Avian Influenza: risk factors and

spatial epidemiology

Mike Tildesley
 Preparing for the next global catastrophe…
The Black Death (1346-1350)
– 50 million deaths

Spanish Influenza (1918-

1920) – more than 20
million deaths

Asian Influenza (1957-1958) – Swine Influenza (2009-10) – Ebola epidemic (2014) –

approx. 2 million deaths approx. 20,000 deaths approx. 10,000 deaths
 Impact of influenza pandemics
1918 flu pandemic: Infected 500 million, killed >20 million.
 Why are Influenza A viruses capable of
causing global pandemics?
 There are several Influenza A virus strains,
categorised into subtypes.

 Virus is notable for following dynamics:

 antigenic drift
 antigenic shift
Influenza A inhabits many hosts

Transmission between different animal species and humans.

Adapted from R. Jennings & R.C. Read, Influenza: Human and Avian.
Royal Society of Medicine Press (2006).
 Impact of H5N1

Source: FAO (2012) H5N1 HPAI Global Overview – Issue No. 31

 Global trends
Cattle & Buffaloes Sheep and Goats
Chicken (/10) Pork
2,500,000,000

2,000,000,000
Heads

1,500,000,000

1,000,000,000

500,000,000

0
1961

1973

1993
1965
1969

1977
1981
1985
1989

1997
2001
2005
2009
 The changing livestock sector
• Livestock revolution
• Massive increase in demand since the
1970s
 The changing livestock sector
• Livestock revolution
• Massive increase in demand since the
1970s

• Demand moving from ruminants to

monogastric (pigs & poultry)
 The changing livestock sector
• Livestock revolution
• Massive increase in demand since the
1970s

• Demand moving from ruminants to

monogastric (pigs & poultry)

• Production intensification
• Industrialization
• Vertical integration
• Geographic concentration
• Intensification: starting situation: backyard chickens
• Intensification: build fences
• Intensification: increase number & farm
• Intensification: used of specialized breeds: invest in trade
• Intensification: increase density – higher outputs
• Intensification: increase biosecurity to prevent disease
• Intensification: have more facilities
• Intensification: vertical integration & biosecurity
 High density
Increases transmission
Reduces immunity
 High density
Increases transmission
Reduces immunity

Low genetic diversity

Selects specialized pathogens
 High density
Increases transmission
Reduces immunity

Low genetic diversity

Selects specialized pathogens

High turnover
No possibility to transmit resistance
 High density
Increases transmission
Reduces immunity

Low genetic diversity

Selects specialized pathogens

High turnover
No possibility to transmit resistance

High trade of live animals and products

Favour long-distance transmission

 The Poultry Industry in South East Asia
Smallholders Large Industrial Farms

Two main industry types

Smallholders: Low input – low outputs (< 2 kg / head /

year)

Large Industrial Farms: High inputs – high outputs:

optimized ratios (> 10 kg / head / year)
• Thailand: broilers / owner at the sub-district level

Number of Farms

Van Boeckel et al. (2012) Agric Ecosyst Environ. 149. 144–153.

 Reality in Asia
Environment
 Reality in Asia
Environment
Highly Pathogenic Avian influenza (HPAI)

• HPAI is highly virulent

• High mortality rate in chickens
• Potential for zoonotic transmission and human deaths
 How do we understand transmission risk?
• Collect occurrence data

Cases
HPAI H5N1 (FAO Empres-I): 2004-2012

Poultry Cases
Human Cases
 How do we understand transmission risk?
• Collect occurrence data

• Compile spatial risk

factors (GIS layers)
 How do we understand transmission risk?
• Collect occurrence data

• Compile spatial risk

factors (GIS layers)
 How do we understand transmission risk?
• Collect occurrence data

• Compile spatial risk

factors (GIS layers)

Elevation
 How do we understand transmission risk?
• Collect occurrence data Likelihood of Disease proportional to: Risk
factor1 + Risk factor 2 + ….

• Compile spatial risk Build a statistical model to assess this risk

factors (GIS layers)

• Determine the values of

these risk factors that
are likely to correspond
to cases
 How do we understand transmission risk?
• Collect occurrence data

• Compile spatial risk

factors (GIS layers)

• Determine the values of Suitability for infection

these risk factors that
are likely to correspond
to cases
• Use this information to
develop a suitability
map
The essence of spatial epidemiology

Help
identifying
important
factors
Map
suitability
for
infection

With other tools, contributes to

better prevention and surveillance
 HPAI H5N1 in Thailand

1 Jan 2004 – 1 Jul 2004 1 Jul 2004 – 1 Jul 2005 1 Jul 2005 – end 2008
 HPAI H5N1 in Indonesia

2004 - 2008

2009

2010

2011
 HPAI H5N1 in India & Bangladesh

2006 2007-2011 2012

 HPAI H5N1 in China

Outbreaks

Human cases

Positive markets
 EMPRES-I HPAI H5N1 records (Asia)

0
200
400
600
800
1000
1200
1400
2004

2005

2006

2007

2008 THA
Time line

2009

2010

2011

2012
IDN
CHN
BGD

VNM
IND
How do we determine transmission risk?
Hosts

• What animal is infected

• Pattern of excretion (quantity, duration)
• Contacts with other hosts

Demographic/behavioural factors

• How host are moved;

• How fomites are moved;
• Surveillance, prevention, control

Environment

• How and where the virus persists outside the host

• How and where poultry are raised
 EMPRES-I HPAI H5N1 records (Asia)

0
200
400
600
800
1000
1200
1400
2004

2005

2006

2007

2008 THA
Time line

2009

2010

2011

2012
IDN
CHN
BGD

VNM
IND
2004: firefighting in Thailand
X-ray survey
introduced in
March 2003 –
nationwide survey
of villages to
detect H5N1 in
poultry
 HPAI H5N1 & risk factors in Thailand

Farmed
chicken
Backyard
HPAI H5N1 chickens

Gilbert et al. (2006) EID 12(2):227-234

 HPAI H5N1 & risk factors in Thailand

Large Density of
HPAI H5N1 Farmed
ducks
farmed ducks in
the East where
we don’t
observe cases.

Gilbert et al. (2006) EID 12(2):227-234

 Other Factors
Many smallholders in Thailand keep “free grazing” ducks.

Housed overnight, graze in rice paddies during the day.

 How do we map free grazing duck intensity?

Free grazing
ducks
Cropping Intensity

Gilbert et al. (2007) Ag., Eco. Env. 119:409-415

 Spatial model: predictions
Using all of these
risk factors we can
use spatial models
to produce risk
maps for HPAI
virus presence.

Gilbert et al. (2008) PNAS 105: 4769-4774

 Risk Maps in Indonesia

Loth et al. (2011) Prev. Vet. Medecine. Doi:10.1016/j.prevetmed.2011.06.006

 Risk Maps in South Asia

Gilbert et al. (2010) Ecohealth 7(4):448-58

 Can we do better?
Bi-modal structure
of broiler and
layer chicken farm
sizes.

Similar structure
observed in meat
and egg type free
grazing ducks.

Van Boeckel et al. (2012) Ag., Eco. Env. 10.1016/j.agee.2011.12.019

 Can we do better?

We investigate separately the risks associated with smallholders

(extensive farms) and large industrial farms (intensive farms).

Van Boeckel et al. (2012) Ag., Eco. Env. 10.1016/j.agee.2011.12.019

 Disaggregating poultry data

Intensive Extensive

Van Boeckel et al. (2012) Ag., Eco. Env. 10.1016/j.agee.2011.12.019

 Disaggregating poultry data

Intensive

Intensive Extensive

Van Boeckel et al. (2012) Ag., Eco. Env. 10.1016/j.agee.2011.12.019

 Risk factor modelling in Thailand
Increased Risk

Van Boeckel et al. PLOS ONE 7(11): e49528. doi:10.1371/journal.pone.0049528

Duck distribution
Intensification of duck production in South
East Asia

First report
of H5N1
Review paper on HPAI H5N1 risk factors
Review paper on HPAI H5N1 risk factors
• Risk factors studied at a range of spatial scales, from
farm to country level;
Review paper on HPAI H5N1 risk factors
• Risk factors studied at a range of spatial scales, from
farm to country level;

• Some factors showed consistent association with the

risk of HPAI H5N1 presence across countries and scales:
– Domestic duck density;
– Demographic (Human pop. density, distance to
roads, markets)
– Indicators of water presence
– The effect of chicken density is variable, most likely
due to differences in production systems
 Review of HPAI H5N1 risk factors
• Factors have been overlooked:

– Socio-economic;
– Trade and market networks;
– Wild bird distribution and movement;
 HPAI H5N1 in China
• Outbreaks have occurred mainly in chicken farms)

• H5N1 positive cases have also been found in markets

Martin et al. (2011) Plos Pathogens 7(3): e1001308

Risk maps for China
• Risk in China is found
to be correlated with
chicken and human
pop. density;
• Highest risk in
intensive productions
areas

Martin et al. (2011) Plos Pathogens 7(3): e1001308

 Risk maps for China
• Risk in China is found
to be correlated with
chicken and human
pop. density;
• Highest risk in
intensive productions
areas

High risk in regions with large human population, high poultry

density and large water bodies.

Martin et al. (2011) Plos Pathogens 7(3): e1001308

 Poyang Lake, China
Region of high mixing between hosts – wild birds and farmed poultry.
Approx. half a million wild
birds (75 species).

Natural wetlands in dark

green.

Cropland in pale green,

gradually invading wetlands.

In this cropland we have:

• Poyang lake: wild geese farms
  main
• Poyang lake: Poyang lakefor
lake populations
migratory watefowls
 0.5 million wild birds (75 species);
 3 millions « farmed » wild birds;

 Surrounded by 10 counties with

 26 million ducks and geese in farms;
 21 million domestic chicken in farms;
 6 million people;
Temporal patterns in Poyang lake
Spatial patterns in Poyang lake
 China
 Intensified poultry production rapidly, duck
population that outweights all other coutries
 In regions with extensive interface with the wild
avifauna
 Connectivity between regions is facilitated by long-
distance trade between live-bird markets
Antigenic shift – the risk to humans
 The H7N9 outbreak in China
In late March 2013, three cases of influenza A H7N9 in humans
were reported in Shanghai and Anhui provinces.

By the end of April, several provinces in China had reported infection

and there were over 30 deaths.

Infected individuals generally came into close contact with domestic

poultry.

China CDC concluded that human to human transmission was

“possible” but evidence suggested that the likelihood of this form of
transmission was low.

Whilst the virus was eventually traced to domestic poultry, it is

mainly subclinical, so it is challenging to predict risk to humans.
H7N9 outbreak in 2013/14

Figure courtesy of the European Centre for Disease Control and Prevention
 H7N9 Infection Waves
Waves of human cases have
appeared in China since 2013.
An example of dangerous
antigenic shift in influenza A
viruses:

• Subclinical in poultry

• Can infect humans

• High Mortality rate: approx.

30%
• Possible human-to-human
transmission

Quan et al. (2018) Journal of Virology.

 H5N1 in East Anglia
In 2007, H5N1 would have a serious impact upon one of Norfolk’s
favourite celebrities.

Bernard Matthews
 H5N1 in East Anglia
On 30th January 2007 over 50 turkeys died at one of Bernard
Matthews’ farms in Holton, Suffolk.

A 3km protection zone (banning all poultry movements) was put in

place around the farm, along with a 10km surveillance zone where
activity was closely monitored.

On 3rd February DEFRA confirmed H5N1 was the cause of the deaths
(that by this stage numbered around 2000).

150,000 birds were culled in

an effort to control the
disease.
 H5N1 in East Anglia
Evidence suggested H5N1 had
been introduced via imports
from the Bernard Matthews
plant in Hungary.

Control measures were lifted by 9th March 2007.

By this stage several workers had been laid off, consumer confidence
was low and several countries were refusing to import British poultry
meat.
 Bernard Goes on the Offensive
In an attempt to restore
confidence, Bernard Matthews
fronted a series of ad
campaigns, declaring his meat
is safe to eat.

Further outbreaks in Suffolk

later in the year on non-
Bernard Matthews premises
delayed restoration of
confidence.
Estimates suggest that Bernard Matthews lost an estimated £20 million
in sales as a result of a single outbreak.
Can mathematical models play a role
in reducing the spread of disease in
the future?
 Conclusion
• Key role of ducks => differ according to
production systems

• Intensification of poultry production increases

transmission risk

• Spread to other poultry and human exposure

facilitated by LBM networks
Thank you Acknowledgments:
M.Gilbert

AND:

J. Cappelle, L. Hogerwerf, L. Loth, V. Martin, S. Newma

Paul, D. Pfeiffer, D. Prosser, T. Robinson, J. Slingenberg
Stevens, W. Thapongtharm, T. Van Boeckel, R. Wallace
Wint, X. Xiao
,