Updated summary of USDA research studies

[Fierkej]

Hello,
For anyone who's interested, below is an updated summary of USDA's bovine tuberculosis in white-tailed deer research studies at Ames, Iowa.
This was received from Dr. Mitch Palmer, D.V.M., Ph.D. of the National Animal Disease Center in Ames, IA.
Jean

Studies on TB in white-tailed deer, Dr. Mitch Palmer

Since 1997, research on tuberculosis in white-tailed deer has been conducted in Ames, IA at the National Animal Disease Center (NADC), a USDA research laboratory. The discovery of tuberculosis in wild deer in Michigan prompted the establishment of this research program. The NADC is involved only in research and does not dictate or enforce regulatory matters of the USDA. During the course of this research effort several studies have been conducted and published in scientific peer-reviewed journals. The following is a brief summary of that information. A number of studies have yet to appear in the scientific literature, but will be forthcoming.

Initially scientists developed a model of infection, allowing experimental infection that results in disease identical to that seen in wild deer.
MV Palmer, DL Whipple, SC Olsen. Development of a model of natural infection with Mycobacterium bovis in white-tailed deer. Journal of Wildlife Diseases 1999;35: 450-457.

Using this model of infection a number of studies have been done to examine transmission of Mycobacterium bovis, the bacterial agent responsible for TB, between deer and between deer and cattle. A number of conclusions have been drawn from these studies.
1. Deer in close contact can transmit M. bovis to one another.
2. Infected deer can shed M. bovis in their nasal secretions, saliva and less commonly in their urine and feces.
3. Indirect contact - through feed exposure only - results in the transmission of M. bovis to other deer or to cattle.

MV Palmer, DL Whipple, W Ray Waters. Experimental deer to deer transmission of Mycobacterium bovis. American Journal of Veterinary Research 2001;62:692-696.

Other research areas involving deer that have yet to be completed include:
1. Doe to fawn transmission of tuberculosis; does it happen and how.
2. How low of a dose is required to establish infection in a deer. We currently have demonstrated that as few as 40 organisms can establish infection in white-tailed deer. Compared to other species in which tuberculosis has been studed, white-tailed deer appear to be very susceptible to infection with Mycobacterium bovis.
3. Improved diagnostic tests to detect tuberculosis in living animals (these would be of more use to deer farmers and would probably not have much of a role in wild deer tuberculosis)
4. Survivability of Mycobacterium bovis on feedstuffs under different environmental conditions.
5. How does this disease develop in white-tailed deer and what are the characteristic findings at different stages of disease.

Other articles of interest published or due out shortly in scientific journals:
MV Palmer, DL Whipple, RW Waters. Tuberculin skin testing in white-tailed deer. Journal of Veterinary Diagnostic Investigation 2001;13:530-533.

MV Palmer, WR Waters, DL Whipple. Lesion development in white-tailed deer experimentally infected with Mycobacterium bovis. Due out in the next issue of Veterinary Pathology

MV Palmer, DL Whipple, KL Butler, SD Fitzgerald, CS Bruning-Fann, SM Schmitt. Tonsillar lesions in white-tailed deer naturally infected with Mycobacterium bovis. Due out this year in the journal Veterinary Record.

We have also concluded 2 studies to examine the susceptibility of raccoons to infection with Mycobacterium bovis. This study is due for release in the next issue of the Journal of Wildlife Diseases. In summary, we found that the feeding of multiple large doses of Mycobacterium bovis were required to establish infection, and even then disease was considered mild. Also, rarely did we find Mycobacterium bovis in nasal secretions or saliva from infected raccoons.

[Joe Archer]

Thank you for the update on TB in whitetail deer. I have a question concerning the following major point;

"2. How low of a dose is required to establish infection in a deer. We currently have demonstrated that as few as 40 organisms can establish infection in white-tailed deer. Compared to other species in which tuberculosis has been studed, white-tailed deer appear to be very susceptible to infection with Mycobacterium bovis."

This statement seems to contrast an earlier post by Dan O’Brien, D.V.M., Ph.D. Dr. Obrien had written;

"So, it’s pretty clear by now that deer in a wild setting have some degree of natural herd immunity, and that killing every single positive deer is, in all likelihood, not going to be necessary in order to break the chain of transmission that allows the TB outbreak to sustain itself in the Michigan herd."

It was this summation from Dr. Obrien that put my mind at ease, and had me at least partially convinced that we were taking the correct action in our fight againts TB. Also, I wanted to state this in the past but never found the opportunity, I want to thank Dr. Obrien for his hard work and dedication. It is obvious from your posts that you are as concerned and dedicated as they come. I do believe that with your help we have a chance of sustaining a resource of white-tail deer in our state.

Anyway, can you shed a little light on these contrasting statements? <----<<<

[Fierkej]

Hi Joe,
I have passed your question on to Dan O'Brien. But he will be unable to give it attention until the end of next week. I will post his reply at that time.
Thanks
Jean

[Fierkej]

Joe Archer,

Thanks for the question. It’s a great one, one that probes both at the limits of what we know about TB, and also points out the reality of how science is done, one piece at time.

The short answer is that in the real world, what determines how diseases behave in populations depends on three main factors, sometimes called the ”host-agent-environment” complex (see Thrushfield, M., 1986, Chapter 5, Determinants of disease, pp. 60-80, in Veterinary Epidemiology, 2nd Edition, Blackwell Science, Ltd., Oxford, for an excellent general discussion). Simplified, this just means that the characteristics of the host (e.g., deer), the agent (e.g., TB), and their environment all play a role in what ultimately happens with a disease in a population of animals or people.

The studies that Dr. Palmer and his colleagues carry out in Ames are experimental studies. Their purpose is mainly to help us better understand the characteristics of the host and agent aspects of TB, that is, the characteristics of the TB bacteria and white-tailed deer, and the interactions between the two, with environmental factors held more or less constant. By doing these kinds of studies in a controlled setting, it eliminates a lot of the environmental variations that can make it difficult to draw clear conclusions. It minimizes the number of things that can effect the results, so that it’s more straightforward to determine what’s causing what. This is a pretty common approach for experimental studies in lots of different scientific disciplines.

More specifically, Dr. Palmer’s experimental work that you referred to tells us that when you look at just the interaction between the TB bacteria and the deer in a controlled setting, deer are very susceptible to the disease compared to other animals. Their work shows us the physiological aspects of the disease in the deer, and is an absolutely essential piece for understanding the scientific puzzle that is TB. However, environmental factors eventually need to be taken into account in order to adequately understand how TB behaves in the wild population.

That’s where the issues I spoke about previously with respect to herd immunity come into play. The factors that make herd immunity work in a population include interactions not just between the TB bacteria and the deer, but also between the deer and their environment, and between the bacteria and the environment. So, to mention just a few, issues such as the ability of the bacteria to survive in the environment, variation in susceptibility to TB between individual deer in the population as a whole, resistance to TB infection that might be acquired by deer that are exposed to doses of bacteria that are too low to cause infection, how the deer interact with each other, climate, stress, changes in susceptibility over time, natural selection, and chance could all play a role in developing herd immunity. All these things and probably lots of others end up shaping how TB behaves in the wild deer population, not just the physiological susceptibility to infection of white-tails as a species. But a detailed understanding of the role that each of these factors plays separately is also important on its own, and will ultimately help us piece together the puzzle as a whole.

Maybe an example will help. Consider the disease anthrax, caused by a bacteria, Bacillus anthracis. Under experimental conditions, cattle (and lots of other animals) can be infected with anthrax, and without treatment, almost all of them will die rapidly. The dose of bacteria it takes to infect different animals will vary somewhat from animal to animal within a species, and from species to species, but in general, relatively low doses can result in infection. If you looked only at the results of experimental infection studies, you could easily come away with the idea that no animal population stands a chance of survival, let alone being disease free, living in an area where anthrax bacteria are around. However, we know that there are areas of the world where anthrax is endemic (i.e., always present at a low level) and cattle are present there, yet actual outbreaks of anthrax in cattle only occur irregularly, with many years sometimes passing between them.

Now, I’m certainly not an anthrax expert, and anthrax isn’t TB, but some of the same issues also apply to TB. You could pick some other disease if you wanted; plague might be a good one. The point I’m trying to make here is that this is where the environment part of the host-agent-environment complex comes into play, and modifies the behavior of the disease that we see in a controlled experimental setting. Looking at the experimental data (or the environmental data, for that matter) in isolation doesn’t provide the whole picture.

This is an incredibly complex (and fascinating) topic, and I haven’t really done it justice here, but hopefully this will help answer your question. If not, or if you want to talk about this in more detail, feel free to give me a call at Rose Lake (517:373-9358). Again, Jean will handle all follow-up questions to the list.

Regards,
Dan O’Brien