Infectious disease epidemiology describes influenza as an acute viral infection typically causing abrupt onset of fever and respiratory symptoms like cough and sore throat. Complications can include primary viral or secondary bacterial pneumonia. Influenza viruses are transmitted through respiratory secretions when people cough, sneeze or talk. There are annual epidemics in winter months in temperate regions that vary in severity each year. Pandemics occur less frequently and represent major antigenic shifts in influenza virus subtypes. Surveillance, vaccines, antiviral drugs, rest, and handwashing help prevent and treat influenza.

1. Infectious disease epidemiologyInfluenza

2. InfluenzaClinical FeaturesAbrupt onset of fever and respiratory symptoms, including cough, rhinorrhea and sore throatMyalgia and headache are more common w/ influenza than with other respiratory infectionsMalaiseProstration GI symptoms not common in adults, but 50% of infant and child infections may have vomiting, abdominal pain and diarrheaUsually lasts 3 to 5 days, but complications can prolong the illness in the elderly and people with chronic illnesses

3. InfluenzaClinical Features – Complications:Some patients can develop primary influenza viral pneumonia, which can be fatal (uncommon)Secondary bacterial pneumonia may occur up to two weeks after the acute viral infectionIn infants and children, otitis media and croup are common complicationsMyocarditis, myositis and encephalitis are less frequent complications

4. InfluenzaTransmission

5. InfluenzaTransmissionSpread through respiratory secretions of infected individuals (may contain up to 105 virus particles/mL)Infectious aerosols are generated during coughing, sneezing and talkingInfectious secretions are also spread by direct (e.g. kissing) or indirect (e.g. nose-finger-doorknob) contact with respiratory mucosa

8. InfluenzaTransmissionThe inhaled virus attaches to columnar epithelial cells of the upper respiratory tract and initiates a new infectionIncubation period is from 1 to 4 daysInfected hosts are capable of transmitting the virus from shortly before the onset of clinical disease up to the 4th or 5th day of illness

10. InfluenzaDiagnosisCannot be diagnosed from clinical signs or symptomsOnly viral culture or serology can definitely identify the presence of influenza virus

11. InfluenzaThe virus

12. InfluenzaThe VirusA, B, and C typesType AHemagglutinin (HA) and neuraminidase (NA) are surface glycoproteins that are important in both pathogenesis and immune protection from infection: subtypes of influenza A virus are determined by these two surface antigens

13. InfluenzaType A virusHA functions as the attachment protein to gylcoproteins on columnar epithelial cells of the respiratory tractSpecific antibodies to HA epitopes prevent attachment and entry of the influenza virus into the host cellsHA specificity for receptor binding is a determinant of which species can be infected (host range)HA is a virulence determinantNA cleaves sialic acid residues to allow virus release from the host epithelial cellSpecific anti-NA antibody presumably diminishes release of virions from host cells

14. InfluenzaMechanisms of Antigenic Variation (most relevant to A type virus)A little background:RNA viruses are low-fidelity, i.e. high rate of spontaneous mutationInfluenza A is segmented, which contributes even more to it’s low-fidelity

15. InfluenzaMechanisms of Antigenic VariationAntigenic drift:The minor yet frequent genetic changes in the HA and NA surface antigens There is roughly a 1% change in the amino acid composition of the HA antigen per year

16. InfluenzaMechanisms of Antigenic VariationAntigenic shift:Major changes in the HA or NA surface antigens, or both, lead to a new subtypeIt is believed that after several decades (typically between 10 and 30 years) of circulation of a specific A subtype, most members of the population will have antibody to that subtypeThis produces selective pressure on the virus and leads to new shift variants

17. InfluenzaEpidemiology – Annual EpidemicsFollow predictable patternIn North America, usually occur between November and March: manifested first by high rates of school and industrial absenteeism, followed by an increase in visits to health care facilities, an increase in pneumonia and influenza hospital admissions, and finally an increase in deaths from pneumonia or influenzaIn any specific locality epidemic influenza often begins abruptly, reaches a peak within three weeks, and usually ends by 8 weeksA city or region can experience two sequential or overlapping epidemics with different strains of viruses in a single winter

18. InfluenzaEpidemiology – Annual EpidemicsIn the southern hemisphere, epidemics usually occur in the May to Sept. winter season; northern, Oct. to MayIn tropics, local/regional disease seasonality can follow the monsoons (or year-round isolation of virus may be observed)Winter season viral spread is thought to be favored by the fact that the virus survives better in environments of lower temperature and humidityIn tropical areas, however, viral spread during the monsoon season suggests that indoor crowding caused by the weather may be a more important factor in such regions

21. InfluenzaEpidemiology – Annual EpidemicsIn general, rates of infection are higher in infants and children than adults, and rates of hospitalization are highest in infants and lower in children and high in the elderly Families with children have the highest rates of infectionTherefore, relatively immunologically naïve children are important in the spread of epidemic strains

22. InfluenzaEpidemiology – Annual EpidemicsEach epidemic varies in size and impact, determined by the degree of antigenic variation of the new virus, its virulence, and the level of existing protective immunity in the infected populationDuring average epidemics in North America, attack rates are generally between 10% and 20% in large populations, however certain subpopulations (school children, nursing home residents) and local outbreaks can have attack rates of 40% to 50%.

23. InfluenzaEpidemiology – Annual EpidemicsIncidence is very difficult to measure because most people infected do not present to a hospital or clinician, and not all people with influenza-like illness have the fluNevertheless, CDC estimates between 35 and 50 million cases each year in the United StatesAccurate global estimates would be near impossible to produce

24. InfluenzaEpidemiology – Annual EpidemicsOver 20,000 influenza-associated excess deaths occurred in the US during each of nine epidemics between 1972 and 1991, and more than 40,000 deaths occurred during three of themAnnual winter increase in all mortality is substantially due to influenzaPeople aged 65 years or older account for 90% of the excess deaths associated with annual epidemicsSince the 1990s, influenza has been associated with an average of 226,000 hospitalizations per year in the US

25. InfluenzaEpidemiology– PandemicsThese are shift eventsFive in the last 100 years:1918 H1N1 – the most catastrophic, with a 20% case-fatality and killing between 50 and 100 million people worldwide1957 H1N1 to H2N21968 H2N2 to H3N21977 H1N1 reappeared causing 50% attack rates in people born after 1956Until 2009 the old H1N1 and H3N2 subtypes co-circulated the world together2009 new H1N1 replaces previous subtypes

26. InfluenzaEpidemiology– SurveillanceSentinel physician surveillance network: apprx 1000 physicians across the US record the total # of patients seen and the total with influenza-like illness from Oct-MayCollaborating lab surveillance system: 75 WHO labs and 50 US labs record the total # of specimens received respiratory virus testing, and the total # positive influenza isolatesThe 122-city mortality reporting system: % of deaths listed with pneumonia or influenza

27. InfluenzaEpidemiology – SurveillanceState and territorial epidemiologists’ report of influenza activity levelsInfluenza pediatric mortality: respiratory deaths in children under 18 is now reportable10 states require reporting of hospital admissions related to influenza in children“True” incidence data is reported by MMWR: comes from influenza hospitalization among children at the county level in three states

28. InfluenzaEpizootic Infections and Evolutionary HistoryBirds – water fowlPigs – epithelial receptors for both avian and human HA antigenHumans – unstable subtypes

29. InfluenzaPrevention and Treatment4 tried and true methods

30. InfluenzaVaccinesOld targets groupsPersons at increased risk for complicationsPersons aged 50-64 yearsPersons who can transmit influenza to those at high riskHealthcare workersPregnant womenPersons infected with HIVBreastfeeding mothersTravelersGeneral populationNew targets groups (CDC 2010): everyone >6 months old

31. InfluenzaVaccines - StrategyVirus mutability and antigenic drift require that a new vaccine is produced each year to counter the new antigenic variants that ariseVaccination of healthy adults should reduce reported respiratory illness by 20% and absenteeism by 36%Vaccination of healthy children should reduce all otitis media episodes by 40% and immunization of day-care children reduces illness in their familiesInactivated versus live attenuated vaccines

32. InfluenzaAnti-viral drugs (eg. Oseltamivir)Can limit disease in persons infectedCan limit the spread of infection among those who are infectious

33. InfluenzaStay home and rest when sick

34. InfluenzaHand washing