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.


Dr Dan Holdsworth said...

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.

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.

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.

Matthew said...

Dr. Holdsworth. Thank you so much.
We have found the lead authors of these projects somewhat prickly when questioned - although they have parted with some useful snippets in the process. We are going to raise your comment to posting, along with the comments of one of the site's professional advisers, a retired veterinary pathologist, who described the 74% assumption as 'outrageous' given the protocol.