User:ZayZayEM/Sandbox

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This page is a user's work in progress page, not an article, and will be incomplete and/or unreliable.

See also User:ZayZayEM/TempDump See also Pandemic Severity Index - Influenza related page brought up to scratch

and original @ Influenza pandemic

General notes:

Use consistent language:

• "Influenza pandemic", not Flu pandemic
• "Influenza type A", not influenza a, influenzavirus A
• "Spanish flu" not Spanish influenza, or 1918 pandemic.

"strain" = variety of Influenza genus "genus" = Influenza A, B or C

Use organisational acronyms after the first use. (WHO, CDC, CIDRAP etc.)

[edit] Introduction

Redone intro by User:Tim Vickers

An influenza pandemic is an epidemic of influenza that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in recent history. Pandemics can cause high levels of mortality – the Spanish influenza being responsible for the deaths of over 50 million people worldwide^{[citation needed]}.

Influenza pandemics occur when a new strain of influenza virus is transmitted from another animal species to humans^{[citation needed]}. Pigs, chickens and ducks are the major species thought to be important in the emergence of new human strains. Novel strains are often unaffected the human population's immunity to previous strains of influenza and therefore have the capacity to spread rapidly and infect large numbers of people.

DATE THIS STATEMENTThe World Health Organization (WHO) warns that there is a substantial risk of an influenza pandemic within the next few years^{[citation needed]}. One of the strongest candidates is a highly pathogenic variation of the H5N1 subtype of Influenza A virus^{[citation needed]}. As of 2006, prepandemic flu vaccines are being developed against the most likely suspects which include H5N1, H7N1, and H9N2.^[1]

[edit] Pandemic influenza

• Brief what is influenzavirus and influenza
• What influenzavirus is involved in pandemics (A genus)
• Characteristics of the virus itself (what is H & N)
• (nomenclature)
• Species involved
• what is difference between pandemic influenza and epidemic influenza (SIZE, TIMING, IMPACT)

[edit] Influenza

TLDR

Too much info. Influenza A is only subtype relevent to this article. Only features of 'flu relevent to pandemic potential nature really need to be discussed.

Main article: Influenza

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 flu, is an infectious disease of birds and mammals 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.^[2] In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Sometimes confused with the common cold, influenza is a much more severe disease and is caused by a different type of virus.^[3] Although nausea and vomiting can be produced, especially in children,^[2] these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu."^[4]

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. Infections occur through contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 °C (32 °F), and indefinitely at very low temperatures (such as lakes in northeast Siberia). Most influenza strains can be inactivated easily by disinfectants and detergents.^[5][6][7]

Flu spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in non-pandemic years. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal species. Since it first killed humans in Asia in the 1990s, a deadly avian strain of H5N1 has posed the greatest risk for a new influenza pandemic; however, this virus has not mutated to spread easily between people.^[8]

Vaccinations against influenza are most commonly given to high-risk humans in industrialized countries^[9] and to farmed poultry.^[10] The most common human vaccine is the trivalent flu 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.^[11] 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.

[edit] Variants and subtypes of Influenzavirus A

MERGE WITH ABOVE SECTION

Main article: Influenzavirus A

Variants of Influenzavirus A 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 (example LP). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu.^[12]

Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. Some variants named using this convention are:^[13]

• Bird flu
• Human Flu
• Swine Flu
• Horse Flu
• Dog Flu

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

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

The Influenza A virus subtypes are labeled according to an H number (for hemagglutinin) 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. Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong Flu.^[12]

Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. "There are 16 different HA antigens (H1 to H16) and nine different NA antigens (N1 to N9) for influenza A. Until recently, 15 HA types had been recognized, but a new type (H16) was isolated from black-headed gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005." ^[14]

[edit] Characteristics

List citable characteristics

1. Wave nature
2. variable mortality
3. Social disruption
   1. Death toll (covered in variable mortality?)
   2. Panic/fear
   3. Distrust of authority as authority attempts to keep things calm
   4. Brings out the worst, possible parallels with natural disasters like Hurricanes^{[citation needed]} - looting, loss of infrastructure, predation by snake oil salesmen
4. Section on category schemes (possible own tier two) - PSI, WHO phases

Some pandemics are relatively minor such as the one in 1957 called "Asian flu".^{[citation needed]}

Others have a higher Pandemic Severity Index whose severity warrants more comprehensive social isolation measures.^[15]

Investigate relevance of PSI? Is this a CDC-specific brainchild, does it actually carry any weight? Are there other international indices?

In a bad pandemic, some communities attempt to cut themselves off totally while others have half (or more) of their population die, and others may not feel many of the effects but may still be affected due to the high degree of illness and the bereavement felt by the members of the community.

Speculative. Vague. What is "bad". Why not use a imperial term, such as from PSI.

Desperate people try anything to cure or prevent the illness.^[16]

Out of Date. Refers to desperate attempts in Spanish Flu (1918) needs to be explained in historical context; is there any evidence (citable!) that says similar would happen today

The 1918 Spanish Flu pandemic killed around 150,000 people in the UK, but even the loss of this relatively small number of people in the population caused upheaval and psychological damage to many people.^[17] There were not enough medical staff to attend to the sick, as they had contracted the disease as well. Additionally hospital rooms and medical supplies were scant. Pandemics cause a great deal of social disruption, not only through loss of life, but by playing into people's fear and diffusing morale. Efforts expended by governments and other authorities to keep the populace calm may be mistrusted, and can even have the opposite effect than what is intended. 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." ^[18] In the same period, a letter from a physician at one U.S. Army camp said:

It is only a matter of a few hours then until death comes [...]. It is horrible. One can stand it to see one, two or twenty men die, but to see these poor devils dropping like flies [...]. We have been averaging about 100 deaths per day [...]. Pneumonia means in about all cases death [...]. We have lost an outrageous number of Nurses and Drs. It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce [...]. ^[19]

Ensure above two sources are accurately portrayed, wording of first source far too alarmist.

[edit] Wave nature

{{expand}} or undeserving of own subsection

Flu pandemics typically come in waves. The 1889–1890 and the 1918-1919 flu pandemics each came in three or four waves of increasing lethality. ^[20] But within a wave, mortality was greater at the beginning of the wave. ^[21]

[edit] Variable mortality

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

In U.S. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9.6 percent, for Indian troops 21.9 percent. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population. ^[22]

[edit] Social impact

Please help improve this article or section by expanding it. Further information might be found on the talk page or at requests for expansion. (May 2008)

[edit] Phases

needs {wikify}. Other articles (a template?) links here. Important to be clear and use independent third party sources. Why is WHO plan in use? Why developed? Anyone paying attention to it? etc. If Can't ahve entire section dedicated to "WHO Action Plan", merge into Characteristics or Intervention/Prevention sections

• IDEA: merge with PSI data for pandemic categorisation schemes section

The World Health Organization (WHO) has developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. ^[23]

Mention any (international) responses^{[citation needed]} to WHO GIPP - eg. CIDRAP below. Reference/note too long. The summarised aims belong in the text here

Investigations of small clusters of cases are currently ongoing^{[citation needed]} in southeast Asia, particularly Vietnam, to rule out limited human-to-human spread (which would signify Phase 4). The phases are defined as:

[edit] Interpandemic period

• Phase 1: Low risk No new influenza virus subtypes dangerous to humans detected in humans or animals.
• Phase 2: New virus A new circulating animal influenza virus subtype poses a substantial risk of human disease but no new influenza virus subtypes have been detected in humans.

[edit] Pandemic alert period

• Phase 3: Self limiting Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact. Even without human intervention it would be self limiting among humans.
• Phase 4: Person to person: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans. An epidemic is possible but has not yet happened.
• Phase 5: Epidemic: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly well adapted to humans, but may not yet be fully transmissible (substantial pandemic risk).

[edit] Pandemic period

• Phase 6: Pandemic: increased and sustained transmission in general population.

[edit] Notes

Avoid such a titled section. End of section sounds like its sponsored by CIDRAP

The distinction between phase 1 and phase 2 is based on the risk of human infection or disease resulting from circulating strains in animals. The distinction is based on various factors and their relative importance according to current scientific knowledge. Factors may include pathogenicity in animals and humans, occurrence in domesticated animals and livestock or only in wildlife, whether the virus is enzootic or epizootic, geographically localized or widespread, and/or other scientific parameters.

The distinction between phase 3, phase 4 and phase 5 is based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal strain), and/or other scientific parameters.

The pandemic stage 6 may be marked by two or more waves. For example, the initial wave of the Spanish Influenza pandemic in the spring of 1918 was so mild in its effects that it received the dismissive nickname of the "three day flu." But when the second wave hit North America a few months later in the summer of 1918, it was lethal.^[24] Apparently in the interim the novel H1N1 pandemic strain had added the gene or genes that made the final wave a killer. Perhaps the effects of the lethal second wave would have been even more devastating if the innocuous first wave had not already passed through the population, leaving in its wake at least some immune response to the surface antigens presented by the H1N1 in both waves.

CIDRAP provides a thoroughgoing overview, which has its roots in materials from the U.S. HHS National Vaccine Program Office. CIDRAP's overview originally set forth a model listing five numbered stages for the pandemic itself, preceded by four additional pre-pandemic stages, each numbered as zero, that overlapped the WHO's first five stages of a pandemic. CIDRAP's overview has since adopted the WHO's 6-stage model. ^[25]

[edit] History

[edit] Spanish Flu (1918–1920)

TLDR -This has its own article, doesn't need all info. Just basics, who, what, where, when and minor context; additionally SPanish flu has been mentioned several times already in terms of describing characteristics and effects of a pandemic

Main article: 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. Many of its victims were healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients.

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).^[27]

The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people^[28] while current estimates say 50 million to 100 million people worldwide were killed.^[29] This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death.^[30] 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.^[28] 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."^[29] 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.^[27]

The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands. The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1%.^[27][29] 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.^[31] This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1919 pandemic is not known, but it is estimated that 2.5% to 5% of the world's population was killed. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years.^[29]

[edit] Asian Flu (1957–1958)

Main article: H2N2

The "Asian Flu" was a category 2 flu pandemic outbreak of avian influenza that originated in China in early 1956 lasting until 1958. It originated from mutation in wild ducks combining with a pre-existing human strain.^[32] The virus was first identified in Guizhou.^[33] It spread to Singapore in February 1957, reached Hong Kong by April, and US by June. Death toll in the US was approximately 69,800.^[32] Estimates of worldwide infection rate varies widely depending on source, ranging from 1 million to 4 million.

[edit] Hong Kong Flu (1968–1969)

Main article: H3N2

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. The Hong Kong Flu pandemic of 1968 and 1969 infected an estimate 500,000 with a low death rate^[34][35]. In the US, 50 million were infected with an estimated 33,000 deaths^[36].

[edit] H5N1

Part of UNDUE wieghting to H5N1

Needs to be merged up in line with Spanish Flu section above, possible deserving {current} tag, check usage guidelines of that template first

Provide only context of H5N1 in pandemic sense

OH, and TLDR

H5N1

Influenza A virus subtype H5N1 Genetic structure Infection Human mortality Global spread in 2004, 2005, 2006, 2007 Social impact Pandemic

Main article: H5N1

Influenza A virus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species.^[37] A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or "bird flu". It is endemic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Most mentions of "bird flu" and H5N1 in the media refer to this strain.^[38]

HPAI A(H5N1) is an avian disease. There is no evidence of efficient human-to-human transmission or of airborne transmission of HPAI A(H5N1) to humans. In almost all cases, those infected with H5N1 had extensive physical contact with infected birds. Still, around 60% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from it, and H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission.^{[39][40][41][42][43][44][45]}

In 2003, world-renowned virologist Robert Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives.^[46] On September 29, 2005, David Nabarro, the newly-appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people.^[47] Experts have identified key events (creating new clades, infecting new species, spreading to new areas) marking the progression of an avian flu virus towards becoming pandemic, and many of those key events have occurred more rapidly than expected.

Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large host reservoir, and its significant ongoing mutations, the H5N1 virus is the world's largest current pandemic threat, and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic.^[48] At least 12 companies and 17 governments are developing pre-pandemic influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly one. Full-scale production of a vaccine that could prevent any illness at all from the strain would require at least three months after the virus's emergence to begin, but it is hoped that vaccine production could increase until one billion doses were produced by one year after the initial identification of the virus.^[49]

H5N1 may cause more than one influenza pandemic as it is expected to continue mutating in birds regardless of whether humans develop herd immunity to a future pandemic strain.^[50] Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1.^[51] While genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the Spanish Flu pandemic^[52], planning for a future influenza pandemic is based on what can be done and there is no higher Pandemic Severity Index level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad the Spanish flu or worse; and for which all intervention measures are to be used.^[53]

To have a flu pandemic several distinct phases must happen. H5N1's next phase is easy person to person transmission. After that occurs, it is theoretically possible to stop it before it becomes an epidemic, or if that opportunity is missed, to stop the epidemic before it becomes a pandemic. It is widely believed by the experts that it will not be possible to prevent any of these phases from occurring with H5N1, but if we are lucky enough to delay it for a few years, we might come up with a solution such as a flu vaccine.

H5N1 is just one of the many subtypes of the species Influenza A virus. Any one of them can combine with each other or with different variant genotypes within its own subtype creating new variants, any one of which could become a pandemic strain. We know enough about the genetics to know what strains to fear most (example: only H5 and H7 subtypes are "highly pathogenic") and we know what genetic factors make a flu virus a human virus (i.e. easily passed human to human); so we know H5N1 is the biggest pandemic threat of all the strains in circulation and we know it is only a few antigenic shift mutations or antigenic drift mutations from being an avian flu virus to being a human flu virus. If it does this it may or may not still be in the H5N1 subtype. Both the drift and the shift can happen in any infected animal and then be passed to a human and spread like wildfire. Possible shift scenarios include the shift occurring in humans, pigs, or cats. To acquire the needed mutation through drift, it simply has to continue being an epidemic in birds long enough for the mutations to occur and then be passed to a human.

[edit] Prevention

Written completely unencyclopediacly, relies on a single source, violates UNDUE, reads like promotional

This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations panel consisting of:

• James F. Hoge, who is Peter G. Peterson chair, editor, Foreign Affairs
• Nancy E. Roman, who is vice president and director, Washington Program, Council on Foreign Relations
• Rita Colwell, who is chair, Royal Institution World Science Assembly's Pandemic Preparedness Project
• Anthony Fauci, who is director of the National Institute of Allergy and Infectious Diseases at the National Institute of Health
• Laurie Garrett, who is the senior fellow for global health, Council on Foreign Relations
• Michael Osterholm, who is director of the Center for Infectious Disease Research and Policy, University of Minnesota; also, associate director, National Center for Food Protection and Defense, Department of Homeland Defense; also a professor at the University of Minnesota School of Public Health.^[54]

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

• Culling and vaccinating livestock
• Vaccinating poultry workers against common flu
• Limiting travel in areas where the virus is found^[54]

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. 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.^[54]

[edit] Research

Refine in context of PANDEMIC, provide short intro to other sections, possible other research modes. Possible looks at B & C strain research (into possibility as pandemic ^{[citation needed]})

See also: Flu research

[edit] Vaccines

A vaccine probably would not be available in the initial stages of population infection ^[55]. Once a potential virus is identified, it normally takes at least several months before a vaccine becomes widely available, as it must be developed, tested and authorized. The capability to produce vaccines varies widely from country to country; in fact, only 19 countries are listed as "Influenza vaccine manufacturers" according to the World Health Organization.^[56] 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 in order to become inmuno-competent. Distribution to and inside countries would probably be problematic.^[57] 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.^[58]

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 (Treanor 2006). 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 (Poland 2006). Trials using adjuvants such as alum 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. Current vaccine research is focussed 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.

[edit] Anti-viral drugs

Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in preparation for a possible pandemic. Oseltamivir (trade name Tamiflu) is the most commonly sought drug, since it is available in pill form. Zanamivir (trade name Relenza) is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza.

Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies ^[59].

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

Tamiflu was originally discovered by Gilead Sciences and licensed to Roche for late-phase development and marketing.

Donald Rumsfeld, a shareholder in Gilead Sciences, has profited from the US government stockpiling of oseltamivir in case of an influenza pandemic.^[60] Critics have used this fact to question both government stockpiling policies and the H5N1 potential pandemic itself.

[edit] Intervention

Unsure about this section, clearly important info, but needs serious restructuring and better sourcing. Sources few and far between, or far too listy

[edit] Global response

• the establishment and maintenance of high standards of poultry biosecurity
• national veterinary services upgraded to OIE standards
• early detection of H5N1
  • early warning system
  • adequate surveillance
  • rapid reporting
  • data-sharing systems
    • web-based
    • facilitate integrated responses and risk management
    • report associated meta-data that allow full analysis of the results
    • facilitate timely and effective risk management
• standardization of national-level reporting
• transparent, structured and science-based risk assessments
• better HPAI field surveillance worldwide
• better veterinary services worldwide
• improved, contemporary and international analysis of existing waterbird ringing and count data at the species level and also in months other than January
• better consolidated information on national trade in poultry and poultry products
• rapid reporting and control measures
• data collection on trade issues
• the development of compensation policies for agricultural losses and impacts on protected areas
• effective communication with the media
• the public and policy makers using scientific facts
• additional research on:
  • the prevalence of H5N1 in wild bird populations
  • existing ringing data to assess migratory systems
  • the ecology of the virus in the environment
  • natural mortality levels in wild bird populations
  • wild bird susceptibility to H5N1
  • effective measures to reduce transmission of H5N1 between wild birds and poultry
• build programmes of sustainable financial measures
• support to ensure the sustainability of short-term measures
• development of mechanisms to restructure agricultural production systems with the goal of reducing stresses on ecosystems and risks to human health
• better information on cultural practices that have the potential to either help or hinder the control of H5N1.
• develop and maintain collaborative approaches and partnerships that integrate wetland and wildlife management expertise with expertise on human health and zoonoses
• better integration of existing data on trade in poultry and other birds and the establishment of a web-based clearing-house mechanism on the spread of H5N1.

Source:SCIENTIFIC SEMINAR ON AVIAN INFLUENZA, THE ENVIRONMENT AND MIGRATORY BIRDS ON 10-11 APRIL 2006 published 14 April 2006.^[61]

[edit] Individual response

(The World Health Organization published a compendium of non-pharmaceutical interventions in November 2005. The following list is not identical to the WHO recommendations.)^[62]

• Social distance. By travelling less, working from home or closing schools there is less opportunity for the virus to spread.
• Respiratory hygiene. Populations should be repeatedly informed of the need for "respiratory hygiene" (covering mouth when coughing or sneezing, careful disposal of soiled tissues or other materials).
• 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).^[62] Any mask may be useful to remind the wearer not to touch his 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.
• Hygiene. Frequent handwashing, especially when there has been contact with other people or with potentially contaminated surfaces can be very helpful. Alcohol-based hand sanitizers also kill both bacteria and viruses.^[63]

[edit] Preparations for a potential influenza pandemic

Possibly best section in the entire article, needs fact checking still c.f. innacuracies throughout article

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.^[64]

"[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."^[65]

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".^[65]

Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention, the World Health Organization, the European Commission, the National Influenza Centers, and others.^[66]

[edit] United Nations

Too short

In September 2005, David Nabarro, a lead UN health official warned that a bird flu outbreak could happen anytime and had the potential to kill 5-150 million people.^[67]

[edit] United States

Too long "[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."^[68]

On August 26, 2004, Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan^[69], 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 September 14, 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 October 5, 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.^[70]

On October 27, 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 the sanofi-aventis Group, for avian flu vaccine.

In October 2005, President Bush urged bird flu vaccine manufacturers to increase their production.^[71]

On November 1, 2005 President Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza^[72]. 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.^[73]

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.^[74]

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.^[75]

On 8 March 2006, Dr. David Nabarro, senior U.N. 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.^[76]

"Jul 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."^[77]

GLOBALIZE SECTION

[edit] China

CHECK WP:FRINGE

In 1982, Kennedy F. Shortridge and Charles Stuart-Harris proposed that China, particularly southern China, is an epicentre for the emergence of pandemic influenza viruses^[78]. This hypothesis was based on three observations:

1. The occurrence of a large number of viruses in domestic poultry notably ducks in the region.

2. The dense populations and proximity of humans, poultry and pigs in villages and farms there.

3. The historical records associating China with epidemics and pandemics and, in the last century, the association of southern China with the emergence of the 1957 Asian and 1968 Hong Kong pandemic strains and the re-emergence of the 1977 H1N1 virus ^[79]. These records have been reinforced by the 1997 H5N1 incident that is considered by some to have been an incipient pandemic and a pandemic averted by the slaughter of poultry across Hong Kong SAR in late 1997.

[edit] References

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