Rev. sci. tech. Off. int. Epiz.

, 2014, 33 (3), 691-709

The scientific rationale for the World

Organisation for Animal Health standards
and recommendations on avian influenza
J. Pasick (1) & S. Kahn (2)*
(1) Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, 1015 Arlington Street,
Winnipeg, Manitoba R3E 3M4, Canada
(2) Consultant, calle Pumacahua, 653. CABA 1406, Argentina
*Corresponding author: [email protected]

Summary
The World Organisation for Animal Health (OIE) prescribes standards for the
diagnosis and control of avian influenza, as well as health measures for safe
trade in birds and avian products, which are based on up-to-date scientific
information and risk management principles, consistent with the role of the
OIE as a reference standard-setting body for the World Trade Organization (WTO).
These standards and recommendations continue to evolve, reflecting advances
in technology and scientific understanding of this important zoonotic disease.
The avian influenza viruses form part of the natural ecosystem by virtue of their
ubiquitous presence in wild aquatic birds, a fact that human intervention cannot
change. For the purposes of the Terrestrial Animal Health Code (Terrestrial
Code), avian influenza is defined as an infection of poultry. However, the scope of
the OIE standards and recommendations is not restricted to poultry, covering
the diagnosis, early detection and management of avian influenza, including
sanitary measures for trade in birds and avian products. The best way to manage
avian influenza-associated risks to human and animal health is for countries
to conduct surveillance using recommended methods, to report results in a
consistent and transparent manner, and to apply the sanitary measures described
in the Terrestrial Code. Surveillance for and timely reporting of avian influenza
in accordance with OIE standards enable the distribution of relevant, up-to-date
information to the global community.

Keywords
Avian influenza – Diagnosis – Notification – OIE – Pig – Poultry – Terrestrial Animal Health
Code – Wild bird – World Organisation for Animal Health – World Trade Organization.

Introduction highly contagious animal diseases and transparency in

reporting listed diseases. The OIE Terrestrial Animal Health
Code (Terrestrial Code) contains science-based standards and
This report is in two parts. Part one reviews scientific
recommendations on listed animal diseases and zoonoses,
information relevant to the diagnosis, pathobiology, ecology
including avian influenza (1). In addition to supporting early
and epidemiology of avian influenza, including scientific
findings and conclusions on the role played by wild birds detection and rapid response, application of the Terrestrial
and pigs in the circulation of avian influenza viruses. Part Code standards can be relied upon to prevent the diseases
two relates this scientific information to the international spreading via international trade. Part two specifically refers
standards set by the World Organisation for Animal Health to the Terrestrial Code, Chapter 10.4. (‘Avian influenza’) and
(OIE). The OIE is an intergovernmental organisation, related texts, as well as Chapter 2.3.4. of the OIE Manual of
established in 1924, with the mandate to support Diagnostic Tests and Vaccines for Terrestrial Animals (Terrestrial
international solidarity in the control and prevention of Manual) (2).

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This report illustrates how advances in the scientific A/duck/England/1956 (H11N6), along with the German
understanding of avian influenza have driven the evolution 1949 and Manitoba 1952 isolates, gave the first indications
of the standards and recommendations contained in the of the variable nature of influenza viruses with respect to
Terrestrial Code. Unless otherwise indicated, all Terrestrial antigenicity and virulence.
Code citations refer to the 22nd edition, 2013.
A conceptual shift in the scientific understanding of the
influenza viruses that could cause HPAI began with the
Part 1: Diagnosis isolation of two viruses that were associated with fowl-
plague-like disease but that were antigenically distinct
and reporting of avian influenza from classical fowl plague virus, which belongs to the
haemagglutinin antigen avian 1 or Hav1 group. The first
involved a self-limiting outbreak on a small chicken farm
Early scientific thinking on avian influenza in Scotland in 1959 and the second involved a die-off of
The first account of avian influenza dates back to 1878 when European common terns (Sterna hirundo) in the Cape area
Edoardo Perroncito, a professor of pathology and of South Africa in 1961 (14). Both of these viruses, known
parasitology at the Veterinary Faculty of the University of respectively by their current nomenclature as A/chicken/
Turin, Italy, described a contagious disease that caused high Scotland/1959 (H5N1) and A/tern/South Africa/
flock mortality, affecting chickens and turkeys in northern 1961 (H5N3), were antigenically related to each other but
Italy (3). In 1901 Centanni and Savonuzzi (4) showed that did not belong to the Hav1 group. In March/April 1966 an
the agent responsible for ‘fowl plague’, a term that was later influenza virus was isolated from turkeys in an outbreak of
coined by Beaudette (5) in 1925, was an ultra-filterable acute disease in an extensive turkey-breeding establishment
agent. This eliminated the initial confusion with the acute in Ontario, Canada (15). This highly pathogenic variant
septicaemic form of fowl cholera caused by Pasteurella Ontario/7732 was related serologically by surface
multocida. However, Newcastle disease, which was first antigens to A/chicken/Scotland/1959 (H5N1) and A/tern/
described in 1926 (6, 7), and is clinically similar to fowl South Africa/1961 (H5N3) and was later designated as
plague in that it is capable of causing high flock mortality A/turkey/Ontario/7732/1966 (H5N9). These three viruses
in susceptible poultry, continued to cause confusion in were placed in the Hav5 subtype. To complicate matters
the diagnosis of fowl plague. In 1934, Burnet and Ferry further, Beard and Easterday (16) reported the isolation
(8) demonstrated that the two diseases were caused by of A/turkey/Oregon/1971, a Hav1 Nav2 virus that was
different viruses. As explained in the review by Alexander found by laboratory studies to be non-pathogenic for
and Brown (9), all the viruses recognised as avian influenza chickens, despite possessing the haemagglutinin of classical
in the first half of the 20th Century were fowl plague virus fowl plague virus. The existence of viruses that were of
isolates (all considered to be the same virus) belonging to high virulence for poultry but were antigenically distinct
what is now recognised as the H7 subtype. Outbreaks of from fowl plague viruses, as well as viruses that were
fowl plague that were associated with imports from northern antigenically related to fowl plague but were avirulent
Italy were widespread across Europe during the early part of for chickens, demonstrated the need for interventions by
the 20th Century (10) and were made notifiable in some of Veterinary Authorities to be based on appropriate criteria
these countries as early as 1903. and definitions of avian influenza viruses. At the time it was
concluded that government intervention should be limited
to influenza viruses of demonstrated virulence to poultry.
Scientific understanding
Reports evaluating the use of in vivo tests for the virulence
of avian influenza after 1955 of avian influenza virus isolates started to appear in the
The relationship of highly pathogenic avian influenza literature in the late 1970s (9). The first of these (17) showed
(HPAI) virus with other influenza viruses began to emerge that the intravenous and intracerebral pathogenicity index
in 1955, when Schäfer (11) showed that ‘fowl plague’ tests, which were normally used for Newcastle disease virus
viruses shared common internal antigens with influenza isolates, could also be used to quantitatively measure the
viruses from humans and swine. Shortly afterwards, it was virulence of avian influenza viruses. These tests also showed
demonstrated that two viruses that were shown not to kill a lack of correlation between virulence and antigenic type.
experimentally inoculated chickens (one virus isolated
from chickens in Germany in 1949 [12] and one isolated First official use of the term ‘highly pathogenic
from ducklings in Manitoba, Canada, in 1952 [13]) were avian influenza’
also influenza viruses. In 1956, two low pathogenicity
avian influenza (LPAI) viruses, which were antigenically At the First International Symposium on Avian Influenza,
distinct from HPAI virus, were isolated from commercial held in Bethesda, Maryland, the United States of America
ducks with respiratory disease. These viruses, currently (USA) in 1981, it was resolved that the term ‘fowl plague’
known as A/duck/Czechoslovokia/1956 (H4N6) and be abandoned and replaced with HPAI. It was agreed that

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HPAI virus strains should be defined by their ability to Evolution in our understanding of the origins
produce not less than 75% mortality within eight days in of highly pathogenic avian influenza viruses
at least eight susceptible four-to-eight-week-old chickens
inoculated by the intramuscular, intravenous or caudal air In April 1983, an H5N2 infection involving chickens,
sac routes with bacteria-free infectious allantoic fluid or which presented as acute respiratory disease, declining
cell culture fluids (18). This definition was adopted by the egg production and increased mortality, was detected in
World Organisation for Animal Health (OIE) in 1983. At Lancaster County, Pennsylvania. This virus was initially
the same symposium, Rudolf Rott presented a summary characterised as being of low pathogenicity, based on in
of the work that he and his co-workers had carried out, vivo tests, and so did not meet the definition of HPAI that
which showed that the pathogenicity of an avian influenza had been proposed at the First International Symposium
virus isolate was related to the proteolytic cleavage of on Avian Influenza and subsequently adopted by the
the viral haemagglutinin (HA) into amino-terminal HA1 OIE. For this reason, statutory control measures were not
and carboxy-terminal HA2 subunits (19). They found brought into play. An additional 25 cases were diagnosed
that the haemagglutinins of non-pathogenic Hav1 strains between April and October 1983 and none of the viruses
had a cleavage site that was structurally similar to that of isolated from these was highly pathogenic for inoculated
human influenza viruses while the haemagglutinins of the chickens or turkeys (30). A dramatically different form of
pathogenic strain had significantly more basic amino acids the disease appeared in early October and the virus that was
within the connecting peptides (19, 20). This set the stage isolated from these new cases was characterised as highly
for understanding the molecular basis of pathogenicity. pathogenic, based on in vivo tests. Control measures were
immediately introduced, including stamping out. However,
It is now understood that, in order for influenza A viruses
diagnosis and control were complicated by the earlier and
to be infectious, the haemagglutinin precursor, HA0, must
continued presence of the virus that exhibited the lower
be post-translationally cleaved by host proteases into HA1
virulence phenotype. In total, the outbreak resulted in
and HA2 subunits (21), thereby exposing a fusion peptide
the loss of over 17 million birds in Pennsylvania and the
at the newly formed amino-terminal end of HA2 (22).
Pathogenicity is determined by which host protease carries surrounding states. Both low pathogenicity and highly
out this post-translational cleavage. The HA0 precursor of pathogenic isolates possessed the identical cleavage site
LPAI viruses has a single arginine at the cleavage site and motif PQKKKR*GLF, typical of highly pathogenic viruses
another basic amino acid (arginine or lysine) at position –3 (31). It was later shown that a point mutation which
or –4. This cleavage site is recognised by extracellular host resulted in a lysine replacing a threonine at amino acid
proteases (e.g. trypsin) that are secreted by cells that line the residue 13 caused the loss of a glycosylation site present
respiratory and digestive tracts. In contrast, the HA0 precursor in the LPAI virus and led to the expression of the highly
of highly pathogenic viruses contains multiple basic amino pathogenic phenotype. The carbohydrate chain associated
acids at its cleavage site, which is recognised by a family of with this glycosylation site had presumably prevented
intracellular proteases known as subtilisin-related proteases, subtilisin-related proteases but not trypsin-like proteases
of which furin is a leading candidate (23). This latter class from gaining access to the HA0 cleavage site (32).
of proteases has a much broader tissue distribution, which
is directly related to the ability of highly pathogenic viruses A subcommittee of the United States Animal Health
to replicate systemically. It is now generally accepted that Association was established to deliberate the problems that
highly pathogenic viruses evolve from low pathogenicity had been encountered in characterising the pathogenicity
virus precursors (24, 25). On the basis of current evidence, of the virus responsible for the 1983 epizootic. It
this evolution appears to be restricted to viruses of the H5 recommended that:
and H7 haemagglutinin subtypes. In the majority of cases,
this evolution appears to take place after low pathogenicity – the in vivo test for pathogenicity testing be retained but
viruses have been introduced from their natural wild bird be limited to intravenous administration
reservoir into gallinaceous poultry. The acquisition of basic
amino acids at the HA0 cleavage site, which is associated with – H5 and H7 viruses that do not meet the in vivo criterion
the evolution to high pathogenicity, can occur by a number for HPAI should have the amino acid sequence of their HA0
of different mechanisms, including: cleavage site determined, and should be treated as highly
pathogenic if additional basic amino acids are present (33).
– nucleotide substitution
– the duplication of purine triplets due to polymerase These recommendations and similar specifications in the
slippage (26), which results in the insertion of basic amino European Union (EU) legislation on avian influenza (34)
acids at the cleavage site were adopted by the OIE Biological Standards Commission
– non-homologous recombination with cellular or viral in 1992 and published in the 14th edition of the Terrestrial
RNA (27, 28, 29). Code in 2005.

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Avian influenza epizootics with characteristics similar also encouraged by minimising unjustified trade restrictions
to those of the Pennsylvania outbreak have occurred in arising from the notification of strains of low pathogenicity.
other locations, such as Mexico (1994) and Italy (1999).
In these epizootics, a virus of low virulence, as determined The above clearly shows the progressive changes that
by molecular and in vivo tests, circulated for some months have been made to the Terrestrial Code. These changes
before mutating to a virulent form. In an outbreak of HPAI in have been science-based and driven by advances in our
poultry in central Mexico, a retrospective study showed that scientific understanding of the pathobiology, ecology and
the highly pathogenic virus was first isolated in December epidemiology of avian influenza. The leadership of the OIE
1994, more than one year after the initial isolation of low in promoting the global control of avian influenza viruses of
pathogenicity virus (26). By the end of 1994, the outbreak low pathogenicity has been crucial. This has helped many
had spread to involve 11 states and in January 1995 a second countries to justify the need for, and to obtain, resources
HPAI virus was confirmed (26, 35, 36). In Italy, an H7N1 for the control of such viruses, and thus to prevent serious
virus of low pathogenicity spread to involve 199 farms outbreaks of disease due to infection with highly pathogenic
between April and December of 1999, before mutating viruses.
to a highly pathogenic form (37). The highly pathogenic
virus, which had an intravenous pathogenicity index of Virulence determinants
3.0 and the HA0 cleavage site sequence PEIKGSRVRR*GLF,
was diagnosed on 17 December 1999. Difficulties similar
of avian influenza viruses
to those experienced in Pennsylvania in 1983 hampered Although the polybasic HA0 cleavage site is considered to
control measures. However, control was eventually achieved be the prime virulence determinant of highly pathogenic
in May 2000 – after 413 farms and nearly 14 million birds viruses, it may not by itself be enough to bestow high
had been affected. pathogenicity on a virus isolate. This was initially
demonstrated with the early low pathogenicity A/chicken/
First use of the term ‘notifiable avian influenza’ Pennsylvania/1983 virus isolates and subsequently
observed with a number of other viruses that have been
The large Italian epizootic triggered a debate about the isolated from field outbreaks or generated in the laboratory.
possible need for further changes to legislative control A/chicken/Texas/298313/04 (H5N2), isolated from a broiler
and trade measures to be applied to avian influenza chicken flock in Gonzales, Texas, in February 2004, was
infection. Ito et al. (38) showed that a highly pathogenic the first reported highly pathogenic virus that possessed an
virus could be generated by experimentally passaging an HPAI HA0 cleavage site motif (PQRKKR*GLF) but was
avirulent H5N3 virus of wild swan origin (A/whistling not virulent in in vivo tests (40). This HPAI designation
swan/Shimane/499/83) multiple times in chickens. This complied with the OIE definition of HPAI that had been in
supported the extensive accumulated epidemiological the Terrestrial Code since 2005. Discordant results between
evidence suggesting that highly pathogenic H5 and molecular and in vivo tests used to characterise virus
H7 viruses arise from chickens and turkeys following pathogenicity were retrospectively recognised for two other
the introduction of virus precursors of low pathogenicity H5 field-virus isolates (41), as well as for non-H5/H7 viruses
from the free-living bird reservoir. Furthermore, since that had been engineered to contain polybasic HA0 cleavage
the evolution to virulence is presumably a random event, sites (42, 43, 44). Stech and co-workers (43) showed that
the longer that low pathogenicity H5 and H7 viruses are inserting a polybasic cleavage site derived from HPAI
allowed to circulate in poultry, the greater the probability A/chicken/Italy/8/98 (H5N2) into the haemagglutinin of the
that a highly pathogenic virus will emerge. For these LPAI A/duck/Ukraine/1/63 (H3N8) virus was not sufficient
reasons, the EU Scientific Committee on Animal Health to immediately transform it into a highly pathogenic virus,
and Welfare in 2000 (39) and OIE ad hoc Expert Group despite the fact that it was able to replicate in tissue culture
Meetings in 2002 and 2004 recommended that standards in the absence of exogenous trypsin. This implied that the
and recommendations involving regulatory control and evolution of highly pathogenic viruses from H5/H7 viruses
trade should be extended to all H5 and H7 viruses in poultry, of low pathogenicity involved other changes, in addition
regardless of their pathogenicity. A revised definition of to a polybasic HA0 cleavage site. In contrast, Veits and
notifiable avian influenza (NAI), including infections with co-workers (44) reported that avian influenza viruses with
H5 and H7 subtype viruses of low pathogenicity, was adopted H2, H4, H8, and H14 haemagglutinins could support a
by the OIE in May 2005. The treatment of these H5 and highly pathogenic phenotype after acquiring a polybasic
H7 subtypes as notifiable disease agents provided an HA0 cleavage site. This approach has yielded different results
impetus for countries to introduce enabling regulatory for H6 viruses. While the insertion of a polybasic cleavage
frameworks and obtain financial support for surveillance, site into A/mallard/Sweden/81/02 (H6N1) (45) supported
reporting, stamping out and paying compensation to farmers a highly pathogenic phenotype in vivo, the insertion of a
whose flocks were depopulated because of the presence of polybasic cleavage site into A/turkey/Germany/R617/07
H5 and H7 viruses of low pathogenicity. Transparency was (H6N2) did not (44), indicating that other ‘cryptic’

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virulence determinants are also involved in the expression terns (Sterna hirundo) in the Cape area of South Africa in
of a highly pathogenic phenotype in vivo. The involvement 1961 (14) and a report of a highly pathogenic virus isolated
of ‘cryptic’ virulence determinants has been supported from two wild duck species during the surveillance of free-
by the results of a number of studies (41, 42, 46). These living waterfowl in Nigeria (54). The latter report found
experiments provoke important questions on the apparent coexisting but genetically distinguishable avian influenza
restriction of the highly pathogenic phenotype to viruses of viruses with a highly pathogenic viral genotype in two co-
the H5 and H7 subtypes. Are H5 and H7 viruses somehow habiting species of wild waterfowl, with evidence of non-
uniquely predisposed to acquiring polybasic HA0 cleavage lethal infection in at least one species, and without evidence
sites? Does a barrier exist in nature that prevents other of prior extensive circulation of the virus in domestic poultry.
HA subtypes from acquiring polybasic cleavage sites? It This finding suggested that some strains with potentially
remains to be seen if a polybasic HA0 cleavage site will ever high pathogenicity for poultry could be maintained in a
be found in a non-H5/H7 field isolate from poultry. community of wild waterfowl (54).

In this vein, the phenomenon of non-homologous Scientific evidence collected in experimental studies and
recombination as a mechanism by which H7 viruses could during the observation of real-life disease outbreaks due
acquire a polybasic HA0 cleavage site first came to light to HPAI overwhelmingly concludes that these disease
as a result of laboratory experiments (47, 48) that were outbreaks originate in domestic poultry (e.g. chickens,
carried out more than a decade before the first reports that ostriches) that are raised in intensive management systems.
this same mechanism was responsible for the evolution to
highly pathogenic virus in the field (27, 28, 29). Taking Nonetheless, epidemiologic investigations and phylogenetic
into account the developments described above, current analysis imply that the wild bird reservoir is the original
scientific evidence supports the recommendations of the source of H5/H7 viruses of low pathogenicity that give rise
Terrestrial Code (1). to highly pathogenic viruses, and that the latter viruses
do not form a separate or unique phylogenetic lineage
The role of wild birds as a reservoir or lineages in waterfowl (24, 25). Although outbreaks
of avian influenza infection for poultry of Eurasian H5N1 HPAI in wild birds have, at times,
resulted in mass mortality events, like the large die-off of
The exposure of gallinaceous poultry to low pathogenicity wild waterfowl at Lake Qinghai, in the People’s Republic
H5/H7 viruses of wild bird origin does not appear to be a of China in May to June 2005 (55), extensive testing
rare event (49). Many, if not the majority, of such exposures of hundreds of thousands of apparently healthy wild
result in subclinical, transient infections with no spread birds has either failed to detect or rarely detected these
to other flocks, which are often only recognised after the H5N1 viruses. In summary, the available scientific evidence
fact on the basis of flock seroconversion (49). The reason supports the hypothesis that HPAI never, or at worst
that these viruses fail to persist in poultry may be due to very rarely, emerges in the free-living wild bird reservoir
the fact that they are poorly adapted to their new host and that these viruses do not persist when introduced
and are unable to replicate and be transmitted efficiently. into this reservoir.
The 50% minimum infectious dose (MID50) has been
used to evaluate virus adaptation to a particular species This is in stark contrast to the situation in domestic poultry.
(50, 51). These studies have shown that wild-bird-origin The reason(s) for this difference are not known; however,
H5/H7 viruses of low pathogenicity are generally not well Lebarbenchon et al. (56) have proposed that the different
adapted to chickens, requiring 100 to 1,000 times more selective pressures which are present in natural ecological
virus to infect chickens when compared with poultry- systems (wild birds) versus artificial ecological systems
adapted viruses. However, experimental studies have (intensive poultry farming, live bird markets, etc.) may
shown that, by repeatedly passaging viruses of wild bird explain why HPAI viruses do not emerge or persist in
origin through poultry, adaptation, as demonstrated by natural ecosystems.
increased levels of virus replication and improved chicken-
to-chicken transmission, can occur (52, 53). The adaptation Differences in the pathobiology of avian
process is unpredictable and appears capable of following
many paths.
influenza in wild birds and in domestic poultry
Influenza A virus replication in waterfowl, which takes place
Wild birds in the orders Anseriformes (ducks, geese and in the intestinal tract, favours faecal-oral and potentially
swans) and Charadriiformes (gulls, terns and waders) are faecal-faecal routes of transmission. In contrast, airborne
the reservoir of influenza A viruses in nature. However, transmission, which is most important in domestic poultry,
reports of HPAI virus infection in wild birds without any is associated with virus replication within the respiratory
involvement of poultry are very rare. Two such reports tract. Lebarbenchon et al. (56) further suggested that the
include a die-off of approximately 1,300 European common evolution of H5/H7 viruses from low to high pathogenicity,

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which occasionally follows the introduction of a wild bird Africa, which occurred in late 2005 and 2006. Of the
virus into poultry, may not be solely due to a change in 23 introductions of H5N1 avian influenza into Europe,
host species or the higher rates of pathogen transmission 20 were associated with migrating wild birds. In
that may indirectly select for higher levels of virulence Europe, mortalities involving mute (Cygnus olor) or
(low virulence may be a selective advantage when host- whooper (C. cygnus) swans were usually the first indication
host contacts are infrequent). These authors suggested that of the presence of H5N1 avian influenza (60, 61). This was
the process may also be driven by a larger set of ecological especially true during the winter of 2005 to 2006, when
parameters which are encountered in artificial ecosystems. spatial and temporal analysis of the outbreaks indicated that
These include a more uniform age structure, lower genetic they were associated with cold weather and the congregation
diversity and more constant environmental conditions, all of waterbirds along the 0°C isotherm (62). In June and
of which could contribute to the selection of more virulent July 2007, mortalities in waterbirds associated with
virus variants. At this stage, scientific evidence does not H5N1 avian influenza were again reported in Germany,
provide a clear basis on which to predict which LPAI H5/H7 France and the Czech Republic. Although swans and some
viruses will remain of low pathogenicity and which will other species that develop serious disease in response
mutate to become highly pathogenic. As discussed above, in to H5N1 avian influenza virus infection are viewed as
addition to a polybasic HA0 cleavage site, cryptic virulence excellent sentinel species, there is no scientific evidence
determinants can also influence the pathogenic phenotype of that they play any significant role as long-distance
a virus. The rate at which an H5/H7 low pathogenicity virus vectors of the virus. Studies using wild ducks that have
acquires the necessary genetic changes to become highly been experimentally infected with H5N1 viruses have
pathogenic is determined in large part by the error rate of demonstrated species variability in virus excretion and
the viral polymerase, which is approximately 10–5 mutations susceptibility to debilitating disease (63). After careful
per site, per genome replication. The emergence of a highly study, the potential role of the mallard (Anas platyrhynchos)
pathogenic virus from a precursor of low pathogenicity as a long-distance vector of H5N1 avian influenza has been
can take several months, as observed in Pennsylvania in largely discounted (64, 65).
1983 (~5 months involving 25 outbreaks), Mexico in
1995 (~13 months and present in 11 states), Italy Large-scale surveillance to detect the presence of H5N1
in 1999 (~8 months and 199 outbreaks), and as has avian influenza in wild birds was initiated in 2006 but
recently been determined for A/turkey/Ontario/7732/ has since been reduced. In its place, targeted surveillance,
1966 (~3 months) (57). The shift towards virulence can which focuses on sick or dead wild birds, is ongoing in
also occur relatively quickly, as observed with the Chile many parts of the world, with the objective of alerting
H7N3 outbreak in 2002 (~1 month), the British Columbia Veterinary Services to the possible exposure of free-ranging
H7N3 outbreak in 2004 (<1 month) and the Saskatchewan poultry to H5N1 avian influenza in countries that are
outbreak of H7N3 in 2007 (~1 month). In general, the currently free from these viruses. The reduced number of
longer that an H5/H7 virus of low pathogenicity is allowed mass mortality events reported in wild birds may be related
to circulate in poultry, particularly in areas of high poultry to a reduced prevalence of H5N1 avian influenza in wild
density, the greater the chances that a highly pathogenic birds after 2006 and/or to a reduced exposure of poultry
virus will emerge. This highlights the need for early to infected domestic ducks in enzootic countries. The true
warning, based on detection and reporting in accordance prevalence and persistence of H5N1 avian influenza in
with the OIE standards. wild bird populations throughout the world remain to be
elucidated. The hypothesis that best fits the accumulated
The significance of wild birds in relation to scientific evidence is that infected poultry, especially
domestic ducks, provide a reservoir of infection for wild
H5N1 avian influenza
waterfowl, and not the converse. Multiple studies of H5N1
The first indication that wild birds might be important in viruses in the live poultry markets of China and Vietnam
the spread of H5N1 avian influenza involved outbreaks in support the hypothesis that ‘backyard’ poultry and small-
wild waterfowl and captive wild birds in Hong Kong in late scale poultry farms are the main reservoir of infection for
2002 (58). However, it was not until the large outbreak H5N1 avian influenza.
among wild birds on Lake Qinghai in May 2005 that
concern over the involvement of wild waterfowl in the The significance of pigs
spread of H5N1 avian influenza came to the forefront. in relation to H5N1 avian influenza
This outbreak, which affected a number of avian species,
including bar-headed geese (Anser indicus), brown-headed H5N1 avian influenza was first isolated from pigs during
gulls (Larus brunnicephalus), great black-headed gulls routine surveillance carried out in Fujian Province in
(L. ichthyaetus) and great cormorants (Phalacrocorax carbo) southern China in 2001 and 2003 (66). This raised
(55, 59), preceded the rapid spread of the virus to north- concerns that pigs might serve as an intermediate host in
western Asia, Europe, the Middle East and eventually which the virus could eventually adapt to humans. Follow-

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up surveillance, involving 25 medium-to-large-scale pig (68, 71) have confirmed the susceptibility of pigs to
farms in Fujian Province, was carried out in 2004 and again H5N1 avian influenza. In both studies, pigs were
in 2007. Of the 499 sera from 2004 and 908 sera from inoculated with 106 50% egg infectious dose (EID50) of
2007, none tested positive for antibodies to H5 as determined H5N1 virus by the intranasal route. Nasal swab specimens
by haemagglutination-inhibition test and confirmed collected from these pigs demonstrated that virus shedding
by the micro-neutralisation test. More recently, the testing occurred from 1 to 5 days post inoculation and that virus
of 1,107 nasal swab samples collected from apparently titres were modest, ranging from ~1 to 4 log10 EID50/ml of
healthy four-to-six-month-old pigs in Jiangsu Province swab sample media. In one study (71), virus was found
of eastern China during the period from October 2008 only in the tissues of the respiratory tract (nasal turbinates,
to May 2009 yielded only two H5N1 viruses, giving an tonsils, trachea and lungs), with no evidence of systemic
isolation rate of 0.18%. The two isolates, A/swine/Jiangsu/ involvement. In the other study (68), virus was also
1/2008 and A/swine/Jiangsu/2/2009, were from clades 7 and found in the liver, in addition to tissues of the respiratory
2.3.4, respectively (67). tract, despite the fact that viraemia was not detectable.
In the study that did address the question of pig-to-pig
In Vietnam, serological evidence for exposure to H5N1 transmission (68), there was no evidence for transmissibility,
avian influenza in pigs has also been reported, albeit at a although the small numbers of infected and in-contact
very low prevalence (68). Out of a total of 3,175 pig sera animals that were used reduced the statistical power of the
that were collected in Vietnamese slaughterhouses between experiments.
September 2003 and June 2004, only 0.25% of the sera
were positive for H5 antibodies as determined by virus In summary, pigs are susceptible to infection with H5N1
neutralisation test and western blot analysis. avian influenza, with virus replication appearing to be
restricted to the respiratory tract. This is associated with a
In Indonesia, virological and serological surveillance brief period of virus shedding and the infection manifesting
carried out during January to February 2005, October itself either subclinically or as a mild respiratory disease.
2006 to February 2007 and November 2008 to April Sporadic field cases may have been the result of poultry-
2009 demonstrated H5N1 avian influenza in pigs in to-pig transmission but more evidence is needed to
2005 to 2007 but not in 2008 to 2009 (69). In 2005, a substantiate this hypothesis. Evidence for pig-to-pig
total of 35 H5N1 viruses were isolated from five out of transmission is scant at present. Although one plague-
seven private or commercial farms located in the Tangerang purified clone of an Indonesian swine H5N1 isolate
district of Banten Province. All of the positive farms had (A/swine/Banten/UT3062/2005) was shown to possess
poultry on site and phylogenetic analysis showed that all of an A134S substitution within the 130-loop of the
the viruses clustered with chicken isolates. receptor-binding pocket that is responsible for
human-type receptor recognition, and could bind to
In 2006 to 2007, a total of 17 H5N1 avian influenza viruses avian-type and human-type sialic acid receptors (69),
were isolated from private, commercial or government farms a fully swine-adapted virus has yet to appear. Based on
as well as slaughterhouse specimens collected in Banten, current scientific evidence, pigs are considered to be dead-
East Java, North Sumatra and South Kalimantan Provinces. end hosts for H5N1 avian influenza.
As during the 2005 surveillance period, poultry were either
found on site or within a kilometre of the affected site. These Because live pigs and porcine products present no significant
results could suggest poultry-to-pig transmission. However, risk of transmitting H5N1 avian influenza viruses either to
they should be interpreted with caution, as the evidence humans or to poultry, the Terrestrial Code does not make
is based on results from a single laboratory and no other recommendations regarding the implementation of health
laboratory has been able to reproduce these results. The measures for pigs and pig products in relation to avian
findings of Löndt et al. (70) argue against the hypothesis influenza (1).
of poultry-to-pig transmission. In this study, pigs that were
co-housed with ducks or chickens infected experimentally
Diagnosing avian influenza
with the H5N1 clade 2.1.1 virus A/turkey/Turkey/1/2005
failed to become infected as determined by polymerase The standards for diagnostic tests, including pathogenicity
chain reaction (PCR) testing of nasal swab samples and testing of influenza A virus isolates from poultry,
haemagglutination-inhibition assay of sera collected at are described in the OIE Terrestrial Manual (2). The
seven and 14 days post contact. prescribed test for agent identification for the purposes of
international trade involves inoculating the allantoic cavity
Setting aside the questions about poultry-to-pig of specific-pathogen-free embryonating fowl eggs that are
transmission, the fact that viruses with nearly identical genes at between nine and 11 days of incubation. The presence
were isolated from pigs on the same farms in Indonesia did of influenza A virus-group-specific-antigen can be
imply pig-to-pig transmission. Two experimental studies confirmed by an immunoassay, such as the agar gel

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immunodiffusion test, or lateral flow devices, which

detect influenza A nucleoprotein or matrix protein. Part 2: Preventing the spread
Alternatively, influenza A virus nucleic acid can
be detected by the use of reverse-transcription PCR of avian influenza through
(RT-PCR), using either nucleoprotein-specific or matrix-
protein-specific primers (72). Antigenic subtyping international trade in birds
of an influenza A virus isolate should be carried out
by haemagglutination-inhibition and neuraminidase- and avian products
inhibition tests, using highly specific reference antisera.
The presence of H5 and H7 subtype influenza A viruses can Introduction to the
also be determined by RT-PCR using H5- and H7-specific World Organisation for Animal Health
primers (72). The pathogenicity of a virus isolate can be
determined by in vivo and molecular-based methods. Using The OIE is an intergovernmental organisation, established
in vivo methods, an HPAI virus is defined as: ‘any virus that in 1924, with the goal of supporting international solidarity
is lethal for six, seven or eight of eight 4-to-8-week-old in the control and prevention of highly contagious animal
susceptible chickens within ten days following intravenous diseases, including through the promotion of transparency
in reporting listed diseases. In 1968, the OIE published the
inoculation with 0.2 ml of a 1/10 dilution of bacteria-free,
first edition of the International Animal Health Code, now
infective allantoic fluid’ or ‘any virus that has an intravenous
called the Terrestrial Animal Health Code (Terrestrial Code)
pathogenicity index (IVPI) greater than 1.2’ (2). For all
(1). In addition to setting standards for the improvement
H5 and H7 viruses that have been determined to be of low
of animal health and welfare and veterinary public health
pathogenicity in chickens, using one of the in vivo methods
worldwide, the Terrestrial Code sets sanitary standards to
described above, the amino acid sequence of the connecting
ensure safe international trade in terrestrial animals and
peptide of the haemagglutinin must be determined. If the
their products. The Terrestrial Code specifies both general
sequence is similar to that observed for other HPAI virus
(‘horizontal’) and disease-specific health measures to
isolates (i.e. it contains a polybasic HA0 cleavage site), the
be used by the Veterinary Authorities of importing and
isolate is then considered to be highly pathogenic.
exporting countries to avoid the transfer of agents that are
pathogenic for animals or humans, while at the same time
The detection of infection with an avian influenza virus avoiding unnecessary barriers to trade (1).
can be based upon isolating and characterising the virus, as
described above, or by identifying the presence of viral RNA The OIE Terrestrial Animal Health Standards Commission
that is specific for a virus of low or high pathogenicity. The (Code Commission) is the elected commission responsible
latter can be achieved using a number of different molecular- for updating the Terrestrial Code each year, based on scientific
based methods. Advances in molecular-based diagnostic information and inputs provided by Member Countries and
techniques have allowed avian influenza infections to be relevant organisations. The Code Commission is supported
detected more rapidly than can be achieved with methods in this activity by two other elected commissions, the
that depend on virus isolation. This can significantly reduce Scientific Commission for Animal Diseases and the
the high-risk period, which is defined as the time interval Biological Standards Commission.
between the introduction and the detection of a pathogen,
which is important for the rapid and effective implementation In 1995, with the signing of the World Trade Organization
of control measures. Identifying viral RNA that is specific (WTO) Agreement on the Application of Sanitary and
for avian influenza can be achieved by a number of different Phytosanitary Measures (SPS Agreement) (77), the OIE was
methods, including PCR-based amplification methods that mandated as a reference organisation to set health standards
can be coupled with either Sanger sequencing or one of the for trade in animals and animal products. As of October
next-generation sequencing methods (reviewed in 73 and 2014, the OIE has 180 Members.
74). As an example, and in response to the westward spread
of H5N1 avian influenza, Hoffmann et al. (75) developed an Background on international trade
H5-specific, real-time RT-PCR assay designed to amplify a in birds and avian products
150 nucleotide region of the H5 gene which incorporates the
HA0 cleavage site. This assay uses two probes: one targeting Poultry is the fastest-growing livestock industry. Global
a sequence that is reasonably conserved among various broiler meat production is forecast at 82.2 million tons
H5 viruses, and a second that is specific for the cleavage for 2012 (78). The top exporters of chicken meat in
site of Qinghai-lineage H5N1 viruses. Another example is a 2012 in decreasing order were: Brazil, the USA, the EU,
pan-haemagglutinin RT-PCR developed by Gall et al. (76). Thailand, China, Argentina, Turkey, Canada and Chile.
This universal primer set targets the HA0 cleavage site of all The top importers of chicken meat in 2012 in decreasing
influenza A virus subtypes; the products of which can then order were: Japan, Saudi Arabia, the EU, Mexico, Russia,
be used in sequencing reactions. Iraq, Hong Kong, Vietnam, the United Arab Emirates

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and Angola. Trade in live poultry is also very significant, Anatidae, within the order Anseriformes. The most
involving hatching eggs, day-old chicks and older poultry. important species, from a commercial viewpoint, are
There is also a significant global trade in pet and hobby chickens (Gallus gallus), turkeys (Meleagris gallopavo),
birds and birds for zoological collections. ducks (Anas platyrhynchos domesticus), geese (Anser anser
var. domestica) and pigeons (Columba livia). Based on their
The risks associated with the trade of live birds and poultry use for the production of meat, eggs or feathers, many other
products in the spread of avian influenza were reviewed in avian species may fall within the OIE definition of poultry,
2009 (79). This study found that the legal and illegal trade including Indian peafowl (Pavo cristatus), guineafowl
of live birds and bird products (with an emphasis on the (Numida meleagris), Japanese quail (Corturnix coturnix
specific role of poultry) may play a major role in the spread japonica), the common pheasant (Phasianus colchicus), emus
of HPAI, including over large distances. Based on findings (Dromaius novaehollandiae) and ostriches (Struthio camelus)
in other papers, the review indicated that illegal poultry in the order Struthioniformes, and rheas (Rhea americana)
movements are extensive in South-East Asia, as is the illegal in the order Rheiformes. All these species are susceptible
trade in fighting cocks, wild birds (particularly birds of to infection with influenza A viruses and can thus
prey) and exotic ‘pet’ or companion animal birds. In view of participate in virus amplification and spread. In addition
the largely illegal nature of cock fighting and the movement to domesticated birds used for commercial or production
of these birds, this trade represents a particular risk for purposes, the Terrestrial Code definition includes fighting
introducing avian influenza, as has occurred in Thailand cocks, which have been implicated in the spread of H5N1
and Laos. The review also reported that the movement of avian influenza, including to humans, in South-East Asia.
fighting cocks was associated with the spread of Newcastle
disease virus in western states of the USA between
2002 and 2003, showing the potential importance of such Definition of avian influenza
birds in spreading avian influenza (79).
Prior to May 2013
Relevant definitions in the Terrestrial Code Before May 2013, NAI was defined in the Terrestrial Code
(1) as an infection of poultry caused by any influenza A
As with all normative publications, it is important to virus of the H5 or H7 subtypes or by any avian influenza
establish clear and unambiguous definitions of key terms and virus with an IVPI greater than 1.2 (or, as an alternative,
concepts. The Terrestrial Code contains several definitions with at least 75% mortality), as described below.
relating to avian influenza, including those for notifiable
avian influenza, poultry, zoning, and compartmentalisation
(1). At the 81st OIE General Session in May 2013, the The ‘NAI viruses’ were divided into highly pathogenic
General Assembly agreed to a number of amendments notifiable avian influenza (HPNAI) and low pathogenicity
of the text in Chapter 10.4. (‘Avian influenza’). These notifiable avian influenza (LPNAI), which were defined as
modifications did not significantly change the requirements; follows:
rather the objective was to present them more clearly.
‘HPNAI viruses have an IVPI in six-week-old chickens
Definition of poultry greater than 1.2 or, as an alternative, cause at least 75%
mortality in four-to-eight-week-old chickens infected
In the Terrestrial Code, poultry is defined as ‘all domesticated intravenously. H5 and H7 viruses which do not have an IVPI
birds, including backyard poultry, used for the production of of greater than 1.2 or cause less than 75% mortality in an
meat or eggs for consumption, for the production of other intravenous lethality test should be sequenced to determine
commercial products, for restocking supplies of game, or whether multiple basic amino acids are present at the cleavage
for breeding these categories of birds, as well as fighting site of the haemagglutinin molecule (HA0); if the amino acid
cocks used for any purpose’. Birds that are kept in captivity motif is similar to that observed for other HPNAI isolates, the
for reasons other than those stated above, including birds isolate being tested should be considered as HPNAI;
that are kept for shows, races, exhibitions, competitions or
for breeding or selling these categories of birds, as well as pet
birds, are not considered to be poultry. For example, hobby ‘LPNAI are all influenza A viruses of H5 and H7 subtype
pigeons do not qualify as poultry, based on this definition. that are not HPNAI viruses.’
So-called ‘backyard poultry’ and fighting cocks were included
in the Terrestrial Code definition of poultry following the Modifications adopted
meeting of the Code Commission of October 2006. at the 81st General Session, May 2013
The OIE definition of poultry is most commonly used in In May 2013, the title of the chapter was changed to
connection with birds in the super-order Galloanserae, ‘Infection with avian influenza viruses’, for consistency
which includes the order Galliformes and the family with the approach used throughout the Terrestrial Code.

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Article 1 was deleted and the definition was modified to required surveillance, control and biosecurity measures
the following: have been applied for the purpose of international trade.

‘For the purposes of the Terrestrial Code, avian influenza is Zone/region: means a clearly defined part of a territory
defined as an infection of poultry caused by any influenza A containing an animal subpopulation with a distinct health
virus of the H5 or H7 subtypes or by any influenza A virus status with respect to a specific disease for which required
with an intravenous pathogenicity index (IVPI) greater than surveillance, control and biosecurity measures have been
1.2 (or as an alternative at least 75% mortality) as described applied for the purpose of international trade.
below. These viruses are divided into high pathogenicity
avian influenza viruses and low pathogenicity avian Veterinary Authority: means the Governmental
influenza viruses.’ Authority of an OIE Member, comprising veterinarians,
other professionals and para-professionals, having the
The text was modified at several points throughout the responsibility and competence for ensuring or supervising
chapter to reflect the amendment of the definition. the implementation of animal health and welfare measures,
international veterinary certification and other standards
and recommendations in the Terrestrial Code in the whole
The occurrence of infection was redefined, as follows:
territory.
‘The virus has been isolated and identified as such or
specific viral RNA has been detected in poultry or a product OIE requirements for reporting avian influenza
derived from poultry.’ In the Terrestrial Code, the requirements for reporting
disease events to the OIE are provided in Chapter 1.1. and
The requirement to report HPAI viruses in birds other than the OIE-listed diseases in Chapter 1.2. According to Article
poultry was not changed. The amended text reads: 1.2.3., infection with avian influenza viruses (defined as an
infection of poultry – see Chapter 10.4.), as well as infection
‘Infection with influenza A viruses of high pathogenicity with influenza A viruses of high pathogenicity in birds other
in birds other than poultry, including wild birds, should than poultry, are listed by the OIE (1). The Terrestrial Code
be notified according to Article 1.2.3. However, a Member requires the notification of highly pathogenic influenza in
should not impose bans on the trade in poultry commodities all birds. In addition, findings of H5/H7 LPAI viruses in
in response to such notification, or other information on poultry should be reported to the OIE. These requirements
the presence of any influenza A virus in birds other than are intended to encourage Members to report avian
poultry, including wild birds.’ influenza virus infection in wild birds without running the
risk of losing international markets due to the imposition of
trade bans that are not based on science.
Complementing this amendment, Article 1.2.3. was
modified to clarify that ‘infection with avian influenza
viruses as well as infection with influenza A viruses of high OIE policies on recognising
pathogenicity in birds other than poultry’ were included the status of a country, zone or compartment
on the OIE list of diseases for the purposes of notification,
according to the requirements set out in Chapter 1.1. For certain diseases the OIE has, since 1995, provided
standardised procedures for the official recognition of the
disease status of Member Countries. Taking effect from May
In summary, these amendments did not change the 2014, this procedure applies to four ruminant diseases, one
requirements for safe trade in any significant way. Rather, equine disease and one disease of pigs. In 1998, the WTO
the presentation of the chapter was improved and clarified. confirmed the OIE mandate to recognise disease-free areas
based on the SPS Agreement. Official recognition of disease-
Other relevant definitions free status provides significant market access benefits.

Further relevant definitions are as follows (1):

As of 2014, the OIE does not grant official recognition for
avian influenza. However, OIE Members may make a self-
Establishment: means the premises in which animals are declaration on the freedom of the entire country or of a zone or
kept. compartment within the national territory. Self-declarations
must be based on sound evidence demonstrating that the
Compartment: means an animal subpopulation contained OIE requirements, particularly those on surveillance, for
in one or more establishments under a common biosecurity the disease in question have been satisfied. The declaration
management system with a distinct health status with is made under the full responsibility of the Member Country
respect to a specific disease or specific diseases for which concerned. The OIE may publish information relevant to

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self-declarations but it does not accept responsibility for OIE standards and recommendations
shortcomings in the information provided, nor does it make on trade in birds and avian products
any undertaking regarding the maintenance of the declared
health status. All of the following text is based on the 22nd edition of the
Terrestrial Code (2013).
Provisions on country, zone or compartment
freedom from avian influenza Findings of avian influenza in birds other than poultry

In Article 10.4.3., the Terrestrial Code makes provision for According to Article 1 in Chapter 10.4., infection with HPAI
considering a country, zone or compartment as being free viruses in birds other than poultry, including wild birds,
from avian influenza. This must be based on documented should be notified according to Article 1.1.3. However, a
Member Country should not impose bans on the trade in
evidence that there has been no infection with avian
poultry commodities in response to such notification, or
influenza viruses in poultry for at least 12 months. The
other information on the presence of any influenza A virus
Terrestrial Code also contains provisions for regaining
in birds other than poultry, including wild birds.
disease-free status after the occurrence of infection with an
avian influenza virus of high or low pathogenicity.
The rationale for this article is that wild birds are considered
to be the natural reservoir for influenza A viruses globally,
Article 10.4.4. contains provisions for considering a and the control of influenza A viruses in the wild bird
country, zone or compartment free from infection with population is not possible. Therefore, all countries have
avian influenza viruses of high pathogenicity, based on some risk with regard to the introduction of avian influenza
documented evidence showing: viruses to poultry. Control of this risk is feasible through
the effective separation of and reduction of transmission
– the absence of infection in poultry with HPAI viruses
between wild and domestic populations. Reports of avian
during the last 12 months, although its status with respect
influenza viruses in wild birds are useful for the purpose
to LPAI viruses may be unknown, or
of global surveillance and should not result in trade
– based on surveillance in accordance with Articles restrictions. Trade bans following such reports do not
10.4.27. to 10.4.33., the country, zone or compartment help to prevent the spread of avian influenza. In fact, such
does not meet the criteria for freedom from avian influenza actions discourage reporting, hinder global surveillance
but any virus detected has not been identified as highly and, therefore, increase the risk of disease spread.
pathogenic.
Risk pathways for the entry of avian influenza viruses
A key concept in the Terrestrial Code is the use of surveillance
The spread of avian influenza viruses of highly pathogenic
to demonstrate the absence of virus circulation. Articles and low pathogenicity subtypes is associated with human
10.4.27. to 10.4.33. specify the key parameters for effective activities involving the movement of infected birds, their
surveillance to demonstrate the absence of virus circulation. products or contaminated fomites.
These parameters depend on historical and geographical
factors, industry structure, population data and proximity
Risk analysis can be used to classify commodities into four
to recent outbreaks.
groups, based on the relative likelihood of virus transmission
(79). These are:
Surveillance should be under the responsibility of the
Veterinary Authority, should include active and passive i) live poultry and other birds
surveillance and, where applicable, targeted surveillance, ii) genetic material, including one-day-old chicks, hatching
and should utilise clinical, virological and serological eggs and semen
surveillance methods.
iii) commodities for human consumption, such as eggs and
meat, and
With respect to the detection of H5 or H7 subtype
antibodies in the absence of virus, the Terrestrial Code states iv) other commodities (e.g. feathers, feather meal and
that, when antibodies to H5 or H7 subtype avian influenza poultry meal).
viruses are detected in poultry and are not a consequence The Terrestrial Code recommendations and scientific
of vaccination, an immediate and thorough epidemiological rationale for each of these groups are set out below.
and laboratory investigation into their source should be The definitions of freedom from avian influenza in the
initiated. This should not be considered as an occurrence Terrestrial Code are explicitly linked to the requirements for
of infection if further investigation fails to isolate virus or surveillance – a fact that underpins the safeguards provided
detect viral RNA. by the measures described below.

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Risk management: live poultry and other birds The Terrestrial Code definitions of freedom from avian
influenza are explicitly linked to the requirements for
Since infected birds are actively shedding virus, their surveillance – a fact that underpins the safeguards provided
movement represents the greatest risk for introducing virus by the measures above.
to a farm, region or country. The incubation period (the
time between exposure to the virus and the first appearance
of clinical signs) is variable and depends on a number of Risk management: poultry meat
factors, including the virus isolate and its adaptation to a When chickens are infected with an HPAI virus, because of
particular host species, the immune status of the host, and the systemic nature of the infection, virus can be found in
environmental stressors, as well as the dose and route of the visceral organs, brain, skin, skeletal muscle, bone and
exposure. Under natural conditions, the incubation period blood, as well as in respiratory secretions and alimentary
for individual birds can be as short as three days and for tract excretions. In contrast, in chickens infected with LPAI
infected flocks as long as 14 days (80). For the purposes viruses, virus is restricted to the respiratory and alimentary
of the Terrestrial Code, the incubation period for avian tracts with no systemic involvement (51). However, there
influenza is defined as 21 days. This definition reflects the is potential for the meat to be contaminated by virus from
longest period that may elapse between the introduction the respiratory or gastrointestinal tracts during processing
of the pathogen into the animal and the occurrence of the of the carcasses, if the birds are in the acute infectious phase
first clinical signs of disease. This provides an important (81). For fresh poultry meat, Article 10.4.19. recommends
added safety margin in reducing the risk of introducing the that, in the case of importation from a country, zone or
virus through trade. In cases of infection with HPAI virus, compartment free from avian influenza, or free from
severe clinical signs are normally found at the individual infection with high pathogenicity viruses in poultry, the
bird and flock levels. This is particularly applicable to Veterinary Authorities require an attestation that the entire
gallinaceous poultry but may not apply to ducks and geese. consignment of meat comes from poultry that have been
In contrast, infection with LPAI viruses may give rise to a kept in a country, zone or compartment free from infection
with HPAI viruses in poultry since they were first hatched, or
range of clinical presentations from subclinical to severe.
for at least the past 21 days; that they have been slaughtered
The more severe clinical presentations usually occur when
in an approved abattoir in a country, zone or compartment
complicated by the presence of other pathogens. For this
free from infection with HPAI viruses in poultry; and
reason, the ‘infectious period’ (which is the time between the
that they have been subjected to ante- and post-mortem
first detection of virus in bodily secretions or excretions and inspections in accordance with Chapter 6.2. and found free
the absence of detectable virus) is more relevant than the of any signs suggestive of avian influenza.
‘incubation period’ in determining the period required for
the application of control measures to prevent transmission.
Risk management for processed poultry meat and products
The infectious period can be longer than the incubation is covered in section 2.9.
period, i.e. virus may be shed in secretions and excretions
before the onset of clinical signs and after clinical signs have
abated. The infectious period typically lasts seven to ten Risk management: eggs for human consumption
days but can be as long as 21 days. As a consequence of cloacal shedding, LPAI virus can be
found on the surface of eggs laid by acutely infected hens,
The Terrestrial Code provisions for the importation of but such virus has not been demonstrated in the internal
poultry (including day-old chicks) take into account the contents of chicken eggs (82). There is one report of a
status of the country, zone or compartment from which the (non-reportable) avian influenza virus being detected
poultry originate, and are based on veterinary attestations in the internal contents of eggs (83). This resulted from
regarding, among other things, the source of the poultry, the experimental infection of breeder turkeys with the H3N2
absence of clinical signs of infection, and the use/non-use subtype virus A/turkey/Ohio/313053/04 (83).
of vaccination.
No studies have demonstrated LPAI virus in the internal
contents of chicken eggs and surface sanitisation of eggs is
For live birds other than poultry, Article 10.4.6. makes therefore considered an effective means of managing the risk
provision for importation regardless of the avian influenza associated with eggs imported from a country or zone that
status of the country of origin. Trade should be based on is infected with such viruses. This, however, may not be the
a veterinary certificate attesting to the absence of clinical case with eggs that originate from a country or zone affected
signs of infection with a virus that would be considered by HPAI viruses, as it has been established that such viruses
avian influenza in poultry; a minimum of 21 days’ isolation can be found on the eggshell surface as well as within the
before shipment; testing of a statistically valid sample of the internal egg contents (82). Provisions for this difference are
birds; and information on vaccination (as appropriate). covered in Article 10.4.15. of the Terrestrial Code, which, in

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effect, recommends processing by heat treatment to destroy purpose of disease control and/or international trade.
the avian influenza virus when importing egg products A compartment is an animal subpopulation with a distinct
from countries/zones/compartments that are not a) free health status, which is contained in establishments that are
from avian influenza or b) free from infection with HPAI under a common biosecurity management system and to
influenza in poultry. which surveillance, control and biosecurity measures have
been applied. The concept of a defined subpopulation of
Risk management for processed eggs for human animals with a ‘higher health status’ also applies to zones.
consumption is covered in section 2.9. While a compartment is defined primarily by management
and husbandry practices that relate to biosecurity, a zone is
Risk management: primarily defined on a geographical basis, with reference
poultry feathers and derived products to natural, artificial or legal boundaries. In practice, spatial
considerations and good management play important
Perkins and Swayne (84) detected influenza A nucleoprotein roles in the application of both concepts. In both cases,
antigen in the basilar and intermediate epithelium of the the Veterinary Authority has authority over the definition
feather follicles of seven gallinaceous species that were and approval of the subpopulation. The compliance of
infected intranasally with A/chicken/Hong Kong/220/ livestock producers and associated industries with the rules
97 (H5N1). Yamamoto et al. (85, 86) reported that established by the Veterinary Authority is paramount to the
H5N1 HPAI can replicate in the feather epidermal successful maintenance of a compartment or zone.
cells of subclinically infected domestic ducks and later
(87) showed that higher viral loads were associated In many countries, commercial poultry production takes
with feather specimens, compared with those found in place in ‘industrial’, vertically integrated production
oropharyngeal or cloacal swabs. Furthermore, infectious systems, where all inputs and outputs are under the control
virus could be recovered from feathers under favourable of a company or consortium of companies. This type of
storage conditions – 15 days if stored at 20°C and production system is well suited to compartmentalisation.
160 days if stored at 4°C (87). At the request of Member Countries, the OIE is providing
advice to help to implement this concept.
There is a significant international trade in feathers used for
commercial purposes. Although the transmission of avian Vaccination against avian influenza
influenza viruses by feathers has not been documented
in practice, it would be valuable to have more scientific The OIE does not recommend the widespread use of
evidence to make a definitive assessment of the risks. The vaccination for the prevention of avian influenza in general
Terrestrial Code recommends processing to inactivate avian but the Terrestrial Code does contain recommendations on
influenza viruses that may be present. Processing parameters vaccination in outbreak situations to prevent the spread
are recommended for feather meal but details of an effective of the virus and to manage the risk of human exposure.
Where vaccination is used, the Terrestrial Code outlines
processing regime are yet to be defined for the feathers and
considerations relevant to achieving a satisfactory level
down of poultry and other birds.
of flock immunity and makes recommendations on
surveillance in vaccinated flocks. The Terrestrial Manual
Inactivation of avian contains standards and recommendations on vaccines and
influenza viruses in poultry products diagnostic tests.

Avian influenza viruses are relatively unstable and can be

inactivated by a number of physical methods, including
heat, extremes of pH, hypertonic conditions and desiccation Conclusions
(88). The Terrestrial Code contains recommendations for the
inactivation of avian influenza virus in eggs, egg products and Both avian influenza and the poultry industry have
meat for human consumption, based on scientific studies undergone significant changes since the establishment of
(82, 89, 90). The times and temperatures listed in Articles the OIE in 1924. Coincident with these changes, the global
10.4.25. and 10.4.26. for the inactivation of avian influenza trade of birds, poultry and poultry products has increased
virus in eggs and meat, respectively, are sufficient to achieve a substantially. The standards in the Terrestrial Code are based
7-log kill, providing an acceptable safety margin. on scientific information and risk assessment, consistent
with the principles of the WTO SPS Agreement. Application
of the OIE standards enables countries to conduct
Compartmentalisation: a tool to safeguard international trade safely and to avoid the imposition of
against avian influenza unjustified sanitary restrictions.
As described in the Terrestrial Code, compartmentalisation
is a procedure that may be used by a country for the

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Justification scientifique des normes

et recommandations de l’Organisation mondiale
de la santé animale en matière d’influenza aviaire

J. Pasick & S. Kahn

Résumé
L’Organisation mondiale de la santé animale (OIE) prescrit des normes applicables
au diagnostic et au contrôle de l’influenza aviaire, ainsi que des mesures sanitaires
visant à sécuriser les échanges internationaux des espèces aviaires et de leurs
produits dérivés, qui reposent intégralement sur des informations scientifiques
actualisées et sur les principes de la gestion des risques, conformément au rôle
dévolu à l’OIE en tant qu’organisme de référence reconnu par l’Organisation
mondiale du commerce (OMC) pour l’élaboration des normes dans le domaine de la
santé animale. Ces normes et recommandations évoluent en permanence, afin de
refléter les avancées technologiques et les nouvelles connaissances scientifiques
sur cette maladie zoonotique majeure. Les virus de l’influenza aviaire font partie
de l’écosystème naturel car ils sont omniprésents dans l’avifaune aquatique ;
l’être humain ne peut pas intervenir sur cette réalité. Aux fins de l’application
du Code sanitaire pour les animaux terrestres (le Code terrestre), l’influenza
aviaire se définit comme une infection des volailles. Néanmoins, la portée des
normes et des recommandations de l’OIE ne se limite pas aux volailles puisqu’elle
recouvre également le diagnostic, la détection précoce et la gestion de l’influenza
aviaire, y compris pour ce qui concerne les mesures sanitaires applicables aux
échanges internationaux des espèces aviaires et de leurs produits dérivés. La
meilleure stratégie que les pays puissent appliquer pour gérer les risques pour
la santé humaine et animale associés à l’influenza aviaire consiste à exercer une
surveillance basée sur des méthodes recommandées, d’en notifier les résultats de
manière cohérente et transparente et de mettre en œuvre les mesures sanitaires
préconisées dans le Code terrestre. La surveillance de l’influenza aviaire et la
notification en temps opportun conformément aux normes de l’OIE permettent
de diffuser à l’ensemble de la communauté mondiale des informations cruciales
et actualisées.

Mots-clés
Avifaune – Code sanitaire pour les animaux terrestres – Diagnostic – Influenza aviaire –
Notification – OIE – Organisation mondiale du commerce – Organisation mondiale de la
santé animale – Porcins – Volailles.

No. 09102014-00045-EN
Rev. sci. tech. Off. int. Epiz., 33 (3) 705

Fundamento científico de las normas

y recomendaciones de la Organización Mundial
de Sanidad Animal sobre la influenza aviar

J. Pasick & S. Kahn

Resumen
Basándose en información científica actualizada y en principios de gestión
del riesgo, la Organización Mundial de Sanidad Animal (OIE) dicta normas de
diagnóstico y control de la influenza aviar, así como medidas sanitarias para un
comercio seguro de aves y productos de origen aviar, en consonancia con la
función normativa que desempeña para la Organización Mundial del Comercio
(OMC). Esas normas y recomendaciones evolucionan sin cesar, al hilo de los
adelantos técnicos y la creciente comprensión científica de esta importante
enfermedad zoonótica. En razón de su ubicua presencia en las aves acuáticas
salvajes, los virus de la influenza aviar forman parte del ecosistema natural,
y este es un hecho que la intervención humana no puede cambiar. Aunque para
los fines del Código sanitario para los animales terrestres (Código terrestre) esta
patología está definida como una infección de las aves de corral, las normas y
recomendaciones de la OIE trascienden este ámbito estricto para cubrir aspectos
como el diagnóstico, la detección precoz y el tratamiento de la enfermedad,
lo que incluye medidas sanitarias en relación con el comercio de aves y
productos aviares. La fórmula más eficaz para gestionar los riesgos sanitarios
y zoosanitarios derivados de la influenza aviar estriba en que los países se ajusten
a los métodos recomendados de vigilancia, comuniquen los resultados de forma
coherente y transparente y apliquen las medidas sanitarias especificadas en el
Código terrestre. Gracias a la vigilancia y notificación puntual de la influenza aviar
con arreglo a las normas de la OIE se puede distribuir información pertinente
y actualizada a la comunidad mundial.

Palabras clave
Aves de corral – Aves salvajes – Código sanitario para los animales terrestres – Diagnóstico
– Influenza aviar – Notificación – OIE – Organización Mundial del Comercio – Organización
Mundial de Sanidad Animal – Porcinos.

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