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Early identification and treatment of Lyme disease can dramatically change patient outcomes, so broad awareness among the public and the medical community is essential. Unfortunately, statistics and case reports continue to suggest that Lyme disease is under-diagnosed. May is Lyme Disease Awareness Month and provides an opportunity to build awareness as we head into the height of flea and tick season.
The Gap Between Seroprevalence and Diagnosis
When the body fights off an infection, even with the help of antibiotics, it generally learns something about the pathogen and makes antibodies to fight against it. Those antibodies can stick around for years, decades, even a lifetime.
Antibodies confirm prior exposure and can indicate current infection. The initial IgM antibodies usually peak within a few weeks after an infection with Borrelia bacteria and start to collapse 4-6 months after infection. The later IgG antibodies are slower to develop, emerging 4-6 weeks after exposure, and may peak 4-6 months after exposure.
Two studies have recently been published comparing seroprevalence (how many people out of the population have positive antibody results against Borrelia burgdorferi) to the reported cases of Lyme disease.
In Finland, researchers published a seroprevalence study, finding 2.7 symptomatic cases for every reported case. In Germany, researchers estimated 12 symptomatic cases for every case reported to the surveillance system in nine of sixteen states that collect information on Lyme disease.
In the United States, a variety of methods have been used to estimate the true number of Lyme disease cases. These include reviewing insurance claims data and large commercial laboratory data. In 2021, the CDC estimated that almost half a million people in the United States were diagnosed with Lyme disease compared to the approximately 35,000 cases that make it into the surveillance database on an average year.
While important, this kind of research is hampered by several complications:
- Some people who become infected with Borrelia species never make antibodies. Delayed conversion from IgM to IgG is also well established.
- Some of those who become infected may not develop clinical symptoms.
- When present, antibodies can persist for months to years or may resolve following therapy, introducing significant statistical complexity.
- Number of cases can vary between regions, making it difficult to develop a measurable comparison.
In addition to these complications, surveillance monitoring data sets may not contain all diagnosed cases. Surveillance cases require extra paperwork to get into systems such as those in the United States and are generally tightly defined in order to generate statistics that can be compared year to year, even as clinical diagnostic standards change.
Why Is Diagnosis Missed?
Lyme disease is notoriously difficult to diagnose. Not all Lyme disease patients remember a tick bite, and only a minority of children and their caregivers recall tick contact. Importantly, not all patients present with the signature bull’s eye rash (erythema migrans) skin lesion, and the lesion is underdiagnosed in people with dark skin. Symptoms can be diverse and nonspecific. Serology testing for Lyme disease is not straight forward and almost always negative immediately after infection.
Direct detection tests are urgently needed. Galaxy Diagnostics launched a more sensitive direct detection test for Lyme disease in 2022.
Find out more about the Lyme Borrelia Nanotrap Antigen Test.
In the United States, financial and insurance characteristics have been linked to the likelihood of being diagnosed early with Lyme disease. In addition, physicians report having received little recent education about Lyme disease, and symptoms of Lyme disease are easily confused with other conditions by both patients and doctors. All of these issues can delay diagnosis and treatment.
Conclusion
Every May, we have an opportunity to build Lyme disease awareness, drawing attention to the complexity of diagnosis and advances in diagnostic tools that support a more accurate diagnosis. While antibody testing can be helpful to support diagnosis, limitations include risks of both false positive and false negative results.
Direct detection has historically presented significant challenges for confirmation of Lyme disease. However, recent diagnostic advances now allow confirmation of the Borrelia outer surface protein A (OspA) antigen in urine, providing doctors with higher confidence in the likelihood of current infection than that provided by antibody testing. These advances are particularly critical in clarifying current infection in the context of reinfection, potential treatment failure, and vaccination for Lyme disease (in Phase 3 clinical trials now).
Centers for Disease Control and Prevention. (2021, January 13). How many people get Lyme disease? https://www.cdc.gov/lyme/stats/humancases.html
Olsen, J. et al. (2023). Estimated number of symptomatic Lyme Borreliosis cases in adults in Finland in 2021 using seroprevalence data to adjust the number of surveillance-reported cases: A general framework for accounting for underascertainment by public health surveillance. Vector Borne and Zoonotic Diseases, 23(4), 265–272. DOI: 10.1089/vbz.2022.0051 https://pubmed.ncbi.nlm.nih.gov/37071408/
Olsen, J. et al. (2023). Estimated number of symptomatic Lyme borreliosis cases in Germany in 2021 after adjusting for under-ascertainment [online ahead of print]. Public Health, 219. DOI: 10.1016/j.puhe.2023.03.002 https://pubmed.ncbi.nlm.nih.gov/37075486/
Johnson, L. B., & Maloney, E. L. (2022). Access to care in Lyme disease: Clinician barriers to providing care. Healthcare (Basel), 10(10), Article 1882. DOI: 10.3390/healthcare10101882 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601439/