2009 (Pandemic) H1N1 Influenza Virus

Transcription

1 2009 (Pandemic) H1N1 Influenza Virus September 15, 2009 Olympia, Washington Anthony A Marfin Washington State Department of Health

2 Goals Understand current situation & pattern of transmission of 2009 H1N1 virus Understand indications for & methods of diagnosis Understand indications for & methods of treatment Know priority groups for vaccination Describe 2009 H1N1 influenza surveillance

3 Outline Influenza virology Influenza, the illness Seasonal vs. pandemic influenza Current situation reports What to expect this fall Hot topics in diagnosis Hot topics in treatment Surveillance [Note: No specific discussion of vaccination or vaccine AEs but willing to answer questions]

4 What Are Influenza Viruses? Orthomyxovirus: 5 species; only 3 cause human illness Influenza A Infects many mammals & avian species Influenza B Infects humans & seals Influenza C Infects humans & pigs Classified by matrix & nucleoproteins Segmented negative sense ssrna viruses 8 RNA / nucleoprotein segments coding 11 proteins Frequent mutation & rare segment reassortment Avian viruses can adapt to new species by sequential point mutation (e.g., 1918 H1N1)

5 Hemagglutinin Neuraminidase Matrix 2 Matrix 1 Influenza viruses classified on basis of 3 proteins in virus capsid H, N, & M proteins generally similar but have species-specific changes make them human, avian, or swine flu viruses

6 Nomenclature Virus Type Virus Subtype A /Human/California/01/ 2009 (H1N1) Type of Animal Year Isolated 6

7 What is influenza-like like illness (ILI)? 2 respiratory disease syndromes Upper tract Core sx: Fever plus cough or sore throat Lots of other symptoms Lower ( severe( acute respiratory illness [SARI]) Core sx plus SOB, tachypnea, hypoxia Pneumonia/Acute Respiratory Distress Syndrome ILI not specific for influenza virus infections

8 Viruses That Cause ILI 12 viruses noted in most epidemiology studies: Influenza A & B viruses Parainfluenza viruses 1 3 Respiratory Syncytial Virus Human metapneumovirus Adenovirus SARS coronavirus Two other newly described human coronaviruses Rhinoviruses

9 How Does Influenza Impact Human Health? Usually,, toddlers, children, & adolescents are primary transmitters of flu viruses Usually,, very young & older persons at risk for more severe disease, complications, & death Since mid-1950s, impact of flu with better clinical care Antibiotics for 2º 2 pneumonia Antivirals Supportive care & ventilator support Underutilize effective vaccine which is best & most cost-effective form of disease control

10 On average, each year, flu accounts for: 36,000 deaths 200,000 hospitalizations ,000,000 ILIs 600? Asymptomatic infections

11 On average, each year, flu accounts for: % 1% 600

12 Etiology of SARI due to Influenza Virus Primary influenza pneumonia ARDS cytokine storm SIRS ( sepsis( sepsis ) Unchecked viral proliferation Secondary bacterial pneumonia Streptococcus pneumoniae Staphylococcus aureus Exacerbation of underlying disease COPD (chronic bronchitis & emphysema) Asthma

13 Different Transmission Patterns: Seasonal vs. Pandemic Flu A viruses always mutating & reassorting segments Interspecies segment reassortment (poultry, pigs, humans) Every year,, virus proteins change a little Cause seasonal flu epidemics each year Control: Fine tune vaccine each year One vaccine dose (residual immunity from previous years) Rarely,, flu A virus protein(s) change a lot Worldwide epidemic transmission ( pandemic( pandemic ) Control: Mitigate impact while making new vaccine Usually two doses (no residual immunity)

14 Current Situation in the United States & Washington Since April 2009

15 Pandemic H1N Influenza Virus Pedigree, Eurasian Swine Influenza H1N1 (1979-present) Avian Influenza viruses Human seasonal Influenza H1N1 ( ) Human seasonal Influenza H2N2 ( ) Human seasonal Influenza H3N2 (1968-present) Human seasonal Influenza H1N1 (Re-merges 1977) No American Swine Influenza H1N1 (1918-present)

16 Pandemic H1N Influenza Virus Pedigree, Eurasian Swine A/H1N1 (1979-present)? 2009 Human A/H1N1 (2009-??) Human seasonal A/H3N2 (1968-present) Avian Influenza viruses No American Swine A/H1N1 (1918-present) Triple reassortant Swine A/H1N2 (1998-present) Human seasonal A/H1N1 (1977-present)

17 Pandemic H1N Influenza Virus Pedigree, Eurasian Swine A/H1N1 (1979-present) Initially identified in 2 girls in So CA in April 2009 Genes from Human 4 flu A seasonal viruses A/H3N2 Human, bird, & two A/sw/H1N1 viruses (1968-present) Efficient human transmission Significantly different than seasonal flu virus Avian Pandemic transmission Influenza viruses? 2009 Human A/H1N1 (2009-??) No American Swine A/H1N1 (1918-present) Triple reassortant Swine A/H1N2 (1998-present) Human seasonal A/H1N1 (1977-present)

18

19

20

21

22 End of August 2009, 2009 H1N1 virus accounts for: 600 deaths (reported) 9,700 SARI cases (reported) ,000,000 ILIs (est.) 3,000? Asymptomatic infections

23 End of August 2009, 2009 H1N1 virus accounts for: % 0.5% 3,000

24 Number of hospitalized and deceased persons with confirmed infections due to 2009 H1N1 influenza virus in Washington

25 Mortality & morbidity of 2009 H1N1 virus, Washington, April 19 September 9, 2009 Age (years) SARI Hospitalized Died (54%) 95 (58%) 3 (19%) (24%) 36 (22%) 7 (44%) (22%) 33 (20%) 6 (38%) Total Pregnant 9 (5%) 7 (4%) 2 (12%)

26 Mortality & morbidity of 2009 H1N1 virus, Washington, April 19 September 9, 2009 Age (years) SARI Hospitalized Died (54%) 95 (58%) 3 (19%) 80% of hospitalized persons are less than 50 year old (24%) 36 (22%) 7 (44%) (22%) 33 (20%) 6 (38%) Total

27 Mortality & morbidity of 2009 H1N1 virus, Washington, April 19 September 9, 2009 Age (years) SARI Hospitalized Died (54%) 95 (58%) 3 (19%) (24%) 36 (22%) 7 (44%) 82% of fatal cases are in persons 25 years old or older (22%) 33 (20%) 6 (38%) Total

28 What can we expect this fall?

29 Co-circulation of Novel and Seasonal Influenza A Viruses

30 Co-circulation of Novel and Seasonal Influenza A Viruses

31 Co-circulation of Novel and Seasonal Influenza A Viruses

32 Situation in Fall 2009: Potentially Three Circulating Human Influenza A Viruses Human Influenza H3N2 (1968-now) Human seasonal Influenza H1N1 ( , 1977-now) Human pandemic Influenza H1N1 (2009) Two seasonal influenza viruses One pandemic influenza viruses

33 National Estimates, PCAST Factor Seasonal Flu Averages 2009 H1N1 virus Attack rate (ILIs) 5-20% 30-50% Hospitalizations/100 ILIs* 1 1 Deaths/100 ILIs* Deaths/year ~36,000 30,000-90,000 (For WA, ~1,800) Age distribution of deaths 90+% deaths >65 yrs 90+% deaths <65 yrs * Due to influenza A viruses.

34 Are those estimates realistic for Washington? 1957 pandemic model* 1968 pandemic model* Age group ILI Hosp Deaths ILI Hosp Deaths K 7.3K K 7K K 5.2K K 6.1K K 4.2K K 7.5K K 1.7K K 3.1K K 0.5K 50 67K 0.6K 70 Total 1.9M 18.9K ~ M 24.3K ~2400 * In the absence of vaccine, improved medical care & other community mitigation factors

35 Planning assumption #1: Assume 2009 A/H1N1 virus will co-circulate with seasonal A/H1N1 & seasonal A/H3N2 viruses. Planning assumption #2: Further gene segment reassortment is possible. Encourage seasonal & pandemic flu vaccination. Planning assumption #3: Cross-strain transfer of Tamiflu (oseltamivir)- resistance is possible. Encourage seasonal & pandemic flu vaccination.

36 Hot topics in diagnosis: General perception that rapid influenza tests (i.e., antigen detection tests) are awful

37 Performance of Rapid Influenza Tests (RIT) Relative to Real-Time Polymerase Chain Reaction (rtpcr) Assays Overall proportion, weighted average (%) Virus type tested High virus conc 2 (n) Lower virus conc 3 (n) 3 RITs 2009 H1N1 72% (77) 27% (31) Seasonal H1N1 78% (8) 67% (6) Seasonal H3N2 100% (28) 43% (14) 1 CDC MMWR Aug ;58(30): rtpcr Ct < 25 3 rtpcr Ct 25-37

38 RIT Assessment Conclusions All RITs more sensitive when virus concentration is higher (early in illness?) Best RIT performance for seasonal H3N2 viruses at higher virus concentration not H1N1 viruses Even at higher concentration, sensitivity of RITs appear greater for H3N2 than H1N1

39 General Clinical Considerations for Influenza Testing Test outpatients for influenza if test result is clinically important or result could change therapy or as part of disease surveillance Test inpatients if influenza suspected (all CAP?) Early, use RIT. If negative & diagnostic needed, consider virus culture, DFA, or rtpcr No role for influenza ELISA (serology) testing by (people seroconvert very rarely) For public health, virus culture most helpful. Allows subtyping & resistance testing Treatment based on clinical impression & patient s risk

40 What is the best test? Well, that depends Illness onset Detection thresholds Virus concentration Antigen detection ( RIT ) Direct fluorescent antibody assays Virus cell culture rtpcr Days from infection

41 Hot topics in treatment: Who should get oseltamivir or zanamivir?

42 Who should get treated? Recommend, lab-confirmed/highly suspected flu in: Adult/child at-risk of flu complications ( 48º after onset) Hospitalized persons despite admission dx, underlying illness, or flu vaccination status ( 48º after onset). Hospitalized persons whose positive flu test obtained >48 h after illness onset may benefit. Consider, lab-confirmed or highly suspected flu in: At risk outpatients with ILI not improving or whose positive flu test obtained >48 h after illness onset. Outpatients not at risk of complications but in close contact with at-risk persons

43 Who is at risk for complications? Children younger than 5 years old (children under 2 years old are at higher risk for complications than older children) Adults 65 years and older Pregnant women People with certain chronic medical or immunosuppressive conditions People younger than 19 years of age who are receiving long-term aspirin therapy

44 Hot topics on treatment: Why shouldn t I just give anyone with an ILI an antiviral medication?

45 Neuraminidase Inhibitors (NI), Resistance & Adverse Reactions Specific for flu A & B viruses ONLY Many viruses cause ILI (clinically indistinguishable) Widespread oseltamivir-resistance in seasonal H1N1 virus Most persons with ILI recover uneventfully without NIs 11 oseltamivir-resistant 2009 H1N1 virus isolates in US Treatment of SARI & ILI in immunocompromised persons Isolated from persons taking oseltamivir for?? indications (presumed emerged) Possible association with neuropsychiatric adverse events Japan limits prescription in adolescents & young adults British Medical Journal 2007 editorial suggests caution More frequent GI complaints in NI recipients

46 For more information from IDSA: Seasonal Influenza in Adults & Children Diagnosis, Treatment, Chemoprophylaxis, & Institutional Outbreak Management: Clinical Practice Guidelines of IDSA. Clinical Infectious Diseases April ;48:

47 For more information from CDC: Interim Guidance for Clinicians on Identifying and Caring for Patients with Swine-origin Influenza A (H1N1) Virus Infection (May 4, 2009; Questions & Answers: Revised Recommendations for the Use of Influenza Antiviral Drugs (September 8, 2009;

48 Influenza Surveillance

49 Goals of Influenza Surveillance Monitor activity & geographic spread of influenza. Estimate morbidity & mortality from influenza. Determine epidemiology of severe 2009 H1N1 cases Collect isolates to improve vaccine development and monitor antiviral resistance. Detect emerging threats such as avian & other novel influenza strains.

50 Estimating Morbidity and Mortality Mandatory reporting in Washington Died Hospitalized 122 Cities Pneumonia & Influenza Mortality Reporting Emerging Infections Program (EIP) Medically attended ILI ILI Net, syndromic surveillance ILI cared for at home Community Surveys Asymptomatic

51 Influenza Surveillance in Washington Mandatory reporting, hospitalized & fatal cases of 2009 H1N1 virus Laboratory surveillance (WHO/NREVSS) ILI-Net Reporting of aggregate influenza test results from laboratories Syndromic surveillance School absenteeism data 122 Cities Mortality Reporting System Pediatric influenza-associated Mortality

52 Mandatory Reporting of 2009 H1N1- Associated Hospitalizations & Deaths June 2, 2009: Emergency rule requiring healthcare providers & hospitals to immediately report hospitalized and fatal cases with confirmed 2009 H1N1 virus to local health jurisdiction where patient resides Emergency rule will be changed in mid-september to require healthcare providers & hospitals to immediately report of all influenza-associated hospitalizations & deaths

53 Thank you. Questions?

54 WA State Department of Health H1N1 Influenza Resources for Health Professionals, Disease Investigators, Laboratorians THURSTON COUNTY INFORMATION LINE DISEASE REPORTING LINE /7 PUBLIC HEALTH EMERGENCY CALL tml