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Transcript
H1N1 Influenza A
pandemic strain
Martha Fulford, MD, FRCPC
Division of Infectious Diseases
McMaster University Medical Centre
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Overview of influenza
Definition of pandemic
pH1N1
Current Status
Influenza
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an orthomyxovirus RNA virus.
contains 8 segments of RNA put together with a
protein.
three types: A, B, C.
Influenza A, thought to be of avian origin, is
responsible for known human pandemics.
two main surface glycoproteins that allow the
virus to attach to and infect a host:
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hemagglutinin (HA)
neuraminidase (NA)
Influenza
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mutations within the HA and/or NA are
called “antigenic drift”.
a continual, ongoing process.
exchange of gene segments between
human and animal (avian or swine)
viruses results in “antigenic shift”.
result is a new virus to which humans (or
animals) have not previously been
exposed.
EID. Volume 12, Number 1, January 2006
Influenza

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influenza viruses cause annual seasonal
outbreaks (‘flu season).
attack rates range between 5 - 20%.
case fatality rate < 0.1%.
3,000 - 8,000 deaths annually in Canada.
Average of 4,000 deaths from seasonal
influenza. (Health Canada, http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseasesmaladies/pandem-eng.php)
Pediatric Influenza Deaths
www.cdc.gov/FLU/ weekly/index.htm
Influenza Pandemic

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The term "pandemic influenza” is used
when there is global spread of an
influenza virus with a new HA subtype.
WHO requires sustained human to human
transmission of a novel virus in at least
two WHO geographic regions.
Previous Influenza
Pandemics

Influenza pandemics:
1761-62
 1833-37 (2% case fatality rate?)
 1889-90
 1918-19 H1N1 – the Spanish ‘flu
 1957-58 H2N2 – the Asian ‘flu
 1968-69 H3N2 – the Hong Kong ‘flu
 2009 - H1N1 – the pH1N1 (swine flu)

pandemic H1N1 Influenza A
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Late March, 2009 an outbreak of a
respiratory illness which predominantly
affected young people was described in
Mexico.
Very quickly, a novel strain of H1N1
Influenza A (swine flu) was identified.
Subsequent rapid worldwide spread.
June 11, 2009 WHO raised its pandemic
alert level to 6, the highest level.
pH1N1 Current Status

As of October 4, 2009 WHO reports:
191 countries reporting cases (out of 195
countries in total)
 375,000 laboratory confirmed cases
 4,500 deaths.
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78 deaths in Canada as of Oct. 13
(including 4 pediatric deaths).
pH1N1 Current Status
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As of Oct 13, 1,504 cases hospitalized.
295 admitted to ICU.
Of the 78 pH1N1 deaths in Canada:
60.5% female
 median age 50
 aboriginal 11.8%
 underlying medical conditions 81.7%
 pregnant 5.1%

http://www.phac-aspc.gc.ca/fluwatch/09-10/w37_09/index-eng.php
pH1N1 Current Status
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increasing ILI across the country.
outbreaks declared in > 40 schools, including 6
schools and one day care in Hamilton.
approx. 97% of positive influenza A specimens
were pH1N1.
Local % positivity for Influenza A Oct 4-10:
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Children < 4: Influenza A 4%, Parainfluenza 11%
Persons > 4 yrs of age: Influenza A 11%
People with mild symptoms do not get tested.
pH1N1 Influenza A
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incubation period - 1 - 3 days.
shedding of virus likely from one day
before onset of symptoms to approx.
seven days after onset of symptoms.
young children and the immunocompromised may shed for longer periods.
majority of infections have resulted in very
mild disease.
pH1N1 Clinical Presentation
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fever
cough
sore throat
malaise and headache
vomiting & diarrhea (not typical of seasonal)
chills
myalgias & arthralgias.
pH1N1 Clinical Presentation
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children may not have typical respiratory tract
symptoms but will have:
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fever
irritability
lethargy.
with severe infection:
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apnea or tachypnea
cyanosis
dehydration
altered mental status.
pH1N1 Risk Factors
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People at risk of developing complications:
Children < 2 years
 Children aged 6 months – 18 years on longterm aspirin therapy (Reye syndrome)
 Pregnant women (particularly 2nd and 3rd
trimesters and up to 4 weeks post delivery)
 People living in isolated / remote communities
 Persons > 65 years
 Residents of long-term care facilities
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Patients with:
chronic respiratory disease
 cardiac disease
 morbid obesity (BMI  40, possibly people with
BMI  30).
 chronic diseases (e.g. diabetes, chronic renal
failure, chronic liver disease, chronic metabolic
diseases, hemoglobinopathies)
 chronic neurologic disorders (which may result
in difficulty managing respiratory secretions)
 Immunosuppressed (e.g. chemotherapy, HIV,
chronic corticosteroids)

H1N1 Severe Disease
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Similar to seasonal influenza:
lower respiratory disease (viral pneumonia)
 secondary bacterial pneumonia / sepsis
 myocarditis / pericarditis
 CNS (encephalitis, cerebellitis, febrile
seizures, post infectious encephalomyelitis)
 toxic shock syndrome
 ARDS.
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H1N1 and the elderly
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Persons born before 1957 seem to be less
likely to get ill with the H1N1.
Thought to be due to immunity acquired
from exposure prior to 1957.
However, if an older person does get this
influenza then she is at risk for developing
complications.
H1N1 Treatment
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Persons with no risk factors for severe
disease  no antiviral medication needed;
symptomatic treatment only.
Persons at risk for developing severe
disease  treat with antiviral medication.
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start within 48 hours of onset of symptoms.
Hospitalized patients  treat.
H1N1 Treatment
Agent, group
Oseltamivir
Adults
15 kg or less
Children • 16-23 kg
12 months
24-40 kg
>40 kg
Zanamivir
Adults
Children (age 7 years or older)
Treatment
5 days
75 mg capsule twice per day for
5 days
30 mg twice per day
45 mg twice per day
60 mg twice per day
75 mg twice per day
5 days
Two 5-mg inhalations (10 mg total)
twice per day
Two 5-mg inhalations (10 mg total)
twice per day
H1N1 Prevention
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Wash your hands.
Cover your nose and mouth when you
cough or sneeze.
Wash your hands.
Avoid touching eyes, nose, mouth.
Avoid contact with sick people.
Wash your hands.
Stay home if you are sick.
Social distancing.
H1N1 Prevention
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Pre-exposure prophylaxis not currently
recommended.
Post-exposure prophylaxis in general is
not recommended.
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It may be considered for high risk individuals
in exceptional circumstances following a
documented exposure.
The current recommended strategy is
close monitoring for symptoms and early
treatment.
H1N1 Vaccine
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Vaccination is considered to be one the
main tools for prevention of widespread
influenza.
In Canada, there will be two vaccines:
adjuvant-inactivated monovalent vaccine
 non-adjuvant inactivated monovalent vaccine
for pregnant women and children under the
age of 3.
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Children under age 10 will need a booster.
H1N1 Vaccine
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The vaccine is being recommended for:
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persons with chronic conditions < 65
pregnant women
children 6 months to less than 5 years of age
persons residing in remote and isolated settings and
communities
Health care workers (all health care system workers
involved with the pandemic response or delivery of
essential health services)
household contacts and care providers of:
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
children < 6 months
immunocompromised individuals.
http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php
H1N1 Vaccine
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Others who might benefit include:
children 5 to 18 (inclusive) years of age
 first responders (police, firefighters)
 Poultry and swine workers
 Adults 19 to 64 (inclusive) years of age
 Adults 65 years of age and over.
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http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php
Ontario Vaccine Plan
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October. Seasonal flu vaccine for:
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November. H1N1 Vaccine for:
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People over the age of 65 and residents of long-term
care homes living in Ontario.
Identified priority groups.
Anyone else who want it.
Next - maybe in January?:
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the seasonal flu vaccine will be available to everyone
who is six months of age and over who lives, works or
attends school in Ontario.
Questions?
Adjuvants
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A substance that is added to a vaccine to
improve the immune response.
This may be done for various reasons:
dose sparing so that more vaccine doses can
be manufactured
 to boost the immune response in some
patients, e.g. the elderly.
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Adjuvants
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GlaxoSmithKline is manufacturing
Canada’s vaccine.
The adjuvant being used is ASO3 - alphatocopherol-based adjuvant system number
3; a squalene based oil-in-water emulsion.
The vaccine is to be supplied in a two-vial
format - one containing the antigen and
the other the adjuvant.

Genetic factors in distinguishing between
"human flu viruses" and “avian influenza viruses"
include:
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PB2: (RNA polymerase): Amino acid (or residue
position 627 in the PB2 protein encoded by the PB2
RNA gene. Until H5N1, all known avian influenza
viruses had a Glu at position 627, while all human
influenza viruses had a lysine.
HA: (hemagglutinin) Avian influenza HA bind alpha 23 sialic acid receptors while human influenza HA bind
alpha 2-6 sialic acid receptors.
Swine influenza viruses have the ability to bind
both types of sialic acid receptors.