Global Influenza Epidemiology and Surveillance

Transcription

1 Global Influenza Epidemiology and Surveillance Lyn Finelli, DrPH, MS Surveillance and Outbreak Team Epidemiology Branch Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention August 1, 2011 The findings and conclusions in this presentation are those of the presenter and do not necessarily represent those of CDC.

2 Outline Influenza pathogenesis and basic virology Influenza epidemiology and burden of disease Global Influenza Surveillance and Seasonality Overview of Influenza Surveillance in the US Conclusions

3 Influenza Highly contagious respiratory illness caused by influenza virus Annual epidemics in temperate zones and cyclical epidemics in tropics and subtropics Sporadic, unpredictable pandemics 1918, 1957, 1968 and 2009

4 Influenza Viruses Belong to the Orthomyxoviridae Family RNA virus Influenza types A, B and C A and B are major human pathogens 8 gene segments Surface proteins (major antigens) Hemagglutinin (HA) Site of attachment to host cells Antibody to HA is protective Neuraminadase (NA) HA NA Helps release virions from cells Antibody to NA can help modify disease severity

5 Influenza A HA and NA Subtypes H1 H2 N1 N2 H3 Other Animals N3 H4 Other Animals N4 H5 Other Animals N5 H6 N6 H7 Other Animals N7 Other Animals H8 N8 Other Animals H9 N9 H10 H11 H12 H13 H14 H15 H16

6 Influenza Virus Type A Current human subtypes: H1N1 & H3N2 Infects multiple species besides humans Birds, swine, horses, whales, seals Capacity for species jumping Capable of epidemics and pandemics

7 Genetic and Antigenic Variation Among Influenza A Viruses Continual development of new strains in response to immune selection Antigenic drift occurs in HA and NA Associated with seasonal epidemics Acquisition of point mutations Antigenic shift occurs in HA and NA Associated with pandemics Acquisition of novel genes through reassortment Appearance of novel influenza A viruses bearing new HA or HA & NA H5N1 in Asia

8 Timeline of Emergence of Influenza A Viruses in Humans H9 H5 H7 H5 H1pnd H1 H3 H2 H1 1998/

9 Influenza Virus Types B and C Influenza B humans only reservoir less mortality than type A associated with epidemics, not pandemics Influenza C Causes mild disease, sporadic cases Not included in vaccine

10 Why is Influenza a Major Public Health Problem? Certain groups can develop severe complications of influenza virus infection Exacerbation of chronic underlying medical conditions (e.g. heart failure, lung disease, etc.) Viral and bacterial pneumonia Complications can result in hospitalization/death Substantial economic impact Lost work / school days Can overwhelm medical care systems during epidemics

11 Influenza Virus Pathogenesis Acute febrile respiratory infection Characterized by Abrupt onset fever, chills, muscle aches, headache, fatigue Cough, pharyngitis, rhinnitis GI sx more common in children Sepsis-like syndrome in infants Elderly often without fever Pronounced systemic symptoms caused by cytokine response Complications Primary viral pneumonia Secondary bacterial pneumonia Worsening of underlying illness, e.g. asthma, CHF

12 Viral Shedding and Incubation Period Influenza A and B viruses primarily infect, replicate and are shed in the upper respiratory tract: Can infect lower respiratory tract Viral shedding occurs the day before illness onset with peak viral shedding on Day 1 of illness Duration of contagious period 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 Incubation period: 1-4 days (typically 2-3 days) 12

13 Transmission Definitions* Droplet Infections droplets >5 micrometers from cough/sneeze that do not remain suspended in the air Airborne (droplet nuclei) Smaller evaporated droplets or infected dust particles remain suspended in the air Contact Direct body-to-body surface contact and physical transmission of pathogen Indirect transmission after contact with contaminated inanimate object e.g. table, dressing * 1996 Guidelines for Isolation Precautions in Hospitals

14 Transmission of Influenza Limited studies, varying interpretations Contact, droplet, and airborne (droplet nuclei) transmission may all occur Relative contribution of each unclear Droplet thought to be most important Generated via coughing, sneezing, talking Most studies either Animals or human experiments under artificial conditions Outbreak investigations Unclear of infection source when community influenza

15 Sneezing and coughing generate a large number of particles of varying sizes Talking generates a significant number of particles Tidal breathing also generates some particles

16 Influenza Virus Viability at C in 5 Relative Humidity Levels Harper G. Airborne microorganisms Survival test with 4 viruses. J Hyg (London), 1961; 59(4):479

17 Influenza Clinical Diagnosis Clinical diagnosis often non-specific Laboratory diagnosis important for assessing disease burden, infection control Even at peak influenza season, nationally about 30-40% specimens tested for influenza are positive Infants can present with sepsis-like syndrome and elderly often present without fever thus influenza is especially under-diagnosed in these age groups

18 Laboratory Testing for Influenza Viral culture Gold standard but results take 7+ days usually Influenza isolates for yearly vaccine development RT-PCR Most sensitive and specific Becoming more widely available, but still expensive Point-of-care tests Generally 70% sensitive in children, lower in adults, 90+% specific Can provide results <30 minutes Immunofluorescence Requires intact cells and laboratory skill/experience Serology Must used paired serum samples >2 week delay for results

19 Annual epidemics Influenza Impact in U.S. 5% - 20% of US population infected highest illness rates in school age children highest complication rates in elderly Annual average of 220,000 hospitalizations About 50% in persons >65 yrs Estimated average of 3,349 to 48,614 influenzaattributable deaths/year (subtype and susceptibility dependent) >90% deaths are in persons >65 yrs ( )

20 Elderly >65 years Infants <6 months Individuals at Increased Risk for Hospitalizations and Death Persons with chronic medical conditions Heart or lung disease, including asthma Metabolic disease, including diabetes HIV/AIDs, other immunosuppression Conditions that can compromise respiratory function or the handling of respiratory secretions Pregnant women Nursing home residents U.S. Centers for Disease Control and Prevention Morbidly obese, Certain populations of indigenous peoples

21 Illness rates per 1000 population Average Influenza-Associated Illness Rates by Age Group* low estimate high estimate >60 25 to to 24 5 to 14 <5 Age group *Low estimate based on Tecumseh community studies. High estimate based on Houston family studies. Adapted from Sullivan KM. PharmacoEconomics 1996;9 Suppl.3:26-33.

22 Resp and Circ Hospitalizations per 100,000 Influenza-Associated Hospitalizations By Age Group (Thompson, JAMA, 2004) yrs 5-49 yrs Age yrs >64 yrs

23 Hospitalizations per 100,000 Mean Annual Influenza Hospitalizations per 100,000 in Children < 5 Years New Vaccine Surveillance Network, mos 6-23 mos Age mos Total <5 yrs

24 Resp and Circ Deaths per 100,000 Influenza-Associated Death Rates By Age Group (Thompson, JAMA 2003) , ,6 0,4 0,5 7,5 >64 yr yr 5-49 yr 1-4 yr <1 yr Age

25 Global Impact of Influenza and Seasonality

26 Global Impact of Influenza Seasonal epidemics in temperate regions Severity varies from year-to-year Most available data from industrialized countries Year-round activity in tropical and subtropical climates Equatorial Africa, Southeast Asia Very limited data on disease burden Sporadic outbreaks Rural populations Madagascar 2002; D.R. Congo 2002 Travelers: Cruise Ships, Group travel

27 Global Burden of Influenza Largely unknown Data from temperate climates Estimated 3-5 million severe cases/year Estimated 300, ,000 deaths/year U.S. Centers for Disease Control and Prevention

28 Relative Influenza Activity (Reichelderfer PS, et al. Current Topics in Medical Virology, 1988) Seasonal Occurrence of Influenza JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC N. Hemisphere Temperate Tropical S. Hemisphere Temperate

29 Influenza Activity and Seasonality, Thailand

30 Seasonality Weekly Frequency of Influenza Virus Isolation Viboud C, Alonso W, Simonsen L. PlosMed (2006)

31 Monthly Influenza Percent Positive in Temperate and Tropical Countries in the Americas Viboud C, Alonso W, Simonsen L PlosMed (2006)

32 How are data collected on influenza activity and seasonality?

33 International Influenza Surveillance (WHO)

34 The WHO Global Influenza Program 1947 WHO Global influenza system initiated First WHO Collaborating Center in UK Global Influenza Surveillance Network (GISN) comprised of National Influenza Centers (NICs) Network established in 1952 Excellent example of international collaboration and cooperation

35 Objectives of Global Influenza Surveillance Monitor circulating influenza viruses to determine new antigenic variants worldwide to update the vaccine annually Serve as the early warning system for novel influenza viruses Understand the impact of influenza on populations to guide policy and resource decisions

36 WHO Influenza Network How does the GISN achieve their objectives? Monitors emergence and spread of influenza variants Records levels of influenza activity by country/region Distributes reagents worldwide for identifying influenza viruses Disseminates information Makes twice yearly recommendations for influenza vaccine composition Pandemic planning

37 WHO Global Influenza Surveillance Network National Influenza Centers (~ 136 Laboratories in 106 Countries) Isolate influenza viruses Identify viruses and send to International Collaborating Center(s) Collect epidemiologic information May coordinate in-county networks International Collaborating Centers (Atlanta, Beijing, London, Melbourne, Tokyo) Analyze influenza viruses received Provide data for annual vaccine recommendations Prepare and distribute candidate vaccine strains World Health Organization (Geneva) Collect information for the Weekly Epidemiological Record (WER) for distribution Make annual vaccine recommendations Vaccine Producers

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39 For official, internal use only, please do not distribute Need for Integrated Lab and Epidemiologic Surveillance Historically, influenza surveillance data collection: Virologic data for vaccine selection Limited epidemiologic data Lacked international standards Gaps remain in understanding: Epidemiology, burden of disease Social factors, clinical risk factors Climatic factors

40 Epidemiologic Objectives of Influenza Surveillance Identify priority groups for prevention and control (risk groups for severe outcomes) Monitor the timing and intensity of influenza season Estimate burden of disease Inform development of public risk communication messages Monitor treatment practices Optional: Provide a platform for surveillance that could be expanded to include additional pathogens

41 WHO/EURO Recommendations for Surveillance Ideal to describe a broad range of medicallyattended influenza but Needs to be minimum basic influenza surveillance for countries with limited resources Sentinel Severe Acute Respiratory Illness

42 Integration into National Clinical Reporting Systems Sentinel sites -- framework could be integrated Adopt standard case definitions Establish small number of sentinel sites within a broader reporting system Aim for representativeness Assure high-quality data collection through intensive training and oversight Systematic laboratory testing from sentinels resource saving

43 Types of Syndromic Sentinel Surveillance Influenza like-illness (ILI) Captures patients with mild, febrile respiratory diseases at outpatient clinics. Acute Respiratory Illness (ARI) Captures patients with mild respiratory diseases at outpatient clinics, irrespective of fever Severe Acute-Respiratory Illness (SARI) Captures patients with severe respiratory disease at inpatient facilities. Will capture cases with exacerbations of chronic conditions, not just those with pneumonia.

44 Prioritizing the Focus of the Surveillance System Simple Model Budget: Low, no existing surveillance Sentinel surveillance for SARI -- as a minimum standard Small number of well-run sentinel sites Epidemiologic data collection Virologic testing

45 Prioritizing the Focus of the Budget: Medium Surveillance System Intermediate Model Sentinel surveillance for: SARI and outpatient ILI or ARI Virologic testing Epidemiologic data collection

46 Prioritizing the Focus of the Surveillance System Advanced Model Budget: High Sentinel surveillance for SARI, ILI and ARI Virologic testing Epidemiologic data collection Multiple pathogens

47 North America Influenza Transmission, May 2010 May 2011 B A(H1N1) 2009 A not subtyped A(H3N2) Mexico USA Canada Source: FluNet

48 Influenza Transmission, May 2010 May 2011, Europe and Asia Source: FluNet Western Europe Eastern Europe and Ctrl Asia East Asia B A(H1N1) 2009 A not subtyped A(H3N2)

49 Influenza Transmission, May 2010 May 2011, Tropical Regions A(H3) A(Not subtyped) A(H1N1)2009 B The Americas Sub-Saharan Africa 300 B A(H1N1) 2009 A not subtyped A(H3N2)

50 Distribution of virus subtypes by influenza transmission zone October 2010 April 2011 Source: WHO/GIP, data in HQ as of 02 May Data used are from FluNet ( 1:01 pm snapshot Virus subtype Influenza transmission zones Note: the available country data were joined in larger geographical areas with similar influenza transmission patterns to be able to give an overview ( The displayed data reports of the stated week, or up to two weeks before if no data were available for the current week of that area. The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO All rights reserved A(H1N1)2009 A(H1N1) A(H3N2) A (not subtyped) B Map_data_zone_global.Pe Map_data_zone_global.Pe

51 Rate per RCGP: Influenza-like illness current and recent seasons 2009/ / / / / Week number 17 August 2011 Return to main menu Return to RCGP menu Return to primary care menu NEXT

52 Australia Weekly Influenza-like Illness (ILI) consultation rates Source: Australia Department of Health and Ageing Beginning in Week 19, the rate of consultations to general practitioners has increased steadily (dark blue line). The rate of consultations to general practitioners increased sharply between Weeks 26 and 27.

53 New Zealand Weekly Influenza-like Illness (ILI) consultation rates to providers Source: New Zealand National Influenza Surveillance System

54 International Updates July 26, 2011 Temperate Southern Hemisphere Increasing activity in Western Pacific, mostly low elsewhere New Zealand (Kenepuru Science Centre, WHO) As of Week 28, Influenza-like illness consultations have increased for 9 weeks and are above baseline Australia (Australia Department of Health and Ageing, WHO) Sharp increase in influenza activity from week 19 through week 29 South America Tropical regions (WHO) Influenza activity lower than usual at this time of year, slight increases but low activity in Chile and Argentina Mostly low activity, some areas with active transmission Central America: increasing flu activity in Dominican Republic Africa: some Influenza B transmission in West Africa Temperate Northern Hemisphere (WHO) Influenza activity low

55 H5N1 Avian Influenza Update 2011 July 26, 2011 January 1 to July 26, confirmed human cases YTD, 23 fatal (50%) Cambodia: 6 cases (6 deaths) Egypt: 31 cases (12 deaths) Indonesia: 7 cases (5 deaths) Bangladesh: 2 cases

56 INFLUENZA SURVEILLANCE IN THE U.S.

57 CDC Seasonal and Pandemic Influenza Data Collection CDC conducts seasonal influenza surveillance for: Influenza viruses (WHO/NREVSS) Outpatient influenza-like illness (ILINet) Influenza-associated hospitalizations Influenza-associated pediatric mortality Mortality from pneumonia and influenza syndrome Geographic distribution of influenza activity Non-medically attended influenza infections (BRFSS Survey) Novel influenza A virus infection All seasonal influenza surveillance systems were used for pandemic influenza

58 VIROLOGIC SURVEILLANCE

59 Monitoring Influenza Viruses: WHO/NREVSS Virologic Surveillance 140 WHO & NREVSS U.S. Laboratories World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) Weekly reports of specimens collected during routine patient care Number of specimens tested and number positive for influenza (type, subtype, age group) Information used to: Identify circulating, and emerging strains with pandemic potential Describe drift away from current vaccine strains Detect antiviral resistance Identify future vaccine strains

60 Monitoring Influenza Viruses Numbers of Specimens Tested and Positive All Specimens Flu Positive

61 Number of Positive Specimens U.S. WHO/NREVSS Collaborating Laboratories, National Summary, Percent Positive A(2009 H1N1) A(Unable to Subtype) A(H3) A(H1) A(Subtyping not performed) B Percent Positive Week ending Week ending

62 ILI SYNDROMIC SURVEILLANCE

63 ILI Syndromic Surveillance ILINet ~3,800-4,000 physicians/clinics enrolled for the season with denominator of more than 36 million patient visits Weekly reports Total # of patient visits # visits for influenza-like illness (ILI) by age group ILI = fever 100 F (38 C) and cough or sore throat, in absence of a known cause Data weighted by state population for analysis Subset of specimens submitted for culture Early, peak, and late season

64 ILI Net Coverage

65 Growth of the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet) 4,500 enrolled providers 40,000,000 4,000 3,500 3,000 2,500 2,000 1,500 1,000 patient visits 35,000,000 30,000,000 25,000,000 20,000,000 15,000,000 10,000, ,000,

66 % of Visits for ILI Percentage of Visits for Influenza-like Illness Reported by the Outpatient Influenza-like Illness Surveillance Network (ILINet), National Summary October 1, 2006 July 16, /7/06 12/2/06 1/27/07 3/24/07 5/19/07 7/14/07 9/8/07 11/3/07 12/29/07 2/23/08 4/19/08 6/14/08 8/9/08 10/4/08 11/29/08 1/24/09 3/21/09 5/16/09 Week % ILI National Baseline 7/11/09 9/5/09 10/31/09 12/26/09 2/20/10 4/17/10 6/12/10 8/7/10 10/2/10 11/27/10 1/22/11 3/19/11 5/14/11 7/9/11

67 ILINet New Interactive Visualization and Data

68 Multi-Indicator System BRFSS Nationally representative household telephone survey Estimates non-medically attended influenza-like-illness biweekly to monthly Collaboration between CDC and States Respondent had ILI Onset timing Medical care was sought Medical diagnosis Influenza testing performed and results Antivirals were prescribed Household members had ILI Household members

69 Monthly % of reported ILI in adults and children, BRFSS, Sept. 1, 2009 March 31, 2010

70 Data Collection 16 Sites (mostly urban, suburban) All sites follow same protocol Case definition: hospitalized and influenza test positive Submit data every 2 weeks via FTP site moving to web-based 8% of US Population Hospitalization Surveillance FluSurvNet

71 Cumulative Rate per 100,000 Cumulative rate of hospitalization by age group per 10,000 population, FluSurvNet, EIP* Laboratory-Confirmed Cumulative Hospitalization Rates (per 100,000), Season Age Group yr 5-17 yr yr yr yr Total All Ages Case Counts Rates (per 100,000) September October November December January February March April MMWR Week *EIP results represent surveillance in the 10 EIP states (CA, CO, CT, GA, MD, MN, NM, NY, OR, TN)

72 MORTALITY SURVEILLANCE

73 Influenza-Associated Pediatric Mortality Became a nationally notifiable condition after severe influenza season in deaths in 40 States Reporting initiated in season Influenza-associated death in a person <18 yrs. Clinical and epidemiologic data Web-based reporting Data submitted daily Data reported weekly in MMWR and influenza update

74 Number of Influenza-Associated Pediatric Deaths by Week of Death: Season to Present Number of deaths Date # Deaths Current Week 28 # Deaths Since October 1, 2010 Influenza A (2009 H1N1) Influenza A (H3N2) Influenza A (Subtype Unknown) Influenza B Total Number of Deaths Reported = Number of Deaths Reported = Number of Deaths Reported= Number of Deaths Reported= Week of Death Deaths Reported Current Week Deaths Reported Previous Weeks

75 122 Cities Mortality Reporting System Purpose: monitor P&I related mortality in a timely manner Weekly reports from vital statistics offices in 122 US cities Total # of death certificates filed # with pneumonia or influenza listed anywhere ~ 25% of US deaths Web-based Timely Reporting lag 1-2 weeks

76 % of All Deaths Due to P&I Pneumonia and Influenza Mortality for 122 U.S. 10 Cities -Week Ending 16 JUL Epidemic Threshold 6 Seasonal Baseline Weeks

77 NOVEL VIRUS SURVEILLANCE

78 Novel Influenza A Virus Infection Novel influenza A viruses transmissible person to person may signal the beginning of a pandemic Human infections with influenza A virus subtypes that are different from the currently circulating human subtypes (A/H1 and A/H3) Substantial pandemic planning resources devoted to improving PCRtesting capacity for novel influenza A at public health laboratories in U.S. Public health labs provided with RT-PCR procedures and training for detection and characterization of human A/H1, A/H3 and Asian avian H5N1 ( ) In 2007, novel influenza A infections to the National Notifiable Diseases Surveillance System (NNDSS) Reporting and widespread lab testing has facilitated prompt investigation and accelerated the implementation of effective public health responses

79 Novel Influenza A Virus Infection

80 ADDITIONAL DATA METHODS FOR SITUATIONAL AWARENESS FOR SEASONAL AND PANDEMIC INFLUENZA

81 Additional Data Collection for Seasonal and Pandemic Influenza ICU Surveillance Conducted in response to pandemic to evaluate severity PALISI and ARDSNET Networks Web-based but no longer in operation Field investigations Conducted in response to an influenza outbreak Schools, Health Care Facilities, Community Special studies Conducted as needed to answer public health questions; typically months to years duration (Hosp and Death Case Series) Domestic Regional Surveillance Team Activated for Pandemic Response Only

82 Additional Data Collection Field Investigations Provide critical information on influenza transmission, severity, and risk factors that surveillance systems do not provide Examples: community attack rate investigations, outbreaks of antiviral resistant infections, novel influenza A clusters in humans Collaboration with state public health mandatory (invitation from state epidemiologist is prerequisite) Requires skills: Infectious diseases epidemiology Study design Sampling methods Contact tracing Specimen collection Data analysis

83 Additional Data Collection Special Studies Provide information describing influenza clinical spectrum, complications, and risk factors that standard systems do not provide Examples: ARI/ILI etiology, clinical case series, pneumonia etiology study Often conducted with partners in: Federal, state, local public health Academia

84 Additional Data Collection for Regional Surveillance Team CDC supports 1-2 FTEs in state and large local health departments for surveillance (epi and lab) through Epidemiology and Lab Capacity Cooperative Agreement Team communicated daily with CDC funded and epi program staff in health departments Structured data collection and situational awareness for Unusual or severe clinical presentations of influenza (incl. deaths) Institutional clusters or closings (prisons, schools, health care facilities) Cases in vulnerable groups (e.g., pregnant women) Laboratory specimens collected (AV resistance, novel influenza A) Reporting or surveillance problems

85 Additional Data Collection Regional Surveillance Team Team also provided epidemiologic and surveillance technical assistance to state and local health department partners Facilitated rapid response to requests for information from CDC (data, media reports) Facilitated field investigations

86 Summary and Conclusions 1 Epidemiology and Pathogenesis Influenza circulates worldwide in cyclical epidemics climate seems to be a strong determinant of the season Pandemics result from antigenic shifts of the virus and infection of a population with little or no pre-existing immunity Route of transmission can be droplet, airborne or contact Droplet has long been thought to be most common but more data are needed Influenza is largely a self-limited illness but severe complications can occur in vulnerable populations (v. young, v. old) The rate of severe complications per case is low but there are so many cases that severe complications are frequently seen during the season

87 Summary and Conclusions 2 Seasonality and Surveillance 8-30% of the worlds population is infected every year with newly evolved clades Seasonality Temperate climates annual outbreak during cold weather Tropical and subtropical climates have biannual to continuous circulation GISN links labs in 106 countries and is essential for Vaccine strain selection Early warning system for novel influenza virus circulation

88 Summary and Conclusions - 3 Surveillance Epidemiologic data are also needed to identify risk groups and make informed prevention and control recommendations Less mature and no international network WHO and CDC have developed basic epidemiology and surveillance recommendations for low, middle and high resource systems U.S. Surveillance 9 influenza surveillance systems that overlap and work together to provide comprehensive national and local information These systems rely on strong partnerships with (and funding of personnel in) state and local health departments to facilitate surveillance

89 Acknowledgements Carolyn Bridges Tim Uyeki Josh Mott Eduardo Azziz-Baumgardner Patrick Glew Lynnette Brammer Lenee Blanton Marc Alain Widdowson Nancy Cox Joseph Bresee Tiffany D Mello Surveillance and Outbreak Response Team Emanuele Montomoli Francesca Marzari ISIRV