Influenza Today

Joseph Mester, Ph.D.September 24, 2009

Control of Infectious Diseases

Control of Infectious Diseases

Sanitation

Diagnosis

Antimicrobials

Vaccines

Still, an ongoing effort

Influenza Surveillance:CDC & WHO

Monitor prevalence of circulating strains and

detect new strains

Rapidly detect outbreaks

Assist disease control through rapid

preventive action

Estimate influenza-related morbidity,

mortality and economic loss

On the Web

http://www.flu.gov/

http://www.cdc.gov/H1N1FLU/

http://www.fda.gov/NewsEvents/PublicHealthFocus/

ucm150305.htm

Influenza Virus:Morbidity and MortalityDebilitating illness lasting 5-7 days

Most severe when there is underlying cardiac or pulmonary

disease

In the USA:

~150,000 influenza-associated hospitalizations per year

~7,000-70,000 average deaths per year

Up to 10x this number of deaths during pandemics

>500,000 (USA) and 20 Million deaths (world wide) in 1918

pandemic

Period Years Avg. DeathsPer year

Pandemic 1918-1920 225,000

Interpandemic 1920-1933 28,300

Interpandemic 1933-1957 10,100

Pandemic 1957-1960 39,000

Interpandemic 1960-1968 14,300

Pandemic 1968-1972 28,000

Interpandemic 1972-1981 22,000

Interpandemic 1981-1991 20,000

Influenza in the USA

Glezen, Epidemiology Revs. 1996. 18:64-76

Influenza Pathogenesis Respiratory & contact transmission

Replication in respiratory epithelium with subsequent

destruction of cells

Viremia rarely documented

Viral shedding in respiratory secretions for 5-10 days

Virus Variables

Virulence of Strain(s) e.g., H5N1 (pandemic) vs. H1N1 (seasonal) Influenza

• Immune suppression?

• Immune over-activation?

Tissue invasiveness

Speed of replication

Amount of necrosis

Dose

Co-infection / multiple infection

Influenza Virus Strains

Type A- moderate to severe illness- all age groups- humans and other animals

Type B- milder epidemics- humans only- primarily affects children

Type C- rarely reported in humans- no epidemics

Influenza Virus

A/Moscow/21/99 (H3N2)

Neuraminidase

Hemagglutinin

Type of nuclearmaterial

Virustype

Geographicorigin

Strainnumber

Year of isolation

Virus subtype

InfluenzaVirus

Enveloped RNA VirusCapsid with helical symmetryPolymorphic shapeSegmented Genome

8 Negative sense RNAs

Influenza Virus EvolutionGenetic Variability

Virus is prone to accrue nucleotide misincorporationserror-prone viral RNA-dependent RNA polymerase with no proof-reading functionMisincorporation rate for Influenza A virus:

1 x 10-4 - 10-5 changes/ nucleotide position/ replication cycle

Antigenic Drift

Replication in Animals(Other Than Man)

Agricultural Animals - Hogs

- Horses- Cattle- Sheep- Goats- Chickens- Turkeys

Aquatic/Wild Birds

- Ducks

- Geese

- Quail

- Pheasants

•Companion Animals

- Dogs- Cats

Antigenic Shift: Reassortment

Shift Timeline

Triple-Reassortant Swine Influenza A (H1)

11 sporadic cases 2006-2008

NEJM 2009

Pandemic Flu

•40 million deaths world-wide•675,000 in US •Mortality 2.5%•Flu killed more than WWI (1918)•Estimated that half of the US WWI casualties were due to Flu

1957 Asian Flu (H2N2)1968 Hong Kong (H3N2)1976 Swine Flu (H1N1)2009 Swine Flu (H1N1)

Avian Flu’s1997 H5N1 Hong Kong1999 H9N2 Hong Kong2004 H5N1

1918 (H1N1)

Others

San Francisco

Phases of the Immune Response to Influenza

Influenza Vaccines

Inactivated subunit (TIV) Intramuscular Trivalent

Live attenuated vaccine (LAIV) Intranasal Trivalent

Composition of the 2009-10 Seasonal Influenza Vaccine

A/Brisbane/10/2007 (H3N2)

A/Brisbane/59/2007 (H1N1)

B/Brisbane/60/2008

VaccineAttenuation

Influenza Antiviral Agents

Amantadine and rimantadine effective against influenza A only approved for treatment and prophylaxis

Zanamivir and oseltamivir neuraminidase inhibitors “generally” effective against influenza A and B

• Most currently circulating seasonal influenza A strains are resistant!

oseltamivir approved for prophylaxis