Email received from Ruth Watkins July 27th 2010I have watched Chris Chapman's film on Bovine TB - a way forward. I think it is a beautiful and sensitive film. The only objection I have to what is said is from Anthony Gibson when he says the "BCG vaccine would conceal infection in sick badgers which is the big danger."' This is the old FMD mantra. In the context of M bovis infection and BCG vaccination I cannot see it has any meaning. M bovis infection is a progressive infection as they describe it in badgers and as the number of organisms, the bacterial load, increases so eventually the badger becomes sick, unto death.
Before it becomes sick it will shed organisms! Therefore it is not only sick badgers that are infectious, whether they are vaccinated or not.
In fact vaccine is unlikely to have any effect at all on a progressive infection when given after exposure when such an infection is underway.
Though in humans BCG has had the finger pointed at it for perhaps causing reactivation and clinical worsening of disease (the Koch's response not seen in badgers according to John Gallagher) This is perhaps why one was vaccinated as a teenager or young adult after having a negative Heaf skin test.
The most striking thing to me is the lack of microbiology to back up the hypothesis put forward.
Such careful mapping and observations cry out for modern microbiology; it is as though the farmers and all in that area are living in the 19th century!
One could even now sequence the isolates from the badgers on a farm going down with bovine TB if isolates were made from both cattle and badgers on the same farm. In microbiology one finds infection in individuals not yet sick, and I think it not unlikely that M bovis infection might not also be present in the 'healthy' setts.
PCR and culture on their latrines would be likely to disclose this (Prof Elizabeth Wellington has done such a study).
I think what Paul Gillett says is eminently sensible and, trying to put it simply, he talks of finding out where M bovis starts and stops. I think he means the distribution and spread of M bovis in badgers, and this knowledge and observation over this area and its correlation equally with M bovis infection on the farms is an ideal opportunity. Is DEFRA listening out there?
I am not sure how the local sanatorium comes into the story other than interest. Unfortunately badgers will live in their setts in close proximity as though all sleeping in one bed. The humans were coping with pulmonary TB in the sanatoria and though some may have recovered, many would have fallen ill again later (I think the overall death rate was 50%). The beds in a ward are shown very close together, though the usual accommodation would have been a single room and veranda.
(Bernard Llewellyn of Carreg Cennen castle gave the DVD to me to comment on.)
with best wishes
NB from warmwell.com Readers who would like to see the DVD for themselves, the 25 minute film can be purchased for the very modest price of £4.99, which includes postage and packing. It is available through Chris Chapman's website at www.chrischapmanphotography.co.uk. The squeamish need feel no reluctance to watch it. We found it to dwell - not on recrimination or sadness - but on positive steps that can be taken. And, as Dr Ruth Watkins says, it is beautifully filmed and edited.
Email received July 25th 2010Dear MaryI was asked by Sally Hall of www.bovinetb.co.uk what I thought of Colin Fink's letter posted on Warmwell about using triple therapy in oral bait for badgers to treat M bovis infection in them. My initial response had been one of rejection but I am glad to have the opportunity to reconsider. Now I am finding out more about M bovis in an effort to understand the infection and disease and to think outside the box.I was not previously aware that latent TB could be treated to prevent its reactivation at any time in future life, (unless reinfection takes place later (reinfection is documented in humans and when opportunity for reinfection is high it commonly occurs)). Latent TB can be treated by 9 months of isoniazid alone (and a shorter course for chemoprophylaxis after exposure), unless the infecting organism was already resistant at the time of initial infection. I believe this is what some camelid owners are doing for exposed camelids. Both camelids and goats as species seem to be particularly susceptible to M bovis and if infected develop a progressive infection from which they die relatively rapidly, within a year.The infection rate in a confined space such as a social group or sett of badgers will be between 25 and 50% if comparable to humans, but genetics and species may make it higher or lower. The diagnosis of latent M bovis infection in badgers is not accurate in microbiological terms as yet and would be likely to be underestimated by any tests currently used on them. Also whatever the badger behaviourists might say if M bovis DNA is present in the sett latrine then there is M bovis infection in the group of badgers associated with that sett.If Isoniazid alone is put out for badgers then the actively infected badgers that eat it (one cannot exclude actively infected badgers from eating the bait) are likely to develop resistance and the M bovis shed will be resistant to isoniazid within weeks or months and infect other badgers with resistant M bovis, so that strategy won't work.In humans active infection is treated with multiple antibiotics taken every day, isoniazid, rifampicin, pyrazinamide and ethambutol for example- 2 months on this combination, then depending on the culture, typing and sensitivity report, reducing to 3 for a further 4 months, but in the case of M bovis dropping pyrazinamide as M bovis is intrinsically resistant so that in M bovis 3 drug treatment is given for 9 months in total. If the treatment is taken reliably then the person is cured of that M tuberculosis or M bovis infection. For example elephants have been cured of M tuberculosis infection (they are only rarely infected with M bovis). (It is unaffordable for farmers to treat cattle).As you have probably heard multiple drug resistant and even extremely drug resistant M tuberculosis is now circulating in humans because they have not taken the full course of treatment, either only taking it intermittently or for too short a time. These organisms can infect hitherto uninfected individuals and may be untreatable and lead to death or indefinite confinement if excretion cannot be stopped by surgical removal of infected lung for example.For this reason I have argued against Colin Fink's idea of putting out triple antibiotic therapy bait for badgers hitherto.However if there is essentially a reservoir of M bovis in badgers and cattle (and deer, camelids, cats etc) that humans almost never get maybe such an approach together with vaccination of badgers and birth control of badgers / population reduction would not be such a bad idea after all. Vaccination of cattle and testing and culling of infected cattle would have to continue to get rid of M bovis infection. The cycles of infection would be broken, stopping reinfection of either badgers or cattle from the other species.The reasoning would be1 The closely observed sett would thus have triple drug treatment of the active and latent M bovis infected badgers and if this was continued for at least 9 months it could eliminate infection from that sett. It could also prevent newborn badgers from becoming infected if treatment was started months before their birth.2 All the setts in possible contact with each other would have to be treated simultaneously.3 If multiple drug resistant M bovis developed (part of the monitoring) then that group of badgers would have to be culled as it could spread to other badgers or the programme halted because it would be useless.4. If such resistant M bovis infected a human which would be very unlikely, that human is anyway very unlikely to pass it on to another human (though this has been recorded on rare occasion that M bovis produces lung disease and shedding in sputum). An epidemic of resistant M bovis in humans would not happen as it is essentially a preventable zoonosis by pasteurisation of milk and indeed is prevented by this means in the UK. Another reason an outbreak of resistant M bovis is unlikely to happen in humans at all is that the resistance of slow growing mycobacteria, M bovis and M tuberculosis, to antibiotics is caused by mutations in chromsomal genes. The resistant organism itself must be acquired as an infection to give rise to an epidemic. The resistance is not on promiscuous genetic elements that can be spread to other mycobacteria species.5 Having small numbers of closely observed and monitored setts would necessitate reduction in the badger population, at least of infected setts (ie latrine PCR positive for M bovis).6 However vaccination with the live attenuated vaccine BCG would not be successful if treatment was being given simultaneously (vaccine is killed by treatment), so perhaps vaccination could follow the treatment in infected areas to try to ensure it does not return. There is no reason why oral vaccinia with an immunity boosting M bovis protein should not be put in oral bait as well. Giving vaccination by aerosol is not something that has been studied at all for TB but this should be looked at as an ideal method for animals in a sett to vaccinate them all.7 Birth control would be a way of reducing the population without the suffering of culling, the consternation of animal rights people, and be unlikely to perturb badger society.A question that I couldn't answer is whether it is possible to get the badgers to eat sufficient of the bait daily for 9 months so that the triple drug therapy had an opportunity to work. In a way the badgers of the treated setts would have to be trained. People have no difficulty getting badgers to come to their gardens and eat peanuts for example. If the setts of the badgers are mapped (as they have been in the North Pembrokeshire Cull area) and badger devotees adopted setts so that all were accounted for the badgers could be 'trained' or accustomed to eating a favourite bait near or at their sett entrances every day, tasty pellets that could then be exchanged for drug containing tasty pellets.A method such as this could only be used in a developed country and would have to have the full co-operation of people.I have corresponded with badger trust people in Wales and they are implacably against population control of badgers by birth control methods.I also suspect that DEFRA and the HPA would never countenance the treatment of badgers with triple drug therapy. The EU rules would be a problem I am sure.In conclusion I do think Colin's idea is more interesting and feasible than I thought as a first reaction. It could be very effective, better than anything else proposed at present.The problem is that to do anything other than killing is obstructed and slowed for lots of different reasons, rules, bureaucracy, vested interests and scientific difficulties, so that nothing new can be given a try. And of course the killing of badgers is also opposed- an exception in the animal world and in the light of our response to FMD infection one that is understandably held as valuable. This is where birth control comes in for population reduction. Such methods are not yet finally developed for mammals but vaccination against chorionic gonadotrophin may be a safe method.Why should the Irish be at the stage of trialling oral vaccine for badgers and yet we be 5 years away from it?with best wishes
BovineTB -use of triple antibiotic loaded baitReturn to warmwell.com's bovone TB page
Email received January 7 2010 from Dr Colin Fink,
There is a problem with badgers highlighted to me by Professor Liz Wellington at Warwick, whose team have done the surveillance work. Evidently there will be a few badgers who are the high excreters of Mycobacterium bovis. They are ill and often excluded from the setts. The question which is difficult to answer is how many unaffected badgers are carrying the bacterium? They may remain healthy and not excrete particularly. We could decide to eliminate whole sett populations. If we do we would have to destroy and disinfect the setts as they will be re-colonised by other individuals and the Mycobacteria will still be there to infect the new population.(Dr Colin Fink is Clinical Virologist & Hon. Senior Lecturer in Biological Sciences University of Warwick, and Company Medical Director, Micropathology Ltd Research and Diagnosis)
It may be possible to both undertake sett elimination if the evidence of infection is available, and also treat geographically around the sett with triple antibiotic loaded bait (repeatedly). So those locally will at least have any infection reduced and carriage eliminated. It may also be possible to bait with contraceptive hormones so populations also naturally decline.
I do not think that any single policy is a panacea and we need to consider combined approaches, to reduce the carriage and excretion of organisms, minimise population pertubation, which creates stress and increases mycobacterial disease ( rather than carriage), by using selective sett culling and also consider in conjunction, both contraception and antibiotic baiting.
Any combined approach will need very careful policing and implementation. Surely that is a better investment than constantly killing herds of cattle and all that which goes into raising these animals?
We have no other alternative as vaccines are not available because the organism is not amenable, and we are losing herds of cattle, alpacas etc and increasing the organism load in the wild population at an alarming rate.
(See also the exchange of views, in September 2009 on the subject of risk to human beings as well as the toll on cows and other mammals between Dr Fink and the farmer, Pat Bird, author of the Bovine TB Blogspot) With their permission, what follows are some of the current thoughts of Dr Colin Fink (in black) and the farmer, Pat Bird (in blue) on the subject of bovine TB
From emails sent to warmwell.com Sept 21 2009 (On suspected human cases)
I read your bovinetb.blogspot reference with interest. M.Bovis is regarded as a zoonoses, of course there are well documented cases of it transferring to man. In the case of the cat diagnosed to have the disease, if the owners and immediate family remain asymptomatic, then all is well . Whether they have been exposed and have been infected with a small amount of the organisms and deal with this infection in the normal immunological way, is rather academic. Many of us meet M.Tuberculosis but remain entirely asymptomatic. The cat owners et al may be reassured. If they were to become ill and remain unwell for longer than a transient infection might be expected to last, then further investigation would be justified. As it happens we are able, and do, diagnose Mycobacteria of all sorts- there are many different types. ( we look for the Mycobacterial DNA and then sequence it to characterise the species of Mycobacteria). But no intrusive investigation ( biopsy of lymph nodes, lung biopsies etc) to find the organism, can be medically justified in someone who is entirely well. - It would be a hazardous undertaking.
22 September 2009 00:11
The real problem is that the organism hides, so unless there is an obvious focus for infection for example, a swollen knee or coughing rusty sputum or an eye with uveitis ( pain and loss of vision) you just do not know whether someone is infected.
You see the skin test is just as useless in us as it is in cattle. It will show that we have mounted a T cell response, so have met the organism ( I am not sure whether the skin test is Mycobacterial species specific: I suspect not) but so what? We have met some of the organisms and raised an immune response. That does not mean we are rampantly infected.
Tuesday, September 22, 2009 11:55 PM (From Pat Bird)
Agree with much of what Dr Fink says, except this:
"...the skin test is just as useless in us as it is in cattle. It will show that we have mounted a T cell response, so have met the organism ( I am not sure whether the skin test is Mycobacterial species specific: I suspect not) but so what? We have met some of the organisms and raised an immune response. That does not mean we are rampantly infected."
Yes and no. The intradermal skin test is the primary universal test for TB in cattle, and with that + slaughter most countries have cleared the disease altogether. The cattle skin test is 'comparative' in UK, as it compares a bovine TB antigen based on AN5 strain, to an avian TB antigen reaction, and records if the animal has mounted an immune response to either, and if so, the difference between the two. The only loopholes in its use are a latency 30/50 days prior to the skin test, or if the animal cannot mount an 'immune' response as it already has the disease. It is then said to be 'anergic'. I have endured years of consecutive 60 day skin tests - or our cattle have - and it does what it says on the tin.
Dr. Fink is quite correct to say, the test does not show that any candidate testing positve is 'rampantly infected'. In the case of cattle, they get no chance - they are shot. In human beings, the first line after contact with either a human case, or animal (farmed or domestic) should be a Mantoux test to detect if exposure has occurred. Which if it is positive, would certainly not mean invasive biopsies.
Records of recent cases describe bloods and PCR to see if sputum was ++ for bTB, together with Xrays. After which, a long course of appropriate antibiotics, if no evidence of operable lesions is detected . The Spanish couple with the alpacas are on a course of prophylactic antibiotics as the infection in their animals is so widespread.
It came as quite a shock to local AHO staff and vets that one of their colleagues contracted bTB via an alpaca postmortem conducted on farm. She developed bTB in the bone of her thumb, which required deep bone scrapes, reconstructive surgery and the inevitable antibiotics. A Cornish woman and her daughter both had clinical bTB and her dog is dead. The mother had lung lesions, the daughter was sputum positive. The dog extensive lesions in many places after selective euthanasia. All had the same 'spoligotype' of bTB that is circulating in tested slaughtered cattle, and the free ranging badgers 'known to inhabit her garden', one of which she 'rescued. She had not worked as veterinary nurse for three years before she became ill.
The amount of cattle we're killing due to 'exposure' to m.bovis in their environment, should be ringing warning bells that the amount of m.bovis is increasing. And it available to any mammal who cares to trip over it.
Any country which ignores a reservoir of bTB as we are doing (in wildlife) , is storing up problems for its human population in the future, and for just the reason Dr. Fink gave. It can wall-up and lurk deep within the body, until the immune system breaks down, when it will release, often decades after exposure. And that is precisely why it is a listed as grade 3 pathogen.
And HPA are not fulfilling their statutory duty if they fail to 'screen' contacts of anything positively confirmed. Particularly children whose immune systems are not fully developed.. (All in my opinion of course.)
September 23, 2009 10:17 AM - From Dr Fink
A very good discourse with much more detail than I gave. I would question one thing: a positive mantoux ( skin test with old tuberculin - a protein from the organism) can show previous exposure. Whether that is recent exposure to a suspected animal infection and thus infection or coincidental from a previous exposure is a bit harder to fathom.
Of course the cattle are not given the benefit of the doubt with a positive skin test. Only very modest numbers on post mortem are found to have lesions.
In my experience looking for any Mycobactarium in the blood ( by PCR ) even in broken down cattle - I had the opportunity with DEFRA a few years back, will not show organisms, so one may be falsely reassured. Sputum testing may show either miliary ( widespread infection ) or a more localised lung infection. But not always. Biology and organisms never do what they are told to in the text book.
The real problem as Pat says, is that there is far too much out there and we need to reduce the load in the animal reservoirs in a humane and satisfactory way. The trouble is we do not have a decent answer to that problem and any attempt will be messy, gird up the badger lovers ( understandably) and may not do the job very well.
I am still of the opinion that feeding stations with high dosage of triple antibiotics for say 6 months coordinated, could be worth a try. It would not be that expensive, but would need very good attention to detail. It would at least reduced the bacterial load in those wild animals that are a reservoir for infection and often excluded from the badger setts.