|From: Dr. Bruce Williams
Date: Oct. 30, 2000
ADV test - false positives
Recently there has been a lot of talk about the veracity of the CIEP test available through United Vaccines, about whether there is a high incidence of false positives - animals that will give a positive test for reasons other than possessing antibodies to the ADV virus. Most of the discussion centers around animals who have been vaccinated against other diseases.
Let me first say that I do not consider myself the last word on this test, but Dr. Marshall Bloom, who may be the most widely published scientist in the area of ADV (and who helped to design the CIEP test), IS.
The main question regarding the test is that whether animals who have been previously vaccinated against canine distemper or canine parvovirus (a common ingredient in dog distemper vaccines) or other subcomponents of that vaccine would test positively for ADV antibodies. Dr. Bloom does not believe that this is a problem, and has never seen this phenomenon. Indeed, all of his experimental animals (mink) are vaccinated against mink enteritis (another parvovirus) and canine distemper, and they don't cross react on the CIEP test.
I think a lot of this "false positive" assumption comes from a number of sources - positive reactors that have ADV but die early of other causes, so are termed "not having the disease", other parties developing competing tests (there are several groups who are in development right now), and a natural desire for hope, however small. Several years ago, people were posting on the Internet about being able to cure distemper by injecting serum from vaccinated animals into affected animals - 1 cc intraperitoneally. I am all for hope, but not when it puts others at risk.
Marshall Bloom is still the expert on this question, and he does not believe that false positives, if the test is run correctly, exist. Until someone can back that up with some real data, I've got to go with his experience. (However, I'd love to see any data to the contrary - if United Vaccines or any other group is saying that there are false positives, I'm hoping they'll share some data with us...)
What actually concerns me more at this point is the possibility of false negatives. Even in the hands of an expert, this test may have 3% false negatives (that's published and in mink) - animals that do not react for some reason or another. But that's another story, and one that has yet to be worked out.
Last weekend Colleen and I adopted two ferrets - you can bet I'll be testing for Aleutian Disease this time around.
With kindest regards,
|From: Robert L. Stephon, Ph.D.
Date: Oct. 31, 2000
Response [ADV testing]
I've been involved in a recent discussion concerning possible false positive results by CIEP for ADV Antibody along with Drs. Williams and Bloom. It is my contention that a false positive reading is possible for two reasons (I respond here with some of the same language used prior in this discussion):
First, the basis of potential false positive results would not be cross-reactivity with distemper virus, antibodies to distemper or any other virus (including parvovirus) or their antibodies. The basis for this is the production in ferrets of antibodies to cellular debris in vaccines, present as a by-product of their manufacture in cell culture. Similar cellular debris may be present in the whole ADV viral lysate (actually a mixture of several ADV-related proteins, or antigens) used in the test. When antibodies to this debris in the ferret serum encounter the ADV lysate in the test a precipitate line can be formed which is similar to an ADV Antibody positive. Especially in cases where the ferret is tested by this technique within 2-3 months of receiving a vaccine I believe there is some likelihood of a false positive result due to this phenomenon. Even United Vaccines notes the possibility of false positives from recently vaccinated ferrets.
Second, and admittedly subjective, is the issue of reading results. As I understand it, the CIEP result is determined by an operator's judgment as to whether a precipitate line is formed in the gel, which is a subjective method itself. In my conversations with Dr. Bloom, he indicated that with any questionable result in his laboratory, the CIEP gel is washed and further treated with a protein dye stain for better visual detection, and the interpretation thus confirmed.
I don't wish to contradict Dr. Williams, but I must respectfully add that Dr. Bloom did not say outright there are no false positives associated with CIEP. He points out that there conceivably are false positives, but there is no peer- reviewed evidence to prove it or the contrary. As I mentioned, even United states concerns about testing around the time of vaccinations. While I have not seen data as to the accuracy, sensitivity or specificity of CIEP, I agree that anyone who has a CIEP positive ferret should take appropriate steps to isolate the ferret and not equivocate, because of the nature of the danger involved.
As a disclaimer, let me say that my organization is one of the groups mentioned by Dr. Williams as being involved in the development of a new diagnostic tool for ADV Antibody. I do think that the ELISA we've developed is a better diagnostic test for ADV Antibody for several reasons. When we are finished with our clinical/other studies I will demonstrate this with the data in the appropriate forum. I plan on being at the Pennsauken show on December 2, and would be happy to discuss these issues with all present.
Aleutian Disease Virus...in FERRETS
Other ADV Web-Site Pages
- Aleutian Disease
A Hidden Danger to Your Ferret
And for some history and a look further: