Tuesday, December 21, 2010

ASA uphold (another) complaint by FUW.

Once again, the Advertising Standards Authority have upheld complaints against misleading statements issued by the so-called protectors of badgers. This time the 'Save the Badger' campaign, operating from the address of 'Secret World Wildlife Rescue' in Somerset, has had the majority of its claims ruled as being 'untrue and unsubstantiated' by the ASA, say the Farmers Union of Wales.

Following a complaint by the FUW (Farmers Union of Wales), the ASA ruled that claims made in advertisements placed by the 'Save the Badger' charity and published in May this year, repeatedly breached Truthfulness, Substantiation, and Matters of Opinion codes. Welcome though this ruling is, it is too late. The 'Save the Badger' campaign encouraged members of the general public to oppose badger culling, and called on them to write to the Welsh Assembly Government and the Rural Affairs Minister opposing plans to cull badgers in north Pembrokeshire. And it used advertisements which repeatedly made statements which the ASA now say breached their standards of 'Truthfulness, Substantiation and 'Matters of Opinion' codes.

Following the ASA’s ruling, the advertisements must not appear again in their current form, and the ASA has written to the operators of 'Save the Badger' instructing them to ensure in future that claims which are not clearly an expression of their view, can be substantiated.

In 2006, publication of unsubstantiated claims by the RSPCA and others, once again brought by the FUW, provoked a similar response from the ASA, as we reported at the time. But the damage - and it is considerable - is done. People are misled, many animals suffer and the only winner is tuberculosis.

We note that similar emotive and misleading generalisations which are today condemned as 'matters of opinion which were untrue and unsubstantiated' by the ASA can still be found on Brian May's 'Save the Badger' website. Including, amusingly, irritatingly, the old assumption that mycobacterium bovis, is a virus. Dr. May's website has the following introductory paragraph:
The disease at the centre of this appalling tragedy is called Bovine TB. The history of the establishment of this virus in populations of Cattle in the British Isles is well documented. It did NOT, of course come from Badgers (or it would presumably have been called "Badger TB") - it was allowed to flourish because of intensive farming methods, and was spread around the UK by farmers moving cattle around to maximise the profit that could be made from them when they were slaughtered. Badgers were infected by the cattle, entirely innocent of any wrong-doing except being in the vicinity of these diseased farm animals.

And that from a superannuated, former pop star with a newly acquired 'ology?

Corrections to all Dr. May's erroneous assumptions may be found in this post and the PQ answer below. We do not intend to go through them again.

But we also note that pictures of badgers adorning his site, do not reflect the true result of tuberculosis on badgers. Emaciation, exclusion from the social group, starvation and finally death? Very nice. Disease in the badger on the right, had developed as tuberculous pleurisy and when the animal was caught, it was emaciated to the point that its death was imminent.

And this badger, weighing a fraction of its optimum weight had starved to death. A postmortem showed that it too, had generalised tuberculosis, the bacteria from which were available to any mammal which crossed its miserable path.

Finally, we would remind readers of the answer to our Parliamentary Questions as to the likely reason for the total and complete clearance of 'bovine' TB from the cattle herds at Thornbury, after a short period of badger clearance. The effect lasted for over a decade:
No confirmed cases of tuberculosis in cattle in the area of the Thornbury operation were disclosed by the tuberculin test in the ten year period following the cessation of gassing" Hansard: 28th Jan 2004 col 385W [150573]
So, what was the cause of the Thornbury success? Whole herd slaughter? Cohort slaughter? Zoning and movement restrictions, licensing and more cattle measures? Biosecurity and stricter testing? Change in the weather? All measures offered today by the Badger Trust, discussed ad infinitum by the T-Beggars ( T-BAG's successor around Defra's TB round table ) - and tried in the past by others, with humiliatingly expensive and ignominious results.

However, we did ask. And remembering that it is a hanging offence to mislead a minister in written parliamentary questions, his answer was thus:

The fundamental difference between the Thornbury area and other areas in the south west of England, where bovine tuberculosis was a problem, was the systematic removal of badgers from the Thornbury area. No other species was similarly removed. No other contemporaneous change was identified that could have accounted for the reduction in TB incidence within the area" (Hansard 24th March 2004: Col 824W [157949]

Congratulations, once again to FUW.

Thursday, December 16, 2010

Deadline for the Welsh consultation.

Just a day to go before the closing of the Welsh Assembly Government's consultation on culling badgers infected with tuberculosis.

Details can be found on the FUW website, which has online links to submit replies.

The deadline for replies to this consultation, is midnight on Friday, December 17th.

Tuesday, December 07, 2010

24 hours to go.

The consultation on whether or not to control infectious badgers to prevent the spread of tuberculosis closes on the 8th. December.

Farmers Guardian has a timely reminder.

Responses can be sent via email to: tbbc@defra.gsi.gov.uk

Monday, December 06, 2010

Professionals comment on that 74%

When we put up a brief glimpse of the source of Defra's '800 badgers, vaccination and 74% efficacy assumption' posting, it attracted the attention of several biologists, veterinary pathologists and other suitably qualified people.

Their somewhat explosive response, we did not expect.

A protocol designed to do one thing cannot and should not be tweaked to fit another scenario, and assumptions made without postmortems to support. That is 'outrageous' was one comment offered. The following snips are from a comment of the efficacy of BCG posting (below) with which we absolutely agree.
"As a biologist, I find these results rather perturbing. I know that BCG isn't all that effective, but results such as this demonstrate that it is so ineffective as to be near-useless, especially given the stress and disruption of vaccinating wild badgers ."

As cattle farmers, the results that even badgers receiving a very high dose of BCG, still developed lesions and still shed m.bovis was not good news to us either. As was the postmortem result for badger D313, (1 of the 9 given high dose BCG after a clear pre-jab screen) and for whom BCG gave no protection at all. The comment continues:
This is worthy of much wider publicity, since the general public seem to think that one dose of vaccine gives immediate, 100% effective, lifelong protection from a disease. This simplistic notion needs to be corrected; people need telling that BGC isn't all that effective, and that M bovis is definitely not a disease only of cows and badgers, but one which can readily spread to people.

We are trying, but when faced with a brick wall of vested interests, lobby money and index linked pensions, a TB riddled badger supports a huge industry on its back. Pushing water uphill may be easier.
This is, I think, a matter of some urgency since if this isn't done then the usual myths and magical thinking regarding vaccination will persist (i.e. the disease isn't a problem for people, and vaccination is a cure) and the necessary widespread badger cull will be that much more difficult to achieve

We think that as soon as Defra delivered this skewed piece of non-science to the Badger Trust, the general media and various assorted celebrities in need of a cause, it was game over.

And you are absolutely correct in thinking that the public and many animal activists genuinely believe that BCG will protect the badger, completely and indefinitely, whatever its current disease status. And yes, the label 'bovine' TB implies the only victims are cattle.
As to what can be done, well we've tried. Lord knows we've tried. But battling against arrogance and vested interests, who are in an armlock with government is a thankless task and one which we are afraid we have lost. The winner is the bacterium known as m.bovis, which will continue to infect any mammal unfortunate enough to fall over it.

Sunday, December 05, 2010

BCG efficacy - does it work?

We have so far concentrated on ploughing through the reams of paper and annexes associated with the 800 badger project, the results of which we explored below. But VLA / FERA have had several goes at vaccinating badgers with BCG, and then chopping them up to see the result.
With nothing better to do on a snowy Sunday afternoon, we trawled a couple of recent documents, where VLA / FERA checked their results with recognised efficacy protocol of a measured challenge and a postmortem of their results.

Briefly, 23 badgers were captured in Suffolk, where cattle sentinels are testing clear, and pre screened them to check they were clear of TB at the time of vaccination.

They were then allocated into three groups. VES1 which received a normal (low) dose of BCG vaccine, VES2 which received a higher dose (10 x higher) and a Control. Interestingly, the measured dose of m.bovis was inconsistent, with low dose vaccinates (VES1) receiving a higher dose of bacteria than the VES2 group.(Table 1, p.5 in the first link)

Of the these 23 animals, 5 were controls with exposure to m.bovis but no BCG, 8 had a low dose vaccine and 9 a high dose. All had m.bovis introduced by measured dose. All were euthanized 29 weeks after vaccination, and 12 weeks after experimental introduction of m.bovis.

The postmortems showed all badgers to have visible lesions in several parts, including lungs, lymph nodes etc. varying in severity. and m.bovis of the spoligotype introduced experimentally (VLA 9 - 8 5 5 5 *3 3 3 ) was recovered from all 23 animals in the trial.

In one test used (Dunns) a statistically significant reduction was found in the high dose animals compared to control. But using another test (Tukey's) all tests revealed 'no statistical significance' between the groups.

Below a couple of quotes from the postmortem reports:
Distribution of infection.
As there was some discordance between culture positive and histologically positive tissues, to describe the dissemination of infection an affected site was defined as either culture positive or histologically positive or both.
The median number of tissues affected by M. bovis was nine in the non-vaccinated group, five in the HD BCG group and eight in the LD BCG group. These differences were not significant.
However, the authors conclude that there was a reduction in excretion of bacteria of 13 per cent (compared with the control animals ) in the low dose VES1 group, twelve weeks after challenge. And a higher reduction of 67 per cent in the VES2 high dose BCG group - with the exception of one animal ( D313) , who was badly affected with tuberculosis and whose protective vaccine, even at high dose, had failed completely. It is not clear from the paper whether this animal was included in the results - or not.

After ploughing through all this, it appears that at twelve weeks after challenge and twenty nine weeks after vaccination, using a dose of BCG ten times 'normal' may reduce bacteria shed, although there is still a measurable quantity. All the vaccinated badgers had lesions and all were shedding bacteria to some degree.

Twenty nine weeks is just over six months, and no animals were kept longer than the three months post vaccination to see if their ability to shed m.bovis remained low, after high dose BCG or increased parallel with their level of disease progression.

More postmortem reports:
Summary of gross and histopathological findings in Vaccine Efficacy Studies VES1 and VES2
Macroscopic visible lesions were observed in the lungs, particularly in the right middle (inoculation point) and other lung lobes. Lesions were typically multifocal to coalescent tuberculous granulomas, variable in size and were found within the lung parenchyma and often protruding to the visceral pleura (Figure A8.1). Multifocal to coalescent granulomas were also frequently observed within the mediastinum The right bronchial lymph node was the most affected (Figure A8.3), but other lymph nodes within the thoracic cavity (posterior mediastinal and left bronchial) showed also visible lesions. The typical observed gross lesion was a multifocal to coalescent granulomatous lymphadenitis, affecting occasionally more than half of the lymph node section.
TB-like lesions were observed in spleen, liver and extrathoracic lymph nodes, and most of them were confirmed caused by M. bovis by culture.

The rest of this pathological description and illustrations can be found on p71 of the second paper to which we linked, but the authors say:
Briefly, the main differences were a higher severity of gross and histopathological lesions in the “most severely diseased” lung lobe and the draining lymph nodes (right bronchial and posterior mediastinal) in the control badgers compared with the vaccinated badgers with the High Dose BCG. In addition, the higher average score of the granulomatous lesions and the presence of more collagen in the non-vaccinated control group, together with a higher number of AFBs, are indicative of more severe/advanced lesions in this group in comparison with the High BCG dose.

Within the Low BCG vaccinated animals, many individual differences have been found, showing features similar to those of the non-vaccinated control group, and on the other hand, some animals showed similar results to those of the High BCG dose.,
In the real world, at twelve months post the first jab, the animal would need another booster jab. And by then it may be clinically infected. All the badgers in this trial, whether vaccinated at high rate BCG or low, had lesions and all were shedding m.bovis Thus the success rate of BCG, in an environment now so contaminated (remember the background level of the 800 captured badgers in the posting below? 43 per cent positive to at least one of the pre screening tests?) may be over estimated.

Friday, December 03, 2010

... and more

In our posting below we explored in a little more detail, Defra's headline grabbing claim:
A key finding of the field study, conducted over four years in a naturally infected population of more than 800 wild badgers in Gloucestershire, was that vaccination resulted in a 74 per cent reduction in the proportion of wild badgers testing positive to the antibody blood test for TB in badgers.
Further explanations have been passed to us which confirm that of the 844 badgers trapped in this project, after the prescreening with three different tests, just 262 were negative to at least one test. We questioned that background level of TB in the posting below, but now we have the words of the author himself which confirm:
"We worked in a high density population of naturally infected badgers, in what was the largest clinical trial in wildlife of its kind. Studies of vaccination are always focused on evaluating the prevention of new incident cases, so our analysis is based on 262 animals in 64 social groups that were test negative when they "entered" the study and which we caught a second time so that we could see how the vaccine had affected them. However, the total population size we report of 844 badgers is important, since it correctly includes all the animals that were already infected and gives an indication of the typical force of infection present in badgers in a TB problem area."
It most certainly does. 69 per cent of the badgers captured presented a result which would have guaranteed the death of a similarly tested bovine, and gives an indication why 34.9 per cent of herds in Glos had TB breakdowns in 2009. And 844 trapped over 55 sqkm gives a captured population density of 15.3 badgers per sq km. which is higher on both counts than the Consultation assumptions and which the Defra press release omitted to mention. But we digress...

In the posting, we quoted work done by Chambers et al, on the sensitivity (ability to detect disease) of the Statpak rapid blood assay. This work was published in 2008, and involved the postmorteming of almost 1500 badgers to more accurately validate this diagnostic test.

The Statpak achieved a very variable sensitivity ranging from 33 - 78 percent, the latter in grossly infected, super excreter badgers. Its average was a published 49.2 per cent only, which we compared with the much rubbished Brock test. If you remember, this is one Prof Bourne described this as 'poorer than hoped' as it 'only' detected about 40 per cent of infected badgers.
And Statpak starts life at 33 per cent? And averages 49 per cent? Do the maths.

But we are now even more puzzled by the Defra headline and inevitable media fest on this '74 per cent reduction' in the same breath as 'tuberculosis' and '800 badgers'.

The lead author on the Statpak validation we quoted in the paper below as 'Chambers et al., 2008, and is none other than Dr. Mark A.Chambers, who was lead author on the Vaccine project running at the same time. As were a number of the et als.

So let's get this right.
* While validating the Statpak blood test at an extremely low sensitivity in 2008, in the paper just published, the same authors attempt to morph their project to assess whether BCG is safe for badgers, into an efficacy test of BCG - even though they say it should not be taken as such?
* From an original trapping of 844 badgers, they then shake out the positives (582) leaving 262 testing negative of which around 160 are vaccinated. (60 percent of the 262, leaving 40 percent as controls ?) So it was not 844 trapped badgers which formed part of this 'efficacy' bit, (that should not be counted as efficacy) but 160?
* Having turned the badgers loose after their annual vaccination, the authors have no knowledge of what (or even if) any challenge from m.bovis has been faced. But they assess the results of the BCG vaccination on approximately 160 naive candidates, with gammaIFN (sensitivity 80.9 percent) and achieve a benefit of 19% to this unknown challenge ?
* Similarly with Statpak, which their own validation procedures give only a 49 percent sensitivity to, and they achieve 74 per cent benefit, again on an unknown, unquantified challenge ?

Having been questioned as more of this comes to light, the authors are keen to stress that :
"It's important to realise that the 74% (73.8%) figure represents a reduction in incidence of positive antibody tests brought about by vaccination and should not be equated to a vaccine efficacy of 74% "
And they do say that in the paper. But it is a pity Defra (or whoever wrote the press release) didn't realise that. Or the media or anyone else similarly taken in mislead by the headlines which followed the press release.

Dr. Chambers is also keen to stress that Statpak is very sensitive when faced with grossly infected badgers. Sure it is, but in this project the badgers were not post mortemed. So was it the 33 percent end of Stakpak's very variable sensitivity which it was flagging up? Or the 'more sensitive' 78 per cent? They don't know because they didn't look.

And then the inevitable wriggle. That annexes may be overlooked,(nope, read those too) and possibly not immediately explicit to 'lay-persons'. ( A wild assumption there.) And the fact that the main paper was prepared for submission to a regulatory authority as a 'health and welfare' issue for badgers. But presumably not submission to the VMD as an indication of efficacy, as the previous Statpak validation paper would have already covered that bit?
Nothing like telling you, you're stooopid is there? And of course cannot be expected to understand papers of this ilk.

And then the nitty gritty (that's not a very 'scientific' term, but hey, we'll live with it):
"...the decision was only taken subsequently by Defra to make the data widely available as part of the public consultation."

Well, well well. Impeccable timing with a startling, if misleading headline. So it was Defra who decided to publish. So that's all right then. And the media fest, headline grabbing, 800 badgers, 74 per cent reduction in TB? Which most of Defra's 'lay readership' swallowed hook, line and sinker? Is that all right too ?

Of course it is. And not a hair of a single badger will be harmed. Even the hairs on the heads of the 43% blood assay positive ones, roaming the Gloucestershire countryside and still available for more research.

Things are never what they seem.

(We have updated the headcount of blood assay positive rejects to this research, after contact from the authors. They offer around '43 per cent' of the 844, a figure which they describe as a 'typical force of infection present in badgers in problem areas'. The remaining 26 per cent comprised badgers which were only trapped once and those which expired during the research.)

Thursday, December 02, 2010

More on that 74 percent.

We touched the surface of the most recent headline grabber from Defra in the posting below, but having had a trawl through the project again, we think we have sorted where the 74% comes from.
How accurate is its reporting, is quite another matter. But it was not only the Badger Trust and media which ran with it, Defra issued the original high profile press release on November 8th, stating that :
A key finding of the field study, conducted over four years in a naturally infected population of more than 800 wild badgers in Gloucestershire, was that vaccination resulted in a 74 per cent reduction in the proportion of wild badgers testing positive to the antibody blood test for TB in badgers.
As we said in the posting below, if that was true, when do we start?

But as usual, the devil is in the detail. This project was not ever about efficacy of BCG. It was to study the health and welfare of badgers vaccinated with BCG. Thus no postmortems were done to support the blood assays, assertions or conclusions. And the project morphed into an 'estimated efficacy' on blood assays and cultures alone.

Blood assays are notorious for giving less than optimum results. Results are measured by 'sensitivity' or the ability to diagnose disease or antibodies associated with that particular disease. The lower the sensitivity, the less confidence can be placed in it.

For example, the opinion of the ISG contained in their Final Report
on the old 'Brock' test:
1.7 [] ... A live test for badgers had been developed and subject to trial from 1994-96, but its sensitivity was much poorer than had been hoped, successfully detecting only about 40% of infected badgers (Clifton-Hadley et al., 1995-a,Woodroffe et al., 1999)
Thus the 'sensitivity' of this Brock blood test test, (which our PQ answers also put at 'very low' and other research at around 47%) was described as 'much poorer than was hoped" by the ISG and hovers around the 47% mark, at which point the live test trial was abandoned. Bookmark that sensitivity rating and the ISG comment on it.

So back to this paper on the Health and Welfare of badgers vaccinated with BCG.

As we pointed out, the original 844 badgers were taken back to secure laboratory facilities and screened using GammaIFN / Elisa and Statpak Rapid blood assays. Out of the headline 844 badgers trapped, 265 took part in the annual research. Does that mean that at the first screening test, and before vaccination, almost 70% had TB antibodies? But we digress. Efficacy of BCG is the subject.

Much if not all, depends on the sensitivity of the test applied, and as we pointed out above, the old 'Brock' test was roundly condemned for a low sensitivity. So what of the blood assays used to estimate BCG efficacy here? The project cites work done on assays which was supported by postmortems, by Chambers et al, in 2008:
4.7 Immunology Results
Two immunological tests were applied in this study: the IFN EIA and the Brock TB Stat-Pak Test (Chembio Diagnostic Systems, Inc.).
The first test [GammaIFN/EIA] measures the production of IFN following stimulation of whole heparinised blood with bovine and avian tuberculins and has an estimated sensitivity of 80.9% and an estimated specificity of 93.6% (Dalley et al., 2008).

So the gamma IFN / Elisa test has a sensitivity of 80.9% and vaccinated badgers in this project had a protection level of - what?
19% according to the results.

And the second blood assay :
The Brock TB Stat-Pak is a lateral flow assay to test for the presence of antibodies in serum to M. bovis antigen MPB83. It has an estimated sensitivity of 49.2% and an estimated specificity of 93.1% based on a study of 1464 badgers naturally infected with M. bovis as determined by culture (Chambers et al., 2008). Sensitivity of the Stat-Pak varies according to disease severity, such that sensitivity was found to be 34.4% in infected badgers with no visible lesions at post mortem, 66.1% in infected badgers with visible lesions at post mortem, 41.7% in infected badgers that excrete M. bovis; rising to 78.1% in so-called "Super-Excretor‟ badgers (Chambers et al., 2008).
From that we see that Chambers postmortemed his badgers to qualify sensitivity, and found the StatPak test variable, with a combined sensitivity of 49.2% , including super excreters and 'badgers which excrete m.bovis'.

So what criteria have the authors of this project used?

"Here an “all test” exclusion criterion was used such that any badger positive by any of the three tests at T1 or at the time of first capture/vaccination (T2 onwards) was excluded from the analysis. This analysis addresses more directly the prophylactic effect of BCG vaccination since the effect of vaccination is measured in badgers considered to be free of TB by virtue of negative results in all three tests. Whilst this does not rule out infection completely, it is the best measure of TB status in the live animal. As the combination of all three tests would not be 100% sensitive, some badgers regarded as TB-free by this criterion would actually harbour infection."

The authors observe that should badgers actually be already infected with TB when vaccinated, "This would have the effect of reducing the measure of vaccine efficacy."

Quite. So, having excluded from the modeling any badger pre screened as positive at the time of vaccination, the results for gammaIFN / Elisa were?

Against this background, the incidence of IFNγ EIA positivity was reduced by vaccination from 35.0% cases (95% confidence interval: 23.0%, 49.3%) to 28.5% cases (95% confidence interval: 20.8%, 37.7%) but it was not significant at the 5% level. The analysis presented currently for the IFNγ EIA test alone provided no conclusive (P < 0.05) evidence that BCG vaccination was able to prevent infection with M. bovis, although the trend was in that direction.

And the modelled result was the '19 percent' reduction contained in the phrase 'Between 19 and 74%'. Gamma has a sensitivity described in this paper of 80.9%

And the StatPak results about which the headlines are so enthusiastic?
In contrast, vaccination was found to have a significant effect on reducing the incidence of positivity for both Stat-Pak or Stat-Pak and culture combined. The incidence of Stat-Pak positivity was reduced by vaccination from 17.1% cases (95% confidence interval: 10.8%, 25.9%) to 4.4% cases (95% confidence interval: 2.4%, 8.2%), which was significant statistically (P < 0.001). [that is the 74% - ed]
The incidence of Stat-Pak and culture combined positivity was reduced by vaccination from 21.7% cases (95% confidence interval: 13.5%, 32.9%) to 8.3% cases (95% confidence interval: 4.9%, 13.9%), which was also significant statistically (P = 0.008). As the likelihood of a positive Stat-Pak result or excretion of M. bovis increases with disease progression/severity (Chambers et al., 2008; Gallagher & Clifton-Hadley 2000) this study provides evidence consistent with the progression/severity of TB being significantly reduced in BCG vaccinated badgers after they become infected.

It does? With a sensitivity very similar to Brock test, abandoned and severly trashed by the ISG? A sensitivity averaging 49.2 per cent, and with no postmortems to confirm?