NS2

Lipid Bilayer

NA (Neuraminidase)

HA (Hemagglutinin)

M2 (Ion channel)

M1 (Matrix protein)

NP (Nucleocapsid)PB1, PB2, PA

(Transcriptase complex)

Infected cell proteinNS1

Influenza A Virus Structure

Natural History of Influenza VirusesNatural History of Influenza Viruses

Topley and Wilson’s Microbiology and Microbial Infections. 9th ed, Vol 1, Virology. Mahy and Collier, eds, 1998, Arnold, page 387, with permission.

18801880 18901890 19001900 19101910 19201920 19301930 19401940 19501950 19601960 19701970 19801980 19901990 20002000

B

H3N2

H1N1

H2N2

H3N8

H2N?

H1N1

Serum antibody Serum antibody prevalenceprevalence

Virus isolationVirus isolation

Adapted from Levine AJ. Viruses. 1992;165, with permission.

Hemagglutinin Subtypes of Hemagglutinin Subtypes of Influenza A VirusInfluenza A Virus

SubtypeSubtype HumanHuman SwineSwine HorseHorseBirdBird

H1H1H2H2H3H3H4H4H5H5H6H6H7H7H8H8H9H9H10H10H11H11H12H12H13H13H14H14H15H15

CDC. Influenza Prevention and Control. Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.

Influenza Type A (H1N1) Influenza Type A (H1N1)

Cause of 1918-1919 pandemic (swine)Cause of 1918-1919 pandemic (swine)

Antigenic drift and subsequent epidemicsAntigenic drift and subsequent epidemics

Disappeared in 1957 with appearance of Disappeared in 1957 with appearance of H2N2 virus H2N2 virus

Reappeared as the “Russian flu” in 1977Reappeared as the “Russian flu” in 1977

Immunity in persons born before 1950Immunity in persons born before 1950

NEJM, June 2009

6

Novel H1N1 Weekly Surveillance Pattern: 2008-09 Through July 11, 2009

CDC: http://www.cdc.gov/flu/weekly/weeklyarchives2008-2009/WhoLab27.htm. Accessed July 30, 2009.

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regularly updated

7

Origins of Novel H1N1 Influenza

First described in April 2009 in Southern California and Mexico

By May 2009 had spread to 43 countries

– >12,000 hospitalizations

– >90 deaths

As of September 11, 2009

– >277,000 cases worldwide

– At least 3200+ deaths

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Trifonov V. N Engl J Med.2009; 361:115-119.

WHO. http://www.who.int/csr/don/2009_09_11/en/index.html. Accessed September 11, 2009.

8

WHO Definitions

Epidemic: human-to-human spread of the virus into at least two countries in one WHO region

Pandemic: human-to-human spread of the virus with community level outbreaks in at least one other country in a different WHO region than initial epidemic

Attack rate: numbers of cases of infection per unit of population

Virulence: severity of illness caused by a particular virus

WHO. http://www.who.int/csr/disease/avian_influenza/phase/en. Accessed July 28, 2009.Gallaher WR. Virology Journal. 2009, 6:51 doi:10.1186/1743-422X-6-51.

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9

Pandemic Severity Categories

Monto AS. Clin Infect Dis. 2009;48:S20–25.

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10

US Hospitalization Rate per 100,000 Population by Age Group Through July 2009

Fiore A. Presentation to Advisory Committee on Immunization Practices (ACIP). July 29,2009.

11

Cross-reactive Antibody to Novel H1N1 Influenza

Serum samples taken before and after vaccination with the 2005-06, 2006-07, 2007-08, or 2008-09 influenza season vaccines

Before vaccination cross-reactive antibody to the novel H1N1 virus seen in:

– Children <18 years = 0%

– 18-64 years = 6%-9%

– >60 years = 33%

Seasonal influenza vaccine did not elicit antibody response to novel H1N1

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CDC. Morbid Mortal Weekly Report. May 22, 2009. 58(19);521-524.

Oseltamivir Treatment: Antiviral Effect in Adults

Treanor JJ. JAMA. 2000;283:1016-1024. Hayden FG. JAMA. 1999;282:1240-1246.

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Time, hours

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Oseltamivir

Drug Administration

The viral titer area under the curve value was lower in the combined oseltamivir group (n=56) compared with placebo (n=13); P=0.02.

Effect of Oral Oseltamivir Treatment on Vital Titers in Nasal Lavages Following Experimental Influenza A/Texas/36/91(H1N1) InfectionViral Titres

Oseltamivir Treatment for Influenza: Adults (16 to 65 Years)

10397

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100

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Influenza infected Intent to treat

Ho

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Placebo Oseltamivir

21 hours**32 hours*

Treanor JJ. JAMA. 2000;283:1016-1024.

*P<0.001; **P=0.004. Treatment initiated within 36 hours of onset of symptoms.

Time to Resolution of All Flu Symptoms

Effects of Oseltamivir on Return to Normal Activities

*P<0.001; **P=0.02. Treatment initiated within 36 hours of onset of symptoms.

Health Status Activity

*

**

1.9d

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Time to Return to Normal Health and Activity

Day

s

Treanor JJ. JAMA. 2000;283:1016-1024.

15

Antiviral Treatment Recommendations

Treatment with oseltamivir or zanamivir is recommended for:

– All patients requiring hospitalization

– Patients at increased risk of complications• Children 0-4 years

• Pregnant women

• Persons with immune suppression, chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus) or > 65 years

Early treatment is key

Clinicians should not wait for confirmatory tests to treat

Postexposure prophylaxis should generally not be used

– Consider for high-risk person with close unprotected exposure

– Do not use if more than 48 hours after exposure

New Slide

Inactivated Vaccine Effectiveness by Age and Risk Group

Age/Risk group Outcome Effectiveness*

6m-16 years, healthy Influenza 50-90%

18-64 years, healthy Influenza 50-90%

>65 years, community Influenza 30-70%

Elderly, nursing home Influenza 30-40%

Elderly, nursing home Hospitalization 30-60%

*Effectiveness may be lower when vaccine and circulating strains antigenically different.

Source: CDC.

Impact of Vaccination of Japanese School Children on Mortality in the Elderly

Reichert TA. N Engl J Med. 2001;344:889-896.

Mandatory vaccination

70

60

50

40

30

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1954

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1962

1966

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1980

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Japan, pneumonia and influenza

Japan, all cause

US,pneumonia

and influenza

US, allcause

18

Host and Lineage Origins For The Gene Segments of 2009 A(H1N1) Virus

Garten RJ. Science. 2009;325:197-201.

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19

Approved Monovalent Vaccines for Novel H1N1 Influenza

New Slide

CDC. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Post-MarketActivities/LotReleases/ucm181956.htm. Accessed Sept. 28, 2009.