Influenza pandemic - AbsoluteAstronomy.com

An influenza pandemic is an epidemic of an influenza

Influenza

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu

Spanish flu

The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...

the most serious pandemic in recent history. Pandemics can cause high levels of mortality, with the Spanish influenza estimated as being responsible for the deaths of over 50 million people. There have been about three influenza pandemics in each century for the last 300 years. The most recent one was the 2009 flu pandemic

2009 flu pandemic

The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...

.

Influenza pandemics occur when a new strain of the influenza virus is transmitted to humans from another animal species. Species that are thought to be important in the emergence of new human strains are pigs, chickens and ducks. These novel strains are unaffected by any immunity people may have to older strains of human influenza and can therefore spread extremely rapidly and infect very large numbers of people. Influenza A viruses can occasionally be transmitted from wild birds to other species causing outbreaks in domestic poultry and may give rise to human influenza pandemics. The transportation of influenza viruses throughout the world is thought in part to be by bird migrations, though commercial shipments of live bird products might also be implicated, as well as human travel plans.

The World Health Organization

World Health Organization

The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

(WHO) has produced a six-stage classification that describes the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. This starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people, and ends with a pandemic when infections from the new virus have spread worldwide.

One strain of virus that may produce a pandemic in the future is a highly pathogen

Pathogen

A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

ic variation of the H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

subtype of Influenza A virus. On 11 June 2009, a new strain of H1N1

Pandemic H1N1/09 virus

The Pandemic H1N1/09 virus is a swine origin Influenza A virus subtype H1N1 virus strain responsible for the 2009 flu pandemic. For other names see the Nomenclature section below.-Virus characteristics:...

influenza was declared to be a global pandemic (Stage 6) by the World Health Organization

World Health Organization

after evidence of spreading in the southern hemisphere. The 13 November 2009 worldwide update by the UN's World Health Organization (WHO) states that "[a]s of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported [503,536] laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6250 deaths."

Influenza

Influenza, commonly known as flu, is an infectious disease

Infectious disease

Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

of birds and mammal

Mammal

Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s caused by an RNA virus

RNA virus

An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

of the family Orthomyxoviridae

Orthomyxoviridae

The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...

(the influenza viruses). In humans, common symptoms of influenza infection are fever, sore throat, muscle pains

Myalgia

Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...

, severe headache, coughing, and weakness and fatigue

Malaise

Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

. In more serious cases, influenza causes

Sequela

A sequela) is a pathological condition resulting from a disease, injury, or other trauma.Chronic kidney disease, for example, is sometimes a sequela of diabetes, and neck pain is a common sequela of whiplash or other trauma to the cervical vertebrae. Post-traumatic stress disorder may be a...

pneumonia

Pneumonia

Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

, which can be fatal, particularly in young children and the elderly. While sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus. Although nausea and vomiting can be produced, especially in children, these symptoms are more characteristic of the unrelated gastroenteritis

Gastroenteritis

Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

, which is sometimes called "stomach flu" or "24-hour flu."

Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings

Feces

Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...

. Influenza can also be transmitted by saliva

Saliva

Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...

, nasal secretions

Mucus

In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...

, feces and blood. Healthy individuals can become infected if they breathe in a virus-laden aerosol directly, or if they touch their eyes, nose or mouth after touching any of the aforementioned bodily fluids (or surfaces contaminated with those fluids). Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and indefinitely at very low temperatures (such as lakes in northeast Siberia

Siberia

Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...

). Most influenza strains can be inactivated easily by disinfectants and detergent

Detergent

A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...

s.

Flu spreads around the world in seasonal epidemics. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain

Strain (biology)

In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species

Species

In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

. When it first killed humans in Asia in the 1990s, a deadly avian strain of H5N1 posed a great risk for a new influenza pandemic; however, this virus did not mutate

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

to spread easily between people.

Vaccination

Vaccination

Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

s against influenza are most commonly given to high-risk humans in industrialized countries and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine that contains purified and inactivated material from three viral strains. Typically this vaccine includes material from two influenza A virus

Influenzavirus A

Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...

subtypes and one influenza B virus

Influenzavirus B

Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...

strain. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time and different strains become dominant. Antiviral drug

Antiviral drug

Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

s can be used to treat influenza, with neuraminidase inhibitor

Neuraminidase inhibitor

Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....

s being particularly effective.

Variants and subtypes of Influenzavirus A

Variants of Influenzavirus A

Influenzavirus A

are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu

Fujian flu

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus...

virus like); according to their typical host (example Human flu

Human flu

Human flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...

virus); according to their subtype (example H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

); and according to their deadliness (example LP). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu.

Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. Some variants named using this convention are:

Bird Flu
Human Flu
Human flu
Human flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
Swine Flu
Swine flu
Swine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...
Horse Flu
Horse flu
Equine influenza is the disease caused by strains of Influenza A that are enzootic in horse species. Equine influenza occurs globally, and is caused by two main strains of virus: equine-1 and equine-2...
Dog Flu

Avian variants have also sometimes been named according to their deadliness in poultry, especially chickens:

Low Pathogenic Avian Influenza (LPAI)
Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu

The Influenza A virus subtypes are labeled according to an H number (for hemagglutinin

Hemagglutinin

Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...

) and an N number (for neuraminidase

Neuraminidase

Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...

). Each subtype virus has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong Flu

Hong Kong flu

The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...

. This e-book is under constant revision and is an excellent guide to Avian Influenza

Influenza A viruses are negative sense, single-stranded, segmented RNA virus

RNA virus

An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

es. "There are 16 different HA antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s (H1 to H16) and nine different NA antigen

Antigen

s (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but a new type (H16) was isolated from black-headed gull

Black-headed Gull

The Black-headed Gull is a small gull which breeds in much of Europe and Asia, and also in coastal eastern Canada. Most of the population is migratory, wintering further south, but some birds in the milder westernmost areas of Europe are resident...

s caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005."

Nature of a flu pandemic

Some pandemics are relatively minor such as the one in 1957 called "Asian flu"

H2N2

H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...

(1 – 4 million dead, depending on source). Others have a higher Pandemic Severity Index

Pandemic Severity Index

The Pandemic Severity Index is a proposed classification scale for reporting the severity of influenza pandemics in the United States. The PSI was accompanied by a set of guidelines intended to help communicate appropriate actions for communities to follow in potential pandemic situations...

whose severity warrants more comprehensive social isolation measures.

The 1918 pandemic killed tens of millions and sickened hundreds of millions; the loss of this many people in the population caused upheaval and psychological damage to many people. There were not enough doctors, hospital rooms, or medical supplies for the living as they contacted the disease. Dead bodies were often left unburied as few people were available to deal with them. There can be great social disruption as well as a sense of fear. Efforts to deal with pandemics can leave a great deal to be desired because of human selfishness, lack of trust, illegal behavior, and ignorance. For example in the 1918 pandemic: "This horrific disconnect between reassurances and reality destroyed the credibility of those in authority. People felt they had no one to turn to, no one to rely on, no one to trust."

A letter from a physician at one U.S. Army camp in the 1918 pandemic said:

It is only a matter of a few hours then until death comes [...]. It is horrible. One can stand it to see one, two or twenty men die, but to see these poor devils dropping like flies [...]. We have been averaging about 100 deaths per day [...]. Pneumonia means in about all cases death [...]. We have lost an outrageous number of Nurses and Drs. It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce [...].

Wave nature

Flu pandemics typically come in waves. The 1889–1890 and 1918–1919 flu pandemics each came in three or four waves of increasing lethality. But within a wave, mortality was greater at the beginning of the wave.

Variable mortality

Mortality varies widely in a pandemic. In the 1918 pandemic:

In U.S. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9.6 percent, for Indian troops 21.9 percent. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population.

Influenza pandemics

Latest flu pandemics
Name of pandemic	Date	Deaths	Subtype involved
Asiatic (Russian) Flu	1889–1890	1 million	possibly H2N2 H2N2 H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
Spanish Flu Spanish flu The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...	1918–1920	50 million	H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
Asian Flu Asian flu Asian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...	1957–1958	1.5 to 2 million	H2N2
Hong Kong Flu Hong Kong flu The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...	1968–1969	1 million	H3N2
Swine Flu Swine flu Swine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...	2009–2010	over 18,209 http://www.who.int/csr/don/2010_06_25/en/index.html	novel H1N1 Pandemic H1N1/09 virus The Pandemic H1N1/09 virus is a swine origin Influenza A virus subtype H1N1 virus strain responsible for the 2009 flu pandemic. For other names see the Nomenclature section below.-Virus characteristics:...

Spanish Flu (1918–1920)

The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5

Pandemic Severity Index

influenza pandemic caused by an unusually severe and deadly Influenza A virus strain

Strain (biology)

of subtype H1N1

H1N1

'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...

The difference between the influenza mortality age-distributions of the 1918 epidemic and normal epidemics. Deaths per 100,000 persons in each age group, United States, for the interpandemic years 1911–1917 (dashed line) and the pandemic year 1918 (solid line).

The Spanish flu

Spanish flu

pandemic lasted from 1918 to 1919, although Price-Smith's data suggest it may have begun in Austria in the Spring of 1917. Older estimates say it killed 40–50 million people while current estimates say 50 million to 100 million people worldwide were killed. This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death

Black Death

The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have...

, although the Black Death is estimated to have killed over a fifth of the world's population at the time, a significantly higher proportion. This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storm

Cytokine storm

A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...

s. Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera

Cholera

Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...

, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages

Petechia

A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...

in the skin also occurred." The majority of deaths were from bacterial pneumonia

Bacterial pneumonia

Bacterial pneumonia is a type of pneumonia caused by bacterial infection.-Sign and symptoms:*Fever*Rigors*Cough*Dyspnea*Chest pain*Pneumococcal pneumonia can cause Hemoptysis-Gram positive:...

, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages

Bleeding

Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

and edema

Edema

Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...

in the lung.

The Spanish flu pandemic was truly global, spreading even to the Arctic

Arctic

The Arctic is a region located at the northern-most part of the Earth. The Arctic consists of the Arctic Ocean and parts of Canada, Russia, Greenland, the United States, Norway, Sweden, Finland, and Iceland. The Arctic region consists of a vast, ice-covered ocean, surrounded by treeless permafrost...

and remote Pacific islands. The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate

Mortality rate

Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

of 0.1%. Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old. This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1919 pandemic is not known, but it is estimated that up to 1% of the world's population was killed. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS

AIDS

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

has killed 25 million in its first 25 years.

The Manchester Influenza Epidemic of 1937

The Epidemic that never escalated to Pandemic
This is an example of an interwar epidemic that public health controls did not allow to develop into a full blown pandemic because of what was already known from 1918, as well as employing very strict patient, contact and family isolation. In 1937 there were 620 claims for sickness benefits made to various insurance companies.

Asian Flu (1957–1958)

The "Asian Flu" was a category 2

Pandemic Severity Index

flu pandemic outbreak of avian influenza that originated in China in early 1956 lasting until 1958. It originated from mutation in wild duck

Wild duck

Wild Duck can refer to:*The Wild Duck, play by Henrik Ibsen*mallard, species of wild duck...

s combining with a pre-existing human strain. The virus was first identified in Guizhou

Guizhou

' is a province of the People's Republic of China located in the southwestern part of the country. Its provincial capital city is Guiyang.- History :...

. It spread to Singapore in February 1957, reached Hong Kong by April, and US by June. Death toll in the US was approximately 69,800. The elderly were particularly vulnerable. Estimates of worldwide deaths vary widely depending on source, ranging from 1 million to 4 million.

Hong Kong Flu (1968–1969)

The Hong Kong Flu was a category 2

Pandemic Severity Index

flu pandemic caused by a strain of H3N2 descended from H2N2

H2N2

H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...

by antigenic shift

Antigenic shift

Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains...

, in which genes from multiple subtypes reassorted to form a new virus. The Hong Kong Flu pandemic of 1968 and 1969 killed an estimated one million people worldwide. Those over 65 had the greatest death rates. In the US, there were about 33,800 deaths.

2009 Flu Pandemic (2009-2010)

An epidemic of influenza-like illness of unknown causation occurred in Mexico in March–April 2009

2009 flu pandemic in Mexico

In March and April 2009, an outbreak of a new strain of influenza commonly referred to as "swine flu" infected many people in Mexico and other parts of the world, causing illness ranging from mild to severe. Initial reports suggested that the outbreak had started in February due to farming...

. On 24 April 2009, following the isolation of an A/H1N1 influenza in 7 ill patients in the southwest US. The WHO

Who

Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

issued a statement on the outbreak of "influenza like illness" in the confirmed cases of A/H1N1 influenza had been reported in Mexico, and that 20 confirmed cases of the disease had been reported in the US.The next day, the number of confirmed cases rose to 40 in the US, 26 in Mexico, 6 in Canada, and 1 in Spain. The disease spread rapidly through the rest the spring, and by 3 May, a total of 787 confirmed cases had been reported worldwide.
On 11 June 2009, the ongoing outbreak of Influenza A/H1N1, commonly referred to as "swine flu", was officially declared by the WHO to be the first influenza pandemic of the 21st century and a new strain of Influenza A virus subtype H1N1 first identified in April 2009. It is thought to be a mutation

Mutation

(reassortment) of four known strains of influenza A virus subtype H1N1: one endemic

Endemic (epidemiology)

In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

in humans, one endemic in birds, and two endemic in pigs (swine). The rapid spread of this new virus was likely due to a general lack of pre-existing antibody-mediated immunity in the human population

In 1 November 2009 a worldwide update by the UN's World Health Organization

World Health Organization

(WHO) stated that "199 countries and overseas territories/communities have officially reported a total of over 482,300 laboratory confirmed cases of the influenza pandemic H1N1 infection, that included 6,071 deaths."

H5N1

Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus

Influenzavirus A

which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogen

Pathogen

ic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu

Transmission and infection of H5N1

Transmission and infection of H5N1 from infected avian sources to humans is a concern due to the global spread of H5N1 that constitutes a pandemic threat....

, commonly known as "avian influenza" or "bird flu". It is endemic

Endemic (epidemiology)

in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally

Global spread of H5N1

The global spread of highly pathogenic H5N1 influenza in birds is considered a significant pandemic threat.While other H5N1 influenza strains are known, they are significantly different from a current, highly pathogenic H5N1 strain on a genetic level, making the global spread of this new strain...

after first appearing in Asia. It is epizootic

Epizootic

In epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...

(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

Culling

Culling is the process of removing animals from a group based on specific criteria. This is done either to reinforce certain desirable characteristics or to remove certain undesirable characteristics from the group...

of hundreds of millions of others to stem its spread. Most mentions of "bird flu" and H5N1 in the media refer to this strain. This was reprinted in 2005:

HPAI A(H5N1) is an avian disease. There is no evidence of efficient human-to-human transmission or of airborne transmission of HPAI A(H5N1) to humans. In almost all cases, those infected with H5N1 had extensive physical contact with infected birds. Still, around 60% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from it, and H5N1 may mutate

Mutation

or reassort

Reassortment

Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...

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
American Scientist
American Scientist is the bimonthly science and technology magazine published since 1913 by Sigma Xi. Each issue includes four to five feature articles written by scientists and engineers. These authors review research in all fields of science...

. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives. On 29 September 2005, David Nabarro

David Nabarro

Dr. David Nabarro , works as the Senior UN System Coordinator for Avian and Human Influenza at United Nations Headquarters in New York. He has been seconded to this position from the World Health Organization.-Biography:...

, 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 clade

Clade

A clade is a group consisting of a species and all its descendants. In the terms of biological systematics, a clade is a single "branch" on the "tree of life". The idea that such a "natural group" of organisms should be grouped together and given a taxonomic name is central to biological...

s, 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

Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

of HPAI A(H5N1), its endemic presence, its increasingly large host

Host (biology)

In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...

reservoir, and its significant ongoing mutations, the H5N1 virus is the world's largest current pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic. At least 12 companies and 17 governments are developing pre-pandemic 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 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 as it is expected to continue mutating in birds regardless of whether humans develop herd immunity

Herd immunity

Herd immunity describes a form of immunity that occurs when the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity...

to a future pandemic strain. Influenza pandemics from its genetic offspring may include influenza A virus

Influenzavirus A

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

Spanish flu

pandemic, planning for a future influenza pandemic is based on what can be done and there is no higher Pandemic Severity Index

Pandemic Severity Index

level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad the Spanish flu or worse; and for which all intervention measures are to be used.

H5N1 is just one of the many subtypes of the species Influenza A virus. Any one of them can combine with each other or with different variant genotypes within its own subtype creating new variants, any one of which could become a pandemic strain. We know enough about the genetics to know what strains to fear most (example: only H5 and H7 subtypes are "highly pathogenic") and we know what genetic factors make a flu virus a human virus (i.e. easily passed human to human); so we know H5N1 is the biggest pandemic threat of all the strains in circulation and we know it is only a few antigenic shift

Antigenic shift

mutations or antigenic drift

Antigenic drift

The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific receptors, which prevent...

mutations from being an avian influenza virus to being a human flu

Human flu

virus. If it does this it may or may not still be in the H5N1 subtype. Both the drift and the shift can happen in any infected animal and then be passed to a human and spread like wildfire. Possible shift scenarios include the shift occurring in humans, pigs, or cats. To acquire the needed mutation through drift, it simply has to continue being an epidemic in birds long enough for the mutations to occur and then be passed to a human.

Other pandemic threat subtypes

"Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1, H1N2

H1N2

H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....

, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans.

Genetic factors in distinguishing between "human flu

Human flu

viruses" and "avian influenza viruses" include:

PB2: (RNA polymerase

RNA polymerase

RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

): Amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

(or residue

Residue (chemistry)

In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....

) position 627 in the PB2 protein encoded by the PB2 RNA

RNA

Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

gene. Until H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

, all known avian influenza viruses had a Glu

Glutamic acid

Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

at position 627, while all human influenza viruses had a lysine

Lysine

Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

HA: (hemagglutinin

Hemagglutinin

): Avian influenza HA bind alpha 2–3 sialic acid

Sialic acid

Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...

receptors while human influenza HA bind alpha 2–6 sialic acid receptors.

"About 52 key genetic changes distinguish avian influenza strains from those that spread easily among people, according to researchers in Taiwan, who analyzed the genes of more than 400 A type flu viruses." "How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict. We have examined sequences from the 1918 strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the 1918 pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses."

Highly pathogenic H5N1 avian influenza kills 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

followed rapidly by a coma without developing respiratory or flu-like symptoms.

The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:

H1N1 caused "Spanish Flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...

" and the 2009 swine flu outbreak (novel H1N1
Pandemic H1N1/09 virus
The Pandemic H1N1/09 virus is a swine origin Influenza A virus subtype H1N1 virus strain responsible for the 2009 flu pandemic. For other names see the Nomenclature section below.-Virus characteristics:...

)
H2N2
H2N2
H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...

caused "Asian Flu"
H3N2
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

caused "Hong Kong Flu"
H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

is "bird flu", endemic in avians
H7N7
H7N7
H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies...

has unusual zoonotic potential
H1N2
H1N2
H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....

is currently endemic in humans and pigs
H9N2
H9N2
H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...

, H7N2
H7N2
H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...

, H7N3
H7N3
H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...

, H10N7
H10N7
H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in...

H1N1

H1N1 is currently endemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu

Spanish flu

pandemic

Pandemic

A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...

that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919. Controversy arose in October 2005, after the H1N1 genome

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

was published in the journal, Science

Science (journal)

Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

. Many fear that this information could be used for bioterrorism

Bioterrorism

Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, or toxins, and may be in a naturally occurring or a human-modified form. For the use of this method in warfare, see biological warfare.-Definition:According to the...

"When he compared the 1918 virus

Spanish flu

with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person."

In mid-April 2009, an H1N1 variant appeared in Mexico, with its center in Mexico City. By 26 April the variant had spread widely; with cases reported in Canada, the US, New Zealand, the UK, France, Spain and Israel. On 29 April WHO

Who

Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

raised the worldwide pandemic phase to 5. On 11 June 2009 the WHO raised the worldwide pandemic phase to 6, which means that the H1N1 swine flu has reached pandemic proportions, with nearly 30,000 confirmed cases worldwide. 8 November 2009 worldwide update by the UN's World Health Organization (WHO) states that "206 countries and overseas territories/communities have officially reported over 503,536 laboratory confirmed cases of the influenza pandemic H1N1 infection, including 6,250 deaths." http://www.who.int/csr/disease/swineflu/updates/en/

1. Microscopic image of the H1N1 virus

2. Microscopic image of the H1N1 virus
H2N2

The Asian Flu

Asian flu

Asian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...

was a pandemic

Pandemic

outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which a influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths.

H3N2

H3N2 is currently endemic in both human and pig populations. It evolved from H2N2 by antigenic shift

Antigenic shift

and caused the Hong Kong Flu

Hong Kong flu

pandemic of 1968 and 1969 that killed up to 750,000."An early-onset, severe form of influenza A H3N2 made headlines when it claimed the lives of several children in the United States in late 2003."

The dominant strain of annual flu in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine

Amantadine

Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...

and rimantadine

Rimantadine

Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug...

in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.

"[C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host."

H7N7

H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies...

has unusual zoonotic potential. In 2003 in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.

H1N2

is currently endemic in both human and pig populations. The new H1N2

H1N2

strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

subtypes. The hemagglutinin

Hemagglutinin

protein of the H1N2

H1N2

virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase

Neuraminidase

protein is similar to that of the current H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

viruses.

Strategies to prevent a flu pandemic

This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations

Council on Foreign Relations

The Council on Foreign Relations is an American nonprofit nonpartisan membership organization, publisher, and think tank specializing in U.S. foreign policy and international affairs...

panel.

If influenza remains an animal problem with limited human-to-human transmission it is not a pandemic, though it continues to pose a risk. To prevent the situation from progressing to a pandemic, the following short-term strategies have been put forward:

Culling and vaccinating
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

livestock
Vaccinating poultry workers against common flu
Limiting travel in areas where the virus is found

The rationale for vaccinating poultry workers against common flu is that it reduces the probability of common influenza virus recombining with avian H5N1 virus to form a pandemic strain. Longer term strategies proposed for regions where highly pathogenic H5N1 is endemic in wild birds have included:

changing local farming practices to increase farm hygiene and reduce contact between livestock and wild birds.
altering farming practices in regions where animals live in close, often unsanitary quarters with people, and changing the practices of open-air "wet markets" where birds are kept for live sale and slaughtered on-site. A challenge to implementing these measures is widespread poverty, frequently in rural areas, coupled with a reliance upon raising fowl for purposes of subsistence farming or income without measures to prevent propagation of the disease.
changing local shopping practices from purchase of live fowl to purchase of slaughtered, pre-packaged fowl.
improving veterinary vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

availability and cost.

Vaccines

A vaccine

Vaccine

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

probably would not be available in the initial stages of population infection. A vaccine cannot be developed to protect against a virus which does not exist yet. The Avian Flu virus H5N1 has the potential to mutate into a pandemic strain, but so do other types of flu virus. Once a potential virus is identified and a vaccine is approved, it normally takes five to six months before the vaccine becomes available.

The capability to produce vaccines varies widely from country to country; in fact, only 19 countries are listed as "influenza vaccine manufacturers" according to the World Health Organization. It is estimated that, in a best scenario situation, 750 million doses could be produced each year, whereas it is likely that each individual would need two doses of the vaccine to become immuno-competent. Distribution to and inside countries would probably be problematic. Several countries, however, have well-developed plans for producing large quantities of vaccine. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country.

Another concern is whether countries which do not manufacture vaccines themselves, including those where a pandemic strain is likely to originate, will be able to purchase vaccine to protect their population. Cost considerations aside, they fear that the countries with vaccine-manufacturing capability will reserve production to protect their own populations and not release vaccines to other countries until their own population is protected. Indonesia has refused to share samples of H5N1 strains which have infected and killed its citizens until it receives assurances that it will have access to vaccines produced with those samples. So far, it has not received those assurances. However, in September 2009, The United States and France agreed to make 10 percent of their H1N1 vaccine supply available to other countries through the World Health Organization.

There are two serious technical problems associated with the development of a vaccine against H5N1. The first problem is this: seasonal influenza vaccines require a single injection of 15 μg haemagluttinin in order to give protection; H5 seems to evoke only a weak immune response and a large multicentre trial found that two injections of 90 µg H5 given 28 days apart provided protection in only 54% of people . Even if it is considered that 54% is an acceptable level of protection, the world is currently capable of producing only 900 million doses at a strength of 15 μg (assuming that all production were immediately converted to manufacturing H5 vaccine); if two injections of 90 μg are needed then this capacity drops to only 70 million . Trials using adjuvant

Adjuvant

An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...

s such as alum

Alum

Alum is both a specific chemical compound and a class of chemical compounds. The specific compound is the hydrated potassium aluminium sulfate with the formula KAl2.12H2O. The wider class of compounds known as alums have the related empirical formula, AB2.12H2O.-Chemical properties:Alums are...

, AS03

AS03

AS03 is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline...

, AS04

AS04

AS04 is a trade name for combination of adjuvants used in various vaccine product by GlaxoSmithKline , in particular the Cervarix HPV vaccine. It consists of aluminum hydroxide and monophosphoryl lipid A . Furthermore it is the successor of AS03 which is a Squalene based adjuvant.-External links:***...

or MF59

MF59

MF59 is an immunologic adjuvant that uses squalene. It is Novartis' proprietary adjuvant that is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells. MF59 is the first oil-in-water influenza vaccine adjuvant to be commercialized in...

to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clade

Clade

s of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Vaccine research has mostly been focused on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus.

Since 2009, most vaccine development efforts have been focused on the current pandemic influenza virus H1N1. As of July 2009, more than 70 known clinical trials are have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus, and expect the initial vaccine lots to be avaialable within the following month.

Anti-viral drugs

Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in preparation for a possible pandemic. Oseltamivir

Oseltamivir

Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...

(trade name Tamiflu) is the most commonly sought drug, since it is available in pill form. Zanamivir
(trade name Relenza) is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza.

Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid

Probenecid

Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...

could double supplies.

There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus.

Tamiflu was originally discovered by Gilead Sciences

Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics. For many years since the company was founded, the company concentrated primarily on antiviral drugs to treat patients infected with HIV, hepatitis B or influenza. In 2006, Gilead acquired two...

and licensed to Roche for late-phase development and marketing.

Public Response Measures

Social distancing: By traveling less, working from home or closing schools, there is less opportunity for the virus to spread. Reduce the time spent in crowded settings if possible. And keep your distance (preferably at least 1 metre) from people who show symptoms of influenza-like illness, such as coughing and sneezing.
Respiratory hygiene: Advise people to cover their coughs and sneezes. If using a tissue, make sure you dispose of it carefully and then clean your hands immediately afterwards. (See "Handwashing Hygiene" below.) If you do not have a tissue handy when you cough or sneeze, cover your mouth as much as possible with the crook of your elbow.
Handwashing Hygiene: Frequent handwashing with soap and water (or with an alcohol-based hand sanitizer) is very important, especially after coughing or sneezing, and after contact with other people or with potentially contaminated surfaces (such as handrails, shared utensils, etc.)
Other hygiene: Avoid touching your eyes, nose and mouth as much as possible.
Masks
Surgical mask
A surgical mask also known as a procedure mask is intended to be worn by health professionals during surgery and at other times to catch the bacteria shed in liquid droplets and aerosols from the wearer's mouth and nose....

: No mask can provide a perfect barrier but products that meet or exceed the NIOSH N95 standard recommended by the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

are thought to provide good protection. WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

recommends that health-care workers wear N95 masks and that patients wear surgical masks (which may prevent respiratory secretions from becoming airborne). Any mask may be useful to remind the wearer not to touch the face. This can reduce infection due to contact with contaminated surfaces, especially in crowded public places where coughing or sneezing people have no way of washing their hands. The mask itself can become contaminated and must be handled as medical waste when removed.

Risk communication: To encourage the public to comply with strategies to reduce the spread of disease, "communications regarding possible community interventions [such as requiring sick people to stay home from work, closing schools] for pandemic influenza that flow from the federal government to communities and from community leaders to the public not overstate the level of confidence or certainty in the effectiveness of these measures."

The Institute of Medicine

Institute of Medicine

The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

has published a number of reports and summaries of workshops on public policy issues related to influenza pandemics. They are collected in Pandemic Influenza: A Guide to Recent Institute of Medicine Studies and Workshops and some strategies from these reports are included in the list above.

Phases

WHO Pandemic Influenza Phases (2009)
Phase	Description
Phase 1	No animal influenza virus circulating among animals have been reported to cause infection in humans.
Phase 2	An animal influenza virus circulating in domesticated or wild animals is known to have caused infection in humans and is therefore considered a specific potential pandemic threat.
Phase 3	An animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks.
Phase 4	Human to human transmission of an animal or human-animal influenza reassortant virus able to sustain community-level outbreaks has been verified.
Phase 5	Human-to-human spread of the virus in two or more countries in one WHO region.
Phase 6	In addition to the criteria defined in Phase 5, the same virus spreads from human-to-human in at least one other country in another WHO region.
Post peak period	Levels of pandemic influenza in most countries with adequate surveillance have dropped below peak levels.
Post pandemic period	Levels of influenza activity have returned to the levels seen for seasonal influenza in most countries with adequate surveillance.

The World Health Organization (WHO) has developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic.

In the 2009 revision of the phase descriptions, the WHO has retained the use of a six-phase approach for easy incorporation of new recommendations and approaches into existing national preparedness and response plans. The grouping and description of pandemic phases have been revised to make them easier to understand, more precise, and based upon observable phenomena. Phases 1–3 correlate with preparedness, including capacity development and response planning activities, while phases 4–6 clearly signal the need for response and mitigation efforts. Furthermore, periods after the first pandemic wave are elaborated to facilitate post pandemic recovery activities.

The phases are defined below.

In nature, influenza viruses circulate continuously among animals, especially birds. Even though such viruses might theoretically develop into pandemic viruses, in Phase 1 no viruses circulating among animals have been reported to cause infections in humans.

In Phase 2 an animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat.

In Phase 3, an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Limited human-to-human transmission may occur under some circumstances, for example, when there is close contact between an infected person and an unprotected caregiver. However, limited transmission under such restricted circumstances does not indicate that the virus has gained the level of transmissibility among humans necessary to cause a pandemic.

Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause "community-level outbreaks". The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Any country that suspects or has verified such an event should urgently consult with the WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a foregone conclusion.

Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.

Phase 6, the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a global pandemic is under way.

During the post-peak period, pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave.

Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave. Pandemic waves can be separated by months and an immediate "at-ease" signal may be premature.

In the post-pandemic period, influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required.

Government preparations for a potential H5N1 pandemic (2003–2009)

According to The New York Times
The New York Times
The New York Times is an American daily newspaper founded and continuously published in New York City since 1851. The New York Times has won 106 Pulitzer Prizes, the most of any news organization...

as of March 2006, "governments worldwide have spent billions planning for a potential influenza pandemic: buying medicines, running disaster drills, [and] developing strategies for tighter border controls" due to the H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

threat.
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 National Wildlife Health Center, the CDC

Centers for Disease Control and Prevention

The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

, the ECDC, the World Health Organization

World Health Organization

, the European Commission

European Commission

The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....

, the National Influenza Centers

National Influenza Centers

National Influenza Centers are institutions which are formally recognized as such by the World Health Organization ."The WHO Global Influenza Surveillance Network was established in 1952...

, and others.

United Nations

In September 2005, David Nabarro

David Nabarro

, a lead UN health official warned that a bird flu outbreak could happen anytime and had the potential to kill 5–150 million people.

World Health Organization

The World Health Organization

World Health Organization

(WHO), believing that the world was closer to another influenza pandemic than it has been any time since 1968, when the last of the 20th century's three pandemics swept the globe, has developed guidelines on pandemic influenza preparedness and response. The March 2005 plan includes guidance on roles and responsibilities in preparedness and response; information on pandemic phases; and recommended actions for before, during, and after a pandemic.

United States

"[E]fforts by the federal government to prepare for pandemic influenza at the national level include a $100 million DHHS initiative in 2003 to build U.S. vaccine

Vaccine

production. Several agencies within Department of Health and Human Services (DHHS) – including the Office of the Secretary, the Food and Drug Administration

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

(FDA), CDC

Centers for Disease Control and Prevention

, and the National Institute of Allergy and Infectious Diseases

National Institute of Allergy and Infectious Diseases

The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...

(NIAID) – are in the process of working with vaccine manufacturers to facilitate production of pilot vaccine lots for both H5N1 and H9N2 strains as well as contracting for the manufacturing of 2 million doses of an H5N1 vaccine. This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic."

Each State and Territory of the United States has a specific Pandemic Flu Plan which covers Avian Flu, Swine Flu (H1N1) and other potential influenza epidemics. The State Plans together with a professionally vetted search engine of flu related research, policies, and plans, is available at the current portal: Pandemic Flu Search.

On 26 August 2004, Secretary of Health and Human Services, Tommy Thompson

Tommy Thompson

Thomas George "Tommy" Thompson , a United States Republican politician, was the 42nd Governor of Wisconsin, after which he served as U.S. Secretary of Health and Human Services. Thompson was a candidate for the 2008 U.S. Presidential Election, but dropped out early after a poor performance in polls...

released a draft Pandemic Influenza Response and Preparedness Plan, which outlined a coordinated national strategy to prepare for and respond to an influenza pandemic. Public comments were accepted for 60 days.

In a speech before the United Nations General Assembly

United Nations General Assembly

For two articles dealing with membership in the General Assembly, see:* General Assembly members* General Assembly observersThe United Nations General Assembly is one of the five principal organs of the United Nations and the only one in which all member nations have equal representation...

on 14 September 2005, President George W. Bush

George W. Bush

George Walker Bush is an American politician who served as the 43rd President of the United States, from 2001 to 2009. Before that, he was the 46th Governor of Texas, having served from 1995 to 2000....

announced the creation of the International Partnership on Avian and Pandemic Influenza

International Partnership on Avian and Pandemic Influenza

President George W. Bush announced the International Partnership on Avian and Pandemic Influenza in his remarks to the High-Level Plenary Meeting of the United Nations General Assembly on September 14, 2005, in New York. On September 15, 2005, Under Secretary of State for Democracy and Global...

. The Partnership brings together nations and international organizations to improve global readiness by:

elevating the issue on national agendas;
coordinating efforts among donor and affected nations;
mobilizing and leveraging resources;
increasing transparency in disease reporting and surveillance; and
building capacity to identify, contain and respond to a pandemic influenza.

On 5 October 2005, Democratic Senators Harry Reid

Harry Reid

Harry Mason Reid is the senior United States Senator from Nevada, serving since 1987. A member of the Democratic Party, he has been the Senate Majority Leader since January 2007, having previously served as Minority Leader and Minority and Majority Whip.Previously, Reid was a member of the U.S...

, Evan Bayh

Evan Bayh

Birch Evans "Evan" Bayh III is a lawyer, advisor and former Democratic politician who served as the junior U.S. Senator from Indiana from 1999 to 2011. He earlier served as the 46th Governor of Indiana from 1989 to 1997. Bayh is a current Fox News contributor as of March 14, 2011.Bayh first held...

, Dick Durbin, Ted Kennedy

Ted Kennedy

Edward Moore "Ted" Kennedy was a United States Senator from Massachusetts and a member of the Democratic Party. Serving almost 47 years, he was the second most senior member of the Senate when he died and is the fourth-longest-serving senator in United States history...

, Barack Obama

Barack Obama

Barack Hussein Obama II is the 44th and current President of the United States. He is the first African American to hold the office. Obama previously served as a United States Senator from Illinois, from January 2005 until he resigned following his victory in the 2008 presidential election.Born in...

, and Tom Harkin

Tom Harkin

Thomas Richard "Tom" Harkin is the junior United States Senator from Iowa and a member of the Democratic Party. He previously served in the United States House of Representatives ....

introduced the Pandemic Preparedness and Response Act

Pandemic Preparedness and Response Act

The Pandemic Preparedness and Response Act is a bill introduced on October 5, 2005 by U.S. Senators Harry Reid, Evan Bayh, Dick Durbin, Ted Kennedy, Barack Obama, and Tom Harkin in response to the growing threat of an outbreak of avian influenza...

as a proposal to deal with a possible outbreak.

On 27 October 2005, the Department of Health and Human Services awarded a $62.5 million contract to Chiron Corporation

Chiron Corporation

Chiron Corporation was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 20, 2006. It had offices and facilities in eighteen countries on five continents. Chiron's business and research was in three main areas:...

to manufacture an avian influenza vaccine designed to protect against the H5N1 influenza virus strain. This followed a previous awarded $100 million contract to sanofi pasteur

Sanofi pasteur

Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...

, the vaccines business of the sanofi-aventis

Sanofi-Aventis

Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...

Group, for avian flu vaccine.

In October 2005, President Bush urged bird flu vaccine manufacturers to increase their production.

On 1 November 2005 President Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza. He also submitted a request to Congress for $7.1 billion to begin implementing the plan. The request includes $251 million to detect and contain outbreaks before they spread around the world; $2.8 billion to accelerate development of cell-culture technology; $800 million for development of new treatments and vaccines; $1.519 billion for the Departments of Health and Human Services (HHS

HHS

-Medicine:*Hyperglycemic hyperosmolar state, a complication of diabetes-Individual high schools:*Hackensack High School - Hackensack, New Jersey, US*Hackettstown High School - Hackettstown, New Jersey, US*Hadleigh High School - Hadleigh, Suffolk, England...

) and Defense to purchase influenza vaccines; $1.029 billion to stockpile antiviral medications; and $644 million to ensure that all levels of government are prepared to respond to a pandemic outbreak.

On 6 March 2006, Mike Leavitt, Secretary of Health and Human Services, said U.S. health agencies are continuing to develop vaccine alternatives that will protect against the evolving avian influenza virus.

The U.S. government, bracing for the possibility that migrating birds could carry a deadly strain of bird flu to North America, plans to test nearly eight times as many wild birds starting in April 2006 as have been tested in the past decade.

On 8 March 2006, Dr. David Nabarro, senior UN coordinator for avian and human influenza, said that given the flight patterns of wild birds that have been spreading avian influenza (bird flu) from Asia to Europe and Africa, birds infected with the H5N1 virus could reach the Americas within the next six to 12 months.

"5 Jul 2006 (CIDRAP News) – In an update on pandemic influenza preparedness efforts, the federal government said last week it had stockpiled enough vaccine against H5N1 avian influenza virus to inoculate about 4 million people and enough antiviral medication to treat about 6.3 million."

Canada

The Public Health Agency of Canada

Public Health Agency of Canada

The Public Health Agency of Canada is an agency of the Government of Canada that is responsible for public health, emergency preparedness, and response and infectious and chronic disease control and prevention...

follows the WHO's

World Health Organization

categories, but has expanded them. The Avian Flu scare of 2006 prompted The Canadian Public Health Agency to release an updated Pandemic Influenza Plan for Health Officials. This document was created to address the growing concern over the hazards faced by public health officials when exposed to sick or dying patients.

Malaysia

Since the Nipah

Henipavirus

Henipavirus is a genus of the family Paramyxoviridae, order Mononegavirales containing two established species, Hendra virus and Nipah virus. The henipaviruses are naturally harboured by Pteropid fruit bats , and some microbat species...

virus outbreak in 1999, the Malaysian Health Ministry

Healthcare in Malaysia

Healthcare in Malaysia is mainly under the responsibility of the government's Ministry of Health. Malaysia generally has an efficient and widespread system of health care, operating a two-tier health care system consisting of both a government-run universal healthcare system and a co-existing...

have put in place processes to be better prepared to protect the Malaysian population from the threat of infectious diseases. Malaysia was fully prepared during the Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory syndrome

Severe Acute Respiratory Syndrome is a respiratory disease in humans which is caused by the SARS coronavirus . Between November 2002 and July 2003 an outbreak of SARS in Hong Kong nearly became a pandemic, with 8,422 cases and 916 deaths worldwide according to the WHO...

situation (Malaysia was not a SARS affected country) and the episode of the H5N1 (bird flu) outbreak in 2004.

The Malaysian government

Politics of Malaysia

The politics of Malaysia takes place in the framework of a federal constitutional monarchy, in which the Yang di-Pertuan Agong is head of state and the Prime Minister of Malaysia is the head of government. Executive power is exercised by the federal government and the 13 state governments. ...

has developed a National Influenza Pandemic Preparedness Plan (NIPPP) which serves as a time bound guide for preparedness and response plan for influenza pandemic. It provides a policy and strategic framework for a multisectoral response and contains specific advice and actions to be undertaken by the Ministry of Health at the different levels, other governmental departments and agencies and non governmental organizations to ensure that resources are mobilized and used most efficiently before, during and after a pandemic episode.

External resources

External links

Health-EU portal EU response to influenza
http://www.timberlanebooks.com/cruel_wind_desc.shtml Award-winning book, "A Cruel Wind: Pandemic Flu in America, 1918–1920," by Dorothy A. Pettit, PhD and Janice Bailie, PhD (Timberlane Books, 2009)
European Commission – Public Health EU coordination on Pandemic (H1N1) 2009

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