Influenza. Tim Uyeki MD, MPH, MPP, FAAP

Transcription

1 Influenza Tim Uyeki MD, MPH, MPP, FAAP Influenza Division National Center for Immunization and Respiratory Diseases Coordinating Center for Infectious Diseases Centers for Disease Control and Prevention August 7, 2006

2 Influenza Acute febrile respiratory illness Symptoms, signs may differ by age Etiology: Infection with influenza viruses Orthomyxoviridae Negative single stranded RNA viruses 4 Genera: 3 Influenza virus types, Thogotoviruses Types A, B, C Types A and B are important for humans 8 single stranded negative sense gene segments code for at least 10 proteins Reassortment (gene exchange) occurs Type A viruses cause greatest morbidity and mortality

3 Influenza Virus

4 Key Influenza Viral Features Surface proteins (major antigens) Hemagglutinin (HA) Site of attachment to host cells Antibody to HA is protective Neuraminadase (NA) HA Helps release virions from cells Antibody to NA can help modify disease severity NA

5 Influenza Viral Shedding Influenza A and B viruses infect and replicate in epithelial cells of the upper respiratory tract: primarily shed in the upper respiratory tract (can infect lower respiratory tract) Viral shedding occurs the day before illness onset Peak viral shedding on Day 1 of illness Duration Adults may shed viruses for 4-6 days Young children may shed for longer periods Immunocompromised can shed for months Sub-clinical infection can occur Best clinical specimens to detect influenza viruses Close to illness onset (<4 days) Nasopharyngeal or nasal swabs, aspirates, washes

6 Influenza Transmission: person-to to-person Large droplets: : coughing, sneezing Highly contagious to susceptible persons Replicates in large airway epithelial cells Viremia has rarely been reported Incubation period: days Viral shedding can begin before symptom onset Peak viral shedding on first day of symptoms Adults may shed for days Children may shed for longer periods Immunosuppressed, immunocompromised can shed for months

7 Log of Nasopharyngeal Virus Titer Viral Shedding Exposure Average Onset of Symptoms Days After Exposure (Adapted from Murphy BR et. al. J Infect Dis 1973)

8 Antigenic Drift Influenza Viruses are Dynamic Point mutations in the hemagglutinin gene of influenza viruses cause minor antigenic changes to hemagglutinin protein Gradual, continuous process Immunity against one strain may be limited Vaccine strains must be updated each year 6-8 month process Targeted at high-risk (inactivated); healthy (LAIV) Bi-annual process for Northern and Southern Hemispheres Antigenic Drift causes seasonal epidemics

9 Global Influenza Surveillance WHO Global Influenza Programme Goals Monitor and identify human influenza viruses for global influenza vaccine strain selection Detect emergence of novel influenza A viruses with human pandemic potential 4 WHO Collaborating Centers Melbourne, Tokyo, London, CDC >110 National Influenza Centers Bi-annual influenza vaccine strain selection process Northern Hemisphere Southern Hemisphere

10 U.S. Influenza Surveillance Pediatric Hospitalization (EIP & NVSN) Sentinel Providers Laboratories State and Territorial Epidemiologists Health Departments CDC Pediatric Mortality Vital Statistics Registrars Other Public Health Officials Physicians Media Public

11 Influenza-like Illness: Case definitions for surveillance CDC: temperature F (37.8 C) and either cough or sore throat WHO: temperature >38.0 C and either cough or sore throat, in the absence of any other known diagnoses Both are non-specific for influenza

12 U.S. Virologic Surveillance ~130 participating WHO/NREVSS laboratories Report weekly: # specimens tested # positive for influenza: type, subtype, age Laboratories submit subset of isolates to CDC strain surveillance lab for: Detailed antigenic characterization Sequencing of some isolates Antiviral resistance testing

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14 Hospitalizations Attributable to Influenza (U.S.) Average of >200,000 influenza-related hospitalizations/year Estimated by modeling studies using retrospective data and influenza surveillance data Children: High rates in young children <2 years Children 2-5 years next highest High rates for children with chronic high-risk conditions Adults: Highest rates in persons 65 years High rates in persons with chronic illness Simonsen L, et al. JID 2000;181: ; Izurieta HS et al., NEJM 2000;342: ; Neuzil KM et al., NEJM 2000;342: ; Thompson WW et al., JAMA 2004;292: ; Neuzil KM et al. JID 2002;185:

15 Outpatient and Emergency Room Presentations Lab-confirmed influenza illness Febrile upper respiratory illness Febrile lower respiratory illness (pneumonia) Gastrointestinal (with dehydration) Sepsis-like syndrome (fever without a source) Common complications Otitis media Exacerbation of chronic illness Other complications Myositis (gastrocnemius) Febrile seizures

16 Hospitalized conditions Exacerbation of chronic illness Coronary artery disease (myocardial infarction, congestive cardiac failure) Respiratory disease Bronchitis, Croup, Bronchiolitis Pneumonia Secondary Bacterial (S. pneumoniae, MSSA, MRSA) Primary viral Sepsis-like syndrome (fever without a source) Dehydration, Gastrointestinal illness Uncommon complications Myocarditis, rhabdomyolysis Invasive bacterial infection (GAS, N. meningitidis) Neurological complications Toxic shock

17 Hospitalizations Per 100,000 Person Years Influenza-Associated Hospitalizations By Age Group* Yrs 5-49 Yrs Yrs > 65 Yrs Age Group *Thompson, CDC, 2004, unpublished data

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19 Mortality attributable to Influenza (U.S.) Average of >36,000 influenza-related deaths/year Estimated by modeling studies using retrospective data and influenza surveillance data Children: Limited data Estimated average of 92 influenza-related deaths among children aged <5 years each year Adults: Majority of deaths occur among persons 65 years Other high-risk groups include persons with chronic illness Thompson WW et al., JAMA 2003;289:

20 Influenza-Associated Deaths By Age Group* R&C Deaths Per 100,000 Person Years < 1 Yrs 1-4 Yrs 5-49 Yrs Yrs 65+ Yrs *Thompson, et al. JAMA 2003 Age Group

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22 Deaths related to Influenza Increasing, U.S., Number of Death Thompson et al. JAMA 2003;289: Years P & I R & C All-cause

23 Global Impact of Influenza Seasonal epidemics in temperate regions U.S., Canada, Europe, Russia, China, Japan, Australia, Brazil, Argentina Severity varies from year-to-year Year-round activity in tropical climates Equatorial Africa, Southeast Asia Sporadic outbreaks Rural populations Madagascar 2002; D.R. Congo 2002 Travelers: Alaska, U.S., Yukon Territory, Canada pandemics in the 20 th century

24 Influenza Activity and Seasonality, Thailand

25 160 Influenza Surveillance in Indonesia NAMRU2, Wet Dry September October NovemberDecember January February March April May June July August Flu A Flu B

26 Influenza A Viruses Subtypes based on surface glycoproteins Hemagglutinin (HA) and Neuraminidase (NA) Current human influenza A virus subtypes: H1N1,, H1N2, H3N2 Cause epidemics and pandemics Infect multiple species Humans Birds (wild birds, domestic poultry) Other animals: pigs, horses, dogs, marine mammals (seals, whales)

27 Natural reservoir for new human influenza A virus subtypes: Wild waterfowl, aquatic ducks Avian Influenza A Viruses H1 - H16 N1 - N9 Human Influenza A Viruses H1 - H3 N1 - N2

28 Antigenic shift causes pandemics Emergence of a new human influenza A virus subtype (new HA subtype) through: Genetic reassortment (human and animal viruses) Direct animal (poultry) to human transmission A pandemic can occur if: (1) A novel influenza A virus infects humans; and (2) Causes disease; and (3) Efficient and SUSTAINED virus transmission occurs among humans (sustained person-to-person spread) A pandemic can result in: Widespread morbidity and mortality worldwide High proportion of deaths among young adults

29 Avian virus Avian reassortant virus Antigenic Shift Pandemic A/HK156/97 (H5N1) Quail/HK/G1/97 (H9N2) Goose/Guangdong/1/96 (H5N1) Teal/HK/W312/97 (H6N1) Avian virus Huma n virus Reassortment in humans Model of the emergence of a pandemic influenza virus Reassortment in swine Avian-human pandemic reassortant virus

30 Estimated Impact of Influenza Pandemics Spanish Flu (H1N1) million deaths worldwide >500,000 U.S. deaths Asian Flu (H2N2) 70,000 U.S. deaths Hong Kong Flu (H3N2) 34,000 U.S. deaths

31 Infectious Disease Mortality, United States--20 th Century Armstrong, et al. JAMA 1999;281:61-66.

32 Emergence of Influenza A Viruses in Humans H1N1 H2N2 H3N2 Spanish Asian Hong Kong Influenza Influenza Influenza H1N1 Russian Influenza H9 H5 H7 H5 Avian Influenza H / Influenza A reservoir Ag drift Ag shift

33 U.S. Impact Estimates for the Next Influenza Pandemic Deaths: ,000 Hospitalizations: ,000 Outpatient care: m Total infected: m %.1-.3% 6-15% 15-35% Health related economic impact Estimated: $71 to $166 billion Meltzer M, et al. Emerging Infectious Diseases 1999;5:

34 Prevention of Influenza Influenza vaccine (trivalent) WHO biannual strain selection Northern Hemisphere strains (February) One Type B strain, 2 type A strains (H1N1, H3N2) U.S. strains selected by FDA VRBAC 6-8 months to produce vaccine for the U.S. Inactivated, for intramuscular injection Live, attenuated, intranasal spray *U.S. Children: 7.4% received 1 or 2 doses; 4.4% fully vaccinated ( season) *CDC. MMWR 2004;53:

35 Influenza Testing Influenza viruses primarily infect epithelial cells of the upper respiratory tract Adults shed viruses for approximately 5 days Young children and immunosuppressed can shed viruses for longer periods Clinical specimens to detect human influenza viruses Close to illness onset (<4 days) Respiratory specimens: Nasopharyngeal swabs, nasal swabs, NP aspirates, nasal aspirates Tests: Viral Culture - isolation ( gold standard ) Immunofluorescence (DFA, IFA) Rapid diagnostic test RT-PCR, rrt-pcr Serology (requires paired sera)

36 Antiviral Medications for Influenza Treatment of Influenza A virus infections 4 approved drugs Amantadine, Rimantadine Oseltamivir, Zanamivir Treatment of Influenza B virus infections 2 approved drugs Oseltamivir, Zanamivir All drugs can decrease viral shedding and symptoms of influenza by one day CDC does not recommend use of Amantadine or Rimantadine due to widespread resistance, 2006

37 Influenza Antiviral Drugs Treatment of influenza Treatment should be started <48 hours from illness onset, for 5 days Can reduce symptoms by one day Chemoprophylaxis 70-90% effective in preventing illness from influenza (infection may still occur) Examples: Control nosocomial outbreaks, Patients who cannot receive vaccine

38 Summary Human influenza virus infection causes substantial morbidity and mortality worldwide, including seasonal outbreaks Because influenza viruses are continuously experiencing antigenic drift, surveillance is needed year-round for vaccine strain selection Antigenic shift can rarely lead to human pandemics with high global morbidity and mortality

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41 WHO Global Preparedness Plan 2005 WHO revised plan (April 2005) Redefines pandemic phases, associated public health risk 3 periods (interpandemic, pandemic alert, pandemic) 6 phases Outlines WHO actions to be taken during each phase and provides guidance for countries to develop national pandemic plans Objectives and actions: Planning and coordination Situation monitoring and assessment Prevention and containment (non pharmaceutical public health interventions, vaccines, antivirals) Health system response Communications

42 WHO Pandemic Periods and Phases, Revised, 2005