One of the most difficult parts of navigating Lyme disease is getting diagnosed in the first place. Sometimes called “the great imitator,” it can be difficult to tell if someone has Lyme disease, especially if they don’t have more pronounced symptoms like an erythema migrans, or “bull’s eye” rash. Symptoms tend to be non-specific, and tick-borne diseases are not usually an initial consideration.
Accurate and reliable testing is essential for those suffering from tick-bone diseases, especially early on, as treatment can prevent long-term complications. Unfortunately, the most-up-to-date testing recommendations are not readily available, including the outdated recommendations on the CDC’s website. Therefore, raising awareness and educating the public is vital, so that healthcare providers and individuals can make the most well-informed decisions for patient health.
There are several testing options for tick-borne diseases, but how do healthcare providers decide which tests are appropriate for their patients? A significant aspect to understand when diagnosing any disease is the difference between direct and indirect testing.
Infections in The Immune System
Before we learn about the different types of testing, it’s helpful to have a basic understanding of the immune system and how it responds to infections. When someone is exposed to a pathogen or a substance that the body doesn’t recognize- a virus, bacteria, fungi, or otherwise– the immune system starts to react. The immune system is reacting to antigens, triggering your body into producing antibodies. Antibodies are proteins that help the immune system fight against antigens.
This is a very simplified explanation of the immune system. However, it’s also the basis for many types of infectious disease testing.
Direct and Indirect Lyme Disease Testing
In the wake of the pandemic, the average person has become savvier about their options when it comes to medical testing—the two main types of Covid-19 testing use either direct or indirect methods.
The science used for tick-borne disease testing is similar to tests used for Covid-19. Direct testing for Lyme disease, and other tick-borne diseases, would look for the pathogen itself, in this case, a bacteria or parasite.
Direct Testing
Direct testing involves looking for a pathogen in a sample, such as blood, urine, tissue, or other miscellaneous sample types. PCR and FISH (Fluoresence in-situ hybridization) are examples of direct tests. PCR can also be used to test the tick itself.
Reasons to use direct testing:
- Not every patient has detectable antibodies (sero-negative)
- Patients may be immune-suppressed
- Antibodies may be bound in immune complexes
- Blood draws can be challenging for younger patients, and therefore, urine specimens are less invasive to collect and can be tested instead
- The antigen itself is being detected. A positive result is more likely to be definitive, and not open to other interpretations
- Useful soon after being bitten by a tick, when the antigens are still present at a higher viral load
Indirect Testing
Indirect testing measures the immune system’s response to the presence of a pathogen. In general, these tests measure the presence of antibodies and T cells. Some common examples include the ELISA (Enzyme-linked Immunosorbent Assay), IFA, Western blot, and the ImmunoBlot. Of these, the ImmunoBlot is the most sensitive and specific.
Reasons to use indirect testing
- Pathogens are not always in the bloodstream and detectable by PCR or FISH
- Superior at detecting early and/or late-stage disease
- Certain tests can detect T-cell response, an early disease indicator and useful in B-cell immune deficiencies
- Important indicator of whether a patient is fighting the infection and health improving after treatment, once retested
- Detects re-infections
Getting Tested for Lyme Disease
Current CDC recommendations for Lyme disease testing involve a two-tiered system of an ELISA, followed by a Western blot. Unfortunately, these aren’t the most up-to-date methods available and can miss active infections due to low sensitivity. IGeneX has other updated direct and indirect methods of Lyme disease testing and other tick-borne disease testing available.
If a tick has bitten you or you display symptoms, how do you know when to test? Many forms of testing, especially indirect ones that depend on the presence of antibodies, are only accurate starting 2-6 weeks after exposure. The Lyme ImmunoBlot IgM, however, may be sensitive as early as two weeks after a tick bite and can remain positive for 6-8 weeks or even longer.
Below are the direct and indirect tests offered by IGeneX:
Direct:
- PCR
- FISH
- LDA
- Culture
Indirect:
- ImmunoBlot
- Western blot
- LSA (combined with the ImmunoBlot, this fulfills the 2-tier testing)
- IgXSpot
- Serology
Testing by multiple methods increases diagnostic accuracy, and both indirect and direct testing are recommended to provide a broad spectrum of tick-borne disease testing.
It can be confusing and scary to navigate tick-borne disease testing, whether or not you’re experiencing symptoms of disease. In terms of direct vs. indirect testing, one is not better than the other. For the most accurate results, combining both methods using different tests is recommended. IGeneX offers panels that combine several testing methods.
