Epidemiology of H5N1 infections in

India: Trends of disease, spatial and

temporal distribution

Dr. Gazanfar AbassDivision of Veterinary Public Health

Bhoj R Singh Division of Epidemiology

IVRI, Izatnagar-243 122, India

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

NAMA

NS

M2

Hemagglutinin

Neuraminidase

M1

•H17 was isolated from fruit bats.•H18N11 was discovered in a Peruvian bat.

(Tong et al., 2013)

Classification of Influenza virus

Orthomyxoviridae

Influenzavirus A Influenzavirus B Influenzavirus C

MAN H1N1H2N2H3N2H5N1H7N7H7N9H9N2

PIGH1N1H1N2H3N1H3N2H5N1H3N3H7N7H7N9H9N2H3N8H4N6H5N2

HORSEH7N7H3N8

WILD WATERFOWL(Natural Host)H 1-16N 1-9

CHICKEN

H 1-7, 9-11N 1-4, 6-9

FERRETH5N1H1N1H3N2

WHALEH1N3H13N2H13N9

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

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

Viral Replication

CAP SNATCHING

Epidemiological Triad of Fowl Plague

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

•Tropical – increased rainfall Shek et al., 2003

The introduction of virulent strain in a susceptible population spreads widely regardless of the season Stephanson et al., 2002

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 atcleavage site of Haemagglutinin.

2. Virulence attributed to E627K substitution in PB2 gene.

3. Deletion of 20 amino acids in NA is associated with highvirulence.

(Masato et al., 2001)

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

International Scenario of Fowl Plague

OutbreaksS.

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)

7 1 China April 2005 6,000 migratory birds died

Disease outbreak map (H5N1)-June 2008

Cumulative confirmed human cases for

avian influenza A(H5N1) WHO, 2003-15

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

State wise Avian influenza reports in India

State where Avian influenza was report

Indian ScenarioState Dated Comments References

Maharashtra

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., 2009OIE, 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 2012-14

•Reported 5 outbreaks. OIE, 2015

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, 2015

•15000 poultry birds died.•213807 poultry birds were destroyed.

OIE, 2015

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

AndhraPradesh

31st July, 2015

•42167 poultry birds & 3 crows died.•181942 poultry birds were destroyed.

OIE, 2015

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.

Indian Scenario…continued

THE HINDUSTAN TIMES, NOV. 2014

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

Transmission Between Birds

• Ducks act as carrier• Pigs…Mixing Pot/Vessel.• Viral shedding – main

transmission routesFeces (most common in poultry)Respiratory secretions

• Contact between infected & healthy birds

• Indirect contact ContaminationUnwashed egg shellsAirborne 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

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

HPAI signs and lesions in Poultry

– Sudden death andhigh mortality rate

– Facial edema;

swollen & cyanotic

combs, wattles;

drastic decline in

egg production

– Mortality nears

100%

– +/- nervous signs

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)

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

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.

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

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)

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.