Sunday, September 23, 2012

How much is enough?

When people (who should know better)  talk about vaccinating badgers, because this over time 'reduces transmission opportunities', what exactly do they mean, and in the case transmission to cattle, by how much?

As we pointed out in many previous posts about this subject, including the posting below, the amount of bacteria left behind is crucial to a sentinel tested cow. And although we are not in the habit of making assumptions, presumably to many other species too.

Secretary of State, Owen Paterson's Parliamentary Questions queried this and received the following answer on January 29th 2004:
Mr. Paterson: To ask the Secretary of State for Environment, Food and Rural Affairs pursuant to the answer of 8 December 2003, Official Report, column 210W, what the presumptive infective dose range of M. bovis is in respect of cattle; and whether some badgers suffering from bovine TB are capable of excreting sufficient numbers of M. bovis bacilli to constitute such an infective dose. [150526]

Mr. Bradshaw: Determination of the minimum infectious dose of Mycobacterium bovis in cattle is part of the TB pathogenesis research programme. Early indications are that the minimum infectious dose for cattle via the respiratory tract is relatively small; the lowest infectious dose recorded so far is 70 colony forming units (CPU) when introduced by the intracheal route or 9,600 CPU by the intranasal route.

Relatively high levels of M. bovis in the urine of badgers with renal TB have been identified. Bacterial loads of up to 300,000 CPU per millilitre of urine have been measured. This suggests that inhalation of as little as 0.03 ml of the urine could result in infection.
 Thus up to now, 70 CPU has been the figure which we have quoted. But coming in under our radar, and once again published in the USA is a paper   prepared by our own VLA which has downgraded that figure to just 1 CPU for calves. The paper explains that four groups of calves were infected with 1,000, 100, 10 or just 1 CPU of M.bovis.  These animals were skin tested twice and blood tested, then subjected to rigorous post mortem. The results were described thus:
 One-half of the animals infected with 1 CFU of M. bovis developed pulmonary pathology typical of bovine tuberculosis. No differences in the severity of pathology were observed for the different M. bovis doses. All animals that developed pathology were skin test positive and produced specific IFN-γ and IL-4 responses. No differences in the sizes of the skin test reactions, the times taken to achieve a positive IFN-γ result, or the levels of the IFN-γ and IL-4 responses were observed for the different M. bovis doses, suggesting that diagnostic assays (tuberculin skin test and IFN-γ test) can detect cattle soon after M. bovis infection regardless of the dose.

So 1 CPU of M.bovis is all it takes to infect a calf. Is this one 'safe'? Does anyone care?

As it is established that badgers can excrete up to 300,000 CPU (colony forming units) of bacteria in each 1 ml of urine, we would respectfully point out, that the amount of  'bacterial reduction' achieved by vaccinating an unscreened population of tuberculous badgers, has to go down a very long way for it not to affect our tested sentinels.

This paper was primarily about the minimum infectious dose needed to infect cattle, but not from any particular source. So we share the author's 'comfort' that the skin test found all the infected cattle.The summary is as follows:
In summary, we found that 1 CFU of M. bovis is sufficient to cause established tuberculous pathology in cattle. This pathology is identical to that resulting from significantly higher experimental doses (up to 1,000 CFU in this study) and reflects the pathology seen in naturally infected field reactor cattle. Cattle infected with 1 CFU that developed pathology exhibited strong positive responses to the diagnostic tuberculin skin test. Furthermore, the infectious dose of M. bovis had no bearing on the time taken to obtain a positive IFN-γ response in the animals that went on to develop pathology.
Our data are in accord with very low numbers of bacilli transmitted aerogenously between cattle, potentially by nasal shedding. Comfortingly, the animals that do go on to develop pathology and therefore become a likely source of contamination within a herd can be detected at an early stage with the IFN-γ test and also provide a positive tuberculin skin test response.

Quite. We kill all our positive skin test reactor sentinels, and leave their herd mates free to be infected by just 1 CFU of M.bovis. Very sensible.

Edit: The term CFU or CPU is a pathological term meaning a cluster of single bacteria, capable of establishing disease. Although Owen Paterson's  PQ referred to CPUs and the second paper CFUs, essentially they mean the same. A colony forming or producing clump of single m. bovis bacteria. 

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