Download Influenza

Influenza
Sara Finestone
April 8, 2010
The influenza virus causes 3-5 million cases of severe
illness and up to 500,000 deaths annually
Pandemics cause millions of
deaths
1918 Spanish flu
1918-1920
> 40 million
H1N1
Asian flu
1957-1958
2 million
H2N2
Hong Kong flu
1968-1969
1 million
H3N3
Swine flu
2009-present
15,000-20,000
H1N1
One study predicted 96% of deaths in a
future pandemic would be in
developing countries!
One study predicted 96% of deaths in a
future pandemic would be in
developing countries!
 Anti-viral medications remain too expensive
One study predicted 96% of deaths in a
future pandemic would be in
developing countries!
 Anti-viral medications remain too expensive
 World production of vaccines too low to provide to all
countries
One study predicted 96% of deaths in
a future pandemic would be in
developing countries!
 Anti-viral medications remain too expensive
 World production of vaccines too low to provide to all
countries
 Weak public health
infrastructure
Disease burden is much higher in
developing countries
Limited access to healthcare
Malnutrition
Immunosuppression
Parasitic diseases
Increased risk of severe complications
Infant pneumonia
Symptoms similar to
common cold
 Fever
 Cough
 Nasal Congestion
 Aches
 Fatigue
 Vomiting
Family Orthomyxoviridae
Influenza A
Thogotovirus
Isavirus
Influenza B
Influenza C
The Virion
 Glycoproteins
 Hemagglutinin (HA)
 Neuraminidase (NA)
The Virion
 Glycoproteins
 Hemagglutinin (HA)
 Neuraminidase (NA)
 Central Core
 7-8 pieces of single,
negative strand
segmented RNA
Virus is transmitted by:
 Airborne- aerosols containing virus
 Hand-eye/nose/mouth
The viral Hemagglutinin (HA) protein
mediates viral entry.
The viral Hemagglutinin (HA) protein
mediates viral entry.
 HA binds to sialic acid
receptors on epithelial cells of
nose, throat, and lungs
 HA determines what species
virus infects and where in the
respiratory tract virus binds
 Enters cell through endocytosis
 Acidic environment of endosome permits:
• Viral envelope to fuse with
vacuole’s membrane
• Protons to enter through
M2 ion channel, acidifying
core of virus
 Core dissembles, viral RNA and
proteins are released, and viral RNA
Polymerase makes mRNAs and
copies genome
 New viral proteins are
transcribed and viral
RNA, RNA-dependent
RNA polymerase and
other proteins are
assembled into new
virion
 Neuraminidase cleaves host sialic acid residue
to detach virion from host cell
Influenza is highly variable!
 RNA-dependent
RNA polymerase
makes about 1
error per replication
 7-8 segments of
RNA allow for
reassortment
This variability leads
to antigenic drift
and explains why
there are so many
strains of the flu.
Treatments target proteins
unique to virus
 M2 protein inhibitors
 Adamantanes
(Amantadine, rimantadine)
 Neuraminidase inhibitors
 Oseltamivir (Tamiflu)
 Zanamivir (Relenza)
Vaccines recommended
for high risk groups
 Inactivated virus or avirulent live virus
 Contain two influenza A subtypes and one influenza B
subtype
Differences between strains and
vaccines and circulating strains
limit vaccine effectiveness
 Produced 6-8 months ahead of flu season
References

Tosh, P.K., R.M. Jacobson, & G. Poland. “From surveillance through production to protection.” Mayo Clinic
Preceedings, 85 (2010): 257-273.

Oshitani, H., T. Kamigaki, and A. Suzuki "Major Issues and Challenges of Influenza Pandemic Preparedness in
Developing Countries." Emerging Infectious Diseases 14.6 (2008): 875-880.

Simonsen, Lone. "Influenza-related Morbidity and Mortality Among Children in Developed and Developing
Countries." International Congress Series 1219 (2001): 13-19

De Clercq, Erik. "Antiviral Agents Active Against Influenza a Viruses." National Reviews Drug Discovery 5
(2006): 1015-1025.

Bouvier, Nicole M., and Peter Palese "The Biology of Influenza Viruses." Vaccine 26.4 (2008): D49-D53.

Karlsson Hedestam, Gunilla B. et al "The Challenges of Eliciting Neutralizing Antibodies to HIV-1 and to
Influenza Virus." Nature Reviews Microbiology 6 (2008): 143-155.

Mitrasinovic, Petar M. Global View of the Fight Against Influenza. New York: Nova Science Publishers, Inc.,
2009. Print.

Ryan, Jeffrey R. Pandemic Influenza: Emergency Planning and Community Preparedness. Florida: CRC P,
2009. Print.

WHO, World Health Organization. <http://www.who.int/en/>.

CDC, Centers for Disease Control. <http://cdc.gov>.