| |

Received: 11 July 2019    Revised: 13 January 2020    Accepted: 13 February 2020

DOI: 10.1111/tbed.13515

REVIEW ARTICLE

Control of avian influenza in China: Strategies and lessons

Shuo Liu | Qingye Zhuang | Suchun Wang | Wenming Jiang  | Jihui Jin |

Cheng Peng | Guangyu Hou | Jinping Li | Jianmin Yu | Xiaohui Yu | Hualei Liu |
Shufang Sun | Liping Yuan | Jiming Chen

China Animal Health and Epidemiology

Center, Qingdao, China
Correspondence
Jiming Chen, China Animal Health and
Epidemiology Center, 369 Nanjing Road,
Qingdao 266032, China.
Email: jmchen678@qq.com
Funding information
Postdoctoral Innovative Support Program of
Shandong Province; Qingdao Postdoctoral
Applied Research Project; The Programme
of China Ministry of Agriculture on Animal
Disease Surveillance and Control
Abstract
In recent decades, multiple subtypes (i.e. H9N2, H5N1 and H7N9) of avian influenza
virus (AIV) have become widespread in China, which has caused enormous economic
losses and posed considerable threats to public health. In this review, with the aim
to provide insights into and guidelines for the control of AIV spread in China and
globally in the future, we analysed the reasons why AIV has persisted in China based
on socio-economic features, including poultry biosecurity, live bird markets, live bird
transportation, wild birds, poultry waterfowl, poultry density, poultry population and
infected birds. We also described the present status of the AIV subtypes H9, H5
and H7 in China to elucidate the effectiveness of the strategies currently employed
in China (i.e. culling, mass vaccination and biosecurity improvement) to control the
disease based on a literature review and our unpublished surveillance data collected
over a 12-year period from 2007 to 2018. We then summarized the lessons to be
learned from the control experience in China, including whether culling of infected
birds is of limited value for disease control and whether improved biosecurity is a
better option than culling and vaccination for the long-term control of AIV, and when
the vaccine strain should be updated.

KEYWORDS

avian influenza, biosecurity, control, H7N9, lesson, strategy, vaccination, vaccine strain

1 |  I NTRO D U C TI O N
The H9, H5 and H7 subtypes of avian influenza virus (AIV) were first
identified in China in 1994, 1996 and 2013, respectively, although
each may have circulated worldwide for hundreds of years (Chen,
2009a; Gao et al., 2013; Qi et al., 2014; Webster, Bean, Gorman,
Chambers, & Kawaoka, 1992; Zhang, Zhang, & Chen, 1994; Zhuang
et al., 2013). AIV infection has led to the bankruptcy of many poultry
farms and resulted in >600 human deaths, leading to significant so-
cial panic in China (Bensyl, Moran, & Conway, 2001; Qi et al., 2014;
Qiang & Kou, 2019; Zhuang et al., 2013). These AIV subtypes could
spark a human pandemic once adapted through mutation. Why have
they persisted in China? How have they been circulating in China?
Shuo Liu, Qingye Zhuang and Suchun Wang contributed equally to this work.
What strategies have been implemented in China to control the
spread of AIV? How scientific and effective are these strategies?
What lessons can we learn from the experience in China for the con-
trol of AIV? We attempted to answer these questions in this review
based on relevant studies in the literature and our unpublished sur-
veillance data collected over a 12-year period from 2007 to 2018
(Tables 1 and 2), with the aim to provide insights to improve guide-
lines for the control of AIV, both in China and globally.
2 | RO OT S O F TH E PRO B LE M S
The prevalence of AIV in China is rooted in its ingrained ecosys-
tem and socio-economic features. First, billions of wild birds come
into contact with domestic birds, either directly or indirectly,

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1464       LIU et al.

TA B L E 1   Percentage of NA subtypes of the H5 HPAIVs during the past 30 years to meet the ever-increasing demands
identified through national surveillance from our unpublished data (China Livestock Yearbook Editorial Committee, 2018), which has
(detailed information are available upon request)
greatly increased the risk of AIV infection in China. Fourth, many
Year H5N1 (%) H5N2 (%) H5N6 (%) H5N8 (%) regions throughout China have extraordinarily high poultry densi-
2007 100.0 0.0 0.0 0.0 ties, which facilitates the transmission of AIV (Martin et al., 2011).
Fifth, as suggested by the FAOSTAT database (http://www.fao.
2008 100.0 0.0 0.0 0.0
org/faost​at/en/#home), >50% ducks and >80% geese worldwide
2009 100.0 0.0 0.0 0.0
are raised in China, as many Chinese individuals consume the meat
2010 100.0 0.0 0.0 0.0
and eggs of ducks and geese, which further increases the risk of
2011 100.0 0.0 0.0 0.0
AIV spread because waterfowl are at a much greater risk of AIV
2012 92.2 4.1 0.0 3.7
infection than chickens due to sharing of wetlands with wild birds
2013 79.6 6.6 0.0 13.8
and that waterfowl can act as silent carriers of many AIV subtypes
2014 6.8 3.8 81.1 8.2 (Chen, 2009b; Su et al., 2015; Webster et al., 1992; Zhou et al.,
2015 11.3 16.1 72.6 0.0 2015). Sixth, billions of birds are sold annually via live bird markets
2016 6.3 30.9 62.5 0.3 (LBMs) in China because many Chinese believe that the birds in
2017 2.0 34.7 62.0 1.2 LBMs are safer and more delicious (our unpublished data). This
2018 0.0 21.8 78.0 0.2 adds fuel to the fire of AIV because LBMs are hubs for viral ag-
gregation, replication, re-assortment, mutation, spread and human
infection (Li et al., 2019; Su et al., 2015; Yu et al., 2014). Seventh,
TA B L E 2   Percentage of HA clades of the H5 HPAIVs identified billions of birds are transported from poultry farms to LBMs, and
through national surveillance from our unpublished data (detailed transportation can transmit AIV to distant poultry farms via ve-
information are available upon request)
hicles and personnel if appropriate biosecurity protocols are not
Clades followed (Lu, Leigh Brown, & Lycett, 2017). Eighth, many more
AIV-infected poultry and wild birds emerge annually in China as
Year 2.3.2 (%) 2.3.4 (%) 7.2 (%)
compared with 30 years ago (Chen, 2009b; Gao et al., 2013; Jiang
2007 0.0 100.0 0.0 et al., 2012), and these infected birds could further increase the
2008 51.8 25.0 23.2 risk of AIV spread of China. Taken together, the ecosystems and
2009 92.3 3.4 4.2 socio-economic features of China are highly favourable for the
2010 58.5 28.3 13.2 spread of AIV, and we assume that the third and eighth factors
2011 80.9 4.6 14.5 given above have been critical for the increased risk of AIV spread
2012 81.4 9.8 8.8 in China over the past 30 years. Additionally, high-producing poul-

2013 62.6 34.3 3.0 try breeds have become dominant in China, and their compro-
mised immune function may also have played an important role in
2014 7.1 92.7 0.2
the epidemiology of AIV in China, as they are reported to be more
2015 7.6 92.4 0.0
sensitive to AIV than indigenous poultry breeds (van der Most,
2016 5.4 94.6 0.0
Jong, Parmentier, & Verhulst, 2011; Swaggerty, Callaway, Kogut,
2017 2.3 97.7 0.0
Piva, & Grilli, 2019).
2018 0.8 99.2 0.0

every year in China, which is thought to promote the spread of
AIV throughout China and other countries (Gilbert et al., 2010;
Kou et al., 2009). The role of wild birds in AIV transmission should
be well recognized due to not only limited biosecurity and free
movement, but also the possibility that wild birds outnumber poul-
try birds worldwide by about 10-fold (Kevin & Blackburn, 1997).
Second, millions of low-income people in China of limited educa-
tion live on small poultry farms. Consequently, billions of poultry
birds are raised in China with limited biosecurity using the facilities
of Sectors 3 and 4 as per the Food and Agriculture Organization
of the United Nations (FAO) classification for poultry produc-
tion systems (Glatz & Pym, 2014), which facilitates the spread of
AIV (Lu, Milinovich, & Hu, 2016; Yu et al., 2014). Third, domestic
fowl in China have increased by 10-fold with limited biosecurity
3 | I N FEC TI O N S TAT U S
3.1 | AIV subtype H9N2
H9N2 was the first AIV subtype identified to have a notable negative
impact on the poultry industry in China. Although vaccines against
AIV subtype H9N2 have been widely used in layer farms in China for
about 25 years, the virus has remained highly prevalent in China for
decades (Jiang et al., 2012; Ma et al., 2018). A total of 10 subtypes of
AIVs (H1–H7 and H9–H11) have been identified through our surveil-
lance of AIVs over a 12-year period from 2007 to 2018. Among these
10 subtypes, H9N2 accounts for about 37.5%−77.9% of the AIVs
identified by surveillance (our unpublished data). Our surveillance
and other studies suggested that about 4.6%−31.5% of birds in LBMs
LIU et al.
in China carry AIV (Ma et al., 2018). Subtype H9N2 is prevalent in
domestic waterfowl, and more prevalent in chickens and pigeons,
but not in wild birds (Jiang et al., 2012). Moreover, most of the H9N2
isolates collected from wild birds and domestic fowl in China were
located in different clades (Jiang et al., 2012), as were most H9N2
isolates circulating in China and neighbouring countries (Jiang et al.,
2012), suggesting that the H9N2 subtype in China has limited poten-
tial for transboundary transmission. The H9N2 subtype causes egg
drop and respiratory diseases in chickens. Although severe human
infections of the H9N2 subtype have been rare over the past three
decades (Liu et al., 2018), the prevalence of human infection by this
subtype might be similar to that of the H5 and H7N9 subtypes, es-
pecially among poultry workers in southern China, as suggested by
serological investigations (Li et al., 2017; Ma et al., 2018).
3.2 | AIV subtype H5
The AIV subtype H5 has been widely circulating in China for more
than 15 years, since several large-scale outbreaks occurred in 2004
(Chen, 2009b). Surveillance data suggested that about 0.3%−3.4%
of birds in LBMs in China carried the viruses (Jiang et al., 2010; Ma
et al., 2018), and the H5 subtype circulating in China before 2012
was almost exclusively the subtype H5N1 highly pathogenic AIVs
(HPAIVs), while the H5N2, H5N6 and H5N8 subtypes emerged
in China thereafter (Table 1). In 2018, 78.0% and 21.8% of all AIV
isolates were identified as subtypes H5N6 and H5N2, respectively
(Table 1).
Subtype H5 has also been widely circulating among poultry
and/or wild birds in many countries in Asia, Europe and Africa.
These viruses have been classified into multiple clades and sub-
clades based on the HA gene sequence (Ma et al., 2018; Zeng
et al., 2016). The H5 HPAIVs in China belonged to clades 2.3.4,
2.3.2 and 7.2 before 2015, and clade 7.2 HPAIVs have not been
identified since 2015 (Table 2). The subtype H5 HPAIVs in
clades 2.3.4 and 2.3.2 was more prevalent in waterfowl (ducks
F I G U R E 1   Six waves of human
infections with H7N9 subtype AIVs in
China based on case reports of World
Health Organization. The sixth wave
disappeared coincidently with mass
vaccination in poultry
|
      1465
and geese) than in terrestrial birds (chickens and pigeons) and
has been frequently identified in wild birds in China and dozens
of other countries, showing a great capability for transbound-
ary transmission. The subtype H5 HPAIVs in clade 7.2 circulated
almost exclusively in chickens in China before disappearing in
2014 (Liu et al., 2016). Our annual surveillance data suggest that
the dominant clade of subtype H5 HPAIVs in China shifted from
clade 2.3.4 to clade 2.3.2 in 2008 and shifted again from clade
2.3.2 to clade 2.3.4 in 2014 with the emerging subclade 2.3.4.4b
within clade 2.3.4 (Table 2). In 2018, 99.2% and 0.8% of subtype
H5 HPAIVs isolates belonged to clades 2.3.4.4 and 2.3.2.1, re-
spectively (Table 2).
3.3 | AIV subtype H7N9
The problems caused by AIV subtype H7N9 were much more severe
than those caused by subtypes H9 and H5 in China in recent years
(Jiang et al., 2019; Quan et al., 2018; Yang et al., 2017). Our annual
surveillance data suggested that the virus was distributed widely in
China, and about 0.1%−3.9% of birds in LBMs in China carry the virus
(Jiang et al., 2019). The prevalence of AIV subtype H7N9 was much
higher in chickens and pigeons than in ducks and geese (Jiang et al.,
2019). The H7N9 viruses have caused >1,500 confirmed human in-
fections and >600 confirmed human deaths since 2013 (Quan et al.,
2018). Because of so many confirmed human cases and deaths,
subtype H7N9 has a significantly higher potential to spark a severe
human pandemic (Gao et al., 2013; Quan et al., 2018; Zhuang et al.,
2013). Additionally, because of a fear of infection, many custom-
ers are unwilling to consume poultry products, which have led to
huge economic losses each year. During the fifth wave of viral cir-
culation between October 2016 and June 2017, human infections
increased by more than 340% as compared with previous waves
(Figure 1), and the zoonotic H7N9 low pathogenic viruses diverged
to HPAIVs, which spread rapidly from southern to northern China,
resulting in multiple outbreaks in chickens (Yang et al., 2017). As
 |
1466       LIU et al.
TA B L E 3   Some advantages and disadvantages of three strategies for control of avian influenza
Strategies Advantages
Culling Able to eliminate the disease with early detection and
solid biosecurity;
Able to minimize the viral spread from confirmed
infected flocks if well implemented
Biosecurity Able to reduce greatly the risk of avian influenza and
many other diseases simultaneously
Vaccination Sometimes able to alleviate severe situations rapidly;
Sometimes able to eliminate the viruses without wild
bird reservoir
described below, this severe situation was rapidly controlled by mass
vaccination.
4 |  CO NTRO L S TR ATEG I E S
The Chinese government has invested tremendous resources to
strengthen veterinary administration, research, education, surveil-
lance, investigation, emergency responses, international coopera-
tion, mass vaccination and biosecurity improvements for the control
of AIV. These activities boil down to three major strategies, namely
culling of infected birds, vaccination and biosecurity improvement,
as described below. The advantages and disadvantages of these
strategies are shown in Table 3.
4.1 | Culling
The Chinese government has culled millions of poultry birds an-
nually for multiple years to minimize the spread of AIV (Chen,
2009b). Culling is conducted under the authority of the veterinary
administration, on confirmation of outbreaks of subtype H5 or
H7. The affected poultry flock and other flocks that have been
exposed to the infection through direct or indirect contact are
killed, and their carcasses are destroyed by burning and/or burial.
This policy is accompanied by standard cleansing and disinfection
procedures. This strategy has been effective with the aid of solid
biosecurity in some countries for elimination of subtypes H5 and
H7. However, this strategy alone cannot control the spread of AIV
in China for many reasons. First, if a dangerous AIV subtype has
spread to China, it can rapidly and widely spread because of the
high risk ecosystem in China which harbours eight major risk fac-
tors as described above. Second, about 5 billion poultry fowl are
raised on approximately 20 million farms in China, and <1% of the
infected birds or flocks can be detected each month through large-
scale surveillance (China Livestock Yearbook Editorial Committee,
Disadvantages
Too costly if the viruses have widely spread;
Of limited or unsustainable effects if poultry biosecurity is weak;
Not applicable for wild birds which move freely and outnumber poultry
birds greatly;
Usually requiring both the government and poultry farms to sacrifice
greatly their direct interests for public good
Usually requiring various strict measures and costly facilities;
Usually restricting freedom of poultry workers and animals;
Usually unable to alleviate severe situations rapidly
Very costly to control multiple diseases;
Sometimes leading to silent infections of highly pathogenic viruses in
chickens;
Sometimes accelerating the viral mutation and diversification, making the
disease more complicate in the long run
2018). Therefore, <1% infected birds or farms can be identified
through surveillance and culling can be conducted thereafter.
Third, wild birds outnumber poultry birds worldwide by about 10-
folds and it is not possible to cull most infected wild birds for obvi-
ous reasons. Fourth, if the culling rate exceeds the infection rate in
the highly risk ecosystem in China without the aid of vaccination,
annual mass surveillance and mass culling may be too expensive
(our unpublished data; Capua & Marangon, 2003). Fifth, mass cull-
ing usually requires great kills from both local governments and
poultry farms, as the local governments should be responsible for
compensation of the affected farms, and such compensation usu-
ally only covers a limited portion of associated economic losses
of the affected farms (Lu et al., 2016). With these considerations,
the culling strategy should actually play only a minor role in the
control of AIV in China (Chen, 2009b).
4.2 | Biosecurity
The poultry biosecurity has been increasing rapidly in recent years
in China. Since 2008, small poultry flocks of limited biosecurity
have decreased annually in China by about 10%, while large poultry
farms with solid biosecurity have increased annually by about 15%,
as suggested by statistical yearbooks of China animal husbandry.
Marketing competition accounts greatly for this transition since
small poultry farms are more likely to be uncompetitive because
of higher disease burdens. Multiple government interventions
are also important for this transition, as the Chinese government
has strengthened biosecurity measures and licensing of poul-
try farms, which has strengthened compulsory detection of AIV
prior to trans-province transportation and marketing. Moreover,
the Chinese government has banned many small poultry farms,
thereby reducing poultry density, while upgrading poultry biosecu-
rity requirements for pollution control over the past 2 years, which
has dramatically improved poultry biosecurity. Rapid urbaniza-
tion and industrialization in China have also facilitated biosecurity
LIU et al.       1467 |
improvements, as many farmers have left the industry to work

2019
in factories, which are often located in cities. Biosecurity meas-

√
 

 
ures are also considered paramount to protect indigenous poultry
breeds in China from infection by AIV and other pathogens.

2018
The sale of poultry is also in rapidly changing in China, as more

√
 

 
and more LBMs have been closed temporarily or permanently,

2017
and most birds are now sold in supermarkets after slaughtering.

√
 

 
Additionally, the number of freshly slaughtered birds sold through

2016
Internet platforms, such as Taobao (www.taobao.com) and Jingdong

√
 

 
(www.jd.com), has increased annually by more than 300% from
2015 to 2018 (our unpublished data), demonstrating the potential

2015
to replace traditional LBMs in the near future. Viral transmission and

√
 

 
replication through freshly slaughtered birds sold by electronic mar-

2014
keting systems can be efficiently reduced as compared with LBMs, as

√
 

 
confirmed by our unpublished data from a survey conducted in 2018.

2013
We assume that risk of AIV infection will dramatically decrease

√
and dangerous AIV subtypes in China are predicted to be well con-

 
trolled without mass vaccination by 2030, because by then most

2012
poultry birds in China will be raised and sold in accordance with solid

√
 

 
biosecurity measures.

2011
Solid biosecurity usually requires strict management measures

√
 

 
and costly facilities and usually sacrifices the freedom of poultry 2010
workers. Moreover, multiple years are needed to establish solid
TA B L E 4   Application periods of the vaccine strains to combat H5 subtype avian influenza viruses in China

√
poultry biosecurity measures in a large country, such as China. For
 

 
example, it is predicted that 13 years are needed for the number of
2009

small-scale poultry flocks of limited biosecurity in China to decrease

√

√
 

 
from the current 20 million to 5 million, if the number declines an-
2008

nually by 10%.
√

√
 

 
2007

4.3 | The vaccination strategy

√

√
 

 
2006

Because neither culling nor biosecurity can prevent the transmis-

√

 
sion of AIV in China in a timely manner, mass vaccination is a ra-
2005

tional alternative to rapidly alleviate the severe situations caused by

√

 
AIV. Mass vaccination strategies implemented in China have dem-
2004

onstrated satisfactory effects. First, H5 outbreaks have declined

√

significantly after a mass vaccination programme was initiated in

 

 
2005. Second, HPAIV clade 7.2 of subtype H5, which was widely
Designations

circulated in northern China from 2006 to 2013 (Liu et al., 2016), has
Re−12
Re−11

been largely eliminated by mass vaccination, as this clade has not

N−28

Re−4

Re−6
Re−8
Re−5
Re−1

Re−7

been identified since the corresponding vaccine strain was updated

in 2014 (Table 4). Third, despite significant opposition from many sci-
Clade

2.3.2

2.3.2
2.3.4

2.3.4

2.3.4

entists and provincial officials, mass vaccination against the zoonotic

7.2

7.2
0
 

H7N9 subtype was implemented in 2017, and coincidently, human

Guangdong/1/1996(H5N1)

cases of the sixth wave (n = 3) declined by 99.6%, as compared with

Guizhou/4/2013(H5N1)

the fifth wave (n = 750; Figure 1), which resulted in huge financial
Seed or HA-donor virus

Shanxi/2/2006(H5N1)

Anhui/1/2006(H5N1)

SD007/2017(H5N1)
S4092/2011(H5N1)

A/duck/Guangdong/
S1322/2010(H5N1)
S4184/2017(H5N6)
A/chicken/Liaoning/

A/chicken/Liaoning/

saving and potentially saved hundreds of human lives. Accordingly,

A/turkey/England/

A/duck/Guizhou/
N−28/73(H5N2)

the relevant pandemic risk and associated social anxiety and panic
have also dramatically declined.
A/chicken/

A/chicken/

A/chicken/
A/goose/

Vaccination strategies have several shortcomings. First, mass

vaccination can lead to silent AIV infections of chickens (Ma et al.,
2014), suggesting that vaccination may extend duration of the
 |
1468       LIU et al.
F I G U R E 2   The transmission cycle of AIVs without wild bird reservoir (Figure 2a) or with wild bird reservoir (Figure 2b) between infected
birds and uninfected birds in the circumstance of mass vaccination in poultry. The dash lines represent that transmission from infected birds
to uninfected birds is naturally rare or blocked by mass vaccination, and thus, uninfected birds are unlikely to become infected birds
infections and facilitate transmission to a greater number of birds,
even though viral replication in each infected bird is reduced.
Second, mass vaccination can accelerate viral mutation and diver-
sification, rendering a more complicated disease situation in the
long term (Cattoli et al., 2011; Swayne, 2012; Wang et al., 2012).
Third, vaccination against AIV usually does not reduce the bur-
dens of other diseases, and it is costly to control multiple diseases
using multiple vaccines. Fourth, vaccination against AIV remains
unpractical for wild birds and somehow unsatisfactory for water-
fowl due to low vaccination coverage and relatively low immune
response to the vaccines (Pantin-Jackwood & Suarez, 2013). Fifth,
effective vaccines are only available for prevention of a few clades
of H5 and H7 AIVs, and have been produced by only a few coun-
tries (e.g. China, Mexico) as most developed countries do not use
the vaccines and most developing countries are unable to produce
the vaccines efficiently.
5 |  LE S S O N S O F C H I N A
5.1 | Integration of multiple strategies
China integrated the three strategies described above to control
AIV, as the government has culled millions of infected birds for mul-
tiple years to minimize viral spread from confirmed infected farms,
and has employed multiple measures to improve poultry biosecurity.
In addition, mass vaccination programmes have been implemented
to control the spread of AIV (Chen, 2009b; Lu et al., 2016; Zeng
et al., 2016). The integration of these three strategies has made the
best use of the advantages and bypassed the disadvantages of the
individual strategies (Table 3). Through strategy integration, severe
epidemics of AIV infection have been alleviated in China.
5.2 | Biosecurity priority
The concept of biosecurity priority proposed here means that bi-
osecurity improvement is more important than the culling and vac-
cination strategies for the long-term control of AIV for multiple
reasons. First, inadequate poultry biosecurity accounts greatly for
incursions of AIVs in developing as well as developed countries (Cui
& Liu, 2016; Ssematimba et al., 2013; Zhou et al., 2015), and solid
poultry biosecurity measures can effectively prevent the spread
of AIVs. Many large poultry farms in Hainan, China, with solid bi-
osecurity measures in place have effectively prevented the spread
of H5 HPAIVs for years without vaccination. Second, solid biosecu-
rity measures can greatly reduce the burdens of culling of infected
birds and mass vaccination by reducing the incidence of outbreaks of
dangerous infectious diseases. Third, solid poultry biosecurity meas-
ures can simultaneously reduce the burdens of many avian diseases
and is, thus, more economical to achieve long-term disease control.
Moreover, biosecurity improvement is directly beneficial to local
governments, poultry farms and the environment.
Multiple effective measures have been implemented in China
to improve poultry biosecurity, which can be considered by other
countries. First, many poultry farms and LBMs of limited biosecu-
rity have been banned in China for pollution control, and this reason
has been accepted by the relevant stakeholders. The banning has
greatly improved poultry biosecurity in many regions throughout
China. Second, electronic marketing is rapidly replacing traditional
risky LBMs in China and should greatly improve poultry biosecu-
rity in the coming years, as the birds are transported to slaughter
houses directly from poultry farms. Third, data collected from our
unpublished surveys suggested that many farmers in China have ef-
fectively prevented AIV infection of small groups of poultry by re-
stricting their birds to small isolated spaces in backyards, rather than
allowing the birds to roam freely as before. However, many large-
scale poultry farms in China are somehow biosecurity defective,
which has led or can lead to disastrous outbreaks of disease. Thus,
operators of these farms should greatly strengthen their knowledge,
vigilance, facilities and measures to improve biosecurity to a level
much higher than that required by small-scale farms (Cui & Liu, 2016;
Leibler, Dalton, Pekosz, Gray, & Silbergeld, 2017).
5.3 | Vaccination effectiveness
Figure 2 suggests that, in principle, the viral transmission cycle can be
fully blocked by mass vaccination in poultry birds if the AIVs have no
wild bird reservoir, but cannot be fully blocked if the viruses have a wild
LIU et al.
bird reservoir. This suggestion has been supported by experience in
China, where mass vaccination has been more effective to minimize in-
fections of AIV subtype H5 clade 7.2, which had no wild bird reservoir,
than to minimize infections of clades 2.3.2 and 2.3.4, which did have
wild bird reservoirs (Table 2; Qu et al., 2019). This was one of the im-
portant reasons why our laboratory first proposed to implement mass
vaccination in China to address the severe H7N9 epidemic in late 2016,
as the H7N9 viruses had no wild bird reservoir (Jiang et al., 2019).
5.4 | Vaccine strain update
The vaccine strains used for control of AIV subtypes H5 and H7
in China are updated every few years to combat the emergence of
vaccine-escape mutants (Table 4). If the vaccine strains are updated
too late, vaccine-escape mutants can cause widespread outbreaks.
Analysis of 14 years of experience (2005–2018) of mass vaccination
in China suggested that it may be better to use the vaccine strain
Re-6 from 2008 rather than 2012 to combat the vaccine-escape
mutant of clade 2.3.2 of subtype H5, which has accounted for >50%
of AIV isolates since 2008 (Table 2), and it should be better to use
the vaccine strain Re-7 from 2011 rather than 2014 to combat the
emergence of vaccine-escape mutants, which accounted for almost
all isolates of subtype H5 clade 7.2 since 2011 (Liu et al., 2016).
Additionally, it should be better to use vaccine strain Re-8 or its an-
alogue from 2014 rather than 2016 to combat the vaccine-escape
mutant of clade 2.3.4, which has accounted for >90% of subtype H5
isolates collected since 2014 (Table 2). Updating of these three vac-
cine strains was delayed because the official inspection was overly
cautious. Fortunately, the Chinese government has simplified the
official inspection procedures and the vaccine strains were updated
in a timely manner in 2019. We proposed empirically that a vaccine
strain should be updated if a vaccine-escape mutant accounts for
more than 30% of the relevant AIV subtype.
The vaccine strains should not be updated too early either, be-
cause most vaccine-escape mutants disappear naturally without
widespread, and only one or two vaccine-escape mutants will be
widely circulated. However, it remains unknown which vaccine-es-
cape mutant will become widely circulated, although this topic re-
garding human influenza viruses has been studied for many years
(Bush, Bender, Subbarao, Cox, & Fitch, 1999; Du, King, Woods, &
Pascual, 2017). Consequently, we should not update vaccine strains
until a few vaccine-escape mutants have demonstrated wide circu-
lation. We propose that a vaccine strain should not be updated for
national application if none of the vaccine-escape mutants has ac-
counted more than 10% of the relevant AIV subtypes identified by
national surveillance.
6 | CO N C LU S I O N S
The risk of AIV spread in China has increased greatly over the past
30 years in China, but is expected to significantly decrease in the
|
      1469
coming decades, due to the changes to ecosystem and socio-eco-
nomic features. The strategies of culling infected birds and mass vac-
cination implemented in China have successfully controlled severe
outbreaks, reduced economic losses and decreased human infections
in a timely manner. Meanwhile, rapid improvement of poultry biosecu-
rity in China is paving the way to effectively prevent and control AIV in
poultry without mass vaccination. The lessons of strategy selection
and integration, biosecurity improvement, vaccination effectiveness
and vaccine strain update discussed in this paper should prove useful
for better control of the spread of AIV in China and globally in the near
future.
AC K N OW L E D G E M E N T S
This work was supported by the programme of China Ministry of
Agriculture on Animal Disease Surveillance and Control and the
Postdoctoral Innovative Support Program of Shandong Province
and the Qingdao Postdoctoral Applied Research Project. We thank
International Science Editing (http://www.inter​natio​nalsc​ience​editi​
ng.com) for editing this manuscript.
E T H I C A L A P P R OVA L
All applicable international, national and/or institutional guidelines
for the care and use of animals were followed.
C O N FL I C T O F I N T E R E S T
All the authors declare that they have no conflict of interest.
AU T H O R C O N T R I B U T I O N S
Jiming Chen contributed to the design of this work and analysis of
the control strategies and wrote the manuscript. Shuo Liu, Qing-Ye
Zhuang and Suchun Wang contributed to analysis of the infec-
tion situation and control strategies, and revised the manuscript.
Wenming Jiang, Jihui Jin, Cheng Peng, Guangyu Hou, Jinping Li,
Jianmin Yu, Xiaohui Yu, Hualei Liu, Shufang Sun and Liping Yuan per-
formed analysis of the infection situation. All authors reviewed the
manuscript.
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on re-
quest from the corresponding author. The data are not publicly avail-
able due to privacy or ethical restrictions.
ORCID
Wenming Jiang  https://orcid.org/0000-0002-1946-7212
Jiming Chen  https://orcid.org/0000-0002-0404-0830
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How to cite this article: Liu S, Zhuang Q, Wang S, et al. Control
of avian influenza in China: Strategies and lessons. Transbound
Emerg Dis. 2020;67:1463–1471. https://doi.org/10.1111/
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