Influenza, novel H1N1 (swine flu), H5N1 (avian influenza) and Occupational Infection

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Influenza, novel H1N1 (swine flu), H5N1 (avian
influenza) and Occupational Infection

• Stephen Born MD, MPH
• University of California, San Francisco
• Division of Occupational and Environmental
  Medicine

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Influenza

• An acute viral disease of the respiratory tract
  characterized by fever, headache, myalgia,
  prostration, coryza, sore throat and cough.
  Cough is often severe and protracted, but other
  manifestations are usually self-limited, with
  recovery in 2-7 days.
• From Control of Communicable Diseases Manual 17th
  edition

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Influenza
IS IT A COLD OR THE FLU? (Adapted from the CDC)
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nH1N1 Symptoms

• Broad clinical spectrum from mild upper
  respiratory tract illness with or without fever
  to acute respiratory distress syndrome (ARDS)
• Some patients present with gastro-intestinal
  symptoms of vomiting or diarrhea
• Many with severe illness have underlying diseases
  such as asthma. Obstructive airways disease,
  diabetes, immunodeficinecy cardiovascular
  disease, renal failure, malignancy and morbid
  obesity. Also, pregnant women, especially 3rd
  trimester (13 fold increased risk of
  hospitalization).
• See PMID 19790188

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Influenza A Nomenclature
Influenza type
Hemagglutinin subtype
Year of isolation
A/Sydney/5/97 (H3N2)
Geographic source
Isolate number
Neuraminidase subtype
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What name for the current Pandemic Influenza?

• The World Health Organization has struggled
  mightily to avoid the ethnic monikers given the
  Spanish, Hong Kong and Asian flus, instructing
  its representatives to shift from swine flu to
  H1N1 to A (H1N1) S-O.I.V. (the last four
  initials stand for swine-origin influenza
  virus) to, recently, Pandemic (H1N1) 2009.
• http//www.nytimes.com/2009/05/01/health/01name.ht
  ml
• IOM refers to nH1N1
• Aka H1N1v

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What Influenza? What Name?

• A/California/7/2009 (H1N1) virus
• According to WHO update 65 dated 11 September
  2009
• Pandemic (H1N1) 2009 influenza virus continues to
  be the predominant circulating virus of
  influenza, both in the northern and southern
  hemisphere. Allviruses analyzed to date have
  been antigenically and genetically similar to
  A/California/7/2009-like pandemic H1N1 virus

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nH1N1

• On August 24, the Presidents Council of Advisors
  on Science and Technology said that H1N1 could
  infect up to half the U.S. population, result in
  the hospitalization of 1.8 million people, and
  cause 30,000 to 90,000 deaths in addition to the
  30,000 to 40,000 deaths from a typical flu
  season.

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Influenza

• Hemagglutinin (HA) spike
• Governs virus binding and entry into cells
• 15 Subtypes, H1 to H15
• In pandemics, a novel subtype arises
• Only H1, H2, and H3 have circulated in humans in
  the past century
• All 15 HA subtypes are found in free-flying birds
• WHO Avian influenza assessing the pandemic
  threat

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Influenza

• Neuraminidase (NA) governs the release of the
  newly formed virus from infected cells
• There are 9 subtypes, N1 to N9
• Immunity to NA subtype reduces the amount of
  virus released from a cell, resulting in less
  severe disease
• All 9 types found in free-flying birds
• Only N1 N2 in stable human lineages
• WHO Avian influenza assessing the pandemic threat

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Influenza

• Influenza A
• Virus mutates rapidly
• Infects pigs, horses, sea mammals and birds
• Large number of subtypes/huge pool of genetic
  diversity
• Only Influenza A known to cause pandemics
• Many genetic replication errors due to lack of a
  proof reading mechanism
• Constant small changes result in antigenic drift
• WHO Avian influenza assessing the pandemic
  threat

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Influenza

• Influenza B and C
• Essentially human viruses
• Influenza B causes sporadic outbreaks of severe
  respiratory disease
• Nomenclature
• B/Shanghai/361/2002
• Also prone to mutation
• Influenza C causes no or very mild symptoms
• Few mutations
• WHO Avian influenza assessing the pandemic threat

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Influenza

• Antigenic Changes
• Drift
• Same subtype, minor changes often involving point
  mutations
• Shift
• New subtype, major changes, may involve genetic
  recombination between different viruses
• Likely responsible for pandemics
• Pigs often thought of as the crucible for genetic
  recombination since they may be infected with
  both human and avian types of viruses

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Improvements on Nature

• Concentrated animal feeding operations (CSFOs)
• During the later stages of the 1918 pandemic,
  farmers noted that their pigs were getting sick
  and called the disease hog flu.
• Generally milder than human disease
• One 2007 study showed that CAFO workers were 50
  times more likely and their spouses were 25 times
  more likely to have elevated H1N1 antibodies

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Avian Influenza

• Avian influenza viruses are excreted in feces and
  secretions
• Wild birds contaminate ponds/lakes
• Domestic foul become infected
• Chicken coops often above pig pens or pigs may be
  fed bird carcasses
• China is often thought of as a major area of risk
  for genetic recombination since pigs, chickens,
  ducks and humans often live in close proximity
• WHO Avian influenza assessing the pandemic
  threat

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Influenza

• Instances of Avian Influenza in Humans
• N5H1, Hong Kong 1997
• 18 people hospitalized/6 died
• 1.5 million chickens killed to stop outbreak
• H9N2, China and Hong Kong 1999
• 2 children infected
• H7N2, Virginia 2002
• One person had serologic evidence of infection
• H5N1 China and Hong Kong 2003
• Ongoing worldwide
• Many, many other sporadic examples

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Influenza

• Since 2003 62 countries/territories have
  experienced outbreaks of HPAI H5N1
• FAO AIDE News May 2009
• Jumped species to tigers in Thailand with 147 out
  of 418 captive tigers developing severe symptoms
  after being fed chicken carcasses in October 2004
• WHO Avian influenza assessing the pandemic threat

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Influenza

• H5N1
• Inefficient human to human transmission

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HPAI H5N1

• H5N1 affects the young, in the prime of life,
  similar to the 1918 pandemic strain
• H5N1 causes viral pneumonia, like the 1918
  strain, without evidence of bacterial pneumonia
• Why has H5N1 not shown sustained human to human
  transmission?
• Is it only a matter of time?
• Is there something that is preventing
  reassortment?
• NEJM January 27, 2005 Editorial

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Mortality Associated with Influenza Pandemics and
Selected Seasonal Epidemic Events, 1918-2009
Morens D et al. N Engl J Med 2009361225-229
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Genetic Relationships among Human and Relevant
Swine Influenza Viruses, 1918-2009
Morens D et al. N Engl J Med 2009361225-229
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Influenza

• Three prerequisites for a pandemic
• A novel virus subtype
• The general population will have little or no
  immunity
• The virus must be able to replicate in humans and
  cause serious disease
• The new virus must be efficiently transmitted
  from one human to another
• The first two conditions have been met by the
  H5N1 avian strain but have been met by nH1N1
• WHO Avian influenza assessing the pandemic
  threat

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Influenza

• The 1918 Spanish Flu pandemic (H1N1) killed
  about 40-50 million people worldwide in less than
  one year, with 500,000 US deaths2.5 estimated
  case fatality rate
• The young and healthy were especially affected
• First wave simultaneously in Europe and USA in
  March 1918Spring and Summer
• Second wave in Augustten fold increase in
  fatality rate
• Some reports of being healthy in the morning,
  dead by night
• The total military deaths in WW1 were 8.3 million
  over 4 years
• WHO Avian influenza assessing the pandemic
  threat

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Pandemic Influenza

• 1957-1958 H2N2 Asian Flu caused 70,000 US
  deaths
• 1968-1969 H3N2 Hong Kong Flu caused 34,000 US
  deaths
• Relatively mild, only 11 years after the previous
  pandemic with the same N2 subtype which may have
  conferred some protection
• One constant feature A rapid surge in cases
  with exponential increases in a matter of weeks
• A severe pathogenic pandemic influenza is likely
  to overwhelm ED and hospital bed capacity
• WHO Avian influenza assessing the pandemic
  threat

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Influenza

• Vaccine development
• Usually produced in fertilized chicken eggs
• (H5N1 kills chicken embryos)
• Modified seed viruses are in development using
  recombinant genetic technology to remove lethal
  genes
• Process of producing vaccine using this
  technology takes monthspandemic basically over
  when vaccine was available in quantity in 1957
  and 1968
• A few companies are developing cell culture
  production techniques
• WHO Avian influenza assessing the pandemic
  threat

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Seasonal Influenza Vaccine

• The vaccines to be used in the 2009-2010
  influenza season in the U.S. contain the
  following
• an A/Brisbane/59/2007 (H1N1)-like virus
• an A/Brisbane/10/2007 (H3N2)-like virus
• a B/Brisbane/60/2008-like virus.
• A/Brisbane/59/2007 is a current vaccine virus
  A/South Dakota/6/2007 (an A/Brisbane/59/2007-like
  virus) is a current vaccine virus used in live
  attenuated vaccines.A/Brisbane/10/2007 and
  A/Uruguay/716/2007 (an A/Brisbane/10/2007-like
  virus) are current vaccine viruses.
• http//www.fda.gov/BiologicsBloodVaccines/Guidance
  ComplianceRegulatoryInformation/Post-MarketActivit
  ies/LotReleases/ucm162050.htm

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nH1N1 Vaccine

• Two recent studies of vaccines derived from the
  A/California/7/2009 (H1N1) virus
• A single 15 microgram dose of the 2009 H1N1
  vaccine was immunogenic in adults, with mild to
  moderate vaccine-associated reactions. PMID
  19745216
• A single 7.5 microgram dose of the
  MF59-adjuvanted vaccine was effective. PMID
  19745215

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Live Attenuated Influenza Vaccine

• Aka FluMist
• Derived from a live influenza A and B virus
  strains modified by cold adaptation creating a
  Master Donor Virus
• Cold adapted
• Temperature Sensitive
• Attenuated
• The MDV is updated annually with hemagglutinin
  (HA) and neuraminidase (NA) genes from
  contemporary flu viruses
• See PMID 19453395

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LAIV

• Replicates primarily in the ciliated epithelial
  cells of the nasopharyngeal mucosa to induce
  immune responses.
• Does not replicate well in warmer temperatures
  found in the lower airways and lung
• In adults, studied in ages 18-64. Studies
  evaluated the effectiveness in preventing any
  febrile illness. Post hoc analysis in adults
  50-64 years old failed to show effectiveness. As
  a result, not approved for use in adults gt50 in
  the United States.
• See PMID 19453395

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LAIV

• Cross protection among antigenically distinct
  viruses within the same subtype may be induced by
  LAIV
• See PMID 19768402
• LAIV may work better in populations that have not
  received multiple influenza vaccinations
• See PMID 19464536

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Influenza

• Antiviral Drugs
• M2 inhibitors including amantadine and
  rimantadine are ineffective against H5N1 and
  nH1N1, but work against seasonal H1N1
• Neuraminidase inhibitors include oseltamivir and
  zanamivir are effective against nH1N1 with
  sporadic resistance
• Better safety profile
• More expensive
• Negligible capacity for surge production
• Resistance does develop (summer camps)

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Influenza

• Short incubation-1 to 3 days
• Individuals infectious before symptoms develop
• Transmitted by person-to-person contact, fomites
  and droplets gt10 microns
• Probable transmission by droplet nuclei, lt5
  microns (airborne)
• Disease may not present with full clinical
  symptoms, but can be spread by the affected person

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DHS Office of Biotechnology Activities Notice of
Proposed Changes September 22, 2009

• Designation of human H2N2 viruses that circulated
  from 1957-8, the fully reconstructed 1918-1919
  H1N1 and HPAI H5N1 as Risk Group 3 agents.
• Requires enhanced biosafety practices, including
  uses of powered air purifying respiratiors and
  other PPE
• Recombinant work using any genes/segments from
  the above strains will require BSL 3 enhanced
  containment
• Federal Register/Voll 74, No. 182/Tuesday
  September 22, 2009/Notices

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ACIP Recommends Five Groups as Priority Targets
for H1N1 Vaccination  

• The CDCs Advisory Committee on Immunization
  Practices (ACIP) has recommended which U.S.
  population groups should be targeted to receive
  H1N1 influenza vaccine when it becomes available.
  People over 65 have the lowest priority.
• The 15-member ACIP says these five groups should
  be targeted
• pregnant women
• household contacts of infants under 6 months
• healthcare and emergency-services workers
• young people between 6 months and 24 years of
  age
• and nonelderly adults with underlying risk
  conditions, such as diabetes and chronic lung
  disease.

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J. Cohen Science 325, 1328-1329 (2009)
Published by AAAS
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CDC Recommended Respiratory Protection

• Occupational (non-health care)
• No novel H1N1 in community Facemask/respirator
  not recommendedFacemask
• Novel H1N1 in community Facemask/respirator not
  recommended but could be considered under certain
  circumstances
• Occupational (health care)
• Caring for persons with known, probable or
  suspected novel H1N1 or influenza-like illness
  Respirator.
• Use respirator and consider temporary
  reassignment for employees at high risk.
• http//www.cdc.gov/h1n1flu/masks.htm

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PUSHBACK!

• Much disagreement with CDC and OSHA guidelines
• Who needs a respirator when surgical masks are
  cheaper and are thought by some to be equally
  effective against droplet spread?
• Examples CCSF DPH and SFGH ID

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Institute of Medicine Report 9/1/09

• (1) Healthcare workers who are in close contact
  with individuals with nH1N1 or ILI should use fit
  tested N95 respirators
• (2) Increase research on Influenza transmission
  and personal respiratory protection
• Investigate relative importance of aerosol vs
  airborne transmission
• See http//www.nap.edu/catalog/12748.html

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Influenza Transmission changes with Humidity and
Temperature

• Cold and Dry conditions favor in the guinea pig
  host model
• PMID 17953482 PMCID PMC2034399
• Same PI hypothesizes that transmission of
  influenza virus in temperate zones is
  predominantly by aerosol, in the tropics by
  contact
• Also hypothesize that current summertime
  transmission in North America is by contact.

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I had a little bird, Its name was Enza. I
opened the window, And in-flu-enza.
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Indications for Hand Hygiene

• When hands are visibly dirty, contaminated, or
  soiled, wash with non-antimicrobial or
  antimicrobial soap and water.
• If hands are not visibly soiled, use an
  alcohol-based handrub for routinely
  decontaminating hands.

Guideline for Hand Hygiene in Health-care
Settings. MMWR 2002 vol. 51, no. RR-16.
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Efficacy of Hand Hygiene Preparations in Killing
Bacteria
Better
Good
Best
Antimicrobial soap
Plain Soap
Alcohol-based handrub
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Influenza

• Past pandemics have typically hit world
  populations like a flash flood. They have
  started abruptly and explosively, swept through
  populations, and left considerable damage in
  their wake. They could not be stopped but peaked
  rapidly and then subsided almost as abruptly as
  they began. The emergence of human cases of
  avian influenza A H5N1 virus infection in Asia is
  an unprecedented warning
• NEJM January 27, 2005 Editorial

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J. Cohen Science 325, 1328-1329 (2009)
Published by AAAS
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Bottom Line Influenza Mortality

• Each year 36,000 US citizens die from seasonal
  influenza which has generally has a mortality
  rate of less than .2
• This year we can expect many more deaths because
  many more people will be infected although the
  mortality rate is less than that of typical
  seasonal influenza

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Table. Model input parameters and outcome
estimates
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Flu Deaths

• The former model uses a high projected mortality
  rate and estimates that the need for mechanically
  assisted ventilation may be increased by 33
  above US baseline in the upcoming influenza
  season
• See RRN_at_ncbi.nlm.nih.gov RRNID RRN1009.1

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Emergence of Influenza A (H1N1) Viruses from
Birds and Swine into Humans
Zimmer S and Burke D. N Engl J Med
2009361279-285
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Acknowledgements and References

• References as noted on each slide
• WHO and CDC Websites especially useful
• CDC H1N1 Website http//www.cdc.gov/h1n1flu/
• California DHS for the color influenza
  slides--available on line
• http//www.dhs.ca.gov/ps/cdic/cdcb/pds/cpe/Documen
  ts/09020420Handouts.ppt
• Unofficial blog for the latest news
  www.promedmial.org
• Photos from 1918 http//nmhm.washingtondc.museum/c
  ollections/archives/agalleries/1918flu/1918flu.htm
  l
• For CAFO references Environmental Health
  Perspectives September 2009
• Check out Emerging Infectious Diseases Journal
  (EID)

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