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Module 1: ABCs of Influenza and Pandemics Airline Team Training 1 Photo: Cynthia Goldsmith 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 2 Influenza Virus Orthomyxovirus 3 The Virus 4 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 5 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 6 Influenza Virus Types A and B Type A (Seasonal and avian influenza) Type B (Seasonal influenza) Can cause significant disease Generally causes milder disease but may also cause severe disease Infects humans and other species (e.g., birds; H5N1) Limited to humans Can cause epidemics and pandemics (worldwide epidemics) Generally causes milder epidemics 7 Influenza A Virus Subtyping • Influenza A subtypes are determined by two surface glycoproteins: –Hemagglutinin (HA) –Neuraminidase (NA) • 16 HA’s and 9 NA’s 8 Species Infected by Influenza A, HA and NA Subtypes H2 N1 N2 H3 H4 N3 N4 H5 H6 H7 H8 N5 N6 N7 N8 N9 H1 H9 H10 H11 H12 H13 H14 H15,16 9 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) 10 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 11 How Do Influenza Viruses Become More Pathogenic? 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 12 What is going on now? Human seasonal influenza virus Avian influenza Virus, may infect humans Current status ????? 13 Migratory birds Reassortment of influenza viruses Avian virus Human virus Reassortment Human virus Reassortment New strain 14 Examples of Re-assortment and Direct Transmission Non-human virus Human virus RE-ASSORTMENT Reassortant virus 15 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 16 http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm 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 17 Seasonal Epidemics vs. Pandemics Seasonal Influenza Influenza Pandemics – A public health problem each year – Appear in the human population rarely and unpredictably – Usually some immunity built up from previous exposures to the same subtype – Human population lacks any immunity – Infants and elderly most at risk – All age groups, including healthy young adults 18 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 19 Timeline of Influenza Pandemics Examples of Current Avian Influenza Strains H9 H7 H5 H3 H2 H1 1915 1925 1918 Spanish Influenza H1N1 1935 1945 1955 1957 Asian Influenza H2N2 1965 1975 1985 1995 2005 1968 Hong Kong Influenza H3N2 20 Avian Influenza in Humans Year Subtype Location 1996 H7N7 United Kingdom 1 0 1997 H5N1 Hong Kong 18 6 1998 H9N2 China 6 0 1999 H9N2 Hong Kong 2 0 2002 H7N2 United States 1 0 2003 H7N2 United States 1 0 2003 H9N2 Hong Kong 1 0 2003 H5N1 Hong Kong 2 1 2003 H7N7 The Netherlands 89 1 2004 H7N3 Canada 2 0 317 19121 2003-07 H5N1 Worldwide Cases Deaths Worldwide H5N1 Outbreak in Humans: 2003 - 2007 Source: WHO 22 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 1N Engl J Med 2005;352:333-340 23 WHO Stages of a Pandemic • Inter-pandemic period • Pandemic alert period – Current status • Pandemic period • Post pandemic period 24 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 usually respiratory infection Transmission – Highly contagious – Primarily through contact with respiratory droplets – Transmission from objects possible H5N1 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 Key Characteristics Communicability Seasonal Influenza H5N1 – Transmission; • 1 - 2 days before onset of symptoms to 4 - 5 days after onset –Transmission; may be similar - not enough data yet – Incubation Period; 1-5 days (Mean 2 days) – Incubation Period; 2 - 8 days (Mean 2-3 days) – Case Fatality Rate; <1% – 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/vol12no04/05-0695G2.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/vol11no11/050608.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/ 41