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Module 1: ABCs of Influenza and Pandemics

Understand influenza viruses, mutation, epidemiology, and past pandemics. Learn about avian strains, antigenic drift, and pandemics versus epidemics. Follow WHO stages.

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Module 1: ABCs of Influenza and Pandemics

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  1. Module 1: ABCs of Influenza and Pandemics Airline Team Training Photo: Cynthia Goldsmith

  2. Learning Objectives • Understand the basic biology of influenza viruses • Describe the ways that influenza viruses can change or mutate • Compare the epidemiology and key characteristics of seasonal and pandemic influenza, including H1N1

  3. Influenza Virus Orthomyxovirus

  4. The Virus

  5. Types of Influenza Virus • Three types: A, B, C • Influenza Type A can infect: People, birds, pigs, horses, seals, whales and others • Influenza Type B: Human virus • Not classified according to Subtype • Cause human epidemics but not pandemics • Influenza Type C cause mild illness in humans • Not classified according to subtype • Do not cause epidemics or pandemics

  6. Low vs. High Pathogenic Avian Influenza • Low Pathogenic Avian Influenza Viruses (LPAI): • May not cause any illness in wild birds • Associated with mild illness in domestic poultry • Can evolve into highly pathogenic viruses • Associated with poultry outbreaks worldwide • Subtypes: H9 • High Pathogenic Avian Influenza Viruses (HPAI): • May not cause any illness in wild birds • High mortality in domestic poultry • High risk of disease in people • Subtypes: H5, H7

  7. Influenza VirusTypes A and B

  8. Influenza A Virus Subtyping • Influenza A subtypes are determined by two surface glycoproteins: • Hemagglutinin (HA) • Neuraminidase (NA) • 16 HA’s and 9 NA’s

  9. Species Infected by Influenza A, HA and NA Subtypes N1 H1 N2 H2 N3 H3 N4 H4 H5 N5 H6 N6 H7 N7 H8 N8 H9 N9 H10 H11 H12 H13 H14 H15,16

  10. Antigenic Drift • Point mutations in the hemagglutinin gene cause minor antigenic changes to HA • Continuous process • Immunity against one strain may be limited • Antigenic drift produces new virus strains that may not be recognized by antibodies to earlier influenza strains • One of the main reasons why people can get the flu more than one time (Seasonal epidemics). • one or two of the three virus strains in the influenza vaccine are updated: • 6-8 months process • Targeted at high-risk (inactivated)

  11. Antigenic Shift • new influenza virus that can infect humans and has (new HA subtype ± NA) through: • Genetic reassortment (human and animal viruses) • Direct animal (poultry) to human transmission • if most people have little or no protection against the new virus: • Spread easily from person to person • Pandemic (worldwide spread) may occur

  12. Antigenic Shift Strong selection pressure acting on mutations or changes in HA or NA Direct infection in humans Re-assortment Two different strains of influenza infect the same host “Reassorted” virus emerges How Do Influenza Viruses Become More Pathogenic?

  13. What is going on now? Human seasonal influenza virus Avian influenza Virus, may infect humans Current status ?????

  14. Migratory birds Avian virus Human virus Human virus Reassortment of influenza viruses Reassortment Reassortment New strain

  15. DIRECT Examples of Re-assortment and Direct Transmission Non-human virus Human virus RE-ASSORTMENT Reassortant virus

  16. Epidemiology Terms • Endemic • A disease that occurs at an expected constant level in a population • “Background” level Red line: Expected deaths each year Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm

  17. Epidemiology Terms • Epidemic • When the cases of a disease exceed what is normally expected • Pandemic • An epidemic that occurs over a large geographic area, or across the whole world

  18. Seasonal Epidemics vs. Pandemics Influenza Pandemics Appear in the human population rarely and unpredictably Human population lacks any immunity All age groups, including healthy young adults Seasonal Influenza A public health problem each year Usually some immunity built up from previous exposures to the same subtype Infants and elderly most at risk

  19. Mortality Impact of Past Pandemics • 1918-19 Spanish Flu (H1N1) • ~ 40 million deaths worldwide • 1957-58 Asian Flu (H2N2) • 1 - 2 million deaths worldwide • 1968-69 Hong Kong Flu (H3N2) • ~ 700,000 deaths worldwide

  20. 1957 1968 Hong Kong Influenza H3N2 Asian Influenza H2N2 Timeline of Influenza Pandemics H9 Examples of Current Avian Influenza Strains H7 H5 H3 H2 H1 1915 1925 1935 1945 1955 1965 1975 1985 1995 2005 1918 Spanish Influenza H1N1

  21. Avian Influenza in Humans

  22. Worldwide H5N1 Outbreak in Humans: 2003 - 2007 Source: WHO

  23. Human H5N1 Epidemiology • Primarily avian-to-human transmission • No evidence of sustained person-to-person spread • Limited probable person-to-person spread1 • Environment-to-human transmission possible 1 N Engl J Med 2005;352:333-340

  24. WHO Stages of a Pandemic • Inter-pandemic period • Pandemic alert period • Current status • Pandemic period • Post pandemic period

  25. WHO Phases of a Pandemic Inter-pandemic Period Phase 1: No new Influenza virus subtypes in humans Phase 2: No new virus subtypes in humans; animal subtype poses a risk of human disease

  26. WHO Phases of a Pandemic Pandemic Alert Period Phase 3: Human infection with novel virus; no instances of human-to-human spread (current status) Phase 4: Small, localized clusters of human-to-human spread Phase 5: Larger clusters, still localized; virus adapting to humans

  27. WHO Phases of a Pandemic Pandemic Period Phase 6: Increased and sustained transmission in the general population. Post Pandemic Period Recovery phase

  28. Prerequisites for pandemic influenza A new influenza virus emerges to which the general population has little/no immunity The new virus must be able to replicate in humans and cause disease The new virus must be efficiently transmitted from one human to another

  29. Influenza Infection in Humans; Seasonal vs H5N1

  30. Key Characteristics Seasonal Influenza H5N1 usually respiratory infection Transmission • Highly contagious • Primarily throughcontact with respiratory droplets • Transmission from objects possible • usually respiratory • may involve GI Transmission • Not highly contagious (now) • Primarily through contact with respiratory droplets • Possible transmission from objects • Possible faecal-oral route

  31. Seasonal Influenza Transmission; 1 - 2 days before onset of symptoms to 4 - 5 days after onset Incubation Period; 1-5 days (Mean 2 days) Case Fatality Rate; <1% Key Characteristics Communicability • H5N1 • Transmission; may be similar - not enough data yet • Incubation Period; 2 - 8 days (Mean 2-3 days) • Case Fatality Rate; • >50%

  32. Vaccination • Influenza vaccine is the best prevention for seasonal influenza. • Inactivated viruses in the vaccine developed from three circulating strains (generally 2 Type A and 1 Type B strain). • Provides little or no protection to H5N1 • No vaccine yet for H5N1 - in development

  33. Summary • Influenza is a serious human and veterinary health concern each year • Influenza virus strains evolve rapidly and can develop into a novel virus with pandemic potential • Influenza pandemics have caused high morbidity and mortality in the past

  34. Summary • H5N1 Avian Influenza is currently spreading through birds with occasional outbreaks among humans • While there is evidence of rare human to human transmission, sustained transmission has not occurred • If H5N1 virus obtains the ability to easily transmit from person to person, a pandemic may result

  35. Questions?

  36. Glossary Virus A small, infectious agent consisting of a core of genetic material (DNA or RNA) surrounded by a shell of protein. A virus needs a living cell [a host] to reproduce. Viral shedding Multiplication of a virus in an infected person with subsequent release of the virus from that infected person, such that others who come into contact with the person may become infected. A state of being contagious. Epidemiology The branch of medicine that deals with the study of the causes, distribution, and control of disease in populations.

  37. Glossary Seasonal Influenza Expected rise in influenza occurrence among humans living in temperate climates; occurs during the winter season with strains of influenza that have minor changes from season to season. Pandemic An epidemic occurring over a wide geographic area and affecting a large proportion of the population. Antigenic Drift A process of small changes in the genetic material of a virus, called point mutations, that occur during the normal virus replication process.

  38. Glossary Antigenic Shift A process of major changes in the genetic material of a virus; for influenza, the H and N proteins change altogether, resulting in a new strain of virus. Highly Pathogenic Avian Influenza (HPAI) Influenza infection in poultry that causes severe illness and often death. Can be transmitted to humans resulting in severe illness or death. Low Pathogenic Avian Influenza (LPAI) The most common influenza infection in birds; causes mild clinical and unapparent infections.

  39. References and Resources • Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm • The Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5.Avian Influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85. • Ungchusak K, et al. Probable Person-to-Person Transmission of Avian Influenza A (H5N1) N Engl J Med 2005;352:333-340.

  40. References and Resources • Tiensin T, et al. Highly Pathogenic Avian Influenza H5N1, Thailand, 2004. EID;2005;11(11):1664-72. http://www.cdc.gov/ncidod/eid/vol11no11/05-0608.htm • World Health Organization. Epidemic and Pandemic Alert and Response. 2006. http://www.who.int/csr/en/ • Center for Food Security and Public Health. Iowa State University: http://www.cfsph.iastate.edu/

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