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Influenza Viruses
 

Influenza Viruses

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Info on H1N1

Info on H1N1

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    Influenza Viruses Influenza Viruses Presentation Transcript

    • Sponsored by: The Gerald Brennan Medical Corporation A proud consumer of Tamiflu® (oseltamivir phosphate) October 30, 2009
    • Agenda
      • Influenza overview
      • Diagnosis and testing
      • Treatment
      • Vaccination
    • Influenza overview
      • What is influenza?
      • What is the difference between Human and Swine influenza?
      • What is special about H1N1?
      • What constitutes a pandemic?
      • What have we seen with Pandemics of the past?
      • What have we seen with past seasonal influenza?
      • What have we seen with H1N1 so far?
      • What can we expect for the fall?
    • What is influenza?
      • ssRNA virus 50-200 nm in diameter of the order of Mononegavirales and of the family Orthomyxoviridae
      • There are 3 immunological types: Influenza type A, type B and type C
        • Type A is the most virulent human pathogen and is responsible for all pandemics
      • Type A can be further broken down into subtypes based on it’s surface proteins: Hemagglutinin and Neuraminidase
        • There are 16 Hemagglutinins (H1-H16)
        • There are 9 Neuraminidases (N1-N9)
        • There are also Nucleocapsid proteins (NP) that coat the RNA strands and Matrix proteins that line the inner side of the viral envelope
    • What is influenza?
      • Influenza virus first binds to the host cells glycoprotein receptors via HA, where it is then adsorbed into the cell via endocytosis
      • The nucleocapsids are then released by the virus and these are taken to the nucleus where transcription of the viral mRNA occurs
      • The mRNA is then translated into viral proteins by the host machinery, but it is also replicated with the help of viral RNA polymerase
      • These materials are then combined in the cytoplasm and new virion particles are assembled and then released via exocytosis, allowing for new cells to become infected
    • What is the difference between Human and Swine influenza?
      • Typically, Influenza type A is species specific, but all have the potential to cross the species barrier
      • Reassortment is the theory that allows for a virus to cross the species barrier
    • What is the difference between Human and Swine influenza?
      • In this example, a pig is infected simultaneously with both an avian and a human influenza virus. The “mixing” of the avian and human viral proteins results in the new subtype H3N2 (the pandemic virus of 1968)
    • What is special about H1N1?
      • By itself, there is nothing special about H1N1
        • It is not a “super virus”
        • It is not much more virulent than other Type A influenza
          • But it has been affecting more young people though
      • It is the result of a reassortment and is new to the human population
          • Because the human population has no immunity, as they would to most seasonal influenza, more people are susceptible
          • Once immunity has built up in the population at large, further outbreaks will be more limited
    • What constitutes a pandemic?
    • What have we seen with Pandemics of the past?
      • 1918 Spanish Flu
      • H1N1
      • 20-40 Million deaths
      • >500 Million people infected
    • What have we seen with Pandemics of the past?
      • 1957 Asian Flu
      • H2N2
      • 1-4 Million Deaths
    • What have we seen with Pandemics of the past?
      • 1968 Hong Kong Flu
      • H3N2
      • 1-4 Million Deaths
    • What have we seen with past seasonal influenza: 2005-06
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 6590
        • Type A = 4028
        • Type B = 2562
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 144
        • >2 years: 230
      • Pediatric Mortality
        • Type A: 3
        • Type B: 2
      • Total cases = 88
        • Type A = 63
        • Type B = 25
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 14
        • >2 years: 16
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
    • What have we seen with past seasonal influenza: 2006-07
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 7023
        • Type A = 6051
        • Type B = 972
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 183
        • >2 years: 187
      • Pediatric Mortality
        • Type A: 1
        • Type B: 1
      • Total cases = 72
        • Type A = 71
        • Type B = 1
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 18
        • >2 years: 13
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
    • What have we seen with past seasonal influenza: 2007-08
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 9130
        • Type A = 5356
        • Type B = 3765
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 231
        • >2 years: 239
      • Pediatric Mortality
        • Type A: 0
        • Type B: 2
      • Total cases = 118
        • Type A = 79
        • Type B = 39
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 18
        • >2 years: 27
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
    • What have we seen with past seasonal influenza: 2008-09 (prior to April 09 when H1N1 appeared)
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 9200
        • Type A = 5588
        • Type B = 3612
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 185
        • >2 years: 225
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
      • Total cases = 110
        • Type A = 63
        • Type B = 37
      • Hospitalizations = n/a
      • Deaths = n/a
      • Pediatric Hospitalizations
        • >2 years: 12
        • >2 years: 38
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
    • What have we seen with H1N1 so far: 2008-09
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 23366
        • Type A = 19464
        • Type B = 3902
      • Hospitalizations = 1454
      • Deaths = 72
      • Pediatric Hospitalizations
        • Total = 737
      • Pediatric Mortality
        • Type A: 4
        • Type B: 0
      • Total cases = 1119 (440 peds)
        • Type A = 1082
        • Type B = 37
      • Hospitalizations = 221
      • Deaths = 7
      • Pediatric Hospitalizations
        • Total = 81
        • PICU = 12
      • Pediatric Mortality
        • Type A: 1
    • What have we seen with H1N1 so far: 2009-10
      • Canada (Sept 1-Aug 31)
      • Manitoba (July 1 – June 30)
      • Total cases = 2818
        • Type A = 2816
        • Type B = 2
      • Hospitalizations = 150
      • Deaths = 11
      • Pediatric Hospitalizations
        • Total = 52
      • Pediatric Mortality
        • Type A: 0
        • Type B: 0
      • Total cases = 94 (27 peds)
        • Type A = 94
        • Type B = 0
      • Hospitalizations = 6
      • Deaths = 0
      • Pediatric Hospitalizations
        • Total = n/a
        • PICU = 1
      • Pediatric Mortality
        • Type A: 0
    • What have we seen with H1N1 so far?
    • Worldwide: 182,166 Cases & 1799 Deaths (current to Aug 13, 2009)
      • WHO Africa
        • 1469 Cases
        • 3 Deaths
      • WHO Americas
        • 105,882 Cases
        • 1579 Deaths
      • WHO Eastern Mediterranean
        • 2532 Cases
        • 8 Deaths
      • WHO Europe
        • > 32,000 Cases
        • 53 Deaths
      • WHO South-East Asia
        • 13,172 Cases
        • 106 Deaths
      • WHO Western Pacific
        • 27,111 Cases
        • 50 Deaths
    • What have we seen with H1N1 so far? (current to Aug 13, 2009)
      • Per PHAC:
      • Median Age
        • All Cases = 18 yo
        • Hospitalizations = 25 yo
        • ICU = 40 yo
        • Deaths = 51 yo
    • What have we seen with H1N1 so far? (current to Aug 13, 2009)
      • Per PHAC:
      • Aboriginal Status
        • All Cases = 12.5%
        • Hospitalizations = 16.5%
        • ICU = 14.5%
        • Deaths = 11.4%
    • What have we seen with H1N1 so far? (current to Aug 13, 2009)
      • Per PHAC:
      • Female (Pregnancy)
        • All Cases = 51.9% (4.1%)
        • Hospitalizations = 51.4% (22.4%)
        • ICU = 56.7% (15.7%)
        • Deaths = 60% (33.3%)
    • What have we seen with H1N1 so far? (current to Aug 13, 2009)
      • Per PHAC:
      • Underlying Medical Conditions
        • All Cases = 36.4%
        • Hospitalizations = 54.2%
        • ICU = 65.3%
        • Deaths = 75.5%
    • What can we expect for the fall?
      • No one knows for sure
      • We can postulate based on past experience with H1N1 in 1918
      • The first wave hit in the spring and was about ¼ to 1/3 the size of the second wave, which hit in the fall
      • We have just started the second wave 
    • What can we expect for the fall?
    • What should we be doing?
      • Influenza virus is spread to person to person by droplets released into the air when an infected person coughs or sneezes
        • Travels about 1 meter (3 feet)
        • Virus enters through the eyes, nose or throat
      • Can also be picked up from contaminated objects
        • Survives 24-48 hours on hard, non-porous surfaces
        • Survives 8-12 hours on cloth, paper and tissue
        • Survives 5 minutes on hands
        • Loves cold, dry climates
          • Which is why we have winter outbreaks
    • What should we be doing?
      • Once infected, symptoms develop within 1-7 days
      • An infected person can be contagious for 24 hours prior to the onset of symptoms and for up to 7 days afterwards
      • It is possible to spread it to others without being sick, but the actual viral load is very low. This is why vaccination will be important for people living with high risk individuals!!!
    • What should we be doing?
      • Signs and symptoms include:
        • Fever
        • Sore throat
        • Cough
        • Runny nose
        • Sore muscles and joints
        • Headache
        • Prostration (feeling like you have no energy)
    • What should we be doing?
      • Because H1N1 will be so difficult to distinguish from other respiratory viruses, we need to be vigilant
        • Identify and treat patients with H1N1
        • Reduce the spread/Protect other patients
          • Hand washing
          • Respiratory precautions/Droplet precautions
          • Housekeeping
          • Cohorting
          • Diverting (avoidance strategies)
        • Protect ourselves
    • Diagnosis and Testing
      • How can we diagnose H1N1?
      • What testing is available?
    • How can we diagnose H1N1?
      • Clinical
        • ILI (Influenza-like Illness)
          • Fever > 38 C AND Cough AND one or more of:
            • Sore throat
            • Arthralgia
            • Myalgia
            • Prostration
          • *** Cough may not be prominent in young children
          • *** Children < 5 years may also present with GI symptoms
      • Laboratory
        • Nasal swab or throat swab
          • Sent to Cadham for viral culture and PCR
        • Rapid Influenza A test (30 min) not available to us at this time
        • There is presently no available antibody test to verify if someone has had H1N1 already
    • Treatment
      • What treatment is available for H1N1?
      • What are the adverse effects from these treatments?
      • Who should be treated and why?
    • What treatment is available for H1N1?
      • There are two antiviral drugs:
        • Oseltamivir (Tamiflu)
        • Zanamivir (Relenza)
        • Canada has a stockpile of 55 million doses (both drugs)
      • They are neuraminidase inhibitors
        • Prevent viral enzymes from cleaving sialic acid thereby preventing virion release from infected cells, thus reducing infection with the host organism
        • Translation: it stops the virus from spreading to other cells and shortens the severity of disease by about 60%
    • What are the adverse effects from these treatments?
      • The drug is “activated” by the liver, so beware of patients with liver dysfunction
      • The drug is cleared by the kidney, so may need to go to once daily dosing in moderate-severe renal dysfunction
      • Major side-effects in the clinical trials of children age 1-12 (>1000 pts) were:
        • Nausea and vomiting (15%)
        • Diarrhea (9%)
        • Abdominal pain (4%)
    • Who should be treated and why?
      • PHAC has stated that treatment should be limited to:
        • Severe disease (hospitalized/ICU) patients
        • High risk patients (as per the WHO):
          • Patients with underlying medical conditions
          • All pregnant women
          • All children under the age of 5 years
          • Aboriginal peoples
    • Who should be treated and why?
      • Treatment, if initiated promptly, has been shown to dramatically reduce the burden of illness
        • Within 12 hours of onset of illness is best
        • Within 48 hours of onset of illness is likely helpful
          • Not considered beneficial if initiated after 48 hours, except in cases of severe illness (i.e., requiring hospitalization)
    • Vaccination
      • Arepanrix H1N1 vaccine was approved for use in Canada this month as a means of decreasing the burden of illness expected from the second wave of H1N1
      • 0.5 cc of vaccine is injected into the deltoid muscle and antibodies to the H1N1 virus are formed within 10-14 days
      • The formed antibodies allow the body’s immune system to protect it from H1N1, resulting in either no disease or very mild illness
    • Vaccination preparation
      • H1N1 is grown inside hens eggs. After 14(ish) days, the virus is extracted and then killed by exposing it first to intense ultraviolet radiation, and then to formaldehyde
      • This results in a neutralization of the virus without altering it’s antigenic properties (the antigens are what allow your body to develop antibodies against the virus)
      • The killed virus is then cleaned and centrifuged in order to concentrate it
    • Vaccination preparation
      • Each dose of vaccine contains:
        • 3.75 mcg of killed H1N1 virus
        • 5 mcg of thimerosol (Mercury based preservative)
        • An adjuvant containing:
          • 11.86 mg of DL-alpha-tocopherol
          • 10.69 mg of Squalene
          • 4.86 mg of Polysorbate 80
    • Vaccination preparation
      • Each dose of vaccine contains:
        • Thimerosol:
          • People are concerned about this because of the mercury content
              • Although it has been a part of vaccine for decades, and has been proven safe, there are many people who still believe that it is the cause of Autism
          • For what it’s worth, Canada regulates the content of mercury acceptable for human consumption to <0.5 ppm (1 mg/kg)
              • This vaccine contains 5 ppm (10 x greater), but the actual total dose is 2.5 mcg of Mercury
              • For comparison, the dose of Mercury in a 75 gram serving of canned tuna is 37.5 mcg
    • Vaccination preparation
      • Each dose of vaccine contains:
        • Adjuvant
          • These are extra ingredients used to “boost” the immune reaction to the vaccine, allowing the manufacturer to produce more usable vaccine with less killed virus per dose
          • Tocopherols are naturally occurring antioxidants that prevent the oxidation of unsaturated fatty acids. Vitamin E is a tocopherol. It is used to keep the squalene from breaking down
          • Squalene is a naturally occurring organic compound found in shark liver oil and vegetable oils. It is what stimulates the immune system
          • Polysorbate 80 is an emulsifier, which means that is allows the oily squalene to become suspended with watery vaccine. It is used mostly in ice-cream
    • Vaccination Efficacy
      • Initial studies done in Canada showed that the vaccine was very efficacious and safe
      • Although the number of test subjects was low in Canada, using this information along with studies done in other parts of the world where this vaccine, or similar vaccines, had been used, Health Canada was able to ensure a safe means of preventing H1N1
      • Additionally, unlike most seasonal influenza that changes frequently, H1N1 has not modified much so far, which will make the vaccine that much more effective when compared to typical seasonal flu shots
    • Vaccination Efficacy
      • H1N1 vaccine (15 mcg/dose)
      • Adjuvanted H1N1 (3.75 mcg/dose)
      • Seroprotection = 93.9 %
        • Refers to the ability of vaccinated people who have no antibodies to develop antibodies above a threshold titer of 1:40
      • Seroconversion = 84.8 %
        • Refers to the ability of vaccinated people who have antibodies to increase the number of antibodies by a factor of 4 or more
      • Seroprotection = 100 %
        • Refers to the ability of vaccinated people who have no antibodies to develop antibodies above a threshold titer of 1:40
      • Seroconversion = 96.7 %
        • Refers to the ability of vaccinated people who have antibodies to increase the number of antibodies by a factor of 4 or more
    • Conclusions
      • We have no innate immunity
      • H1N1 is not a super virus
      • Because this virus hasn’t been seen for many years, persons living today have no antibody “memory” for this virus, which is why so many more people have and will get sick
      • For seasonal flu, even though it differs somewhat from season to season, most of us have some immunity – which is why healthy adolescents and adults don’t usually get sick
      • In of itself, H1N1 is not more virulent than regular seasonal flu
      • More people are getting sick because fewer people are immune to it
      • Because so many more people are becoming ill, there are increases in hospitalizations and deaths
    • Conclusions
      • The second wave will be worse
      • It is hard to predict who will get severe disease
      • We have to assume that the pattern of this pandemic will follow the one from 1918 (as it has so far), which means that we will see 3-4 times more sick people
      • This will likely result in 3-4 times the number of admissions to hospital and in the number of deaths
      • Usually, with seasonal influenza, the very young and the very old get sick and have severe disease
      • With the lack of immunity, we are seeing otherwise healthy individuals who have gotten gravely ill
        • 2/3 of all cases were healthy people
        • ½ of hospitalizations were “healthy”
        • ¼ of all deaths were in people who had no underlying medical conditions
    • Conclusions
      • Simple precautions decrease the spread
      • Vaccination is safe and effective
      • Hand washing
      • Coughing into your sleeve
      • Staying home when you are sick
        • or at least until you are without fever for at least 24 hours
      • The more people who are vaccinated, the fewer people who are going to get sick and the less disruption to the lives of Canadians (not to mention Emergency physicians)
      • There are many outrageous claims, but none are supported by credible or reproducible evidence
      • The risks of contracting H1N1 and having a severe illness are much greater than the risk of serious adverse effects from the vaccine
    • My advice:
      • If you get sick:
        • Stay home, get plenty of rest, drink lots of fluids, eat properly and for God’s sake stop coughing on me…
        • If you feel very short of breath or find it difficult to breath, seek the assessment of a physician or nurse-practitioner
      • If you haven’t gotten sick:
        • Get the vaccination, especially if you have risk factors or live/work with people who do?
        • Wash your hands, get plenty of sleep, exercise and eat right
    • Questions?
    • Thanks for reading!!!