BIRD FLU

MARIA FIDELIS C.MANALO, MD,

MSc Epidemiology
VICENTE C. MANALO, JR.
Doctor of Veterinary Medicine
PHILIPPINES
 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.
 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.
 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.
 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.
 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.
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.
 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.
 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.
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
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.
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.
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
 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.
 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
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).
 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.
 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).
 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.
 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.
 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).
 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.
 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
 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.
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.
 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
 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.
 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.
 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.
 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.
 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.
 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.
 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).