AVIAN INFLUENZA

AVIAN INFLUENZA

INTRODUCTION

• Avian Influenza is one of the primary infection disease affecting public health
• The subtypes H5N1of human influenza A viruses cause influenza with high morbidity and mortality
• Avian Influenza (H5N1) has mortality rate > 50% while novel pandemic H1N1(swine Influenza)  has <1%.

PAST INFLUENZA PANDEMICS

1918   

“Spanish flu”
Killed 40-50 million
H1N1

 1997
“Hong Kong”
First Human H5N1 (AVIAN FLU)

HUMAN INFLUENZA PANDEMICS

HIGHLY PATHOGENIC AVIAN INFLUENZA
(HPAI) VIRUS H5N1

Nov 2003 - 2012, 595 cases, from 5 countries, 350 (58.8%), the patient died

In Indonesia between 2005 and december 2012, total 187 cases, with 155 (82.8%) deaths

CUMULATIVE NUMBER OF CONFIRMED HUMAN CASES FOR AVIAN INFLUENZA REPORTED TO WHO, 2003-2012

THE SPREAD OF AVIAN INFLUENZA
 IN THE EASTERN HEMISPHERE

Cumulative Number Of Confirmed Human Cases

For Avian Influenza, In Indonesia, 2003-2011

H5N1 avian influenza in humans in Indonesia was first reported in 2005. Highest number of cases reported in 2006 as many as 55 cases. Trunk or blue bars indicate positive cases of H5N1 and red bars show the number of deaths. Throughout 2005 to 2012 cases tended to decline from year to year.

RNA VIRUS

INFLUENZA VIRUS

•         pathogenic variants

•         persistent infections

•         Emerging viruses

•         Antigenic variation

•         Zoonotic disease

CLASSIFICATION

INFLUENZA SUBGROUPS

VIRUS STRUCTURE

•    The viral particles
•  The central core

        •         -ss RNA

        •          matrix proteins

        •          2 envelope glycoproteins

        •          haemagglutinin (H or HA)

   •          receptor binding

   •          uncoating

       •          neuraminidase (N or NA)

  •          release

  •          receptor binding

The central core contains the viral RNA genome and other viral proteins that package and protect this RNA

GENOME SEGMENTS OF AVIAN INFLUENZA VIRUS

EKSTERNAL GENE

4: Hemagglutinin (HA)           

6: Neuraminidase (NA)

INTERNAL GENE

7: M1/M2 Matrix proteins

5: Nucleoprotein (NP)

1,2,3: Polymerase machinery  (PB-2, PB-1, PA)

8: Non-structural proteins

    ( NS1, NEP)

HEMAGGLUTININ

• Structure: trimer of “lollipops” containing the  sialic acid receptor site
• Function: Sialic acid receptor sites bind to host cell’s glycoproteins allows virus to adhere to endothelial cells in the respiratory tract and allowing for infection to occur
•  Responsible for pathogenicity of the virus

NEURAMINIDASE

•         Structure: Box-shaped tetramer  with stalk that anchors it to the   membrane

•         Function: cleaves terminal sialic acid residues from cell surface     receptors the influenza virus.

•         release of virions from infected   cells and removes sialic acid from newly synthesized  HA and NA molecules

•         Determinant of disease severity

INLUENZA VIRUS LIFE CYCLE

 THE VIRUS NOMENCLATURE

Classification of the human influenza viruses

HA AND HOST SPECIFICITY

DISTRIBUTION OF INFLUENZA VIRUS RECEPTORS  

In Human trachea, SA α2,6-Gal receptor was abudantly expressed on ciliated and non ciliated epithelial cells and SA α2,3-Gal receptor was only sparsely detected on non- ciliated cell.

On human non ciliated cuboid bronchial epithelial cells SA α2,3-Gal was readily detected.

PATHOGENESIS

A person becomes infected when they inhale microdroplets containing the virus.

Upper and lower respiratory tract epithelial cells have sialic acid molecules to which the HA binds.

As the virus causes the cells to die, inflammation occurs – a cough reflex results thereby spreading the virus again.

Additional “flu-like” symptoms (sneezing, fever, chills, muscle aches, headaches, fatigue) occur as a result of interferon production triggered by the presence of dsRNA during viral replication.

More severe infections (i.e. pneumonia) are sometimes associated with Influenza because of the increased susceptibility to other infections as a result of a damaged airway.

RESERVOIRS OF INFLUENZA  A

TRANSMISSION AVIAN INFLUENZA TO HUMANS

 

ANTIGENIC DRIFT/SHIFT

1. Antigenic Drift results from the error prone transcriptase that copies the vRNA
2. Antigenic Shift major change due to  gene reassortment and results in an influenza A virus with new HA and/or NA proteins

ANTIGENIC SHIFT

Pigs Serve As Mixing Vessels For Reassortants

ANTIGENIC DRIFT

spontaneous mutations in surface antigens Ü selection ofvariants in a partially immune population

 WHERE H5N1 CAME FROM?

TRANSMISSION

•         Directly from bird and contaminated environment

•         Contaminated faces from poultry

•         Spread between human has not proven

Risk Factors Transmission of Avian Influenza (%) in Indonesis from 2005 to 2011