The most common and well-known of tick-related infections, Lyme disease is easy to treat, but hard to diagnose. Virax Biolabs is aiming to change that.
By Chris Wolski
Summary: Lyme disease, the most prevalent tick-borne illness, remains difficult to diagnose despite being easy to treat, with diagnostic advancements by companies like Virax aiming to improve early detection and treatment monitoring.
Takeaways:
- Challenges with Diagnosis: Traditional Lyme disease tests, such as ELISA and Western Blot, often lack sensitivity, leading to false negatives or positives and delayed detection.
- Innovative Diagnostics: Virax is developing improved ELISpot technology, designed to detect early infections and monitor immune response, offering more accurate results than current serological methods.
- Post-Acute Infections: The rise in post-treatment Lyme disease syndrome and conditions like long COVID underscores the growing need for precise diagnostic tools to guide timely and effective treatment.
One of the most common, and, certainly, the most well-known tick-related disease, Lyme disease has seen an increase since it was first discovered in Lyme, Conn., in the mid-1970s.
With about 63,000 cases reported to the Centers for Disease Control and Prevention (CDC) in 2022, which is an all-time high, after the 43,000 cases reported in 2017. On its website, the CDC suggests that 476,000 people are treated for Lyme disease each year—including those who may not have the disease.1
Whatever the statistics, there is one overriding truth for Lyme disease and many other tick-related afflictions—it’s easy to treat, but hard to diagnose.
Virax is working to make the second half of that equation meet the first. In a recent conversation with Virax COO Nigel McCracken, he outlined why Lyme disease is tough to diagnose, breakthroughs in diagnosing and treating the disease, how Virax is working to develop effective diagnostics, and the growing prevalence of post-acute diseases, such as long COVID.
His responses have been edited for length and clarity.
CLP: What breakthroughs have there been for Lyme disease diagnostics?
Nigel McCracken: Direct diagnosis, mainly based on the detection of the pathogen, is for many infectious diseases the gold standard for proving an active infection. The bacterium causing Lyme disease, however, is difficult to culture so the current test for Lyme disease is based on serology using two tests: an enzyme-linked immunosorbent assay (ELISA) and a Western Blot (WB). These serological tests are indirect diagnostic methods measuring the presence of anti-Bb antibodies and suffer from a lack of sensitivity. Currently there are a number of different approaches being developed to help identify early infection, which involve monitoring the immune cellular response following infection.
Similarly to viral infections, intracellular activation of type II interferons (IFN-γ) plays an important role in Borrelia burgdorferi infection (Bb), which can be exploited to detect the presence of antigens from Bb using ELISpot. ELISpot measures the antigen-specific cellular responses by quantifying the number of T cells producing IFN-γ. The noticeable difference with ELISA is that an ELISpot test will detect an infection even in the absence or low concentration of anti-Bb or antigen in the blood.
CLP: What continues to make Lyme disease and other tick-borne diseases so tough to diagnose and diagnose correctly?
McCracken: Patients suffering from Lyme disease have various non-focal and focal symptoms depending on the stage of the infection. If Lyme disease is detected correctly, and at an early stage its treatment is simple with the use of antibiotic therapy, which is effective in 80% to 90% of Borrelia infection cases. The problem is that according to the CDC and other sources, 70% to 80% of patients with Lyme disease eventually exhibit an erythema migrans (EM) rash, which is the only recognized characteristic symptom, appearing during the first stage, at the site of the tick bite. In addition, the EM rash is not systematically detected by affected individuals.
Most Lyme disease tests are designed to detect antibodies made by the body in response to infection, which comes with a number of limitations:
- Specific antibodies can take several weeks to develop, so patients may test negative if infected only recently.
- Antibodies normally persist in the blood for months after the infection is gone; therefore, the test cannot be used to determine cure.
- Infection with other diseases, including other tickborne diseases, or some viral, bacterial, or autoimmune diseases, can result in false positive test results.
As a result, this makes the current serology tests unsuitable for monitoring response to treatment or identifying new infections.
CLP: What diagnostic tools has Virax developed to address Lyme disease and tick-borne illnesses generally?
McCracken: We are developing a unique detection method based on improved ELISpot technology, which allows the detection of antibodies coupled to specific immune response, which will be more accurate with less false positive results than the current diagnostics. We believe the diagnostic test will be able to provide confirmation of an existing infection, information on the infection stage, i.e., early infection/late, as well as information on whether the immune system has successfully cleared the pathogen off the body. In this regard we have the opportunity to provide a cost-effective diagnostic test, which is more sensitive to identify the initial infection as well as provide guidance on the effectiveness of antibiotic treatment through the assessment of an individual’s protective immunity
CLP: Will these new tests be difficult to add to the testing menus, or can they be easily integrated into a workflow?
McCracken: As you mentioned it is extremely important that any future diagnostic tests are both cost effective and easily implemented. Our planned diagnostic will be based on a format that can be easily integrated into standard laboratory environments, without the need for major equipment investment. Since the detection is done by a cocktail of antibodies with standard labels, they can be read using either a microscope or a basic ELISpot reader.
CLP: How big a threat are tick-borne illnesses to individual and public health? What are the benefits of having more sensitive and specific tests for Lyme disease and other tick-borne illnesses?
McCracken: Lyme disease is the most frequent tick-borne disease in the world. Even if EM is the traditional clinical manifestation, the pathogen can spread to other tissues and organs, leading to blurred symptoms. Many direct and indirect tests for Lyme diagnosis are available, however, early diagnosis is still a problem as many people do not remember a tick bite and only around 30% of individuals show any early characteristic symptoms. If diagnosis of the infection is late or antibiotic treatment is ineffective then individuals can progress to chronic Lyme disease, also known as post-treatment Lyme disease syndrome. The symptoms of chronic Lyme disease include severe fatigue, cognitive problems and musculoskeletal pain, and can severely impact an individual’s health and quality of life. More sensitive tests that have the ability to detect the earlier stage of the infection as well as provide guidance on the effectiveness of the antibiotic treatment are essential for the future management of tick-borne illnesses to reduce the risk of progression to a more chronic syndrome.
CLP: More generally, how do you think the growing prevalence of post-acute infections/or late infections going to affect approaches to testing and medicine?
McCracken: Post acute infection syndromes (PAISs) like chronic Lyme disease, long COVID and myalgic encephalomyelitis (ME/CFS) are a range of complex conditions that manifest after an acute infection, where chronic inflammation; autoimmunity and improper functioning of T cells are believed to play a central role. The patient’s journey is long and complex where symptoms can be long lasting and debilitating and currently there are no reliable diagnostics available for early detection. With continued exposure to infections and vaccines it is predicted that the annual incidence of post-acute infections will be in the region of 1% to 2% of the population, where there will be the need for multiple tests for longitudinal assessments of their symptoms.
Currently, there is a huge medical need to develop a diagnostic test to help with the early detection of individuals experiencing symptoms associated with PAISs. This will hopefully inform and expedite diagnosis and appropriate clinical management to improve patient outcomes.
Chris Wolski is the chief editor of CLP.
Featured Photo: Dmitrii Melnikov | Dreamstime.com
Reference
- “Lyme Disease Surveillance and Data.” The Centers for Disease Control and Prevention (CDC). May 15, 2024. https://www.cdc.gov/lyme/data-research/facts-stats/index.html