1. H1N1 Influenza A pandemic strain Martha Fulford, MD, FRCPC Division of Infectious Diseases McMaster University Medical Centre

2. Overview of influenza Overview of influenza Definition of pandemic Definition of pandemic pH1N1 pH1N1 Current Status Current Status

3. Influenza an orthomyxovirus RNA virus. an orthomyxovirus RNA virus. contains 8 segments of RNA put together with a protein. contains 8 segments of RNA put together with a protein. three types: A, B, C. three types: A, B, C. Influenza A, thought to be of avian origin, is responsible for known human pandemics. 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: two main surface glycoproteins that allow the virus to attach to and infect a host: hemagglutinin (HA) hemagglutinin (HA) neuraminidase (NA) neuraminidase (NA)

4. Influenza mutations within the HA and/or NA are called “antigenic drift”. mutations within the HA and/or NA are called “antigenic drift”. a continual, ongoing process. a continual, ongoing process. exchange of gene segments between human and animal (avian or swine) viruses results in “antigenic shift”. 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. result is a new virus to which humans (or animals) have not previously been exposed.

5. EID. Volume 12, Number 1, January 2006

6. Influenza influenza viruses cause annual seasonal outbreaks (‘flu season). influenza viruses cause annual seasonal 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 influenza. (Health Canada, http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases- maladies/pandem-eng.php) Average of 4,000 deaths from seasonal influenza. (Health Canada, http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases- maladies/pandem-eng.php)http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases- maladies/pandem-eng.phphttp://www.hc-sc.gc.ca/hl-vs/iyh-vsv/diseases- maladies/pandem-eng.php

7. Pediatric Influenza Deaths www.cdc.gov/FLU/ weekly/index.htm

8. Influenza Pandemic The term "pandemic influenza” is used when there is global spread of an influenza virus with a new HA subtype. 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. WHO requires sustained human to human transmission of a novel virus in at least two WHO geographic regions.

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

10. pandemic H1N1 Influenza A Late March, 2009 an outbreak of a respiratory illness which predominantly affected young people was described in Mexico. 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. Very quickly, a novel strain of H1N1 Influenza A (swine flu) was identified. Subsequent rapid worldwide spread. Subsequent rapid worldwide spread. June 11, 2009 WHO raised its pandemic alert level to 6, the highest level. June 11, 2009 WHO raised its pandemic alert level to 6, the highest level.

11. pH1N1 Current Status As of October 4, 2009 WHO reports: As of October 4, 2009 WHO reports: 191 countries reporting cases (out of 195 countries in total) 191 countries reporting cases (out of 195 countries in total) 375,000 laboratory confirmed cases 375,000 laboratory confirmed cases 4,500 deaths. 4,500 deaths. 78 deaths in Canada as of Oct. 13 (including 4 pediatric deaths). 78 deaths in Canada as of Oct. 13 (including 4 pediatric deaths).

12. pH1N1 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% female 60.5% female median age 50 median 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

13. pH1N1 Current Status increasing ILI across the country. increasing ILI across the country. outbreaks declared in > 40 schools, including 6 schools and one day care in Hamilton. outbreaks declared in > 40 schools, including 6 schools and one day care in Hamilton. approx. 97% of positive influenza A specimens were pH1N1. approx. 97% of positive influenza A specimens were pH1N1. Local % positivity for Influenza A Oct 4-10: Local % positivity for Influenza A Oct 4-10: 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.

14. pH1N1 Influenza A incubation period - 1 - 3 days. incubation period - 1 - 3 days. shedding of virus likely from one day before onset of symptoms to approx. seven days after onset of symptoms. shedding of virus likely from one day before onset of symptoms to approx. seven days after onset of symptoms. young children and the immuno- compromised may shed for longer periods. young children and the immuno- compromised may shed for longer periods. majority of infections have resulted in very mild disease. majority of infections have resulted in very mild disease.

15. pH1N1 Clinical Presentation fever fever cough cough sore throat sore throat malaise and headache malaise and headache vomiting & diarrhea (not typical of seasonal) vomiting & diarrhea (not typical of seasonal) chills chills myalgias & arthralgias. myalgias & arthralgias.

16. pH1N1 Clinical Presentation pH1N1 Clinical Presentation children may not have typical respiratory tract symptoms but will have: children may not have typical respiratory tract symptoms but will have: fever fever irritability irritability lethargy. lethargy. with severe infection: with severe infection: apnea or tachypnea apnea or tachypnea cyanosis cyanosis dehydration dehydration altered mental status. altered mental status.

17. pH1N1 Risk Factors People at risk of developing complications: People at risk of developing complications: Children < 2 years Children < 2 years Children aged 6 months – 18 years on long- term aspirin therapy (Reye syndrome) Children aged 6 months – 18 years on long- term aspirin therapy (Reye syndrome) Pregnant women (particularly 2 nd and 3 rd trimesters and up to 4 weeks post delivery) Pregnant women (particularly 2 nd and 3 rd trimesters and up to 4 weeks post delivery) People living in isolated / remote communities People living in isolated / remote communities Persons > 65 years Persons > 65 years Residents of long-term care facilities Residents of long-term care facilities

18. Patients with: Patients with: chronic respiratory disease chronic respiratory disease cardiac disease cardiac disease morbid obesity (BMI  40, possibly people with BMI  30). 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 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) chronic neurologic disorders (which may result in difficulty managing respiratory secretions) Immunosuppressed (e.g. chemotherapy, HIV, chronic corticosteroids) Immunosuppressed (e.g. chemotherapy, HIV, chronic corticosteroids)

19. H1N1 Severe Disease Similar to seasonal influenza: Similar to seasonal influenza: lower respiratory disease (viral pneumonia) lower respiratory disease (viral pneumonia) secondary bacterial pneumonia / sepsis secondary bacterial pneumonia / sepsis myocarditis / pericarditis myocarditis / pericarditis CNS (encephalitis, cerebellitis, febrile seizures, post infectious encephalomyelitis) CNS (encephalitis, cerebellitis, febrile seizures, post infectious encephalomyelitis) toxic shock syndrome toxic shock syndrome ARDS. ARDS.

20. H1N1 and the elderly Persons born before 1957 seem to be less likely to get ill with the H1N1. 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. 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. However, if an older person does get this influenza then she is at risk for developing complications.

21. H1N1 Treatment Persons with no risk factors for severe disease  no antiviral medication needed; symptomatic treatment only. 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. Persons at risk for developing severe disease  treat with antiviral medication. start within 48 hours of onset of symptoms. start within 48 hours of onset of symptoms. Hospitalized patients  treat. Hospitalized patients  treat.

22. H1N1 Treatment

23. H1N1 Prevention Wash your hands. Wash your hands. Cover your nose and mouth when you cough or sneeze. Cover your nose and mouth when you 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.

24. H1N1 Prevention Pre-exposure prophylaxis not currently recommended. Pre-exposure prophylaxis not currently recommended. Post-exposure prophylaxis in general is not recommended. Post-exposure prophylaxis in general is not recommended. It may be considered for high risk individuals in exceptional circumstances following a documented exposure. 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. The current recommended strategy is close monitoring for symptoms and early treatment.

25. H1N1 Vaccine Vaccination is considered to be one the main tools for prevention of widespread influenza. Vaccination is considered to be one the main tools for prevention of widespread influenza. In Canada, there will be two vaccines: In Canada, there will be two vaccines: adjuvant-inactivated monovalent vaccine adjuvant-inactivated monovalent vaccine non-adjuvant inactivated monovalent vaccine for pregnant women and children under the age of 3. non-adjuvant inactivated monovalent vaccine for pregnant women and children under the age of 3. Children under age 10 will need a booster. Children under age 10 will need a booster.

26. H1N1 Vaccine The vaccine is being recommended for: The vaccine is being recommended for: persons with chronic conditions < 65 persons with chronic conditions < 65 pregnant women pregnant women children 6 months to less than 5 years of age children 6 months to less than 5 years of age persons residing in remote and isolated settings and communities 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: children < 6 months immunocompromised individuals.http://www.phac-aspc.gc.ca/alert-alerte/h1n1/vacc/vacc-eng.php

27. H1N1 Vaccine Others who might benefit include: Others who might benefit include: children 5 to 18 (inclusive) years of age children 5 to 18 (inclusive) years of age first responders (police, firefighters) first responders (police, firefighters) Poultry and swine workers Poultry and swine workers Adults 19 to 64 (inclusive) years of age Adults 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.php

28. Ontario 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.

29. Questions?

30. Adjuvants 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.

31. Adjuvants GlaxoSmithKline is manufacturing Canada’s vaccine. GlaxoSmithKline is manufacturing Canada’s vaccine. The adjuvant being used is ASO3 - alpha- tocopherol-based adjuvant system number 3; a squalene based oil-in-water emulsion. The adjuvant being used is ASO3 - alpha- tocopherol-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. The vaccine is to be supplied in a two-vial format - one containing the antigen and the other the adjuvant.

32. Genetic factors in distinguishing between "human flu viruses" and “avian influenza viruses" include: Genetic factors in distinguishing between "human flu viruses" and “avian influenza viruses" include: 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. 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 2- 3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. HA: (hemagglutinin) Avian influenza HA bind alpha 2- 3 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. Swine influenza viruses have the ability to bind both types of sialic acid receptors.