BIRD FLU

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BIRD FLU

• MARIA FIDELIS C.MANALO, MD, MSc Epidemiology
• VICENTE C. MANALO, JR.
• Doctor of Veterinary Medicine
• PHILIPPINES

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Influenza A viruses

• Avian species, particularly waterfowl, are the
  natural hosts
• Influenza viruses bearing each of the 15
  hemagglutinin (H) and nine neuraminidase (N)
  subtypes infect birds and serve as a reservoir
  from which influenza viruses or genes are
  introduced into the human population.

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Influenza A viruses

• Have been found to occur in the last two decades,
  throughout the animal kingdom, mainly in birds,
  notably aquatic ones, in which infection is
  largely intestinal, waterborne, and asymptomatic.
  
• The domestic duck of southern China, raised in
  countless numbers all year round mainly as an
  adjunct to rice farming, is the principal host of
  influenza A viruses.

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Human Transmission of H3N2 Virus

• Pandemic strains are transmitted to humans via
  the domestic pig, which acts as a "mixing vessel"
  for two-way transmission of viruses.
• This provides further support for the hypothesis
  that Southern China is a hypothetical influenza
  epicenter.
• Rural dwellers in the epicenter show serological
  evidence of contact with non-human influenza A
  viruses.

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Influenza pandemics definition

• Global outbreaks of the disease due to viruses
  with novel hemagglutinin genes derived from avian
  influenza viruses, with or without other
  accompanying avian influenza virus genes, when
  the human population lacks protective immunity
  against the new hemagglutinin.

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20th Century Pandemics

• Molecular analysis support the hypothesis that
  all influenza viruses are derived, in part or
  entirely, from influenza viruses found in the
  avian reservoir host, the wild aquatic birds
  (Webster et al, 1992)
• The last two pandemics were caused by hybrid
  viruses, or reassortants, that harbored a
  combination of avian and human viral genes.

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BIRD FLU Definition

• Viral disease affecting respiratory, enteric or
  nervous system of many kinds of poultry and
  birds.
• Most virulent is the acute, generalized disease
  with short course and extremely high mortality.

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Definition

• Used to be called fowl plague but replaced in
  1981 during the International Symposium on AI
  with the term highly virulent influenza virus
  infection.
• First occurred in Italy over a hundred years ago,
  becoming widespread till 1930s, then becoming
  sporadic and localized.

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Avian influenza viruses

• Key contributors to the emergence of human
  influenza pandemics.
• Thought to be limited in their ability to
  directly infect humans until 1997 when an H5N1
  influenza virus was directly transmitted from
  birds in live poultry markets in Hong Kong to
  humans.

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H5N1 Hong Kong Outbreak

• 18 people infected,
  six of whom died
• This avian virus exhibited high virulence in both
  avian and mammalian species
• First documented case where H5 subtype AI was
  directly transmitted to humans causing
  respiratory problems and death

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Human influenza A H5N1 virus related to a highly
pathogenic avian influenza virus.

• BACKGROUND In May, 1997,
  a 3-year-old boy in Hong Kong was
  admitted to the hospital and subsequently died
  from influenza pneumonia, acute respiratory
  distress syndrome, Reye's syndrome, multiorgan
  failure, and disseminated
  intravascular coagulation.

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Human influenza A H5N1 virus related to a highly
pathogenic avian influenza virus.

• An influenza A H5N1 virus was isolated from a
  tracheal aspirate of the boy.
• Preceding this incident, avian influenza
  outbreaks of high mortality were reported from
  three chicken farms in Hong Kong, and the virus
  involved was also found to be of the H5 subtype.

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Human influenza A H5N1 virus related to a highly
pathogenic avian influenza virus.

• METHODS Antigenic and molecular comparison of
  the virus isolated from the boy with one of the
  viruses isolated from outbreaks of avian
  influenza by haemagglutination-inhibition (HI)
  and neuraminidase-inhibition assays and
  nucleotide sequence analysis was done

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• FINDINGS Differences were observed in the
  antigenic reactivities of the viruses by the
  HI assay.
• However, nucleotide sequence analysis of all gene
  segments revealed that the human virus A/Hong
  Kong/156/97 was genetically closely related to
  the avian A/chicken/Hong Kong/258/97.

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• INTERPRETATION Although direct contact between
  the sick child and affected chickens has not been
  established, results suggest transmission of the
  virus from infected chickens to the child without
  another intermediate mammalian host acting as a
  "mixing vessel".
• Class et al.
• Lancet, 1998

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H5N1 Case Series, Nov-Dec 1997

• Out of the 18 cases of human infection, eleven
  had severe infection with symptoms of pneumonia
  and multi-organ failure.
• All severe cases presented with lower respiratory
  infection and lymphopenia and six eventually
  died.
• Case-fatality ratio was high among patients over
  12 years of age (five out
  of nine).

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Case-Control Study of Risk Factors for Avian
Influenza A (H5N1) Disease, Hong Kong, 1997

• A case-control study of 15 of these patients
  hospitalized for influenza A (H5N1) disease was
  conducted using controls matched by age, sex, and
  neighborhood to determine risk factors for
  disease.

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Case-Control Study of Risk Factors for Avian
Influenza A (H5N1) Disease, Hong Kong, 1997

• Exposure to live poultry (by visiting either a
  retail poultry stall or a market selling live
  poultry) in the week before illness began was
  significantly associated with H5N1 disease (64
  of cases vs. 29 of controls, odds ratio, 4.5, P
  .045).

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Case-Control Study of Risk Factors for Avian
Influenza A (H5N1) Disease, Hong Kong, 1997

• By contrast, travel, eating or preparing poultry
  products, recent exposure to persons with
  respiratory illness, including persons with known
  influenza A (H5N1) infection, were not associated
  with H5N1 disease.

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Risk of influenza A (H5N1) infection among health
care workers exposed to patients with influenza A
(H5N1), Hong Kong.

• A retrospective cohort study was
  conducted to compare the prevalence of H5N1
  antibody among health care workers (HCWs) exposed
  to H5N1 case-patients in Hong Kong in 1997 with
  the prevalence among nonexposed HCWs.

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• Information on H5N1 case-patient and poultry
  exposures and blood samples for H5N1-specific
  antibody testing were collected.
• Eight (3.7) of 217 exposed and 2
  (0.7) of 309 nonexposed HCWs were H5N1
  seropositive (P.01).
• The difference remained significant after
  controlling for poultry exposure (P.01).

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Risk of influenza A (H5N1) infection among health
care workers exposed to patients with influenza A
(H5N1), Hong Kong.

• This study presents the first epidemiologic
  evidence that H5N1 viruses were transmitted from
  patients to HCWs.
• Human-to-human transmission of avian influenza
  may increase the chances for the emergence of a
  novel influenza virus with pandemic potential.

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Control Measures to Reduce Human Exposure in Hong
Kong

• Culling of all poultry
• Segregation of water fowls and chicken and
• Introduction of import control measures for
  chickens
• Had successfully controlled the outbreak and
  continuous surveillance of the poultry in Hong
  Kong of H5N1 infection is maintained.

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Lack of Evidence for Human-to-Human Transmission
of Avian Influenza A (H9N2) Viruses in Hong Kong,
China

• Subsequently, another avian virus with the H9N2
  subtype was directly transmitted from birds to
  humans in Hong Kong in April 1999.
• The genes encoding the internal proteins of the
  H9N2 virus are genetically highly related to
  those of the H5N1 virus, suggesting a unique
  property of these gene products.

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Lack of Evidence for Human-to-Human Transmission
of Avian Influenza A (H9N2) Viruses in Hong Kong,
China 1999

• H9N2 viruses were isolated from nasopharyngeal
  aspirate specimens collected from two children
  who were hospitalized with uncomplicated,
  febrile, upper respiratory tract illnesses in
  Hong Kong during March 1999.

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• Four retrospective cohort studies of persons
  exposed to these two H9N2 patients were
  conducted.
• No serologic evidence of H9N2 infection was found
  in family members or health-care workers who had
  close contact with the H9N2-infected children,
  suggesting that these H9N2 viruses were not
  easily transmitted from person to person.
• Timothy M. Uyeki et al
• CDC, USA

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Present scenario

• In 2000-2002, H5N1 avian viruses reappeared in
  the poultry markets of Hong Kong, although they
  have not infected humans.
• Continued circulation of H5N1 and other avian
  viruses in Hong Kong raises the possibility of
  future human influenza outbreaks.

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Laboratory diagnosis of influenza--virology or
serology?

• For early diagnosis of acute influenza virus
  infections, virus detection using rapid
  procedures for virus isolation or antigen
  staining and molecular biological techniques have
  been developed.
• The determination of specific antibodies (IgG,
  IgM) has traditionally been widely used
  diagnostically.

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• Conventional serological diagnosis is possible by
  means of the complement fixation and
  hemagglutination inhibition tests and allows the
  detection of type and subtype-specific
  antibodies, respectively.
• As part of an automated serology,
  immunofluorescence test and enzyme-linked
  immunosorbent assay are the mostly widely
  available methods.

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Detection of influenza a subtypes in
community-based surveillance

• A rapid microtitre cell enzyme immuno assay
  (cell-EIA) was developed for detection in
  nasopharyngeal swabs
• Results reflected the results obtained by
  traditional virus culture within the age
  distribution of samples, clinical symptoms,
  time between date of illness onset and sampling
  of cases.

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Detection of influenza a subtypes in
community-based surveillance

• The cell EIA can also be used to detect different
  influenza A subtypes (H3N2, H1N1, H5N3, H5N1,
  H7N7, and H9N2).
• The cell EIA can thus provide a rapid, efficient,
  inexpensive method for the screening of influenza
  A cases during an outbreak or pandemic situation.

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Laboratory diagnosis of influenza--virology or
serology?

• In comparison, virus detection is clearly
  superior to antibody determination for diagnosis
  of influenza virus infections.
• However, antibody testing may be useful as a
  complementary tool to confirm the diagnosis
  retrospectively.

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Influenza vaccines

• An H5N3 vaccine adjuvanted with microfluidised
  emulsion (MF) 59 stimulated antibody levels that
  complied with the European Union (EU) Committee
  for Proprietary Medicinal Products (CPMP)
  criteria after two half strength doses
  (i.e. 7.5
  micro g haemagglutinin).