Dear Mary
 
I 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 be
 
1  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

Ruth


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