False Positive, False Negative
Run a test. Get a result. Sounds simple enough, doesn’t it.
However, the wicket gets sticky when you realize that every test we run requires interpretation. Few are simply “yes” or “no,” “black” or “white.”
When results are dramatically different from what we expect, suspicions rise of “false positive” or “false negative.”
A false positive result sometimes occurs when something in the patient’s body interferes with the normal function of the test. When the test result is suspect, another test must be performed to confirm or deny the first test’s result.
Freckles, the inspiration for this post, is an excellent example. Approaching 2 years of age Freckles came in for a routine examination, vaccinations, semiannual heartworm test and stool test for intestinal parasites. Everything went smoothly until we read his heartworm test. Despite getting heartworm preventive right on schedule every month, Freckles’ test was positive, indicating he was infested with heartworms!
As we have written previously, all heartworm preventives have a certain failure rate. No medication is perfect. The more common scenario is that a patient misses one or more doses or fails to be dosed on schedule every 30-31 days. So, it wasn’t totally out of the question that Freckles could have heartworms, just unlikely.
We checked his purchase history, and his Mom had bought more than enough Revolution to account for each month’s dosing. Of course, buying heartworm preventive and administering heartworm preventive aren’t the same thing, but we knew this Mom to be quite conscientious, plus, she assured us that his doses had not ever been late.
We obtained another blood sample and sent it to a reference laboratory for a confirmation test. If that test was also positive, we would be convinced that, indeed, Freckles would require a heartworm treatment to remove Dirofilaria immitis from his body.
If the confirmation test was negative, we would be strongly suspicious that the first test was in error.
Fortunately, the second test was negative, leading us to conclude that Freckles was triggering a positive result with our in-house heartworm test because of something in his body that most dogs don’t have. Which was odd, because he had a heartworm test six months prior that was negative.
It was also odd because canine antigen heartworm testing has a high specificity. Specificity is a measure of the likelihood of a positive result actually being true. Heartworm tests measure molecules from the uterus of the female adult heartworm. That’s pretty specific! So, a test with high specificity means that a positive result is highly believable.
Another characteristic of the quality of a test is sensitivity. Heartworm tests typically give a positive result with as few as 1-3 adult heartworms. That is approximately the number of heartworms required to release enough molecules of the female heartworm’s uterus escaping her body and entering circulating blood. Therefore, this test has a high sensitivity and would be expected to give a positive result on every dog with 3 or more sexually mature adult heartworms, and a negative test result is highly believable.
Put another way, a test with a high specificity means you can almost always believe in a positive result and a test with a high sensitivity means you can almost always believe in a negative result. Mnemonics used to stimulate memory of these principles are SPPIN and SNNOUT. A SPecific test, when Positive, rules IN a disease. A SeNsitive test, when Negative, rules OUT a disease.
Here are some examples of false negative tests that occur commonly in practice.
Whipworms are intestinal parasites of dogs which notoriously produce small numbers of eggs and produce them sporadically. A fecal flotation test is designed to detect eggs of intestinal parasites. That test, performed at a time when no eggs were being produced, in a dog known to harbor whipworms, would give us a false negative result. Test enough times, however, and one would expect to eventually confirm the worms’ presence.
Researchers know that as many as one-third of cats harboring Feline Leukemia Virus (FeLV) sequester it in their bone marrow, where a test on a sample of peripheral (arterial or venous) blood would not detect it. So, an in-house blood test for the disease would deliver a false negative, and a positive bone marrow test would confirm our suspicion that the kitty was FeLV-positive.
False positive and false negative test results can be complicated to understand, but it is important to comprehending your pet’s doctor’s interpretation when results seem confounding.
See you next week, Dr. Randolph.