{{Short description|Pandemic involving influenza}} {{Use dmy dates|date=October 2020}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Flu}} [[File:SpanishFluWardWalterReed.jpg|thumb|250px|Influenza ward at Walter Reed Hospital, in Washington, D.C., during the 1918 flu pandemic]]
An '''influenza pandemic''' is an epidemic of an influenza virus that spreads across a large region (either multiple continents or worldwide) and infects a large proportion of the human population. There have been five major influenza pandemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic 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 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.<ref name=sobrino6>{{cite book |chapter-url=http://www.horizonpress.com/avir | vauthors = Klenk HD, Matrosovich M, Stech J |year=2008 |chapter=Avian Influenza: Molecular Mechanisms of Pathogenesis and Host Range |title=Animal Viruses: Molecular Biology | veditors = Mettenleiter TC, Sobrino F |publisher=Caister Academic Press |isbn=978-1-904455-22-6 }}</ref><ref name=Kawaoka>{{cite book | veditors = Kawaoka Y | title = Influenza Virology: Current Topics | publisher=Caister Academic Press | year = 2006 | url=http://www.horizonpress.com/flu | isbn = 978-1-904455-06-6}}</ref> The propagation of influenza viruses throughout the world is thought to be in part by bird migrations, though commercial shipments of live bird products might also be implicated, as well as human travel patterns.<ref>{{Cite journal |last1=Tian |first1=Huaiyu |last2=Zhou |first2=Sen |last3=Dong |first3=Lu |last4=Van Boeckel |first4=Thomas P. |last5=Cui |first5=Yujun |last6=Newman |first6=Scott H. |last7=Takekawa |first7=John Y. |last8=Prosser |first8=Diann J. |last9=Xiao |first9=Xiangming |last10=Wu |first10=Yarong |last11=Cazelles |first11=Bernard |last12=Huang |first12=Shanqian |last13=Yang |first13=Ruifu |last14=Grenfell |first14=Bryan T. |last15=Xu |first15=Bing |date=2015-01-06 |title=Avian influenza H5N1 viral and bird migration networks in Asia |journal=Proceedings of the National Academy of Sciences |volume=112 |issue=1 |pages=172–177 |doi=10.1073/pnas.1405216112 |doi-access=free |pmc=4291667 |pmid=25535385|bibcode=2015PNAS..112..172T }}</ref>
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.<ref>[https://web.archive.org/web/20060329125016/http://www.who.int/csr/disease/avian_influenza/phase/en/ "Current WHO phase of pandemic alert"]. World Health Organization, 2009</ref>
One strain of virus that may produce a pandemic in the future is a highly pathogenic variation of the H5N1 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.<ref>World Health Organization. [https://web.archive.org/web/20090611173204/http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html "World now at the start of 2009 influenza pandemic"].</ref> The 13 November 2009 worldwide update by the WHO stated 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 6,250 deaths."<ref>{{cite web |url=https://www.who.int/csr/don/2009_11_13/en/index.html |archive-url=https://web.archive.org/web/20091115071544/http://www.who.int/csr/don/2009_11_13/en/index.html |url-status=dead |archive-date=15 November 2009 |title=Pandemic (H1N1) 2009 – update 74 |date=13 November 2009 |work=Situation updates – Pandemic (H1N1) 2009 |publisher=World Health Organization |access-date=29 March 2011}}</ref>
==Influenza== {{Main|Influenza}} [[File:3D Influenza virus.png|thumb|400px|right|Structure of the influenza viron. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).]]
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.<ref name="amflu"/> 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, severe headache, coughing, and weakness and fatigue.<ref name=Merck>{{cite web |author=Merck Manual Home Edition |title=Influenza |url= https://www.merckmanuals.com/professional/infectious-diseases/respiratory-viruses/influenza|access-date=13 August 2020}}</ref> In more serious cases, influenza causes pneumonia, 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.<ref name=Eccles>{{cite journal | vauthors = Eccles R | title = Understanding the symptoms of the common cold and influenza | journal=The Lancet Infectious Diseases | volume = 5 | issue = 11 | pages = 718–25 | year = 2005 | pmid = 16253889 | doi = 10.1016/S1473-3099(05)70270-X | pmc = 7185637}}</ref> Although nausea and vomiting can be produced, especially in children,<ref name=Merck/> these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu."<ref>{{cite web | url = http://coldflu.about.com/od/flumisconceptions/f/stomachflu.htm | title = Seasonal Flu vs. Stomach Flu | vauthors = Duda K | access-date = 12 March 2007 | work = About, Inc., A part of The New York Times Company | archive-date = 7 July 2011 | archive-url = https://web.archive.org/web/20110707074827/http://coldflu.about.com/od/flumisconceptions/f/stomachflu.htm | url-status = dead }}</ref><ref>{{Cite web |title=Flu Symptoms 2025: What to Expect & How to Protect Yourself? |url=https://wellnessextract.com/blogs/wellness/flu-symptoms-2025-what-to-expect-and-how-to-protect-yourself |access-date=2025-02-18 |website=Wellness Extract USA |language=en}}</ref>
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. Influenza can also be transmitted by saliva, 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 {{convert|0|C|F}}, and indefinitely at very low temperatures (such as lakes in northeast Siberia). Most influenza strains can be inactivated easily by disinfectants and detergents.<ref>{{cite journal | vauthors = Suarez DL, Spackman E, Senne DA, Bulaga L, Welsch AC, Froberg K | title = The effect of various disinfectants on detection of avian influenza virus by real time RT-PCR | journal = Avian Diseases | volume = 47 | issue = 3 Suppl | pages = 1091–1095 | year = 2003 | pmid = 14575118 | doi = 10.1637/0005-2086-47.s3.1091 | s2cid = 8612187 }}</ref><ref>[http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html Avian Influenza (Bird Flu)]: Implications for Human Disease. Physical characteristics of influenza A viruses. UMN CIDRAP.</ref><ref name="NHZ2006-11-30"> {{cite news | url = https://www.nzherald.co.nz/technology/news/article.cfm?c_id=5&objectid=10413124 | title = Flu viruses 'can live for decades' on ice | date = 2006-11-30 | agency = Reuters | newspaper = The New Zealand Herald | access-date = 2011-10-04 | archive-url = https://web.archive.org/web/20190628201605/https://www.nzherald.co.nz/technology/news/article.cfm?c_id=5&objectid=10413124 | archive-date = 2019-06-28 | url-status = live}}</ref>
Flu spreads around the world in seasonal epidemics. Ten pandemics were recorded before the Spanish flu of 1918.<ref name="amflu"/> 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, so close proximity between humans and animals can promote epidemics. Additionally, the wartime practice of packing together the severely ill in field hospitals can promote the spread of more virulent strains of influenza when such people would otherwise be isolated from others during peacetime.<ref>{{Cite journal| vauthors = Copeland CS |date=Nov–Dec 2013|title=Deadliest Catch: Elusive, evolving flu difficult to predict|url=https://claudiacopeland.com/uploads/3/5/5/6/35560346/hjbr_deadliest_catch.pdf|journal=Healthcare Journal of Baton Rouge|pages=32–36}}</ref>
Vaccinations against influenza are most commonly given to high-risk humans in industrialized countries<ref name=WHOvaccines> {{cite journal | url=https://www.who.int/wer/2005/wer8033.pdf | title=Influenza vaccines: WHO position paper | journal=Weekly Epidemiological Record | date=19 August 2005 |volume=80 |issue=33 | pages=277–88}}</ref> and to farmed poultry.<ref>{{cite journal| vauthors = Villegas P| title = Viral diseases of the respiratory system| journal = Poultry Science| volume = 77| issue = 8| pages = 1143–45| date = August 1998| pmid = 9706079| doi = 10.1093/ps/77.8.1143| pmc = 7107121| url = http://ps.fass.org/cgi/reprint/77/8/1143| access-date = 4 November 2009| doi-access = free| archive-date = 18 April 2009| archive-url = https://web.archive.org/web/20090418043840/http://ps.fass.org/cgi/reprint/77/8/1143| url-status = dead}}</ref> 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 subtypes and one influenza B virus strain.<ref>{{cite journal |vauthors=Horwood F, Macfarlane J |title=Pneumococcal and influenza vaccination: current situation and future prospects |journal=Thorax |volume=57 |pages=II24–30 |year=2002 |issue=Suppl 2 |pmid=12364707 |pmc=1766003}}</ref> 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 drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.<ref>{{Cite web |last=CDC |date=2024-10-11 |title=Factors Influencing Flu Vaccine Effectiveness |url=https://www.cdc.gov/flu-vaccines-work/how-well/index.html |access-date=2025-02-18 |website=Flu Vaccines Work |language=en-us}}</ref>
==Variants and subtypes of ''Influenza A virus''== {{Main|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 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.<ref>{{Cite journal |date=12 September 2008 |title=The biology of influenza viruses |pmc=3074182 |journal=Vaccine |volume=26 |issue=Suppl 4 |pages=D49–D53 |doi=10.1016/j.vaccine.2008.07.039 |pmid=19230160 | vauthors = Bouvier NM, Palese P }}</ref> [[File:Influenza subtypes.svg|thumb|right|375px|The various types of influenza viruses in humans. Solid squares show the appearance of a new strain, causing recurring influenza pandemics. Broken lines indicate uncertain strain identifications.<ref name=Palese>{{cite journal | vauthors = Palese P |s2cid=1668689 |title=Influenza: old and new threats |journal=Nature Medicine |volume=10 |issue=12 Suppl |pages=S82–87 |date=December 2004 |pmid=15577936 |doi=10.1038/nm1141 |doi-access=free }}</ref>]]
Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. Some variants named using this convention are:<ref>See the articles for references that use these names.</ref> * Bird flu * Dog flu * Horse flu * Human flu * Swine 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 mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Frequently, a newer strain will completely replace an older strain.<ref>{{cite journal | vauthors = Palese P, Wang TT | title = Why do influenza virus subtypes die out? A hypothesis | journal = mBio | volume = 2 | issue = 5 | date = November 2011 | pmid = 21878571 | pmc = 3163940 | doi = 10.1128/mBio.00150-11 | doi-access = free}}</ref>
Because of the impact of avian influenza on economically important chicken farms, a classification system was devised in 1981 which divided avian virus strains as either highly pathogenic (and therefore potentially requiring vigorous control measures) or low pathogenic. The test for this is based solely on the effect on chickens - a virus strain is '''highly pathogenic avian influenza''' (HPAI) if 75% or more of chickens die after being deliberately infected with it. The alternative classification is '''low pathogenic avian influenza''' (LPAI).<ref name=":AA6">{{cite journal |last1=Alexander |first1=D. J. |last2=Brown |first2=I. H. |year=2009 |title=History of high pathogenic avian influenza |journal=Rev. Sci. Tech. |volume=28 |issue=1 |pages=19–38 |doi=10.20506/rst.28.1.1856 |pmid=19618616 |doi-access=}}</ref> This classification system has since been modified to take into account the structure of the virus' haemagglutinin protein.<ref>{{Cite web |date=2017-06-15 |title=Factsheet on A(H5N1) |url=https://www.ecdc.europa.eu/en/zoonotic-influenza/facts/factsheet-h5n1 |access-date=2024-05-21 |website=www.ecdc.europa.eu |language=en}}</ref> Other species of birds, especially water birds, can become infected with HPAI virus without experiencing severe symptoms and can spread the infection over large distances; the exact symptoms depend on the species of bird and the strain of virus.<ref name=":AA6" /> Classification of an avian virus strain as HPAI or LPAI does not predict how serious the disease might be if it infects humans or other mammals.<ref name=":AA6" /><ref>{{Cite web |last=CDC |date=2024-04-05 |title=Current U.S. Bird Flu Situation in Humans |url=https://www.cdc.gov/flu/avianflu/inhumans.htm |access-date=2024-05-22 |website=Centers for Disease Control and Prevention |language=en-us}}</ref>
==Nature of a flu pandemic== Some pandemics are relatively minor such as the one in 1957 called Asian flu (1–4 million dead, depending on source). Others have a higher Pandemic Severity Index whose severity warrants more comprehensive social isolation measures.<ref name=CIDRAP>{{cite web | url=http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/feb0107pandemic.html|access-date=3 February 2007|date=1 February 2007| vauthors = Roos R, Schnirring L |title=HHS ties pandemic mitigation advice to severity|publisher=University of Minnesota Center for Infectious Disease Research and Policy (CIDRAP)}}</ref>
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.<ref>{{cite book | editor-link = Institute of Medicine | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM | title = The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) | chapter= Chapter 1: The Story of Influenza: 1918 Revisited: Lessons and Suggestions for Further Inquiry | vauthors = Barry JM | publisher=The National Academies Press | year= 2005 | chapter-url = http://www.nap.edu/books/0309095042/html/62.html | isbn = 978-0-309-09504-4 | page = 62 | doi=10.17226/11150 | pmid=20669448 }} </ref> 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."<ref>{{cite book | editor-link = Institute of Medicine | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM | title = The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) | chapter= Chapter 1: The Story of Influenza: 1918 Revisited: Lessons and Suggestions for Further Inquiry | vauthors = Barry JM | publisher=The National Academies Press | year= 2005 | chapter-url = http://www.nap.edu/books/0309095042/html/66.html | isbn = 978-0-309-09504-4 | page = 66 | doi=10.17226/11150 | pmid=20669448 }}</ref>
A letter from a physician at one U.S. Army camp in the 1918 pandemic said:
<blockquote>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 [...].<ref>{{cite book | editor-link = Institute of Medicine | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM | title = The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) | chapter= Chapter 1: The Story of Influenza: 1918 Revisited: Lessons and Suggestions for Further Inquiry | vauthors = Barry JM | publisher=The National Academies Press | year= 2005 | chapter-url = http://www.nap.edu/books/0309095042/html/59.html | isbn = 978-0-309-09504-4 | page = 59 | doi=10.17226/11150 | pmid=20669448 }}</ref></blockquote>
===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. Within a wave, mortality was greater at the beginning of the wave.<ref name="Knobler">{{cite book |title=The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) |vauthors=Barry JM |publisher=The National Academies Press |year=2005 |isbn=978-0-309-09504-4 |veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM |pages=60–63 |chapter=Chapter 1: The Story of Influenza: 1918 Revisited: Lessons and Suggestions for Further Inquiry |doi=10.17226/11150 |pmid=20669448 |chapter-url=http://www.nap.edu/books/0309095042/html/60.html}}</ref>
===Variable mortality=== Mortality varies widely in a pandemic. In the 1918 pandemic:
<blockquote>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.<ref name="Knobler" /></blockquote>
==Influenza pandemics== A 1921 book lists nine influenza pandemics prior to the 1889–1890 flu, the first in 1510.<ref name="amflu">{{cite book | vauthors = St Mouritz AA |author-link1=Arthur Albert St. Mouritz |title='The Flu' A Brief World History of Influenza |date=1921 |publisher=Advertiser Publishing Co., Ltd. |location=Honolulu |url=http://www.gutenberg.org/ebooks/61607 |access-date=6 April 2020}}</ref> A more modern source lists six.<ref>{{cite journal | vauthors=Potter CW | title=A History of Influenza | journal=J Appl Microbiol |date=October 2006 |volume=91 |issue= 4 | pages = 572–79 | pmid = 11576290| doi=10.1046/j.1365-2672.2001.01492.x| doi-access=free }}</ref> {{Notable flu pandemics}} <!-- No preceding blank line. It introduces whitespace in page. Sigh. -->
=== Asiatic flu (1889–1890) === {{Main|1889–1890 pandemic}} The 1889–1890 pandemic, often referred to as the ''Asiatic flu''<ref name="Ryan_2008">{{cite book | vauthors = Ryan JR |chapter=Chapter 1 - Past Pandemics and Their Outcome | veditors = Ryan JR |title=Pandemic Influenza: Emergency Planning and Community Preparedness |date=2008 |publisher=CRC Press |isbn=978-1-42006088-1 |page=16 |chapter-url=https://books.google.com/books?id=t13C_eWhOX4C&pg=PA16 |quote=The Asiatic Flu of 1889-1890 was first reported in Bukhara, Russia}}</ref> or ''Russian flu'', killed about 1 million people<ref name="Shally-Jensen_2010">{{cite book |title=Encyclopedia of Contemporary American Social Issues |volume=2 |date=2010 | veditors = Shally-Jensen M |publisher=ABC-CLIO |isbn=978-0-31339205-4 |page=1510 |chapter-url=https://books.google.com/books?id=BjKWfAz0tx4C&pg=PA1510 |chapter=Influenza |quote=The Asiatic flu killed roughly one million individuals}}</ref><ref name="Williams_2015">{{cite web | vauthors = Williams MH, Preas MA |title=Influenza and Pneumonia Basics Facts and Fiction |date=2015 |url= https://dda.health.maryland.gov/Pages/Developments/2015/Influenza%20and%20Pneumonia%20Caring%20for%20patients%20in%20community.pdf |work=Maryland Department of Health - Developmental Disabilities Administration |publisher=University of Maryland |access-date=25 March 2020 |archive-url=https://web.archive.org/web/20171212211549/https://dda.health.maryland.gov/Pages/Developments/2015/Influenza%20and%20Pneumonia%20Caring%20for%20patients%20in%20community.pdf |archive-date=12 December 2017 |at=Pandemics |quote=Asiatic Flu 1889-1890 1 million}}</ref> out of a world population of about 1.5 billion. It was long believed to be caused by an influenza A subtype (most often H2N2), but recent analysis largely brought on by the 2002-2004 SARS outbreak and the COVID-19 pandemic determined the outbreak to be more likely caused by a coronavirus.<ref>{{Cite journal |last=Berche |first=Patrick |date=29 July 2023 |title=The enigma of the 1889 Russian flu pandemic: A coronavirus? |journal= La Presse Médicale|volume=51 |issue=3 |article-number=104111 |doi=10.1016/j.lpm.2022.104111 |pmid=35124103 |pmc=8813723 }}</ref>
===Spanish flu (1918–1920)=== {{Main|Spanish flu}}
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.
thumb|300px|right|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).<ref name = "Taubenberger">{{cite journal |vauthors = Taubenberger JK, Morens DM |title=1918 Influenza: the mother of all pandemics |journal=Emerging Infect. Dis. |volume=12 |issue=1 |pages=15–22 |year=2006 |pmid=16494711 |pmc=3291398 |doi=10.3201/eid1201.050979}}</ref>
The Spanish flu pandemic lasted from 1918 to 1920.<ref>{{cite book | vauthors = Price-Smith A | title = Contagion and Chaos | location = Cambridge, MA | publisher = MIT Press | date = 2009 }}</ref> Various estimates say it killed between 17 million and 100 million people<ref name=Patterson1>{{cite journal | vauthors = Patterson KD, Pyle GF | title = The geography and mortality of the 1918 influenza pandemic | journal = Bulletin of the History of Medicine | volume = 65 | issue = 1 | pages = 4–21 | year = 1991 | pmid = 2021692 }}</ref><ref name=Knobler/><ref name="pmid30202996">{{cite journal | vauthors = Spreeuwenberg P, Kroneman M, Paget J | title = Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic | journal = American Journal of Epidemiology | volume = 187 | issue = 12 | pages = 2561–67 | date = December 2018 | pmid = 30202996 | pmc = 7314216 | doi = 10.1093/aje/kwy191 | publisher = Oxford University Press }}</ref> This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death,<ref name=Potter>{{cite journal | vauthors = Potter CW | title = A history of influenza | journal = Journal of Applied Microbiology | volume = 91 | issue = 4 | pages = 572–9 | date = October 2001 | pmid = 11576290 | doi = 10.1046/j.1365-2672.2001.01492.x | doi-access = free }}</ref> although the Black Death is estimated to have killed over a fifth of the world's population at the time,<ref>{{cite web |url=https://www.census.gov/ipc/www/worldhis.html |title=Historical Estimates of World Population |publisher=Census.gov |access-date=3 November 2008 |archive-url=https://web.archive.org/web/20131013110506/http://www.census.gov/ipc/www/worldhis.html |archive-date=13 October 2013 |url-status=dead }}</ref> 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 storms.<ref name=Patterson1/> Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera, 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."<ref name=Knobler/> The majority of deaths were from bacterial pneumonia, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung.<ref name="pmid11779381">{{cite journal | vauthors = Taubenberger JK, Reid AH, Janczewski TA, Fanning TG | title = Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 356 | issue = 1416 | pages = 1829–39 | date = December 2001 | pmid = 11779381 | pmc = 1088558 | doi = 10.1098/rstb.2001.1020 }}</ref>
The Spanish flu pandemic was truly global, spreading even to the Arctic 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 of 0.1%.<ref name=Knobler/><ref name=Taubenberger/> 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.<ref>{{cite journal | vauthors = Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K | title = Pandemic versus epidemic influenza mortality: a pattern of changing age distribution | journal=J Infect Dis | volume = 178 | issue = 1 | pages = 53–60 |date=July 1998 | pmid = 9652423 | doi=10.1086/515616| citeseerx = 10.1.1.327.2581 }}</ref> 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''.<ref name=Knobler/>
===Asian flu (1957–1958)=== {{Main|1957–58 influenza pandemic}} 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 ducks combining with a pre-existing human strain.<ref name="Greene">{{cite book | vauthors = Greene J, Moline K | date = 2006 | title = Bird Flu Pandemic Can It Happen? Will It Happen? How to Protect Yourself and Your Family If It Does | publisher = St. Martin's Press | isbn = 978-1-4299-0486-5 }}</ref> The virus was first identified in Guizhou in late February; by mid-March it had spread across the entire mainland.<ref>{{cite book | vauthors = Goldsmith D | date = 2007 | title = Influenza: The Next Pandemic? | location = Minneapolis, MN | publisher = 21st Century Publishing | isbn = 978-0-7613-9457-0 }}</ref> 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.<ref name="Murray_1969">{{cite journal | vauthors = Murray R |date=1969 |title=Production and testing in the USA of influenza virus vaccine made from the Hong Kong variant in 1968-69 |journal=Bulletin of the World Health Organization |volume=41 |issue=3 |pages=495–496 |pmid=5309463 |pmc=2427701 |hdl=10665/262478}}</ref> The World Health Organization was officially informed when the virus arrived in Singapore, which operated the only influenza surveillance laboratory in Southeast Asia,<ref>{{cite journal | vauthors = Ziegler T, Mamahit A, Cox NJ | title = 65 years of influenza surveillance by a World Health Organization-coordinated global network | journal = Influenza and Other Respiratory Viruses | volume = 12 | issue = 5 | pages = 558–565 | date = September 2018 | pmid = 29727518 | pmc = 6086847 | doi = 10.1111/irv.12570 }}</ref> in early May.<ref name="Weekly Epidemiological Record_1957">{{Cite journal |date=10 May 1957 |title=Weekly Epidemiological Record, 1957, vol. 32, 19 |url=http://apps.who.int/iris/handle/10665/211021 |journal=Weekly Epidemiological Record |volume=19 |pages=231–244 |via=IRIS |hdl=10665/211021}}</ref> 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.<ref name="Gomes_1958">{{Cite journal | vauthors = Gomes C |date=6 August 2013 |orig-date=April 1958 |title=The work of WHO, 1957: annual report of the Director-General to the World Health Assembly and to the United Nations |url=http://apps.who.int/iris/handle/10665/85693 |journal=Official Records of the World Health Organization |via=IRIS |hdl=10665/85693|isbn=9789241600828 }}</ref>
This was the first pandemic to occur during what is considered the "era of modern virology".<ref>{{cite journal | vauthors = Kilbourne ED | title = Influenza pandemics of the 20th century | journal = Emerging Infectious Diseases | volume = 12 | issue = 1 | pages = 9–14 | date = January 2006 | pmid = 16494710 | pmc = 3291411 | doi = 10.3201/eid1201.051254 }}</ref> One significant development since the 1918 pandemic was the identification of the causative agent behind the flu.<ref>{{cite journal | vauthors = Taubenberger JK, Morens DM | title = Influenza: the once and future pandemic | journal = Public Health Reports | volume = 125 | issue = Suppl 3 | pages = 16–26 | date = April 2010 | pmid = 20568566 | pmc = 2862331 | doi = 10.1177/00333549101250S305 }}</ref> Later, it was recognized that the influenza virus changes over time, typically only slightly (a process called "antigenic drift"), sometimes significantly enough to result in a new subtype ("antigenic shift").<ref>{{Cite web | vauthors = Offit PA |title=Maurice R. Hilleman |url=http://www.nasonline.org/member-directory/deceased-members/54574.html |access-date=15 July 2022 |website=www.nasonline.org}}</ref> 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.<ref name="Proceedings of the Royal Society of Medicine_1958">{{Cite journal |date=1958-12-01 |title=Symposium on the Asian Influenza Epidemic, 1957 |journal=Proceedings of the Royal Society of Medicine |language=en |volume=51 |issue=12 |pages=1009–1018 |doi=10.1177/003591575805101205 |issn=0035-9157 |doi-access=free|pmc=1889875 }}</ref> Chinese researchers had already come to a similar conclusion in March,<ref name="Proceedings of the Royal Society of Medicine_1958" /> 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.<ref name="Gomes_1958" />
The virus swept across the Middle East, Africa, 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.<ref name="Proceedings of the Royal Society of Medicine_1958" /> Around this time, extensive epidemics developed in the Northern Hemisphere following the opening of schools, generally peaking in North America and Europe in October.<ref name="Eickhoff_1960">{{Cite conference | vauthors = Eickhoff TC |date=July 1960 |title=The Epidemiology of Asian Influenza, 1957-1960 |url=https://stacks.cdc.gov/view/cdc/7695 | conference = International Conference on Asian Influenza | location = Bethesda, MD. |via=CDC}}</ref> Some countries experienced a second wave in the final months of the year; Japan experienced a particularly severe resurgence in October.<ref name="Proceedings of the Royal Society of Medicine_1958" /><ref name="Eickhoff_1960" /> 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.<ref name="Proceedings of the Royal Society of Medicine_1958" />
The disease tended to resemble seasonal influenza in its presentation; the WHO described it at the time as "uniformly benign".<ref name="Proceedings of the Royal Society of Medicine_1958" /><ref name="Gomes_1958" /> However, there was the potential for complications, of which there was some variability.<ref>{{cite journal | vauthors = Burch GE, Walsh JJ, Mogabgab WJ | title = Asian influenza; clinical picture | journal = A.M.A. Archives of Internal Medicine | volume = 103 | issue = 5 | pages = 696–707 | date = May 1959 | pmid = 13636488 | doi = 10.1001/archinte.1959.00270050018005 }}</ref> 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.<ref name="Proceedings of the Royal Society of Medicine_1958" /><ref name="Louria_1959">{{cite journal | vauthors = Louria DB, Blumenfeld HL, Ellis JT, Kilbourne ED, Rogers DE | title = Studies on influenza in the pandemic of 1957-1958. II. Pulmonary complications of influenza | journal = The Journal of Clinical Investigation | volume = 38 | issue = 1 Part 2 | pages = 213–265 | date = January 1959 | pmid = 13620784 | pmc = 444127 | doi = 10.1172/JCI103791 }}</ref> There were also detailed accounts of fatal primary influenza pneumonia, with no indication of bacterial infection.<ref name="Louria_1959" /> Those with underlying conditions such as cardiovascular disease were at greater risk of developing these pneumonias; pregnant women were also vulnerable to complications.<ref name="Dauer_1958">{{cite journal | vauthors = Dauer CC | title = Mortality in the 1957-58 influenza epidemic | journal = Public Health Reports | volume = 73 | issue = 9 | pages = 803–810 | date = September 1958 | doi = 10.2307/4590246 | jstor = 4590246 | pmid = 13579118 | pmc = 1951613 }}</ref><ref name="Louria_1959" /> In general, the elderly experienced the greatest rates of mortality.<ref name="Dauer_1958" /> Estimates of worldwide deaths vary widely depending on the source, ranging from 1 million to 4 million.<ref name="WHO_2013">{{Cite web | date=2013|title=Pandemic Influenza Risk Management: WHO Interim Guidance|url=https://www.who.int/influenza/preparedness/pandemic/GIP_PandemicInfluenzaRiskManagementInterimGuidance_Jun2013.pdf?ua=1|url-status=live|archive-url=https://web.archive.org/web/20210121225326/https://www.who.int/influenza/preparedness/pandemic/GIP_PandemicInfluenzaRiskManagementInterimGuidance_Jun2013.pdf?ua=1|archive-date=2021-01-21|access-date=|website=World Health Organization|page=19}}</ref> Mortality in the US has been estimated between 60,000 and 80,000 deaths.<ref>{{cite journal | vauthors = Burney LE | title = Influenza immunization: Statement | journal = Public Health Reports | volume = 75 | issue = 10 | pages = 944 | date = October 1960 | pmid = 19316369 | pmc = 1929542 | doi = 10.2307/4590965 | jstor = 4590965 }}</ref><ref>{{cite journal | vauthors = Eickhoff TC, Sherman IL, Serfling RE | title = Observations on excess mortality associated with epidemic influenza | journal = JAMA | volume = 176 | issue = 9 | pages = 776–782 | date = June 1961 | pmid = 13726091 | doi = 10.1001/jama.1961.03040220024005 }}</ref><ref>{{cite journal | vauthors = Housworth J, Langmuir AD | title = Excess mortality from epidemic influenza, 1957-1966 | journal = American Journal of Epidemiology | volume = 100 | issue = 1 | pages = 40–48 | date = July 1974 | pmid = 4858301 | doi = 10.1093/oxfordjournals.aje.a112007 }}</ref><ref name="Dauer_1958" /> Pandemic impact continued over several years in many countries, with Latin America experiencing considerable excess mortality through 1959.<ref>{{cite journal | vauthors = Viboud C, Simonsen L, Fuentes R, Flores J, Miller MA, Chowell G | title = Global Mortality Impact of the 1957-1959 Influenza Pandemic | journal = The Journal of Infectious Diseases | volume = 213 | issue = 5 | pages = 738–745 | date = March 2016 | pmid = 26908781 | pmc = 4747626 | doi = 10.1093/infdis/jiv534 }}</ref> Chile experienced notably severe mortality over the course of two waves during this period.<ref>{{cite journal | vauthors = Chowell G, Simonsen L, Fuentes R, Flores J, Miller MA, Viboud C | title = Severe mortality impact of the 1957 influenza pandemic in Chile | journal = Influenza and Other Respiratory Viruses | volume = 11 | issue = 3 | pages = 230–239 | date = May 2017 | pmid = 27883281 | pmc = 5410718 | doi = 10.1111/irv.12439 }}</ref>
This was the most publicized influenza epidemic at the time of its occurrence.<ref>{{cite journal | vauthors = Shope RE | title = Influenza: history, epidemiology, and speculation | journal = Public Health Reports | volume = 73 | issue = 2 | pages = 165–178 | date = February 1958 | pmid = 13506005 | pmc = 1951634 | doi = 10.2307/4590072 | jstor = 4590072 }}</ref> 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.<ref name="Proceedings of the Royal Society of Medicine_1958" /><ref>{{cite journal | vauthors = Trotter Y, Dunn FL, Drachman RH, Henderson DA, Pizzi M, Langmuir AD | title = Asian influenza in the United States, 1957-1958 | journal = American Journal of Hygiene | volume = 70 | issue = 1 | pages = 34–50 | date = July 1959 | pmid = 13670166 | doi = 10.1093/oxfordjournals.aje.a120063 }}</ref> 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.<ref name="Gomes_1958" /><ref>{{cite journal | vauthors = Murray R | title = Production and testing in the USA of influenza virus vaccine made from the Hong Kong variant in 1968-69 | journal = Bulletin of the World Health Organization | volume = 41 | issue = 3 | pages = 495–496 | date = 1969 | pmid = 5309463 | pmc = 2427701 }}</ref>
===Hong Kong flu (1968–1970)=== {{Main|Hong Kong flu}} The Hong Kong flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift, in which genes from multiple subtypes reassorted to form a new virus. This pandemic killed an estimated 1–4 million people worldwide.<ref name="WHO_2013" /><ref>{{cite book| vauthors = Paul WE |title=Fundamental Immunology|page=1273|url=https://books.google.com/books?id=oPSG1PGmZUkC|isbn=978-0-306-44407-4|year=1993|publisher=Plenum Press|location=New York}}</ref><ref>{{cite news | url = http://archive.jsonline.com/news/usandworld/43705182.html/ | title = World health group issues alert Mexican president tries to isolate those with swine flu | date = 2009-04-25 | publisher = Associated Press | access-date = 2009-04-26 | archive-url = https://web.archive.org/web/20200324123728/http://archive.jsonline.com/news/usandworld/43705182.html/ | archive-date = 24 March 2020 | url-status = dead }}</ref> Those over 65 had the greatest death rates.<ref name="news.bbc.co.uk">{{cite news |date=27 April 2009 |title=Asia on high alert for flu virus |publisher=BBC News |url=https://news.bbc.co.uk/1/hi/world/americas/8019907.stm |access-date=5 May 2010}}</ref> In the US, there were about 100,000 deaths.<ref>{{cite web | title = 1968 Pandemic (H3N2 virus) | work = Centers for Disease Control and Prevention | publisher = U.S. Department of Health & Human Services | url = https://www.cdc.gov/flu/pandemic-resources/1968-pandemic.html | archive-url = https://web.archive.org/web/20190130020732/https://www.cdc.gov/flu/pandemic-resources/1968-pandemic.html | archive-date = 30 January 2019 }}</ref>
=== Russian flu (1977–1979) === {{Main|1977 Russian flu}} The 1977 Russian flu was a relatively benign flu pandemic, mostly affecting population younger than the age of 26 or 25.<ref name="World Health Organization_1999">{{Cite web|date=April 1999|title=Influenza Pandemic Plan. The Role of WHO and Guidelines for National and Regional Planning|url=https://www.who.int/csr/resources/publications/influenza/whocdscsredc991.pdf|url-status=live|archive-url=https://web.archive.org/web/20201203084733/https://www.who.int/csr/resources/publications/influenza/whocdscsredc991.pdf|archive-date=2020-12-03|website=World Health Organization|pages=38, 41}}</ref><ref name="Rozo_2015">{{cite journal | vauthors = Rozo M, Gronvall GK | title = The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate | journal = mBio | volume = 6 | issue = 4 | date = August 2015 | pmid = 26286690 | pmc = 4542197 | doi = 10.1128/mBio.01013-15 | doi-access = free}}</ref> It is estimated that 700,000 people died due to the pandemic worldwide.<ref name="Michaelis_2009">{{cite journal | vauthors = Michaelis M, Doerr HW, Cinatl J | title = Novel swine-origin influenza A virus in humans: another pandemic knocking at the door | journal = Medical Microbiology and Immunology | volume = 198 | issue = 3 | pages = 175–83 | date = August 2009 | pmid = 19543913 | doi = 10.1007/s00430-009-0118-5 | s2cid = 20496301 | doi-access = free }}</ref> The cause was H1N1 virus strain, which was not seen after 1957 until its re-appearance in China and the Soviet Union in 1977.<ref name="Rozo_2015a">{{cite journal | vauthors = Rozo M, Gronvall GK | title = The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate | journal = mBio | volume = 6 | issue = 4 | date = August 2015 | pmid = 26286690 | pmc = 4542197 | doi = 10.1128/mBio.01013-15 | doi-access = free}}</ref><ref name="Rozo_2015" /><ref name="Mermel_2009">{{cite journal | vauthors = Mermel LA | title = Swine-origin influenza virus in young age groups | language = English | journal = Lancet | volume = 373 | issue = 9681 | pages = 2108–9 | date = June 2009 | pmid = 19541030 | doi = 10.1016/S0140-6736(09)61145-4 | s2cid = 27656702 | url = https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61145-4/abstract | url-access = subscription }}</ref> Genetic analysis and several unusual characteristics of the pandemic have prompted speculation that the virus was released to the public through a laboratory accident.<ref name="Rozo_2015" /><ref name="Wertheim_2010">{{cite journal | vauthors = Wertheim JO | title = The re-emergence of H1N1 influenza virus in 1977: a cautionary tale for estimating divergence times using biologically unrealistic sampling dates | journal = PLOS ONE | volume = 5 | issue = 6 | article-number = e11184 | date = June 2010 | pmid = 20567599 | pmc = 2887442 | doi = 10.1371/journal.pone.0011184 | bibcode = 2010PLoSO...511184W | doi-access = free }}</ref><ref name="Furmanski_2015">{{cite journal | vauthors = Furmanski M | title = The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards | journal = mBio | volume = 6 | issue = 5 | article-number = e01434-15 | date = September 2015 | pmid = 26419881 | pmc = 4611044 | doi = 10.1128/mBio.01434-15 | doi-access = free}}</ref><ref name="Zimmer_2009">{{cite journal | vauthors = Zimmer SM, Burke DS | title = Historical perspective--Emergence of influenza A (H1N1) viruses | journal = The New England Journal of Medicine | volume = 361 | issue = 3 | pages = 279–85 | date = July 2009 | pmid = 19564632 | doi = 10.1056/NEJMra0904322 | doi-access = free }}</ref><ref name="Nolan_2009">{{Cite web| vauthors = Nolan T |date=2009-07-02|title=Was H1N1 leaked from a laboratory?|url=https://blogs.bmj.com/bmj/2009/07/02/tom-nolan-was-h1n1-leaked-from-a-laboratory/|access-date=2021-01-24|website=The BMJ|language=en-US}}</ref>{{citation overkill|date=June 2022}}
===H1N1/09 flu pandemic (2009–2010)=== {{Main|2009 flu pandemic}} 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.<ref>{{cite web |url=https://www.who.int/csr/don/2009_05_03/en/index.html |archive-url=https://web.archive.org/web/20090503110831/http://www.who.int/csr/don/2009_05_03/en/index.html |url-status=dead |archive-date=3 May 2009 |title=Influenza A (H1N1) – update 11 |publisher=WHO}}</ref>
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.<ref>{{cite news |url=https://www.google.com/hostednews/ap/article/ALeqM5jTkkEKE5LtPih_5Jcc-3MpD0gOYQD98OH0U00 |title=WHO: Swine flu pandemic has begun, 1st in 41 years |date=11 June 2009 |access-date=11 June 2009 |publisher=Associated Press |url-status=dead |archive-url=https://web.archive.org/web/20090614173823/https://www.google.com/hostednews/ap/article/ALeqM5jTkkEKE5LtPih_5Jcc-3MpD0gOYQD98OH0U00 |archive-date=14 June 2009 }}</ref> 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).<ref name="NewSci-20090424-pandemic">{{cite news |url=https://www.newscientist.com/article/dn17025-deadly-new-flu-virus-in-us-and-mexico-may-go-pandemic.html |title=Deadly new flu virus in U.S. and Mexico may go pandemic |work=New Scientist |date=28 April 2009 |access-date=28 April 2009 |archive-url=https://web.archive.org/web/20090426045144/http://www.newscientist.com/article/dn17025-deadly-new-flu-virus-in-us-and-mexico-may-go-pandemic.html |archive-date=26 April 2009 |url-status=dead}}</ref> The rapid spread of this new virus was likely due to a general lack of pre-existing antibody-mediated immunity in the human population.<ref>{{cite journal | vauthors = Greenbaum JA, Kotturi MF, Kim Y, Oseroff C, Vaughan K, Salimi N, Vita R, Ponomarenko J, Scheuermann RH, Sette A, Peters B | title = Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 48 | pages = 20365–70 | date = December 2009 | pmid = 19918065 | pmc = 2777968 | doi = 10.1073/pnas.0911580106 | author10-link = Alessandro Sette | bibcode = 2009PNAS..10620365G | doi-access = free }}</ref>
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."<ref>[https://web.archive.org/web/20091017165051/http://www.who.int/csr/don/2009_10_16/en/index.html Pandemic (H1N1) 2009 – update 70], "As of 1 November 2009 [...] Laboratory-confirmed cases of the pandemic influenza H1N1 as officially reported to the WHO by States Parties to the International Health Regulations (2005)". Also see the WHO page [https://web.archive.org/web/20090502163440/http://www.who.int/csr/disease/swineflu/updates/en/ Situation updates – Pandemic (H1N1) 2009], which has clickable links for all 70 updates, starting with the initial report of 24 April 2009.</ref> By the end of the pandemic, declared on 10 August 2010, there were more than 18,000 laboratory-confirmed deaths from H1N1.<ref>{{cite news|title=WHO Declares Official End to H1N1 'Swine Flu' Pandemic| vauthors = Enserink M |url=https://www.science.org/content/article/who-declares-official-end-h1n1-swine-flu-pandemic|newspaper=Science Insider|date=10 August 2010|access-date=7 June 2013}}</ref> 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.<ref name="CDC 2012">{{cite web|url=https://www.cdc.gov/flu/spotlights/pandemic-global-estimates.htm|title=First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration|date=25 June 2012|publisher=Centers for Disease Control and Prevention (CDC)|access-date=7 July 2012}}</ref><ref>{{cite journal |vauthors=Dawood FS, Iuliano AD, Reed C, etal |title=Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study |journal=Lancet Infect Dis |volume=12 |issue=9 |pages=687–95 |date=September 2012 |pmid=22738893 |doi=10.1016/S1473-3099(12)70121-4 |url=https://zenodo.org/record/1260250 }}</ref>
==Other pandemic threat subtypes== "Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans.<ref>{{cite web | title = Key Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus | url = https://www.cdc.gov/flu/avian/gen-info/facts.htm | publisher = CDC | archive-url = https://web.archive.org/web/20050316034306/http://www.cdc.gov/flu/avian/gen-info/facts.htm | archive-date = 2005-03-16 | url-status = dead}}</ref>
Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include: :'''PB2''': (RNA polymerase): Amino acid (or residue) position 627 in the PB2 protein encoded by the PB2 RNA gene. Until H5N1, all known avian influenza viruses had a glutamic acid at position 627, while all human influenza viruses had a lysine.<ref>{{Cite journal |date=12 September 2006 |title=Genomic Signatures of Human versus Avian Influenza A Viruses |pmc=3294750 |journal=Emerging Infectious Diseases |volume=12 |issue=9 |pages=1353–1360 |doi=10.3201/eid1209.060276 |pmid=17073083 | vauthors = Chen GW, Chang SC, Mok CK, Lo YL, Kung YN, Huang JH, Shih YH, Wang JY, Chiang C, Chen CJ, Shih SR }}</ref> :'''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."<ref>{{cite news | title = Scientists Move Closer to Understanding Flu Virus Evolution | date = 2006-08-28 | url = https://www.bloomberg.com/apps/news?pid=20601086&sid=a6S3ZQwqZkS4&refer=latin_america | work = Bloomberg News | archive-url = https://web.archive.org/web/20070930063009/http://www.bloomberg.com/apps/news?pid=20601086&sid=a6S3ZQwqZkS4&refer=latin_america | archive-date = 2007-09-30 | url-status = dead}}</ref> "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."<ref name="ChenChang2006">{{cite journal | vauthors = Chen GW, Chang SC, Mok CK, Lo YL, Kung YN, Huang JH, Shih YH, Wang JY, Chiang C, Chen CJ, Shih SR | title = Genomic signatures of human versus avian influenza A viruses | journal = Emerging Infectious Diseases | volume = 12 | issue = 9 | pages = 1353–60 | date = September 2006 | pmid = 17073083 | pmc = 3294750 | doi = 10.3201/eid1209.060276 | doi-access = free }}</ref>
Highly pathogenic H5N1 avian influenza kills 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms.<ref> {{cite journal|vauthors=de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VV, Tran TH, Do QH, Farrar J | title = Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma| journal=N. Engl. J. Med.| volume = 352| issue = 7| pages = 686–91| date = 17 February 2005| doi = 10.1056/NEJMoa044307| pmid = 15716562 | doi-access = free}}</ref>
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:<ref>{{Cite web |title=The burden of Influenza |url=https://www.who.int/news-room/feature-stories/detail/the-burden-of-influenza |access-date=2025-02-18 |website=www.who.int |language=en}}</ref> * H1N1 caused Spanish flu, 1977 Russian flu, and the 2009 swine flu pandemic (novel H1N1) * H2N2 caused Asian flu * H3N2 caused Hong Kong flu * H5N1 is bird flu, endemic in avians * H7N7 has unusual zoonotic potential * H1N2 is currently endemic in humans and pigs * H9N2, H7N2, H7N3, H10N7
;H1N1 {{main|H1N1|Pandemic H1N1/09 virus}} {{further|2009 swine flu pandemic}}
{{external media | float = right | width = | image1 = [https://web.archive.org/web/20100216055535/http://imgs.sfgate.com/blogs/images/sfgate/ybenjamin/2009/10/01/B00528_H1N1_flu_blue_med-1325x382.jpg Microscopic image of the H1N1 virus] | image2 = [https://newsimg.bbc.co.uk/media/images/46648000/jpg/_46648957_swineflu.jpg Microscopic image of the H1N1 virus] }}
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.<ref>[http://www.nap.edu/books/0309095042/html/7.html "The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)"] The National Academies Press, p. 7</ref> 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.<ref>{{cite book | year = 2010 | url = https://books.google.com/books?id=UsyvAwAAQBAJ&pg=PA185 | title = Plagues and Epidemics: Infected Spaces Past and Present | edition = 1st | veditors = Herring DA, Swedlund AC | publisher = Routledge | isbn = 978-1847885487 | page = 185 | series = Wenner-Gren International Symposium Series }}</ref>
<blockquote>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.<ref>[https://www.nytimes.com/2005/11/08/science/08flu.html "Hazard in Hunt for New Flu: Looking for Bugs in All the Wrong Places"]. ''The New York Times'', 8 November 2005.</ref></blockquote>
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.<ref>{{cite news| url=https://news.bbc.co.uk/1/hi/world/americas/8025931.stm |publisher=BBC News | title=WHO fears pandemic is 'imminent' | date=30 April 2009 | access-date=5 May 2010}}</ref> 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.<ref>{{cite news| url=https://news.bbc.co.uk/2/hi/health/8094655.stm |publisher=BBC News | title=WHO declares swine flu pandemic | date=11 June 2009 | access-date=5 May 2010}}</ref> 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."<ref>{{Cite web | url = https://www.who.int/csr/don/2009_11_13/en/ | title = Pandemic (H1N1) 2009 - update 74 | archive-url = https://web.archive.org/web/20200510095620/https://www.who.int/csr/don/2009_11_13/en/ | archive-date = 2020-05-10 | url-status = dead}}</ref>
;H2N2 {{Main|H2N2}} The Asian Flu 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.<ref>{{Cite web |title=Asian Flu (1957 Influenza Pandemic) |url=https://www.sinobiological.com/research/virus/1957-influenza-pandemic-asian-flu |access-date=18 February 2025 |website=SinoBiological}}</ref>
;H3N2 {{Main|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.<ref>Detailed chart of its evolution [http://www.eletrica.ufsj.edu.br/~nepomuceno/references/epidemiology/ear_eal02.pdf here] at PDF called ''Ecology and Evolution of the Flu'' {{webarchive |url=https://web.archive.org/web/20090509025529/http://www.eletrica.ufsj.edu.br/~nepomuceno/references/epidemiology/ear_eal02.pdf |date=9 May 2009 }}</ref>"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."<ref>[http://www.nap.edu/books/0309095042/html/115.html "The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005)"] The National Academies Press, p. 115 – "There is particular pressure to recognize and heed the lessons of past influenza pandemics in the shadow of the worrisome 2003–2004 flu season. 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. As a result, stronger than usual demand for annual flu inactivated vaccine outstripped the vaccine supply, of which 10 to 20 percent typically goes unused. Because statistics on pediatric flu deaths had not been collected previously, it is unknown if the 2003–2004 season witnessed a significant change in mortality patterns."</ref>
The dominant strain of annual flu in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.<ref>[http://www.reason.com/rb/rb101905.shtml Reason] {{webarchive|url=https://web.archive.org/web/20061026092508/http://www.reason.com/rb/rb101905.shtml |date=26 October 2006 }} [https://www.nytimes.com/2006/01/15/health/15drugs.html ''This Season's Flu Virus Is Resistant to 2 Standard Drugs''] By Altman LK, The New York Times, Published: 15 January 2006</ref>
<blockquote>[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.<ref>[http://www.nap.edu/books/0309095042/html/126.html "The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) "] The National Academies Press, p. 126</ref></blockquote>
;H7N7 {{Main|H7N7}} H7N7 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 {{Main|H1N2}} H1N2 is currently endemic in both human and pig populations. The new H1N2 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 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.
=== Severity === {{see also|Pandemic#Severity|Pandemic Severity Assessment Framework}}
{{ multiple image | align = right | direction = horizontal
| image1 = Model of Influenza Deaths in 2010 US Population.jpg | caption1 = Estimates of hypothetical influenza deaths in the 2010 United States population (308,745,538 persons) across varying values of case-fatality ratio and the cumulative incidence of infection in the population. Selected estimated numbers of deaths are indicated with a black line, across each relevant combination of case-fatality ratio and cumulative incidence. In addition, the background color transitions from blue to yellow to red as the estimated absolute number of deaths increases. Case-fatality ratio is an example of a clinical severity measure and cumulative incidence of infection is an example of a transmissibility measure in the Pandemic Severity Assessment Framework.<ref name="Reed2013"/>
| image2 = Past Influenza Outbreaks on the Pandemic Severity Assessment Framework.jpg | caption2 = Scaled examples of past influenza pandemics and past influenza seasons. Color scheme included to represent corresponding hypothetical estimates of influenza deaths in the 2010 US population, with the same color scale as the previous figure.<ref name="Reed2013"/> }}
In 2014, the CDC adopted the Pandemic Severity Assessment Framework (PSAF) to assess the severity of pandemics.<ref name="Holloway2014">{{cite journal |vauthors=Holloway R, Rasmussen SA, Zaza S, Cox NJ, Jernigan DB |date=September 2014 |title=Updated preparedness and response framework for influenza pandemics |url=https://www.cdc.gov/flu/pandemic-resources/pdf/mmwr-rr6306.pdf |journal=MMWR. Recommendations and Reports |publisher=Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention |volume=63 |issue=RR-06 |pages=1–18 |pmid=25254666 |access-date=10 May 2020}}</ref> The PSAF superseded the 2007 linear Pandemic Severity Index, which assumed 30% spread and measured case fatality rate (CFR) to assess the severity and evolution of the pandemic.<ref name="Qualls2017">{{cite journal | vauthors = Qualls N, Levitt A, Kanade N, Wright-Jegede N, Dopson S, Biggerstaff M, Reed C, Uzicanin A | title = Community Mitigation Guidelines to Prevent Pandemic Influenza - United States, 2017 | language = en-us | journal = MMWR. Recommendations and Reports | volume = 66 | issue = 1 | pages = 1–34 | date = April 2017 | pmid = 28426646 | pmc = 5837128 | doi = 10.15585/mmwr.rr6601a1 | url = https://www.cdc.gov/mmwr/volumes/66/rr/pdfs/rr6601.pdf | publisher = Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention | doi-access = free }}</ref>
Historically, measures of pandemic severity were based on the case fatality rate.<ref name="CDC2007">{{cite book |title=Interim Pre-Pandemic Planning Guidance: Community Strategy for Pandemic Influenza Mitigation in the United States |url=https://www.cdc.gov/flu/pandemic-resources/pdf/community_mitigation-sm.pdf |publisher=Centers for Disease Control and Prevention |page=9 |date=February 2007}}</ref> However, the case fatality rate might not be an adequate measure of pandemic severity during a pandemic response because:<ref name="Reed2013"/> * 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<ref name="Rajgor2020">{{cite journal | vauthors = Rajgor DD, Lee MH, Archuleta S, Bagdasarian N, Quek SC | title = The many estimates of the COVID-19 case fatality rate | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 7 | pages = 776–777 | date = July 2020 | pmid = 32224313 | pmc = 7270047 | doi = 10.1016/S1473-3099(20)30244-9 | publisher = Elsevier Ltd. | doi-access = free }}</ref> * 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.<ref name="Reed2013">{{cite journal | vauthors = Reed C, Biggerstaff M, Finelli L, Koonin LM, Beauvais D, Uzicanin A, Plummer A, Bresee J, Redd SC, Jernigan DB | title = Novel framework for assessing epidemiologic effects of influenza epidemics and pandemics | journal = Emerging Infectious Diseases | volume = 19 | issue = 1 | pages = 85–91 | date = January 2013 | pmid = 23260039 | pmc = 3557974 | doi = 10.3201/eid1901.120124 }}</ref> 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 == {{see also|Pandemic#Management}}
=== Assessment === 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. This included a classification system for assessing the progress of an outbreak. 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.<ref>{{Cite book |date=2009 |title=Pandemic influenza preparedness and response: a WHO guidance document |url=https://apps.who.int/iris/bitstream/handle/10665/44123/9789241547680_eng.pdf |access-date=17 August 2023 |pages=24–27 |publisher=World Health Organization |isbn=978-92-4-154768-0}}</ref> In February 2020, WHO announced that it 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."<ref>{{Cite news |date=2020-02-24 |title=WHO says it no longer uses 'pandemic' category, but virus still emergency |language=en |work=Reuters |url=https://www.reuters.com/article/uk-china-health-who-idUKKCN20I0PD |access-date=2020-02-29}}</ref> thumb|Influenza intervals in the CDC's Pandemic Intervals Framework In 2014, the United States Centers for Disease Control and Prevention (CDC) introduced the '''Pandemic Intervals Framework''' for assessing influenza outbreaks.<ref name="Holloway20142">{{cite journal |vauthors=Holloway R, Rasmussen SA, Zaza S, Cox NJ, Jernigan DB |date=September 2014 |title=Updated preparedness and response framework for influenza pandemics |url=https://www.cdc.gov/flu/pandemic-resources/pdf/mmwr-rr6306.pdf |journal=MMWR. Recommendations and Reports |publisher=Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention |volume=63 |issue=RR-06 |pages=1–18 |pmid=25254666 |access-date=10 May 2020}}</ref> It includes two pre-pandemic intervals: -
* Investigation * Recognition
and four pandemic intervals,
* Initiation * Acceleration * Deceleration * Preparation<ref>{{Cite web |date=January 2013 |title=Pandemic Severity Assessment Framework (PSAF) {{!}} Pandemic Influenza (Flu) |url=https://www.cdc.gov/flu/pandemic-resources/national-strategy/severity-assessment-framework.html |access-date=2023-08-17 |website=Centers for Disease Control and Prevention |language=en-us}}</ref><ref>{{cite journal | vauthors = Reed C, Biggerstaff M, Finelli L, Koonin LM, Beauvais D, Uzicanin A, Plummer A, Bresee J, Redd SC, Jernigan DB | title = Novel framework for assessing epidemiologic effects of influenza epidemics and pandemics | language = en-us | journal = Emerging Infectious Diseases | volume = 19 | issue = 1 | pages = 85–91 | date = January 2013 | pmid = 23260039 | pmc = 3557974 | doi = 10.3201/eid1901.120124 }}</ref>
=== Strategies to prevent a flu pandemic === This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations panel.<ref name="The Threat of Global Pandemics">{{cite web | collaboration = Council on Foreign Relations | vauthors = Osterholm M, Colwell R, Garrett L, Fauci AS, Hoge JF, Roman NE | title = The Threat of Global Pandemics | publisher = Council on Foreign Relations | date = 16 June 2005 | location = Washington, DC | url = http://www.cfr.org/pub8198/laurie_garrett_anthony_s_fauci_michael_osterholm_rita_colwell/the_threat_of_global_pandemics.php | access-date = 13 September 2006 | archive-url = https://web.archive.org/web/20081013053617/http://www.cfr.org/pub8198/laurie_garrett_anthony_s_fauci_michael_osterholm_rita_colwell/the_threat_of_global_pandemics.php | archive-date = 13 October 2008 | url-status = dead}}</ref>
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:{{cn|date=June 2022}} * Culling and vaccinating livestock * Vaccinating poultry workers against common flu * Limiting travel in areas where the virus is found<ref name="The Threat of Global Pandemics"/>
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 availability and cost.<ref name="The Threat of Global Pandemics"/>
===Strategies to slow down a flu pandemic=== {{See also|Flu research}}
====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.<ref>{{cite journal | vauthors = Rubin GJ, Bakhshi S, Amlôt R, Fear N, Potts HW, Michie S | year = 2014| title = The design of a survey questionnaire to measure perceptions and behaviour during an influenza pandemic: the Flu TElephone Survey Template (FluTEST) | journal = Health Services and Delivery Research| volume = 2| issue = 41| pages = 1–126| doi = 10.3310/hsdr02410 | pmid = 25642523| doi-access = free}}</ref> * '''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.<ref name="WHO-What-can-I-do">{{cite web | title = Pandemic (H1N1) 2009: frequently asked questions: What can I do? | publisher=World Health Organization |date=January 2010 | url =https://www.who.int/csr/disease/swineflu/frequently_asked_questions/what/en/index.html | archive-url =https://web.archive.org/web/20090501210730/http://www.who.int/csr/disease/swineflu/frequently_asked_questions/what/en/index.html | url-status =dead | archive-date =1 May 2009 | access-date = 28 February 2010 }}</ref> However, social distancing during a pandemic flu will likely carry severe mental health consequences; therefore, sequestration protocols should take mental health issues into consideration.<ref>{{cite journal | vauthors = Douglas PK |title=Preparing for pandemic influenza and its aftermath: Mental health issues considered |journal=International Journal of Emergency Mental Health |date=2009 |volume=11 |issue=3 |pages=137–44 |pmid=20437844 |ref=ISSN 1522-4821}}</ref> * '''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.<ref name="WHO-What-can-I-do" /> * '''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.)<ref>{{cite web | title = Stop Germs, Stay Healthy! | publisher=King County, Washington, web site | url = http://www.metrokc.gov/health/stopgerms/index.htm | access-date = 13 September 2006 |archive-url=https://web.archive.org/web/20050205163024/http://www.metrokc.gov/health/stopgerms/index.htm|archive-date=5 February 2005}}</ref> * '''Other hygiene:''' Avoid touching your eyes, nose and mouth as much as possible.<ref name="WHO-What-can-I-do" /> * '''Masks:''' 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 and that patients wear surgical masks (which may prevent respiratory secretions from becoming airborne).<ref name="non-pharm-interven">{{cite web|title=Non-pharmaceutical interventions: their role in reducing transmission and spread |publisher=World Health Organization |date=November 2006 |url=https://www.who.int/csr/disease/avian_influenza/pharmaintervention2005_11_3/en/index.html |access-date=13 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060920002731/http://www.who.int/csr/disease/avian_influenza/pharmaintervention2005_11_3/en/index.html |archive-date=20 September 2006 }}</ref> 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."<ref>{{cite book | last = Committee on Modeling Community Containment for Pandemic Influenza | title = Modeling Community Containment for Pandemic Influenza: A Letter Report | page = 47 | publisher = The National Academies Press | date = 11 December 2006 | isbn = 978-0-309-66819-4 | url = http://www.iom.edu/?id=39066 | access-date = 6 May 2009 | archive-date = 26 May 2011 | archive-url = https://web.archive.org/web/20110526110838/http://www.iom.edu/?id=39066 | url-status = dead }}</ref>
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'',<ref>{{Cite web | url=http://www.iom.edu/Reports/2011/Preventing-Transmission-of-Pandemic-Influenza-and-Other-Viral-Respiratory-Diseases.aspx | archive-url=https://web.archive.org/web/20110526192606/http://www.iom.edu/Reports/2011/Preventing-Transmission-of-Pandemic-Influenza-and-Other-Viral-Respiratory-Diseases.aspx | url-status=dead | archive-date=26 May 2011 |title = Preventing Transmission of Pandemic Influenza and Other Viral Respiratory Diseases: Personal Protective Equipment for Healthcare Personnel Update 2010}}</ref> 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.<ref>{{cite journal | vauthors = Caress AL, Duxbury P, Woodcock A, Luker KA, Ward D, Campbell M, Austin L | title = Exploring the needs, concerns and behaviours of people with existing respiratory conditions in relation to the H1N1 'swine influenza' pandemic: a multicentre survey and qualitative study | journal = Health Technology Assessment | volume = 14 | issue = 34 | pages = 1–108 | date = July 2010 | pmid = 20630122 | doi = 10.3310/hta14340-01 | doi-access = free }}</ref><ref>Yates et al., 2010</ref><ref>{{cite journal | vauthors = Rubin GJ, Potts HW, Michie S | title = The impact of communications about swine flu (influenza A H1N1v) on public responses to the outbreak: results from 36 national telephone surveys in the UK | journal = Health Technology Assessment | volume = 14 | issue = 34 | pages = 183–266 | date = July 2010 | pmid = 20630124 | doi = 10.3310/hta14340-03 | doi-access = free }}</ref><ref name="pmid20630125">{{cite journal | vauthors = Eames KT, Tilston NL, White PJ, Adams E, Edmunds WJ | title = The impact of illness and the impact of school closure on social contact patterns | journal = Health Technology Assessment | volume = 14 | issue = 34 | pages = 267–312 | date = July 2010 | pmid = 20630125 | doi = 10.3310/hta14340-04 | doi-access = free }}</ref><ref name="pmid20630126">{{cite journal | vauthors = Simpson CR, Ritchie LD, Robertson C, Sheikh A, McMenamin J | title = Vaccine effectiveness in pandemic influenza - primary care reporting (VIPER): an observational study to assess the effectiveness of the pandemic influenza A (H1N1)v vaccine | journal = Health Technology Assessment | volume = 14 | issue = 34 | pages = 313–46 | date = July 2010 | pmid = 20630126 | doi = 10.3310/hta14340-05 | doi-access = free }}</ref> Asymptomatic transmission appears to play a small role, but was not well studied by 2009.<ref>{{cite journal | vauthors = Patrozou E, Mermel LA | title = Does influenza transmission occur from asymptomatic infection or prior to symptom onset? | journal = Public Health Reports | volume = 124 | issue = 2 | pages = 193–6 | date = March 2009 | pmid = 19320359 | pmc = 2646474 | doi = 10.1177/003335490912400205 | quote = scant, if any, evidence that asymptomatic or presymptomatic individuals play an important role in influenza transmission. More definitive transmission studies are sorely needed. }}</ref>
====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 (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.<ref>{{cite web|title=Pandemic Influenza: Use of Antiviral Agents|date=12 October 2023 |url=http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/biofacts/panflu_antiviral.html|publisher=Center for Infectious Disease Research and Policy (CIDRAP)}}</ref>
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.<ref>{{Cite journal |doi=10.1038/438006a|pmid=16267514|title=Wartime tactic doubles power of scarce bird-flu drug|journal=Nature|volume=438|issue=7064|page=6|year=2005| vauthors = Butler D |bibcode=2005Natur.438....6B|doi-access=free}}</ref>
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.<ref>{{cite web|url=https://www.cdc.gov/flu/avian/gen-info/pandemics.htm|title=Information on Avian Influenza|date=21 March 2019}}</ref> 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.<ref>{{cite web|url=https://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090806/en/|title= Pandemic influenza vaccine manufacturing process and timeline|website=www.WHO.int|access-date=19 January 2018}}</ref>
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.<ref>{{cite web|title=Influenza vaccine manufacturers |publisher=World Health Organization |url=https://www.who.int/csr/disease/influenza/manulist/en/index.html |access-date=13 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060822222456/http://www.who.int/csr/disease/influenza/manulist/en/index.html |archive-date=22 August 2006 }}</ref> 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.<ref>{{cite web | title = The clock is ticking | publisher = Phacilitate | url = http://www.phacilitate.co.uk/pages/phaciliate/article_fedson.html | access-date = 13 September 2006 | archive-url = https://web.archive.org/web/20060717005219/http://www.phacilitate.co.uk/pages/phaciliate/article_fedson.html | archive-date = 17 July 2006 | url-status = dead}}</ref> 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.<ref>{{cite news | title = Canada to launch avian flu vaccine trial | publisher=CTV.ca |date= 20 April 2005 | url = http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/1114000609146_109409809/ | archive-url = https://web.archive.org/web/20090430183058/http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/1114000609146_109409809/ | url-status = dead | archive-date = 30 April 2009 | access-date = 13 September 2006}}</ref>
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.<ref>{{cite web | title = GAO cites barriers to antiviral, vaccine roles in pandemic | publisher=CIDRAP | url = http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jan2308gao.html | access-date = 6 February 2007 }}</ref> 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.<ref>{{cite news|url=https://www.france24.com/en/20090918-10-swine-flu-vaccine-supply-be-given-less-developed-nations-|title=10% of swine flu vaccine supply to be given to less-developed nations|date=18 September 2009|access-date=7 January 2021|agency=France24}}</ref>
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.<ref>{{cite journal | vauthors = Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M | title = Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine | journal = The New England Journal of Medicine | volume = 354 | issue = 13 | pages = 1343–51 | date = March 2006 | pmid = 16571878 | doi = 10.1056/NEJMoa055778 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Poland GA | title = Vaccines against avian influenza--a race against time | journal = The New England Journal of Medicine | volume = 354 | issue = 13 | pages = 1411–3 | date = March 2006 | pmid = 16571885 | doi = 10.1056/NEJMe068047 | doi-access = free }}</ref> Trials using adjuvants such as alum, AS03, AS04 or MF59 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.{{citation needed|date=June 2022}}
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.<ref>{{cite web|url=https://www.who.int/vaccine_research/immunogenicity/immunogenicity_table.xls|archive-url=https://web.archive.org/web/20090306161241/http://www.who.int/vaccine_research/immunogenicity/immunogenicity_table.xls|url-status=dead|archive-date=6 March 2009|title=World Health Organization. Tables on the Clinical trials of pandemic influenza prototype vaccines. July 2009.|website=WHO.int|access-date=19 January 2018}}</ref> 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.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm|archive-url=https://web.archive.org/web/20090917022924/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm|archive-date=17 September 2009|title=US Food & Drug Administration. FDA Approves Vaccines for 2009 H1N1 Influenza Virus Approval Provides Important Tool to Fight Pandemic. 15 September 2009.|website=FDA.gov|access-date=19 January 2018}}</ref>
==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, [and] developing strategies for tighter border controls" due to the H5N1 threat.<ref>{{cite news | vauthors = Rosenthal E, Bradsher K | title = Is Business Ready for a Flu Pandemic? | work=The New York Times | date= 16 March 2006 | url = https://www.nytimes.com/2006/03/16/business/16bird.html | access-date = 13 September 2006 }}</ref>
{{blockquote|[T]he United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Departments of State, Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government.<ref name="usaid" />}}
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".<ref name="usaid">{{cite web|title=Avian Influenza Response: Key Actions to Date |publisher=USAID |url=http://www.usaid.gov/our_work/global_health/home/News/news_items/ai_activities.html |access-date=16 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060417211212/http://www.usaid.gov/our_work/global_health/home/News/news_items/ai_activities.html |archive-date=17 April 2006}}</ref>
===United Nations=== In September 2005, David Nabarro, 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.<ref>{{cite news | title = Bird flu 'could kill 150m people' | publisher=BBC News |date= 30 September 2005 | url = https://news.bbc.co.uk/2/hi/asia-pacific/4292426.stm | access-date = 16 September 2006 }}</ref>
===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.<ref>{{cite book|url=https://www.who.int/csr/disease/influenza/PIPGuidance09.pdf |title=Pandemic influenza preparedness and response: A WHO guidance document. | date = 2009 |publisher=World Health Organization | isbn = 978-92-4-154768-0 |access-date=2011-05-13 |url-status=dead |archive-url=https://web.archive.org/web/20110513194204/http://www.who.int/csr/disease/influenza/PIPGuidance09.pdf |archive-date=13 May 2011}}.</ref>
===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 production. Several agencies within Department of Health and Human Services (DHHS)—including the Office of the Secretary, the Food and Drug Administration (FDA), CDC, 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."<ref>{{cite book | vauthors = Knobler SL, Mack A, Mahmoud A, Lemon SM | collaboration = Institute of Medicine (US) Forum on Microbial Threats | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM | title = The Threat of Pandemic Influenza: Are We Ready? Workshop Summary (2005) | chapter = Summary and Assessment | publisher=The National Academies Press | year= 2005 | chapter-url = http://www.nap.edu/books/0309095042/html/23.html | isbn = 978-0-309-09504-4 | page = 23 |doi=10.17226/11150 |pmid=20669448 }}</ref>
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: [http://www.pandemicflusearch.net Pandemic Flu Search] {{Webarchive|url=https://web.archive.org/web/20191118195733/http://pandemicflusearch.net/ |date=18 November 2019 }}.
On 26 August 2004, Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan,<ref>{{cite web | title = HHS Pandemic Influenza Plan | publisher=United States Department of Health and Human Services | date= 20 March 2006 | url = https://www.hhs.gov/nvpo/pandemicplan/index.html | archive-url = https://web.archive.org/web/20041017132629/http://hhs.gov/nvpo/pandemicplan/index.html | url-status = dead | archive-date = 17 October 2004 }}</ref> 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 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, Ted Kennedy, Barack Obama, and Tom Harkin introduced the Pandemic Preparedness and Response Act as a proposal to deal with a possible outbreak.<ref>{{cite press release | title = Democrats Work to Protect Americans From Avian Flu | publisher = Senate Democratic Communications Center | date = 5 October 2005 | url = http://democrats.senate.gov/~dpc/press/05/2005A06424.html | access-date = 16 September 2006 | archive-url = https://web.archive.org/web/20070311100500/http://democrats.senate.gov/~dpc/press/05/2005A06424.html | archive-date = 11 March 2007 | url-status = dead }}</ref>
On 27 October 2005, the Department of Health and Human Services awarded a $62.5 million contract to Chiron Corporation 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, the vaccines business of Sanofi, for avian flu vaccine.
In October 2005, Bush urged bird flu vaccine manufacturers to increase their production.<ref>{{cite news | title = Bush focuses on bird flu vaccines | publisher=BBC News |date= 8 October 2005 | url = https://news.bbc.co.uk/1/hi/world/americas/4320678.stm | access-date = 16 September 2006 }}</ref>
On 1 November 2005, Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza.<ref>{{cite web|title=National Strategy for Pandemic Influenza |date=1 November 2005 |url=https://georgewbush-whitehouse.archives.gov/homeland/pandemic-influenza.html |access-date=16 September 2006 |url-status=live |archive-url=https://web.archive.org/web/20090221080521/http://georgewbush-whitehouse.archives.gov/homeland/pandemic-influenza.html |via=National Archives |work=whitehouse.gov |archive-date=21 February 2009}}</ref> 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.<ref>{{cite web|title=Bush Outlines $7 Billion Pandemic Flu Preparedness Plan |publisher=usinfo.state.gov web site |date=1 November 2005 |url=http://usinfo.state.gov/gi/Archive/2005/Nov/01-432345.html |access-date=16 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060914184240/http://usinfo.state.gov/gi/Archive/2005/Nov/01-432345.html |archive-date=14 September 2006 }}</ref>
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.<ref>{{cite web|title=U.S. Health Secretary Says More Bird Flu Vaccines Coming |publisher=usinfo.state.gov web site |date=7 March 2006 |url=http://usinfo.state.gov/gi/Archive/2006/Mar/07-312370.html |access-date=16 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060914184926/http://usinfo.state.gov/gi/Archive/2006/Mar/07-312370.html |archive-date=14 September 2006 }}</ref>
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.<ref>{{cite news | vauthors = Manning A | title = With avian flu spreading, U.S. to expand its testing |work=USA Today |date= 7 March 2006 | url = https://www.usatoday.com/tech/science/2006-03-07-bird-migration_x.htm | access-date = 16 September 2006 }}</ref>
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.<ref>{{cite news| vauthors = Aita J |title=United Nations Predicts Bird Flu in the Americas within a Year |publisher=usinfo.state.gov web site |date=9 March 2006 |url=http://usinfo.state.gov/gi/Archive/2006/Mar/09-520042.html?chanlid=globalissues |access-date=16 September 2006 |url-status=dead |archive-url=https://web.archive.org/web/20060516023155/http://usinfo.state.gov/gi/Archive/2006/Mar/09-520042.html?chanlid=globalissues |archive-date=16 May 2006 }}</ref>
July 5, 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."<ref>{{cite news | title = HHS has enough H5N1 vaccine for 4 million people | publisher=Center for Infectious Disease Research & Policy |date= 5 July 2006 | url = http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/jul0506hhsreport.html }} article ''HHS has enough H5N1 vaccine for 4 million people'' published 5 July 2006</ref>
===Canada=== The Public Health Agency of Canada follows the WHO's categories, but has expanded them.<ref>{{cite web | url = http://www.phac-aspc.gc.ca/cpip-pclcpi/index-eng.php | publisher=Public Health Agency of Canada | title = The Canadian Pandemic Influenza Plan for the Health Sector| date=8 December 2006 }}</ref> 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.{{cn|date=June 2022}}
===Malaysia=== Since the Nipah 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 has developed a National Influenza Pandemic Preparedness Plan (NIPPP), which serves as "a time bound guide for preparedness and [a] response plan for influenza pandemic". According to the Director-General of Health Malaysia, the plan "provides a policy and strategic framework for a multisectoral response", offering "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".<ref>Ministry of Health Malaysia, [https://web.archive.org/web/20090509001006/http://www.moh.gov.my/MohPortal/DownloadServlet?id=2873&type=2 National Preparedness Plans for Pandemic Influenza (NIPPP): Strategies], published in January 2006, archived on 9 May 2009, accessed on 28 July 2024</ref>
==See also== {{Portal |Viruses|Medicine}} * Timeline of influenza * List of epidemics
== Citations == {{Reflist}} <!-- Will move this to Influenza but need to know if it's Cite or Cite Journal & is it hand Numbering ?
102. Notes 103–128 Reflect Some of the Earlier [http://www.google.co.uk/search?hl=en&q=HOYLE+ISOLATION+OF+THE+INFLUENZA+VIRUS&meta= Research] into Influenza by Dr L Hoyle who also published in cooperation with Springer Verlang The Influenza Viruses in 1968 103. Fractionation of the influenza virus with the object of producing subunit vaccine. Hoyle L, Barker SM. Postgrad Med J. 1973 Mar;49(569):193–94. 104. The nature of the toxic reaction of influenza virus towards lung tissue. Barker SM, Hoyle L. J Hyg (Lond). 1972 Sep;70(3):425–37 105. The chemical reactions of the haemagglutinins and neuraminidases of different strains of influenza viruses. 3. Effects of proteolytic enzymes. Hoyle L, Almeida JD. J Hyg (Lond). 1971 Sep;69(3):461–69. 106. The chemical reactions of the haemagglutinins and neuraminidases of different strains of influenza viruses. II. Effects of reagents modifying the higher order structure of the protein molecule. Hoyle L. J Hyg (Lond). 1969 Jun;67(2):301–10. 107. The chemical reactions of the haemagglutinins and neuraminidases of different strains of influenza viruses. I. Effect of reagents reacting with amino acids in the active centres. Hoyle L. J Hyg (Lond). 1969 Jun;67(2):289–99. 108. The chemical reactions of influenza virus proteins. Hoyle L, Hana L. J Pathol Bacteriol. 1966 Oct;92(2):447–60. 109. The structure and composition of the myxoviruses. III. The interaction of influenza virus particles with cytoplasmic particles derived from normal chorioallantoic membrane cells. Hoyle L, Horne RW, Waterson AP. Virology. 1962 Aug;17:533–42. 110. The entry of myxoviruses into the cell. Hoyle L. Cold Spring Harb Symp Quant Biol. 1962;27:113–21. 111. The structure and composition of the myxoviruses. II. Components released from the influenza virus particle by ether. Hoyle L, Horne RW, Waterson AP. Virology. 1961 Apr;13:448–59. 112. Amino acid composition of the protein components of influenza virus A. Hoyle L, Davies SP. Virology. 1961 Jan;13:53–57. 113. The use of influenza virus labelled with radio-sulphur in studies of the early stages of the interaction of virus with the host cell. Hoyle L, Finter NB. J Hyg (Lond). 1957 Jun;55(2):290–97. 114. The nucleic acid and carbohydrate content of influenza virus A and of virus fractions produced by ether disintegration. Frisch-Niggemeyer W, Hoyle L. J Hyg (Lond). 1956 Jun;54(2):201–12. 115. The disintegration of influenza virus particles on entry into the host cell; studies with virus labelled with radiophosphorus. Hoyle L, Frisch-Niggemeyer W. J Hyg (Lond). 1955 Dec;53(4):474–86. 116. Release of influenza virus from the infected cell. Hoyle L. J Hyg (Lond). 1954 Jun;52(2):180–88. 117. The incorporation of radioactive phosphorus in the influenza virus and its distribution in serologically active virus fractions. Hoyle L, Jolles B, Mitchell RG. J Hyg (Lond). 1954 Mar;52(1):119–27. 118. Electron microscope studies of the structure of the influenza virus. Hoyle L, Reed R, Astbury WT. Nature. 1953 Feb 7;171(4345):256–57. 119. Structure of the influenza virus; the relation between biological activity and chemical structure of virus fractions. Hoyle L. J Hyg (Lond). 1952 Jun;50(2):229–45. 120. The multiplication of complement-fixing antigen and red-cell agglutinin in the chorio- allantoic membrane of fertile eggs inoculated with influenza virus. Hoyle L. J Pathol Bacteriol. 1952 Apr;64(2):419–23. 121. Modern trends in the diagnosis and treatment of influenza. Hoyle L. Med Press. 1950 Nov 8;224(19):439–41. 122. Growth-cycle of influenza virus. Hoyle L. Nature. 1949 Dec 31;164(4183):1137. 123. The effect of triphenylmethane dyes on the intracellular growth of influenza virus A. Hoyle L. Br J Exp Pathol. 1949 Apr;30(2):123–29. 124. Difficulty experienced in the bacteriological diagnosis of paratyphoid fever in cases treated with sulphonamides. Hoyle L. Mon Bull Minist Health Public Health Lab Serv. 1949 Jan;8:22. 125. Influenza virus A; a study of the relations between virus, soluble antigen and host cell in fertile eggs inoculated with influenza virus. Hoyle L. Br J Exp Pathol. 1948 Oct;29(5):390–99. 126. Technique of the complement-fixation test in influenza. Hoyle L. Mon Bull Minist Health Public Health Lab Serv. 1948 May;7:114–16. 127. Diagnosis of epidemic influenza by the complement-fixation reaction. Hoyle L, Fairbrother RW. Br Med J. 1947 Dec 20;2(4537):991–94. 128. Isolation of the Influenza Virus and the Relation of Antibodies to Infection and Immunity The Manchester Influenza Epidemic of 1937 Hoyle L, Fairbrother RW. 27 March 1937 Isolation of the Influenza Virus BMJ p. 655 -->
==External links== * [http://ec.europa.eu/health-eu/health_problems/avian_influenza/index_en.htm EU response to influenza] – Health – EU portal * [http://euro.who.int/en/health-topics/communicable-diseases/influenza/pandemic-influenza WHO European Region pandemic influenza website] {{Webarchive|url=https://web.archive.org/web/20221123061509/https://www.euro.who.int/en/health-topics/communicable-diseases/influenza/pandemic-influenza |date=23 November 2022 }} * [http://ec.europa.eu/health/ph_threats/com/Influenza/h1n1_en.htm EU coordination on Pandemic (H1N1) 2009] – European Commission – Public Health * [https://web.archive.org/web/20090910134149/http://1918.pandemicflu.gov/ The Great Pandemic: The United States in 1918] * [http://pandemicflu.gov PandemicFlu.gov] * [http://www.fludb.org/brc/homeExtraPage.do?decorator=influenza&extraPage=separate Pandemic Viruses at the Influenza Research Database] * [http://www.timberlanebooks.com/cruel_wind_desc.shtml ''A Cruel Wind: Pandemic Flu in America, 1918–1920''] {{Webarchive|url=https://web.archive.org/web/20090726094910/http://www.timberlanebooks.com/cruel_wind_desc.shtml |date=26 July 2009 }}, by Dorothy A. Pettit, PhD and Janice Bailie, PhD (Timberlane Books, 2009) * [https://wellnessextract.com/blogs/wellness/flu-symptoms-2025 Flu, Influenza or Covid-19? What to Expect and How to Protect Yourself]
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