Transcript - Avian Influenza What is Happening and How Should We Prepare?

Avian Influenza What is Happening and How
Should We Prepare?
--------John M. Matsen, M.D.
August 9, 2006
Influenza Virology
 “There are three types of influenza
viruses, A, B, and C.
 Only Influenza A viruses are further
classified by subtype on the basis of the
two main surface glycoproteins
hemagglutinin (HA) and neuramininidase
(NA). Dx by inhibition tests.
 Influenza A subtypes and B viruses are
further classified by strains.”
(CDC 1/06)
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DEFINITION:
 Avian influenza is an infectious
disease caused by Type A influenza
virus strains that commonly infect
poultry and other avian species. The
term is synonymous with “bird flu.”
 The natural reservoir species for
avian flu are ducks, shorebirds and
gulls.
(USDA)
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TUFTED DUCK
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All type A influenza viruses,
including human strains:
 They are genetically labile RNA
viruses.
 Other RNA viruses are, e.g., HIV,
SARS, etc.
 They lack the critical mechanisms for
correcting replication errors.
 The genetic composition of the viruses
changes as they replicate.
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Constant Mutation
 Now with a huge new amount of genetic
data, we have the ability to better
understand multigenic traits for the first
time. As they carry RNA instead of DNA,
influenza viruses mutate constantly
because the enzyme that generates RNA
makes frequent mistakes during
replication.
(NatureMed 2006; 12(258))
 “H5N1 mutates rapidly and has a
documented propensity to acquire genes
from viruses infecting other animal
species.”
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Avian Flu Virus Makeup
 Only influenza A viruses infect birds, and all
known subtypes of the A viruses can
infect birds.
 In the influenza A genetic makeup, there are
6 internal genes plus the HA and NA
genes.
 A specific gene of these 8 in the 1918 H1N1
virus had the unexpected capacity for
sending the body's immune system into
overdrive, causing inflammation,
hemorrhagic pneumonia and death.
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Pathotype Definition
There are two primary pathotypes of
Avian Influenza virus:
– the most common is low pathogenic AI
(LPAI) which is found in a few poultry
flocks in the United States and elsewhere
every year—usually spread from wild birds.
– the other is the highly pathogenic AI
(HPAI), which is much less common and is
associated with higher mortality in poultry.
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Pathotypes Can Change
• Avian flu viruses of low pathogenicity (LPAI) can,
after circulation for just short periods of time,
in a poultry population, mutate into HPAI.
 During a 1983–1984 poultry epidemic in the US,
the H5N2 virus was of low pathogenicity initially,
but within 6 months mutated to become HPAI,
with a mortality approaching 90%.
 During a 1999–2001 poultry epidemic in Italy, the
H7N1 virus, initially of low pathogenicity,
mutated within 9 months to a HPAI form.
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(WHO)
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Influenza Viruses Continually Evolve
 They continually manifest small changes
or antigenic “drift.”
 Can swap or “reassort” genetic materials
and merge with other flu viruses
 This occasional reassortment process is
known as antigenic “shift.”
 The resulting novel subtype is different
from both parent viruses.
(WHO & CDC)
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Avian Flu Spread
“Here, we report that genetically and
antigenically distinct sub lineages of
H5N1 virus have become established in
poultry in different geographical regions
of Southeast Asia, indicating the longterm endemicity of the virus, and the
isolation of H5N1 virus from apparently
healthy migratory birds in southern
China.”
(PNAS 02/10/06)
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Avian Flu Spread
The H5N1 bird flu in humans has
evolved into two separate strains,
or “clades,” a development that
will complicate the search for a
vaccine and the prevention of a
pandemic, US researchers
reported.
(Garten RJ, et al. International Conference on Emerging Infectious
Diseases. March 2006. Paper # 64)
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H5N1 Presence 2006
.
Nations With Confirmed Cases (070706)
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Confirmed Human H5N1 Cases
2004
2005
TOTALS
2006
COUNTRY
cases
Azerbaijan
0
0
0
0
8
5
8
5
Cambodia
0
0
4
4
2
2
6
6
China
0
0
8
5
11
7
19
12
Indonesia
0
0
17
11
37
31
54
42
Iraq
0
0
0
0
2
2
2
2
17
12
5
2
1
1
23
15
Turkey
0
0
0
0
12
4
12
4
Vietnam
29
20
61
19
0
0
93
42
TOTAL
46
32
95
41
40
27
232
134
Thailand
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deaths cases deaths cases deaths cases deaths
7/20/2006
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Highly Pathogenic Avian Influenza
The H5N1 strain has now (4/06) been
reported in over 50 countries, and
governments throughout the world
have slaughtered the enormous
number of well over 200 million
chickens, ducks, other poultry and
wild birds in an effort to keep the
H5N1 virus from spreading.
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PNAS 2/10/06
“Our data show that H5N1 influenza virus
has continued to spread from its
established source in southern China to
other regions through transport of
poultry and bird migration. The
identification of regionally distinct sub
lineages contributes to the understanding
of the mechanism for the perpetuation
and spread of H5N1…”
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Nature 442, 37(6 July 2006)
“As the avian influenza virus H5N1 swept
from Asia across Russia to Europe,
Nigeria was the first country in Africa
to report the emergence of this highly
pathogenic virus. Here we analyze H5N1
sequences in poultry from two different
farms in Lagos state and find that three
H5N1 lineages were independently
introduced through routes that coincide
with the flight paths of migratory birds,
although independent trade imports
cannot be excluded.”
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Avian Influenza A Viruses
Human-to-human transmission of the H5N1
avian influenza would be cause for great
concern, but WHO investigations have in the
past identified only one “likely” / “probable”
instance of human-to-human spread, in 2004,
with one additional possible case in 2005. The
increasing number of reported family clusters
of H5N1 in Asia may mean human-to-human
transmission. Some suspect there have been
other human-to-human transmissions.
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Critical Gene a Suspect in Lethal
1918-1919 Epidemic (1)
By recreating the influenza virus that killed
50 or more million people in 1918-19, Kobasa,
et al. may have identified the gene that
turned it into one of the most lethal in
human history. The gene, one of eight in the
virus, seems to have an unexpected capacity
for sending the body's immune system into
overdrive, causing inflammation, hemorrhagic
pneumonia and death.
(From Kobasa, et al. Nature. 10/07/04)
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Critical Gene a Suspect in Lethal
1918-1919 Epidemic (2)
Using reverse genetics, they synthesized
the hemagglutinin antigen and the
neuraminidase genes based on the genetic
sequences of the 1918-1919 influenza
pandemic strain, and in recreating the
virus, they have shown that the resulting
virus is significantly more virulent than the
wild-type strain in a mouse model.
(From Kobasa, et al. Nature. 10/07/04; Hoft, et al. NEJM. 12/9/04)
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Critical Gene a Suspect in Lethal
1918-1919 Epidemic (3)
 “Different strains of influenza virus have
different pathologic effects... These
events were associated with more severe
pathological features and higher mortality,
suggesting that overactive host immune
response...may trigger severe disease.
 “Death rates in the 1918 pandemic were
highest among young to middle aged adults,
and lower in the elderly.”
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(Hoft, et al. NEJM. 12/9/04)
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Resurrected 1918 Flu Virus
The team resurrected the 1918 pandemic
virus by using gene sequences obtained
from formalin-preserved specimens and
from preserved tissue from a 1918 Inuit
flu victim exhumed from the Alaskan
permafrost. The virus is as lethal as
expected, killing mice more quickly than
any other human flu virus known.
Recreating the 1918 strain “had to be
done, and it's produced some extremely
interesting results.”
(Tumpey, et al. Science. 2005;310(77)).
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Chemokine Storm
In 1997, avian influenza virus H5N1 was
transmitted directly from chicken to human and
resulted in a severe disease that had a higher
mortality rate in adults than in children. The
characteristic mononuclear leukocyte infiltration
in the lung and the high inflammatory response in
H5N1 infection prompted comparison of the
chemokine responses between influenza virus–
infected adult and neonatal monocyte-derived
macrophages (MDMs). The demonstrated strong
induction of chemokines and their receptors by
avian influenza viruses, particularly in adult
MDMs, may account for the severity of H5N1
disease.
(Zhou, et al. J. Inf. Dis. July1, 06; 194.)
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Pathogenicity Change
• Avian flu viruses of low pathogenicity (LPAI) can,
after circulation for just short periods of time,
in a poultry population, mutate into HPAI.
 During a 1983–1984 poultry epidemic in the US.,
the H5N2 virus was of low pathogenicity initially,
but within 6 months mutated to become HPAI,
with a mortality approaching 90%.
 During a 1999–2001 poultry epidemic in Italy, the
H7N1 virus, initially of low pathogenicity,
mutated within 9 months to a HPAI form.
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 “Of the 16 avian influenza virus subtypes,
H5N1 is of particular concern for several
reasons.
 “H5N1 mutates rapidly and has a
documented propensity to acquire genes
from viruses infecting other animal species.
 “H5N1’s ability to cause severe disease in
humans has now been documented. In
addition, laboratory studies have
demonstrated that isolates from this virus
have a high pathogenicity for humans.” (WHO)
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HOW DEADLY THE PANDEMIC ?
 “Even in the best-case scenarios of the
next pandemic, 2 to 7 million people
will die and tens of millions will
require medical attention.
 “If the next pandemic virus is a very
virulent strain, deaths could be
dramatically higher.
 “The global spread of a pandemic cannot
be stopped, but preparedness will
reduce its impact.”
(WHO)
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Human-to-human transmission
raises demand for DNA data.
 A strain of avian flu that spread through a
family in Indonesia, killing seven of the eight
people infected, was accumulating mutations as
it spread from person to person, according to
confidential sequence data seen by Nature.
 The cluster of cases of the deadly H5N1
strain, which occurred earlier this year, is the
first in which the World Health Organization
(WHO) has admitted that human-to-human
transmission was the most likely cause of
spread.
(See Nature 441, 554–555 and 442, 114-115; 2006).
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Human-to-Human
Transmission
Sequence data show
that mutations were
accumulating as it
spread from person
to person.
(Nature 442, 114-115; 2006)
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“Something in the Airway”
“The existences of a molecular barrier that
may contribute to [transmissability] has now
been confirmed in patients. The key is the
distribution in the human airway of the
different receptors preferred by avian and
human derived viruses. The [H5N1] virus binds
preferentially to binding molecules that are
common in the lower respiratory tract but are
less well represented in the upper respiratory
tract. As a result, the [current H5N1] virus is
not readily spread by droplet infection or
cough.”
(Editor’s Comment. Nature. 2006;440:436)
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Needs Better Transmissibility
“The H5 strain of avian flu has so far
failed to develop a pandemic form. Some
virologists fear it may need only better
transmissibility. The new findings suggest
that the virus could acquire such a
property by switching its preference
from the cell receptor found in the lower
lung, known as alpha 2-3, to the receptor
found on cells in the upper airways, known
as alpha 2-6.”
(Ibid)
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2-step Mutation
“A team of scientists at the Scripps
Research Institute reported in Science
(March 17, 2006) that only a couple of
mutations might be needed to enable the
H5 virus to make this switch to the alpha
2-6 receptor. This is the about same
number of mutations made by the H1, H2
and H3 (pandemic) viruses when they
adapted to infect people. Since (RNA)
viruses can mutate fast, a two-mutation
step is not such a big hurdle.”
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Dr. Anthony Fauci - 4/11/06
“It is entirely conceivable that this
virus is inherently programmed that it
will never be able to go efficiently
from human to human,'' Fauci said.
''Hopefully the epidemic (in birds) will
burn itself out, which epidemics do,
before the virus evolves the capability
of being more efficient in going from
human to human.'‘
(NYT 4/12/06)
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BMJ 4/15/06
David King, the UK government's
chief scientific adviser, states
that the chances of the virus
mutating into a form that could
spread between humans were
"very low," and it was "totally
misleading" to say that such a
mutation was inevitable.
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Current Vaccine Status
 The US already has several million doses of a
bird flu vaccine based on a sample of a virus
taken in 2004 from Vietnam.
 But researchers have noted the emergence
of a second strain or clade of bird flu.
 US-HHS plans to create a new vaccine
targeted at the second variety. "In order to
be prepared, we need to continue to develop
new vaccines," HHS’s Mike Leavitt said at an
immunization conference in Atlanta.
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(AP 3/6/06)
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Current Vaccine Status
“The second vaccine will be based on a
virus sample taken from Indonesia last
year, said Ruben Donis, leader of the
molecular genetics team at the CDC's
influenza branch. The virus circulating in
Indonesia is related to the Vietnamese
virus, but it is not a descendant and it
causes a different immune system
response, he said.”
(AP 3/6/06)
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WHO Proposed Immediate
Prevention Actions
Because of uncertainties about
the disease situation in poultry
and the potentially severe
consequences for human health,
WHO has defined the following
proposed actions:
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WHO Proposed Immediate
Prevention Actions
1. Continue to work towards elimination
of H5N1 in all poultry populations: small
holdings as well as commercial flocks.
2. Promptly report to relevant
authorities and organizations new
outbreaks in poultry.
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WHO Proposed Immediate
Prevention Actions
3. Put in place mechanisms to verify
control progress and eventually
monitor freedom from the disease.
4. Ensure close collaboration between
public health and agricultural sectors
and veterinary services.
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WHO Proposed Immediate
Prevention Actions
5. Strengthen communicable disease
surveillance in humans and collect
and provide the data needed for an
accurate assessment of risks to
human health.
6. Share viruses with laboratories in
the WHO Global Influenza
Surveillance Network.
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WHO Phase of Pandemic Alert
‘
April 8, 2006
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PANDEMIC PREPAREDNESS
“Given the current threat, WHO has
urged all countries to develop or
update their influenza pandemic
preparedness plans for responding to
the widespread socioeconomic
disruptions that would result from
having large numbers of people unwell
or dying.”
(WHO)
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CDC, DOS, FDA, NGA, USDA,
WHO and all 50 States
The Web sites of these and other
resource and administrative units all
have pertinent pandemic planning and
preparation documents. Units within
our purview, and, indeed, all of our
family units should have copies of
these. We have distributed these
widely. All state governments also
have such for distribution.
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HHS and State Governors
Holding Pandemic Summits
‘
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Advanced Planning Importance
"A pandemic flu outbreak in any part of
the world would potentially cripple
supply chains, and dramatically reduce
available labor pools," the Deloite report
said. "In a world where the global supply
chain and real-time inventories
determine most everything we do, down
to the food available for purchase in our
grocery stores, one begins to
understand the importance of advanced
planning.”
(NYT 3/16/06)
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Worst-case Scenario
SYDNEY, Feb 16/06 (Reuters)—A worstcase scenario bird flu pandemic could wipe
US$4.4 trillion off global economic output
and kill more than 140 million people,
according to an Australian Lowry Institute
for International Policy report which
detailed four scenarios—mild, moderate,
severe and ultra pandemics—using
historical data on previous influenza
pandemics and the economic fallout from
the
SARS crisis in Asia in 2003.
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“A Nightmare Scenario”
“The havoc that would be wrought by
an avian-flu pandemic is so awful that
we must act now to be able to prevent
such a disaster.”
“. . . A pandemic could well bring global,
national and regional economies to an
abrupt halt. . . Imagine the chaos.”
(M. Zuckerman, Editor-in-Chief. US News & World Report.
June 27, 2005)
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“On a Wing and a Prayer.”
(Edit.) Nature. May 26, 2005
“This issue's focus on avian flu highlights
progress and incoherence in the world's
response to a potential human pandemic.
But the threat is enormous, and some
priorities are clear enough. Millions of
people killed in highly developed countries
within months, and tens of millions
worldwide. The global economy in tatters.
A Hollywood fantasy? No—it's now a
plausible scenario.”
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Effect and Survival
 The effect of an influenza pandemic
on individual communities will be
relatively severe and prolonged when
compared to other natural disasters,
as it is expected that outbreaks will
reoccur in waves.
 Life or death (survival) for many will
be determined by how well they and
their communities are prepared.
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What Can Happen—
TRANSPORTATION:
COMMERCE:
Planes don’t fly
Trains are halted
Buses don’t run
Travel curtailed
Gasoline supplies
dwindle
 Mobility crisis
 Travelers stranded
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Services unavailable
Food scarce
Medicines rationed
Household goods gone
Supplies in general
are in short supply
 Inventories shrink
 Banks are closed
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What Can Happen—
CIVIL:
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Safety
Law enforcement
Civil compromise
Desperation
Criminal element
Utilities
Water, etc.
Communication
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PEOPLE:
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Social distancing
40% + could be ill
Personal resources
Failure to cope
The sick, dying & dead
Grief
The vulnerable
“Being alone” concerns
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What Can Happen—
HEALTH CARE:
EMPLOYMENT:
 Medical facilities will
be overwhelmed
 Vaccines & antivirals
in short supply and
unevenly available
 Nursing supplies ??
 Rx & Medicines—
Need to “stock up”
 2o infections Rx
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Offices closed
Transit problems
Work from home
Loss of jobs/wages
Business failures
Urge prior planning
where it is lacking
 Inability to make
payments
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“Hunkering down...”
“I’ll just camp down, probably in
the secretariat, and stay there
for 6 to 10 weeks . . . and my
family will have to hunker down
where they are (Switzerland).”
(David Navarro, UN. NYT 3/28/06)
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Dr. Anthony Fauci - 4/11/06
The government still must prepare for the
worst - ''it would be unconscionable not
to'' – Dr. Fauci added. He recommended
families stock up on supplies, including
canned food and water, as they would
anyway for a hurricane or winter storm.
People who require regular medication for
diabetes or other chronic illnesses should
have an extra . . . supply, like they would
for a vacation.
(NYT 4/12/06)
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Support “in Place”
RESOURCES:
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Water
Food necessities
Personal hygiene
Cleaning items
Sanitation
Fuel, lighting
Cash
Etc.
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FUNCTION:
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Guidelines, manuals, etc.
Computer (Work from home)
Cell phone
Bicycles, motor bikes
Equipment and tools
Reading materials
Entertainment items
Radio, batteries, etc.
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U.S. State Department DVD
“Being Prepared for Pandemic
Influenza”
In June, 2006, the U.S. State Department
produced a DVD entitled “Being Prepared
for Pandemic Influenza”. This is
potentially a most helpful study and
resource guide, particularly for individuals
in distant locations. It is a video
presentation of key preparation “musts”.
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“When Influenza Takes Flight”
“The governments concerned and the
international community (and individuals)
need to act now to find solutions to the
challenges posed by these outbreaks.
The threat of an influenza pandemic
transcends the capacities of any
individual nation or region. For the
tsunami, the world had no warning. For
avian influenza, the warning is there.”
(Troedsson & Rychener. NYT. 2/5/05)
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What Do We Need to Do—NOW
“Preparing for a potential
pandemic is tremendously
challenging, given the
potential scope and the large
number of unknowns,” said
NIH Director Elias A.
Zerhouni, M.D.
(http://www.nigms.nih.gov/News/Results/FluModel040306)
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What Do We Need to Do—NOW
Our challenge as Missionary Health
Services is also “tremendously
challenging, given the potential
scope and the large number of
unknowns” for thousands of
missionaries in many distant,
diverse and often underdeveloped
locations.
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Personal and Public Health
 Our responsibilities are defined as
relating to personal, physical, dental,
mental, safety, nutritional and public
health matters.
 MHS advises in security matters when
that advice is sought, but ultimate
circumstance security decisions are in
the hands of Priesthood leadership
and Church Security.
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Personal Health of Missionaries
A Caveat:
 The Church has accepted legal
responsibility and liability for
missionaries, we are told . . .
 Parents and grandparents assume,
and rightly so, that all necessary
precautions, oversight and
appropriate preparations will be
implemented and in place.
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Personal and Public Health
 We need to provide general guidelines
about health maintenance, preparations
for possible “supporting in-place” and
treatment of disease in those stranded by
potential precipitous border closures,
quarantines, and transportation absence.
 If a pandemic occurs, civil chaos will be
variable, and health systems will be
overwhelmed. Food will be lacking.
 Personal safety reality will be variable.
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Decision Makers Up-to-Speed
Because timing will likely be critical:
 We need the mechanism to keep key
decision makers in SLC and area
offices up-to-speed and ready to act.
 To be appropriately ready they need to
understand the workings of avian flu.
 We need the guidance of the Spirit and
the unanimity stated in D&C 107:27.
 We need prophetic inspiration.
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MissionaryMedical.org
 More and more this Web site has
become a key informational resource.
Our compliments to our colleagues.
 It now needs a sophisticated, userfriendly up-to-date section on
Pandemic Influenza Understanding and
Planning for use by AMAs and mission
presidents, their spouses, and other
key mission personnel.
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MissionaryMedical.org
 We need “Fact Sheets.”
 We need circumstance FAQs.
 We need key URLs for emergency.
 We need list of supplies to be on
hand in mission offices.
 We need a list of tools that may
be needed in the field.
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MissionaryMedical.org

AMAs and MPs need to be brought
up to speed and kept there, and
their understanding needs to be
continually assessed and validated.
 Preferably the Web site should be
interactive, in order to respond to
unique circumstances and individual
questions.
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MissionaryMedical.org
 An effort, conducted with public
relations help, needs to be mounted to
convince and train our remote
colleagues to use this Web site.
 Its value as a message center needs to
be explored, the “kinks” worked out
and its use and utility continually
enhanced.
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MissionaryMedical.org
 A section in this Web site, and also
printed copies, needs to be prepared
outlining the care of a seriously ill flu
victim unable to access professional
help due to health system overload.
 Lists of supplies, medications, etc., for
the care of ill missionaries, need to be
carefully assembled and shipped with
the help of the PBO to Area or
mission offices.
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MissionaryMedical.org
 Satellite service connectivity needs to
be explored as an assured linkage
service for computers and phones in
the event of an emergency /
pandemic.
 In the event of a pandemic, with
communication failures and
infrastructure challenges, we need
to be able to connect, for many
reasons.
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Missionary Health
 We need to obviate and preclude a panic
mentality, but at the same time we and
they need to realize we are talking about
missionary lives and suffering.
 Life or death (survival) for many will be
determined by how well they and their
missions and their geographic
communities are prepared and respond.
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We Need to Practice / Drill
In order to ensure the highest likelihood
of success for whatever is to happen,
plans for evacuation, “stay in place,” or
other responses need to be carefully
outlined, formatted, distributed, and
“run throughs” or practice drills need to
be carefully carried out and reviewed /
assessed. Adjustments need to be made
where advisable. AMAs should be
involved. We need a tight ship ! ! ! !
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We need Mission Contingency
Plans Specific for a Pandemic
 Geography and mission physical
facilities will play a role in what a
mission should do.
 If the ultimate reality is a “stay in
place” result, some prior planning is
imperative in light of potential food
and supply shortages.
 If we will look to members, don’t we
need to help them prepare ???
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District Conference Instruction
Specific for a Pandemic
 We need district conference and
mission-specific presentations for a
variety of geographic locations.
 These should also be available on our
Web site, with appropriate updates.
 Missionaries need to understand the
seriousness, and the need for
optimal compliance.
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Missionaries Need to be Ready to Act
• To move in a very rapid fashion to a
defined assembly location.
• To already know what can be taken and
what is left behind.
• To understand critical timing factors.
• To have “ready to go” the key carry items.
• To have a cash reserve.
• Recommended food / survival items.
• Social distancing.
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U.S. Embassy Relations
 Maintain consistent and close contact
with the U.S. embassy or consulate and
the embassies of other non-US
missionaries. Know the embassy URL.
 Get to know the personnel. Don’t send a
different person each time. Establish
regular contacts using “savvy” persons.
 Make certain the various embassies know
of their citizens and their locations.
 Assess embassies capacity for help.
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U.S. Embassy Relations
 Have someone in each mission / area
obtain information about what each
embassy / consulate is planning with
respect to their own employees and
families in the event of a pandemic.
 Obtain copies of the DOS Avian Flu Fact
sheet and FAQs.
 Learn about the “warden system.”
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US Embassy “Warden System”
A U.S. Embassy’s primary means of
communication with U.S. citizens during an
emergency is the warden system. The
warden system is used to communicate
both emergency and non-emergency
information of interest to known U.S.
citizens. The embassy can also distribute
this information directly via e-mail or fax
to any U.S. citizen who asks to be included
in the warden notification network.
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Consular Response to A.I. Scenarios
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Embassy Reality in a Pandemic
 Likely limit Phase 6 air evacuations to
“official Americans”.
 “A drawdown or ‘stay in place’ response
would limit overall consular
services.”
 “In the event of deaths, Embassy will
work with NOK on disposition of
remains, in accordance with local
regulations and feasible options.”
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What Should We Be Doing?
 Knowledgeable awareness
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Up-to-date information and instruction
Appropriate preparedness
Validate understanding
Agreed-upon compliance & readiness
Savvy linkages and connectivity
Optimal communication
Create the spiritual environment to go
with prayerful seeking for inspiration