Avian Influenza H5n1 Virus Ppt

Avian Influenza A (H5N1) viruses among birds continues to

human

cause disease with high mortality and to pose the threat of a pandemic

Patients with confirmed Influenza A (H5N1) illness

Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. N Engl J Med 2008;358:261-273

Pandemic  According to the

World Health Organization (WHO), a pandemic can start when three conditions have been met:  the emergence of a disease new to the population.  the agent infects humans, causing serious illness.  the agent spreads easily and sustainably among

humans.

 The Influenza of 1918

Epizootic  In epizoology, an epizootic (from Greek epi- upon + zoion animal) is a disease that appears as; new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience (i.e. a sharp elevation in the incidence rate).

 High population density is a major

Published online 6 january, 2008



The Journal of Immunology E-



pub (www.jimmunol.org)

Published online 6 January 2008 Nature Biotechnology

Influenza virus particles mostly spherical/ovoid, 80-120nm diameter  The outer surface of the

particle consists of a lipid envelope-which project two types of

 glycoprotein

spikes

:

 haemagglutinin (HA), a

Paul Digard, Dept of Pathology, University of Cambridge

135Å trimer  neuraminidase (NA), a 60Å tetramer

Host Range

Species barrier between birds and human:

Replication

PB2, PB1 and PA

Ns1

Hemaggluti nin

Neuraminid ase

M 2

Hemagglutinin Determine species specificity for avian α 2,3 –linked or human α 2,6 –linked sialic acid Residues

Epidemiology of Human Infections  Incidence and Demographic Characteristics  Transmission  Handling of dead and sick poultry during the week before the onset of illness –  Consuming raw or uncooked poultry

 Incubation Period 2-5 days If happened human –to -human transmission it could be 3-5 days or 8-9 days.

Incidence and Demographic Characteristics  Influenza A (H5N1) disease in human is very rare.  Number of confirmed

cases of H5N1 virus infection is

th

, 2007.

cooler months.



Increases in human cases of H5N1 have been observed during



Infection rate and case fatality is more prevalent among younger individual ( compare to older individual

340 as of Dec 14

age 40 or below

( 50 yrs of age or older)

)

How age can be a factor for the ability of the virus to infect and cause fatality ?

Whether preexisting immunity and exposure could contribute ?

Most Probably Yes  Healthy Human Subjects Have CD4 T Cells Directed Against  H5N1 Influenza Virus

Michelle Roti,* Junbao Yang,* DeAnna Berger,* Laurie Huston,* Eddie A. James,*and William W. Kwok2*†

Human immune system is naïve to the newly emerged H5N1 virus Most adults immune system are acquainted with H1N1 and H3N2 viruses through vaccination or infection Adult born before 1968 have likely been exposed to H2N2 virus CD4+T cells generated in response to H1N1, H3N2 and H2N2 influenza A viruses also recognize H5N1 epitopesImmunological memory

Immunological memory - After infection (antigen) is cleared majority of effector cells die by apoptosis (programmed cell death). - However, a significant number persist as memory cells – immunological memory. - Immunological memory ensures rapid response on a second encounter with a pathogen, and thereby usually

Pathogenesis Viral Factors Viral Replication •Bronchiolar and alveolar cells, upper and lower respiratory track •Viral RNA persists in the respiratory track upto 3 months

Pathological Findings

•Diffuse alveolar damage, inflammatory cells and apoptosis in alveolar cells

Host Responses

•Increased level of imflammatory cytokines IFN-γ, TNF-α, IL-5,IL-13.

H5N1 binds to

α2,3-linked sialic acid receptor on avian cells

Ta ce rg lls et

L ung L

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H5N1 virus can acquire mutations that permit binding to both α 2,3-linked sialic acid receptor and α2,6-linked sialic acid receptor Changes in multiple viral genes are probably required to generate a potentially pandemic

Now the question arises how H5N1 can cause infection in human ?

 A

switch in specificity of H5N1

hemagglutinin (HA) from avian like

(α2-3-linked sialyated glycans ) to human- like (α2-6 sialyated glycans) receptors is believed to be associated with their adaptation to infect human

Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin :

 a characteristic structural topology—and not the a2-6 linkage itself—enables specific binding of HA to a2-6 sialylated glycans  recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans.

Why H5N1 viruses have not yet gained a foothold in the human

biochemical, analytical and data mining approach demonstrates

 An integrated

that from the human-adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long α2-6 sialylated glycans with this

Clinical features Severe pneumonia/ Acute respiratory distress syndrome Other syndromes (listed in the Laboratory diagnostic

•

•

•

Initial diagnosis by Real –time PCR ( from nasal swab, throat swab) Hemagglitination-inhibition assay/microneutralization assay— labor –intensive and require BSL3 facility.

Treatment  Antiviral agents  Oseltamivir  Zanamivir

 Amantadine ion  Rimantadine channels

Synthetic sialic acid analogues

Block membrane

 Combined Oseltamivir and amantadine

Immune suppression -adverse effect of steroid

VIRAL LATENCY /OPPORTUNISTIC INFECTION

Prevention

Increased Virus threat

 increasing open trade in food

/ animal products / pets  faster human transportation in the shrinking world  species jump

Viruses listed as threat Human deficiency virus (from Africa) From chimpanzee or other non human primates West Nile Virus (WNV) (from the middle east) From birds via mosquitoes H5N1 avian influenza virus (from east Asia ) From birds directly • SARS( Severe acute respiratory syndrome virus )(from Guangdong