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Transcript
Module 1: ABCs of Influenza
and Pandemics
Airline Team Training
1
Photo: Cynthia Goldsmith
Learning Objectives
• Understand the basic biology of
influenza viruses
• Describe the ways that influenza
viruses can change or mutate
• Compare the epidemiology and key
characteristics of seasonal and
pandemic influenza, including H1N1
2
Influenza Virus
Orthomyxovirus
3
The Virus
4
Types of Influenza Virus
• Three types: A, B, C
• Influenza Type A can infect: People, birds,
pigs, horses, seals, whales and others
• Influenza Type B: Human virus
– Not classified according to Subtype
– Cause human epidemics but not pandemics
• Influenza Type C cause mild illness in
humans
– Not classified according to subtype
– Do not cause epidemics or pandemics
5
Low vs. High Pathogenic
Avian Influenza
• Low Pathogenic Avian Influenza Viruses (LPAI):
–
–
–
–
–
May not cause any illness in wild birds
Associated with mild illness in domestic poultry
Can evolve into highly pathogenic viruses
Associated with poultry outbreaks worldwide
Subtypes: H9
• High Pathogenic Avian Influenza Viruses (HPAI):
–
–
–
–
May not cause any illness in wild birds
High mortality in domestic poultry
High risk of disease in people
Subtypes: H5, H7
6
Influenza Virus
Types A and B
Type A
(Seasonal and avian
influenza)
Type B
(Seasonal influenza)
Can cause significant disease
Generally causes milder
disease but may also cause
severe disease
Infects humans and other
species (e.g., birds; H5N1)
Limited to humans
Can cause epidemics and
pandemics (worldwide epidemics)
Generally causes milder
epidemics
7
Influenza A Virus Subtyping
• Influenza A subtypes are determined by
two surface glycoproteins:
–Hemagglutinin (HA)
–Neuraminidase (NA)
• 16 HA’s and 9 NA’s
8
Species Infected by Influenza A, HA and NA
Subtypes
H2
N1
N2
H3
H4
N3
N4
H5
H6
H7
H8
N5
N6
N7
N8
N9
H1
H9
H10
H11
H12
H13
H14
H15,16
9
Antigenic Drift
• Point mutations in the hemagglutinin gene
cause minor antigenic changes to HA
– Continuous process
– Immunity against one strain may be limited
• Antigenic drift produces new virus strains that
may not be recognized by antibodies to earlier
influenza strains
• One of the main reasons why people can get
the flu more than one time (Seasonal epidemics).
• one or two of the three virus strains in the
influenza vaccine are updated:
– 6-8 months process
– Targeted at high-risk (inactivated)
10
Antigenic Shift
• new influenza virus that can infect humans
and has (new HA subtype ± NA) through:
– Genetic reassortment (human and animal
viruses)
– Direct animal (poultry) to human
transmission
• if most people have little or no protection
against the new virus:
– Spread easily from person to person
– Pandemic (worldwide spread) may occur
11
How Do Influenza Viruses Become
More Pathogenic?
Antigenic Shift
• Strong selection pressure acting on
mutations or changes in HA or NA
– Direct infection in humans
• Re-assortment
– Two different strains of influenza
infect the same host
– “Reassorted” virus emerges
12
What is going on now?
Human
seasonal
influenza
virus
Avian
influenza
Virus, may
infect
humans
Current status
?????
13
Migratory
birds
Reassortment of influenza
viruses
Avian
virus
Human
virus
Reassortment
Human
virus
Reassortment
New strain
14
Examples of Re-assortment and
Direct Transmission
Non-human
virus
Human
virus
RE-ASSORTMENT
Reassortant
virus 15
Epidemiology Terms
• Endemic
– A disease that occurs at an expected constant
level in a population
– “Background” level
Red line: Expected deaths each year
Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet]. 2006 Apr. Available from 16
http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm
Epidemiology Terms
• Epidemic
– When the cases of a disease exceed what is
normally expected
• Pandemic
– An epidemic that occurs over a large geographic
area, or across the whole world
17
Seasonal Epidemics vs. Pandemics
Seasonal Influenza
Influenza Pandemics
– A public health
problem each year
– Appear in the human
population rarely and
unpredictably
– Usually some
immunity built up
from previous
exposures to the
same subtype
– Human population
lacks any immunity
– Infants and elderly
most at risk
– All age groups,
including healthy
young adults
18
Mortality Impact of
Past Pandemics
1918-19 Spanish Flu (H1N1)
– ~ 40 million deaths worldwide
1957-58 Asian Flu (H2N2)
– 1 - 2 million deaths worldwide
1968-69 Hong Kong Flu (H3N2)
– ~ 700,000 deaths worldwide
19
Timeline of Influenza Pandemics
Examples of
Current Avian
Influenza
Strains
H9
H7
H5
H3
H2
H1
1915
1925
1918
Spanish
Influenza
H1N1
1935
1945
1955
1957
Asian
Influenza
H2N2
1965
1975
1985
1995
2005
1968
Hong Kong
Influenza
H3N2
20
Avian Influenza in Humans
Year
Subtype
Location
1996
H7N7
United Kingdom
1
0
1997
H5N1
Hong Kong
18
6
1998
H9N2
China
6
0
1999
H9N2
Hong Kong
2
0
2002
H7N2
United States
1
0
2003
H7N2
United States
1
0
2003
H9N2
Hong Kong
1
0
2003
H5N1
Hong Kong
2
1
2003
H7N7
The Netherlands
89
1
2004
H7N3
Canada
2
0
317
19121
2003-07 H5N1
Worldwide
Cases
Deaths
Worldwide H5N1 Outbreak
in Humans: 2003 - 2007
Source: WHO
22
Human H5N1 Epidemiology
• Primarily avian-to-human transmission
• No evidence of sustained person-to-person
spread
• Limited probable person-to-person spread1
• Environment-to-human transmission
possible
1N
Engl J Med 2005;352:333-340
23
WHO Stages of a Pandemic
•
Inter-pandemic period
•
Pandemic alert period
–
Current status
•
Pandemic period
•
Post pandemic period
24
25
WHO Phases of a Pandemic
Inter-pandemic Period
Phase 1: No new Influenza virus subtypes
in humans
Phase 2: No new virus subtypes in
humans; animal subtype poses a risk of
human disease
26
WHO Phases of a Pandemic
Pandemic Alert Period
Phase 3: Human infection with novel
virus; no instances of human-to-human
spread (current status)
Phase 4: Small, localized clusters of
human-to-human spread
Phase 5: Larger clusters, still localized;
virus adapting to humans
27
WHO Phases of a Pandemic
Pandemic Period
Phase 6: Increased and sustained
transmission in the general population.
Post Pandemic Period
Recovery phase
28
Prerequisites for pandemic influenza
A new influenza virus emerges to which
the general population has little/no
immunity
The new virus must be able to replicate
in humans and cause disease
The new virus must be efficiently
transmitted from one human to another
29
Influenza Infection in
Humans; Seasonal vs H5N1
30
Key Characteristics
Seasonal Influenza
usually respiratory
infection
Transmission
– Highly contagious
– Primarily through
contact with
respiratory droplets
– Transmission from
objects possible
H5N1
usually respiratory
may involve GI
Transmission
– Not highly contagious (now)
– Primarily through contact
with respiratory droplets
– Possible transmission from
objects
– Possible faecal-oral route
31
Key Characteristics
Communicability
Seasonal Influenza
H5N1
– Transmission;
• 1 - 2 days before
onset of symptoms
to 4 - 5 days after
onset
–Transmission;
may be similar - not
enough data yet
– Incubation Period;
1-5 days (Mean 2 days)
– Incubation Period;
2 - 8 days (Mean 2-3 days)
– Case Fatality Rate;
<1%
– Case Fatality Rate;
>50%
32
Vaccination
• Influenza vaccine is the best prevention for
seasonal influenza.
• Inactivated viruses in the vaccine
developed from three circulating strains
(generally 2 Type A and 1 Type B strain).
• Provides little or no protection to H5N1
• No vaccine yet for H5N1 - in development
33
Summary
• Influenza is a serious human and veterinary
health concern each year
• Influenza virus strains evolve rapidly and can
develop into a novel virus with pandemic
potential
• Influenza pandemics have caused high
morbidity and mortality in the past
34
Summary
• H5N1 Avian Influenza is currently spreading
through birds with occasional outbreaks
among humans
• While there is evidence of rare human to
human transmission, sustained transmission
has not occurred
• If H5N1 virus obtains the ability to easily
transmit from person to person, a pandemic
may result
35
Questions?
36
Glossary
Virus
A small, infectious agent consisting of a core of genetic
material (DNA or RNA) surrounded by a shell of protein. A
virus needs a living cell [a host] to reproduce.
Viral shedding
Multiplication of a virus in an infected person with
subsequent release of the virus from that infected person,
such that others who come into contact with the person
may become infected. A state of being contagious.
Epidemiology
The branch of medicine that deals with the study of the
causes, distribution, and control of disease in populations.
37
Glossary
Seasonal Influenza
Expected rise in influenza occurrence among humans
living in temperate climates; occurs during the winter
season with strains of influenza that have minor
changes from season to season.
Pandemic
An epidemic occurring over a wide geographic area
and affecting a large proportion of the population.
Antigenic Drift
A process of small changes in the genetic material of a
virus, called point mutations, that occur during the
normal virus replication process.
38
Glossary
Antigenic Shift
A process of major changes in the genetic material of a
virus; for influenza, the H and N proteins change
altogether, resulting in a new strain of virus.
Highly Pathogenic Avian Influenza (HPAI)
Influenza infection in poultry that causes severe illness
and often death. Can be transmitted to humans
resulting in severe illness or death.
Low Pathogenic Avian Influenza (LPAI)
The most common influenza infection in birds; causes
mild clinical and unapparent infections.
39
References and Resources
• Cécile Viboud, et al. Emerg Infect Dis [serial on the
Internet]. 2006 Apr. Available from
http://www.cdc.gov/ncidod/EID/vol12no04/05-0695G2.htm
• The Writing Committee of the World Health
Organization (WHO) Consultation on Human
Influenza A/H5. Avian Influenza A (H5N1) infection in
humans. N Engl J Med. 2005 Sep 29;353(13):1374-85.
• Ungchusak K, et al. Probable Person-to-Person
Transmission of Avian Influenza A (H5N1) N Engl J
Med 2005;352:333-340.
40
References and Resources
• Tiensin T, et al. Highly Pathogenic Avian Influenza
H5N1, Thailand, 2004. EID;2005;11(11):1664-72.
http://www.cdc.gov/ncidod/eid/vol11no11/050608.htm
• World Health Organization. Epidemic and Pandemic
Alert and Response. 2006. http://www.who.int/csr/en/
• Center for Food Security and Public Health. Iowa
State University: http://www.cfsph.iastate.edu/
41