Avian influenza is an age old disease but haunting in a big way decade after decade due to it ability to renew its artillery and amunations through continuous interactions with fellow viruses. Interaction, collaboration and exchange always yield.

1. Epidemiology of H5N1 infections in
India: Trends of disease, spatial and
temporal distribution
Dr. Gazanfar Abass
Division of Veterinary Public Health
Bhoj R Singh
Division of Epidemiology
IVRI, Izatnagar-243 122, India

2. Avian Influenza (Fowl Plague)
• E. Centanni and E. Savonuzzi ( 1901) , discovered
flu agent as filterable.
• W. Schäfer in Germany (1955) identified influenza
A virus.
• All influenza A virus subtypes identified to date
have also been isolated from birds. (Palese, et al.,
2006)
• The belonged to Family---- Orthomyxoviridae
• (-) ssRNA, enveloped virus
• Segmented (8) genome
• Possess spikes of HA (trimer) =18subtypes & NA
(Tetramer) = 11 subtypes (Tong et al., 2013)
• HA:NA= 4-5:1
• Multiply in nucleus
HA
PB1
PB2
PA
NP
NA
MA
NS
M2
Hemagglutinin
Neuraminidase
M1
•H17 was isolated from fruit bats.
•H18N11 was discovered in a Peruvian bat.
(Tong et al., 2013)

3. Classification of Influenza virus
Orthomyxoviridae
Influenzavirus A Influenzavirus B Influenzavirus C
MAN
H1N1
H2N2
H3N2
H5N1
H7N7
H7N9
H9N2
PIG
H1N1
H1N2
H3N1
H3N2
H5N1
H3N3
H7N7
H7N9
H9N2
H3N8
H4N6
H5N2
HORSE
H7N7
H3N8
WILD WATERFOWL
(Natural Host)
H 1-16
N 1-9
CHICKEN
H 1-7, 9-11
N 1-4, 6-9
FERRET
H5N1
H1N1
H3N2
WHALE
H1N3
H13N2
H13N9

4. Hosts of Influenza A HA and NA Subtypes
H15, H16
H14
H13
H12
H11
H10
H3
H2
H1
H9
H8
H7
H6
H5
H4
N9
N8
N7
N6
N5
N3
N4
N2
N1

5. Major Types of Avian Influenza type A
HPAI
• Derived from LPAI
• Mortality– Very High(can reach
100%)
• Small genetic pool
• Actually cause the Fowl Plaque
• Zoonotically important
• 18 severe human influenza cases in
Hong Kong in 1997
(Kawaoka et al., 1989)
• Can be activated both intracellularly &
extracellularly
LPAI
• Wild aquatic birds are- natural hosts of all
LPAI viruses
• Mortality—Low
• Large genetic pool .
• Zoonotically less important
• Most of influenza A viruses have the so-
called LPAI phenotype for poultry, cause
mild infection in poultry except H9N2
(Palese et al., 2006)
• Require extracellular activation

6. Viral Replication
CAP SNATCHING

7. Epidemiological Triad of Fowl Plague

8. Determinants Associated with Agent, Host, Environment
Determinants Associated Reference
Agent •HA & NA- majorly determine antiginicity. Lamb et al., 2007
Katz et al., 2008
Peiris et al., 2009
•Antigenic drift & antigenic shift
•Segmented genome
Katz et al., 2008
Peiris et al., 2009
Neumann et al.,
2009
•Difference of 8 amino acids between a pair of viruses isolated from
same patient
Taronna et al., 2004
Host •All known influenza viruses are perpetuated in aquatic birds and have
wide host range
Webster et al., 1992
Fouchier et al., 2005
Peiris et al., 2009
•Virus subtypes have receptor specificity
-alpha 2-3= Avian
-alpha 2-6=Humans
-both alpha 2-3 & alpha 2-6=Pigs
Wang et al., 2009
Environme
nt
•Influenza virus are highly resilient in the environment Galwankar et al.,
2009
• Temperate- low temperature & low humidity Wang et al., 2009
The introduction of virulent strain in a susceptible population spreads widely regardless of the season
Stephanson et al., 2002

9. H5N1 (Hong Kong-1997) gene
Sequencing Outcome
Three peculiar characteristics have been found
H5N1- Outcome of Triple re-assortment of swine viruses
(H1N1,H3N2,H1N2).
1. The sequence PQGERRRKKR/G- Multiple basic amino acid at
cleavage site of Haemagglutinin.
2. Virulence attributed to E627K substitution in PB2 gene.
3. Deletion of 20 amino acids in NA is associated with high
virulence.
(Masato et al., 2001)

10. Human pandemic of Type A Influenza virus is potentially just a few mutations away
Peraz et al., 2009

11. International Scenario of Fowl Plague
Outbreaks
S.
No.
No. Of
Outbreaks
Location Year Comments
1 1 Scotland 1959 1.5 million birds were destroyed
2 4 Australia 1976,1985,
1992,1994
Last case reported in 2013
3 1 Ireland 1983 0.27 million Ducks were slaughtered
4 3 USA 1983-84 17 million birds were destroyed
5 1 Hong Kong 1997 18 documented human H5N1 infections
with 6 fatalities were identified in
conjunction with outbreaks of H5N1
disease among domestic poultry
(Snacken et al.,
1999)
6 1 Vietnam 2003-4 forced killing of nearly 1.2 million
poultry.15 human cases were also
recorded.
(Li et al., 2004)

14. Disease outbreak map (H5N1)-June 2008

15. Cumulative confirmed human cases for
avian influenza A(H5N1) WHO, 2003-15

16. Cumulative confirmed human cases for
avian influenza A (H5N1) WHO, 2003-15
282
24
34
20
25
22
42
468
48
62
32
39
52
143
0 50 100 150 200 250 300 350 400 450 500
2003-09
2010
2011
2012
2013
2014
2015
Total Dead
Total Infected

17. State wise Avian influenza reports in India
State where Avian
influenza was report

18. Indian Scenario
State Dated Comments References
Maharashtr
a
18 Feb.
2006
•Reported FIRST case of bird flu
•Nandurbar Slaughter House in West Maharashtra
•1500 poultry birds reported Positive.
•253000 poultry birds & 587,000 eggs were destroyed.
•Nagarajan et al.,
2006
•Tosh et al., 2007
•Murugkar et al.,
2008
•Pranav et al., 2013
West
Bengal 2008-
11
•Reported 12 outbreaks.
•13 districts reported the cases of H5N1.
•Cause attributed to high poultry density, moist cold
climate, mismanagement.
Chakrabarti et al.,
2009
OIE, 2011
Tripura 2008-
12
•Reported 6 outbreaks
•Cause attributed to – Poor hygienic conditions at
poultry farms, lack of adequate surveillance
OIE, 2012
Assam 2008-
11
•Reported 3 outbreaks.
•Cause attributed to – Fluctuating Temperature, Poor
hygienic conditions at poultry farms, lack of adequate
surveillance.
OIE, 2011
Sikkim 2009 •High poultry density followed by a moist cold climate
has led to the spread of the virus.
OIE, 2009
Orissa 2012- •Reported 5 outbreaks. OIE, 2015

19. Indian Scenario…continued
State Dated Comments References
Jharkhand 2012 •500 crows died
•NIV confirmed it as new strain , resembling to Vietnam strain,
of Avian flu.
OIE, 2012
Bihar 2013 •Cause attributed to – Fluctuating Temperature, Poor hygienic
conditions at poultry farms, lack of adequate surveillance
OIE, 2008
Chhattisgarh August,
2013
•Cause attributed to – Fluctuating Temperature, Poor hygienic
conditions at poultry farms, lack of adequate surveillance.
OIE, 2013
Chandigarh 18th
Dec.,
2014
•Reported at Sukhana lake.
•30 Ducks & 220 Geese died.
•H5N1 confirmed from 1 Duck by NIHSADL Bhopal.
OIE, 2013
Orisha 17th
April,
2014
•Reported at Ganjam OIE, 2014
UP 18th
March,
2015
•350 poultry birds died. OIE, 2015
Chandigarh 19th May,
2015
•22 poultry birds died. OIE, 2015
Kerala 10th July, •15000 poultry birds died. OIE, 2015

20. Indian Scenario…continued
State Dated Comments References
UP 31st July,
2015
•187 poultry birds & 3 crows died.
•844 poultry birds were destroyed.
OIE, 2015
Manipur 31st July,
2015
•940 poultry birds died.
•20874 poultry birds were destroyed
OIE, 2015
Andhra
Pradesh
31st July,
2015
•42167 poultry birds & 3 crows died.
•181942 poultry birds were destroyed.
OIE, 2015

21. Indian Scenario…continued
• Epicenter of outbreak-
--------Turkey Unit
Hassanghatta village .
•17 ducks & 206
chickens died.
•33000 birds (19235
chicken,13673
ducks,369 emu) were
culled, within 1km
radius.

22. Indian Scenario…continued
THE HINDUSTAN TIMES, NOV. 2014

23. Indian Scenario…continued
•Avian flu outbreak in Telangana
•Outbreak reported at VSR poultry
Farrm’s Unit 111 at Thoroor Village of
Hayathnagar Mandal in Ranga Reddy
district.
•Birds culled = 0.145 Million.
•NIHSADL , Bhopal confirmed
“positive Strong” in all 11 samples
within 24 hours .
•Migratory birds migrated from
Siberia & shed virus here

24. Transmission Between Birds
• Ducks act as carrier
• Pigs…Mixing Pot/Vessel.
• Viral shedding – main
transmission routes
Feces (most common in poultry)
Respiratory secretions
• Contact between infected &
healthy birds
• Indirect contact
Contamination
Unwashed egg shells
Airborne transmission
Improper carcass disposal
AI viruses can remain infectious for about one week at 37 °C , over 30 days at 0 °C , &
indefinitely at very low temperatures

25. Geographic Spread of Virus
• Movement of birds
 Migratory and free-ranging birds
 Legal poultry trade
 Illegal poultry trade
• Movement of equipment
 Vehicles, tractors, buckets
• Movement of people
 Hands, hair, clothing, shoes

26. HPAI signs and lesions in Poultry
– Sudden death and
high mortality rate
– Facial edema;
swollen & cyanotic
combs, wattles;
drastic decline in
egg production
– Mortality nears
100%
– +/- nervous signs

27. HPAI Can Cause Human Infection
• Transmission
– Contact with infected sick or dead birds
– Contact with contaminated poultry or bird products
• Human disease
– Usually due to infection with HPAI
Severity varies by virus strain
– LPAI infections documented
Usually mild symptoms
Examples: H7 and H9 viruses
– Mortality rate is ---60%(HPAI)

28. HPAI Diagnosis
• Clinical features in commercial poultry give a tentative diagnostic
Sudden death and high mortality rate
• RT-PCR and sequencing
• Virus isolation and identification is the gold standard, achieved on
 Embryonated Chicken egg.
 Cell Culture lines( vero cell line, Darby Canine Kidney Cell Line),
Fibroblast cell line, etc
• Serology: ELISA, HI, VNT, CFT

29. Treatment
Antiviral Drugs
 Neuraminidase inhibitors
 Oseltamivir – was used in India during 2006 outbreak, under trade
name “Tamiflu”. (Burch et al., 2009)
 Zanamivir
 M2 Protein blockers
 Amantadine and Rimantadine
 Vaccines
 Sanofi Pasteur’s vaccine approved by the US in April 2007
 GlaoSmithkline's vaccine , approved by European Union in May
2008.
 CSL Limited's vaccine approved by Australia in June 2008.

30. Protective and Mitigating responses
• Governmental preparedness
• Cross Sector planning and collaboration
• Cross Boundary planning and collaboration
• Expansion of Surveillance, Case tracking and
Epidemiology
• Laboratory Diagnostic Enhancement
• Improved information systems

31. Control Measures
• There is no "one" control strategy for avian influenza to fit every
country and all the bird species.
• Control- difficult under small backyard poultry production.
• Rapid culling of all infected or exposed birds,
• Proper disposal of carcasses.
• The quarantining and rigorous disinfection of farms.
• The implementation of strict sanitary, or “bio-security”, measures .
• Restrictions on the movement of live poultry, both within and between
countries.
• Decrease the local movements of ducks, support in-door keeping of
ducks, offering feed subsidies and construction of enclosures.
(Thailand, 2004-05)
• Nationwide vaccination of all poultry (Vet Nam, 2004, 2006-07)

32. WHO Recommendations
• Travelers traveling to affected areas should avoid contact with live
animal markets and poultry farms, and any free-ranging or caged
poultry.
• Populations in affected countries are advised to avoid contact with dead
migratory birds or wild birds showing signs of disease.
• Protection of persons at risk of occupational exposure-
1. Protective clothing, preferably coveralls plus an impermeable apron
or surgical gowns with long cuffed sleeves plus an impermeable apron;
2. Heavy-duty rubber work gloves that may be disinfected.
3.Standard well-fitted surgical masks should be used if high-efficiency
N95 respiratory masks (NIOSH-certified N-95 or equivalent) are not
available. Masks should be fit-tested and training in their use should be
provided;
4. Goggles;
5. Rubber or polyurethane boots that can be disinfected or protective
foot covers that can be discarded.