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Influenza: Basic Features

Influenza: Basic Features. Niranjan Bhat, MD Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention. Impact of Influenza. An annual public health problem Substantial health impact

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Influenza: Basic Features

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  1. Influenza:Basic Features Niranjan Bhat, MD Influenza Branch Division of Viral and Rickettsial Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention

  2. Impact of Influenza • An annual public health problem • Substantial health impact • 10-35% of children each year • 5-20% of adults each year • Substantial economic impact • Lost work / school days • Overwhelmed medical care systems • “A singular global infectious disease threat”

  3. What is Influenza • “The flu” = acute febrile respiratory illness • Caused by infection with an influenza virus CDC WHO • Fever ≥100F (37.8C) • AND • cough and/or sore throat • In the absence of a known cause other than influenza • Fever >38.0 C • AND • cough and/or sore throat

  4. Transmission • Highly contagious • Primarily person-to-person • Respiratory droplets: coughing and sneezing • Direct and indirect contact • Airborne transmission occurs very rarely, if ever • Incubation period: 1-4 days • Subclinical infection can occur

  5. Transmission Infectious period • May begin 1 day before symptom onset • Peak viral shedding on day 1 of symptoms • Adults shed for 4-6 days • Infants and children may shed longer • Immunocompromised patients can shed for months

  6. Other Features • Headache, fatigue, body aches • Range of symptoms differ by age • Vomiting and diarrhea in children • Fever alone in infants • Often confused with other illnesses • “Viral illness” • “Cold” • “Stomach flu”

  7. Influenza Complications • Primary viral pneumonia/pneumonitis • Exacerbation of chronic conditions • Congestive heart failure, emphysema • New bacterial infections • Pneumonia, bacteremia, ear infections • Neurologic • Encephalopathy, transverse myelitis, GBS, febrile seizures • Less common • Shock, myositis, myocarditis, Reye syndrome

  8. Influenza Complications • Complications can lead to hospitalization or death • Certain groups are at higher risk

  9. High-Risk Groups • Certain underlying conditions are associated with increased risk of complications due to influenza: Pulmonary disease Cardiovascular disease Metabolic disorders Renal dysfunction Hemoglobinopathy Immunosuppression Long-term aspirin therapy Pregnancy Conditions leading to compromise in respiratory function

  10. Morbidity - Infections Monto et al. Am J Epidemiol 985;121(6):811-22

  11. Influenza Hospitalizations • Average of >200,000 influenza-related hospitalizations/year • Estimated by modeling studies using retrospective data and influenza surveillance data • High rates in persons with chronic high-risk conditions in all age groups • Children: • Highest rates in young children <2 years • Children 2-5 years next highest • Adults: • Highest rates in persons 65 years Simonsen, JID 2000; Izurieta, NEJM 2000; Neuzil, NEJM 2000; Thompson, JAMA 2004; Neuzil, JID 2002

  12. Morbidity - Hospitalizations Glezen, et al. J Infect Dis 1987;155(6):1119-26.

  13. Influenza Mortality • Average of >36,000 influenza-related deaths/year • Estimated by modeling studies using retrospective data and influenza surveillance data • Adults: • Majority of deaths (90%) occur among persons 65 years • Other high-risk groups include persons with chronic illness • Children: • Estimated average of 92 influenza-related deaths among children aged <5 years each year • 153 influenza-related deaths reported to CDC for the 2003-04 season • Fewer cases reported during 2004-05 season Thompson, JAMA 2003; Bhat, NEJM 2005

  14. Mortality Thompson, et al. JAMA 2003;289(2):179-86. Note: rates are 10-fold lower than graph represents the for first four age groups

  15. Deaths Related to InfluenzaU.S., 1976-1999 Thompson, JAMA 2003

  16. Influenza Vaccination • Recommendations of the Advisory Committee on Immunization Practices (ACIP) • Persons aged: • ≥65 years • 6-23 months • 50-49 years • All high-risk persons ≥6 months of age • Household contacts of high risk persons and health care workers

  17. Influenza Vaccine • Inactivated virus by intramuscular injection • Approved for all persons ≥6 months old • Live, attenuated virus by intranasal spray • Approved for healthy persons 5-49 years old • U.S. vaccine strains selected by FDA with CDC guidance (VRBPAC) (March) • Annual vaccine production requires 6-8 months • Must be administered annually

  18. Influenza Antiviral Drugs • Treatment • 5 day course • Should be started <48 hours from illness onset • Shown to reduce symptoms by approximately 1 day • Reduces viral shedding • Chemoprophylaxis • 70 - 90% effective in preventing illness from influenza • Infection may still occur Examples: • For control of nosocomial outbreaks • For patients who cannot receive vaccine

  19. Influenza Antiviral Drugs • Amantadine, rimantadine • Influenza A only • Oseltamivir, zanamivir • Influenza A and B • Approved ages vary by drug and indication • No treatment or prophylaxis approved for children aged <1 year

  20. Influenza Antiviral Drugs • Approved ages vary by drug and indication • None are approved for children aged <1 year • Neither treatment nor prophylaxis *New approval

  21. Relative Cost of AntiviralTreatment for 5 days Amantadine: $3.70 Rimantadine: $20.40 Oseltamivir: $63.40 Zanamivir: $51.40

  22. Influenza Testing • Viral culture (gold standard) • Serology (requires paired samples) • Immunofluorescence (IFA, DFA) • Reverse-transcriptase polymerase chain reaction • Rapid diagnostic testing • Specimens: nasopharyngeal swab is ideal • Also, nasal swab, NP or nasal aspirate • Best if close to illness onset (<4 days)

  23. Influenza Viruses • Illness caused by infection with an influenza virus • Primarily infects the upper respiratory tract • Negative single-stranded RNA virus • 8 gene segments code for 10 proteins • Influenza viruses classified into types A, B, and C

  24. Influenza A Viruses • Influenza A viruses further categorized by subtype • Subtypes are determined by two surface glycoproteins • Hemagglutinin (HA) • Site of attachment to host cell surface receptors • Antibody to HA is protective • Neuraminidase (NA) • Takes part in the release of virions from the cell

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

  26. Avian and Human Influenza A viruses Human Influenza A Viruses Avian Influenza A Viruses H1 - H16 N1 - N9 H1 - H3 N1 - N2

  27. Antigenic “drift” Minor antigenic changes to the hemagglutinin protein • Continuous process • Escapes immunity in the population • Vaccine strains must be updated each year • Two type A strains (H1N1, H3N2), one type B strain • Antigenic drift leads to seasonal epidemics

  28. Annual Influenza Epidemics

  29. Annual Influenza Epidemics

  30. Annual Influenza Epidemics

  31. Global Impact • Seasonal epidemics in temperate regions • U.S., Canada, Europe, Russia, China, Japan, Australia, Brazil, Argentina • Year-round activity in tropical climates • Equatorial Africa, Southeast Asia • Sporadic outbreaks among rural populations • Madagascar 2002; D.R. Congo 2002 • Sporadic outbreaks among travelers • Alaska, U.S., Yukon Territory, Canada 1998 • 3 pandemics in the 20th century

  32. Antigenic “shift” • Emergence of a novel human influenza A subtype: • Direct bird-to-human transmission • Through adaptation to a human host or • Genetic reassortment between human and animal influenza viruses • Co-infection within a human host • Co-infection within an intermediate host (eg, swine)

  33. Transmission to Humans Avian virus Avian virus Reassortment in humans Avian virus Human virus Reassortment in swine

  34. Influenza Pandemics Requirements: • Emergence of a novel human influenza A subtype (antigenic shift) AND • Efficient human-to-human transmission A pandemic can result in: • Increased overall morbidity and mortality • Higher proportion of deaths in younger adults

  35. Impact of Influenza Pandemics • 1918-19 Spanish Flu (H1N1) • 20-50 million deaths worldwide • >500,000 U.S. deaths • 1957-58 Asian Flu (H2N2) • 70,000 U.S. deaths • 1968-69 Hong Kong Flu (H3N2) • 34,000 U.S. deaths

  36. Belshe, NEJM 353(21):2209-11, 2005

  37. Infectious Disease Mortality(all causes), United States--20th Century Armstrong, et al. JAMA 1999;281:61-66.

  38. Estimated Impact of a Future Influenza Pandemic in the U.S. Meltzer, Emerg Infect Dis 1999

  39. Microbial Threats to Health: Emergence, Detection, and Response Institute of Medicine report Released March 18, 2003

  40. Factors in Infectious Disease Emergence • Ecological Changes • Human Demographics and Behavior • International Travel and Commerce • Technology and Industry • Microbial Adaptation and Change • Breakdown in Public Health Infrastructure • Human Susceptibility to Infection • Economic Development and Land Use • Climate and Weather • War and Famine • Lack of Political Will • Poverty and Social Inequality • Intent to Harm

  41. Timeline of Emergence of Influenza Viruses in Humans B Russian Influenza H1 Established Human Viruses Hong Kong Influenza H3 Asian Influenza Spanish Influenza H2 H1 1998/9 1918 1957 1968 1977 1997 2003

  42. Timeline of Emergence of Influenza Viruses in Humans Avian Influenza H9 H7 Avian Viruses H5 H5 B Russian Influenza H1 Established Human Viruses Hong Kong Influenza H3 Asian Influenza Spanish Influenza H2 H1 1998/9 1918 1957 1968 1977 1997 2003

  43. Seasonal, Avian, and Pandemic Influenza • Seasonal influenza viruses • A public health problem every year • Circulate throughout the human population • Spread easily from person to person • Avian influenza A (H5N1) • Devastating global outbreak in poultry • Rare but severe human infections • Does not spread easily from person to person • Pandemic influenza viruses • Appears in the human population periodically • H5N1 is a likely candidate, butis not a pandemic virus yet

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