Serendipity down on the farm

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Serendipity down on the farm
JOAN ROBINSON MD STOLLERY CHILDRENS
HOSPTIAL EDMONTON, ALBERTA JUNE 2007
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• 7-month old boy from a communal farm admitted to
  hospital Sept 2006 with 3-day history of fever,
  rhinitis, and cough
• No ill contacts
• Communal farm has horses, cows, swine, sheep,
  dogs, cats, turkeys, geese, ducks, and chickens
• Term infant admitted for 21 days at 5 weeks of
  age with respiratory syncytial virus (RSV) and
  ventilated 6 days

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• Afebrile, HR 120/min, RR 56/min, 02 saturation
  85 on room air
• Diffuse wheeze
• CXR normal
• Admitted with diagnosis of bronchiolitis (common
  problem in this age group but a bit unexpected in
  September most commonly from RSV)
• Discharged well 2 days later
• Brother developed URI symptoms the day the index
  case was admitted to hospital but was never seen
  by a health care worker

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• DFA positive for influenza A
• Culture later confirmed this
• Isolate sent to NML in Winnipeg as no influenza
  identified in northern Alberta for months
• H3N2 very closely related to A/Swine/Ontario/33853
  /2005 (swine strain isolated from a farm worker
  in the only previously recognized case of human
  infection with swine influenza in Canada)
• Our virus has now been designated A/Canada/1158/06

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Can we prove the isolate came from the child? Can
we prove the child had infection and not just
colonization?

• HI titre to our swine isolate 132 in both
  parents, 1256 in index case and 19-month-old
  sibling who developed respiratory symptoms during
  his admission (serology negative in Ontario case)
• All had undetectable titres to A/NewCaledonia/20/9
  9(H1N1) and A/Wisconsin/67/05 (H3N2)

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So could this be the beginning of the next
influenza pandemic?
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Avian influenza hits Disneyland
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(No Transcript)
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• Hemagglutinin binds to sialic acid on target
  cells to let virus into cells (with different
  receptors in humans vs. birds) must be cleaved
  by a protease to be activated, and more virulent
  strains have hemagglutinins that are susceptible
  to more proteases
• Virus multiples in the cell and then binds to
  sialic acid again on the way out
• Neuraminidase cleaves the bond and lets the virus
  go free to infect other cells

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• Avian influenza has one of 15 hemagglutinin
  (H1-H15) and 9 neuramindase types
• (N1-N9) while human disease up until recently
  was always H1-3, N1-2 (possibly N8 in 1800s)
• Shifting is when a whole new H or N type appears
  on the scene (resulting in a pandemic if it is an
  H type) while drifting is the minor changes in H
  or N types that occur every year or two

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Does swine influenza have the potential to cause
human pandemics?

• All influenza A pandemics of the 20th century
  resulted from adaptation of avian strains to
  allow for human-to-human transmission (1918) or
  reassortment of avian and human strains (1957,
  1968)
• Avian and human strains preferentially bind to
  different sialic acid-galactose receptors (2,3
  versus 2,6 linkage) but swine contain both types
  of receptors (and have been shown to be infected
  with human strains) so would be the perfect
  mixing vessel

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So other than in the case I just presented, what
is the evidence humans have been infected with
swine influenza?

• Great excitement occurred in January 1976 when 5
  army recruits at Fort Dix,NJ developed
  influenza-like illness (ILI) and had swine H1N1
  isolated one died
• In retrospect, another 8 recruits who had been
  seem with ILI had HI titre of / 120 to same
  strain
• An estimated 250 people at Fort Dix were
  seropositive with no history of an ILI
• None had swine contact!

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• Resulted in a massive campaign to immunize as
  many American and Canadian adults as possible
  against swine flu
• After 45 MILLION doses, campaign halted Dec 1976
  when increase of cases of Guillain Barre noted in
  immunized adults

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• Another 4 cases of human infection with H1N1
  swine strains documented prior to the Fort Dix
  incident and another 29 cases since (Myers KP et
  al. Clin Infect Dis 2007441084-8)
• Human infection with swine H3N2 documented in
  Netherlands in 1993 (n2), Switzerland in 1999,
  Ontario in 2005 and then in our case
• No swine contact in 28 of the 50 previous cases
• Mainly previously well patients (12 children, 38
  adults)
• Full spectrum of ILI with 6 deaths

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• Therefore, it is clear that swine influenza
  causes human disease, with cases like ours likely
  being the tip of the iceberg, with most never
  being recognized as most influenza isolates are
  not even sub-typed, let alone identified as a
  specific strain.
• Seems possible swine influenza could cause a
  pandemic if a mutation occurred that resulted in
  more efficient person-to-person spread ( a higher
  basic reproductive rate or Ro)

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Why are we starting to see H3N2 cases in humans?

• swine in North America had almost exclusively
  H1N1 strains until 1998, but now often have H3N2
  strains, with these strains not being recognized
  in Canada until 2005 also found in turkeys in
  Canada
• Our strain and other recent H3N2s are triple
  reassortant strains with genetic material from
  human (hemagglutinin, neuraminidase, and RNA
  polymerase PB1), swine (nucleoprotein, matrix,
  and nonstructural genes), and avian (RNA
  polymerase PA and PB2) strains

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Back to our case, what was the evidence for swine
influenza in the pigs currently on the farm?
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• Last documented influenza one year prior, but
  breeding animals come from a herd in Manitoba
  with recent H3N2 swine influenza
• Nasal swabs on 10 grower pigs negative for
  influenza
• Serology drawn on 10 grower-finisher pigs all
  negative for H1N1 but 4 had antibodies to H3N2
  and one of these had antibodies to
  A/Canada/1158/06
• Autopsies on 5 well pigs showed subacute
  bronchointerstitial pneumonia but no definite
  findings of recent influenza

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So where did our babys virus come from?
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• Based on the literature, it is not surprising
  that a baby with no swine contact developed swine
  influenza with the source presumably being
  another person, either via direct spread or via
  fomites
• No one else on the farm was reported to have a
  recent influenza-like illness, but the question
  was How many other people on the farm had been
  infected with swine influenza?

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• Ethics approval obtained
• Written informed consent obtained
• Serology for our strain of swine influenza and
  the human H3N2 and H1N1 strains from 2005-6 were
  performed on as many residents of the farm as
  possible on a sunny December morning
• Age, time spent in swine barn, and history of
  influenza-like illness recorded

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Results of study

• 54 of the 90 farm residents were tested (includes
  the testing of the family that was already
  mentioned)
• 4 of the 7 household contacts of index case were
  seropositive for swine influenza
• 16 other households had one or more members in
  the study
• 3 children seropositive in one household (father
  worked in swine barn and was not tested and
  mother was seronegative) and one child in another
  (father and one sibling negative)
• 20 other adults and 19 other children from 14
  other households all seronegative, including 3
  teens who worked in the swine barns

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Results of study

• Only 2 of the 54 subjects were seropositive for
  human influenza (H3N2 in one of the subjects who
  was seropositive for swine influenza and H1N1 in
  a subject seronegative for swine influenza)
• Only 2 of the subjects described an
  influenza-like illness in the preceding year,
  including a 3-yr-old who was seropositive for
  swine influenza (not admitted to hospital and not
  tested for influenza when ill)

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CONCLUSIONS

• Swine influenza strains can infect humans and can
  cause severe disease
• Unrecognized cases of human infection with swine
  influenza occur in Canada
• Person-to-person spread does occur, but to date
  the basic reproductive rate (Ro) has been too low
  to initiate a major epidemic
• Surveillance for ILI in swine workers may allow
  for early detection of a strain with an increased
  Ro