Avian Influenza What is Happening and How Should We Prepare

1
Avian Influenza -What is Happening and How
Should We Prepare?- - - - - - - - -

• John M. Matsen, M.D.
• August 9, 2006

2
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)

3

• 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)

4
TUFTED DUCK
5
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.

6
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.

7
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.

8
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 yearusually 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.

9
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 19831984 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 19992001 poultry epidemic in Italy, the
  H7N1 virus, initially of low pathogenicity,
  mutated within 9 months to a HPAI form.
  (WHO)

10

• 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)

11
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 long-term endemicity of the virus,
  and the isolation of H5N1 virus from apparently
  healthy migratory birds in southern China.
  (PNAS 02/10/06)

12
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)

13
H5N1 Presence 2006

• .

Nations With Confirmed Cases (070706)
14
Confirmed Human H5N1 Cases
7/20/2006
15
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.

16
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

17
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.

18
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.
19
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)

20
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)

21
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.
• 
  (Hoft, et al. NEJM. 12/9/04)

22
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. 2005310(77)).
23
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
  virusinfected 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.)

24
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 19831984 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 19992001 poultry epidemic in Italy, the
  H7N1 virus, initially of low pathogenicity,
  mutated within 9 months to a HPAI form.
  (WHO)

25

• 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.
• H5N1s 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)

26
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)

27
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, 554555 and 442, 114-115
  2006).

28
Human-to-Human Transmission

• Sequence data show that mutations were
  accumulating as it spread from person to person.
• (Nature 442, 114-115 2006)

29
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.
  (Editors Comment. Nature. 2006440436)

30
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)

31
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.

32
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)

33
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.

34
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," HHSs
  Mike Leavitt said at an immunization conference
  in Atlanta.

(AP 3/6/06)
35
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)

36
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

37
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.

38
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.

39
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.

40
WHO Phase of Pandemic Alert

April 8, 2006
41
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)

42
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.

43
HHS and State Governors Holding Pandemic Summits

44
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)

45
Worst-case Scenario

• SYDNEY, Feb 16/06 (Reuters)A worst-case
  scenario bird flu pandemic could wipe US4.4
  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 scenariosmild,
  moderate, severe and ultra pandemicsusing
  historical data on previous influenza pandemics
  and the economic fallout from the SARS crisis in
  Asia in 2003.

46
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)

47
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? Noit's now a plausible
  scenario.

48
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.

49
What Can Happen

• TRANSPORTATION
• Planes dont fly
• Trains are halted
• Buses dont run
• Travel curtailed
• Gasoline supplies dwindle
• Mobility crisis
• Travelers stranded

• COMMERCE
• Services unavailable
• Food scarce
• Medicines rationed
• Household goods gone
• Supplies in general
• are in short supply
• Inventories shrink
• Banks are closed

50
What Can Happen

• CIVIL
• Safety
• Law enforcement
• Civil compromise
• Desperation
• Criminal element
• Utilities
• Water, etc.
• Communication

• PEOPLE
• Social distancing
• 40 could be ill
• Personal resources
• Failure to cope
• The sick, dying dead
• Grief
• The vulnerable
• Being alone concerns

51
What Can Happen

• HEALTH CARE
• Medical facilities will be overwhelmed
• Vaccines antivirals in short supply and
  unevenly available
• Nursing supplies ??
• Rx Medicines Need to stock up
• 2o infections Rx

• EMPLOYMENT
• Offices closed
• Transit problems
• Work from home
• Loss of jobs/wages
• Business failures
• Urge prior planning where it is lacking
• Inability to make payments

52
Hunkering down...

• Ill 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)

53
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)
  
  

54
Support in Place

• RESOURCES
• Water
• Food necessities
• Personal hygiene
• Cleaning items
• Sanitation
• Fuel, lighting
• Cash
• Etc.

• FUNCTION
• Guidelines, manuals, etc.
• Computer (Work from home)
• Cell phone
• Bicycles, motor bikes
• Equipment and tools
• Reading materials
• Entertainment items
• Radio, batteries, etc.

55
U.S. State Department DVDBeing 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.

56
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)

57
What Do We Need to DoNOW

• 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/Re
  sults/FluModel040306)

58
What Do We Need to DoNOW

• 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.

59
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.

60
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.

61
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.

62
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 DC 10727.
• We need prophetic inspiration.

63
MissionaryMedical.org

• More and more this Web site has become a key
  informational resource.
• Our compliments to our colleagues.
• It now needs a sophisticated, user- friendly
  up-to-date section on Pandemic Influenza
  Understanding and Planning for use by AMAs and
  mission presidents, their spouses, and other
  key mission personnel.

64
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.

65
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.

66
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.

67
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.

68
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.

69
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.

70
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 ! ! ! !

71
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, dont we need to help
  them prepare ???

72
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.

73
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.

74
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. Dont 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.

75
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.

76
US Embassy Warden System

• A U.S. Embassys 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.

77
Consular Response to A.I. Scenarios
78
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.

79
What Should We Be Doing?

• Knowledgeable awareness
• 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