BIRD FLU MARIA FIDELIS C.MANALO, MD, MSc Epidemiology VICENTE C. MANALO, JR. Doctor of Veterinary...

BIRD FLUBIRD FLU

MARIA FIDELIS C.MANALO, MD,MARIA FIDELIS C.MANALO, MD, MSc EpidemiologyMSc Epidemiology

VICENTE C. MANALO, JR.VICENTE C. MANALO, JR.Doctor of Veterinary MedicineDoctor of Veterinary Medicine

PHILIPPINESPHILIPPINES

Influenza A virusesInfluenza A viruses Avian species, particularly Avian species, particularly

waterfowl, are the natural hosts waterfowl, are the natural hosts Influenza viruses bearing each of Influenza viruses bearing each of

the 15 hemagglutinin (H) and the 15 hemagglutinin (H) and nine neuraminidase (N) subtypes nine neuraminidase (N) subtypes infect birds and serve as a infect birds and serve as a reservoir from which influenza reservoir from which influenza viruses or genes are introduced viruses or genes are introduced into the human population.into the human population.

Influenza A virusesInfluenza A viruses Have been found to occur in the last two Have been found to occur in the last two

decades, throughout the animal kingdom, decades, throughout the animal kingdom, mainly in birds, notably aquatic ones, in mainly in birds, notably aquatic ones, in which infection is largely intestinal, which infection is largely intestinal, waterborne, and asymptomatic. waterborne, and asymptomatic.

The domestic duck of southern China, The domestic duck of southern China, raised in countless numbers all year round raised in countless numbers all year round mainly as an adjunct to rice farming, is the mainly as an adjunct to rice farming, is the principal host of influenza A viruses.principal host of influenza A viruses.

Human Transmission of Human Transmission of H3N2 VirusH3N2 Virus

Pandemic strains are transmitted to Pandemic strains are transmitted to humans via the domestic pig, which humans via the domestic pig, which acts as a "mixing vessel" for two-way acts as a "mixing vessel" for two-way transmission of viruses. transmission of viruses.

This provides further support for the This provides further support for the hypothesis that Southern China is a hypothesis that Southern China is a hypothetical influenza epicenter. hypothetical influenza epicenter.

Rural dwellers in the epicenter show Rural dwellers in the epicenter show serological evidence of contact with serological evidence of contact with non-human influenza A viruses.non-human influenza A viruses.

Influenza pandemics: Influenza pandemics: definitiondefinition

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

2020thth Century Pandemics Century Pandemics Molecular analysis support the Molecular analysis support the

hypothesis that all influenza viruses hypothesis that all influenza viruses are derived, in part or entirely, from are derived, in part or entirely, from influenza viruses found in the avian influenza viruses found in the avian reservoir host, the wild aquatic birds reservoir host, the wild aquatic birds (Webster et al, 1992)(Webster et al, 1992)

The last two pandemics were caused The last two pandemics were caused by hybrid viruses, or reassortants, by hybrid viruses, or reassortants, that harbored a combination of avian that harbored a combination of avian and human viral genes. and human viral genes.

BIRD FLU: DefinitionBIRD FLU: Definition Viral disease affecting Viral disease affecting

respiratory, enteric or nervous respiratory, enteric or nervous system of many kinds of poultry system of many kinds of poultry and birds.and birds.

Most virulent is the acute, Most virulent is the acute, generalized disease with short generalized disease with short course and extremely high course and extremely high mortality.mortality.

DefinitionDefinition Used to be called ‘fowl plague’ but Used to be called ‘fowl plague’ but

replaced in 1981 during the replaced in 1981 during the International Symposium on AI International Symposium on AI with the term ‘highly virulent’ with the term ‘highly virulent’ influenza virus infection.influenza virus infection.

First occurred in Italy over a First occurred in Italy over a hundred years ago, becoming hundred years ago, becoming widespread till 1930s, then widespread till 1930s, then becoming sporadic and localized.becoming sporadic and localized.

Avian influenza virusesAvian influenza viruses Key contributors to the emergence Key contributors to the emergence

of human influenza pandemics. of human influenza pandemics. Thought to be limited in their ability Thought to be limited in their ability

to directly infect humans until 1997 to directly infect humans until 1997 when an H5N1 influenza virus was when an H5N1 influenza virus was directly transmitted from birds in directly transmitted from birds in live poultry markets in Hong Kong to live poultry markets in Hong Kong to humans.humans.

H5N1 Hong Kong OutbreakH5N1 Hong Kong Outbreak 18 people infected, 18 people infected,

six of whom died six of whom died This avian virus exhibited high This avian virus exhibited high

virulence in both avian and mammalian virulence in both avian and mammalian speciesspecies

First documented case where H5 First documented case where H5 subtype AI was directly transmitted to subtype AI was directly transmitted to humans causing respiratory problems humans causing respiratory problems and deathand death

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

avian influenza virus.avian influenza virus. BACKGROUND: In May, 1997, BACKGROUND: In May, 1997,

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


avian influenza virus.avian influenza virus.

An influenza A H5N1 virus was An influenza A H5N1 virus was isolated from a tracheal aspirate isolated from a tracheal aspirate of the boy. of the boy.

Preceding this incident, avian Preceding this incident, avian influenza outbreaks of high influenza outbreaks of high mortality were reported from three mortality were reported from three chicken farms in Hong Kong, and chicken farms in Hong Kong, and the virus involved was also found the virus involved was also found to be of the H5 subtype.to be of the H5 subtype.


avian influenza virus.avian influenza virus. METHODS: Antigenic and molecular METHODS: Antigenic and molecular

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

FINDINGS: Differences were observed in FINDINGS: Differences were observed in the antigenic reactivities of the viruses the antigenic reactivities of the viruses by the HI assay. by the HI assay.

However, nucleotide sequence analysis However, nucleotide sequence analysis of all gene segments revealed that the of all gene segments revealed that the human virus A/Hong Kong/156/97 was human virus A/Hong Kong/156/97 was genetically closely related to the avian genetically closely related to the avian A/chicken/Hong Kong/258/97. A/chicken/Hong Kong/258/97.

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

Class Class et al. et al.

Lancet,Lancet, 1998 1998

H5N1 Case Series, Nov-Dec 1997H5N1 Case Series, Nov-Dec 1997

Out of the 18 cases of human Out of the 18 cases of human infection, eleven had severe infection infection, eleven had severe infection with symptoms of pneumonia and with symptoms of pneumonia and multi-organ failure. multi-organ failure.

All severe cases presented with lower All severe cases presented with lower respiratory infection and lymphopenia respiratory infection and lymphopenia and six eventually died.and six eventually died.

Case-fatality ratio was high among Case-fatality ratio was high among patients over 12 years of age patients over 12 years of age (five out of nine). (five out of nine).

Case-Control Study of Risk Case-Control Study of Risk Factors for Avian Influenza A Factors for Avian Influenza A

(H5N1) Disease, Hong Kong, 1997 (H5N1) Disease, Hong Kong, 1997

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



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



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

Risk of influenza A (H5N1) Risk of influenza A (H5N1) infection among health care infection among health care

workers exposed to patients with workers exposed to patients with influenza A (H5N1), Hong Kong.influenza A (H5N1), Hong Kong.

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

Information on H5N1 case-patient and Information on H5N1 case-patient and poultry exposures and blood samples poultry exposures and blood samples for H5N1-specific antibody testing for H5N1-specific antibody testing were collected. were collected.

Eight (3.7%) of 217 exposed and Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). were H5N1 seropositive (P=.01).

The difference remained significant The difference remained significant after controlling for poultry exposure after controlling for poultry exposure (P=.01).(P=.01).

Risk of influenza A (H5N1) Risk of influenza A (H5N1) infection among health care infection among health care

workers exposed to patients with workers exposed to patients with influenza A (H5N1), Hong Kong.influenza A (H5N1), Hong Kong.

This study presents the first This study presents the first epidemiologic evidence that epidemiologic evidence that H5N1 viruses were transmitted H5N1 viruses were transmitted from patients to HCWs.from patients to HCWs.

Human-to-human transmission Human-to-human transmission of avian influenza may increase of avian influenza may increase the chances for the emergence the chances for the emergence of a novel influenza virus with of a novel influenza virus with pandemic potential.pandemic potential.

Control Measures to Reduce Control Measures to Reduce Human Exposure in Hong KongHuman Exposure in Hong Kong Culling of all poultryCulling of all poultry Segregation of water fowls and chicken Segregation of water fowls and chicken

and and Introduction of import control measures Introduction of import control measures

for chickens for chickens Had successfully controlled the outbreak Had successfully controlled the outbreak

and continuous surveillance of the and continuous surveillance of the poultry in Hong Kong of H5N1 infection poultry in Hong Kong of H5N1 infection is maintained.is maintained.

Lack of Evidence for Human-Lack of Evidence for Human-to-Human Transmission of to-Human Transmission of Avian Influenza A (H9N2) Avian Influenza A (H9N2)

Viruses in Hong Kong, ChinaViruses in Hong Kong, China Subsequently, another avian virus Subsequently, another avian virus

with the H9N2 subtype was directly with the H9N2 subtype was directly transmitted from birds to humans in transmitted from birds to humans in Hong Kong in April 1999. Hong Kong in April 1999.

The genes encoding the internal The genes encoding the internal proteins of the H9N2 virus are proteins of the H9N2 virus are genetically highly related to those of genetically highly related to those of the H5N1 virus, suggesting a unique the H5N1 virus, suggesting a unique property of these gene products.property of these gene products.

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

Hong Kong, China 1999 Hong Kong, China 1999

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

Four Four retrospective cohort studiesretrospective cohort studies of of persons exposed to these two H9N2 persons exposed to these two H9N2 patients were conducted. patients were conducted.

No serologic evidence of H9N2 infection No serologic evidence of H9N2 infection was found in family members or health-was found in family members or health-care workers who had close contact with care workers who had close contact with the H9N2-infected children, suggesting the H9N2-infected children, suggesting that these H9N2 viruses were not easily that these H9N2 viruses were not easily transmitted from person to person. transmitted from person to person.

Timothy M. Uyeki Timothy M. Uyeki et alet al CDC, USACDC, USA

Present scenarioPresent scenario In 2000-2002, H5N1 avian viruses In 2000-2002, H5N1 avian viruses

reappeared in the poultry markets reappeared in the poultry markets of Hong Kong, although they have of Hong Kong, although they have not infected humans.not infected humans.

Continued circulation of H5N1 and Continued circulation of H5N1 and other avian viruses in Hong Kong other avian viruses in Hong Kong raises the possibility of future raises the possibility of future human influenza outbreaks. human influenza outbreaks.

Laboratory diagnosis of Laboratory diagnosis of influenza--virology or serology?influenza--virology or serology?

For early diagnosis of acute influenza For early diagnosis of acute influenza virus infections, virus detection using virus infections, virus detection using rapid procedures for virus isolation or rapid procedures for virus isolation or antigen staining and molecular antigen staining and molecular biological techniques have been biological techniques have been developed. developed.

The determination of specific The determination of specific antibodies (IgG, IgM) has traditionally antibodies (IgG, IgM) has traditionally been widely used diagnostically.been widely used diagnostically.

Conventional serological diagnosis is Conventional serological diagnosis is possible by means of the complement possible by means of the complement fixation and hemagglutination inhibition fixation and hemagglutination inhibition tests and allows the detection of type and tests and allows the detection of type and subtype-specific antibodies, respectively.subtype-specific antibodies, respectively.

As part of an automated serology, As part of an automated serology, immunofluorescence test and enzyme-immunofluorescence test and enzyme-linked immunosorbent assay are the linked immunosorbent assay are the mostly widely available methods.mostly widely available methods.

Detection of influenza a Detection of influenza a subtypes in community-based subtypes in community-based

surveillancesurveillance A rapid microtitre cell enzyme immuno A rapid microtitre cell enzyme immuno

assay (cell-EIA) was developed for assay (cell-EIA) was developed for detection in nasopharyngeal swabs detection in nasopharyngeal swabs

Results reflected the results obtained Results reflected the results obtained by traditional virus culture within the by traditional virus culture within the age distribution of samples, clinical age distribution of samples, clinical symptoms, & time between date of symptoms, & time between date of illness onset and sampling of cases.illness onset and sampling of cases.

Detection of influenza a Detection of influenza a subtypes in community-based subtypes in community-based

surveillancesurveillance The cell EIA can also be used to The cell EIA can also be used to

detect different influenza A subtypes detect different influenza A subtypes (H3N2, H1N1, H5N3, H5N1, H7N7, and (H3N2, H1N1, H5N3, H5N1, H7N7, and H9N2).H9N2).

The cell EIA can thus provide a rapid, The cell EIA can thus provide a rapid, efficient, inexpensive method for the efficient, inexpensive method for the screening of influenza A cases during screening of influenza A cases during an outbreak or pandemic situation.an outbreak or pandemic situation.

In comparison, virus detection is In comparison, virus detection is clearly superior to antibody clearly superior to antibody determination for diagnosis of determination for diagnosis of influenza virus infections. influenza virus infections.

However, antibody testing may be However, antibody testing may be useful as a complementary tool to useful as a complementary tool to confirm the diagnosis retrospectively.confirm the diagnosis retrospectively.

Laboratory diagnosis of Laboratory diagnosis of influenza--virology or influenza--virology or

serology?serology?

Influenza vaccines Influenza vaccines An H5N3 vaccine adjuvanted with An H5N3 vaccine adjuvanted with

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

BIRD FLU MARIA FIDELIS C.MANALO, MD, MSc Epidemiology VICENTE C. MANALO, JR. Doctor of Veterinary...

Documents

Transcript of BIRD FLU MARIA FIDELIS C.MANALO, MD, MSc Epidemiology VICENTE C. MANALO, JR. Doctor of Veterinary...