H1N1 Influenza AH1N1 Influenza Apandemic strainpandemic strain

Martha Fulford, MD, FRCPCMartha Fulford, MD, FRCPCDivision of Infectious DiseasesDivision of Infectious Diseases

McMaster University Medical CentreMcMaster University Medical Centre

Overview of influenzaOverview of influenza Definition of pandemicDefinition of pandemic pH1N1pH1N1 Current StatusCurrent Status

InfluenzaInfluenza

an orthomyxovirus RNA virus.an orthomyxovirus RNA virus. contains 8 segments of RNA put together with a contains 8 segments of RNA put together with a

protein.protein. three types: A, B, C.three types: A, B, C. Influenza A, thought to be of avian origin, is Influenza A, thought to be of avian origin, is

responsible for known human pandemics.responsible for known human pandemics. two main surface glycoproteins that allow the two main surface glycoproteins that allow the

virus to attach to and infect a host:virus to attach to and infect a host: hemagglutinin (HA)hemagglutinin (HA) neuraminidase (NA)neuraminidase (NA)

InfluenzaInfluenza

mutations within the HA and/or NA are mutations within the HA and/or NA are called “antigenic drift”.called “antigenic drift”.

a continual, ongoing process.a continual, ongoing process. exchange of gene segments between exchange of gene segments between

human and animal (avian or swine) human and animal (avian or swine) viruses results in “antigenic shift”.viruses results in “antigenic shift”.

result is a new virus to which humans (or result is a new virus to which humans (or animals) have not previously been animals) have not previously been exposed.exposed.

EID. Volume 12, Number 1, January 2006

InfluenzaInfluenza

influenza viruses cause annual seasonal influenza viruses cause annual seasonal outbreaks (‘flu season).outbreaks (‘flu season).

attack rates range between 5 - 20%.attack rates range between 5 - 20%. case fatality rate < 0.1%.case fatality rate < 0.1%. 3,000 - 8,000 deaths annually in Canada.3,000 - 8,000 deaths annually in Canada. Average of 4,000 deaths from seasonal Average of 4,000 deaths from seasonal

influenza. influenza. (Health Canada, (Health Canada,

http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases-maladies/pandem-eng.php) )

Pediatric Influenza DeathsPediatric Influenza Deaths

www.cdc.gov/FLU/ weekly/index.htm

Influenza PandemicInfluenza Pandemic

The term "pandemic influenza” is used The term "pandemic influenza” is used when there is global spread of an when there is global spread of an influenza virus with a new HAinfluenza virus with a new HA subtype.subtype.

WHO requires sustained human to human WHO requires sustained human to human transmission of a novel virus in at least transmission of a novel virus in at least two WHO geographic regions.two WHO geographic regions.

Previous Influenza Previous Influenza PandemicsPandemics

Influenza pandemics:Influenza pandemics: 1761-621761-62 1833-37 (2% case fatality rate?)1833-37 (2% case fatality rate?) 1889-901889-90 1918-19 H1N1 – the Spanish ‘flu1918-19 H1N1 – the Spanish ‘flu 1957-58 H2N2 – the Asian ‘flu1957-58 H2N2 – the Asian ‘flu 1968-69 H3N2 – the Hong Kong ‘flu1968-69 H3N2 – the Hong Kong ‘flu 2009 -2009 - H1N1 – the pH1N1 (swine flu) H1N1 – the pH1N1 (swine flu)

pandemic H1N1 Influenza Apandemic H1N1 Influenza A

Late March, 2009 an outbreak of a Late March, 2009 an outbreak of a respiratory illness which predominantly respiratory illness which predominantly affected young people was described in affected young people was described in Mexico.Mexico.

Very quickly, a novel strain of H1N1 Very quickly, a novel strain of H1N1 Influenza A (swine flu) was identified.Influenza A (swine flu) was identified.

Subsequent rapid worldwide spread.Subsequent rapid worldwide spread. June 11, 2009 WHO raised its pandemic June 11, 2009 WHO raised its pandemic

alert level to 6, the highest level.alert level to 6, the highest level.

pH1N1 Current StatuspH1N1 Current Status

As of October 4, 2009 WHO reports:As of October 4, 2009 WHO reports: 191 countries reporting cases (out of 195 191 countries reporting cases (out of 195

countries in total)countries in total) 375,000 laboratory confirmed cases375,000 laboratory confirmed cases 4,500 deaths.4,500 deaths.

78 deaths in Canada as of Oct. 13 78 deaths in Canada as of Oct. 13 (including 4 pediatric deaths).(including 4 pediatric deaths).

pH1N1 Current StatuspH1N1 Current Status

As of Oct 13, 1,504 cases hospitalized.As of Oct 13, 1,504 cases hospitalized. 295 admitted to ICU.295 admitted to ICU. Of the 78 pH1N1 deaths in Canada:Of the 78 pH1N1 deaths in Canada:

60.5% female60.5% female median age 50median age 50 aboriginal 11.8%aboriginal 11.8% underlying medical conditions 81.7%underlying medical conditions 81.7% pregnant 5.1%pregnant 5.1%

http://www.phac-aspc.gc.ca/fluwatch/09-10/w37_09/index-eng.php

pH1N1 Current StatuspH1N1 Current Status

increasing ILI across the country.increasing ILI across the country. outbreaks declared in > 40 schools, including 6 outbreaks declared in > 40 schools, including 6

schools and one day care in Hamilton.schools and one day care in Hamilton. approx. 97% of positive influenza A specimens approx. 97% of positive influenza A specimens

were pH1N1.were pH1N1. Local % positivity for Influenza A Oct 4Local % positivity for Influenza A Oct 4--10:10:

Children < 4:  Influenza A 4%, Parainfluenza 11%Children < 4:  Influenza A 4%, Parainfluenza 11% Persons > 4 yrs of age:  Influenza A 11%Persons > 4 yrs of age:  Influenza A 11%

People with mild symptoms do not get tested.People with mild symptoms do not get tested.

pH1N1 Influenza ApH1N1 Influenza A

incubation period - 1 - 3 days.incubation period - 1 - 3 days. shedding of virus likely from one day shedding of virus likely from one day

before onset of symptoms to approx. before onset of symptoms to approx. seven days after onset of symptoms.seven days after onset of symptoms.

young children and the immuno-young children and the immuno-compromised may shed for longer periods.compromised may shed for longer periods.

majority of infections have resulted in very majority of infections have resulted in very mild disease.mild disease.

pH1N1 Clinical PresentationpH1N1 Clinical Presentation

feverfever coughcough sore throatsore throat malaise and headachemalaise and headache vomiting & diarrhea (not typical of seasonal)vomiting & diarrhea (not typical of seasonal) chillschills myalgias & arthralgias.myalgias & arthralgias.

pH1N1 Clinical PresentationpH1N1 Clinical Presentation

children may not have typical respiratory tract children may not have typical respiratory tract symptoms but will have:symptoms but will have: feverfever irritabilityirritability lethargy.lethargy.

with severe infection:with severe infection: apnea or tachypneaapnea or tachypnea cyanosiscyanosis dehydrationdehydration altered mental status.altered mental status.

pH1N1 Risk FactorspH1N1 Risk Factors

People at risk of developing complications:People at risk of developing complications: Children < 2 yearsChildren < 2 years Children aged 6 months – 18 years on long-Children aged 6 months – 18 years on long-

term aspirin therapy (Reye syndrome)term aspirin therapy (Reye syndrome) Pregnant women (particularly 2Pregnant women (particularly 2ndnd and 3 and 3rdrd

trimesters and up to 4 weeks post delivery)trimesters and up to 4 weeks post delivery) People living in isolated / remote communitiesPeople living in isolated / remote communities Persons > 65 yearsPersons > 65 years Residents of long-term care facilitiesResidents of long-term care facilities

Patients with:Patients with: chronic respiratory diseasechronic respiratory disease cardiac diseasecardiac disease morbid obesity (BMI morbid obesity (BMI 40, possibly people with 40, possibly people with

BMI BMI 30). 30). chronic diseases (e.g. diabetes, chronic renal chronic diseases (e.g. diabetes, chronic renal

failure, chronic liver disease, chronic metabolic failure, chronic liver disease, chronic metabolic diseases, hemoglobinopathies)diseases, hemoglobinopathies)

chronic neurologic disorders (which may result chronic neurologic disorders (which may result in difficulty managing respiratory secretions)in difficulty managing respiratory secretions)

Immunosuppressed (e.g. chemotherapy, HIV, Immunosuppressed (e.g. chemotherapy, HIV, chronic corticosteroids)chronic corticosteroids)

H1N1 Severe DiseaseH1N1 Severe Disease

Similar to seasonal influenza:Similar to seasonal influenza: lower respiratory disease (viral pneumonia)lower respiratory disease (viral pneumonia) secondary bacterial pneumonia / sepsissecondary bacterial pneumonia / sepsis myocarditis / pericarditismyocarditis / pericarditis CNS (encephalitis, cerebellitis, febrile CNS (encephalitis, cerebellitis, febrile

seizures, post infectious encephalomyelitis)seizures, post infectious encephalomyelitis) toxic shock syndrometoxic shock syndrome ARDS.ARDS.

H1N1 and the elderlyH1N1 and the elderly

Persons born before 1957 seem to be less Persons born before 1957 seem to be less likely to get ill with the H1N1.likely to get ill with the H1N1.

Thought to be due to immunity acquired Thought to be due to immunity acquired from exposure prior to 1957.from exposure prior to 1957.

However, if an older person does get this However, if an older person does get this influenza then she is at risk for developing influenza then she is at risk for developing complications.complications.

H1N1 Treatment H1N1 Treatment

Persons with Persons with no risk factorsno risk factors for severe for severe disease disease no antiviral medication neededno antiviral medication needed; ; symptomatic treatment only.symptomatic treatment only.

Persons at risk for developing severe Persons at risk for developing severe disease disease treat with antiviral medication. treat with antiviral medication. start within 48 hours of onset of symptoms.start within 48 hours of onset of symptoms.

Hospitalized patients Hospitalized patients treat. treat.

H1N1 TreatmentH1N1 Treatment

Agent, group Treatment Oseltamivir 5 days

Adults 75 mg capsule twice per day for 5 days

15 kg or less 30 mg twice per day

16-23 kg 45 mg twice per day 24-40 kg 60 mg twice per day

Children 12 months

>40 kg 75 mg twice per day Zanamivir 5 days

Adults Two 5 -mg inhalations (10 mg total) twice per day

Children (age 7 years or older) Two 5 -mg inhalations (10 mg total) twice per day

H1N1 PreventionH1N1 Prevention

Wash your hands.Wash your hands. Cover your nose and mouth when you Cover your nose and mouth when you

cough or sneeze.cough or sneeze. Wash your hands.Wash your hands. Avoid touching eyes, nose, mouth.Avoid touching eyes, nose, mouth. Avoid contact with sick people.Avoid contact with sick people. Wash your hands.Wash your hands. Stay home if you are sick.Stay home if you are sick. Social distancing.Social distancing.

H1N1 PreventionH1N1 Prevention

Pre-exposure prophylaxis not currently Pre-exposure prophylaxis not currently recommended.recommended.

Post-exposure prophylaxis in general is Post-exposure prophylaxis in general is not recommended.not recommended. It may be considered for high risk individuals It may be considered for high risk individuals

in exceptional circumstances following a in exceptional circumstances following a documented exposure.documented exposure.

The current recommended strategy is The current recommended strategy is close monitoring for symptoms and early close monitoring for symptoms and early treatment.treatment.

H1N1 VaccineH1N1 Vaccine

Vaccination is considered to be one the Vaccination is considered to be one the main tools for prevention of widespread main tools for prevention of widespread influenza.influenza.

In Canada, there will be two vaccines:In Canada, there will be two vaccines: adjuvant-inactivated monovalent vaccineadjuvant-inactivated monovalent vaccine non-adjuvant inactivated monovalent vaccine non-adjuvant inactivated monovalent vaccine

for pregnant women and children under the for pregnant women and children under the age of 3. age of 3.

Children under age 10 will need a booster.Children under age 10 will need a booster.

H1N1 VaccineH1N1 Vaccine

The vaccine is being recommended for:The vaccine is being recommended for: persons with chronic conditions < 65persons with chronic conditions < 65 pregnant womenpregnant women children 6 months to less than 5 years of agechildren 6 months to less than 5 years of age persons residing in remote and isolated settings and persons residing in remote and isolated settings and

communitiescommunities 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: children < 6 months immunocompromised individuals.

http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.phphttp://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php

H1N1 VaccineH1N1 Vaccine

Others who might benefit include:Others who might benefit include: children 5 to 18 (inclusive) years of agechildren 5 to 18 (inclusive) years of age first responders (police, firefighters)first responders (police, firefighters) Poultry and swine workersPoultry and swine workers Adults 19 to 64 (inclusive) years of ageAdults 19 to 64 (inclusive) years of age Adults 65 years of age and over.Adults 65 years of age and over.

http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.phphttp://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php

Ontario Vaccine PlanOntario Vaccine Plan

October. Seasonal flu vaccine for: People over the age of 65 and residents of long-term

care homes living in Ontario. November. H1N1 Vaccine for:

Identified priority groups. Anyone else who want it.

Next - maybe in January?: 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?Questions?

AdjuvantsAdjuvants

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.

AdjuvantsAdjuvants

GlaxoSmithKline is manufacturing GlaxoSmithKline is manufacturing Canada’s vaccine.Canada’s vaccine.

The adjuvant being used is ASO3 - alpha-The adjuvant being used is ASO3 - alpha-tocopherol-based adjuvant system number tocopherol-based adjuvant system number 3; a squalene based oil-in-water emulsion.3; a squalene based oil-in-water emulsion.

The vaccine is to be supplied in a two-vial The vaccine is to be supplied in a two-vial format - one containing the antigen and format - one containing the antigen and the other the adjuvant.the other the adjuvant.

Genetic factors in distinguishing Genetic factors in distinguishing between "human flu viruses" and “avian between "human flu viruses" and “avian influenza viruses" include:influenza viruses" include: PB2PB2: (RNA polymerase): Amino acid (or : (RNA polymerase): Amino acid (or residue position 627 in the PB2 protein residue position 627 in the PB2 protein encoded by the PB2 RNA gene. Until H5N1, encoded by the PB2 RNA gene. Until H5N1, all known avian influenza viruses had a Glu all known avian influenza viruses had a Glu at position 627, while all human influenza at position 627, while all human influenza viruses had a lysine.viruses had a lysine.

HAHA: (hemagglutinin) Avian influenza HA bind : (hemagglutinin) Avian influenza HA bind alpha 2-3 sialic acid receptors while human alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid influenza HA bind alpha 2-6 sialic acid receptors. receptors.

Swine influenza viruses have the Swine influenza viruses have the ability to bind both types of sialic ability to bind both types of sialic acid receptors.acid receptors.