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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  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

  16. 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).

  17. 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.

  18. 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).

  19. 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.

  20. 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.

  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).

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  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

  27. 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.

  28. 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.

  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.

  30. 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.

  31. 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.

  32. 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.

  33. 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).