The websites of De Limburger, the Reformatorisch Dagblad, Radar and the ANP recently featured news items about Lyme disease. New, so-called cellular tests for Lyme disease would not appear to work. The messages referred to a recent scientific publication by our hand. Here, as co-authors of that article, we would like to provide context and explanation for these posts.
A review by: Freek van de Schoor, physician and researcher internal medicine Radboudumc & Ewoud Baarsma, physician and researcher internal medicine Amsterdam UMC.
Link to news item: click here
Link to original source: click here
What does the headline suggest?
With headlines like ‘Research: New Lyme Disease Tests Are Unreliable’, the posts suggest that all new Lyme disease tests are unreliable. But, which new tests are these exactly about and are they real? at New Lyme Disease Tests Unreliable?
What is Lyme Disease?
Lyme disease is an infectious disease caused by a bacteria called Borrelia burgdorferi† You can get this bacteria through a tick bite. In the Netherlands, an average of 20% of ticks are infected with Borrelia burgdorferi and not every bite from an infected tick successfully transmits the bacteria. It has been calculated in a Dutch study that the chance of Lyme disease after a tick bite is 2.5%. If you do contract Lyme disease, then in the majority of cases there is a local skin inflammation, the typical red circle or spot called erythema migrans† The bacterium can eventually also spread throughout the body and cause inflammation in, among other things, joints, the nervous system and the conduction system of the heart.
Where does this news item come from?
It is not always easy to determine whether someone has Lyme disease with a blood test. The current standard ‘antibody tests’ have their limitations. For example, up to 50% false negative test results occur in the early stages of infection. This means that the test result is (still) negative, but the patient is infected with the Borrelia bacteria. It is therefore not recommended to do blood tests if you suspect early Lyme disease (a erythema migrans), but instead treat it directly with antibiotics.
Some doctors, scientists and patients believe that new so-called cellular tests do not have these drawbacks. These cellular tests could detect Lyme disease earlier, so doctors can identify who has Lyme disease just after the infection starts. This would help us identify the correct diagnosis more quickly in patients with Lyme disease and, on the other hand, reduce unnecessary antibiotic use in people who do not appear to have Lyme disease.
These cellular tests alone have never been examined in a thorough study by independent researchers. As a result, we know nothing about the sensitivity (do patients with Lyme disease indeed get a positive test?) and the reliability (do healthy people indeed get a negative test?). Our study examined the sensitivity and reliability of a number of cellular assays.
We conducted a study with three groups of people: those with a confirmed Lyme disease diagnosis, healthy controls, and controls with a disease that can ‘confuse’ Lyme testing. Because we had to be sure that the patients really had Lyme disease, we used strict criteria and had the diagnosis established by a doctor (usually our own GP). In this way, we included 271 people with Lyme disease in the study. In addition, 228 people from all over the Netherlands participated as a control group, of whom we had established that they had no (complaints of) Lyme disease. Finally, control subjects with diseases such as syphilis, rheumatism and Weil’s disease, because these diseases can lead to false-positive results in Lyme tests. All these people donated their blood so that we could do the cellular tests and serology on it.
The cellular tests were successful in detecting Lyme disease in only 11.7-54.3% of the cases. As we expected, the antibody test was also not good at this: 28.1-50% of patients with doctor-diagnosed early Lyme disease had a positive antibody test. However, in the healthy controls there was a clear difference between the cellular tests and the antibody tests. Only 31.1 to 81.9% of the control subjects got the correct cellular test result. Thus, in 18.1 to 68.9% of the cases, healthy persons were incorrectly designated as Lyme disease patients. So up to 70% of people without Lyme disease can get a positive test result! The antibody test has proven to be a reliable test in this area: in 93-94.7% of the cases, this test correctly gave a negative result in the control subjects.
Is this really something new?
Cellular tests have been available for many years through commercial labs at home and abroad. Someone can send their own blood and receive a test result at home. These tests are not used in regular healthcare in the Netherlands. Our research now shows that several cellular tests are very unreliable.
What can we do with this now?
Many people have paid for cellular tests to find out whether their symptoms are explained by Lyme disease. But due to the poor reliability of these tests, both a positive and negative result can cause a lot of unrest and confusion.
Our research shows that the tested tests are not usable in practice. We have conducted research with a test that looks at the division of cells (a lymphocyte transformation test/LTT) and two ‘Elispot tests’ (the iSpot Lyme and the Spirofind† However, there are many different types of cellular tests and each commercial lab has a different test.
We can only say something with certainty about the precise tests that we have investigated, and therefore not about all cellular tests. That important nuance is missing in various news items. Nevertheless, our research emphasizes that you should be careful with blood tests for Lyme disease whose reliability is uncertain: using such tests carries a high risk of false positive or false negative results. That warning is also missing in the reporting.
Finally, the research findings also mean that we still don’t have a solution to the problems associated with Lyme testing. We will therefore continue to work with Radboudumc, RIVM and Amsterdam UMC to improve diagnostics for Lyme disease.
Do you want more information, but visually? Watch an animation below explaining our research and how cellular tests work.