay SagymbayAmanzhol MakbuzAbylay SansyzbayBerik Khairullin
Research Institute for Biological Safety Problems (RIBSP), Zhambyl Region, Republic of Kazakhstan
External links
Influenza Research Database
– Database of influenza genomic sequences and related information.
* WHO World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
*
WHO's Avian Flu Facts Sheet for 2006
*
Epidemic and Pandemic Alert and Response
Guide to WHO's H5N1 pages
*
Avian Influenza Resources (updated)
– tracks human cases and deaths
*
*
WHO Collaborating Centres and Reference Laboratories
Centers, names, locations, and phone numbers
Information resources, animations, videos, photos
*
Food and Agriculture Organisation – Bi-weekly Avian Influenza Maps – tracks animal cases and deaths
*
*
Projects, Information resources
* OIE World Organisation for Animal Health
The World Organisation for Animal Health (WOAH), formerly the (OIE), is an intergovernmental organization coordinating, supporting and promoting animal disease control.
Mission and status
The main objective of the WOAH is to control epizo ...
– tracks animal cases and deaths
*
Official outbreak reports by country
*
*
Chart of outbreaks by country
;European Union
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...
''Health-EU Portal''
EU response to Avian Influenza.
*
;United Kingdom
Exotic Animal Disease Generic Contingency Plan
– DEFRA DEFRA may refer to:
* Deficit Reduction Act of 1984, United States law
* Department for Environment, Food and Rural Affairs, United Kingdom government department
{{Disambiguation ...
generic contingency plan for controlling and eradicating an outbreak of an exotic animal disease. PDF hosted by BBC #REDIRECT BBC #REDIRECT BBC
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...
.
UK Influenza Pandemic Contingency Plan
by the National Health Service
The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
– a government entity. PDF hosted by BBC #REDIRECT BBC #REDIRECT BBC
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...
Avian Influenza (Bird Flu): Implications for Human Disease – An overview of Avian Influenza
U.S. Government's avian flu information site
U.S. Agency for International Development – Avian Influenza Response
– responsible agency for avian influenza in humans in US – Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus
National Wildlife Health Center – responsible agency for avian influenza in animals in US
A part of the National Biological Information Infrastructure and partner of the NWHC, this agency collects and distributes news and information about wildlife diseases such as avian influenza and coordinates collaborative information sharing efforts.
U.S.