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