ADV Series 3
Written By Danee DeVore
I realize that what most people are probably interested in hearing about it what is actually happening at the U of GA with their ADV research and how our donations are being spent, and so today I will begin to pass some of that information along.
I am not going to give an accounting of exactly where the money has gone, although I do understand that such an accounting will be provided to Kris Barnes, who heads up CSI, and will be made available for everyone to see when the CSI ADV Research Benefit Raffle starts. Instead, I am going to address what has happened so far, and my understanding of where things are going.
Let me start by saying that medical research, even veterinary medical research, does not happen overnight. To be done correctly, there are many steps that must be taken, and the accuracy of each step must be verified before moving on. Look at how long we have been studying cancer and AIDS. While progress has been made, there are still no cures or vaccines for them.
ADV is a rather tricky disease to find a cure or vaccine for. With ADV, it is usually not the actual virus that causes the health problems, but instead it is the body’s natural response to the virus that does the damage. ADV causes the body to produce large quantities of antibodies that do not affect the virus, but that do eventually build up in the organs and blood stream, causing the damage that is associated with the disease.
Because of the way ADV works, it is harder, but not impossible, to find a cure or vaccine.
Usually the first step in a research program like the one at U of GA, is to look at the disease and what it does to the body, and to develop both qualitative and quantitative methods to measure things. This can go very slowly, and is not very exciting to talk about. But, it is this phase of the research that has been going on over the last 5 years. And, it is now nearing completion.
When the U of GA started into this project, they (Dr. M. A. Stevenson) published an article in the Compendium on Continuing Education for the Practicing Veterinarian reviewing what was known about ADV. As they are finishing the first phase of the project, they are now publishing a second paper.
This fall, in the Journal of Veterinary Diagnostic Investigation, there will be a paper about the findings and results of this first phase of the process. The primary author of the paper is Kate Pennick, who is the research technician that has been running tests on the samples that have been sent to the U of GA. She has also used the research she has been doing for her Master’s thesis, and will be receiving her Master’s in Veterinary Pathology.
Now this news may cause some of you may feel that the research is being pursued for personal the gain of the people doing it, and to some degree that is true. Universities pursue research in part to train students in the scientific process, and in part to get funds for their work. Graduate students are cheap labor, getting only small stipends for their work, but at the same time learning things in their chosen field. It would cost a lot more for a major drug company to do this work, as the salaries of their technicians would be much higher then the stipends graduate students receive.
I do not know what Kate’s paper will say, as I have not yet seen it. I do know in general terms what it is likely about, though.
For the past 5 years, the team at UGA has been looking at tissue samples from ferrets with ADV to see exactly what the disease is doing, and also they have been developing the tests they will need to begin the next phase of the project.
When they started out, they determined that the tests that were currently available were not accurate enough, and not specific enough for their purposes. They needed to do more then verify the presence of ADV. They needed tests that would qualitatively and quantitatively describe what was there.
And so, starting with the CEP test, and working from there, they have worked with developed several tests that will meet their needs. With the CEP test, they started reporting results using titers, rather then just reporting a positive or negative result. Titers give an idea of the concentration of the antibodies in the animals blood stream. With studies that were previously done on mink, there was a correlation between the titer level and the health of the animal. Once the titer reached a certain level, the mink usually died within a few weeks.
What they found was that with ferrets this did not appear to hold true. Many ferrets with high antibody titers went on to live years with the titer remaining constant.
One of the first tests they worked with after the CEP was the PCR, or polymerase chain reaction. The PCR test can be used to detect any kind of viral DNA in a sample, and yields a simple positive or negative result. The PCR is not used only for ADV, and in fact, there are not PCR tests for AIDS that are commercially available.
The PCR test was useful, because it detected when a ferret was likely to be shedding the disease.
With ADV, often the virus settles in the organs. When this happens, the ferret is not in a contagious state, because unless his organs are eaten by another animal, there is no way for the virus to move to another animal.
But sometimes, in some ferrets, the virus moves into the bodily fluids, and can then be transmitted through the fluids to other ferrets. When a ferret’s blood or urine tests positive with a PCR test, then that ferret can transmit ADV to other animals.
The PCR test is unlikely to ever be available at a vet’s office. To run it requires very expensive equipment, and a highly trained technician who is familiar with the procedure. Some of the commercial labs may decide to offer the test, but since there would be a lag time in getting the results, it may loose some of its meaning. The test would only tell you what was occurring at the time the sample was taken, and while it is unlikely the status changes rapidly (like overnight), it is possible. So, the PCR test is something that is more useful from just the research standpoint.
One test that the U of GA developed, and has made commercially available is the the DNA in situ hybridization test. This is a test run on tissue samples taken either during necropsy or biopsy of organs, and is extremely accurate. Again, this test can be set up to find a number of different viruses. But, UGA has modified it to use in identifying ADV viral particles.
Finally, the UGA team has been perfecting an ELISA test for ADV. ELISA is an abbreviation for "enzyme-linked immunosorbent assay. ELISA tests are widely utilized to detect substances that have antigenic properties, primarily proteins (as opposed to small molecules and ions such as glucose and potassium). The substances detected by ELISA tests include hormones, bacterial antigens and antibodies. The ELISA test that UGA has developed for ADV will give a result expressed in titers. They may be making this test commercially available in the near future.
Developing these tests and insuring their accuracy was an important first step in the process, and was necessary before any other steps were taken. During this time, the team was accepting samples from ferrets from members of the ferret community. This was beneficial to both parties. The team had samples without having to infect more ferrets with ADV, and the owners who provided the samples got free testing.
Now that the test development stage is over, the tests that are useful to vets and owners will be offered commercially. This also benefits the program, because it brings in money to cover expenses, freeing up the money that gets donated to cover the next phase of the research.