1. Will it be just a scare … or a scar on human history? Bird flu

2. It has become the headlines of news channels It’s circulating largely among bird flocks in Asia … Thailand on Monday 7/11/05 reported its 20 th human victim since 2003 … China reports sixth case in this year … It’s bird flu …that’s spreading through ! High mortality rate : 62% human fatal cases WHO

3. “A pandemic of bird flu” Health experts fear that the avian flu virus could mutate and acquire the ability to infect large numbers of people... Should that happen, without immediate and effective interventions to contain it … the Global Impact could be incalculable

4.  Influenza (Flu) is a contagious disease, caused by RNA virus  First identified in 1930’s. There are 3 major types of influenza: Type A, B, and C  Influenza A infects both mammals and birds and can cause epidemic as well as pandemic  Influenza B and C infects only humans  Symptoms: cough, fever, sore throat, muscle aches, conjunctivitis, pneumonia FLU

5.  Caused by a subtype of the type A influenza virus  First identified in Italy in 1900 and was thought not to be transmissible to humans  The virus is divided into subtypes based on 2 surface proteins Hem agglutinin (HA ; 15) Neuraminidase (NA ; 9)  In birds, type A influenza has two forms: Highly Pathogenic Avian Influenza (HPAI) Low Pathogenic Avian Influenza (LPAI) BIRD / AVIAN FLU

6.  Migratory wild birds are a natural reservoir of avian influenza viruses  Domestic poultry can be infected by wild aquatic birds, including migratory birds which fly long distances  Birds are susceptible to all subtypes of A, while the subtypes currently circulating in humans are H1N1, H1N2, H3N2

7. TRANSMISSION Farm to Farm Bird droppings Contaminated dust, soils,equipment Vehicles, feed, cages or clothing Mechanical vectors Country to Country Bird trade or migration of migratory birds infected with the virus Can be passed bird → bird, or bird → human when virus is inhaled, as it is an air-borne disease WHO

8. Hong Kong 1997, H5N1 HK, China 1999, H9N2 Netherlands 2003, H7N7 Hong Kong 2003, H5N1 Vietnam & Thailand 2004, H5N1 AVIAN INFLUENZA : BIRDS TO HUMANS Migratory water birds Domestic birds Humans

9. HOW FLU VIRUSES CHANGE Type A viruses undergo changes in their surface antigens or proteins  Minor changes - antigenic drift  Major changes - antigenic shift WHO

10. ANTIGENIC DRIFT  Small changes/ mutations that occurs in circulating subtypes  Acquisition of new strains of the same subtype  New variants result in seasonal flu each winter  Some years are worse than others – partly related to degree of ‘drift’ WHO

11. ANTIGENIC SHIFT  Emergence of completely new subtype  Occurs due to “genetic exchange” or “reassortment”  Can occur when an animal becomes infected with human and avian flu viruses at the same time  Animal within which this genetic exchange takes place is known as “mixing vessel” WHO

12. REASSORTMENT : Pigs New subtype influenza

13. REASSORTMENT : Humans New subtype influenza

14. CONSEQUENCES : ANTIGENIC SHIFT  Produces a new virus capable of causing a pandemic in humans  Population will have little or no immunity to new virus: - all or most people will not previously have had infection due to it - will not have been vaccinated against it  Lack of immunity allows virus to spread more rapidly and more widely than “ordinary” flu viruses WHO

15. Circulating influenza strains and pandemics in 20 th century 19201940196019802000 H1N1 1918: “Spanish Flu” 20-40 million deaths WHO H2N2 1957: “Asian Flu” 1 million deaths H3N2 1968: “Hong Kong Flu” 1 million deaths

16. H5N1 : WHY SUCH CONCERN ?  Highly pathogenic strain  Unique capacity to jump the species barrier, causing severe illness with high mortality  Can exchange genes with human influenza virus, making a completely new subtype  If new virus contains sufficient human genes, transmission directly from one person to another is possible  Humans would have little or no immunity nor would the existing vaccine be effective  Unlike influenza viruses we are more familiar within which respiratory symptoms dominate, H5N1 replicates in a wide range of cell types  This results in severe disseminated disease affecting multiple organs and causing high mortality WHO

17. Opportunities for virus emergence and spread  Global population in 18th century was <1 billion, vs 6 billion today  Human crowding has increased  Modern pig and poultry production create conditions for mass animal influenza outbreaks  Proximity of humans and animals in many markets creates potential for virus recombination  Intercontinental travel is in hours rather than months and in millions rather than hundreds

18. WHO IS AT RISK?  Everyone is at risk  Certain groups may be at greater risk of serious illness than others  Until the virus starts circulating, it is not known for sure who is at most risk

19. MANAGEMENT Vaccine Social measures Antiviral Medicines Adamantanes Amantadine Rimantadine Neuraminidase inhibitors Oseltamavir (Tamiflu) Zanamavir

20. Fusion with host cell Attachment to host cell receptor – sialic acids Virus Replicates its genetic material inside host cell Viral progeny Attached to host cell receptor-sialic acids Releases the attached progeny; removing sialic acid LIFE CYCLE OF INFLUENZA H spike N spike M 2 protein NEJM 2005 NEURAMINIDASE INHIBITORS Prevent the virus from infecting new cell

21. NEURAMINIDASE vs ADAMANTANES  Newer, more potent class of antiviral  Associated with less toxicity  Less likely to promote resistance  Effective against all subtypes of type A  Have great potential for diminishing the effects of influenza infection  Older class of antiviral  Associated with several toxic effects  Leads to rapid development of resistance; including few cases of H5N1  Resistant strains are easily transmissible to susceptible contacts NEJM 2005; 353: 1363-73

22. Bird Flu : H5N1 Here’s what we don’t know at the moment  If H5N1 Influenza A will make the transition from rare and sporadic bird → human transmissibility, to full-fledged human → human transmissibility  If it does, whether it will retain the virulence seen in the human cases thus far  If these things happen, whether an avian influenza pandemic will be this year, next year or never Here’s what we know  All the ingredients are in the soup  If it happens, we aren’t ready