Transcript Slide 1

ABCs of Influenza and Pandemics
Photo: Cynthia Goldsmith, CDC
1
Learning Objectives
• Describe the characteristics of influenza virus
infection in humans
• Understand different types of influenza viruses
and how they can infect humans and animals
• Describe the ways that influenza viruses can
change or mutate
2
Learning Objectives
• Describe the epidemiology of influenza, and
contrast seasonal (or human) influenza with
avian and pandemic influenza
• Understand the recent history of avian
influenza virus infections in humans
• Describe the epidemiology and clinical
characteristics of influenza A (H5N1) in
humans
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Outline
• Fundamentals of influenza viruses
• Human infection with seasonal influenza:
characteristics, diagnosis, and control
• Avian influenza viruses and zoonotic infection
• Human infection with H5N1 viruses
• Pandemic influenza
4
Fundamentals of Influenza
Viruses
5
Definitions of Terms
• Seasonal influenza: Influenza that occurs every year
with gradual variations in the previous year’s virus
surface proteins (antigenic drift)
• Avian Influenza: a disease of birds that occasionally
jumps species and infects humans. Ultimately is the
source of new influenza A viruses in humans that can
lead to pandemics
• Pandemic influenza: a worldwide surge in human
influenza cases caused by the introduction of a new
type A virus surface protein (antigenic shift)
6
Pandemic
Avian
http://www.pandemicflu.gov/
Seasonal
http://www.cdc.gov/flu/weekly/
TIMEasia, February 9, 2004
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Seasonal Influenza
Preparedness
Pandemic Influenza
Preparedness
8
Influenza Viruses
• Illness caused by
infection of the
respiratory tract with
influenza virus
• Negative singlestranded RNA virus
• 8 gene segments
code for 11 proteins
This file has been released into the public domain by the copyright holder,
http://en.wikipedia.org/wiki/Influenza_virus
9
Influenza Viruses
• Classified into types A, B,
and C
• Types A and B cause
significant disease worldwide
• Types B and C limited to
humans
• Type A viruses
More virulent
Wild waterfowl reservoir
Affect many species
Photo: Cynthia Goldsmith, CDC
10
Influenza A Viruses
Categorized by subtype
• Classified according to two
surface proteins
• Hemagglutinin (HA) – 16 known
subtypes
Site of attachment to host cells
Antibody to HA is protective
• Neuraminidase (NA) – 9 known
subtypes
Helps release virions from cells
Antibody to NA can help modify
disease severity
Hemagglutinin
This image is in the public domain in the United States
11
Nomenclature
Virus type
Strain number
Virus subtype
A /Duck/ Hunan/ 795 / 2002 (H5N1)
Optional:
Type of
Animal
Place virus
isolated
Year isolated
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Influenza Types/Influenza A Subtypes
Circulating in Tropical Country X, January
2006 through June 2007
45
40
35
30
25
20
15
10
5
H1N1
06
1/
07
2/
07
3/
07
4/
07
5/
07
6/
07
12
/
06
11
/
06
10
/
06
9/
06
8/
06
7/
06
6/
06
5/
06
4/
06
3/
06
2/
06
0
1/
% ILI testing Positive for Influenza
Positive(%)
B
Month and Year
H3N2
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Influenza A HA and NA Subtypes
H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11
H12
H13
H14
H15
H16
N1
N2
Other Animals
Other Animals
Other Animals
Other Animals
N3
N4
N5
N6
N7
N8
N9
Other Animals
Other Animals
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Review Question 1
Which influenza virus type affects humans, pigs, and
birds:
A, B, or C?
Answer: Influenza A viruses can infect multiple
species including humans pigs and birds.
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Influenza Virus Infection in
Humans
U.S. Centers for Disease Control and Prevention
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Importance of Influenza
• Global burden largely unknown
• Data from temperate climates
• 3-5 million severe cases/year
• 300,000 - 500,000 deaths/year
http://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm
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Transmission
• Influenza is an acute respiratory disease
•
•
•
Signs and symptoms reflect respiratory
route
Fever, cough, headache, muscle aches
Sometimes lower respiratory
• Transmission of influenza viruses
•
•
•
Person-to-person through droplets from
coughing or sneezing
Transmission from objects (fomites) possible
Infectious 1 day before and up to 5 days after
becoming sick
U.S. Centers for Disease Control and Prevention
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Communicability
•
•
•
•
Viral shedding can begin 1
day before symptom onset
Peak shedding first 3 days
of illness
Subsides usually by 5-7th
day in adults
Infants, children and the
immunosuppressed may
shed virus longer
U.S. Centers for Disease Control and Prevention
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Seasonality
Incubation period
•
•
•
Time from exposure to onset of symptoms
Average 2 days (range = 1-4 days)
Peak shedding first 3 days of illness
Seasonality
•
In temperate zones, increases in winter months
•
•
Driven by mutations and viral preference for cold, dry weather
conditions
In tropical zones, circulates year-round
•
•
Fall-winter and rainy season increase has been observed
More international data are needed
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Human Influenza Clinical Diagnosis
• Clinical symptoms nonspecific
• Symptoms overlap with many
•
•
pathogens
Couple with laboratory data to
verify diagnosis
Even during peak seasonal
influenza activity, only about
30% specimens tested for
influenza are positive in the
United States
U.S. Centers for Disease Control and Prevention
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Clinical Illness, Human Influenza
•
•
Abrupt onset
Fever, chills, body aches,
sore throat, non-productive
cough, runny nose,
headache.
U.S. Centers for Disease Control and Prevention
•
GI symptoms and muscle
inflammation more
common in young children
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Human Influenza Complications
• Sinus and ear infections
• Viral and bacterial pneumonia
• Myocarditis and Pericarditis
• Myositis
• Encephalopathy and
encephalitis
• Febrile seizures
• Worsening of underlying
chronic conditions
• Sepsis-like syndrome in infants
U.S. Centers for Disease Control and Prevention
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Individuals at Increased Risk for
Hospitalizations and Death
•
•
•
•
•
Adults>65 years
Adults and children with chronic medical
conditions







Neruomuscular dysfunction
Heart disease
Asthma
Chronic lung disease
Liver disease
Diabetes
Immune compromised
U.S. Centers for Disease Control and Prevention
Pregnant women
Nursing home residents
Children on long-term aspirin therapy
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Laboratory Testing for Influenza
•
Rapid diagnostic tests
•
 Can provide results
<30 minutes
 ~ 70+% sensitive,
90+% specific
•
Serology
 Must used paired
serum samples
 >2 week delay for
results
Viral culture
 “Gold standard”
 Results take 2-7 days
 Influenza isolates for yearly
vaccine development
•
RT-PCR
 Most sensitive
 Becoming more widely
available
•
Immunofluorescence
 Requires intact cells and
laboratory skill/experience
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Influenza Surveillance in the U.S.:
What Are We Trying to Measure?
U.S. population ~300 million
1
Lab Tested
~5%-20% Infected
(15-60 million)
Hospitalized
>200,000
Seek Care
Death
~36,000
~50% Symptomatic
(15-30 million)
Treat at Home
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Influenza Vaccination
•
•
•
•
•
Best way to prevent influenza
Developed from 3 circulating strains
(2 Type A and 1 Type B strain)
Seasonal “flu shot” only works for 3
influenza subtypes and will not work
on pandemic strains
Inactivated, intramuscular vaccine
injection for persons 6 months and
older
Live, intranasal spray vaccine for
healthy non-pregnant persons (2 – 49
years old)
U.S. Centers for Disease Control and Prevention
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The Two Classes of Influenza
Antiviral Medications
• Can be used for both prevention and for treatment
• Adamantanes
 Rimantadine and Amantadine
 Only for Type A viruses
 Currently not recommended for use due to resistance
among circulating influenza A viruses
• Neuraminidase inhibitors
 Oseltamivir (Tamiflu®) and Zanamivir (Relenza®)
 Type A and B viruses
 Emergence of global resistance to Oseltamivir in influenza
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A (H1N1) viruses in 2007-08
Infection Control Measures for Seasonal,
Avian, and Pandemic Influenza
•
•
Mostly in healthcare settings and
nursing homes
Standard precautions
For example, gloves, hand washing
and cough etiquette
•
Transmission-based precautions
For example, contact, droplet and
sometimes droplet nuclei precautions
•
U.S. Centers for Disease Control and Prevention
Annual influenza vaccination of all
healthcare workers
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Non-Pharmaceutical Interventions
• Social distancing
• Personal protective
measures (e.g., masks)
• Travel screening and
restriction
• Public health
communication
campaigns
This image is in the public domain of the United States
http://en.wikipedia.org/wiki/Respirator
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Review Question 2
After an adult is infected with an influenza virus, during
what time period are they most likely to shed virus?
Answer: Peak shedding occurs during the first 3 days of
illness. (Shedding can occur up to one day before illness
and usually declines within 5-7 days)
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Review Question 3
During the 2009-2009 influenza season, what class(es)
of antivirals is recommended by the CDC for
treatment of Influenza A (H1N1) virus infection or
suspected exposure?
A.
B.
C.
D.
E.
Oseltamivir
Zanamivir
Oseltamivir and rimantadine
Both B and C
None
Answer: D
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Avian Influenza
This image has been released to the public domain of the United States
http://en.wikipedia.org/wiki/Chicken
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H5N1 Epizootic – 2003-2008
•
•
Since December 2003
 >60 countries have reported H5N1
among domestic poultry or wild
birds
 Current outbreaks in many countries
 Expanded from Asia to the Middle
East, Europe, and Africa
Largest epizootic of avian influenza
ever described
 Over 200 million birds died or
destroyed
Photo: Tim Uyeki, CDC
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Cause for Concern
• Avian influenza can have a large impact on
poultry
• Can cause morbidity/mortality in poultry
• Significant economic impact
• Rarely, avian influenza A virus infection can cause
illness in humans
• Highly pathogenic avian influenza A viruses
could be a source of the next pandemic
influenza virus strain
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Avian Influenza Viruses
•
•
•
•
•
Type A influenza
Endemic in birds
May be low pathogenic or high
pathogenic
H5, H7 subtypes can be highly
pathogenic and cause serious
disease or death in wild birds; often
cause death in poultry
Virus in saliva and feces of wild
birds and poultry can be directly
transmitted to humans and other
animals
This image has been released into the public domain by the copyright holder,
http://en.wikipedia.org/wiki/Waterfowl
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Avian Influenza Virus Pathogenicity
•
•
•
Low pathogenic AI (LPAI) viruses
 Most common influenza virus infection in birds
 Causes mild clinical and
unapparent infections
 May be any subtype (H1 to H16)
Highly pathogenic AI (HPAI) viruses
 Some H5 or H7 virus strains to date
 Causes severe illness in poultry and often death
 LPAI H5 or H7 virus subtypes can mutate
into HPAI H5 or H7 virus subtypes
 Usually no symptoms or mild symptoms in wild birds
Determined by molecular and pathogenicity criteria
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Highly Pathogenic Avian Influenza
A (H5N1) Virus
• Currently spreading through Asia, Africa, Europe,
Middle East
• Can be highly lethal to domestic poultry and other
animal species
• Occasional human cases but no sustained human-tohuman transmission
• Virus of greatest concern for pandemic potential, but
other influenza viruses in animals also of concern
*As of September 2008
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Influenza A (H5N1) viruses in Other
Animals
H5N1 viruses can infect
other animals:
•
•
•
•
•
Pigs (China, Vietnam)
Dogs
Domestic cats; has
infected civet cats
Tigers, leopards
(Thailand, China)
Tiger-to-tiger
transmission (Thailand)
These images have been released into the public domain by the copyright holders,
http://commons.wikimedia.org/wiki/Category:Felis_silvestris_catus
http://en.wikipedia.org/wiki/Image:Sow_with_piglet.jpg
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Avian Influenza Virus Infections
• Usually do not jump species
Wild bird strains do not usually infect domestic
poultry
• Usually do not infect people
• Humans can become infected with avian
influenza viruses
Usually through close exposure to infected
domestic poultry
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Transmission Across Species
Wild Water
Fowl
Influenza A subtypes
circulate in wild birds
which can then infect
domestic birds.
Domestic
Birds
Wild birds are the natural
reservoir for Influenza A strains
and are the source for viruses
infecting other species.
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Review Question 4
What is the natural reservoir for avian influenza A
(H5N1) viruses, and how can humans be infected
with H5N1 virus?
Answer: The natural reservoir for all avian influenza
viruses are wild aquatic birds. Currently, humans
are chiefly infected by exposure to infected poultry.
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Human Infection with H5N1 Virus
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H5N1 in Humans: Clinical Features
• Case fatality proportion: 63%
• Median age: 18 years
• Previously healthy children, young adults
• Incubation period: 2-7 days
• Fever, cough, shortness of breath, diarrhea
• Pneumonia, acute respiratory disease
syndrome, multi-organ failure
World Health Organization. New England J Medicine 2008;358:261-73.
*WHO WER;26:249-260
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H5N1 Clinical Illness
• Very severe with high mortality
• Has primarily affected children and young adults
• Severe pneumonia is common
• Incubation period may be longer than for seasonal
•
•
influenza
Duration of infectious period likely longer than
seasonal influenza, particularly among adults
Multi-organ dysfunction is common
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Avian Influenza in Humans
Year
Subtype
Location
Cases
Deaths
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
2007
H7N2
United Kingdom
4
0
2003-08
H5N1
Worldwide
412
256
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(March 23, 2009)
Worldwide H5N1 Outbreak
in Birds: 2003 - 2008
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Source: WHO
Worldwide H5N1 Outbreak
in Humans: 2003 - 2008
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Source: WHO
Human H5N1 Epidemiology
• Direct and close contact with sick or dead
poultry
Slaughtering or cleaning poultry
Visiting a live poultry market
• No evidence of sustained person-to-person
spread
• Limited probable person-to-person spread1
1 World
Health Organization. New England
J Medicine 2008;358:261-73.
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Possible Mechanisms of
International Spread
• Legal poultry business
• Illegal bird trade
• Migrating birds
• Humans
(contaminated objects)
• Untreated fertilizer
This image has been released into the public domain by the copyright holder.
http://commons.wikimedia.org/wiki/Image:Industrial-Chicken-Coop.JPG
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The Possibility of a Pandemic
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What is Pandemic Influenza?
• Pandemic: epidemic spreading around the
world affecting hundreds of thousands of
people, across many countries
• Flu pandemic: global epidemic of new
influenza A virus subtype that:
Passes easily from person to person
Causes severe disease
• Essentially no pre-existing immunity;
everybody at risk
52
Influenza Viruses
Characterized by ability to change:
• Continually (antigenic drift) → yearly
epidemics
• Drastically (antigenic shift) → rare pandemics
U.S. Centers for Disease Control and Prevention
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Antigenic “Drift”
Minor antigenic changes to the hemagglutinin
protein
•
•
•
•
•
Point mutation in viral RNA
Continuous process during viral replication
Cause of seasonal epidemics
Immunity may be limited to a specific strain
Vaccine strains must be updated each year
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Antigenic “Shift”
Major antigenic changes leading to emergence
of a new human influenza A virus subtype
through:
• Genetic reassortment (human and animal viruses)
• Direct animal (poultry) to human transmission
A pandemic can occur if:
• Efficient and sustained virus transmission occurs
among humans (sustained person-to-person
spread)
55
Drift and Shift, Illustrated
This image has been released into the public domain by the copyright holder.
http://en.wikipedia.org/wiki/Influenza
56
Re-assortment and
Direct Transmission
Non-human
virus
Human
virus
Reassortant
virus
57
Requirements for an Influenza
Pandemic Virus
• A new influenza A subtype virus emerges that
can infect humans
AND
• Causes serious illness
AND
• Spreads easily from human-to-human in a
sustained manner
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Pandemic Influenza
• Timing unpredictable
• High illness rates across age groups
• Increased mortality
 Higher proportion deaths in younger persons
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Estimated Mortality from Previous
Influenza Pandemics
• 1918-19 (H1N1)
>500,000 deaths US
20 -100 million
worldwide
• 1957-58 (H2N2)
70,000 excess deaths
US
• 1968-69 (H3N2)
34,000 excess deaths
US
US National Archives at College Park, MD.
Record number 165-WW-269B-25
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Why worry?
Total deaths in 1918-1919 estimated to be 20-100
million worldwide. U.S. Deaths = 550,000-675,000
U.S. Life Expectancy 1900-1960
70
65
Age
60
55
50
45
40
35
1900
1918
Source: CDC Pandemic Influenza Update, May, 2006; http://www.immunize.org/pandemic/panflu506.pdf
Date
1960
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U.S. Impact Estimates for the Next
Influenza Pandemic
Deaths: 89-207,000
Hospitalizations: 314-733,000
Outpatient care: 18-42 m
Total infected: 43-100 m
.03-.07%
.1-.3%
6-15%
15-35%
Health related economic impact
Estimated: $71 to $166 billion
Meltzer M, et al. Emerging Infectious Diseases 1999;5:659-671
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Geographic spread: 1918-19
06/18
?
03/18
04/18
06/18
05/18
?
01/19
06/18
JVT – IVW, Lisbon
C.W. Potter, Textbook of Influenza, 1998
63
Seasonal Epidemics vs. Pandemics
•
•
•
•
Human Influenza
A public health problem
each year
Usually some immunity
built up from previous
exposures to the same
subtype
Infants and elderly most at
risk
Result of Antigenic Drift
Influenza Pandemics
•
•
•
•
Appear in the human
population rarely and
unpredictably
Human population lacks
immunity to a new influenza
A virus subtype
All age groups, including
healthy young adults, may
be at increased risk for
serious complications
Result of Antigenic Shift
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Timeline of New Influenza A Subtype
Virus Infections in Humans
Avian
Influenza
H9
H7
H5
H3
H2
H1
H1
1915
1925
1935
1945
1955
1965
1975
1985
1995
1918
1957
1968
1977
Spanish
Influenza
H1N1
Asian
Influenza
H2N2
Hong Kong
Influenza
H3N2
Emergence
of H1N1
2005
65
Concerns about Pandemic Influenza
• Rapid global spread (morbidity and mortality)
• Shortages and delays – vaccines and antiviral
medications
• Increased burden on hospitals and outpatient
care systems
• Disruption of national and community
infrastructures
66
Review Question 4
Match each term to the statement that it best fits
• Seasonal Flu
• Occurred 3 times in the
20th century
• Avian Flu
• Pandemic Flu
• Outbreaks result from
antigenic drift
• Usually does not infect
people
67
Potential Strategies to Decrease the
Impact of a Pandemic
• Prevent or delay introduction, slow spread
• Decrease illness and death
 Vaccine when available
 Antiviral treatment and isolation for people with illness
 Non-pharmaceutical interventions
Unprepared
Impact
Prepared
Weeks
68
WHO Phases of a Pandemic
http://www.who.int/csr/disease/avian_influenza/phase/en/index.html
69
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
70
WHO Phases of a Pandemic
Pandemic Alert Period
Phase 3: Human infection with novel virus; no or
very limited human-to-human spread
Phase 4: Small, localized clusters of human-tohuman spread
Phase 5: Larger clusters, still localized; virus
adapting to humans
71
WHO Phases of a Pandemic
Pandemic Period
Phase 6: Increased and sustained transmission in
the general population.
Post Pandemic Period
Recovery phase
72
Influenza Pandemic Viruses
A new influenza A subtype virus can infect humans
AND
Causes serious illness
AND
Spreads easily from human-to-human in a sustained
manner
The first two prerequisites have been met,
but not the last
73
Summary
• Seasonal influenza differs slightly each year
Disease often mild but may have serious complications
• Avian influenza viruses may experience antigenic
shift and infect humans
Current concern over influenza A (H5N1) virus
• Pandemic requirements for H5N1 virus have not
been met
Virus does not transmit easily between humans, no
sustained transmission
74
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.
75
Glossary
Seasonal Influenza
Refers to annual influenza epidemics occurring during
winter among people living in temperate climates; caused by
circulating strains of human influenza A and B viruses that
have minor antigenic changes each season and are
transmitted from person-to-person.
Pandemic Influenza
A global epidemic causing widespread morbidity and
mortality among a high proportion of people, caused by the
emergence of a novel influenza A subtype virus among
people that is spread from person-to-person in a sustained
manner.
76
Glossary
Antigenic Drift
A process of small changes in the genetic material of human
influenza A and B viruses, called point mutations, that occur
during the normal virus replication process and result in
changes to the surface proteins producing new strains;
causes seasonal influenza epidemics
Antigenic Shift
Refers to human infection by novel influenza A viruses (not
circulating among people) with a new hemagglutinin
subtype virus, and may also include infection with both a
new hemagglutinin and a new neuraminidase protein. Can
result from direct transmission from an animal influenza A
virus, or through genetic reassortment between human and
animal influenza A viruses; the new virus has pandemic
potential among humans.
77
Glossary
Highly Pathogenic Avian Influenza (HPAI) Virus
Kind of avian influenza viruses (H5 or H7 subtypes) that
usually causes high mortality among domestic poultry and
other bird species. Can be transmitted to other kinds of
animals and rarely to humans resulting in a range of
symptoms including severe illness and death.
Low Pathogenic Avian Influenza (LPAI) Virus
Kind of avian influenza viruses that infect many wild bird
species and poultry. Can evolve into highly pathogenic
viruses. Can cause rare human infection that is usually
clinically mild.
78
References and Resources
•
•
•
Cécile Viboud, et al. Emerg Infect Dis [serial on the Internet].
2006 Apr. Available from
http://www.cdc.gov/ncidod/EID/vol12no04/05-0695-G2.htm
Writing Committee of the Second World Health Organization
(WHO) Consultation on Clinical Aspects of Human Infection
with Avian Influenza A (H5N1) Virus. Update on Avian
Influenza A (H5N1) Virus Infection in Humans. N Engl J
Med. 2008;358;261-73.
Ungchusak K, et al. Probable Person-to-Person Transmission
of Avian Influenza A (H5N1) N Engl J Med 2005;352:333340.
79
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/vol11no11/05-0608.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/
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