Sponsored by:The Gerald Brennan Medical Corporation
A proud consumer of Tamiflu® (oseltamivir phosphate)
October 30, 2009
AgendaInfluenza overviewDiagnosis and testingTreatmentVaccination
Influenza overviewWhat 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 FluH1N120-40 Million deaths>500 Million people infected
What have we seen with Pandemics of the past?1957 Asian FluH2N21-4 Million Deaths
What have we seen with Pandemics of the past?1968 Hong Kong FluH3N21-4 Million Deaths
What have we seen with past seasonal influenza: 2005-06Canada (Sept 1-Aug 31) Manitoba (July 1 – June
30)Total cases = 6590
Type A = 4028 Type B = 2562
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 144 >2 years: 230
Pediatric Mortality Type A: 3 Type B: 2
Total cases = 88Type A = 63Type B = 25
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 14>2 years: 16
Pediatric MortalityType A: 0Type B: 0
What have we seen with past seasonal influenza: 2006-07Canada (Sept 1-Aug 31) Manitoba (July 1 – June
30)Total cases = 7023
Type A = 6051 Type B = 972
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 183 >2 years: 187
Pediatric Mortality Type A: 1 Type B: 1
Total cases = 72Type A = 71Type B = 1
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 18>2 years: 13
Pediatric MortalityType A: 0Type B: 0
What have we seen with past seasonal influenza: 2007-08Canada (Sept 1-Aug 31) Manitoba (July 1 – June
30)Total cases = 9130
Type A = 5356 Type B = 3765
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 231 >2 years: 239
Pediatric Mortality Type A: 0 Type B: 2
Total cases = 118Type A = 79Type B = 39
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 18>2 years: 27
Pediatric MortalityType A: 0Type 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/aDeaths = n/aPediatric Hospitalizations
>2 years: 185 >2 years: 225
Pediatric Mortality Type A: 0 Type B: 0
Total cases = 110Type A = 63Type B = 37
Hospitalizations = n/aDeaths = n/aPediatric Hospitalizations
>2 years: 12>2 years: 38
Pediatric MortalityType A: 0Type 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 = 19464Type B = 3902
Hospitalizations = 1454Deaths = 72Pediatric Hospitalizations
Total = 737Pediatric Mortality
Type A: 4Type B: 0
Total cases = 1119 (440 peds)Type A = 1082Type B = 37
Hospitalizations = 221Deaths = 7Pediatric Hospitalizations
Total = 81PICU = 12
Pediatric MortalityType A: 1
What have we seen with H1N1 so far: 2009-10Canada (Sept 1-Aug 31) Manitoba (July 1 – June
30)Total cases = 2818
Type A = 2816Type B = 2
Hospitalizations = 150Deaths = 11Pediatric Hospitalizations
Total = 52Pediatric Mortality
Type A: 0Type B: 0
Total cases = 94 (27 peds)Type A = 94Type B = 0
Hospitalizations = 6Deaths = 0Pediatric Hospitalizations
Total = n/aPICU = 1
Pediatric MortalityType A: 0
What have we seen with H1N1 so far?
Worldwide: 182,166 Cases & 1799 Deaths (current to Aug 13, 2009)
WHO Africa1469 Cases3 Deaths
WHO Americas105,882 Cases1579 Deaths
WHO Eastern Mediterranean2532 Cases8 Deaths
WHO Europe> 32,000 Cases53 Deaths
WHO South-East Asia13,172 Cases106 Deaths
WHO Western Pacific27,111 Cases50 Deaths
What have we seen with H1N1 so far? (current to Aug 13, 2009)
Per PHAC:Median Age
All Cases = 18 yoHospitalizations =
25 yoICU = 40 yoDeaths = 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
ConditionsAll Cases = 36.4%Hospitalizations =
54.2%ICU = 65.3%Deaths = 75.5%
What can we expect for the fall?No one knows for sureWe 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 sneezesTravels about 1 meter (3 feet)Virus enters through the eyes, nose or throat
Can also be picked up from contaminated objectsSurvives 24-48 hours on hard, non-porous surfacesSurvives 8-12 hours on cloth, paper and tissueSurvives 5 minutes on handsLoves cold, dry climates
Which is why we have winter outbreaks
What should we be doing?Once infected, symptoms develop within 1-7
daysAn 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:
FeverSore throatCoughRunny noseSore muscles and jointsHeadacheProstration (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 vigilantIdentify and treat patients with H1N1Reduce the spread/Protect other patients
Hand washing Respiratory precautions/Droplet precautions Housekeeping Cohorting Diverting (avoidance strategies)
Protect ourselves
Diagnosis and TestingHow 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
LaboratoryNasal swab or throat swab
Sent to Cadham for viral culture and PCRRapid Influenza A test (30 min) not available to us at this
timeThere is presently no available antibody test to verify if
someone has had H1N1 already
TreatmentWhat 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 dysfunctionThe 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) patientsHigh 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 illnessWithin 12 hours of onset of illness is bestWithin 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)
VaccinationArepanrix 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 preparationH1N1 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 preparationEach dose of vaccine contains:
3.75 mcg of killed H1N1 virus5 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 preparationEach 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 preparationEach 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 EfficacyInitial studies done in Canada showed that the
vaccine was very efficacious and safeAlthough 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 EfficacyH1N1 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
ConclusionsWe 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
ConclusionsThe 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
ConclusionsSimple precautions decrease the spread
Vaccination is safe and effective
Hand washingCoughing into your
sleeveStaying 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!!!