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H1N1 Pandemic

H1N1 Pandemic. Epi 258: Environmental & Occupational Epidemiology Katie Nishimura April 26, 2012. Overview. Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1. Influenza. Introduction to influenza

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H1N1 Pandemic

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  1. H1N1 Pandemic Epi 258: Environmental & Occupational Epidemiology Katie Nishimura April 26, 2012

  2. Overview Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1

  3. Influenza Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Viral infection of the respiratory tract • Caused by an RNA virus • 3 types: • Influenza A • Multiple species identified by type of Hemagglutinin& Neuraminidase (ex: H1N1, H5N1) • Avian reservoir • Most virulent in humans • Influenza B • Only 1 species • Mostly humans • Less common than A • Slower mutation rate than A • Influenza C • Only 1 species • Humans, dogs, pigs • Least common • Usually only mild disease

  4. Symptoms Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Fever 102-106’F Cough Congestion Body aches Fatigue Headache Nausea, vomiting Sudden onset of symptoms (1-2 days post infection) Usually resolves in 4-7 days

  5. Cold versus Flu Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic

  6. Transmission Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • 3 routes of transmission 1) Direct contact: mucus, saliva from an infected person to a non-infected person 2) Airborne: aerosolized respiratory secretions during sneezing, coughing 3) Indirect contact: via hand contact, contaminated surfaces • Viral shedding • starts before symptoms • lasts 5-7 days • peak infectiveness at 2-3rd day

  7. Influenza A Proteins Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Influenza has only 8 genes total • Different protein variants denote result in different flu strains

  8. 2 Proteins used in Identification Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Hemagglutinin (17 types) • Viral attachment to respiratory tract cells • Receptor-mediate endocytosis • Neuraminidase (9 types) • Release of newly replicated viral particles from host cell

  9. Pathogenesis Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Hemagglutinin attaches viral particle to epithelial cells in the supper and lower respiratory tract Viral particle is enveloped (endocytosis) Viral genome takes over cellular machinery, forces production of viral proteins New viral particle buds from cell and infects other cells

  10. Epidemiology Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Peak prevalence in winter • 2 flu seasons globally (winter in the Northern + Southern hemisphere) • Annually in the US: • 114,000 – 116,000 hospitalizations • 20,000 – 40,000 deaths • Annually worldwide: • 3-5 million cases • 500,000 deaths • Pandemic occurs roughly 3x per century http://www.cdc.gov/mmwr/pdf/wk/mm5947.pdf

  11. Costs of the Flu Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic http://www.ncbi.nlm.nih.gov/pubmed/17544181 study published 2007 based on 2003 US population • $10.4 billion in direct medical costs: (hospitalizations, medications, etc.) • 25 million physician visits • $16.3 billion projected in lost earnings due to illness and loss of life (sick days, lost productivity, income) • $87 billion in total annual economic burden

  12. Epidemiology Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Small proportion of individuals have serious illness • Individuals at high risk for complications: • Infants and elderly • Those with chronic medical problems • Pregnant women (2nd or 3rd trimester) • Residents of chronic care facilities

  13. Treatments Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Fever reducers like acetominophen (tylenol) or ibuprofen (advil, motorin) Do not use aspirin (may cause Reye’s syndrome in those with viral infections) Do not use antibiotics (not effective against viral infections) Extreme cases, antiviral drugs: zanamivir, oseltamivir (Tamiflu) (neuraminidase inhibitors)

  14. Seasonal Flu Vaccination Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Must predict which strains will be highly prevalent in the next season Monitor flu in the Southern hemisphere

  15. Why we need a new vaccine every year Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Drift (antigenic drift): • Influenza lacks “proofreading” mechanisms to repair errors before replication • Mutations are copied and slowly spread through the viral population • Usually small genetic changes • New strains are reasonably similar to older strains • Partial protective immunity to previous infections (cross-reactivity) • Shift (antigenic shift): • Can swap or “reassort” genetic materials • Results in a novel subtype different from both parent viruses • New antigens means large proportion of people will be susceptible to infection

  16. Mixing Vessel Hypothesis Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Waterfowl are the primary reservoir for influenza A (also horses, pigs, chickens) Exchange of genetic material b/w 2 viruses can occur in co-infections

  17. Influenza Reassortment Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Epidemiology:

  18. Prevention Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Vaccination! (effective in 70-90% of young adults) Isolation of sick Avoid sharing food, utensils, cups, bottles Cover coughing/sneezing, through away tissues Avoid touching eyes, nose, mouth Wash hands, use hand sanitizer

  19. ID Definitions Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Pathogen = organism that causes disease Pathogenicity = ability to cause disease Virulence = degree of pathogenicity Virulence factors = properties that influence ability to be transmitted or cause disease (toxins, enzymes, etc.) Etiology = the study of the cause of a disease Infectivity = ability of an agent to survive and multiply within a host Transmissibility = ability of an agent to spread and infect another host Reservoirs = living/nonliving sources of infectious disease Zoonotic disease = diseases of animals that can be spread to humans Vector = organisms (usually insect) that actively transmits a disease Nosocomial infections = acquired by patients in the health care setting Fomites = inanimate objects that can transmit disease

  20. ID Definitions Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Endemic = disease that is always in the population Epidemic = disease that many people acquire over a short period (incidence rate > norm) Pandemic = worldwide epidemic (epidemic occurring on >= 2 continents at the same time) Index case = the first case of a disease to be identified Attack rate = incidence proportion (#cases / # people at risk) Carrier = person who is infectious but who shows no symptoms Convalescent = ability to remain infectious after clinical illness has subsided Routes of transmission: person to person, air-borne, food-borne, vector-borne, vehicle-borne Direct transmission = spread through direct contact (touching) Indirect transmission = spread through indirect contact, objects Active immunity = attained naturally via infection or vaccination Passive immunity = attained from mother to fetus across the placenta

  21. ID Definitions Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Herd immunity = the lowered risk of infection to a minority of susceptible individuals living in a population with a high proportion of resistance Elimination = reduction of incidence to 0, but still required intervention measures Eradication = reduction of incidence to 0, no further intervention measures required Quarantine = restriction of the activities of healthy people who have been exposed to an infectious case during its period of infectiveness to prevent transmission Isolation = separation of infected persons during the period of infectiveness to prevent transmission to those who are susceptible Passive vs active surveillance – data routinely collected vs data that is actively collected during an outbreak

  22. CDC’s 10 Steps of an Outbreak Investigation Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Prepare for field work • Establish existence of an outbreak Surveillance records Hospital records • Verify the diagnosis (with addition testing) • Define and identify cases (case definition) • Describe data in terms of Time Place Person • Develop hypothesis Source of disease Mode of transmission Exposures • Evaluate hypothesis • Refine hypothesis • Implement control and prevention measures Break the cycle of transmission Limit exposure by isolation, quarantine • Communicate findings

  23. Epidemic Curve Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Histogram of number of cases over time Progression over time Seasonality Common or continuous source of infection Influenced by reporting delay

  24. Reproductive Rate Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic The average number of new infections that one infectious case generates during his/her infectious lifetime in a community of susceptible individuals R0 = beta * kappa * D Beta = average probability that a susceptibly partner will become infected over the duration of a relationship Kappa = average number of new contacts per unit time D = average duration of illness R0 < 0 = leads to the eradication of the disease

  25. Surveillance Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Purpose:predict, observe, minimize harm caused by an outbreak, epidemic, or pandemic Requires disease case reporting Notifiable disease: any disease that is required by law to be reported to government authorities (TB, plague, HIV, anthrax, etc) One of WHO’s primary responsibilities

  26. West Nile Surveillance Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Virus transmitted via mosquito vectors to birds (amplifying host). Can then be transmitted to humans by mosquito bite Flocks of sentinel chickens are used to monitor for West Nile Virus Wild birds are periodically tested for West Nile infection

  27. Contact Tracing Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic 2010 outbreak of 9 cases of measles in Australia, possibly linked to an index case who travelled on an international flight from S. Africa Identification and diagnosis of persons who may have come in contact with an infected individual

  28. 1918 Flu Pandemic Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic

  29. Mortality Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Caused by H1N1 Jan 1918 – Dec 1920 50-100 million died, 25 million in the first 4 months (50million = 3% of the world’s population). Killed more people than all of the wars of the 20th century combined

  30. Timeline Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • 2 peaks in disease rate • 0.5% of the US population died • Resulted in a measurable drop in life expectancy in 1919 • “Spanish flu” b/c was perceived to be particularly severe in Spain (a neutral country at the time). US, Britain, Germany, France had media blackouts and didn’t want to disclose the number of deaths to their enemies

  31. Mortality Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Cytokine storm = extreme inflammatory reactions resulting in high fever and body aches (destruction of infected cells) • Virus believed to kill through cytokine storm (overreaction of the body’s immune system) • Unusually high rate of young adults, who had stronger immune systems (compared to children and elderly, who are commonly victims of flu) • Close troop quarters and troop movements likely hastened transmission

  32. Infectious Causes of Death in 20th Century Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic

  33. 2009 H1N1 Pandemic Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic

  34. Timeline Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic March 28: first known case (Mexico) March 28: first US case (9yo girl in Imperial County, CA) March 30: 10yo boy in San Diego County, CA April 13: first casualty (Oaxaca, Mexico) April 15: CDC identifies first novel influenza strain from 10yo boy April 17: CDC confirms novel influenza strain in second clinical sample from 9yo girl April 21: health officials alert US doctors April 24: 8 confirmed cases in US

  35. Timeline Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic April 25: WHO emergency meeting to declare international public health emergency April 26: 20 US cases, US declares public health emergency April 27: confirmed cases in Spain, Scotland, 149 deaths in Mexico, WHO pandemic Level 4 April 28: 68 cases in US, Obama asks for $1.5 billion in emergency funds April 29: WHO raises pandemic to Level 5, Egypt begins to slaughter 300,000 pigs as a precaution

  36. Timeline Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic April 30: 300 US schools closed to stop spread of infection May 5: 500 US cases, first US death May 7: 1000 US cases May 20: 10,000 cases worldwide June 11: 30,000 cases worldwide, WHO declares global pandemic Sept 10: new vaccine developed Sept 15: govt approves vaccine Oct 5: first vaccines available

  37. WHO Pandemic Scale Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Phase 1-3 = sporadic cases or small clusters of disease in people, no sustained human-to-human transmission or community level outbreaks Phase 4 = capable of causing community-level outbreaks Phase 5 = human-to-human spread in at least 2 countries in one WHO region Phase 6 = global pandemic, outbreaks in two countries in different WHO regions

  38. Epidemic Curve in Mexico Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Describe the shape of the curve When is there a switch from passive to active surveillance? How does the curve change after active surveillance starts? How would you characterize the validity of the incidence measurements collected during passive surveillance?

  39. US Epidemic Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Confirmed cases by state, June 3, 2009 What patterns do you see?

  40. US Epidemic Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • From April-October, 2009, the CDC estimates: • 22million people infected • 98,000 hospitalization • 3,900 H1N1 related deaths • Highest rates among 5-24yo, lowest rates among those >65yo • Median age of hospitalized patients was 20yo • Outbreaks common in settings where young people congregate (schools, colleges)

  41. Surveillance in the Age of Google Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Real-time estimates of disease occurrence http://flutracker.rhizalabs.com/

  42. Vaccine Development Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Takes 4-6 months from receipt of virus to vaccine production. Both live-attenuated, and inactive vaccines produced. Addition of adjuvant considered • May 27: GlaxoSmithKline received virus from CDC for production of vaccine • July: production of vaccine begins • Vaccine production: growing viral particles from clinical samples with another influenza virus in chicken eggs. Identify recombinant virus that has sufficient antigenic properties (to lead to immunity). Optimize growing conditions for large-scale growth

  43. H1N1 Vaccine Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • At first limited to high risk individuals: • Health care workers • Pregnant women • The young (6mo – 24yo) • Younger than 64 with conditions that increase risk for flu related complications (asthmatics, diabetics) • Caregivers of newborns

  44. Previous Flu Pandemics Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Reference: D. Heymann, World Health Organization * Estimate as of May 2, 2010: WHO † Estimate April 12, 2009 – April 10, 2010 Srestha using CDCs EIPL Compared to other flu pandemics, H1N1 was extremely mild

  45. Why all the fuss? Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Two scenarios for pandemic influenza in the US in the 21st century (CID April 1, 2008) One study estimated that a virus with similar mortality rates as 1918 flu pandemic could kill 50-80 million people

  46. H1N1 Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic • Triple-reassortment • Swine viral genes (HA, NP, NA, M, NS) • Avian viral genes (PB2, PA) • Human viral genes (PB1) • HA of H1N1 has a unique genetic sequence • New version of HA different enough that exposure to prior version of HA is not protective • Antigenically similar to 1918 H1N1

  47. “Swine Flu” Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Originally called swine flu b/c was demonstrated to be a descendent of a virus that primarily infected pigs Later shown to be a recombinant virus that had swine, avian, and human influenza genes Public health movement to call it “H1N1” instead of “swine flu” b/c people began fearing that it could be transmitted via pork products (Egypt ordered the slaughter of 300,000 pigs to prevent transmission)

  48. Swine Flu Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic

  49. H1N1 Today Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Post-Pandemic Period WHO expects that H1N1 virus will take on the behavior of a seasonal flu and continue to circulate for several years Vaccination, vigilance, and quick detection have weakened the transmission cycle Currently seeing a mix of viruses during seasonal flu 20-40% of populations have been infected, vaccination has protected at-risk populations

  50. What Have We Learned Introduction to influenza Infectious disease definitions Outbreak epidemiology The 1918 Flu Pandemic The 2009 H1N1 Pandemic Quick mobilization of physicians and public health workers Active disease monitoring important Rapid vaccine development Global surveillance and collaboration Communication with public, media important step Dodged a bullet (did not see mutation to more lethal form, no widespread development of resistance to Tamiflu) Better safe than sorry!

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