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An influenza pandemic is an
epidemic An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time. Epidemics of infectious d ...
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 140 years, with 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 ...
being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The most recent, the
2009 swine 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 Sp ...
, resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly. 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 Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity de ...
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 propagation of influenza viruses throughout the world is thought in part to be by
bird migration Bird migration is the regular seasonal movement, often north and south along a flyway, between breeding and wintering grounds. Many species of bird migrate. Migration carries high costs in predation and mortality, including from hunting b ...
s, though commercial shipments of live bird products might also be implicated, as well as human travel patterns. The World Health Organization (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 pathogenic variation of the
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 ...
subtype of influenza A virus. On 11 June 2009, a new strain of H1N1 influenza was declared to be a pandemic (Stage 6) by the WHO after evidence of spreading in the southern hemisphere. The 13 November 2009 worldwide update by the WHO stated that " of 8 November 2009, worldwide more than 206 countries and overseas territories or communities have reported 03,536laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6,250 deaths."


Influenza

Influenza, commonly known as the flu, is an infectious disease of birds and mammals. It was thought to be caused by comets, earthquakes, volcanoes, cosmic dust, the rising and setting of the sun, vapors arising from the air and ground, or a blast from the stars. Now we know that it is caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). In humans, common symptoms of influenza infection are fever, sore throat,
muscle pains Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another lik ...
, severe headache, coughing, and weakness and fatigue. In more serious cases, influenza
causes Causes, or causality, is the relationship between one event and another. It may also refer to: * Causes (band), an indie band based in the Netherlands * Causes (company) Causes.com is a civic-technology app and website that enables users to orga ...
pneumonia, which can be fatal, particularly in young children and the elderly. While sometimes confused with the
common cold The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposur ...
, 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, 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 An aerosol is a suspension of fine solid particles or liquid droplets in air or another gas. Aerosols can be natural or anthropogenic. Examples of natural aerosols are fog or mist, dust, forest exudates, and geyser steam. Examples of anthropogen ...
containing the virus, and from infected birds through their
droppings Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...
. Influenza can also be transmitted by
saliva Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be ...
, nasal secretions, 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). Most influenza strains can be inactivated easily by
disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than st ...
s and
detergent A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are mor ...
s. Flu spreads around the world in seasonal epidemics. Ten
pandemics A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic disease with a stable number of in ...
were recorded before the Spanish flu of 1918. Three influenza pandemics occurred during the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal
species In biology, a species is the basic unit of Taxonomy (biology), classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of ...
, so close proximity between humans and animals can promote epidemics. In addition, epidemiological factors, such as the WWI practice of packing soldiers with severe influenza illness into field hospitals while soldiers with mild illness stayed outside on the battlefield, are an important determinant of whether or not a new strain of influenza virus will spur a pandemic. (During the 1918 Spanish flu pandemic, this practice served to promote the evolution of more virulent viral strains over those that produced mild illness.) When it first killed humans in
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
in the 1990s, a deadly avian strain of
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 ...
posed a great risk for a new influenza pandemic; however, this virus did not
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, mitosi ...
to spread easily between people. Vaccinations 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 Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fro ...
that contains purified and inactivated material from three viral strains. Typically this vaccine includes material from two influenza A virus subtypes and one
influenza B virus ''Influenza B virus'' is the only species in the genus ''Betainfluenzavirus'' in the virus family ''Orthomyxoviridae''. Influenza B virus is known only to infect humans and seals. This limited host range is apparently responsible for the lack ...
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 drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...
s can be used to treat influenza, with neuraminidase inhibitors being particularly effective.


Variants and subtypes of ''Influenza A virus''

Variants of ''Influenza A virus'' are identified and named according to the isolate that they are like and thus are presumed to share lineage (example
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 ...
virus like); according to their typical host (example Human flu virus); according to their subtype (example H3N2); and according to their deadliness (e.g., Low Pathogenic as discussed below). 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 *
Dog flu The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the wolf. Also called the domestic dog, it is derived from the extinct Pleistocene wolf, and the modern wolf is the dog's nearest living relative. D ...
* Horse flu * Human flu *
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 o ...
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) and an N number (for neuraminidase). Each subtype virus has
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, mitosi ...
d 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. Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. "There are 16 different HA
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 response. ...
s (H1 to H16) and nine different NA
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 response. ...
s (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but recently two new types were isolated: a new type (H16) was isolated from
black-headed gull The black-headed gull (''Chroicocephalus ridibundus'') is a small gull that breeds in much of the Palearctic including Europe and also in coastal eastern Canada. Most of the population is migratory and winters further south, but some birds re ...
s caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005." "The other, H17, was isolated from
fruit bats In botany, a fruit is the seed-bearing structure in flowering plants that is formed from the ovary after flowering. Fruits are the means by which flowering plants (also known as angiosperms) disseminate their seeds. Edible fruits in particul ...
caught in Guatemala and reported in the literature in 2013."


Nature of a flu pandemic

Some pandemics are relatively minor such as the one in 1957 called
Asian flu Asian may refer to: * Items from or related to the continent of Asia: ** Asian people, people in or descending from Asia ** Asian culture, the culture of the people from Asia ** Asian cuisine, food based on the style of food of the people from Asi ...
(1–4 million dead, depending on source). Others have a higher Pandemic Severity Index 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 contracted 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 1918–1920 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

A 1921 book lists nine influenza pandemics prior to the 1889–1890 flu, the first in 1510. A more modern source lists six.


Asiatic flu (1889–1890)

The 1889–1890 pandemic, often referred to as the ''Asiatic flu'' or ''Russian flu'', killed about 1 million people out of a world population of about 1.5 billion. It was the last great pandemic of the 19th century, and is among the deadliest pandemics in history. The most reported effects of the pandemic took place from October 1889 to December 1890, with recurrences in 1891 to 1895.


Spanish flu (1918–1920)

The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. The Spanish flu pandemic lasted from 1918 to 1920. Various estimates say it killed between 17 million and 100 million people This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the
Black Death The Black Death (also known as the Pestilence, the Great Mortality or the Plague) was a bubonic plague pandemic occurring in Western Eurasia and North Africa from 1346 to 1353. It is the most fatal pandemic recorded in human history, causing ...
, 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 A cytokine storm, also called hypercytokinemia, is a physiological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Norma ...
s. Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue,
cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...
, 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 in the skin also occurred." The majority of deaths were from
bacterial pneumonia Bacterial pneumonia is a type of pneumonia caused by bacterial infection. Types Gram-positive ''Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae' ...
, a
secondary infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
caused by influenza, but the virus also killed people directly, causing massive
hemorrhages Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagi ...
and edema in the lung. The Spanish flu pandemic was truly global, spreading even to the
Arctic The Arctic ( or ) is a polar region located at the northernmost part of Earth. The Arctic consists of the Arctic Ocean, adjacent seas, and parts of Canada (Yukon, Northwest Territories, Nunavut), Danish Realm (Greenland), Finland, Iceland, N ...
and remote Pacific islands. The unusually severe disease killed between 10 and 20% of those infected, as opposed to the more usual flu epidemic
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 de ...
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 1918–1920 pandemic is estimated to be between 17 and 100 million people, constituting approximately 1–6% of the world's population. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 ''years''.


Asian flu (1957–1958)

The Asian flu was a category 2 flu pandemic outbreak caused by a strain of H2N2 that originated in China in early 1957, lasting until 1958. The virus originated from a mutation in
wild duck The wild duck is the non-domesticated ancestor of the domestic duck. Wild duck may refer to: * Mallard * Muscovy duck The Muscovy duck (''Cairina moschata'') is a large duck native to the Americas, from the Rio Grande Valley of Texas and ...
s combining with a pre-existing human strain.Greene, Jeffrey. Moline, Karen.
006 Alec Trevelyan (006) is a fictional character and the main antagonist in the 1995 James Bond film ''GoldenEye'', the first film to feature actor Pierce Brosnan as Bond. Trevelyan is portrayed by actor Sean Bean. The likeness of Bean as Alec Tre ...
(2006) The Bird Flu Pandemic. .
The virus was first identified in Guizhou in late February; by mid-March it had spread across the entire mainland. It was not until the virus had reached Hong Kong in April, however, that the world was alerted to the unusual situation, when the international press began to report on the outbreak. The World Health Organization was officially informed when the virus arrived in Singapore, which operated the only influenza surveillance laboratory in Southeast Asia, in early May. From that point on, as the virus continued to sweep the region, the WHO remained attuned to the developing outbreak and helped coordinate the global response for the duration of the pandemic. This was the first pandemic to occur during what is considered the "era of modern virology". One significant development since the 1918 pandemic was the identification of the causative agent behind the flu. Later, it was recognized that the influenza virus changes over time, typically only slightly (a process called "
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 ...
"), sometimes significantly enough to result in a new subtype ("
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. The term is ...
"). Within weeks of the report out of Hong Kong, laboratories in the United States, the United Kingdom, and Australia had analyzed the virus and concluded that it was a novel strain of influenza A. Chinese researchers had already come to a similar conclusion in March, but as China was not a member of the WHO nor a part of its network of National Influenza Centers, this information did not reach the rest of the world, a fact which the WHO would lament after the pandemic. The virus swept across the Middle East,
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 ...
, and the Southern Hemisphere in the middle months of the year, causing widespread outbreaks. By the end of September, nearly the entire inhabited world had been infected or at least seeded with the virus. Around this time, extensive epidemics developed in the Northern Hemisphere following the opening of schools, generally peaking in North America and Europe in October. Some countries experienced a second wave in the final months of the year; Japan experienced a particularly severe resurgence in October. Influenza activity had largely subsided by the end of the year and remained apparently low during the first months of 1958, though some countries, such as the United States, experienced another rise in mortality from respiratory disease, of unclear origin. The disease tended to resemble seasonal influenza in its presentation; the WHO described it at the time as "uniformly benign". However, there was the potential for complications, of which there was some variability. Most deaths were a result of bacterial pneumonia, though cases of this condition were attenuated through the use of antibiotics that did not exist in 1918. There were also detailed accounts of fatal primary influenza pneumonia, with no indication of bacterial infection. Those with underlying conditions such as cardiovascular disease were at greater risk of developing these pneumonias; pregnant women were also vulnerable to complications. In general, the elderly experienced the greatest rates of mortality. Estimates of worldwide deaths vary widely depending on the source, ranging from 1 million to 4 million. Mortality in the US has been estimated between 60,000 and 80,000 deaths. Pandemic impact continued over several years in many countries, with Latin America experiencing considerable excess mortality through 1959.
Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the east a ...
experienced notably severe mortality over the course of two waves during this period. This was the most publicized influenza epidemic at the time of its occurrence. As the first pandemic to occur in the context of a global surveillance network, it was also the first time that preparations could be made ahead of an anticipated epidemic. Vaccination efforts were undertaken in some countries such as the US, though it is doubtful how successful such campaigns were with altering the courses of individual epidemics, mainly due to the timing of when the vaccines became widely available and how many people were able to be effectively immunized before the peak.


Hong Kong flu (1968–1970)

The Hong Kong flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by
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. The term is ...
, in which genes from multiple subtypes reassorted to form a new virus. This pandemic killed an estimated 1–4 million people worldwide. Those over 65 had the greatest death rates. In the US, there were about 100,000 deaths.


Russian flu (1977–1979)

The 1977 Russian flu was a relatively benign flu pandemic, mostly affecting population younger than the age of 26 or 25. It is estimated that 700,000 people died due to the pandemic worldwide. The cause was H1N1 virus strain, which was not seen after 1957 until its re-appearance in China and the Soviet Union in 1977. Genetic analysis and several unusual characteristics of the pandemic have prompted speculation that the virus was released to the public through a laboratory accident.


H1N1/09 flu pandemic (2009–2010)

An epidemic of influenza-like illness of unknown causation occurred in Mexico in March–April 2009. On 24 April 2009, following the isolation of an A/H1N1 influenza in seven ill patients in the southwest US, the WHO issued a statement on the outbreak of "influenza like illness" that 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, six in Canada, and one in Spain. The disease spread rapidly through the rest of 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 (reassortment) of four known strains of influenza A virus subtype H1N1: one endemic 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. On 1 November 2009, a worldwide update by the 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." By the end of the pandemic, declared on 10 August 2010, there were more than 18,000 laboratory-confirmed deaths from H1N1. Due to inadequate surveillance and lack of healthcare in many countries, the actual total of cases and deaths was likely much higher than reported. Experts, including the WHO, have since agreed that an estimated 284,500 people were killed by the disease, about 15 times the number of deaths in the initial death toll.


Other pandemic threat subtypes

"Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1,
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 ...
, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans. Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include: :PB2: (
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
):
Amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
(or
residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applie ...
) position 627 in the PB2 protein encoded by the PB2 RNA gene. Until
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 ...
, all known avian influenza viruses had a
glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
at position 627, while all human influenza viruses had a
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −CO ...
. :HA: ( hemagglutinin): Avian influenza HA bind alpha 2–3 sialic 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, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
followed rapidly by a coma 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,
1977 Russian flu The 1977 Russian flu was an influenza pandemic that was first reported by the Soviet Union in 1977 and lasted until 1979. The outbreak in northern China started in May 1977, slightly earlier than that in the Soviet Union. The pandemic mostly affec ...
, and the
2009 swine 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 Sp ...
( novel H1N1) *
H2N2 Influenza A virus subtype H2N2 (A/H2N2) is a subtype of '' Influenza A virus''. H2N2 has mutated into various strains including the " Asian flu" strain (now extinct in the wild), H3N2, and various strains found in birds. It is also suspected o ...
caused
Asian flu Asian may refer to: * Items from or related to the continent of Asia: ** Asian people, people in or descending from Asia ** Asian culture, the culture of the people from Asia ** Asian cuisine, food based on the style of food of the people from Asi ...
* H3N2 caused Hong Kong 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 ...
is bird flu, endemic in avians *
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, bird ...
has unusual zoonotic potential *
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 ...
is currently endemic in humans and pigs *
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 ...
,
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 & ...
,
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 ...
,
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 Ism ...
;H1N1 H1N1 is currently endemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu 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 was published in the journal, '' Science''. Many fear that this information could be used for
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 sa ...
.
When he compared the 1918 virus 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 the WHO 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. A 13 November 2009 worldwide update by the 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." ;H2N2 The
Asian Flu Asian may refer to: * Items from or related to the continent of Asia: ** Asian people, people in or descending from Asia ** Asian culture, the culture of the people from Asia ** Asian cuisine, food based on the style of food of the people from Asi ...
was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which an 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 and caused the Hong Kong flu pandemic 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, sold under the brand name Gocovri among others, is a medication used to treat dyskinesia associated with parkinsonism and influenza caused by type A influenzavirus, though its use for the latter is no longer recommended due to wid ...
and
rimantadine Rimantadine ( INN, sold under the trade name 'Flumadine'') is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can s ...
in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.
ntemporary 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 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, bird ...
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
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 ...
is currently endemic in both human and pig populations. The new
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 ...
strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the
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 ...
virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.


Assessment of a flu pandemic


Stages

The World Health Organization (WHO) 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 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. In February 2020, WHO spokesperson Tarik Jasarevic explained that the WHO no longer uses this six-phase classification model: "For the sake of clarification, WHO does not use the old system of 6 phases—that ranged from phase 1 (no reports of animal influenza causing human infections) to phase 6 (a pandemic)—that some people may be familiar with from H1N1 in 2009." For reference, 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 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. In 2014, the United States
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
(CDC) introduced an analogous framework to the WHO's pandemic stages titled the Pandemic Intervals Framework. It includes two pre-pandemic intervals, * Investigation * Recognition and four pandemic intervals, * Initiation * Acceleration * Deceleration * Preparation It also includes a table defining the intervals and mapping them to the WHO pandemic stages.


Severity

In 2014, the CDC adopted the
Pandemic Severity Assessment Framework The Pandemic Severity Assessment Framework (PSAF) is an evaluation framework which uses quadrants to evaluate both the transmissibility and clinical severity of a pandemic and to combine these into an overall impact estimate. Clinical severity is c ...
(PSAF) to assess the severity of pandemics. The PSAF superseded the 2007 linear Pandemic Severity Index, which assumed 30% spread and measured
case fatality rate In epidemiology, case fatality rate (CFR) – or sometimes more accurately case-fatality risk – is the proportion of people diagnosed with a certain disease, who end up dying of it. Unlike a disease's mortality rate, the CFR does not take int ...
(CFR) to assess the severity and evolution of the pandemic. Historically, measures of pandemic severity were based on the case fatality rate. However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because: * Deaths may lag several weeks behind cases, making the case fatality rate an underestimate * The total number of cases may not be known, making the case fatality rate an overestimate * A single case fatality rate for the entire population may obscure the effect on vulnerable sub-populations, such as children, the elderly, those with chronic conditions, and members of certain racial and ethnic minorities * Fatalities alone may not account for the full effects of the pandemic, such as absenteeism or demand on healthcare services To account for the limitations of measuring the case fatality rate alone, the PSAF rates severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population. Each dimension can be measured using more than one measure, which are scaled to allow comparison of the different measures.


Management of a flu pandemic


Strategies to prevent a flu pandemic

This section contains strategies to prevent a flu pandemic by a
Council on Foreign Relations The Council on Foreign Relations (CFR) is an American think tank specializing in U.S. foreign policy and international relations. Founded in 1921, it is a nonprofit organization that is independent and nonpartisan. CFR is based in New York City ...
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 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 A wet market (also called a public market or a traditional market) is a marketplace selling fresh foods such as meat, fish, produce and other consumption-oriented perishable goods in a non-supermarket setting, as distinguished from " dry market ...
" 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 availability and cost.


Strategies to slow down a flu pandemic


Public response measures

The main ways available to tackle a flu pandemic initially are behavioural. Doing so requires a good public health communication strategy and the ability to track public concerns, attitudes and behaviour. For example, the Flu TElephone Survey Template (FluTEST) was developed for the UK Department of Health as a set of questions for use in national surveys during a flu pandemic. * Social distancing: By traveling less, implementing remote work, 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. However, social distancing during a pandemic flu will likely carry severe mental health consequences; therefore, sequestration protocols should take mental health issues into consideration. * 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 A mask is an object normally worn on the face, typically for protection, disguise, performance, or entertainment and often they have been employed for rituals and rights. Masks have been used since antiquity for both ceremonial and pract ...
: No mask can provide a perfect barrier, but products that meet or exceed the NIOSH N95 standard recommended by the World Health Organization are thought to provide good protection. WHO recommends that health-care workers wear
N95 masks An N95 filtering facepiece respirator, commonly abbreviated N95 respirator, is a particulate-filtering facepiece respirator that meets the U.S. National Institute for Occupational Safety and Health (NIOSH) N95 classification of air filtratio ...
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 Risk communication is a complex cross-disciplinary academic field that is part of risk management and related to fields like crisis communication. The goal is to make sure that targeted audiences understand how risks effect to them or their commun ...
: To encourage the public to comply with strategies to reduce the spread of disease, "communications regarding possible community interventions uch as requiring sick people to stay home from work, closing schoolsfor 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 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. Relevant learning from the 2009 flu pandemic in the UK was published in ''Health Technology Assessment'', volume 14, issue 34.
Asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection but experiences no symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it might be considered asym ...
transmission appears to play a small role, but was not well studied by 2009.


Anti-viral drugs

There are two groups of antiviral drugs available for the treatment and prophylaxis of influenza: neuraminidase inhibitors such as Oseltamivir (trade name Tamiflu) and
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 ...
(trade name Relenza), and adamantanes such as amantadine and rimantadine. Due to the high rate of side effects and risk of antiviral resistance, use of adamantanes to fight influenza is limited. Many nations, as well as the World Health Organization, are working to stockpile antiviral drugs in preparation for a possible pandemic. Oseltamivir is the most commonly sought drug, since it is available in pill form. Zanamivir 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 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.


Vaccines

A vaccine probably would not be available in the initial stages of population infection. To date, there is no known mechanism to develop a vaccine to protect against a virus which does not yet exist. 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; 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, Australia, Brazil, France, Italy, New Zealand, Norway, Switzerland, the UK, and the USA agreed to make 10 percent of their H1N1 vaccine supply available to less-developed countries. 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 In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesi ...
s such as
alum An alum () is a type of chemical compound, usually a hydrated double sulfate salt of aluminium with the general formula , where is a monovalent cation such as potassium or ammonium. By itself, "alum" often refers to potassium alum, with the ...
,
AS03 AS03 (for "Adjuvant System 03") is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline (GSK). It is used, for example, in GSK's A/H1N1 pandemic flu vaccine Pandemrix. It is also in Arepanrix ...
,
AS04 Adjuvant System 04 or AS04 is a trade name for combination of adjuvants used in various vaccine products by GlaxoSmithKline, in particular the Fendrix hepatitis B vaccine. It is also one of the ingredients of the human papillomavirus vaccine (HPV) ...
or
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 ...
to try and lower the dose of vaccine are urgently needed. The second problem is this: there are two circulating clades 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 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 expected the initial vaccine lots to be available within the following month.


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

According to '' The New York Times'' as of March 2006, "governments worldwide have spent billions planning for a potential influenza pandemic: buying medicines, running disaster drills, nddeveloping strategies for tighter border controls" due to the
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 ...
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, the ECDC, the World Health Organization, the European Commission, the National Influenza Centers, and others.


United Nations

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


World Health Organization

The 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

" forts 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 production. Several agencies within
Department of Health and Human Services The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is ...
(DHHS)—including the Office of the Secretary, the Food and Drug Administration (FDA),
CDC 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, Georg ...
, and the National Institute of Allergy and Infectious Diseases (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 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 on 14 September 2005, President
George W. Bush George Walker Bush (born July 6, 1946) is an American politician who served as the 43rd president of the United States from 2001 to 2009. A member of the Republican Party, Bush family, and son of the 41st president George H. W. Bush, he ...
announced the creation of the International Partnership on Avian and Pandemic Influenza. 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, Evan Bayh,
Dick Durbin Richard Joseph Durbin (born November 21, 1944) is an American lawyer and politician serving as the senior United States senator from Illinois, a seat he has held since 1997. A member of the Democratic Party, Durbin has served as the Senate De ...
,
Ted Kennedy Edward Moore Kennedy (February 22, 1932 – August 25, 2009) was an American lawyer and politician who served as a United States senator from Massachusetts for almost 47 years, from 1962 until his death in 2009. A member of the Democratic ...
,
Barack Obama Barack Hussein Obama II ( ; born August 4, 1961) is an American politician who served as the 44th president of the United States from 2009 to 2017. A member of the Democratic Party, Obama was the first African-American president of the U ...
, and
Tom Harkin Thomas Richard Harkin (born November 19, 1939) is an American lawyer, author, and politician who served as a United States senator from Iowa from 1985 to 2015. A member of the Democratic Party, he previously was the U.S. representative for Iow ...
introduced the
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. T ...
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 ( ) was an American multinational biotechnology firm founded in 1981, based in Emeryville, California, that was acquired by Novartis on April 20, 2006. It had offices and facilities in eighteen countries on five continents. C ...
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 is the vaccines division of the French multinational pharmaceutical company Sanofi. Sanofi Pasteur is the largest company in the world devoted entirely to vaccines. It is one of four global producers of the yellow fever vaccine. ...
, the vaccines business of
Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Sy ...
, for avian flu vaccine. In October 2005, Bush urged bird flu vaccine manufacturers to increase their production. On 1 November 2005, 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) 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 Michael Okerlund Leavitt (born February 11, 1951) is an American politician who served as the 14th Governor of Utah from 1993 to 2003 in the Republican Party, as Administrator of the Environmental Protection Agency (EPA) from 2003 to 2005 and ...
, 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 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 ...
, 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. July 5, 2006, (
CIDRAP The Center for Infectious Disease Research and Policy (CIDRAP) is a center within the University of Minnesota that focuses on addressing public health preparedness and emerging infectious disease response. It was founded in 2001 by Dr. Michael Os ...
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 follows the WHO's 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 NIPA, Nipa or nipah may refer to: * Shamim Ara Nipa, Bangladeshi dancer and choreographer * Nipa hut, a type of stilt house indigenous to the cultures of the Philippines * Nipah virus, a Henipavirus NIPA * National Income and Product Accounts ...
virus outbreak in 1999, the Malaysian Health Ministry 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) situation (Malaysia was not a SARS-affected country) and the episode of the H5N1 outbreak in 2004. The
Malaysian government The Government of Malaysia, officially the Federal Government of Malaysia ( ms, Kerajaan Persekutuan Malaysia), is based in the Federal Territory of Putrajaya with the exception of the legislative branch, which is located in Kuala Lumpur. Mal ...
has developed
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.


See also

* Timeline of influenza * List of epidemics


Citations


External links



– Health – EU portal
WHO European Region pandemic influenza website


– European Commission – Public Health
The Great Pandemic: The United States in 1918

PandemicFlu.gov

Pandemic Viruses at the Influenza Research Database

''A Cruel Wind: Pandemic Flu in America, 1918–1920''
by Dorothy A. Pettit, PhD and Janice Bailie, PhD (Timberlane Books, 2009) {{DEFAULTSORT:Influenza Pandemic Prevention Pandemic