Influenza: Nothing to sneeze at

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Influenza Nothing to sneeze at

• Laura Banks, DVM, MPH
• Mike Richards, MD, MPA
• University of New Mexico Health Sciences Center
• Center for Disaster Medicine
• http//hsc.unm.edu/cdm

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Basic Description of Influenza

• Orthomyxoviridae Virus
• Single-stranded RNA
• Three Types of Influenza Virus
• A Primary form for human infections, also a
  zoonotic disease
• B Sporadic outbreaks, rare
• C Milder form

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Influenza Structure
Hemagglutinin
Lipid membrane
M1 protein
M2
Neuraminidase
RNP Polymerase Nucleoprotein vRNA
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Influenza A Typing

• Influenza A is classified into subtypes based on
  the presence of the genes for these proteins
• Hemagglutinin protein 15 subtypes
• Neuraminidase proteins 9 subtypes
• Example Subtype H3N2 hemagglutinin 3 and
  neuraminidase 2.
• The most common prevailing human influenza A
  subtypes Influenza A (H1N1) and Influenza A
  (H3N2)

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Pathophysiology

• Infection occurs by respiratory secretions
• Virus invades airway and respiratory tract cells
• cellular dysfunction and degeneration occur
• viral replication and release of viral progeny
• Systemic symptoms from inflammatory mediators,
  similar to other viruses.
• Incubation period
• 1 to 5 days from exposure to onset of symptoms
• Communicability
• 1-2 days before to 4-5 days after onset of
  symptoms
• Children shed for several weeks

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Signs and Symptoms

• Abrupt high fever 38-40º C (100-104º F)
• Chills, shivering, myalgias, headache, malaise,
  and anorexia
• Conjuntivitis, pharyngitis, and dry cough

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Physical Findings

• Mild illness ? Severely Ill, toxic
• Fever, Tachycardia
• Pharyngitis/ inflammation
• Eyes red and watery Nasal discharge is usually
  absent
• Skin may be warm-to-hot, signs of mild volume
  depletion with dry skin.
• Pulmonary with active cough, wheezing, and/or
  rhonchi.
• Secondary infection Strep. pneum, H. influenzae
• DX - Screen with rapid test for Influenza A (OP
  swab)
• - Labs use RT-PCR (best method), culture
  and
• seroconversion

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Influenza Epidemiology U.S.

• Infects over 30 million people
• Over 150,000 people are hospitalized annually
• Influenza and its complications are the sixth
  leading cause of death - Killing 20,000-40,000
  people a year
• Mortality/Morbidity increased for
• Extremes of age
• Pre-existing illnesses
• Third trimester pregnancy

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Influenza Epidemiology U.S.

• 60 of those with influenza are misdiagnosed and
  begun on antibiotics
• Flu season" increases emergency department
  wait-times
• Business productivity drastically drops due to
  flu sick time
• Total costs exceed 10,000,000,000 in the U.S.

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Influenza Vaccination

• If the vaccine works so great then why not just
  get it once and put an end to the worry?

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A Changing Virus

• Antigenic Drift (A and B)
• Same H and N combination, but newer virus strains
  appear by point mutation of individual amino
  acids on the H and N molecules
• Circulating antibodies may no longer work
• Need to get flu shot update
• Antigenic Shift  (A only)
• Re-assortment or recombination of H and N
  molecules abrupt and major change
• Likely the result of reassortment of genes within
  animals infected by multiple subtypes, followed
  by transmission to humans
• Most people will have little or no protection

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Influenza vaccinations

• Vaccine includes three components two A strains
  and the B strain.
• Changing nature of the virus (drift and shift)
  requires new vaccines.
• New emergence of an old strain may necessitate
  vaccinations in younger patients no immunologic
  memory

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2005-2006 Season

• A/New Caledonia/20/99 (H1N1)
• A/California/7/04 (H3N2)
• B/Shanghai/361/02

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• Pandemic Influenza

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Definition

• A pandemic is a worldwide epidemic of a disease. 
  
• An Influenza pandemic requires that
• A new subtype of flu virus forms due to antigenic
  shift
• The new virus causes illness in people
• The disease can be spread easily from person to
  person

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Epidemics and Pandemics of the 20th Century
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1918-19, Spanish flu

• Influenza A(H1N1)
• Caused the highest number of known flu deaths
• more than 500,000 people died in the United
  States
• 20-50 million people may have died worldwide
• Many died within the first few days after
  infection
• Almost half of the people who died were young,
  healthy adults

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Spanish Flu Facts

• Spread faster than any disease in history
• It took little more than a week to sweep across
  America
• Three months to sweep around the world

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Photo National Archives
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Spanish Flu Facts

• World War 1, which had just ended, took 9 million
  lives this epidemic would quadruple that.
• Despite the name "Spanish", it probably began in
  America

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Source Stanford University
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Spanish Flu Facts

• Killed more people in less time than all of the
  great plagues of history.
• In Alaska, 60 of the Eskimo population was wiped
  out.
• Islands in the South Pacific lost 20 of their
  populations, primarily adults.

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Spanish Flu in New Mexico

• The City of Albuquerque Board of Health spent 25
  of its entire budget for 1918 on a line item
  described simply as Spanish Flu
• A quote from the Albuquerque newspaper included
  the ghost of fear walked everywhere
• The New Mexico Department of Health was created
  in 1919 in response to the Spanish Flu pandemic

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1957-58, Asian flu

• Influenza A(H2N2)
• Caused approximately 70,000 deaths in the United
  States
• First identified in late February, 1957 in China
  and spread to the United States by June, 1957

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1968-69, Hong Kong flu

• Influenza A (H3N2)
• Caused approximately 34,000 deaths in the United
  States. 
• First detected in Hong Kong in early 1968 and
  spread to the U.S. later that year.
• A(H3N2) viruses still circulate today.

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The Avian Connection

• Wild waterfowl are the natural reservoir for all
  subtypes of Influenza A, but rarely get sick
• Domestic fowl do get sick
• H5, H7 and H9 infections in humans have been
  confirmed with close contact of birds
• Pathogenicity in birds in not clearly related to
  pathogenicity in humans
• H5 and H7 viruses are highly pathogenic to the
  embryonated chicken eggs that are used to grow
  vaccine

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But wait

• There has been no sustained person-to-person
  transmission of H5N1 avian influenza.
• There are no historical data, either in 1918 or
  in any other pandemic, for establishing that a
  pandemic precurser virus caused a highly
  pathogenic outbreak in poultry and no highly
  pathogenic avian influenza virus has ever been
  know to cause a major human epidemic.
• Taubenberger and Morens, 2006

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The Next Pandemic

• Many experts consider influenza pandemics to be
  inevitable.
• There may be very little warning.
• Outbreaks are expected to occur simultaneously
  throughout the U.S., preventing shifts in
  resources.
• The effect on individual communities will be
  relatively prolonged compared to most other
  natural disasters.

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What to Expect?

• Vaccines and antiviral agents -- will likely be
  in short supply
• Health-care workers and other first responders
  will likely be at even higher risk - further
  impeding the care of victims.
• Significant shortages of personnel military
  personnel, police, fire, utility workers, and
  transportation workers, just to name a few.

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Next pandemic estimates of impact

• Attack rate ranging from 15 to 35
• Typical mortality 0.1
• US Deaths 89,000 - 207,000
• US Hospitalizations 314,000 - 733,000
• NM Deaths 1,500 - 2,000
• NM Hospitalizations 9,000 (4,000
  beds)

Source Meltzer et al. EID 19995659-71
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Modeling the Impact at UNMH
Admits1,320 Deaths259
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Pandemic Vaccine

• In development
• Plan advocates cell-based technology (rather than
  hens eggs)
• Developing capacity to produce 300 million
  courses in 6 months
• Current production 60-100 million doses per year
• 2 doses one month apart may be necessary to
  ensure immunity

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Influenza control antiviral medications

• Uses
• Prophylaxis needs to be continued for duration
  of epidemic
• Treatment dose, duration, efficacy all unknown
  at this point for new strains

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Influenza control antiviral medications

• Issues
• Limited supply-20 million courses for US
  projected for end 2006
• Need for prioritization
• among risk groups
• prophylaxis versus treatment
• Emergence of resistance in H5N1
• Limited data coming from less than a dozen cases
  in Asia

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World Health Organization

• Recognizes the limitations of pharmacological
  therapy during a pandemic
• Recommends national and community measures to
  control spread
• Isolation and quarantine
• Traveler warnings
• Social distancing measures
• Personal protection and hygiene

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• Questions?
• LBanks_at_salud.unm.edu
• 505-272-6240