Pandemic flu –
Are you ready?
Robert
Robert R.
R. Orford,
Orford, MD
MD
Mayo
Mayo Clinic
Clinic Arizona,
Arizona, USA
USA
February
February 27,
27, 2007
2007
Source: Danitza Tomianovic, MPH, CDC, 2/06
Source: Danitza Tomianovic, MPH, CDC, 2/06
Outline
Biology of influenza (flu)
„ Epidemiology of influenza and
avian/bird/pandemic flu
„ Planning for Pandemic Flu
„
• International, National, Businesses
• Aviation
• Personal and family
BIOLOGY OF INFLUENZA
Biology of Influenza
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Viral family Orthomyxoviridae (RNA)
Three distinct types: A, B, and C, which
are antigenically distinct from one another
Influenza A virus affects humans and
animals and causes widespread outbreaks
(categorized by H and N type, e.g. H1N1)
Influenza B is only found in humans and
causes localized outbreaks (not
categorized by H or N type)
Influenza C is of little medical concern
(morphologically and genetically different,
generally asymptomatic)
Influenza A Virus
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RNA virus,
8 segment
genome
80 to 120
nanometers in
diameter
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Genetically
unstable
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2 glycoprotein
antigens
• Hemagglutinin
• Neuraminidase
Subbarao 2004
Biology of Influenza
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Influenza A varieties are named
according to their surface protein
types:
• Hemagglutinin, which attaches the virus
to the host cell for cell entry, 13 major
types
• Neuraminidase, which releases the
virus progeny by cleaving sialic acid
receptors that attach them to cells, 9
types
Biology of Influenza
„
New strains of the influenza virus
result from:
• antigenic drift, slow accumulation of
mutations over time
• antigenic shift, recombination of the
influenza genome, when a cell becomes
simultaneously infected by two different
strains
Biology of Influenza
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Birds can only be affected by
Influenza Type A viruses
Birds are susceptible to all subtypes
of the Influenza A
Humans and other animals are
susceptible to only selected subtypes
Biology of Influenza
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99% of human influenza is caused by
influenza A
99% of influenza cases in “normal”
years are caused by H3N2
H1N1, H2N2, and H5N1 affect
humans and swine as well as birds
H5N1 also affects cats
Biology of Influenza
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Hemagglutinin: H1 - H16 –is the “key in”
Neuraminidase: N 1 – H9 is the “key out”
Humans: H1N1, H2N2, H3N2, H5N1, H5N1, H7N7,
H7N3, H7N2, H9N2, H10N7H7N7, H7N3, H7N2, H9N2,
H10N7
Avian: H1N1, H2N2, H3N2, H3N8, H4N8, H5N1, H5N2,
H5N3, H6N1, H6N2, H6N9, H7N2, H7N3, H7N2,
H7N3,H7N4, H7N7, H8N4, H9N2, H9N2, H10N7, H11N1,
H11N8, H11N9, H12N5, H13N6, H14N5, H15N6
Other:
•
•
•
•
•
Swine: H1N1, H3N2, H5N1
Equine: H3N8, H7N7
Feline: H5N1
Canine: H3N8
Seals: H4N7, H7N7
Strains for 2007/08 Vaccine
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Anticipated circulating strains for
2007/08 in the northern hemisphere
• A/Solomon Islands/3/2006 (H1N1)-like
• A/Wisconsin/67/2005 (H3N2)-like virus
• B/Malaysia/2506/2004-like virus
Influenza Spread
Droplet vs aerosol
„ Surface contamination
„ Water and food
„ Implications for airlines
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Influenza Spread
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A jet airliner with 54 persons aboard was delayed on the
ground for three hours because of engine failure during a
takeoff attempt.
Most passengers stayed on the airplane during the delay.
Within 72 hours, 72 per cent of the passengers became ill
with symptoms of cough, fever, fatigue, headache, sore
throat and myalgia.
One passenger, the apparent index case, was ill on the
airplane, and the clinical attack rate among the others
varied with the amount of time spent aboard.
Virus antigenically similar to A/Texas/1/77(H3N2) was
isolated from 8 of 31 passengers cultured, and 20 of 22 ill
persons tested had serologic evidence of infection with this
virus.
The airplane ventilation system was inoperative during the
delay and this may account for the high attack rate.
Moser MR, Bender TR, Margolis
Margolis HS et al. An outbreak of influenza aboard
a commercial airliner.
airliner. Am J Epidemiol 1979;110:11979;110:1-6.
Symptoms of Influenza A
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Incubation period 1 to 3 days
Sudden Onset
Common flu symptoms in adults and
children over five*:
•Fever
•Chills & Sweats
•Cough
•Muscle & Joint Pain
• Headache
• Fatigue &
Weakness
• Sore Throat
* Flu symptoms are different for children <5 yo and the elderly
Prevention and Treatment
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Adequate rest
Plenty of fluids
Avoid exertion. For 24 to 48 hours after
the body temperature returns to normal
Symptomatic treatment with
acetaminophen, aspirin (ASA), or
ibuprofen (note: because of the risk of
Reye's syndrome, children should not be
given aspirin)
Nasal decongestants and steam inhalation
may also help relieve symptoms.
Prevention and Treatment
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Measures to combat flu:
• Vaccine (vaccines against new strains are
prepared and distributed each year)
• Antiviral medications:
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amantadine and rimantadine work by hindering the
change in pH that is necessary for the flu virion to
release its contents into the cytosol of a host cell, but
many influenza A virus strains are now resistant.
zanamavir and oseltamivir block the glycoprotein
neuraminidase so that the release of new virus
particles is inhibited and their spread is limited
• Antibiotics are sometimes given to prevent or
treat opportunistic infections
Biology of Influenza
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HPAI –Highly Pathogenic Avian Influenza
Characterized by the presence of either H5 or H7
Not all H5 avian flu is highly pathogenic (low
pathogenicity avian flu, LPAI, occurs mainly in
wild birds and does not affect humans)
Pathogenicity can only be determined through
genetic analysis and biological testing
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Inoculation of embryonated chicken eggs, chicks and adult
chickens
Genetic characterization of relevant parts of the viral
genome
Biology of Influenza
Symptoms of Avian Flu
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Incubation Period: 2 to 4 d.
Exposure to poultry ~90%
Age: 5 to 35 yrs.
Symptoms: fever, cough, dyspnea
CXR: infiltrates, ~7d post fever
Course: vent support within 48 hrs.
Outcome: ~50% die of resp failure.
NEJM 2005;353:1364-1385.
Vietnam and Thailand Case
Characteristics
EID 2005;11(2):201-209, NEJM 2004;350:1179-88
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Cough, dyspnea,
and fever
22/22 (100%)
Diarrhea
12/22 (55%)
Myalgia
5/22 (23%)
Conjunctivitis 0/22
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Leukopenia
14/22 (64%)
Thrombocytopenia
13/22 (59%)
Hepatic abn.
15/16 (94%)
Renal abn.
7/18 (39%)
EPIDEMIOLOGY OF INFLUENZA
“Of the more than 1,500 microbes
known to cause disease in humans,
influenza continues to be the king in
terms of overall mortality.”
Michael T. Osterholm, Ph.D.
Foreign Affairs, July/August 2005
Epidemic Influenza Has
a Substantial Impact
Estimates for the US
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Cases
25–50+ million
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Days of illness
100–200 million
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Work & school days lost
Tens of millions
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Hospitalizations
85,000–550,000*
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Deaths
34,000†–51,000‡
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Costs
Billions of dollars
*Average respiratory & circulatory = 294,000 (1979-80 through 2000-01)
†Average all cause (1976-77 through 1998-99)
‡Average all cause (1990-91 through 1998-99)
Adapted from CDC. MMWR Recomm Rep. 2005;54 (RR-8):1-40.
Thompson W et al. JAMA. 2003;289:179-186. Thompson W et al. JAMA. 2004;292:1333-1340.
Adams P et al. Vital Health Stat. 1999;10:1-203.
Influenza Is the Leading Cause of US
Vaccine-Preventable Disease Deaths
VPD Cases & Deaths, US 1989-1998
Disease
Cases
Deaths
Influenza
(millions)
~500,000
Pneumococcal diseases
(millions)
~120,000
Hepatitis A
282,650
1013
Hepatitis B
146,644
9694
Measles
60,189
132
Mumps
24,075
7
Rubella
4412
21
Pertussis
53,634
65
Tetanus
486
77
CDC. MMWR. 2006;55;511-515.
Thompson W et al. JAMA. 2003;289:179-186.
Felkin D et al. Am J Public Health. 2000;90:223-229.
Epidemiology of Influenza
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Records of pandemics probably
caused by influenza go back to the
16th Century
Longest interval between probable
pandemics = 108 years, between the
1580 and 1688 outbreaks
Shortest interval = nine years,
between the 1699 and 1708
pandemics (periodicity irregular?)
Epidemiology of Influenza
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Annual average US winter epidemics
affect 5% to 20% of the population
with approximately 200,000
influenza-related hospitalizations
during the 1990’s and 36,000
influenza related deaths
A pandemic would be expected to
affect at least 33% of the population
Air travel and flu
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Influenza epidemics occur annually during the winter flu
season.
Researchers at the Children's Hospital Boston investigated
effects of air travel on the annual spread of flu in the US.
Between 1996 and 2005, the usual time taken for a flu
epidemic to reach peak levels across the US averaged two
weeks
The national peak date was within two days of the average
date – February 17 - except following September 11, 2001
when it was was delayed, by 13 days, to March 2
Air travel in the US was significantly lower in the 20012002 flu season. In contrast, the researchers found no
delay in the 2001–2002 flu season in France, where there
were no flight restrictions.
The peak date then returned to February 17 over the
subsequent two flu seasons, when international airline
travel went back to its previous level.
Brownstein JS, Wolfe CJ, Mandl KD (2006) Empirical evidence for the effect of airline travel
on interinter-regional influenza spread in the United States. PLoS Med 3(10): e401.
20th Century Pandemics
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Three influenza pandemics occurred
during the 20th century.
1918 Spanish flu (H1N1) - 675,000
deaths* (20 to 40 percent of the world's
population affected, with more than 50
million deaths worldwide)
1957 Asian flu (H2N2) - 70,000 deaths*
1968 Hong Kong Flu (H3N2) - 34,000
deaths*
*in the United States alone.
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Epidemiology of Influenza
There is a theory that pandemics
are correlated with 11 year
peaks of sunspot activity (SSN*
>10)
„ The last peak of sunspot activity
was in 2001. The next will likely
be in 2011 (range 2008 – 2013).
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*SSN = sun spot number (i.e. number of sunspots)
Influenza and Solar Activity
Fred Hoyle and Chandra W. Cardiff
A Case Of Stratospheric Influenza
- Space Daily, January 21, 2000
Influenza and Solar Activity
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Where does the word influenza come
from?
It is derived from Medieval Latin
influentia (the modern Italian word is
influenza), meaning influence (so
called apparently from the belief that
epidemics were due to the influence
of the stars).
Pandemic Influenza
• Recipe for a human pandemic:
Emergence of a novel sub-type
of influenza to which the
population is immunologically
naïve
„ Replication in humans Î disease
„ Efficient human-to-human
transmission
„ Note: H5N1 has meet all criteria
except the third one.
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Epidemiology
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Possible reason why H5N1 is not able
to cause human-to-human
transmission is that haemagglutinin
of avian origin has not acquired
human receptor-binding specificity
Epidemiology
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Hong Kong 1997 outbreak of H5N1 AI in
poultry resulted in the first human cases:
18 infected, 6 died
The epidemic was halted by aggressive
culling of poultry flocks
In late 2003 - early 2004 there was a
poultry outbreak in 8 countries in Asia Cambodia, China, Indonesia, Japan, Laos,
South Korea, Thailand, Vietnam. Over 100
million birds died or were culled
Epidemiology
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The first human death due to a new
subtype of H5N1 AI was reported in
Vietnam on December 30, 2003. Two
years later, China admitted that a
man had died in Beijing in Nov. 2003
23 deaths were reported in Thailand
(12) and Vietnam (23) over the next
three months, raising international
concern
CDC 7/21/05
Epidemiology
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Since then, new poultry outbreaks
have continued to be reported in Asia
(Cambodia, China, Indonesia,
Malaysia, Thailand, Vietnam, China)
September 2004 - first report of
limited human-to-human
transmission in Thailand. Possible
human-to-human transmission was
also reported in Indonesia in 2006
Epidemiology
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Total human cases 274
as of 2/19/07
Total deaths 167
The new subtypes produces a
mortality rate of nearly 70%
in humans compared to 33%
of the initial Hong Kong H5N1
Cumulative cases of H5N1 Flu
to Feb 19, 2007
Nations With Confirmed Cases
H5N1 Avian Influenza (to Feb 6, 2007)
Nations With Confirmed Cases
H5N1 Avian Influenza (Feb 19, 2007)
H5N1 Genotype Z CDC 7/21/05, Hong
Kong Med J 2005;11(3):189-199
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H5N1 genotype Z is dominant strain
Stable in the environment for 6 days
May be acquired from water and food
Genetic sequence from human
isolates show resistance to
amantadine, rimantadine
Current H5N1 strains susceptible to
neuraminidase inhibitors zanamavir
and oseltamivir
So, Will 1918 Flu Mortality Recur?
Mortality Caused by 1918 Flu May
Not a Model for Future Pandemics
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National and international disease
surveillance networks are in place
High speed information and
communications networks
Worldwide health-systems are improved
Pandemic preparedness plans are being
readied or are in place
Antibiotic and antiviral medications are
available and vaccine is possible
International cooperation to understand
and control disease is better
HYPOTHETICAL CASE
PLANNING FOR PANDEMIC FLU
"The pandemic clock is ticking. We
just don't know what time it is."
Ed Marcuse,
Former Chairman, National Vaccine
Advisory Committee
Avian Influenza - Challenges
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Global surveillance is poor – WHO has
system in place, but in 2003-2004, only
one sample was analyzed per >100,000
influenza cases worldwide
There has been little evidence of
subclinical cases of avian flu in humans
Almost no one has natural antibodies to
H5N1, and prior flu vaccines are of little or
no value against this strain
Avian Influenza - Challenges
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H5N1-specific vaccine will take 3-4
months or more to manufacture, more
time to distribute
Once human-to-human transmission
occurs easily, global spread will occur
within days, and pandemic will likely be
well established within two months
Efficacy of antivirals (eg Oseltamivir)
against the pandemic strain is uncertain
Avian Influenza - Challenges
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Human society is more interdependent and
transportation is far more efficient than in
1918.
Public health system in US is under-funded
Certain industries are particularly
vulnerable to failure, for example:
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Hospitals and Medical Care, Public Health Workers
EMTs, firefighters, police
Telecommunications
Utilities (water, electricity, gas etc.)
Waste management
Food manufacturing and distribution
Avian Influenza - Challenges
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There is limited science behind the
planning that has been done to date, and
there will be a very short time frame for
planning and implementation of measures
once a pandemic occurs
Too little, too late misses chances to
contain the pandemic but too much, too
early risks economy and pandemic fatigue
– a phased response is needed
Avian Influenza - Plans
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International (WHO)
National (e.g. US Federal Plan)
State, Province
Local (City, County Public Health Depts.)
Hospitals and medical care
Schools
Corporations and Business Operations
Individuals
http://www.who.int
http://www.pandemicflu.gov
WHO Plan Phase Definitions
Interpandemic period:
• Phase 1: No new influenza virus subtypes have been detected
in humans.
• Phase 2: No new influenza virus subtypes have been detected
in humans, but an animal variant threatens human disease.
Pandemic alert period
• Phase 3: Human infection(s) with a new subtype but no
human-to-human spread.
• Phase 4: Small cluster(s) with limited localized human-tohuman transmission
• Phase 5: Larger cluster(s) but human-to-human spread still
localized.
Pandemic period:
• Phase 6: Pandemic: increased and sustained transmission in
general population.
Current WHO phase of pandemic alert is
categorized as phase 3
WHO General Recommendations
for all high risk Occupations
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High Risk Workers should have priority to
receive seasonal flu vaccination
Personal Protective Equipment (PPE) is
recommended for all high risk occupations
Pre-exposure and post-exposure
prophylactic medications may be used for
high risk occupations
• Canada states up to 6 weeks, with 2 week break away
from exposure (Oseltamivir 75 mg qD)
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High Risk Workers should be monitored for
flu symptoms
• Suspected Cases should be isolated and tested for virus
US Business Pandemic
Influenza Planning Checklist
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Plan for the impact of a pandemic on your
business
Plan for the impact of a pandemic on your
employees and customers
Establish policies to be implemented
during a pandemic
Allocate resources to protect your
employees and customers during a
pandemic
Communicate to and educate your
employees
Coordinate with external organizations
and help your community
Aviation Planning
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WHO does not recommend travel
restrictions to areas experiencing
outbreaks of highly pathogenic H5N1
avian influenza in birds, including
countries which have reported
associated cases of human infection,
and does not, at present, recommend
routine screening of travelers coming
from affected areas.
Aviation Planning
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WHO continues to recommend that
travelers to affected areas should
avoid contact with live animal
markets and poultry farms, and any
free-ranging or caged poultry. Large
amounts of the virus are known to
be excreted in the droppings from
infected birds.
Aviation Planning
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In addition, CDC advises careful and
frequent hand washing (or waterless
alcohol-based hand gels) to remove
potentially infectious material from
the skin and helps prevent disease
transmission, and advises that all
foods from poultry, including eggs
and poultry blood should be cooked
thoroughly
Aviation Planning
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Airport administrators have
developed plans
Hong Kong International Airport
conducted a drill in March, 2006 with
more than 300 volunteers and staff
to assess its preparedness to
manage infectious-disease outbreaks
Aviation Planning
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The Manila International Airport
Authority is planning to use thermal
scanners at the Ninoy Aquino
International Airport to screen
arriving passengers.
Several airports are checking
travelers arriving from infected areas
for bird products, some using “sniffer
dogs”
Aviation Planning
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New Zealand has announced plans to
"shut the borders and quarantine
people at airports" in the event of a
bird flu outbreak (up to 6,000
passengers arrive there daily!)
USA Quarantine
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Every year, roughly 120 million people
travel into or out of the USA through the
nation's 474 airports, seaports, and landborder crossings
In 2003 Congress began to allocate funds
to bring the number of quarantine stations
from eight to 25 (covering more than 75
million international travelers and
immigrants annually)
USA Quarantine
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Currently, 11 quarantine stations staffed
by CDC personnel are fully active in
Atlanta; Chicago; El Paso, Texas;
Honolulu; Houston; Los Angeles; Miami;
New York City; San Francisco; Seattle;
and Washington, D.C.
CDC will open stations by the end of the
year in Anchorage, Alaska; Boston;
Detroit; Minneapolis; Newark, N.J.; San
Diego; and San Juan, Puerto Rico.
Additional cities under consideration are
Charlotte, N.C.; Dallas; Denver; Kansas
City, Mo.; New Orleans; Philadelphia; and
Phoenix.
Aviation Planning
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The captain of an airliner bound for
the United States is required by law
to report the illness to the nearest
US Quarantine Station prior to arrival
or as soon as illness is noted.
Quarantine officials will arrange for
appropriate medical assistance to be
available when the airplane lands
and will notify state and local health
departments and the appropriate
CDC officials.
Aviation Planning
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LAX airport plans to provide a facility
for CDC and US Customs and border
protection that will be able to
quarantine as many as 400 people
for 48 hours
Aviation Planning
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CDC does not recommend the routine use
of personal protective equipment (PPE),
such as respirators, gloves, or surgical
masks, for protection against avian
influenza exposure, except in health carerelated situations
An ill person can wear a paper or gauze
surgical mask to reduce the number of
droplets coughed into the air, or if a mask
is not available, tissues can be used to
cover the nose and mouth, just as one
should do for a common cold.
Aviation Planning
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CDC has issued guidance specifically
addressing cleaning procedures for
avian influenza, which directs airlines
to wipe down lavatory surfaces and
frequently touched surfaces in the
cabin, such as armrests, tray tables,
light and air controls, and adjacent
walls and windows using a household
cleaner or detergent.
Aviation Planning
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FAA’s William J. Hughes Tech Center
in Atlantic City convened a Crisis
Response Working Group (CRWG) in
January, 2006 which is coordinating
the development of a pandemic
influenza action plan in the event
they are directly impacted by an
influenza outbreak, or indirectly
affected by an outbreak near them
Aviation Planning
Photo of the
infamous
“bird gun” or
“chicken gun”
Aviation Planning
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CDC has issued guidance addressing
cleanup of aircraft exteriors after
collisions with birds in Avian
Influenza A (H5N1)-affected areas
(no use of pressurized water or
cleaner, use of gloves and disposable
overalls, safety goggles, mask,
disposal in closed plastic bags, hand
thorough washing after cleanup etc.)
Aviation Planning
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The Federal Aviation Administration
(FAA), Air Transport Association
(ATA) and the International Air
Transport Association (IATA) all have
websites on bird flu. IATA has
developed a template for air carriers
to use in developing emergency
response plans.
IATA (International Air Transport
Association)
EMERGENCY RESPONSE PLAN
PUBLIC HEALTH EMERGENCY
VERSION 1.0 DATED 30 NOVEMBER
2005
IATA Emergency Response Plan
A template for Air Carriers which identifies
in broad terms how to prepare for a public
health emergency and provides checklists
of actions that should be built into a public
health emergency plan.
Recommends that all air carriers have an
emergency response plan in consultation
with and aligned with plans developed by
their national health authorities.
IATA Emergency Response Plan
Air carriers are encouraged to establish an
Emergency Response Team (ERT)
consisting of executive, core and support
members.
Executive members:
• Director Emergency Response
• Medical Advisor (or designated medical
representative)
• Communications Director (or equivalent)
IATA Emergency Response Plan
Core members:
• Flight Operations
• In-Flight Services
• Maintenance
• Airports
• Cargo
• Security & Facilitation
• Station & Passenger
Handling
• Operations Control
Support members:
• Legal
• Risk Management
• Human resources
• Finance/Purchasing
IATA Emergency Response Plan
An Emergency Response Centre (ERC) should be
established, office space equipped with all of the
communications and planning tools required to
manage a response to a public health emergency.
Air carriers that do not have such a facility are
encouraged to establish one.
Roles and Responsibilities are defined in a checklist
specific to each member of the Emergency
Response Team.
IATA plan is available at www.iata.org
IATA Emergency Response Plan
5.2 Medical Representative (MR)
• Initiate and maintain contact with health authorities.
• Contact the IATA Medical Advisor if appropriate.
„ Contact the company Medical Officer closest to the
airport(s) where the emergency is in effect.
• Make appropriate recommendations applicable to
specific departments of the company, based on
information received from the health authorities.
„ If appropriate for the emergency, contact the
hospital(s) that are receiving passengers in order to
obtain relevant information.
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Determine whether there is a requirement to
quarantine any equipment.
Determine whether there is a requirement to disinfect
the aircraft.
Advise the Director Emergency Response of the
actions required.
Advise Company Maintenance of the actions required
and ensure that the aircraft is properly disinfected.
Assist Corporate Communications with press releases
as required.
If necessary, advise Flight Operations and In-Flight
Services.
of the requirements for medical examinations for
crewmembers.
Aviation Planning
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A good, though non-technical source
of information on this topic is
http://aircrewhealth.com. It has upto-date information and links to
recent aviation news on bird flu
The International Society for
Infectious Diseases provides an
email update once or twice daily on
avian flu and other emerging
infectious diseases called ProMed
Digest (http://www.isid.org)
Pandemic Preparedness is
Everyone’s Business
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Get vaccinated every year with the
seasonal human influenza vaccine
• Supply and demand for vaccine manufacturers
• Avoid co-infection with avian and human
influenza strains if exposed
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Stay home when you are ill
Respiratory Hygiene/Cough Etiquette
• self
• patients
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Hand Hygiene
Summary
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Avian Influenza A (H5N1)
• Has infected multiple species, and is
likely endemic in birds in Asia
• Is able to infect humans with high
mortality
• Confronts a global immunologically
naive human population
• Has not shown efficient human-tohuman transmission… yet
In Conclusion
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Aviation specialists play an important
role in planning for pandemic flu, in
concert with airlines, airports, and
public health authorities.
We must understand, interpret, and
implement international, national
and state plans at the level of our
responsibility
An avian influenza pandemic is
possible, and requires us to be
prepared
Resources
www.who.int
www.oie.int
www.fao.org
www.pandemicflu.gov
www.cdc.gov/flu
www.OHDEN.net/pandemic
www.wbgh.com
www.acoem.org
www.pandemicflu.ca
Source: Danitza Tomianovic, MPH, CDC, 2/06
Questions?
Contact Information:
Robert R. Orford, MD.
Chair, Preventive, Occupational, and
Aerospace Medicine,
Mayo Clinic Arizona,
Scottsdale, AZ, USA
rorford@mayo.edu