INFLUENZA From Routine Response to Pandemic Preparedness

1
INFLUENZAFrom Routine Responseto Pandemic
Preparedness
2
Case

• It is mid-December
• A 35 year-old-man, previously healthy, presents
  to the Emergency Department (ED) with a one day
  history of fever, severe myalgias, dry cough, and
  retro-orbital pain

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Case (contd)

• He can barely sit up to be examined
• He is a healthcare worker
• Received influenza vaccine last year
• No history of international travel or animal
  exposure
• He is febrile, tachycardic, and appears toxic

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Case (contd)

• Over the course of the shift, the ED physician
  sees several cases with similar complaints. Some
  require IV fluids, some are admitted, some sent
  home.
• ED physician calls the local health department
  and learns that other EDs in the area are seeing
  an unusual number of patients with fever,
  myalgias, cough and weakness.
• Beds on the floors quickly fill. Backup nursing
  staff are being called in. The physician
  covering the next shift shows up sick and is sent
  home by the ICP.

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Case (contd)

• At the same time, the local TV station calls the
  ED and urgently requests an interview in order to
  prepare for a news story that evening

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Case (contd)

• Is it an outbreak? Is it a routine influenza
  season?
• What other infectious diseases could present
  similarly?
• What is the role of the healthcare provider in
  recognition and reporting, as well as in a
  multidisciplinary response?
• If situation became markedly worse / evolved into
  a mass casualty event, how would the health care
  system respond?

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INFLUENZA Objectives

• Discuss influenza epidemiology and virology
• Describe the 3 systems for influenza surveillance
  
• Discuss primary prevention and treatment options
• Review changes in recommendations for the 2004-05
  season, given shortage of vaccine
• Review the risk of influenza pandemics
• Understand flu as a model for bioterrorism and
  other public health disaster planning

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INFLUENZA Clinical Features

• Typical symptoms fever, chills, myalgias, sore
  throat, cough, retro-orbital pain
• Most symptoms resolve in a week, cough may
  persist for more than one week
• Symptoms may be prolonged in immunosuppressed
  hosts
• Childrens max temp tends to be higher. Febrile
  seizures can occur

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INFLUENZA Complications

• Very young and elderly ? 65 y and those with
  underlying illness
• Sinusitis, otitis, exacerbation of COPD,
  bronchitis, bronchiolitis, croup
• Primary viral pneumonia 3-5 days,
• Superimposed bacterial pneumonia -- 5-10 days

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INFLUENZA Non-Pulmonary Complications

• Myositis, rhabdomyolysis rare, reported mostly
  in children
• Cardiac - Myocarditis, pericarditis
• Toxic shock syndrome
• Nervous system
• Transverse myelitis
• Guillain-Barrè Syndrome
• Encephalitis in children lt 5y Japan
• Encephalitis lethargica temporally associated
  with 1918 pandemic
• Reyes Syndrome

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INFLUENZA EPIDEMIOLOGY AND VIROLOGY

• Including Avian Flu and
• Potential Pandemic Viruses

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INFLUENZA Epidemiology (contd)

• Incubation period 1-4 days
• Virus first detected just before onset of
  illness. Virus usually not detected after 5 - 10
  days.
• More prolonged shedding in children,
  immunosuppressed hosts
• Transmission via respiratory droplets
• person to person,
• direct contact,
• aerosols--sneezing, coughing, etc.

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INFLUENZA Epidemiology (contd)

• Attack rates 10-20 general population,
• selected populations 40-50
• Typical Season 200,000 hospitalizations and
  36,000 deaths
• INFLUENZA IS THE SINGLE MOST COMMON VACCINE
  PREVENTABLE DISEASE

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INFLUENZA Epidemiology (contd)

• Epidemics
• Begin abruptly
• Peak 2-3 weeks, last 5-6 weeks
• Severity of outbreak
• Virulence of strain
• Mismatch between vaccine strain andcirculating
  strain
• Susceptibility of population
• Influenza is predictably unpredictable

15
Transmission electron micrograph of influenza A
virus, late passage. Source CDC/Dr. Erskine
Palmer
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INFLUENZA Virology

• Family orthomyxoviridae
• Enveloped viruses 80-120 nm, negative stranded
  RNA with 8 different segments. Allows for
  genetic reassortment when gt1 virus infects a
  single cell
• Types A, B, and C Significant differences in
  structure, genetics, organization, host range,
  epidemiologic and clinical characteristics
• Covered with surface projections or spikes --
  Hemagglutinin and neuraminidaseused to subtype
  influenza A virus types.

Source Aventis Pasteur
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INFLUENZA Virology (contd)

• Named by type / place isolated / culture / yr
  isolation
• A/Fujian/411/2002 (H3N2)
• B/Shanghai/361/2002-like

SourceAventis Pasteur
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INFLUENZA Virology (contd)

• Influenza A
• Occurs in humans, pigs, horses, birds, and
  certain marine mammals
• Human disease historically linked to H1 - H3 and
  N1 - N2
• All human pandemics have been due to Influenza A
• Avian flu viruses are Influenza A viruses
  (H1-H15 N1-N9) H5 and H7 typically cause
  severe outbreaks in birds

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INFLUENZA Virology (contd)

• Amazing ability to change
• Antigenic Drift (A and B)
• Comparatively minor antigenic change
• Why we need a new vaccine each year
• Causes epidemics a higher than normal level in
  the population, usually much higher than endemic,
  and usually short-term
• Antigenic Shift (A only)
• Major antigenic change
• Leads to pandemicsnovel strain, little immunity,
  epidemic spreading between continents

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INFLUENZA Virology / Epidemiology

• Hypothesis that all mammalian influenza viruses
  derive from avian influenza reservoir
• Influenza viruses replicate in intestinal tract,
  excreted in feces of birds
• Many birds infected by virus shed into water

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INFLUENZA Virology / Epidemiology

• Link Between Avian and Mammalian Influenza
• Transmission of avian influenza viruses to
  mammals including pigs and horses probably by
  direct transmission and fecal contamination of
  water
• After transmission to pigs, horses, or humans,
  method of spread of influenza mainly respiratory
• Avian influenza outbreaks and human disease
  1997-2004

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Vietnamese woman selling chickens at market. Food
and Agriculture Organization, U.N.
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INFLUENZA Epidemiology (contd)

• 2003-04 Avian flu outbreaks (genetic. distinct
  H5N1)
• S. Korea, Japan, Cambodia, Laos, Vietnam,
  Thailand, Indonesia, China, Malaysia
• As of Oct 4, 2004
• 27 cases and 20 deaths in Vietnam
• 16 cases and 11 deaths in Thailand
• Suspect one person to person transmission in a
  family
• No sustained person to person transmission to
  date
• Concern is for a genetic reassortment allowing
  high transmissibility person to person.

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Whats needed for a pandemic strain?

• Novel virus (little to no immunity)
• Capable of causing disease in humans
• Highly pathogenic / virulent
• Capable of sustained person to person transmission

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INFLUENZA Epidemiology (contd)

• 6 billion chickens and 850 million ducks in SE
  Asia
• China and Thailand account for 15 of the worlds
  poultry shipments
• In many SE Asian countries, 80 of poultry is in
  small backyard farms (poultry, swine, humans,
  etc.)
• Since late 2003, 200 million birds have been
  culled or died
• Economic impact
• could exceed 12 billion (Chinese Academy of
  Social Sciences)
• Marked on individual farmers already at low
  income

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INFLUENZA SURVEILLANCE
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INFLUENZA Surveillance Systems

• First Method Increased deaths
• 122 US Cities Pneumonia and Influenza Mortality
  Surveillance (CDC)

Background and Threshold for Epidemic Diagnosis
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INFLUENZA Surveillance Systems

• Second Method Sentinel Providers
• Office visits for Influenza like Illness
  (Health Departments and CDC)
• Sentinel Provider Offices visits for
  influenza like illnesses -- fever sore throat
  or cough without another identified cause
• 1000 Sentinel Providers nationally (70 in WV)

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WV Sentinel Provider Network Influenza-like
Illness (ILI) Reporting

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INFLUENZA Surveillance Systems

• Third Method Laboratory Surveillance-WV

WV data 2003-04
WV data 2002-03
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INFLUENZA Surveillance Systems

• Third Method Laboratory Surveillance--WHO

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INFLUENZA PREVENTION AND TREATMENT

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INFLUENZA Management (contd)

• Primarily symptomatic, including hydration
• Antivirals Adamantanes
• Amantadine, rimantidine decrease duration of
  symptoms by 50 if initiated within lt 48 hours in
  trials
• Decrease in viral shedding
• Appearance and transmission of resistant virus
• Side effects predominantly CNS type, amantadine
  greater than rimantidine

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INFLUENZA Management (contd)

• Side effects Neuraminidase Inhibitors
• Oseltamivir nausea, vomiting, headache, cough
• Zanamivir not recommended for COPD, asthma
  because of bronchospasm
• No controlled trials comparing neuraminidase
  inhibitors to adamantanes

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CDC Interim Recommendations on use of Antiviral
Medications for the 2004-05 Influenza Season

• TREATMENT
• Any person experiencing a potentially
  life-threatening influenza-related illness
• Any person at high risk for serious complications
  of influenza and who is within the first 2 days
  of illness onset
• Interim Guidelines not intended to guide the use
  of these medications in other situations, such as
  outbreaks of avian influenza.

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CDC Interim Recommendations on use of Antiviral
Medications for the 2004-05 Influenza Season

• PROPHYLAXIS--Antivirals
• Institutional Outbreaks
• Other High Risk Individuals exposed to influenza
• CDC encourages the use of amantadine or
  rimantadine for chemoprophylaxis and use of
  oseltamivir or zanamivir for treatment as
  supplies allow

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INFLUENZA PREVENTION

• VACCINE
• Inactivated Influenza Vaccine
• Live Attenuated Influenza Vaccine
• 2004-05 Vaccine Recommendations
• Future directions

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INFLUENZA PREVENTION (contd)

• INACTIVATED INFLUENZA VACCINE
• First developed in US by Armed
• Services 1940s
• Made of split viruses or viral subunits
  containing hemaglutinin and neuraminidase
• Contain 2 type A viruses and 1 type B virus
• Try to match what will most likely be in
  circulation each season

Source CDC
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INFLUENZA PREVENTION (contd)

• INACTIVATED INFLUENZA VACCINE
• WHO convenes meeting to determine vaccine
  composition (Feb Northern Hemisphere Sept
  Southern)

SourceWHO
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INFLUENZA PREVENTION (contd)

• INACTIVATED INFLUENZA VACCINE
• Strains circulating detected by WHO Global
  Surveillance Network (since 1948)
• Serologic studies to determine antigenicity
• 4-6 month egg based manufacturing process
• 18 Manufacturers worldwide
• 2 licensed in US in 2004

SourceAventis Pasteur
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INFLUENZA PREVENTION (contd)

• LIVE ATTENUATED INFLUENZA VACCINE
• FluMist, produced by MedImmune
• Produced by reassortant gene technology
• Viruses express contemporary influenza vaccine
  antigens
• Administered by
• nasal spray

Source CDC
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INFLUENZA VACCINE 2004-05 SEASON

• Contamination limited to a few lots reported by
  Chiron Corporation (Summer, 2004)
• The UK Regulatory Agency (MHRA) suspended
  Chirons license to manufacture Fluvirin vaccine
  for 3 months (Liverpool facility)
• On October 5, 2004, Chiron informed CDC that none
  of its influenza vaccine (48 million doses)
  would be available for distribution this season

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2004-05 INFLUENZA SEASON (contd)

• Influenza Vaccine Shortage
• Reduction in vaccine supply by about 50
• Available doses in the U.S.
• 58 million doses of inactivated vaccine
• About 3 million doses of Live Attenuated Vaccine

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ESTIMATING VACCINE NEED

• 2002-03 SEASON
• Estimated at risk population 84.9 million
• Other targeted pop 102.9 million
• Total target group 187.8 million
• vaccinated varied widely
• Children with chronic illness 10
• gt65 year olds 66
• Est. 57.6 doses administered
• 2004-05 SEASON
• Target group narrowed to 98.2 million
• Estimate vaccine acceptance rate (5 increase
  demand) 42.8 million

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Priority Groups For Influenza Vaccination,
2004-2005

• Children 6-23 months of age
• Adults gt65 years
• Persons 2-64 years of age with underlying chronic
  medical conditions
• Women who will be pregnant during influenza
  season

MMWR 200453(39)923-4
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Inactivated Influenza VaccineRecommendations

• Persons with the following chronic illnesses
  should be considered for inactivated influenza
  vaccine
• pulmonary (e.g., asthma, COPD)
• cardiovascular (e.g., CHF)
• metabolic (e.g., diabetes)
• renal dysfunction
• hemoglobinopathy
• immunosuppression, including HIV infection

MMWR 200453 (RR-6)1-40
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Priority Groups For Influenza Vaccination,
2004-2005

• Residents of nursing homes and long-term care
  facilities
• Children 6 months-18 years of age on chronic
  aspirin therapy
• Healthcare workers with direct, face-to-face
  patient contact
• Household contacts and out-of-home caregivers of
  children aged lt6 months

MMWR 200453(39)923-4
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Who Should NOT Receive Influenza Vaccine This Year

• Healthy persons 2-64 years of age
• Household contacts of high-risk persons EXCEPT
  children lt6 months of age
• Providers of essential community services
• Foreign travelers
• Students

except those who are in a priority group because
of age or medical condition
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Prevention and Control of Influenza in Healthcare
Facilities

• The most important measure to protect patients
  from influenza in a healthcare setting is
  vaccination of both patients and healthcare
  workers
• In a vaccine shortage situation vaccination of
  HCWs becomes even more critical
• In 2002, only 38 of HCWs were vaccinated!

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Influenza Vaccination of Healthcare Workers

• Reduces influenza-related death among nursing
  home residents
• Reduces overall illness in nursing home residents
  
• Reduces illness and illness-related absenteeism

Reference Improving Influenza Vaccination Rates
in Healthcare Workers. Strategies to Increase
Protection for Workers and Patients. Available at
www.nfid.org
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Influenza Vaccination of Children 2004-05

• Current influenza vaccine not licensed for
  children lt6 months of age
• 2 doses separated by gt1 month recommended for
  children lt9 years who are receiving influenza
  vaccine for the first time
• Children being vaccinated for the first time last
  year who only received 1 dose should receive 1
  dose this year and in subsequent years

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Influenza Vaccination of Children 2004-05

• Do NOT reserve vaccine for second doses for
  children being vaccinated for the first time this
  year
• Children should be vaccinated (first or second
  dose) on a first-come, first-served basis

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Live Attenuated Influenza Vaccine (LAIV)
(FLUMIST) Indications

• Healthy persons 549 years of age
• Household contacts of persons at increased risk
  of complications of influenza
• for 2004-05, just household contacts of those lt6
  months of age
• Health care workers

Persons who do not have medical conditions that
increase their risk of complications of influenza
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Live Attenuated Influenza VaccinePersons Who
Should NOT Be Vaccinated

• Children lt5 years of age
• Persons gt50 years of age
• Persons with underlying medical conditions
• asthma, reactive airways disease or other chronic
  pulmonary condition
• cardiovascular disease
• metabolic diseases (e.g. diabetes)
• renal disease
• hemoglobinopathy (e.g. sickle cell disease)

These persons should receive inactivated
influenza vaccine
57
Live Attenuated Influenza VaccinePersons Who
Should NOT Be Vaccinated

• Pregnant women
• Persons immunosuppressed from disease (including
  HIV) or drugs
• Children or adolescents receiving long-term
  therapy with aspirin or other salicylates
• Severe (anaphylactic) allergy to egg or other
  vaccine components
• History of Guillain-Barre syndrome

These persons should receive inactivated
influenza vaccine
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Live Attenuated Influenza VaccineTransmission of
Vaccine Virus

• Vaccinated children shed vaccine viruses for up
  to 3 weeks (mean, 7.6 days)
• One documented instance of transmission of
  vaccine virus to a contact (in a daycare setting)
• Transmitted virus remained attenuated
• Frequency of shedding among adults unknown

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Use of LAIV Among Healthcare Personnel

• No data regarding transmission from adults
  vaccinated with LAIV to immunosuppressed persons
  (but no evidence of transmission during 2003-2004
  influenza season)
• ACIP recommends that LAIV can be given to
  eligible HCWs except those who may expose
  severely immuno-suppressed persons

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Use of LAIV Among Close Contacts of High Risk
Persons

• Persons who receive LAIV should refrain from
  contact with severely immunosuppressed persons
  for 7 days after vaccination
• Persons who receive LAIV need NOT be excluded
  from visitation of patients who are not severely
  immunosuppressed

MMWR 200453(RR-6)17
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Influenza Prevention (contd)

• INFLUENZA VACCINE FUTURE DIRECTIONS
• Cell culture vaccines (non-egg reliant)
• Injectable and intranasal
• Intradermal administration? (NEJM 11/04)
• Federal guarantees against financial risk?

Source CDC
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Prevention Beyond Vaccine

• Avoid close contact with people who are sick
• Cover Your Cough
• Frequent handwashing
• Avoid touching eyes, nose or mouth
• Antiviral drugs
• Stay home when you are sick!

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Influenza as a Model for Disaster Preparedness

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The 1918 Spanish flu pandemic
National Museum of Health and Medicine, Armed
Forces Institute of Pathology
65
INFLUENZA History

• Epidemics and pandemics
• Most well known pandemic 1918-1919
• 40-50 million deaths worldwide
• Subsequent pandemics
• 1957 Asian flu
• 1968 Hong Kong flu
• 1.5 million deaths
• Economic impact estimated at 32 billion dollars

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Images from the 1918 Influenza Epidemic National
Museum of Heath and Medicine
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Images from the 1918 Influenza Epidemic National
Museum of Heath and Medicine
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Images from the 1918 Influenza Epidemic National
Museum of Heath and Medicine
69
THE NEXT PANDEMIC?

• Potential impact of next pandemic (CDC)
• 2-7.4 million deaths globally
• In high income countries
• 134-233 million outpatient visits
• 1.5-5.2 million hospitalizations
• 25 increase demand for ICU beds, ventilators,
  etc.

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Preparing for Health Disasters

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World Trade Center Attack - September 11,
2001Emergency Response
72
Bioterrorism
Anthrax by MailOct. 2001
Salmonella to alter electionsOR 1984
Ricin -- Feb 2004
Risk of Smallpox?
Pneumonic Plague
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INFLUENZA OR BIOTERRORISM?

• Global travel rapid spread / little
  warning
• Vaccines and antivirals in short supply
• Medical facilities overwhelmed
• Personnel shortages among essential community
  workers (including HCWs)
• Longer impact than many disasters
• Simultaneous impact in many communities
• Disruptions in community infrastructure
  (utilities, transport, etc.)
• Requires an intersector response

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Commonalities

• Good disease Surveillance is critical
• Clinicians must be able to Recognize and Report
  to PH!
• Laboratory Capacity is critical!
• Contingency Planning is key
• Incident Command Structures
• Beds, vents, supplies
• Health Care Personnel
• Epi investigation drives control measures
• Mass vaccination strategies
• Communication to address changing situations
• Mental Health Response
• Coordinated Multidisciplinary Response
• Etc.

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The Benefits of All Hazard PlanningBoth
require

• Developing facility and jurisdictional plans
• Defined command and coordination systems
  (facility and jurisdictional)
• Strengthening Surveillance and Reporting
• Strengthening Laboratory Capacity
• Enhancing Epi Investigation Capacity
• Planning for surge capacitybeds, personnel,
  supplies
• Planning for Mass vaccination / prophylaxis
• Workforce Training in advance and just in
  time.
• Credentialing volunteers
• Interagency and interjurisdictional MOUs
• Building relationships and Exercising plans
  together

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CDC and HRSA Preparedness Funds

• HRSA Hospital Preparedness Program
• Aimed at strengthening capacity of hospitals and
  the health care systems that support them in
  disaster response
• CDC Preparedness and Response Program
• Strengthening public health systems to address
  bioterrorism, infectious disease outbreaks, and
  other public health threats and emergencies

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Health Care System Preparedness Program WV
Projects (HRSA)

• Hospital and other facility bio plan template
  developed
• Regional health care system plan development
• HEICS Training
• Communications equipment
• Linking hospital labs to WVEDSSelectronic
  reporting
• Education and Training
• Isolation and Decontamination Capacity
• Registering and Credentialing Volunteers
• Etc.

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PH Preparedness and Response Program (CDC)WV
Projects

• Agency and jurisdictional planning
• Strategic National Stockpile Receipt and
  Deployment
• Mass vaccination / medication planning
• Building surveillance and epi skills
• BSL 3 Laboratory
• Health Alert Network
• Enhancing Risk Communication Skills
• Workforce Education

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WVU VMC Bioterrorism Continuing Education Grant
(HRSA)

• WV Prepares Project

• 3 online courses
• Terrorism Recognition Reporting
• Multidisciplinary Response
• Acute Care of Patients from WMD Events

www.vmc.wvu.edu/hrsa/
80
Pandemic Preparedness

• Strengthening virus surveillanceto detect novel
  strains and monitor impact
• Research to enhance vaccine production / supply /
  delivery systems
• Enhancing Antiviral Supply in SNS and setting
  priorities for its use
• Strengthening annual vaccination programs
• Assuring an adequate alert system

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Pandemic Preparedness (contd)

• Public Health System Planning SNS, Epi
  protocols, etc.
• Health Care System Planning HEICS, infection
  control, bed / personnel / supplies surge
  capacity, triage sites, alternative sites, etc.
• Building PartnershipsPublic Health, Clinical
  Medicine, Emergency Management, Law enforcement,
  etc.

82
INFLUENZA and DISASTER RESPONSE - SUMMARY

• The changing nature of Influenza virus continues
  to pose a threat. The threat is global.
• Extensive avian influenza activity does spread to
  humans and is now a serious concern.
• Influenza provides a real life and anticipated
  situation for which we must plan. It is not
  unlike bioterrorism scenarios.
• Global surveillance is critical for identifying
  new viruses, detecting outbreaks, tracking
  morbidity and mortality, determining vaccine
  composition, etc.

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INFLUENZA and DISASTER RESPONSE Summary (contd)

• We may not fully prevent illness and death from
  the next flu pandemic, however
• With advance planning (agency, jurisdictional,
  and regional), much can be done to reduce its
  impact.
• Get involved now!

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Further Influenza Resources

• http//www.cdc.gov/flu
• (various materials on flu, training
  opportunities, etc.)
• http//www.wvdhhr.org/Immunizations/
• (fact sheets, press releases, etc.)
• http//www.wvdhhr.org/IDEP/a-z/a-z-influenza.asp
• (WV flu surveillance data and other items of
  interest)

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Resources / Linking into WV Preparedness Efforts

• Regional Health Care System Planning
• Terry Shorr, WVBPH 304-558-1218
• Amy Veazey, WVHA 304-344-9744
• Local Jurisdictional Planning Contact your
  Local Health Department and Office of Emergency
  Services
• WVU/VMC WV Prepares Courses www.vmc.wvu.edu/hrsa
  /