PREPAREDNESS FOR AN INFLUENZA PANDEMIC: FOCUS ON VACCINE DEVELOPMENT AND UNC HOSPITALS PREPAREDNESS

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PREPAREDNESS FOR AN INFLUENZA PANDEMIC FOCUS ON
VACCINE DEVELOPMENT AND UNC HOSPITALS
PREPAREDNESS

• David Jay Weber, M.D., M.P.H.
• Professor of Medicine, Pediatrics Epidemiology
• Medical Director, Hospital Epidemiology and
  Occupational Health
• University of North Carolina at Chapel Hill

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SOURCE OF SLIDES

• Robert Belshe, Washington University
• Nancy Cox, CDC
• Jeffrey Engel, NC Health Department
• James Matthews, Sanofi Pasteur
• Andrew Pavia, University of Utah
• Bill Schaffner, Vanderbilt
• David Shay, CDC
• Jay Steinberg, Emory

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INFLUENZA PRIMER
4
Influenza Disease Burden to U.S. Societyin an
Average Year
Deaths 25,000 - 72,000
Hospitalizations 114,000 - 257,500
Physician visits 25 million
Infections and illnesses 50 - 60 million
Thompson WW et al. JAMA. 2003289179-86. Couch
RB. Ann Intern Med. 2000133992-8. Patriarca PA.
JAMA. 199928275-7. ACIP. MMWR.
200453(RR06)1-40.
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INFLUENZA BIOLOGY IMPACT

• Single-stranded, enveloped, RNA virus
  (orthomyxoviridae family)
• Influenza A
• Potentially severe illness epidemic and
  pandemics
• Rapidly changing
• Influenza B
• Usually less severe illness may cause epidemics
• More uniform
• Influenza C
• Usually mild or asymptomatic illness

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INFLUENZA BIOLOGY IMPACT

• Impact
• 25-50 million people contract influenza annually
  (attack rate of 10-20)
• 226,000 hospitalizations per year
• 36,000 deaths per year
• Cost 1 to 3 billion dollars per year
• Causes respiratory tract disease
• Sudden onset
• More severe pneumonia during pregnancy
• No carrier state (but inapparent illness may
  occur)

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Influenza Activity Can Peak From December
Through May
Month of peak influenza activity during influenza
seasons in the United States, 19762002
11
6
4
3
1
1
www.cdc.gov/nip/publications/pink/flu.pdf.
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Structure of the Influenza Virus
Hemagglutinin (HA)
Neuraminidase (NA)
M2
Nucleoprotein (NP)
M1
Polymerase (P) Proteins
Adapted from Hayden FG et al. Clin Virol.
1997911-42.
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Viral Nomenclature
Type of Nuclear Material
Hemagglutinin
Neuraminidase
A / Sydney / 184 / 93 (H3N2)
Virus subtype
Virus type
Geographic origin
Year of isolation
Strain number
CDC. Atkinson W, et al. Chapter 13 Influenza.
In Epidemiology and Prevention of
Vaccine-Preventable Diseases, 4th ed. Department
of Health and Human Services, Public Health
Service, 1998, 220
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Timeline of Emergence of Influenza A Viruses
in Humans
Avian Influenza
H7
H9
H5
Russian Influenza
H5
H1
Asian Influenza
H3
Spanish Influenza
H2
Hong Kong Influenza
H1
1918
1957
1968
1977
1997
2003
1998/9
11
Antigenic Drift
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Antigenic Shift
13
Why the Concern? During the past 100 years,
there have been three major pandemics, and there
are strong signals in recent years of pandemic
potential (epizootics of avian flu)
H5N1
H7N7
H5N1
H9N2
H5N1
H1N1
H3N2
Different Viruses Migratory Birds Domestic Poultry
H2N2
DIFFERENT VIRUSES Migratory Birds Domestic Poultry
H1N1
2003
1968
1957
1918
2004/5
1977
1997
1999
1918
1918
50 - 100 millions
1 million
800 000
?
Mortality
Asian Flu
Hong Kong Flu
Spanish flu
1950
1925
1975
2000
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Antigenic Change - Shift
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INFLUENA PANDEMICS IN THE 20th CENTURY
HHS Pandemic Influenza Plan, October 2005
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Americas deaths from influenza were greater than
the number of U.S. servicemen killed in any war
Thousands
Civil WWI 1918-19 WWII
Korean Vietnam War
Influenza War War

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Worldwide Spread in 6 Months Spread of H2N2
Influenza in 1957 Asian Flu
Feb-Mar 1957Apr-May 1957Jun-Jul-Aug 1957
68,000 deaths, US
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INFLUENZA ANTIVIRAL THERAPIES

• Amantadine Influenza A
• Treatment and prophylaxis dose adjust in renal
  failure
• Rimantadine Influenza A
• Treatment and prophylaxis dose adjust in renal
  and hepatic failure
• Oseltamivir Tamiflu Influenza A B
• Treatment (5 days) and prophylaxis (PEP 7 days
  Seasonal 42 days) dose adjust in renal failure
• Zanamivir Relenza Influenza A B
• Treatment only
• Must begin therapy within 2 days of onset of
  illness

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Antiviral Agents for Treatment
Modified from Couch RB, Ann Intern Med.
2000133992-998
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Antiviral Agents for Prophylaxis
Not FDA approved
Modified from Couch RB, Ann Intern Med.
2000133992-998
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Moscona, A. N Engl J Med 20053531363-1373
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INFLUENZA - ANTIVIRAL THERAPIESTOXICITIES

• Amantadine and rimantadine
• CNS (anxiety, insomnia, seizures,
  hallucinations), GI
• CNS toxicity greater in patients on amantadine
• Resistance develops in 10-30 during treatment
  course
• Teratogenic and embryogenic in animals
• Zanamivir
• Brochospasm (avoid in asthmatics)
• Oseltamivir
• GI (nausea and/or vomiting 5-10)

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ANTIVIRAL THERAPY OF INFLUENZA
? No placebo-controlled study or not reported
Source Andrew Pavia, Pandemic Influenza
Planning, Emory, Nov. 2005
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ANTIVIRAL RESISTANT INFLUENZA DURING TREATMENT
Roberts N. Trans R Roc Lond 20013561895 Kiao,
et al. Lancet 2004364750
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OSELTAMIVIR EFFICACY
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Tamiflu (oseltamivir phosphate) Seasonal
Prophylaxis in a Vaccinated Frail Elderly
Population Results
of patients with laboratory-confirmed clinical
influenza
Data on file (Ref. 155-027). Hoffmann-La Roche
Inc.
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OSELTAMIVIR IMPACT ON LOWER RESIRATORY TRACT
COMPLICATIONS (LRTC)

• Analysis of prospective data from patients
  enrolled in 10 placebo controlled trials (N3564)
• Results confirmed influenza (oseltamivir vs
  placebo)
• Reduced overall antibiotic use 14.0 vs 19.1
  (p
• Reduced LRTCs-associated antibiotic use 4.6 vs
  10.3 (p
• Reduced LRTCs leading to antibiotics in high risk
  patients 12.2 vs 18.5 (p0.02)
• Reduce overall hospitalizations 1.0 vs 1.7
  (p0.02)
• Unconfirmed influenza No difference in
  incidence of LRTC, overall antibiotic use or
  hospitalizations

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Day of onset of antibiotic therapy for lower
respiratory tract complications in oseltamivir
(75 mg twice daily) and placebo recipients with
influenza infection
Kaiser, L. et al. Arch Intern Med
20031631667-1672.
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Day of hospitalization among placebo- or
oseltamivir (75 mg twice daily) - treated adults
with influenza infection
Kaiser, L. et al. Arch Intern Med
20031631667-1672.
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ANTIVIRALS FOR CHEMOPROPHYLAXIS CDC
RECOMMENDATIONS

• Community outbreak (usual duration 6-8 weeks)
• Persons at high risk of serious complications
• Persons at high risk of serious complications
  following vaccination until immunity develops (2
  weeks for adults, 6 weeks for first time
  pediatric vaccinees)
• Persons who are not expected to mount a
  sufficient immune response due to
  immunosuppression
• Healthcare workers with direct patient care
  responsibilities unable to obtain vaccine

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AVIAN INFLUENZA
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PANDEMIC INFLUENZA PLANNING CHALLENGES

• Worldwide distribution
• Simultaneous appearance in multiple
  states/locales
• Long duration (2 years)
• Surge capacity Medications, ventilators,
  hospital beds, personnel
• Personnel Exhaustion, concerns about infection
• Inadequate antivirals and distribution/allocation
• Vaccine development and distribution/allocation
• Maintaining infrastructure
• Maintaining quarantine

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CHARACTERISTICS OF AN INFLUENZA PANDEMIC

• The ability of the virus to spread worldwide
• Simultaneous outbreaks throughout the US,
  limiting the ability of an jurisdiction to
  provide assistance to other areas
• The fact that many people may be asymptomatic
  while infectious
• Enormous demands on the healthcare system
• Delays and shortages in the availability of
  vaccines and antivirals
• Potential disruption of national and community
  infrastructures including transportation,
  commerce, utilities and public safety due to
  illness and death among workers and their
  families
• Duration 2 years

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AVIAN INFLUENZA EPIDEMIOLOGY
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Current Influenza A/H3N2 is Partly Derived from
the 1918 Virus
Taubenberger et al, Nature, Oct 2005
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Defining a Pandemic WHO Phases

• Phase 1. No new influenza virus subtypes detected
  in humans. If animals are infected, risk to
  humans is low.
• Phase 2. No new influenza virus subtypes detected
  in humans. However, a circulating animal
  influenza virus subtype poses a substantial risk
  of human disease.
• Phase 3. Isolated human infections, no
  human-to-human spread except rare close contacts.
  
• Phase 4. Small, highly localized cluster(s),
  limited human-to-human transmission.
• Phase 5. Larger localized cluster(s) limited
  human-to-human spread. Substantial pandemic
  risk.
• Phase 6. Pandemic phase Sustained transmission
  among humans occurs.

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AVIAN INFLUENZA EPIDEMIOLOGY

• Multiple outbreaks of H5N1 in Asia since 1997
• Recently animal evidence of H5N1 infection (duck
  strain)
• Pigs serologic/culture in china (ProMed)
• Cats experimental infection (Kuiken. Science,
  2004 9/02)

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AVIAN INFLUENZA EPIDEMIOLOGY

• Human-to-human cases reported
• Retrospective serologic evidence 1997
• Outbreak (Chan CID)
• 3.7 healthcare workers
• 6/51 household contacts
• Possible one family cluster (N2) in current
  Thailand outbreak
• Requires close contact, inefficient transmission

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AVIAN INFLUENZA

• Treatment
• Neuraminidase inhibitors
• Oseltamivir (Tamiflu)
• Zanamivir (Inhaled)
• Current H5N1 Amantadine and Rimantadine Resistant
• For influenza clinical activity only if given in
  1st 48 hours
• Likely would also work for chemoprophylaxis
• Eradication
• Large scale culling of birds

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Some Avian-to-Human Influenza Transmissions
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H5N1 SNAPSHOT NOVEMBER 2005

• 124 human cases, 63 deaths (50)
• N5H1 strains now present in 17 countries
• Virus spreading beyond the original geographic
  region to mainland China, Philippines, Siberia,
  Indonesia, Malayasia, Turkey (5 new countries
  since July)
• 150 million birds culled (cost 10 billion)

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FACTORS LEADING TO CONCERN OF AN H5N1 INFLUENZA
PANDEMIC

• Avian H5N1 is widespread and endemic in Asia with
  spread to Russia and Europe
• Avian H5N1 is becoming more deadly in a growing
  number of bird and mammals species
• Wild birds and domestic ducks may be
  asymptomatically infected
• The virus is able to transmit directly from birds
  to some mammals and in some circumstances to
  people
• Sporadic spread directly from animals to humans
  suspected human-to-human transmission in rare
  instances
• Genetic studies demonstrated ongoing evolution of
  H5N1

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AVIAN INFLUENA PREPAREDNESS
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PANDEMIC INFLUENZA IMPACT, US
HHS Pandemic Influenza Plan, October 2005
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PANDEMIC INFLUENZA IMPACT, NC
Assumes a 25 attack rate NC Pandemic Influenza
Plan, October 2005
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AVIAN INFLUENZA IMPACT, NC

• Number of cases 1,856,296
• Hospitalizations 65,637
• Deaths 14,987
• Assumptions strain 3x more lethal than 1968-69
  Hong Kong influenza
• Source USA Today, 11 October 2005

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NATIONAL PROBLEMS(Not Under Control of Hospital)

• General issues
• Lack of surge capacity (ICU beds, ventilators,
  floor beds)
• Nursing shortage
• Just in time delivery of goods
• Response to avian influenza
• Inadequate supply of PPE
• Inadequate supply of antivirals
• Lack of effective vaccine for avian influenza
• Public hysteria

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NATIONAL PROBLEMS(Not Under Control of Hospital)

• Other issues
• No defined CDC isolation category for isolation
  of highly communicable diseases (i.e., diseases
  for whom airborne with eye protection
  recommended) Avian influenza, SARS, certain
  viral hemorrhagic fevers

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AVIAN INFLUENZA ANTIVIRALS

• IDSA RECOMMENDATIONS

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Recommendations - Priority groups

• 1. Hospitalized patients with influenza
• 2. HCWs and EMS workers with direct patient
  contact
• 3. Highest risk outpatients
• 4. Pandemic health responders, public safety
  key government decision makers
• 5. Other high risk outpatients

• 6. Outbreak response (eg PEP in nursing homes)
• 7. Prophylaxis HCWs in ER, ICU, EMS, dialysis
• 8. Pandemic societal responders other HCWs
• 9. Other outpatients
• 1O. Prophylaxis for highest risk outpatients
• 11. Prophylaxis for other HCWs w/ patient contact

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Proposed Priority Target Groups
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Estimated Pandemic Mortality, UK, 1918-19
Gani et al. Emerging Infect Dis 111355, 2005
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EFFICACY OF OSELTAMIVIR IN A MOUSE MODEL
(A/Vietnam/1203/04 H5N1)
Yen H-L, et al. JID 2005192665
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ANTIVIRALS

• Demand
• 40 million courses minimum needed to support
  critical pandemic responses
• 133 million courses minimum to treat all
  infected and provide prophylaxis for critical
  personnel
• Supply
• 4 million courses in US National Stockpile
• Current stockpile based on used drugs for
  treatment (more needed to provide prophylaxis)
• Mouse model suggests need to treat for 8 days
  rather than 5 days

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AVIAN INFLUENZA VACCINES
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VACCINE BY THE NUMBERS

• 40 million estimated number of deaths worldwide
  for 1918 pandemic
• 6.2 billion worlds population
• 300 million doses worldwide capacity for
  trivalent influenza vaccine
• 900 million doses worldwide capacity for
  monovalent vaccine (issues include yield,
  adjuvant, process used, antigen content
• 1 or 2 doses?
• /- 2 years expected duration of pandemic
• /- 6 months time from recognition of pandemic
  till vaccine available
• 9 countries number of countries with vaccine
  capacity (70 in EU)
• 3-5 million doses/week (15 ?g) current capacity
  of US manufacturers

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Selected US Regulatory Issues Regarding a
Pandemic Antigenic Strain in Approved Vaccines

• Pandemic vaccine likely would be approved under
  existing regulations for updating strains in
  currently approved vaccines
• WHO recommended pandemic strain could be
  substituted into a monovalent preparation
• Updating strains to monovalent, pandemic type
  would be less burdened than approval of novel
  vaccines
• Issues of antigen quantity and number of doses
  might require clinical trials

Wood Levandowski, Vaccine 211786-88, 2003
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Generalized Influenza Vaccine Global Production
Timetable (NH - Representative Year)
Egg supply organization
Egg supply for production
Seed lots
Monovalent batches
Formulation
Filling / Packaging
Packaging documentation
Ref Member State Release
Pharmaceutical file
MA
Clinical trial
Vaccine Delivery
WHO meeting D0 mid Feb
D0
Reagent availabilityEnd of May
Mid May
July/August
D0 - 6 months
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Vaccine Development
Jan
Feb
Mar
Apr
May
Jun
Jul
Aug
Sep
Oct
Nov
Dec
WHO/CDC)
WHO/CDC/FDA
CDC/FDA
FDA
FDA
FDA
manufacturers
clinic
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Sources of Information on Pandemic Influenza A
Vaccines

• Studies of contemporary, novel egg grown HA in
  adults, (e.g., H9 and H5)
• Studies of H2 in naïve subjects after 1968
• Studies of Swine Flu vaccine in 1976 or H1N1 in
  younger adults in 1977
• Studies of TIV or LAIV in seronegative children

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Characteristics of Influenza Vaccines in Naïve
Subjects

• Different HAs exhibit different immunogenicity
• Two or three doses of HA required
• Adjuvants may reduce the number of doses of HA
  needed
• High doses of HA or adjuvant may broaden the
  immune responses
• LAIV single dose immunogenic, induces broad
  immune responses
• Unexpected interactions may occur (e.g. H2 and
  H9)

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Experiences with Pandemic Vaccines

• A/USSR/92/77 (H1N1) - Immunogenicity studies
  compared results in younger persons (born after
  1957, naïve to H1) to older persons (born before
  1957, likely previously infected with H1)
• Large doses of vaccine, 60?g HA required for one
  dose to be immunogenic
• Two doses of 5?g was immunogenic
• Whole virus vaccines more immunogenic than split
  virus, but whole virus vaccine was more
  reactogenic
• Adjuvants can enhance the immune responses and be
  dose sparing in unprimed persons

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Breadth of Antibody Responses to H5N3 Vaccine
(A/Duck/Singapore/97)
Vaccine 30?g egg grown HA with ( ) or
without ( ) MF59 adjuvant, 3 doses,
neutralizing Ab
Stephenson et al, JID 1911210-1215, 2005
NEUT Ab
Three doses of adjuvanted influenza vaccine
produced with a 1997 avian strain can prime and
induce antibodies against H5N1 strains isolated
in 2003 and 2004
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Clinical Trials with Egg Grown HA-H5 Vaccine

• Healthy adults age 18-40 (J.Treanor, PI)
• Dose response study
• Compare placebo, 7.5µg, 15µg, 45µg or 90µg
• Vaccine given at times 0, 1 month
• Study completed, data pending, but HHS reports 2
  doses of 90 mcg was immunogenic
• Booster planned
• Healthy Children, Age 2-9, to begin soon
• Elderly, Age ?65, to begin soon

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Neutralizing Antibody Response to Two Doses of
rHA0 (H5) to A/HK/156/97 H5N1
with neut. response
45 ?g x2
Placebo
90 ?g x2
25 ?g x2
Treanor et al, Vaccine 191732-37, 2001
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Clinical Trials of Vaccines Designed for Pandemic
Influenza, Other Ongoing and Future Trials
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LAIV Induces Broad Immune Responses
Belshe et al, Peds ID, 2000
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H9/AA ca Live Virus Vaccine Provides Complete
Protection from Replication of Homologous and
Heterologous H9N2 Challenge Viruses in the A
(upper) and B (lower) Respiratory Tract in Mice
(A)
Virus titer (log10 TCID50/ml)
H9 Challenge Virus
1073 Immunizing Virus
(B)
Virus titer (log10 TCID50/ml)
Chen et al, Vaccine, 2003
H9 Challenge Virus
1073 Immunizing Virus
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Conclusions

• Hemagglutinins have different properties, several
  need to be studied
• 2 or 3 doses and high doses of purified HA will
  be needed to induce antibodies to novel HAs
• Strain variation will remain a significant
  problem i.e. difficult to predict which vaccine
  to stockpile
• Developing vaccines to mimic priming by natural
  infection is important
• LAIV
• Adjuvanted HA subunit or rHA0
• Novel vaccines need to be developed
• Novel methods of production (I.e., cell culture
  need to be commercialized)

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VACCINE RESPONSE

• Presidents proposed plan 7.1 billion
• Produce and stockpile H5N1 vaccine
• Develop cell culture systems for vaccine
  development
• HHS pandemic influenza plan
• Ensure domestic production capable of producing
  vaccine within 6 mo
• Stockpile oseltamivir
• NC State plan
• Responsible for distribution/allocation of
  antivirals and vaccines

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NVAC/ACIP ALLOCATION PRIORITIES 1A

• Priority Groups
• Vaccine and antiviral manufacturers and others
  essential to manufacturing and critical support
  (40,000)
• Medical workers and public health workers who are
  involved in direct patient contact, other support
  services essential for direct patient care, and
  vaccinators (8-9 million)

• Rationale
• Need to assure maximum production of vaccine and
  antiviral drugs
• Healthcare workers are required for quality
  medical care (studies show outcome is associated
  with staff-to-patient ratios). There is little
  surge capacity among healthcare sector personnel
  to meet increased demand

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NVAC/ACIP ALLOCATION PRIORITIES 1B

• Priority Groups
• Persons 65 years with 1 or more influenza
  high-risk conditions, not including essential
  hypertension (18.2 million)
• Persons 6 mo - 64 years with 2 or more influenza
  high-risk conditions, not including essential
  hypertension (6.9 million)
• Persons 6 months or older with history of
  hospitalization for pneumonia or influenza or
  other influenza high-risk condition in the past
  year (740,000)

• Rationale
• These groups are at high risk of hospitalization
  and death. Excludes elderly in nursing homes and
  those who are immunocompromised and would not
  likely be protected by vaccination

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NVAC/ACIP ALLOCATION PRIORITIES 1C

• Priority Groups
• Pregnant women (3.0 million)
• Household contacts of severely immunocompromised
  persons who would not be vaccinated due to likely
  poor response to vaccine (1.95 million with
  transplants, AIDS, and incident cancer x 1.4
  household contacts per person 2.7 million
  persons)
• Household contacts of children million)

• Rationale
• In past pandemics and for annual influenza,
  pregnant women have been at high risk
  vaccination will also protect the infant who
  cannot receive vaccine.
• Vaccination of household contacts of
  immunocompromised and young infants will decrease
  risk of exposure and infection among those who
  cannot be directly protected by vaccination.

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NVAC/ACIP ALLOCATION PRIORITIES 1D

• Priority Groups
• Public health emergency response workers critical
  to pandemic response (assumed one-third of
  estimated public health workforce 150,000)
• Key government leaders

• Rationale
• Critical to implement pandemic response, such as
  providing vaccinations and managing/monitoring
  response activities
• Preserving decision-making capacity also critical
  for managing and implementing a response

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NVAC/ACIP ALLOCATION PRIORITIES 2A

• Priority Group
• Healthy 65 years and older (17.7 million)
• 6 months to 64 years with 1 high-risk condition
  (35.8 million)
• 6-23 months old, healthy (5.6 million)

• Rationale
• Groups that are also at increased risk but not as
  high risk as population in Tier 1B

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NVAC/ACIP ALLOCATION PRIORITIES 2B

• Priority Groups
• Other public health emergency responders
  (300,000)
• Public safety workers including police, fire, and
  correctional facility staff (2.99 million)
• Utility workers essential for maintenance of
  power, water, and sewage systems (364,000)
• Transportation workers transporting fuel, water,
  food, and medical supplies as well as public
  ground public transportation (3.8 mil)
• Telecommunications/IT for essential network
  operations and maintenance (1.08 million)

• Rationale
• Includes critical infrastructure groups that have
  impact on maintaining health (e.g., public safety
  or transportation of medical supplies and food)
  implementing a pandemic response and on
  maintaining societal functions

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NVAC/ACIP ALLOCATION PRIORITIES 3

• Priority Groups
• Other key government health decision-makers
  (estimated number not yet determined)
• Funeral Directors and embalmers (62,000)

• Rationale
• Other important societal groups for a pandemic
  response but of lower priority

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NVAC/ACIP ALLOCATION PRIORITIES 4

• Priority Groups
• Healthy persons 2-64 years not included in above
  categories (179.3 million)

• Rationale
• All persons not included in other groups based on
  objective to vaccinate all those who want
  protection

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LOCAL PREPAREDNESS
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LESSONS FROM SARS
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SARS CASES AND OUTCOME
WHO 21 April 2004
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Total SARS Cases and Healthcare Workers by
Country
HCW
Total No. SARS cases
HCW
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Time-line NC Confirmed SARS Case, 2003

• 5/15-18 Visited Toronto
• 5/19-23 Worked at UNC
• 5/24 Developed fever (did not work)
• 5/27, 5/28, 6/1, 6/3 Visited LMD (free standing
  clinic)
• 5/30 Doxycycline begun for suspected RMSF
• 6/2 Respiratory symptoms
• 6/3 CXR with infiltrate SARS suspected, health
  department notified

• 6/3, 6/9 Serum collected sent to CDC
• 6/9 Seroconversion to SARS-CoV
• 2 workplace contacts investigated for atypical
  pneumonia
• 6/13 Contact 1 diagnosed with mycoplasma 6/13
• 6/13 Contact 2 dies with pneumonia/ARDS

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SARS in Toronto, 2003
Orange County mans travel dates
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Index Case, June 8
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AIR CONDITIONING
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SARS CONTROL MEASURES

• Hospital Infection Control
• Early detection
• Containment Proper infection control,
  environmental cleaning
• Protection of personnel PPE, hand hygiene
• Community
• Active Surveillance
• Disease Investigation
• Isolation and Quarantine

105
Hospital-based SARS surveillance Options for
Enhanced Surveillance
Facility with no SARS cases
Be alert for clusters of pneumonia among HCWs
Monitor HCWs taking care of SARS patients daily
for fever, cough or SOB
Screen all visitors
Fever, cough, or shortness of breath? SARS Risk
Factors?
Monitor daily healthcare workers
inpatients
Facility with unlinked nosocomial transmission
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LESSONS FROM SARS

• Need to nestle response to a highly communicable
  disease in hospital disaster plan
• Solution Revised disaster plan
• Concern about being labeled SARS hospital
• Work with NC State Health Department
• Must manage worker and public concern (i.e.,
  provide public relations use local/state health
  departments)
• Improved communication within hospital and with
  health departments
• Inadequate supplies of PPE
• 3 months PPE stockpiled by hospital (being
  increased to 6 months)

107
LESSONS FROM SARS

• Inadequate outpatient facilities to handle highly
  communicable diseases
• Solution New ID clinic (all rooms meet CDC
  airborne isolation requirements)
• Need to screen for travel to endemic area at
  entry to hospital or clinic
• Message on phone while awaiting operator, signs
  at hospital entry
• Need for UNC Health Care System to have its own
  diagnostic laboratory capacity (i.e., not rely on
  CDC)
• PCR developed for SARS-coV

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LESSONS FROM SARS

• Need for State policy on transport of patients
  with highly communicable diseases
• Solution Ongoing discussions with State Health
  Department
• Must manage worker exhaustion
• Solution enforced rest periods
• Inability of workers to adhere exactly to
  guidelines for placing and removing PPE
• Solution PPE monitor

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LOCAL PREPAREDNESS
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FEDERAL AND STATE LOCAL PREPAREDNESS

• HHS pandemic influenza plan
• Stockpile ventilators and other equipment in
  Strategic National Stockpile
• Widely available accurate rapid diagnostic tests
• Assist communities with surge mortuary services
• Provide psychosocial support to responders

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AVIAN INFLUENZA IMPACT, NC

• Number of cases 1,856,296
• Hospitalizations 65,637
• Deaths 14,987
• Assumptions strain 3x more lethal than 1968-69
  Hong Kong influenza
• Source USA Today, 11 October 2005

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UNC HOSPITAL PREPAREDNESS

• Surveillance
• Influenza like activity (ILI) in NC sentinel
  sites, UNC ED
• Laboratory tests for influenza (number and
  frequency positive)
• Diagnosis (detection)
• Rapid testing available for influenza A B, and
  RSV (24/7)
• PCR available to diagnosis all influenza A
  strains (unable to differentiate H5N1 strains
  from other influenza A strains)
• Graded response (i.e., hierarchy of response
  depending on threat)
• Hospital response plan
• Modeled on SARS response plan

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INFLUENZA LIKE ILLNESS ACTIVITY, NC AND UNC ED,
2004-05
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INFLUENZA TESTS AND RESULTS, UNC, 2004-05
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UNC HOSPITAL PREPAREDNESS

• Cooperation with county and state public health
  authorities
• State response plan
• Communication pathways established (PHE network,
  SPICE, others)
• Nestle influenza response in disaster planning
• Hospital disaster plan
• Frequent drills
• Incident command system
• Access to senior administrators
• Ad Hoc Committee for vaccine distribution
  (reports to MSEC)

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UNC HOSPITAL PREPAREDNESS

• Minimizing exposure
• Universal respiratory hygiene (signs in
  clinics/ED, method to provide persons with
  symptoms of URI tissues, mask, education)
• Droplet precautions for persons with URI until
  diagnosis rules out need for isolation
• Adequate PPE supplies
• 3 month stockpile of PPE (especially N95
  respirators)
• Training and institution of special airborne
  isolation
• Components N95 respiratory, airborne isolation
  room (negative pressure, direct out exhausted
  air), eye protection

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UNC HOSPITAL PREPAREDNESS

• Ability to rapidly train large numbers of
  healthcare workers in use of N95
• Use train the trainers approach
• Multiple screeners available (NX)
• Plan for evaluating ill employees with URI
  symptoms
• Fever plus symptoms Relieve from duty, care per
  LMD
• Symptoms (work in PICU, NICU, BMTU) Rapid RSV
  and influenza testing (positive test exclusion
  from these units)
• Symptoms without fever allowed to work while
  wearing mask

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UNC HOSPITAL PREPAREDNESS

• Availability of facilities to safely screen
  outpatients for highly communicable diseases
• Infectious disease clinic 8 clinic rooms, all
  meet airborne isolation requirements (direct out
  exhausted air, negative pressure), separate
  entrance that does not require movement through
  hospital
• Family Practice center Free standing facility
  with multiple exam rooms, laboratory capacity,
  near main hospital
• Adequate number of isolation beds
• Airborne isolation beds available at UNC 75
  (Adult ICU 13, Ped/Neonatal ICU 8, Adult floor
  48, Peds floor 9)

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UNC HOSPITAL PREPAREDNESSUNDECIDED ISSUES

• Management of patients if beds unavailable and
  transfer impossible
• Use of unlicensed beds? (e.g., PACU, 24 hours
  holding unit, clinics)?
• Use of temporary facilities
• Triage/management of patients if ventilators
  unavailable
• Who lives and who dies
• Stockpiling of oseltamavir
• Pros Reduce anxiety among HCWs, availability
  even if national shortage
• Cons Expense, out dating of drug, reduce
  availability to public
• Currently unavailable
• Use for prophylaxis at discretion of Medical
  Director, OHS

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