Improved multi-strain diagnostic tests for Lyme disease

by Jacqui van Teulingen

At the LivLyme Summit in Colorado we heard about the progression in laboratory testing for Lyme disease and Tick-borne Relapsing Fevers via Dr Jyotsna Shah, CEO and president of IGeneX. It was timely given the Infectious Disease Society of America’s (IDSA) journal has just acknowledged the shortcomings of existing tests established as part of the 1994 Dearborn testing guidelines.

It is broadly accepted that the current and recommended indirect tests for Lyme disease, those that rely on an immune response to show up in your blood, are inadequate. Research just released in the IDSA’s Clinical Infectious Disease journal discusses these shortcomings as well as the inability of existing tests to show an infection early in the disease.

Controversy about test sensitivity and specificity

There is also controversy about test sensitivity and specificity and we are not immune from this in Australia. If you are new to Lyme disease testing these are the two most important characteristics discussed when testing for Lyme disease. Put simply, sensitivity refers to the likelihood that a positive test result is in fact positive – you do have the disease. Specificity refers to the likelihood that a negative test result really means the test is negative – in other words you don’t have the disease.

Due to these controversies, our Health department commissioned an investigation into the performance of the testing assays used to test for Lyme disease in Australia. It concluded that higher generation tests, developed using latest technologies provide better test accuracy.

Dr Shah reminds us of the increasing incidence of tick-borne illness worldwide and asserts that there are two groups of Borrelia that cause significant disease in people, the first is called the Lyme group - Borrelia burgdorferi senso lato (Bb), the second is the Tick-borne Relapsing Fever group (TBRF).

Currently the recommended diagnostic tests available are not only insensitive, but many species of Borrelia are missed. We know from previous research that there are 53 known strains of Borrelia; yet in Australia we test for only 3 of them. Given the debilitating illness that results from undiagnosed disease, there is a critical need for better diagnostic tests that can detect both Bb and TBRF antibodies.

Dr Shah, presented on IGeneX’s work developing ImmunoBlot tests and reporting data indicating the tests are specific and sensitive, and they can detect all stages of the disease and test for multiple strains of Borrelia.

Using statistics from the study Dr Zhang conducted on the Economic impact of Lyme disease, Dr Shah highlighted the importance of early and accurate diagnosis. With an average out of pocket cost of $1,30 per patient with early Lyme, and $16,200 in costs for a patient with a chronic form of Lyme disease its not difficult to do the sums. Sadly, in Australia the out-of-pocket cost situation is compounded by the fact that most Australian patients are already long term sufferers.

ImmunoBlot

Using the currently available serological tests, a patient would require around 30 different tests to adequately cover all the strains in the B.burgdorferi sensu lato group. Instead IGeneX has developed an ImmunoBlot with improved sensitivity and specificity.

A clinical validation study of 178 samples demonstrated increased sensitivity at 100% by in-house criteria and 88.5% by CDC criteria when compared to existing Lyme Western Blots. The specificity test demonstrates 99% for IgM and 97.4% for IgG by in-house criteria. Dr Shah concludes that Lyme immunoblots are intentionally more inclusive than the available Wester Blots because we now know that other species of Borrelia - mayonii, californiensis, speilmanii - all cause disease in the USA.

Comparing Sensitivities

When compared to the existing two-tier testing method set out by the CDC and recommended in Australia (that is an ELISA test followed by a Western Blot) the sensitivity of the ImmunoBlots is still impressively more than currently available.

Figure 1 Comparison of 2-tier Serological Testing vs. Lyme ImmunoBlots - IGeneX Presentation data

You can access the complete results in the article Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for Laboratory Diagnosis of Lyme Disease.

If you are worried about the need to test for Relapsing fever Borrelia (RFB), it’s important that you consider recent findings from overseas research showing that a dual infection with Borrelia burgdorferi and RFB was widespread in California; 11% of the 321 patients studied. The research concluded that dual exposure to Bb and RFB may complicate the diagnosis of tick-borne disease. It also noted that an RFB infection may explain ‘Lyme-like’ symptoms in patients who are negative when tested for Lyme disease only. This issue is important for us, as Dr Shah’s research on Australian samples indicates that 20% of patients in a sample of 100 are testing positive to RFB.

The good news is you can order these new and improved tests from IGeneX even from Australia. You’ll find information on how to send blood to IGeneX for testing as well as test requisition forms and pricing of each of the tests available.