Richard North has picked up on our comments regarding the blood testing on
the Brecon Beacons.  Bear in mind from previous messages that there are five
classes of antibody (Ig) raised against FMD virus and that an ELISA test is
specific to one of these:


Alan & Rosie

I think you are getting a little confused about the validity of the ELISA
test.  As you know, the particular test on which DEFRA relies measures the
antibody IgG.  This is a 'slow-response' antibody which is not measurable in
blood until 2-3 weeks after initial exposure to the disease.  Therefore, if
an animal has only recently been exposed to infection, the ELISA will not
detect the infection even though the animal is infected.  It is in that
sense that the ELISA is capable of throwing up 'false negatives'.

Also, there is a sensitivity threshold to the ELISA test which means that an
animal with low titres of antibodies (either because of recent infection or
because the exposure has been some time distant) will not show positive.
The
test can therefore be, in the same sense as the above, a 'false negative'.

In that sense, there is actually no such thing as a 'negative' result.  In
bacteriology when we report  so-called 'negative' findings, the convention
is
to report 'ND', standing for 'not detected', reflecting the fact that all
tests have sensitivity limits and it cannot therefore be taken that because
evidence of an infection (or presence of an organism, as the case may be)
has
not been found, it is necessarily absent.

In the context of the Brecon Beacon sheep, with 112 animals found with
suffiently high titre levels to be detectable, this represents (on the basis
of the 600 animals tested) evidence of nearly 20 percent of the sheep having
been exposed to infection.  Of the other 80 percent, this could mean a
number
of things - not least that some of the animals were infected so long ago
that
their titre levels are no longer detectable.  Of course, if the animals were
incubating the disease, this could be picked by by using the first response
antibody, IgM but, for some reason, MAFF and now DEFRA have always been
reluctant to use IgM-bnased ELISAs.  Furthermore, by calculating IgG/IgM
ratios, it is possible to get some idea of whether you are dealing with a
recent or old infection.  Needless to say, this technology seems to be
beyond
the capability of MAFF/DEFRA scientists.

However, in the round, you need to be a little careful in your assumptions -
negative does not mean negative: it simply means 'not detected'.

Richard

ENDS


If that hasn't confused you enough, we asked Andrew King at Pirbright to
comment on Richard's message:


Dear Alan

We are not DEFRA scientists.

Yes! In an ideal world it would help to have IgM data as well as IgG, but:

(i) It wouldn't help the practicalities, with millions of samples!

(ii) IgM is less specific than IgG. Any test for anti-FMDV IgM will be more
prone to ambiguity. Only the lawyers want that! The (IgG) test we have
developed, and are using, is accepted by OIE (and by implication the WTO),
fast, and as clean and unambigous as this kind of rapid technology allows.

(iii) Two further points:

FIRST, Dr North is correct in saying that IgM is a faster responding
indicator than IgM, but there is still bound to be a window of opportunity,
prior to the moment when you get the test result, during which the infection
could have spread to fresh animals without yet having elicited an IgM
response in them. Even IgM takes a few days to appear in the bloodstream,
longer if the infective dose is small, and to that period one has to add
time taken over blood sampling, transportation, testing, reporting, etc, to
estimate how long the total window is (the risk of spread during this latter
period is especially high since the animals at this stage are all penned
together). In reality, therefore, switching over to an IgM test would not
greatly change the situation, and would certainly not solve the basic
problem. No conceivable test could.

The antibody test was originally looked upon as a retrospective test to
enable the government to declare regions free of disease (the "exit
strategy"), but it has now become a leading diagnostic tool for disease
control in an animal population where the symptoms are hard to spot. We have
done this previously on a much smaller scale with swine vesicular disease
virus (an FMDV look-alike in pigs), and other viruses, but this is a new
scenario with FMDV. In regions where signs of infection ARE being found, I
suppose we may find ourselves having to screen surviving animals a second
time. Heck!

As for the existence of "false negatives", Dr North has a valid, if obvious,
point. As I understand it, the test DOES guarantee to detect ALL genuine
positives, but only when the animal has mounted its antibody response, which
takes time. I guess I assumed that was common sense. It takes time for the
vaccine to kick in for the same reason.

SECOND Yes! IgG/IgM ratios would be helpful for indicating how old the
infection is; a high IgG/IgM ratio would give ministry vets some comfort
that any ongoing infection isn't likely to be acute, and therefore that the
animals concerned are unlikely to be at their most infectious. That
information would/will be of interest for reconstructing the epidemiology,
and it may well be that some of the sera are being subjected to IgM
analysis, or will be when staff are able to get back to doing research.
However, the information would be of limited operational use now since sheep
can remain persistently infected for nine months, and all antibody-positive
flocks have to be eliminated, regardless of their IgM ratios.

Andrew

ENDS

Our comment:  Just for good measure, we asked Michaela about the response
times of the various classes of antibodies and she said: "IgG is detectable
about 4/5 days after exposure to virus/ Ag and peaks around day 14. "

Having digested all the above, we think (and hope) it can be summarised
thus:

#  The ELISA test can detect antibodies (IgG) from five to fourteen days
beyond first infection, depending on the level of exposure to disease and
the animals immune response.  Before detection levels of antibodies have
built up in the bloodstream, the test result can be a "false negative" i.e.
finding no antibodies although early-stage disease is, or could be, present.

#  The ELISA test does not miss any positive results, while "false
positives" can be accurately screened out using a second test (Virus
Neutralisation Test) to identify genuine antibody response to FMD.

So why, we ask, is the ELISA test being used at all in the Brecon Beacons?
If the authorities are genuinely interested to discover whether live FMD is
present, rather than the antibodies left after it has passed through and
gone, why aren't they testing for live virus directly with the existing fast
and specific test?  Why instead are they drawing one of several possible
conclusions from antibody testing?

The answer, surely,  lies within Andrew's quote above " sheep can remain
persistently infected for nine months, and all antibody-positive flocks have
to be eliminated".  We believe that all antibody-positive sheep and their
contacts will be slaughtered regardless to meet the EU requirements for
FMD-free status, but the politicians will not admit this in so many words to
the UK public, as it serves only to re-inforce the view that we have
sacrificed our independence in such matters.  No, they want to portray this
as a disease-control measure, seizing on the possibility of hidden disease
to eradicate, instead of testing to find that there is no live virus, then
having to admit that it's really just a matter of following
politically-devised rules set in Brussels.

Or maybe we are cynical?

#                                    #                               #


From the Financial Times:


Foot-and-mouth 'cost $3.25bn'
By Ed Crooks and Jim Pickard
Published: July 30 2001 20:28GMT | Last Updated: July 30 2001 21:18GMT


The cost of foot-and-mouth disease to the British taxpayer has risen to
$3.25bn (#2.28bn), the Department for the Environment, Food and Rural
Affairs revealed on Monday.

The size of the bill has led to urgent attempts by the government to bring
the costs of cleaning up farms and the slaughter and disposal programme
under control.

On Monday night ministers halted the practice of paying standard sums, often
well above market prices, as compensation for some slaughtered livestock.
From now on independent valuers will asses all compensation levels based on
market prices.

The figure for the cost of foot-and-mouth covers government spending on
vets, slaughter and disposal of animals, disinfection and other clean-up
costs. It does not include lost tax revenues or other losses borne by
farmers and other businesses.

In less than six months since the first outbreak of foot-and-mouth disease
in February, the bill is already more than twice this year's budget for
current spending for the old Ministry of Agriculture Fisheries and Food
allocated in last year's spending review, and more than half the total
#3.5bn cost of tackling BSE.

With the slowdown in the economy threatening to bring tax revenues under
pressure, and commitments to historically large sustained increases in
public services, the government is determined to make sure that the costs of
foot-and-mouth do not become a serious problem for the public finances.

The government on Monday played down reports that it was investigating
farmers who had deliberately infected their stock with foot and mouth
disease, saying that only two possible cases were under investigation.

But last week it launched an investigation into the costs of the clean-up
operation, after reports of inflated prices paid for equipment hire and in
compensation for slaughtered livestock.

Persistent rumours that some farmers had been deliberately infecting their
farms appeared to gain credibility after a farmer from Pembrokeshire in
Wales told how she was offered #2,000 in exchange for infecting her animals
with the virus.

The National Farmers' Union said that such rumours had been in circulation
since March, but none had been proved. Hugh Richards, president of the Wales
NFU, said: "You hear these rumours that somebody has met somebody in a pub
who offered them the disease, but there has been nothing more than that."

However, Mr Richards said it was true that farmers who had had the disease
were much better off than those who had not.

On the Brecon Beacons, farmers have been receiving up to #200 a ewe in
compensation, compared with #30 or #40 on the open market.

ENDS


From the Yorkshire Post:

David Garner
NFU leader calls for renewed effort to kill foot and mouth

A FARMERS' leader yesterday called for a massive effort to stop the
"doomsday scenario" of foot and mouth spreading to intensive pig rearing
units in the Vale of York and East Yorkshire.

National Farmers' Union president Ben Gill insisted the hot weather provided
an ideal opportunity to stamp out the disease.

Mr Gill is backing the new bio-security cordon which is being thrown around
a 900-square mile area in North Yorkshire in an attempt to isolate the
infection hotspot near Thirsk.

The Department for Environment, Food and Rural Affairs yesterday gave
details of the measures announced by Food Chain Minister Lord Whitty last
week. They include the bio-security intensification around 1,200 livestock
holdings stretching from North-allerton to the outskirts of York and from
Harrogate and Ripon to Malton and Helmsley.

A large buffer zone taking in North Yorkshire and parts of West and East
Yorkshire has also been announced together with a series of strict controls
both on animal movement and that of vehicles on to and off holdings where
there are livestock present. Vehicles such as milk tankers and feed lorries
will have to undergo intensive cleaning and disinfection.

Joint teams of Defra officials, police and trading standards officers will
be patrolling around the clock for the next 30 days at least to enforce the
restrictions in the bio-security intensification area. Farmbound vehicles
and those coming from farms which are judged to need additional cleaning and
disinfection will be ordered to a network of cleaning depots.

Clothing and footwear worn by people handling susceptible livestock will
have to be left on the farm and farmers will have to maintain footbaths at
every exit from their premises and to recharge them with disinfectant on a
regular basis.

Mr Gill, whose own farm near Easingwold is within the new bio-security zone,
acknowledged that the tighter security would come as a blow to North
Yorkshire farmers.

"We have hot dry weather which gives us the opportunity to kill this virus
off. People should realise the scale of the problem in North Yorkshire if it
is not controlled," he said. If the disease breaks south from the area
around Thirsk, Mr Gill warned that the consequences would be "calamitous".

He conceded that after five months of pressure, some farmers may have
dropped their guard over routine bio-security as the number of reported
cases of the disease dwindled.

"We just want to beat this disease. One month of intense pain now will yield
a far greater dividend in the end. It's far better that than we have the
doomsday scenario of foot and mouth getting into the pig sector," he said.

Defra's regional operations director Dr Stephen Hunter said 40,000 sheep in
the Vale of York would be blood-tested in the next fortnight to establish if
they had the disease. Vets in the new restricted area had been asked to
contact all their clients with livestock to stress the need for
bio-security. "We are very concerned to try to ensure that this disease
doesn't break out from the Thirsk area," he said.

Dr Hunter defended the delay in the introduction of the measures, saying it
took time to arrive at reasonable, enforceable and practical solutions.

ENDS

And from the same newspaper:

More foot and mouth found in Brecon Beacons despite cull

Further tests on 2,000 sheep in the Brecon Beacons have found positive
results of foot and mouth, the National Assembly for Wales said last night.

A spokeswoman for the Assembly said officials were now contacting graziers
in the area individually to discuss what steps to take next.

The news comes after 4,000 sheep in the Beacons were culled because of foot
and mouth.

Graziers had feared the worst after tests were carried out on more sheep in
the area.

The 4,000 animals at the Welsh beauty spot were slaughtered over the weekend
after blood tests for sheep in five areas of the mountain range showed a
significant number of positive results.

Welsh Assembly officials have said a further mass cull is the worst case
scenario but a decision will be taken this morning.

The new cases are more worrying because it means the disease has spread
further into the Brecon Beacons.

The animals culled at the weekend were close to a cluster of the disease at
Libanus.

The latest news comes the night before Assembly members are called back from
their summer recess for a Rural Affairs Committee meeting to discuss a #65m
rural recovery plan announced by Rural Affairs Minister Carwyn Jones last
week.

 Glyn Davies, chairman of the committee, said there appeared to be a
reservoir of the disease in the Beacons.

Sheep are still being gathered so results from those are expected later in
the week.

Later, farmers' leaders said the results were very worrying.

Farmers' Union of Wales spokesman Alan Morris said: "This is very bad news.
Our biggest worry is that the disease seems to have spread further into the
Beacons.

"We need to sit down now and look at the results and see how far it has
spread and in which direction."

Welsh Rural Affairs Minister Carwyn Jones defended the weekend cull as
appropriate policy.

He said although the slaughter of thousands of animals was distressing it
was in the interests of both tourism and farming.

"Sealing off the Beacons, without culling the sheep, is not an option. We
cannot be certain that the disease would burn itself out, and there would
also be an unacceptable risk of the disease escaping from the area," he
added.

"Vaccination is not appropriate either. Many of the sheep are already
infected, and others will be incubating the disease.

"Vaccination will not protect these animals. Tests to distinguish vaccinated
animals from those with the disease exist, but are complex and just not
practical for widespread use."

ENDS


From the Farmers Weekly website:

 31 July 2001
Farmers 'kept in dark' over virus cash


By FWi staff

FARMERS' leaders have accused the government of keeping them in the dark
when it suddenly scrapped standard rates of foot-and-mouth compensation.

Ministers have taken away the option of standard valuations of animals amid
concern that the cost of the disease was spiralling out of control.

The change in law came into effect one minute after midnight on Monday (30
July), before the National Farmers' Union was told.

A spokesperson told The Daily Telegraph that the announcement from the
Department for Environment, Food and Rural Affairs was "a complete
surprise".

A fax was apparently sent to the office of NFU president Ben Gill, who was
away, and no-one from DEFRA checked to see if it had been received.

Later the NFU hit out at the announcement, which followed the suspension of
all second-stage disinfection and cleaning, and cuts to welfare payments.

Deputy president Tim Bennett said that "every farmer should be treated
equally" and "no one should be placed in a disadvantaged position when they
go to bid for replacement livestock".

He added: "The NFU's priority remains the eradication of foot-and-mouth
disease. This should be the government's priority too.

"Neither this decision nor last week's to suspend second-stage cleansing and
disinfection do anything to help this."

The Times says the valuations system was deeply flawed as it set a floor,
pushing up rates for those who opted for independent valuation.

"Ministers have effectively opened the public purse to the farming community
and invited it to help itself," says the newspaper.

"Unsurprisingly, some farmers have taken the opportunity to do so."

It warns that taxpayers will not be laughing when the National Audit Office
produces its first official history next summer.

DEFRA has estimated that the crisis could cost taxpayers #2.28 billion.

Ministers are too willing to blame other people for the crisis while
refusing to scrutinise their own actions, says the Daily Mail.

Claims that farmers are conniving in the infection of their own stock are
very convenient for a government struggling to control the disease, it says.

This strategy was employed back in March with suggestions that sheep
movements motivated by subsidy fraud helped spread the disease.

The Mail berates the government for "refusing to allow its own role in this
tragedy to be scrutinised in a public inquiry".

In contrast, "it has no qualms about putting farmers' behaviour under the
spotlight".

ENDS


Here's something to cheer up us "locals" - from the BBC Devon website:


Welsh carcasses brought to Devon
The Department for Environment, Food and Rural Affairs has confirmed that
foot-and-mouth carcasses from the Brecon Beacons are being brought to Devon
for incineration.

Defra has confirmed that Peninsula Proteins in Torrington, is burning
lorry-loads of carcasses from the Brecon Beacons. Some nearby farmers are
worried about the risk of the disease breaking out again in the county. But
regional National Farmers' Union spokesman Ian Johnson says it is reasonable
for the county's spare rendering capacity to be used - and it should be
safe.

The ministry has also confirmed that ash and other waste from pyres is being
stored at Arscott Farm near Holsworthy before it goes to landfill.

ENDS


That's all


from Alan & Rosie