Download Influenza Infection in Humans

Module-1
ABCs of Influenza and
Pandemics
Joshua A. Mott. MA, EMT-P, PhD
Influenza Division, CDC
1
Learning Objectives
• Describe the characteristics of influenza
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 outbreaks in humans
• Describe the epidemiology and clinical
characteristics of influenza A (H5N1) in
humans
3
4
Seasonal Influenza
Preparedness
Pandemic Influenza
Preparedness
5
Influenza Viruses
• Illness caused by
infection with an
influenza virus
• Negative singlestranded RNA virus
• 8 gene segments
code for 10 proteins
6
Influenza Viruses
• Classified into types
A, B, and C
• Only Types A and B
cause significant
disease
C Goldsmith, CDC
• Types B and C limited
to humans
• Type A viruses
• More virulent
• Affect many species
7
Influenza A Viruses
• Influenza A viruses categorized by subtype
• Classified according to two surface proteins
• Hemagglutinin (H) – 16 known
– Site of attachment to host cells
– Antibody to HA is protective
• Neuraminidase (N) – 9 known
– Helps release virions from cells
– Antibody to NA can help modify disease severity
N
H
8
Nomenclature
Virus type
Strain number
Virus subtype
A / Sydney / 05 / 97 (H3N2)
Place virus
isolated
Year isolated
9
Influenza Infection in
Humans
10
Key Characteristics
Influenza is a respiratory
infection
Transmission of influenza
viruses
– person-to-person
transmission through close
contact
– Primarily through contact
with respiratory droplets
– Transmission from objects
(fomites) possible
11
Shedding
– Viral shedding can begin 1
day before symptom onset
– Peak shedding first 3 days of
illness
– Correlates with temperature
– Subsides usually by 5-7th
day in adults
– can be longer in children
– Infants, children and the
immunocompromised may
shed the virus longer
12
Key Characteristics
Incubation period
– Time from exposure to onset of symptoms
– 1 to 4 days (average = 2-3 days)
Seasonality
– In temperate zones, sharp peaks in winter months
– In tropical zones, circulates year-round with
seasonal increases.
• A fall-winter seasonal increase, and secondary rainy
season increase has been observed in some tropical
countries.
– More international data is needed
13
Clinical Illness, Human Influenza
• Abrupt onset
• Fever and constitutional symptoms: body aches,
headaches, fatigue
• Cough, rhinnitis, sore throat
• GI symptoms and myositis more common in
young children
• Sepsis-like syndrome in infants
• Complications: sinus and ear infections, viral and
bacterial pneumonia, myocarditis, pericarditis,
encephalopathy/encephalitis, febrile seizures,
worsening underlying chronic conditions
14
Human Influenza - Clinical
Diagnosis
• Clinical symptoms non-specific
– Symptoms overlap with many
pathogens
– Coupling with laboratory data to verify
diagnosis
– Even at peak seasonal influenza
season, about 30% specimens tested
for influenza are positive in the United
States
15
Laboratory Testing for
Influenza
• Viral culture
– Gold standard but results take 7+ days usually
– Influenza isolates for yearly vaccine development
• RT-PCR
– Most sensitive
– Becoming more widely available
• Immunofluorescence
– Requires intact cells and laboratory skill/experience
• Point-of-care rapid diagnositc tests
– Can provide results <30 minutes
– Generally 70+% sensitive, 90+% specific
• Serology
− Must used paired serum samples
− >2 week delay for results
16
Individuals at Increased Risk for
Hospitalizations and Death
• Elderly > 65 years
• Young Infants
• Persons with chronic medical conditions
– Heart or lung disease, including asthma
– Metabolic disease, including diabetes
– HIV/AIDs, other immunosuppression
– Conditions that can compromise respiratory function or the
handling of respiratory secretions
• Pregnant women
• Nursing home residents
• Children on long-term aspirin therapy
17
600
100
500
400
80
300
60
200
40
100
20
Deaths Per 100,000 Person Years
Hospitalizations Per 100,000 Person Years
Influenza-Associated Hospitalizations,
United States Deaths By Age Group
0
0
0 - 4 Yrs
5 - 49 Yrs
50 - 64 Yrs
65+ Yrs
Age Group
*Thompson WW, JAMA, 2004
18
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)
– Therefore, seasonal “flu shot” only works for 3 influenza
subtypes and will not work on pandemic strains.
• Inactivated, injectable vaccine for persons 6
months and older
• Live, intranasal spray vaccine for healthy nonpregnant persons 5-49 years
19
Influenza Antiviral
Medications
• Can be used for both prevention and
for treatment
• Two classes
– Adamantanes – rimantadine and
amantadine
• Currently not recommended for use due to
resistance among circulating influenza A
viruses
– Neuraminidae inhibitors
• Oseltamivir and zanamivir
20
Infection control measures
• use of droplet precautions
(masks, gowning, gloves)
• isolating or cohorting influenza
patients
• limiting exposures
• having ill workers stay home
• screening and limiting visitors
• annually vaccinating all
healthcare workers
21
Non-Pharmaceutical
Interventions
• Voluntary isolation of sick people
• Voluntary quarantine of healthy
contacts
• School closures
• Social distancing
22
Avian Influenza
23
Cause for Concern
• Avian influenza can have a large impact
on poultry
– Can cause high mortality
– Significant economic impact
• Rarely, avian influenza can cause
illness in humans
• Avian influenza viruses can serve as
source of next pandemic strain
24
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
25
Avian Influenza
• Type A influenza
• Endemic in birds
• H5, H7 subtypes can 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
26
Avian Influenza
• Low pathogenic AI (LPAI)
– Most common influenza infection in birds
– Causes mild clinical and unapparent infections
– May be any subtype (H1 to H15)
• Highly pathogenic AI (HPAI)
– Some H5 or H7 subtypes
– Causes severe illness in poultry and often death
– LPAI H5 or H7 subtypes can mutate
into HPAI H5 or H7 subtypes
27
Avian Influenza Viruses
• Usually do not jump species
– Each “subtype” infects a specific set of animals
– Wild bird strains do not usually infect domestic
poultry
• Usually do not infect people
• Humans can become infected with avian
influenza viruses
– Usually through exposure to infected domestic
poultry that have become infected with wild bird
avian viruses
28
Avian influenza
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.
29
H5N1 Avian Influenza
• Currently spreading through Asia, Africa,
Europe, Middle East
• Can be highly lethal to domestic poultry and
other animal species
• Occasional human cases but no efficient
human-to-human transmission
• Virus of greatest concern for pandemic
potential, but other influenza viruses in
animals also of concern
*As of March 8, 2007
30
H5N1 Epizootic – 2003-2006
• Since December 2003,
– >50 countries have
reported H5N1 among
domestic poultry and wild
birds
– Current outbreaks in a
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
31
H5N1 Clinical Features
• Case fatality ratio: 60%
• Median age: 20 years (range 3 mos-75
yrs)*
• Previously healthy children, young
adults
• Incubation: 2-7 days
• Fever, cough, shortness of breath,
diarrhea
• Pneumonia, acute respiratory disease
syndrome, multi-organ failure
32
Beigel JH, et al. NEJM 2005;353:1374-85
*WHO WER;26:249-260
Clinical illness with H5N1
compared with typical human
influenza illness
• More severe illness in younger persons
• Primary viral pneumonia appears to be
more common and with rapid onset
• Incubation period may be longer
• Duration of infectious period likely
longer, particularly among adults
33
Avian Influenza in Humans
(July 17, 2007)
Year
1996
1997
Subtype Location
H7N7
United Kingdom
H5N1
Hong Kong
Cases
1
18
Deaths
0
6
1998
1999
2002
2003
H9N2
H9N2
H7N2
H7N2
China
Hong Kong
United States
United States
6
2
1
1
0
0
0
0
2003
2003
2003
H9N2
H5N1
H7N7
Hong Kong
Hong Kong
The Netherlands
1
2
89
0
1
1
Canada
Worldwide
2
0
318
192
* As of March 21, 2007
2004
H7N3
2003-07 H5N1
34
Worldwide H5N1 Outbreak
in Humans: 2003 - 2007
35
Source: WHO
Human H5N1 Epidemiology
• Primarily avian-to-human transmission
• No evidence of sustained person-toperson spread
• Limited probable person-to-person
spread1
1N
Engl J Med 2005;352:333-340
36
H5N1 Possible Travel Routes
• Legal poultry business
• Illegal bird trade
• Untreated fertilizer
• Migrating birds
• Humans
(contaminated objects)
37
What is Pandemic Influenza?
• Pandemic: epidemic spreading
around the world affecting
hundreds of thousands of people,
across many countries
• Flu pandemics: global influenza
epidemics of newly emerged
strain of influenza that
– passes easily from person to person
– causes severe disease
• Essentially no pre-existing
immunity; every body at risk
38
Influenza Viruses
• Characterized by ability to change
‒Continually → yearly epidemics
‒Drastically → sporadic pandemics
39
Antigenic “drift”
Minor antigenic changes to the
hemagglutinin protein
• Point mutation in viral RNA
• Continuous process
• Cause of seasonal epidemics
• Immunity may be limited to an individual
strain
• Vaccine strains must be updated each
year
40
Antigenic “shift”
Major antigenic changes leading to emergence
of a new human influenza A virus subtype (e.g.
new HA 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)
41
Re-assortment and
Direct Transmission
Non-human
virus
Human
virus
Reassortant
virus
42
Seasonal Epidemics vs. Pandemics
Human 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, may
be at increased risk for
serious complications
– Result of Antigenic Drift
– Result of Antigenic Shift
43
Pandemic Influenza
• Timing unpredictable
• High illness rates across age groups
• Increased mortality
–Higher proportion deaths in younger
persons
44
Estimated Mortality from
Influenza Pandemics
• 1918-19 (H1N1)
• >500,000 deaths US
• 20 -100 million worldwide
• 1957-58 (H2N2)
• 70,000 deaths US
• 1968-69 (H3N2)
• 34,000 deaths US
45
Timeline of Influenza Pandemics
Avian
Influenza
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
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Why Worry?
• Total deaths in 1918-1919 estimated to be 20-50 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
1960
Date
47
Geographic spread: 1918-19
06/18
?
03/18
04/18
06/18
05/18
?
01/19
06/18
C.W. Potter, Textbook of Influenza, 1998
JVT – IVW, Lisbon
48
U.S. Impact Estimates for the Next
Influenza Pandemic
Deaths: 89-207,000
Hospitalizations: 314-733,000
.03-.07%
.1-.3%
Outpatient care: 18-42 m
Total infected: 43-100 m
6-15%
15-35%
Health related economic impact
Estimated: $71 to $166 billion
Meltzer M, et al. Emerging Infectious Diseases 1999;5:659-671
49
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
50
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
51
Weeks
WHO Stages of a Pandemic
•
Inter-pandemic period
•
Pandemic alert period
•
Pandemic period
•
Post pandemic period
52
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
53
WHO Phases of a Pandemic
Pandemic Alert Period
Phase 3: Human infection with novel
virus; no instances of human-to-human
spread
Phase 4: Small, localized clusters of
human-to-human spread
Phase 5: Larger clusters, still localized;
virus adapting to humans
54
WHO Phases of a Pandemic
Pandemic Period
Phase 6: Increased and sustained
transmission in the general population.
Post Pandemic Period
Recovery phase
55
Efforts by Governments and Others
to Address H5N1
Limit Animal Infections
• Improving farming practices to reduce contact between wild and
domestic birds
• Culling sick/exposed farms animals to limit further spread
• Vaccinating poultry to limit infection/transmission
Limit Human Infections
• Using protective gear when working with sick animals & humans
• Isolating and treating human cases
• Conducting public awareness campaigns
Coordinate Preparedness and Response
• Preparedness planning, interagency/donor coordination
• Stockpiling medicines, protective gear, animal vaccines, etc.
56
Influenza Pandemic Viruses
A new influenza A subtype can infect humans
AND
Causes serious illness
AND
Spreads easily from human-to-human
The first two prerequisites have been met,
but not the last
– Each new human infection is an opportunity for57the
virus to change
Summary
• Influenza is a serious human 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
58
Summary
• H5N1 Avian Influenza is currently spreading
through birds with occasional cases among
humans
• While there is evidence of rare human-tohuman transmission, sustained transmission
has not occurred
• If H5N1 virus obtains the ability to easily
transmit from person-to-person, a pandemic
may result
59
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.
60
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.
61
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.
62
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.
63
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/
64