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Avian flu
Dr Ruth Watkins
Penygraig Goch, Llanddeusant, Llangadog, Carmarthenshire
Filed 09 Mar 06
www.land-care.org.uk
This report, expressing the
personal views of retired clinical virologist and
current farmer in the Welsh hills, Dr Ruth Watkins, is dated
28th Februrary 2006.
Land-Care is grateful to Dr Watkins for her kind permission to publish
the report in its full and condensed forms on this website.
The report makes an important
contribution to the fuller debate that is urgently needed regarding
the management of Avian Influenza and its implications,
both globally and in relation to the UK
For the condensed version Click
Here
What is the nature of the highly pathogenic
avian influenza A virus H5N1 that has travelled from China across
Asia to India Africa and Europe, and if it is not already here,
to Britain’s borders?
Previously when a highly pathogenic avian
influenza virus (HPAI) outbreak occurred in domestic poultry it
vanished once the infection was eliminated from domestic flocks.
It appears not to have been sustained in wild bird populations -
such was the case with the H7N7 outbreak in Dutch poultry in 2003.
An HPAI virus may arise in domestic poultry from a low pathogenicity
virus that has been circulating without symptoms, as in Pennsylvania
in 1983/4; intensively reared poultry appear to select for pathogenic
avian influenza strains. The current lineage of the current avian
HPAI H5N1 virus has been continuously present in China in domestic
poultry for a decade. Several different genetic variants have emerged
over this time in China, the epicentre of this epidemic, and they
have spread locally first recorded in Hong Kong in 1997, and then
to SE Asia where for example on 3 occasions a different variant
of avian HPAI H5N1 has appeared in Vietnam. The genetic variant
of HPAI H5N1 now in Europe, let us call it Zq, was first identified
in spring 2005 at Lake Qinghai in Northern China when some 2000
bar-headed geese and other birds died of it. In fact this virus
is thought to have originated some 1000 miles south. The persistence
and spread of this HPAI H5N1 virus strain, Zq, is an extraordinary
phenomenon without precedent.
Whilst spread in China and SE Asia, and
even into the Middle East, India and Africa has been very largely
due to human intervention moving infected poultry and its products,
it has also been aided by the FAO approved practice of integrated
farming when poultry manure is used to feed farmed fish- in Lake
Qinghai also. This allows the spread of the virus to water birds,
ducks are particularly significant. Avian influenza viruses infect
the gut of ducks, and are spread by the faeco-oral route amongst
them. Virus present in the water can be swallowed and establish
an enteric infection in a duck. Unlike other bird species, ducks
may shed avian influenza viruses for months, remaining persistently
infected without producing antibody and remaining well- they are
carriers shedding infectious virus from the gut. Other aquatic birds
are also considered to be the reservoir host for avian influenza
viruses e.g. terns. It is clear that the variant of HPAI H5N1 from
Qinghai, Zq, has been spread across Western Europe by wild birds.
This has given rise to a trail of dead swans across Europe, as well
as other bird species at wetland areas.
Even ducks may become ill with the HPAI
H5N1 infection, and have been found dead, infected with the Zq strain.
Other wild birds, passerines, geese, quail, pheasants, raptors etc
are more likely to fall ill and die as a result of infection than
ducks, as are domestic chickens , turkeys etc. The HPAI H5N1 virus
gives rise to an acute infection via the respiratory tract in these
birds with an incubation period before illness of a few days after
exposure. The virus is virulent, spreads outside the respiratory
tract and is able to multiply in any tissue including the brain
to high titre. The bird usually dies after a short illness. If there
is recovery it is accompanied by a good antibody response, the antibody
is protective. The virus infection is acute and cleared by the immune
response.
The HPAI virus has at least two genetic
changes, as compared with the low pathogenicity viruses that are
the usual form of avian influenza found in wild birds. The changes
allow the virus to replicate to very high levels in infected cells
and in all tissues. There is a short sequence of basic amino acids
at the cleavage site of the haemagglutinin in HPAI viruses allowing
cleavage by protease enzymes present in all tissues. In the low
pathogenicity viruses this process is confined to the respiratory
tract as the haemagglutinin can only be cleaved by a respiratory
tissue specific protease as it has a different sequence of amino
acids at the cleavage site. This is an important difference as the
newly formed virus can only infect a cell if the haemagglutinin
protein has been cleaved to produce a spike that can penetrate the
cell membrane to allow entry.
The HPAI form of avian influenza viruses
is highly virulent and infectious. By the time one domestic bird
in a flock is sick or dead many others will already be infected
and incubating the disease. They will also be shedding virus even
before they are ill. The mortality rate can be as high as 100%.
Thus the infected flock will be decimated or wiped out even if it
is not culled.
HPAI virus is shed in every secretion and
is in feathers, flesh, manure and if not in eggs then upon their
surface. Infection can be spread indirectly between farms or poultry
houses by contamination of hands, feet, tyres, straw, feed, water
and by infected wild birds or by rodents, infected or contaminated.
Other animals can become infected such as felines and pigs. Biosecurity
for domestic poultry will be hard to maintain for years in the face
of the persistence of this virus in the wild bird population or
its repeated reintroduction into wild birds. Amplification of the
risk of infection to domestic flocks or wild birds occurs with every
outbreak of HPAI in domestic poultry when enormous quantities of
the virus are generated. Safe disposal of infected manure is important.
A laboratory level of cleanliness is required and may be impossible
to maintain when the virus is present for many years in the environment
where wild birds act as a reservoir. The source of the outbreak
in a commercial turkey farm in France, where all the birds were
inside and subject to biosecurity, is being investigated and it
is thought it may have been introduced by infected wild bird droppings
on straw or a shoe. In Nigeria, Egypt and India infection occurred
initially in commercial intensive poultry production units, but
was very likely introduced in those countries by the international
trade in eggs, birds or products incorporating, or contaminated,
with poultry manure. It is said avian influenza virus can remain
infectious for up to 2 weeks dried onto fomites and for several
months in infected meat and eggs at 4degC.
The influenza virus is an enveloped virus
with two viral proteins embedded in the surface, the haemagglutinin,
H, and the neuraminidase, N. The H protein binds to cell receptors
in order for the virus to gain entrance to and infect a cell (see
above), and the N protein acts as an enzyme releasing newly formed
budding viruses from the infected cell surface. There are at least
15 different H types and 9 different N types of influenza A viruses
and all are found in aquatic birds in various combinations e.g.
H5N1, H5N2 etc. Influenza A viruses have also adapted to man, pigs,
seals and horses but these species-adapted viruses have limited
H and N types e.g. horses have H7N7 (equi 1) and H3N8 (equi 2).
Inside the loose envelope of the influenza
virus, the 8 RNA segments that comprise the genome are found. Each
codes for a different viral protein, e.g. one for H and one for
N and one for the polymerase protein concerned with replication
and 5 others coding for proteins concerned with either structure
or replication.
The segmented genome allows reassortment
of the 8 genes. reassortment has been documented. It occurs when
the same cell is infected with two different viruses, a rare event
but one that can occur naturally when there is a simultaneous infection
with two different influenza viruses e.g. a human is infected with
a human influenza A virus and an avian virus. In most instances
the reassorted viruses are not shed, or are not competent, or never
get the opportunity to establish a chain of infection. However the
pandemics in humans of H2N2 in 1957 and H3N2 in 1968 did arise from
newly reassorted viruses, with one or more avian genes, from China.
The new H genes were derived from avian viruses. These two viruses
each caused a pandemic in humans because no one had immunity to
H2 or H3 as these haemagglutinin types were not found in the circulating
human influenza A virus at the time of their introduction. For mysterious
reasons H3 replaced H2 in 1968. In 1977 H1N1 reappeared, a laboratory
escapee from the 1950s, and currently H3N2 and H1N1 co-circulate
in humans.
The influenza pandemic in humans that followed
the First World War, the 1918 and 1919 pandemic, was caused by a
virus that had all 8 gene segments derived from an avian H1N1 influenza
A virus. A number of point mutations in several of the avian genes
had to have taken place to humanise the avian virus sufficiently
to pass from human to human. That virus also infected pigs and became
host adapted; it still circulates amongst them albeit now distantly
related to its ancestor. The H1N1 pig adapted virus is present worldwide
in pigs.
There is concern that either of these two
courses, reassortment or a number of point mutations, might change
the avian HPAI H5N1 virus enabling it to pass efficiently between
humans. This has not happened yet. However the emergence of a new
human pandemic virus has never been observed under close scrutiny
before but has simply appeared as a fait accompli. Humans have been
infected by the current avian HPAI H5N1 strains by close contact
with an infected bird. The mortality may not be quite as high as
50% if cases present early for treatment and intensive care. Either
living with the sick birds or handling them, particularly preparing
them for eating such as plucking gutting and so on, has given rise
to human infections. There have been clusters but most are thought
to be from a point source, an infected bird, and there have been
very few instances of spread between humans. Both anti-virals and
vaccines are being stockpiled and developed in case of the emergence
of a human pandemic strain of H5N1 with, it is feared, virulence
similar to that of the 1918-1919 influenza pandemic.
It is not appropriate to treat birds with
anti-virals, not wishing to induce resistance, but to reserve these
for the treatment of human cases.
What of vaccines should biosecurity fail
to protect domestic flocks, whether housed or free range or totally
free range pheasants, from infection?
Both Haemagglutinin and Neuraminidase are
important in raising immunity but of the two Haemagglutinin is the
most important providing protection against infection of the respiratory
tract.
The Dutch vaccine is an H5N2 virus and has
been inactivated. Thus the vaccine is not infectious and harmless
to eat. Two shots two weeks apart are needed to produce a good level
of immunity. This is typical of an inactivated vaccine when sufficient
quantity of protein must be introduced to the immune system to prime
and then boost the antibody response to a protective level. Whatever
vaccine is used the H5 in the vaccine must be sufficiently closely
related to the H5 in the virus strain, Zq, now present in wild birds
in Europe and threatening to infect our UK poultry to provide a
protective immunity. All H5 molecules will have an immune cross
reactivity but distantly related H5 will not induce a solid protective
immunity.
A number of other vaccines have been developed,
and will be in development now in response to the world pandemic
of avian HPAI H5N1. The HPAI H5N1 virus destroys eggs or tissue
culture cells that could be used to grow it. Thus molecular methods
must be used to insert the part of H5 that is immunogenic into other
viruses that can be grown up in culture and be administered as a
vaccine. The H5 can be inserted into a non-pathogenic influenza
virus, or as a foreign gene into an avian pox virus or an adenovirus.
The protection given by vaccination may
not be complete in all vaccinated animals exposed to a high infective
dose. No vaccine is perfect and the influenza vaccines are not very
good. Vaccination of horses against equine influenza is recommended
for horses taking part in events and travelling abroad and has been
very successful in preventing outbreaks. There are instances of
a vaccinated horse shedding virus asymptomatically and infecting
a non-vaccinated animal. Also the H3N8 vaccine strain has had to
be updated because of drift, the accumulation of point mutations
over years resulting in the current strain being too distant from
the vaccine strain so that protective immunity is not evoked by
vaccination, as occurs more rapidly in human influenza when the
vaccine is updated annually to ensure its efficacy. Of note is the
fact that vaccination of all domestic poultry against the H5N1 strains
infecting poultry in Vietnam appears to have been successful in
eradication of outbreaks in poultry and put a stop to human cases
of infection. Diseased flocks were culled. It is said that 150 million
doses of vaccine were given. If a vaccinated bird is infected it
is asymptomatic so must therefore have a limited infection, perhaps
confined to the respiratory tract, and shed a lesser amount of virus.
In the context of a fully vaccinated flock the HPAI infection must
peter out. This would mean the overall viral load and contamination
of the environment is less, it is safer for humans, and does not
allow infection to amplify in local wild birds and reach other vaccinated
poultry flocks. An epidemic infection is eliminated when one infected
individual cannot infect as much as even one other on average.
Vaccination of domestic poultry may be the
only way of eliminating the HPAI H5N1 virus from wild bird populations
in the long-term. The annual reproductive rate of wild birds ensures
there are large annual populations of young birds susceptible to
infection. The use of poultry manure to feed fish in lakes must
be prohibited. International movement of poultry and its products
such as manure must be controlled and prohibited as much as possible.
Pheasants and free-range poultry would seem to be especially vulnerable
to infection from wild birds. In the case of pheasants these are
shot in Autumn, for the most part less than one year old, and then
plucked and prepared by individuals taking part in the shoot as
well as local butchers. Pheasants are reared in Spring and then
released saturating the local habitat. There is a significant pheasant
sector in Wales and problems with HPAI H5N1 infection could arise
in the released birds infecting the local wild birds and poultry,
and in the shooting of infected birds when significant contact is
made with humans handling the birds and preparing them for the table.
Vaccinating young pheasants before release would be the sensible
option.
Outbreaks of infection in commercial domestic
flocks will result in loss of consumer confidence. Whilst DEFRA
have not chosen vaccination as at least part of their strategy to
combat this pandemic of HPAI H5N1 at least they have moved forward
on diagnosis in contrast to the 2001 FMD outbreak. A bird or flock
will not be declared infected unless a positive viral diagnosis
has been made. The means of diagnosis is by PCR and the products
are probed or sequenced in order to define the type and strain of
influenza virus. Progress indeed. Why not vaccinate free- range
poultry and pheasants as well as hold vaccine in reserve to ring
vaccinate an outbreak in a domestic flock? Vaccination may be found
necessary in bio-secure flocks to prevent breakdowns of infection
in intensive poultry systems. If we do not order or make any vaccine
for birds then we can never use it. Are we heading for another disaster
on the scale of 2001?
©Ruth Watkins
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