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
Influenza Influenza • Acute febrile respiratory illness • Acute febrile respiratory illness • Symptoms, signs may differ by age Symptoms, signs may differ by age • • Etiology: Infection with influenza viruses • Etiology: Infection with influenza viruses • • Orthomyxoviridae Orthomyxoviridae • Negative single stranded RNA viruses • Negative single stranded RNA viruses • 4 Genera: 3 Influenza virus types, • 4 Genera: 3 Influenza virus types, Thogotoviruses Thogotoviruses • Types A, B, C • Types A, B, C • Types A and B are important for humans • Types A and B are important for humans • 8 single stranded negative sense gene • 8 single stranded negative sense gene segments code for at least 10 proteins segments code for at least 10 proteins • Reassortment • Reassortment (gene exchange) occurs (gene exchange) occurs • Type A viruses cause greatest morbidity and • Type A viruses cause greatest morbidity and mortality mortality
Influenza Virus
Key I nfluenza Viral Features Surface proteins (major antigens) • Hemagglutinin (HA) • Site of attachment to host cells • Antibody to HA is protective • Neuraminadase (NA) • Helps release virions from cells • Antibody to NA can help modify disease severity HA NA
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
Influenza Influenza Transmission: person- -to to- -person person Transmission: person • Large droplets • Large droplets: coughing, sneezing : coughing, sneezing • Highly contagious to susceptible persons • Highly contagious to susceptible persons • Replicates in large airway epithelial cells • Replicates in large airway epithelial cells • Viremia • Viremia has rarely been reported has rarely been reported Incubation period: 1- - 4 days 4 days Incubation period: 1 • Viral shedding can begin before symptom onset • Viral shedding can begin before symptom onset • Peak viral shedding on first day of symptoms • Peak viral shedding on first day of symptoms • Adults may shed for 4 • Adults may shed for 4- -6 days 6 days • Children may shed for longer periods • Children may shed for longer periods • Immunosuppressed • Immunosuppressed, , immunocompromised immunocompromised can can shed for months shed for months
Viral Shedding Exposure Average Onset of Symptoms Log of Nasopharyngeal 6 5 Virus Titer 4 3 2 1 0 0 2 4 6 8 Days After Exposure (Adapted from Murphy BR et. al. J Infect Dis 1973)
“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
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
U.S. Influenza Surveillance State and Territorial Pediatric Epidemiologists Hospitalization Pediatric Mortality (EIP & NVSN) Health Departments Vital Statistics Sentinel Providers Registrars CDC Laboratories Other Public Health Public Officials Physicians Media
Influenza-like Illness: Case definitions for surveillance • CDC: temperature ≥ 100.0 °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
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
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;181:831-837; Izurieta HS et al., NEJM 2000;342:232-239; Neuzil KM et al., NEJM 2000;342:225-231; Thompson WW et al., JAMA 2004;292:1333-1340; Neuzil KM et al. JID 2002;185:147-152
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
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
Influenza- -Associated Hospitalizations Associated Hospitalizations Influenza By Age Group* By Age Group* 600 Hospitalizations Per 100,000 Person Years 472 500 400 300 200 115 90 100 22 0 0 - 4 Yrs 5 - 49 Yrs 50 - 64 Yrs > 65 Yrs Age Group * Thompson, CDC, 2004, unpublished data
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;289:179-186
Influenza- -Associated Deaths By Age Group* Associated Deaths By Age Group* Influenza 120 R&C Deaths Per 100,000 Person Years 98.3 100 80 60 40 20 7.5 0.6 0.4 0.5 0 < 1 Yrs 1 - 4 Yrs 5 - 49 Yrs 50 - 64 Yrs 65+ Yrs Age Group * Thompson, et al. JAMA 2003
Deaths related to Influenza Increasing, U.S., 1976-1999 80000 70000 Number of Death 60000 50000 P & I 40000 R & C 30000 All-cause 20000 10000 0 7 9 1 3 5 7 9 1 3 5 7 9 7 7 8 8 8 8 8 9 9 9 9 9 - - - - - - - - - - - - 6 8 0 2 4 6 8 0 2 4 6 8 7 7 8 8 8 8 8 9 9 9 9 9 Years Thompson et al. JAMA 2003;289:179-86 .
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 1998 • 3 pandemics in the 20 th century
Influenza Activity and Seasonality, Thailand
Influenza Surveillance in Indonesia Influenza Surveillance in Indonesia NAMRU2, 1999-2005 NAMRU2, 1999-2005 Wet Dry 160 120 80 40 0 September October November December January February March April May June July August Flu A Flu B
Recommend
More recommend
