5/14/2009
Coping with Global Influenza: Consequences of Novel‐Swine
Consequences of Novel‐Swine Origin Influenza Epidemic Deoraj Caussy PhD Virologist/Epidemiologist
Deoraj Caussy PhD, Virologist/Epidemiologist
International Epidemiology Consulting text
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email caussyone @yahoo.com
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Consequences of Novel Influenzavirus found in Mexico/USA in April 2008, fast spreading
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Major public health problem
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• Morbidity (high) and mortality (low)
• Overwhelmed medical care systems
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Substantial economic impact • LLost work / school days (billion of $$$$ loss)
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• Trade and Commerce disrupted
EU banned imports of pork from México US and
• EU banned imports of pork from México, US and Canada
• Travel restrictions impact tourism
• Mexican, Canadian tourists quarantined in China
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Any novel influenza is reportable to WHO under IHR (2005)
• WHO may issue travel restrictions etc
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Introduction: Three types of influenza infections in humans
zSeasonal‐human influenza virus.
– A contagious respiratory illness caused by influenza viruses
– Viruses fixed and circulating in the human population‐Influenza A (H3N2, H1N1 and B strains. Vaccine formulations change regularly.
zPandemic: animal‐to‐human =>to human‐to human
P d i
i lt h
>t h
t h
– Animal influenza virus adapts and transmits in humans‐new subtype
– Flu
Flu that causes a global outbreaks and spread that causes a global outbreaks and spread
easily from human to human ( Spanish flu 1918)
– Currently there is H1N1 in pandemic phase 5 zSporadic‐
Sporadic animal to human
animal to human
– Animal influenza viruses infectious for humans under special circumstances. – Most common Avian and swine
Most common Avian and swine
– Current avian H5N1 infections GLOBAL
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Epidemiology Terms
p de o ogy e s
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Epidemic
– When the cases of a disease exceed what is normally expected z
Pandemic
– An
An epidemic that occurs over a large geographic area, or epidemic that occurs over a large geographic area or
across the whole world
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Recycling of seasonal and Pandemic Influenza Disease
Seasonal Influenza
Pandemic Influenza
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Recycling of seasonal and Pandemic Influenza Disease
3. Undergoes mutation called g
“antigenic drift”
Produces new seasonal flu
2. Seasonal Influenza
1. Pandemic Influenza
4. Process is called “ ti i hift”
“antigenic shift” or genetic reassortment
combines with animal virus 6
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Structure of Influenza A viruses
8 genes 8
(RNA)
Hemagglutinin (HA)
Hemagglutinin (HA)
Neuraminidase (N)
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Role of Hemagglutinin (H) and Neuraminidase (N) proteins
gg
( )
( )p
Virus attaches by the H Vi
tt h b th H
H proteins
Virus detaches by the N Vi
d t h b th N
proteins
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Ecology of influenza viruses in Nature
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Repertoire of H and N in animals can be used for generation of novel viruses
H1
H2
N1
N2
H3
H4
N3
H5
H6
H7
H8
N5
N6
N7
N8
N9
H9
H10
H11
H12
H13
N4
Birds have the whole repertoire of H and N genes
Swine: H1, H3, H9, N1 & N2
H14
H15,16
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Nomenclature of the 2009 novel human virus of swine origin
A / California/ 04 / 2009 (H1N1)
A / California/ 04 / 2009
Virus type
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Geographic Geographic
origin
Strain Strain
number
Year of Year
of
Isolation
Virus subtype
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Pandemic generated by genetic reassortment
Reassortment can be generated in the Laboratory
Influenza has 8 segmented genes
Parental influenza one
Parental influenza one
Segmented genes facilitate exchange of genetic materials
P
Parental influenza two
l i fl
Segmented genes facilitate exchange of genetic materials
Progeny influenza has genes of both parents: reassortants
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Juxtaposition of susceptible species of animal: Environmental Test tube for breeding novel influenza virus
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Generation of Pandemic Influenza Strains from repertoire of influenza genes
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The novel H1N1 virus is a mongrel:
will it cause a pandemic?
ll
d
?
Triple reassortants: swine, avian, human
The HA gene closer to classical swine 15
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Epidemiology of Novel Swine‐origin p
gy
g
Influenza A (HIN1) in Humans
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Epidemiologic Curve of Confirmed Cases of Human Infection with Swine-Origin Influenza A
(H1N1) Virus with Known Date of Illness Onset in the United States (March 28-May 5, 2009)
Distribution in Time: Epidemic Curve of Confirmed Novel H1N1 human cases
H1N1 human cases
Curve: point C
i t
source with secondary transmission
Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. N Engl J Med
2009;10.1056/NEJMoa0903810
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Distribution of novel H1N1 in persons
st but o o o e
pe so s
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Persons with travel history to Mexico within 7 days
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Median age 20 (3 months to 81 years)
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P k i 10 18 d 19 50
Peak in 10‐18 and 19‐50 age group
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Equal in Male and female 18
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Distribution in Place: Epicenter of novel H1N1 virus
The virus was first detected in Mexico followed by USA
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Person‐to‐person transmission is widespread in US
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WHO map
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30 countries affected
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Groups at Risk for morbidity and mortality with Novel H1N1
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y
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Complications same as for seasonal flu ( so far)
Complications same as for seasonal flu ( so far)
– Pneumonia, worsening of chronic lung and heart problems, and death
High Risk Groups same as for seasonal flu
–
–
–
–
–
–
Persons 65 years and older
Persons with chronic diseases Infants between 6 months and 2 years
Pregnant women
Pregnant women
Nursing home/institutional/ residents & military personnel
Children on long‐term aspirin therapy
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Prevention and Control: Novel H1N1 Influenza Virus (same a seasonal flu)
Virus (same a seasonal flu)
1.
Non pharmaceuticals
Chemotherapy
2.
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3.
Vaccines (?)
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Transmission of H1N1
a s ss o o
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Viral peak shedding in prodrome phase
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Incubation period between 2‐7 days
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Contact and Droplet
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Hand to hand
Hand to hand
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Droplet nuclei (within 3 feet)
– Droplets generated by coughing, talking, sneezing, close contact
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Non‐pharmaceutical interventions: Decrease Contacts by Social Distancing
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Protect children and teens ( México USA)
Protect children and teens ( México, USA)
– School closures (dismissals) – Reduce children and teen gatherings
Reduce children and teen gatherings
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Cancellation of mass gatherings ( Mexico)
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Alternatives to face‐to‐face contact at work
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Increasing distance between people (>3 feet) (Lebanon)
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Effectiveness of these measures in Mexico not assessed
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Infection Control Measures
to Decrease Transmission
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Hand hygiene
Hand hygiene
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Facemasks
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C
Cough etiquette
h ti
tt
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Sick people stay home (isolation)
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Perhaps stay home if have an ill household member (voluntary home quarantine)
home quarantine)
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Environmental cleaning
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Use of Tamiflu for treating H1N1
zthe novel H1N1 is sensitive to the novel H1N1 is sensitive to
Tamiflu
zWidespread use may lead to R it
Resistance to Tamiflu t T ifl
z limited supply for global market if pandemic starts
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75 mg, twice daily for 5 days
zLimited surge capacity for mass production/licensing etc
zPrice beyond most health care budget
zLimitation for containing an Limitation for containing an
established epidemic
zRecommended for preempting the i iti l t
initial stage of the epidemic
f th
id i
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Current Seasonal Influenza Vaccine Production Timeline: 6 ‐ 9 months
Manufacturers must see profitable market to make novel H1N1 vaccine
C
Currently making seasonal vaccine
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Critical Assessment of Pandemic Potential: Novel H1N1 Influenza Virus
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Major Challenges in Applying the Risk Analysis Paradigm to influenza
Uncertain art to predict a pandemic
Alternative Approach Use Precautionary Principle to implement the zero‐ risk policy Implication
Implication of wrong risk analysis:
Implication of wrong risk analysis
of wrong risk analysis:
analysis
Raise unnecessary fears
Waste scare resources
Ignore important Problem
Accurate Representation of Uncertainties
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Compute scenarios of best estimates and worst estimates based on past pandemics
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Why are we concerned with pandemic?
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1918: “Spanish Flu”
1957: “Asian Flu”
1968: “Hong Kong Flu”
40-50 million deaths
1-4 million deaths
>1 million deaths
H1N1
H2N2
H3N2
20th century major influenza epidemics
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Grim Images of “helplessness” in 1918 Pandemic
Minimizing contagion by use of masks
Emergency influenza hospital
mergency influen a hospital
Overcrowded make shift shelters
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Pandemics must be quelled in the b i i
beginning stage
t
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WHO uses “ precautionary principle” by declaring phase 5
WHO web‐site lumps phase 5/6: but phase 5 and 6 differ in epidemiology
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A tale of two candidate pandemic virus
H5N1 (avian)
H1N1 (novel of swine‐origin)
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Animal origin
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Animal origin
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Predominant in developing Predominant
in developing
world
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Confined to Western Confined
to Western
Hemispheres
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High mortality
High mortality
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Low mortality
Low mortality
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Has vaccine ready
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No vaccine
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Virus is evolving into new Vi
i
l i i t
clades
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Genetically too soon to G
ti ll t
t
predict
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The two candidates occupy different niches
h
Global distribution of avian flu
Global distribution of novel flu
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Epidemiologic signatures of past pandemic influenza
Past Pandemic viruses
‘Candidate’ novel H1N1
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Higher death in younger age
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More transmissible than seasonal z Not definite: (?surveillance)
More transmissible than seasonal
N t d fi it (?
ill
)
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Regional differences in epidemic
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More severe in Mexico only
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Shif i i l i l l d
Shift in virological clades
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No sign yet
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Strikes in “non‐flu” season
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Just about
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Successive pandemic waves
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Need to monitor
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Not seen yet
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Weekly Mortality Record from US Public Health Service
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Mortality Distributions and Timing of Waves of Previous Influenza Pandemics
“Epidemiologic Signatures” of past Influenza P d i
Pandemics
Mild in Summer, ,
severe in Winter
First Mild wave
Second severe wave
3 winter waves in 5 years
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So e po ts o co s de at o
Some points for consideration
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Over reactions: swine vaccine in 1976: Gerald Ford
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Manifestation of Rye syndrome in vaccinees
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1918 conditions of environmental and health 1918
conditions of environmental and health
conditions are different than 2009 but jet age has come 40
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Risk Analysis for Mauritius
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a ys s o au t us
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Risk may be lower or may be higher than global risks
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Lower risk than the world
™ Insularity protects from outside viruses
Insularity protects from outside viruses
™ Disruption of air travel may spare Mauritius
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Higher risk than the world
Higher risk than the world
™ Pandemic may quickly spread in the island
™ Tourism and trade may be negatively affected
Tourism and trade may be negatively affected
™ Diagnostic reagents and essential drugs may be unavailable
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A Pandemic is due: When and which virus?
Avian Influenza
H9
H7
H5
H3
H2
H1
1915 1925 1935 1945 1955 1965 1975 1985 1995
1915 1925 1935 1945 1955 1965 1975 1985 1995 2005
2005
1918
Spanish
I fl
Influenza H1N1
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1957
Asian
Infl en a
Influenza
H2N2
1968
Hong Kong
Influenza
H3N2
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Continue Surveillance for Influenza variant viruses!
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