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Influenza
TEM of negatively stained influenza virons, magnified approximately 70,000 times
ICD-10 J10, J11
ICD-9 487
DiseasesDB 6791
MedlinePlus 000080
MeSH D007251

Template:Flu

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Historical perspective

Classification

Diagnosis

History & Symptoms

Laboratory tests

The available laboratory tests for influenza continue to improve. The United States Centers for Disease Control and Prevention (CDC) maintains an up-to-date summary of available laboratory tests.[1] According to the CDC, rapid diagnostic tests have a sensitivity of 70–75% and specificity of 90–95% when compared with viral culture. These tests may be especially useful during the influenza season (prevalence=25%) but in the absence of a local outbreak, or peri-influenza season (prevalence=10%[2]).

Epidemiology & Demographics

Prevention

Vaccination and infection control

U.S. Navy personnel receiving influenza vaccination

Vaccination against influenza with a flu vaccine is strongly recommended for high-risk groups, such as children and the elderly.

Flu vaccines can be produced in several ways; the most common method is to grow the virus in fertilised hen eggs. After purification, the virus is inactivated (for example, by treatment with detergent) to produce an inactivated-virus vaccine. Alternatively, the virus can be grown in eggs until it loses virulence and the avirulent virus given as a live vaccine.[3] The effectiveness of these flu vaccines is variable. Due to the high mutation rate of the virus, a particular flu vaccine usually confers protection for no more than a few years. Every year, the World Health Organization predicts which strains of the virus are most likely to be circulating in the next year, allowing pharmaceutical companies to develop vaccines that will provide the best immunity against these strains.[4] Vaccines have also been developed to protect poultry from avian influenza. These vaccines can be effective against multiple strains and are used either as part of a preventative strategy, or combined with culling in attempts to eradicate outbreaks.[5]

It is possible to get vaccinated and still get influenza. The vaccine is reformulated each season for a few specific flu strains, but cannot possibly include all the strains actively infecting people in the world for that season. It takes about six months for the manufacturers to formulate and produce the millions of doses required to deal with the seasonal epidemics; occasionally, a new or overlooked strain becomes prominent during that time and infects people although they have been vaccinated (as by the H3N2 Fujian flu in the 2003–2004 flu season).[6] It is also possible to get infected just before vaccination and get sick with the very strain that the vaccine is supposed to prevent, as the vaccine takes about two weeks to become effective.[7]

The 2006–2007 season is the first in which the CDC has recommended that children younger than 59 months receive the annual flu vaccine.[8] Vaccines can cause the immune system to react as if the body were actually being infected, and general infection symptoms (many cold and flu symptoms are just general infection symptoms) can appear, though these symptoms are usually not as severe or long-lasting as influenza. The most dangerous side-effect is a severe allergic reaction to either the virus material itself, or residues from the hen eggs used to grow the influenza; however, these reactions are extremely rare.[9]

Good personal health and hygiene habits are reasonably effective in avoiding and minimizing influenza. People who contract influenza are most infective between the second and third days after infection and infectivity lasts for around 10 days.[10] Children are notably more infectious than adults, and shed virus from just before they develop symptoms until 2 weeks after infection.[10][11]

Since influenza spreads through aerosols and contact with contaminated surfaces, it is important to persuade people to cover their mouths while sneezing and to wash their hands regularly.[8] Surface sanitizing is recommended in areas where influenza may be present on surfaces.[12] Alcohol is an effective sanitizer against influenza viruses, while quaternary ammonium compounds can be used with alcohol, to increase the duration of the sanitizing action.[13] In hospitals, quaternary ammonium compounds and halogen-releasing agents such as sodium hypochlorite are commonly used to sanitize rooms or equipment that have been occupied by patients with influenza symptoms.[13] During past pandemics, closing schools, churches and theaters slowed the spread of the virus but did not have a large effect on the overall death rate.[14][15]

Treatment

People with the flu are advised to get plenty of rest, drink a lot of liquids, avoid using alcohol and tobacco and, if necessary, take medications such as paracetamol (acetaminophen) to relieve the fever and muscle aches associated with the flu. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin during an influenza infection (especially influenza type B) because doing so can lead to Reye's syndrome, a rare but potentially fatal disease of the liver.[16] Since influenza is caused by a virus, antibiotics have no effect on the infection; unless prescribed for secondary infections such as bacterial pneumonia, they may lead to resistant bacteria. Antiviral medication is sometimes effective, but viruses can develop resistance to the standard antiviral drugs.

The two classes of anti-virals are neuraminidase inhibitors and M2 inhibitors (adamantane derivatives). Neuraminidase inhibitors are currently preferred for flu virus infections. The CDC recommended against using M2 inhibitors during the 2005–06 influenza season.[17]

Neuraminidase inhibitors

Antiviral drugs such as oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitors that are designed to halt the spread of the virus in the body.[18] These drugs are often effective against both influenza A and B.[19] The Cochrane Collaboration reviewed these drugs and concluded that they reduce symptoms and complications.[20] Different strains of influenza virus have differing degrees of resistance against these antivirals and it is impossible to predict what degree of resistance a future pandemic strain might have.[21]

M2 inhibitors (adamantanes)

The antiviral drugs amantadine and rimantadine are designed to block a viral ion channel and prevent the virus from infecting cells. These drugs are sometimes effective against influenza A if given early in the infection, but are always ineffective against influenza B.[19] Measured resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005.[22]

Research

CDC scientist working on influenza under high bio-safety conditions

Research on influenza includes studies on molecular virology, how the virus produces disease (pathogenesis), host immune responses, viral genomics, and how the virus spreads (epidemiology). These studies help in developing influenza countermeasures; for example, a better understanding of the body's immune response helps vaccine development, and a detailed picture of how influenza invades cells aids the development of antiviral drugs. One important basic research program is the Influenza Genome Sequencing Project, which is creating a library of influenza sequences; this library should help clarify which factors make one strain more lethal than another, which genes most affect immunogenicity, and how the virus evolves over time.[23]

Research into new vaccines is particularly important: as current vaccines are slow and expensive to produce and must be reformulated every year. The sequencing of the influenza genome and recombinant DNA technology may accelerate the generation of new vaccine strains by allowing scientists to substitute new antigens into a previously-developed vaccine strain.[24] New technologies are also being developed to grow virus in cell culture; which promises higher yields, less cost, better quality and surge capacity.[25] The U.S. government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines.[26] The UK government is also stockpiling millions of antiviral drugs(tamiflu, oseltamivir, zanimivir) to give to its citizens in the event of an outbreak, the UK Health Protection Agency has also gathered a limited amount of HPAI H5N1 vaccines for experimental purposes.

Infection in other animals

Template:H5N1

Influenza infects many animal species and transfer of viral strains between species can occur. Birds are thought to be the main animal reservoirs of influenza viruses.[27] Sixteen forms of hemagglutinin and 9 forms of neuraminidase have been identified. All known subtypes (HxNy) are found in birds but many subtypes are endemic in humans, dogs, horses, and pigs; populations of camels, ferrets, cats, seals, mink, and whales also show evidence of prior infection or exposure to influenza.[28] Variants of flu virus are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are: Bird flu, Human Flu, Swine Flu, Horse Flu and Dog Flu. (Cat flu generally refers to Feline viral rhinotracheitis or Feline calicivirus and not infection from an influenza virus.) In pigs, horses and dogs, influenza symptoms are similar to humans, with cough, fever and loss of appetite.[28] The frequency of animal diseases are not as well-studied as human infection, but an outbreak of influenza in harbour seals caused approximately 500 seal deaths off the New England coast in 1979–1980.[29] On the other hand, outbreaks in pigs are common and do not cause severe mortality.[28]

Flu symptoms in birds are variable and can be unspecific.[30] The symptoms following infection with low-pathogenicity avian influenza may be as mild as ruffled feathers, a small reduction in egg production, or weight loss combined with minor respiratory disease.[31] Since these mild symptoms can make diagnosis in the field difficult, tracking the spread of avian influenza requires laboratory testing of samples from infected birds. Some strains such as Asian H9N2 are highly virulent to poultry, and may cause more extreme symptoms and significant mortality.[32] In its most highly pathogenic form, influenza in chickens and turkeys produces a sudden appearance of severe symptoms and almost 100% mortality within two days.[33] As the virus spreads rapidly in the crowded conditions seen in the intensive farming of chickens and turkeys, these outbreaks can cause large economic losses to poultry farmers.

An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") causes H5N1 flu, commonly known as "avian influenza" or simply "bird flu", and is endemic in many bird populations, especially in Southeast Asia. This Asian lineage strain of HPAI A(H5N1) is spreading globally. It is epizootic (an epidemic in non-humans) and panzootic (a disease 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 other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.[34][35]

At present, HPAI A(H5N1) is an avian disease and there is no evidence suggesting efficient human-to-human transmission of HPAI A(H5N1). In almost all cases, those infected have had extensive physical contact with infected birds.[36] In the future, H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. Due to its high lethality and virulence, its endemic presence, and its large and increasing biological host reservoir, the H5N1 virus is the world's pandemic threat in the 2006–7 flu season, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential influenza pandemic.[37]

Economic impact

Influenza produces direct costs due to lost productivity and associated medical treatment, as well as indirect costs of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs.[38] However, the economic impact of past pandemics have not been intensively studied, and some authors have suggested that the Spanish influenza actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive effects.[39] Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy, where 30% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease gross domestic product by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.[40]

Preventative costs are also high. Governments worldwide have spent billions of U.S. dollars preparing and planning for a potential H5N1 avian influenza pandemic, with costs associated with purchasing drugs and vaccines as well as developing disaster drills and strategies for improved border controls.[37] On November 1 2005, President George W. Bush unveiled the National Strategy to Safeguard Against the Danger of Pandemic Influenza[41] backed by a request to Congress for $7.1 billion to begin implementing the plan.[42] Internationally, on January 18 2006 donor nations pledged US$2 billion to combat bird flu at the two-day International Pledging Conference on Avian and Human Influenza held in China.[43]

Up to 2006, over ten billion dollars have been spent and over two hundred million birds have been killed to try to contain H5N1 avian influenza.[44] However, as these efforts have been largely ineffective at controlling the spread of the virus, other approaches are being tried: for example, the Vietnamese government in 2005 adopted a combination of mass poultry vaccination, disinfecting, culling, information campaigns and bans on live poultry in cities.[45] As a result of such measures, the cost of poultry farming has increased, while the cost to consumers has gone down due to demand for poultry falling below supply. This has resulted in devastating losses for many farmers. Poor poultry farmers cannot afford mandated measures which keep their bird livestock from contact with wild birds (and other measures), thus risking losing their livelihood altogether. Multinational poultry farming is increasingly becoming unprofitable as H5N1 avian influenza becomes endemic in wild birds worldwide.[46] Financial ruin for poor poultry farmers, which can be as severe as threatening starvation, has caused some to commit suicide and many others to stop cooperating with efforts to deal with this virus – further increasing the human toll, the spread of the disease, and the chances of a pandemic mutation.[47][48]

See also

Information concerning flu research can be found at

References and notes

  1. Centers for Disease Control and Prevention. Lab Diagnosis of Influenza. Accessed on January 1, 2007
  2. Capua, I (2006). "The challenge of avian influenza to the veterinary community" (PDF). Avian Pathol. 35 (3): 189–205. PMID 16753610. Unknown parameter |coauthors= ignored (help)
  3. Holmes, E (2005). "Whole-genome analysis of human influenza A virus reveals multiple persistent lineages and reassortment among recent H3N2 viruses". PLoS Biol. 3 (9): e300. PMID 16026181. Unknown parameter |coauthors= ignored (help)
  4. 8.0 8.1 Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP) CDC report (MMWR 2006 Jul 28;55(RR10):1–42) accessed 19 Oct 2006.
  5. Questions & Answers: Flu Shot CDC publication updated Jul 24, 2006. Accessed 19 Oct 06.
  6. 10.0 10.1 Carrat F, Luong J, Lao H, Sallé A, Lajaunie C, Wackernagel H. "A 'small-world-like' model for comparing interventions aimed at preventing and controlling influenza pandemics". BMC Med. 4: 26. PMID 17059593.
  7. Mitamura K, Sugaya N (2006). "[Diagnosis and Treatment of influenza—clinical investigation on viral shedding in children with influenza]". Uirusu. 56 (1): 109–16. PMID 17038819.
  8. Hota B (2004). "Contamination, disinfection, and cross-colonization: are hospital surfaces reservoirs for nosocomial infection?". Clin Infect Dis. 39 (8): 1182–9. PMID 15486843.
  9. 13.0 13.1 McDonnell G, Russell A (1999). "Antiseptics and disinfectants: activity, action, and resistance". Clin Microbiol Rev. 12 (1): 147–79. PMID 9880479.
  10. Hatchett RJ, Mecher CE, Lipsitch M (2007). "Public health interventions and epidemic intensity during the 1918 influenza pandemic". Proc Natl Acad Sci U S A. 104 (18): 7582–7587. PMID 17416679.
  11. Bootsma MC, Ferguson NM (2007). "The effect of public health measures on the 1918 influenza pandemic in U.S. cities". Proc Natl Acad Sci U S A. 104 (18): 7588–7593. PMID 17416677.
  12. Glasgow, J (2001). "Reye syndrome — insights on causation and prognosis". Arch Dis Child. 85 (5): 351–3. PMID 11668090. Unknown parameter |coauthors= ignored (help)
  13. Centers for Disease Control and Prevention. CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season. January 14, 2006. Retrieved on 2007-01-01
  14. Moscona, A (2005). "Neuraminidase inhibitors for influenza". N Engl J Med. 353 (13): 1363–73. PMID 16192481.
  15. 19.0 19.1 Stephenson, I (1999). "Chemotherapeutic control of influenza". J Antimicrob Chemother. 44 (1): 6–10. PMID 10459804. Unknown parameter |coauthors= ignored (help)
  16. Jefferson, T. "Neuraminidase inhibitors for preventing and treating influenza in healthy adults". Cochrane Database Syst Rev. 3: CD001265. doi:10.1002/14651858.CD001265.pub2. PMID 16855962. Unknown parameter |coauthors= ignored (help)
  17. Webster, Robert G. (2006). "H5N1 Influenza — Continuing Evolution and Spread". N Engl J Med. 355 (21): 2174–77. PMID 16192481.
  18. "High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents — United States, 2005–06 influenza season". MMWR Morb Mortal Wkly Rep. 55 (2): 44–6. 2006. PMID 16424859.
  19. Influenza A Virus Genome Project at The Institute of Genomic Research. Accessed 19 Oct 06
  20. Subbarao K, Katz J. "Influenza vaccines generated by reverse genetics". Curr Top Microbiol Immunol. 283: 313–42. PMID 15298174.
  21. Bardiya N, Bae J (2005). "Influenza vaccines: recent advances in production technologies". Appl Microbiol Biotechnol. 67 (3): 299–305. PMID 15660212.
  22. New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu"" by Denise Grady. Published: March 30, 2006. Accessed 19 Oct 06
  23. Gorman O, Bean W, Kawaoka Y, Webster R (1990). "Evolution of the nucleoprotein gene of influenza A virus". J Virol. 64 (4): 1487–97. PMID 2319644.
  24. 28.0 28.1 28.2
  25. Hinshaw V, Bean W, Webster R, Rehg J, Fiorelli P, Early G, Geraci J, St Aubin D (1984). "Are seals frequently infected with avian influenza viruses?". J Virol. 51 (3): 863–5. PMID 6471169.
  26. Elbers A, Koch G, Bouma A (2005). "Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003". Avian Pathol. 34 (3): 181–7. PMID 16191700.
  27. Capua I, Mutinelli F. "Low pathogenicity (LPAI) and highly pathogenic (HPAI) avian influenza in turkeys and chicken." In: Capua I, Mutinelli F. (eds.), A Colour Atlas and Text on Avian Influenza, Papi Editore, Bologna, 2001, pp. 13–20
  28. Bano S, Naeem K, Malik S (2003). "Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in chickens". Avian Dis. 47 (3 Suppl): 817–22. PMID 14575070.
  29. Swayne D, Suarez D (2000). "Highly pathogenic avian influenza". Rev Sci Tech. 19 (2): 463–82. PMID 10935274.
  30. Li K, Guan Y, Wang J, Smith G, Xu K, Duan L, Rahardjo A, Puthavathana P, Buranathai C, Nguyen T, Estoepangestie A, Chaisingh A, Auewarakul P, Long H, Hanh N, Webby R, Poon L, Chen H, Shortridge K, Yuen K, Webster R, Peiris J (2004). "Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia". Nature. 430 (6996): 209–13. PMID 15241415.
  31. Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS. "The Threat of Pandemic Influenza: Are We Ready?" Workshop Summary The National Academies Press (2005) "Today's Pandemic Threat: Genesis of a Highly Pathogenic and Potentially Pandemic H5N1 Influenza Virus in Eastern Asia", pages 116–130
  32. Liu J (2006). "Avian influenza—a pandemic waiting to happen?" (PDF). J Microbiol Immunol Infect. 39 (1): 4–10. PMID 16440117.
  33. 37.0 37.1 Rosenthal, E. and Bradsher, K. Is Business Ready for a Flu Pandemic? The New York Times 16-03-2006 Accessed 17-04-2006
  34. Statement from President George W. Bush on Influenza Accessed 26 Oct 2006
  35. Brainerd, E. and M. Siegler (2003), “The Economic Effects of the 1918 Influenza Epidemic”, CEPR Discussion Paper, no. 3791.
  36. Poland G (2006). "Vaccines against avian influenza—a race against time". N Engl J Med. 354 (13): 1411–3. PMID 16571885.
  37. National Strategy for Pandemic Influenza Whitehouse.gov Accessed 26 Oct 2006.
  38. Bush Outlines $7 Billion Pandemic Flu Preparedness Plan State.gov. Accessed 26 Oct 2006
  39. Donor Nations Pledge $1.85 Billion to Combat Bird Flu Newswire Accessed 26 Oct 2006.
  40. Avian Influenza and its Global Implications US AID. Accessed 26 Oct 2006.
  41. Reuters Vietnam to unveil advanced plan to fight bird flu published on April 28, 2006. Accessed 26 Oct 2006
  42. Poultry sector suffers despite absence of bird flu UN Office for the Coordination of Humanitarian Affairs. Accessed 26 Oct 2006
  43. Nine poultry farmers commit suicide in flu-hit India Reuters. Published on April 12, 2006. Accessed 26 Oct 2006.
  44. In the Nile Delta, Bird Flu Preys on Ignorance and Poverty The New York Times. Published on April 13, 2006. Accessed 26 Oct 2006.

Further reading

Template:Col-1-of-2General
  • NEJM's Avian Influenza
  • Bernd Sebastian Kamps, Christian Hoffmann and Wolfgang Preiser (Eds.) Influenza Report 2006 Flying publisher 2006.
  • Arnold J. Levine 'Viruses' Scientific American Library, WH Freeman, 1992 ISBN 0-7167-5031-7
  • Samuel Baron et al. 'Medical Microbiology' Fourth Edition, The University of Texas Medical Branch at Galveston 1996 ISBN 0-9631172-1-1.
  • Cox NJ, Subbarao K. 'Influenza.' Lancet. 1999 Oct 9;354(9186):1277–82. PMID 10520648
History
  • Edwin D. Kilbourne Influenza Pandemics of the 20th Century Emerging Infectious Diseases Special Issue: Influenza Vol. 12, No. 1 January 2006
  • Richard Collier 'The Plague of the Spanish Lady' Macmillan publishers (London) 1974 ISBN 0-7490-0246-8
  • John M. Barry 'The Great Influenza: the Epic Story of the Deadliest Plague in History' Penguin 2004 ISBN 0-670-89473-7
Microbiology
  • Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. "Evolution and ecology of influenza A viruses." Microbiol Rev. 1992 Mar;56(1):152–79. PMID 1579108
  • Scholtissek C. 'Molecular epidemiology of influenza.' Arch Virol Suppl. 1997;13:99–103. PMID 9413530
Template:Col-2-of-2Pathogenesis
  • Adolfo García-Sastre Antiviral Response in Pandemic Influenza Viruses 'Emerging Infectious Diseases Special Issue: Influenza Vol. 12, No. 1 January 2006
  • Zambon MC. 'The pathogenesis of influenza in humans.' Rev Med Virol. 2001 Jul–Aug;11(4):227–41. PMID 11479929
EpidemiologyTreatment and preventionResearch

External links

Influenza Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Influenza from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Influenza On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Influenza

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Influenza

CDC on Influenza

Influenza in the news

Blogs on Influenza

Directions to Hospitals Treating Influenza

Risk calculators and risk factors for Influenza

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