Title: BIRD FLU
1BIRD FLU
- MARIA FIDELIS C.MANALO, MD, MSc Epidemiology
- VICENTE C. MANALO, JR.
- Doctor of Veterinary Medicine
- PHILIPPINES
2Influenza 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.
3Influenza 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.
4Human 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.
5Influenza 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.
620th 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.
7BIRD 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.
8Definition
- 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.
9Avian 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.
10H5N1 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
11Human 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.
12Human 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.
13Human 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
14- 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.
15- 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
16H5N1 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).
17Case-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.
18Case-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).
19Case-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.
20Risk 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. -
21- 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).
22Risk 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.
23Control 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.
24Lack 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.
25Lack 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.
26- 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
27Present 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.
28Laboratory 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.
29- 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.
30Detection 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.
31Detection 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.
32Laboratory 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.
33Influenza 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).