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Transcript
The Avian flu
H5N1
The Next Pandemic ?
• At the end of every summer million of
ducks and wild geese mass on Canadian
and Siberian lakes for their annual
migration.
• Influenza blooms.
– In intestinal tract of juveniles
– Diverse strains
– Shed virus as they migrate south
Influenza in Mammals
• In humans and pigs influenza
is very pathogenic.
– Infects the respiratory tract.
– Spread by aerosol.
• Three genera of Influenza: A,
B, and C.
– B and C endemic to human
population
– Type A is mostly found in birds
• A, is most lethal to humans.
The common symptoms of the flu
include:
•
•
•
•
•
•
•
Fever (usually high)
Headache
Muscle aches
Chills
Extreme tiredness
Dry cough
Runny nose may also occur but is more common in
children than adults
• Stomach symptoms, such as nausea, vomiting, and
diarrhea, may also occur but are more common in
children than adults
Virulence factors
• Portal of entry
– Respiratory mucus membrane
• Attachment
– Hemagglutinin
• Evade the immune system
– Antigenic drift or shift
– Envelope contains host proteins
• Tissue Distruction
– Inflamation of the respritory system.
Transmission
• Vehicle transmission through the Air.
• Flu season in northern latitudes is from
November to March, the coldest months. In
southern latitudes, it is from May until
September. In the tropics, there is not much flu
at all and no real flu season.
• In Italian, it was originally named influenza di
freddo, or “influence of the cold.”
– The virus is much more stable in cold dry wheather.
Influenza A
• Hemagglutinin (HA)
– Species specificity
– Main antigenic determinant
• Pandemic result of new HA
•
•
•
•
Neuraminidase
M2 (protein pump)
Lipid envelope
Single stranded RNA
– Eight segments called
ribonucleoproteins (RNAPs)
– make up 10 genes
NA removes
sialic acid and
allows for
escape
HA binds to
Sialic acid on
Intestinal and
respiratory
cells
M2 pumps ions into the
interior of endosome to
uncoat virus and
release RNAPs
Evolutionary Shape Shifters
• Compared to other pathogens, influenza A is
evolving at record breaking speed.
• From year to year its proteins change amino
acids to create modified strains requiring new
vaccines (antigenic drift).
• About every 20 -30 years influenza A will change
drastically enough to jump species (antigenic
Shift).
Mutation rate of Influenza
• The synthesis of RNA is radically error prone
– DNA polymerases proof read and auto corrects their
mistakes.
• 1 mutation every billion nucleotides
– RNA polymerases does not proof or correct their copy
• Error rate is 1 million times higher than DNA pol.
• Progeny often referred to as a “mutant swarm”.
– Lives on the edge of error catastrophe.
The Making of a Pandemic
• Influenza can mutate by great leaps.
– RNA is packaged in separate segments. a
co-infection of a host by two different
subtypes can result in a reassortment of their
genes and cause an antigenic shift.
• Influenza can trade RNP’s between different
strains. This antigenic shift produce new hybrids.
• These new hybrids have never been seen by the
human population. A pandemic will ensue.
History tells us it is not a matter
of “IF” but a matter of “When”
1918 Flu
• Researchers have Isolated and
sequenced the genes from the 1918 flu.
• The 1918 flu came from birds.
• It killed more people in 2 months than HIV
has killed in 20 years.
Scenario for a Pandemic
What we can expect
N1H5
1.
2.
Infect as much as a quarter of the world's population
and killing at least seven times the number of AIDS
deaths, all within a matter of weeks.
Travel will be restricted.
Food supply will shut down. People won’t travel between
countries.
Drugs come from other countries. We will run short on
pharmaceuticals.
Oil shipments are likely to lag as transportation between
countries grinds to a halt. Heat in the winter months may be
short supply
H5N1
• We have very little surge room in our
hospitals.
• Patients will be in gymnasiums and
coliseums.
– In Katrina we had 48 other states and other
countries that weren’t effected that could help.
But in a pandemic no one will be there to
help, everyone will be asking for help.
N1H5
• Mask (N95 ) will run out.
– No one will be allowed to leave their house
without a mask.
– Church and schools will all close.
– Many businesses will shut down
– Quarantines will be enforced.
– President Bush is talking about Marshal Law.
N1H5
• How do we handle the dead.
– 1.5 million dead in this country alone.
– We need to start planning for this.
• How many Body bags does our community have?
FDA Approves First U.S. Vaccine
for Humans Against the Avian
Influenza Virus H5N1
• The vaccine could be used in the event the
current H5N1 avian virus were to develop the
capability to efficiently spread from human to
human, resulting in the rapid spread of the
disease across the globe. Should such an
influenza pandemic emerge, the vaccine may
provide early limited protection in the months
before a vaccine tailored to the pandemic strain
of the virus could be developed and produced.
What vaccines are being tested?
• In 2004, NIAID awarded two contracts for
production and clinical testing of investigational
vaccines against H5N1. Both Sanofi Pasteur
(Swiftwater, PA) and Chiron (Emeryville, CA) are
producing vaccines made from inactivated H5N1
viruses for NIAID to test in clinical trials. Under
these contracts, sanofi pasteur has already
delivered more than 8,000 doses to NIAID;
Chiron will produce 10,000 doses, which are
expected to be delivered to NIAID within the next
few months.
When did NIAID begin testing the
H5N1 vaccines?
• The first clinical trial began in April 2005; it is
testing the vaccine produced by sanofi pasteur
in 451 healthy adults ages 18 to 64. This trial,is
investigating the safety of the vaccine and its
ability to generate an immune response
• So far the vaccine has failed to provide
adequate immunity even after a second booster.
(For more info, visit www.ClinicalTrials.gov.)