Tag Archives: lyme disease test

The need for an alternative to current antibody-based Lyme disease diagnostic tests

by Timothy J. Sellati, Ph.D., Chief Scientific Officer, Global Lyme Alliance

An early and accurate test result is critical to effectively treat most diseases. Especially Lyme disease. The earlier one is diagnosed and treated, the better the odds are for recovery. Unfortunately, current Lyme disease diagnostics are highly inaccurate for early diagnosis, having a direct negative impact on patients’ health.

The most common means of laboratory diagnosis of Lyme disease is an indirect test that detects the immune response (antibodies) triggered by the presence of Borrelia burgdorferi, the causative agent of Lyme disease. The current standard two-tiered test (STTT) relies on a first-tier enzyme immunoassay (EIS), that is relatively sensitive but not extremely specific. If positive or equivocal the EIA is followed by a second-tier Western immunoblot assay, that shows improved specificity. Shortcomings associated with the STTT include missing as much as 60% of early Lyme cases due to no or low antibodies levels during the first few weeks of infection.  Moreover, the second-tier assay is technically difficult and time-consuming to perform and the results are prone to subjective interpretation resulting in both false negative and false positive results.  Beyond the tests’ limitations, detection of antibodies as a basis for diagnosis is confounded by the fact some patients may not produce antibodies against B. burgdorferi, while others will start and then stop producing them, and still others will continue to produce antibodies long after treatment and treatment/cure and resolution of symptoms.

As part of our mission to conquer Lyme disease, in 2017 Global Lyme Alliance was responsible for a report that publicly addressed the limitations of current two-tiered tests while simultaneously seeing the real potential of newer technologies to overcome many of the limitations. This finding supports GLA’s ongoing work with top researchers to develop a more accurate diagnostic test that will better serve patients and the community.

Also in 2017, GLA partnered with Ionica Sciences, a startup diagnostics company based at Cornell University’s McGovern Center life sciences incubator in Ithaca, New York, to accelerate the development of a highly sensitive direct Lyme disease diagnostic test. Called IonLymeTM, this novel testing strategy recognizes a specific bacterial protein [Outer surface protein A (OspA)] shed in minute quantities by B. burgdorferi into the bloodstream during early infection rather than waiting weeks for antibodies to be produced. OspA is thought to only be in the blood during active infection. So, IonLyme not only detects early Lyme disease much better than current solutions, it also allows testing for reinfection, and can help to determine if a person is cured of active Lyme disease.

While still in the validation phase of development Ionica Sciences has made a significant advance by demonstrating excellent diagnostic accuracy with IonLymeTM using biobanked blood samples. Currently, the assay generates statistically significant results with >90% clinical sensitivity and >95% clinical specificity. Thus, while other companies have made important strides in developing modified two-tiered tests (MTTTs), that rely on two EIAs rather than an EIA and Western immunoblot, which show increased sensitivity in diagnosing early Lyme disease, their approach is still limited by their focus on measuring antibody responses.

GLA is a strong believer that the more minds that work toward a goal, the better. Partnerships like we have with Ionica will speed the delivery of the tools and resources that will help patients, from diagnostics to treatment. If you are interested in supporting Ionica’s current endeavor and want to participate in their current fundraising campaign, click here.

Related posts:
Progress in New Ionica Sciences Lyme Disease Diagnostic Test Funded by Global Lyme Alliance
The Advantage of Public-Private Partnerships to Accelerate Progress for Patients
Global Lyme Alliance Partners with Ionica Sciences to Develop New Lyme Disease Diagnostic Test

GLA Point of View on New Tick-Borne Co-infection Diagnostic Test

by Timothy Sellati, Ph.D., Chief Scientific Officer, GLA

Lyme disease is the most commonly occurring vector-borne disease in the United States. The number of cases reported to the Centers for Disease Control and Prevention (CDC) has increased steadily over the past 25 years. The actual number of cases that occur annually is difficult to pinpoint given several shortcomings associated with the current FDA-approved two-tier serologic testing protocol. Laboratory methods for the diagnosis of Lyme disease fall into two categories: (1) direct methods to detect the Borrelia burgdorferi,bacterium, the causative agent of Lyme disease, and (2) indirect methods that detect the immune response (antibodies) against it. Shortcomings associated with the current testing protocol include low sensitivity in those newly infected, subjectivity in the interpretation of Western immunoblot results, and the inability of the test to discriminate between current active infection versus past exposure.

Despite the annual estimated number of cases being 300,000 to 329,000 nearly 3.4 million Lyme serologic tests are performed each year.  The predictive value of a test is determined by its sensitivity, specificity, and the prevalence of the disease in the population to be tested. Given the Lyme testing protocol’s shortcomings, coupled with sometimes inappropriate use of the test (prior to production of antibodies against B. burgdorferi) and the ability of the pathogen to shut down antibody production during later disease, there is an unacceptably high rate of false-negative and false-positive results.  The most effective treatment options can only be pursued when rapid and accurate diagnosis occurs. Compounding the challenge faced by physicians in choosing the correct course of treatment is the fact that the black-legged (“deer”) tick, Ixodes scapularis, also serves as a vector for Powassan virus, Borrelia miyamotoi and mayonii infections, and the causative agents of anaplasmosis, babesiosis. Lack of knowledge about the co-infection status of an individual can delay provision of appropriate treatment(s) to combat all the symptoms experienced by a patient. Recognizing that the longer a pathogen remains in the body the more likely the severity and duration of disease will be greater, there is a critical medical need for rapid, sensitive, and specific diagnosis.

It is for this latter reason that so much excitement surrounds the announcement that Global Lyme Diagnostics (GLD), which launched its ground-breaking Lyme diagnostic in 2017, and is now launching its tick-borne co-infections diagnostic test. This new co-infection panel offers physicians the ability to test patient samples for evidence of the most common tick-borne diseases (i.e., Anaplasma, Babesia microti and B. duncani, Bartonella henselae and B. quintana, and Rickettsia including the Spotted Fever Group).

According to GLD’s CEO, Mickey Ramchandani, “The new co-infection test is the most affordable on the market with the quickest turnaround time from test to results and allows physicians to custom-pick the co-infections they want to test for—not forcing them to run a battery of tests for a co-infection they have already deemed unnecessary through their own analysis.” Ramchandani also states that “Our mission at Global Lyme Diagnostics has been to reduce false negatives plaguing the Lyme testing assays with a test that is not only reliable but is also affordable to a wider population. We are now expanding our test menu to also include multiple different co-infections that result from tick bites.”

GLD licensed the technology platform and related intellectual property surrounding chimeritopes developed by Richard T. Marconi, Ph.D., a Professor in the Department of Microbiology and Immunology at Virginia Commonwealth University. Dr. Marconi also serves on the Scientific Advisory Board of Global Lyme Alliance.


timothy sellatiTimothy J. Sellati, PH.D. is Chief Scientific Officer at Global Lyme Alliance

As GLA’s Chief Scientific Officer, Dr. Sellati leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis and treatment of Lyme and other tick-borne diseases.

GLA Point of View on “First Multiplex Test for Tick-Borne Disease”

by Timothy Sellati, Ph.D., Chief Scientific Officer, GLA

Advances in Serodiagnostic Testing for Lyme Disease Are at Hand

…the TBD-Serochip represents an important advance and significant improvement over existing tests for tick-borne diseases (TBDs), which have poor diagnostic accuracy and cannot test for more than a single infection at a time.

The testing arsenal available to front-line physicians responsible for accurately diagnosing tick-borne diseases has recently been bolstered by a new blood test called the Tick-Borne Disease Serochip (TBD-Serochip).  Described in the journal Nature Scientific Reports, the TBD-Serochip represents an important advance and significant improvement over existing tests for tick-borne diseases (TBDs), which have poor diagnostic accuracy and cannot test for more than a single infection at a time.  Currently, the two-tier diagnostic test for Lyme disease identifies fewer than 40 percent of patients with early Lyme disease and results in false positives 28 percent of the time.

The TBD-Serochip research team was led by co-lead authors Rafal Tokarz, Ph.D. and Nischay Mishra, Ph.D., who are associate research scientists at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health.  As a true cross-disciplinary and multi-institutional effort, the team also included Brian Fallon, M.D. from the Global Lyme Alliance-funded Columbia University Lyme and Tick-Borne Diseases Research Center, who contributed to the study design, as well as researchers from the Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, Roche Sequencing Solutions, Farmingdale State College, and State University of New York-Stony Brook.

According to Dr. Tokarz, “The number of Americans diagnosed with tick-borne disease is steadily increasing as tick populations have expanded geographically.”  “Each year, approximately 3 million clinical specimens are tested for TBDs in the U.S.  Nonetheless, the true incidence of TBDs is likely greatly underestimated, as patients with presumed TBDs are rarely tested for the full range of tick-borne pathogens, and only a fraction of positive cases are properly reported,” added Dr. Mishra.  The power and promise of the TBD-Serochip derives from its ability to simultaneously test 170,000 individual protein fragments for the existence of pathogens connected to eight different TBDs including Anaplasma phagocytophilum (agent of human granulocytic anaplasmosis), Babesia microti (babesiosis), Borrelia burgdorferi (Lyme disease), Borrelia miyamotoi, Ehrlichia chaffeensis (human monocytic ehrlichiosis), Rickettsia rickettsii (Rocky Mountain spotted fever), Heartland virus and Powassan virus.

As such, a single sample via TBD-Serochip can determine whether an individual is infected with more than one tick-borne pathogen.  This diagnostic capability is essential as individual ticks frequently harbor more than one pathogen and appropriate treatment of patients with multiple TBDs would potentially require the use of different antibiotics to effectively kill them.  More importantly is the new discovery’s capacity for scalability, for as new tick-borne infectious agents are discovered, TBD-Serochip can be modified to target them, a process the researchers say can be done in less than four weeks.

Despite the significance of the TBD-Serochip being added to a physician’s diagnostics arsenal, as pointed out in another GLA POV titled “Advances in Serodiagnostic Testing for Lyme Disease Are at Hand” improvements in serologic testing methods or protocols will not address their inability to differentiate active infection from past exposure.  Thus, ideally, use of tests like TBD-Serochip will be coupled with diagnostic methods to directly detect the presence of B. burgdorferi and other tick-borne pathogens in patient’s samples, thereby discriminating between active rather than past infection in patients.  GLA is actively supporting research efforts to develop such direct detection methods.

 


timothy sellatiTimothy J. Sellati, PH.D. is Chief Scientific Officer at Global Lyme Alliance

As GLA’s Chief Scientific Officer, Dr. Sellati leads GLA’s research initiatives to accelerate the development of more effective methods of diagnosis and treatment of Lyme and other tick-borne diseases.