Understanding Spirochete Infection Tests: A Patient's Guide to Lyme Disease, Relapsing Fever, and Syphilis Diagnostics

Table of Contents

• Key Points
• Background: What Are Spirochetes and Why Are They Hard to Diagnose?
• Quality Standards: How Diagnostic Tests Are Regulated in France and Europe
• Lyme Disease Diagnosis: Direct Detection Methods
• Lyme Disease Diagnosis: Serology (Antibody Testing)
• Lyme Disease: Different Species, Different Test Responses
• Lyme Disease: Alternative and Unproven Tests
• Relapsing Fever Diagnosis
• Syphilis Diagnosis
• Key Limitations of Current Diagnostic Tools
• What This Means for Patients
• Frequently Asked Questions
• Source Information

Key Points

• No single diagnostic test for Lyme, relapsing fever, syphilis, or leptospirosis is perfect; false positives and negatives occur.
• Two-tiered Lyme testing (ELISA followed by immunoblot) improves accuracy; single tests can give up to 27% false IgM positives.
• Lyme serology is often negative in early erythema migrans (>50% in Europe) but very sensitive in late stages (arthritis 95%, acrodermatitis 98%).
• Unproven tests like lymphocyte transformation tests and CD57 markers lack validation; use only accredited laboratories for reliable results.

Background: What Are Spirochetes and Why Are They Hard to Diagnose?

Spirochetes are a unique family of spiral-shaped bacteria that move using internal structures called pseudoflagella, which allow them to swim through thick fluids such as mucus and connective tissue. Several spirochete species cause significant human diseases, and this review focuses on four of them: Borrelia burgdorferi sensu lato (the cause of Lyme disease), relapsing fever borreliae (transmitted by ticks or lice), Leptospira (the cause of leptospirosis, a worldwide animal-borne infection transmitted through contact with rodent urine), and Treponema pallidum (the cause of syphilis, a sexually transmitted infection).

Why are these infections so difficult to diagnose? The bacteria share several frustrating characteristics. They do not stain with the standard Gram stain used in most microbiology labs, and they cannot be grown on ordinary culture media. Some species are so fragile or slow-growing that culturing them takes weeks, and a few cannot be cultured at all in the laboratory.

These diagnostic challenges have sparked considerable public debate—particularly from patient advocacy groups and some physicians—who question the reliability of Lyme disease testing. Interestingly, the authors note, there is no comparable debate for the other spirochetal infections. This review was written to assess what the scientific literature actually says about the value of diagnostic tests for all four of these infections.

Quality Standards: How Diagnostic Tests Are Regulated in France and Europe

Before diving into test performance, the authors emphasize an important fact: laboratories in Europe and France that perform and sell diagnostic tests for humans must follow strict regulatory standards. These include CE marking (a certification that a product meets European legal requirements), inspections by the French Agency for the Safety of Health Products (ANSM), and COFRAC accreditation—a national accreditation required for laboratories performing biological tests.

For molecular biology techniques like PCR (polymerase chain reaction, a method that amplifies and detects bacterial DNA), laboratories must have their methods formally validated. This includes additional testing to ensure there is no contamination in the laboratory that could cause false results. The authors stress an important caveat: the quality of tests performed by laboratories that do not meet these standards cannot be guaranteed.

One particularly notable regulation: veterinary laboratories have not been allowed to perform human biological tests since May 30, 2013. This matters because some patients, frustrated with conventional testing, have turned to veterinary labs for Lyme testing—a practice that is now illegal in France and whose results are not validated for human diagnosis.

Lyme Disease Diagnosis: Direct Detection Methods

For most conditions, the most straightforward way to diagnose an infection is to find the bacterium itself. With Lyme disease, this is easier said than done. The bacterium cannot be detected using standard optical microscopy or Gram staining. Specialized techniques like dark-field microscopy or phase-contrast microscopy can theoretically visualize the spiral-shaped bacteria, but in practice, the bacteria rarely appear in blood samples. In Lyme disease—especially in European clinical presentations—bacteremia (bacteria in the bloodstream) is moderate, short-lived, and occurs only at the very beginning of the infection's spread. Testing blood for the bacterium when a patient has no fever is therefore useless. The few reports of "positive" microscopy results have actually been shown to be artifacts—not Borrelia bacteria at all. The review authors conclude that microscopy simply does not perform well enough to be a useful diagnostic tool for Lyme disease.

Culture: Slow and Technically Demanding

Culturing Borrelia from tissue samples (such as skin biopsies, synovial membrane, or cerebrospinal fluid) is possible but requires specialized liquid media—BSK-II, MKP, or BSK-H—incubated at 32–34°C (about 90–93°F). Because Borrelia divides very slowly (the mean time to bacterial growth is 7–20 hours), cultures typically take more than 15 days to become positive, and sometimes up to 8 weeks or longer. Laboratories must check cultures once a week using dark-field microscopy for at least 8 weeks before declaring a negative result. Adding to the difficulty, Borrelia growth does not cloud the culture medium the way many other bacteria do, so special expertise is required to spot it.

Borrelia are also extremely fragile bacteria. Specimens must be inoculated directly into culture media at the patient's bedside—they cannot simply be shipped to a lab. Because of these demanding technical requirements, only a few specialized laboratories in Europe perform Borrelia cultures from human specimens. Even then, while cultures perform well with specimens from erythema migrans (the classic "bull's-eye" rash), they lack sensitivity when used on other biological specimens such as cerebrospinal fluid, skin biopsies of acrodermatitis chronica atrophicans (a late-stage skin condition caused by Lyme), and synovial fluid (joint fluid), where only a few bacterial isolates are observed. Importantly, no strain has ever been isolated from the blood of patients with chronic symptoms appearing years after a tick bite, and blood culture is therefore currently not recommended.

PCR: A Powerful Tool with Limits

PCR testing detects the genetic material (DNA) of the bacterium and avoids many of the constraints of culture. Several PCR techniques are available, and their performance varies in terms of sensitivity, specificity, and the range of bacterial targets they can detect. Several PCR kits are marketed, but their performance is poorly documented. The authors advise that direct detection of Borrelia by PCR should only be performed by official, accredited specialized laboratories.

The sensitivity of PCR is much higher than culture for the disseminated (spread) skin and joint forms of Lyme disease. However—and this is critical—a negative PCR test result cannot rule out Lyme disease. The authors also offer a specific warning: prescribing Borrelia PCR when serology (antibody testing) is negative is not recommended, except for patients with early atypical skin lesions of erythema migrans or very early Lyme neuroborreliosis (neurological Lyme disease).

Among all direct diagnostic techniques, only PCR and culture—despite their limitations—have been validated for detection of Borrelia. Microscopy techniques are too often associated with artifacts and should be avoided.

Lyme Disease Diagnosis: Serology (Antibody Testing)

Because direct detection is so difficult, the biological diagnosis of Lyme disease today relies mainly on serological testing—that is, testing blood for antibodies the immune system produces against the bacterium. In France, as in most European countries and the United States, Lyme disease diagnosis is based on a two-tiered testing strategy. The first test is usually an ELISA (enzyme-linked immunosorbent assay), which is sensitive but not highly specific. If the ELISA is positive or borderline, a second confirmatory test is performed using an immunoblot technique (also called Western blot) to verify the specificity of the anti-Borrelia antibodies. This two-step approach improves the specificity of the final result.

What the Research Shows About Test Performance

A recent European meta-analysis (a statistical analysis that combines the results of multiple studies) examined whether immunoblot tests alone performed better than ELISA tests alone for diagnosing Lyme disease in Europe. The findings were striking:

• For Lyme neuroborreliosis (neurological Lyme disease): ELISA sensitivity was 81% (confidence interval 70–89%), and immunoblot sensitivity was also 81% (confidence interval 57–96%). Specificity was 92% (confidence interval 88–89%) for ELISA and 94% (confidence interval 91–96%) for immunoblot.
• For Lyme arthritis: ELISA sensitivity was 94% (confidence interval 86–98%) and immunoblot sensitivity was 95% (confidence interval 84–98%). Specificity was 97% (confidence interval 94–98%) for ELISA and 92% (confidence interval 84–96%) for immunoblot.

In plain language, this means the two tests perform similarly when used alone—neither is clearly better than the other. The authors also noted a slight—though statistically non-significant—improvement in performance when purified or recombinant antigens (synthetic pieces of bacterial proteins) were used, particularly in patients with Lyme neuroborreliosis.

Why use both tests then? Because the two-tiered process improves the positive predictive value (the chance that a positive result truly means infection) compared with a single test. Using a single ELISA or immunoblot can produce up to 27% false IgM positive results. IgM antibodies are the first antibodies produced during an infection, and false positives here can lead to unnecessary treatment and anxiety. Since both methods have some degree of specificity, using them in succession increases the reliability of a positive final result.

Test Accuracy Varies by Disease Stage

One of the most important messages in this review is that serology performance varies dramatically depending on when during the infection the test is performed.

• Erythema migrans (the bull's-eye rash): No biological test is required for typical cases because the serological test is negative in more than 50% of cases in Europe at this stage. Erythema migrans is a localized infection that triggers only a weak immune response. A negative test here should not be used to rule out the diagnosis.
• Lyme neuroborreliosis (acute phase): Examination of cerebrospinal fluid (CSF) reveals a lymphocytic cellular reaction (an increase in a type of white blood cell) in more than 93% of patients with meningoradiculitis (inflammation of the nerve roots and meninges, a classic neurological manifestation of Lyme). Serum (blood) serology is positive in 70–89% of cases during the acute phase, and CSF sensitivity is greater than 90%.
• Late-stage disease: At the stage of Lyme arthritis (joint inflammation), serology sensitivity is 95%. At the stage of acrodermatitis chronica atrophicans (a late skin manifestation), sensitivity reaches 98%.

The authors highlight that the very high negative predictive value of serology in late-stage disease means doctors should question a Lyme disease diagnosis if serology is negative in a patient with late-stage symptoms. However, they also add a crucial caveat about treatment: after effective treatment, anti-Borrelia antibodies (including IgM) may persist for months or even years after clinical cure. Serological testing is therefore not useful for monitoring treated patients, and the presence of IgM antibodies does not indicate an ongoing infection.

Lyme Disease: Different Species, Different Test Responses

The Borrelia burgdorferi sensu lato complex includes several species with different geographic distributions and clinical presentations. The predominant species in Europe are Borrelia garinii and Borrelia afzelii, while Borrelia burgdorferi sensu stricto is most frequently observed in the United States. These differences matter for diagnosis.

Serological tests can partially distinguish between these species because of molecular and antigen differences in their surface proteins. In 1994, Wilske and colleagues developed an immunoblot technique using five recombinant antigens that could detect seroreactivity differences between patients infected with B. afzelii, B. garinii, or B. burgdorferi sensu stricto. Two years later, Norman and colleagues developed an immunoblot using several strains of all three species and made an important discovery: European patient sera reacted more strongly to B. garinii and B. afzelii strains, while North American patient sera reacted more strongly to B. burgdorferi sensu stricto antigens.

The same study found that sera from patients with neurological symptoms reacted more strongly to B. garinii antigens, while sera from patients with dermatological (skin) presentations reacted more strongly to B. afzelii antigens. However, the authors noted that in about 8% of tested specimens, the Western blot interpretation (positive vs. negative) could vary depending on which strain was used—a troubling level of variability.

Other European studies confirmed these patterns: a preferential association of B. garinii with neurological disorders, B. afzelii with late skin manifestations, and a slight predominance of B. burgdorferi sensu stricto in joint manifestations. As early as 1999, researchers suggested standardizing Western blot techniques using B. garinii and B. afzelii strains across Europe, using a panel of patient sera from various European regions provided by the European Union Concerted Action on Lyme Borreliosis (EUCALB).

Commercially available tests in European markets vary in composition and performance. Most are prepared with a mixture of recombinant antigens from the three main pathogenic species (B. burgdorferi sensu stricto, B. garinii, and B. afzelii) to improve sensitivity. However, the authors caution that accurate differentiation of Borrelia species can only be achieved through molecular techniques. Reactivity differences observed in serological tests do not always correspond to what culture or PCR reveals, and relying on them may lead to interpretation errors.

Lyme Disease: Alternative and Unproven Tests

Several alternative tests are sometimes marketed for Lyme disease diagnosis, but the review authors are clear that their scientific validation is lacking.

Lymphocyte transformation tests (LTT) measure how a patient's immune cells respond to Borrelia antigens in the laboratory. The authors report that LTTs currently lack validation, and published studies have substantial methodological biases. In Lyme neuroborreliosis specifically, the diagnostic value is low: only 36% sensitivity and 82% specificity—meaning the test misses nearly two-thirds of true cases.

CD57 marker detection (a test that measures a specific type of immune cell) has been promoted by some practitioners. However, little data exists, and the only case-control study performed (the NIH study) reported a complete lack of specificity for this test.

As for rapid diagnostic tests for self-testing at home, the authors state that sensitivity and specificity data are currently very limited. They do not recommend these tests.

Relapsing Fever Diagnosis

Relapsing fever borreliae are mainly found in tropical and subtropical regions, particularly in Africa. The causative species include Borrelia duttonii, Borrelia crocidurae, Borrelia recurrentis, Borrelia persica, and Borrelia hispanica. They are transmitted by soft ticks (family Argasidae), and one species—Borrelia recurrentis—is transmitted by body lice. An emerging species, Borrelia miyamotoi, is transmitted by hard ticks.

Relapsing fever is different from Lyme disease in an important way: these bacteria do cause significant bacteremia (bacteria in the bloodstream) during febrile episodes. This makes direct detection much more feasible.

Direct Diagnosis of Relapsing Fever

The usual diagnostic method is optical microscopy after Giemsa staining of a blood smear or thick blood drop. This technique can detect bacterial concentrations of 10³ to 10⁵ microorganisms per milliliter of blood. Comparative studies have shown that additional methods can increase the sensitivity of optical microscopy:

• Quantitative buffy coat (QBC)—a technique that concentrates white blood cells and any bacteria in them—is supposed to be 100 times more sensitive than thick blood drop for diagnosing relapsing fever borreliae. However, it requires specialized laboratory equipment that is often unavailable in the endemic regions where relapsing fever occurs.
• Differential centrifugation, acridine orange staining, and fluorescence microscopy can also contribute to increased sensitivity.

PCR techniques have also been developed and show better sensitivity than microscopy. The review includes specific performance data:

• A multiplex quantitative PCR (qPCR) for B. crocidurae, B. duttonii/recurrentis, and B. hispanica has a cut-off of 36 Ct (cycle threshold) = 100 copies of plasmids per 5 µl.
• A B. recurrentis qPCR can detect as few as 3 copies at cycle 40.94 and 32 copies at cycle 36.92—a remarkably sensitive test.
• Thick blood drop detects 10⁴–10⁵ organisms/mL, while quantitative buffy coat detects down to 10³ organisms/mL.
• Inoculation into mice is another method, detecting live Borrelia that can survive in culture.

Culture remains possible using the same BSK-H medium used for Lyme Borrelia, but it requires expert skills and is rarely used in routine clinical practice. Notably, not all relapsing fever Borrelia species grow on this medium. Antigen detection tests (using specific monoclonal antibodies to detect B. crocidurae and B. hermsii) are being developed but are not yet available in clinical practice. Even an innovative technique called MALDI-TOF has been used experimentally to detect B. crocidurae in Ornithodoros sonrai ticks.

Indirect Diagnosis of Relapsing Fever

Serological tests for relapsing fever use specific antigens called GlpQ or BipA, which are supposed to be absent from the Lyme disease group of Borrelia. However, several studies have reported cross-reactions with Borrelia burgdorferi sensu lato (the Lyme group). For instance, cross-reactions have been observed between B. miyamotoi, B. burgdorferi, and B. hermsii in the United States. Another limitation: serology is often negative during the first fever episodes of relapsing fever, meaning it should be used primarily as a retrospective diagnostic tool (to confirm an infection that has already occurred) rather than for early diagnosis.

Syphilis Diagnosis

Syphilis, caused by Treponema pallidum, is a sexually transmitted infection that has been on the rise in France since the year 2000—a significant public health concern. The main obstacle to diagnosis and study of this bacterium is its inability to be cultured in any artificial laboratory medium. This makes laboratory diagnosis entirely dependent on other methods.

Direct Diagnosis of Syphilis

Dark-field microscopy of chancre (the primary ulcer) or skin lesion samples is highly contributory and gives immediate results. However, performance varies by laboratory and staff expertise, and specialized equipment and qualified personnel are required. Both false positives (caused by commensal spirochetes, especially in the mouth or anus) and false negatives (a negative examination should not rule out syphilis) can occur. Sensitivity is higher during the primary and secondary phases and in early congenital syphilis (when chancres, condyloma latum, mucous patches, and adenopathy are present).

Direct immunofluorescence (a technique that uses fluorescently labeled antibodies to detect the bacterium) has shown satisfactory results on mucous, skin, or tissue samples, with sensitivity close to 80%. However, these techniques have become obsolete since PCR tests were commercialized.

Various PCR methods—standard PCR, nested PCR, RT-PCR, and quantitative PCR—have been developed, targeting several genes including bmp, tpp47, tmpA (genes encoding surface lipoproteins), and polA (a gene involved in genome replication). Recent studies found no performance differences between PCR tests targeting the 47 Kd membrane protein gene and those targeting the polA polymerase gene. Overall, PCR sensitivity is approximately 80%, with 95% specificity. The negative predictive value is 95% and positive predictive value is 89%.

As with other spirochetes, PCR performance depends on the biological sample tested and the infection stage. Patients with secondary syphilis or HIV co-infection with low CD4 lymphocyte counts have higher rates of spirochetemia (bacteria in the blood) than patients with primary syphilis or early latent syphilis. Blood PCR therefore has better sensitivity in these patients. PCR has been evaluated on swabs of chancres, cutaneous biopsies of secondary syphilis, bone samples, and biological fluids such as serum and cerebrospinal fluid.

Non-Treponemal Tests (NTT)

Non-treponemal tests detect antibodies against lipids (fats) released when tissues are damaged by the infection, rather than antibodies against the bacterium itself. They use a complex antigen made of cardiolipin, lecithin, and cholesterol. The two most commonly used are the VDRL (Venereal Disease Research Laboratory) test and the RPR (rapid plasma reagin) test, which uses charcoal particles coated with a mixture of lipid antigens.

Because these tests detect anti-lipid antibodies, they are not specific to Treponema infection—any disease causing tissue damage can produce positive results. This means:

• False positives can occur in acute conditions such as hepatitis, infectious mononucleosis, pneumonia, chickenpox, measles, pregnancy, and malaria.
• Chronic conditions such as autoimmune diseases (mainly lupus), cancers, leprosy, and intravenous drug use may also cause positive results.
• Therefore, NTTs alone cannot confirm a syphilis diagnosis.

In terms of timing, NTTs become positive 10 to 15 days after the primary chancre appears, which is about 6 weeks after the infectious contact. Without treatment, antibody levels reach their highest point between one and two years after infection, then remain positive at lower levels during the late phases. Complete seronegativity (antibodies disappearing) during tertiary syphilis is extremely rare.

NTT titers (concentration levels) correlate with infection activity, which makes them useful for monitoring treatment effectiveness. Sensitivity varies by disease stage:

• Primary phase (chancre stage): RPR sensitivity is 86%, VDRL sensitivity is 78%
• Secondary phase: Both tests are 100% sensitive
• Late phase: Both VDRL and RPR drop to 71% sensitivity
• Specificity is 98% at all infection stages

A particularly tricky problem with NTTs is the prozone reaction—a phenomenon observed in up to 2% of patients with secondary syphilis. In serum specimens with an extremely high number of antibodies, the normal antigen-antibody reaction is inhibited, leading to weakly positive, doubtful, or even negative results. The authors explain the solution: samples should be diluted so that titers first increase, then progressively decrease—a classic pattern that alerts the laboratory to the prozone effect.

Key Limitations of Current Diagnostic Tools

Across all four infections, the authors identify recurring limitations:

• Direct detection methods lack sensitivity. Whether microscopy, culture, or PCR, all direct methods can miss infections, especially when bacterial loads are low or transient.
• Serological tests have variable sensitivity depending on disease stage. Testing too early (as with erythema migrans in Lyme, or primary syphilis) may produce false negatives because antibodies haven't developed yet.
• Cross-reactions between species occur. Antibodies against one spirochete can react with antigens from another, leading to false positives.
• Antibodies persist after cure. For Lyme disease and other infections, antibodies can remain detectable for months or years after successful treatment, meaning a positive test doesn't necessarily mean active infection.
• Some widely promoted tests lack scientific validation. Tests like lymphocyte transformation tests and CD57 markers for Lyme disease have poor or unproven performance in peer-reviewed studies.
• Laboratory quality varies. Tests performed outside accredited laboratories—including veterinary labs—may not meet quality standards, and their results cannot be trusted.

The authors also note that the medical literature includes claims about microscopy-based detection of Lyme disease that have been shown to be artifacts, not real bacteria—a cautionary tale about the importance of properly validated testing.

What This Means for Patients

Based on this comprehensive review, patients and healthcare providers should keep several key principles in mind:

1. Clinical context is king. Test results must always be interpreted alongside symptoms, physical examination findings, tick exposure history, and geographic risk. A positive test in someone with no compatible symptoms—or a negative test in someone with classic symptoms—should prompt discussion, not blind acceptance.
2. Two-tiered testing matters. For Lyme disease, the standard two-step approach (ELISA followed by immunoblot for confirmation) significantly improves accuracy compared with a single test. Up to 27% of single-test IgM results can be false positives.
3. Negative tests don't always rule out infection. In early Lyme disease (erythema migrans), more than 50% of serology tests are negative in Europe. In such cases, the characteristic rash itself is sufficient for diagnosis—no test is needed.
4. Positive tests don't always mean active infection. Antibodies can persist for years after successful treatment. Serology is not useful for monitoring treatment success or determining whether a patient is "cured."
5. Use accredited laboratories. Only use laboratories that meet regulatory standards (CE marking, ANSM inspection, COFRAC accreditation). Since 2013, veterinary laboratories in France are not permitted to perform human tests.
6. Be wary of unproven tests. Lymphocyte transformation tests, CD57 markers, and home self-testing kits for Lyme disease lack proper scientific validation. Money spent on these tests might be better directed toward evaluation by a knowledgeable physician.
7. For syphilis, combination testing is essential. Non-treponemal tests (VDRL/RPR) must be combined with specific treponemal tests (like PCR or immunofluorescence) to confirm diagnosis. NTTs alone are vulnerable to false positives from many common conditions.

Frequently Asked Questions

What is the most reliable way to test for Lyme disease?

There is no single perfect test. Doctors in Europe and the US usually use a two-tiered strategy: first an ELISA, and if that is positive or borderline, a second confirmatory immunoblot. This two-step approach significantly improves accuracy because a single test can produce up to 27% false IgM positive results.

Can a negative Lyme disease test completely rule out the infection?

No. A negative test cannot reliably rule out Lyme disease, especially early on. In Europe, more than 50% of serology tests are negative when a patient has erythema migrans, the classic bull's-eye rash. In that situation, the rash itself is enough to diagnose, and no test is needed.

Are home self-testing kits for Lyme disease reliable?

The review authors state that data on sensitivity and specificity for rapid diagnostic tests for self-testing at home are very limited. They do not recommend these tests. For accurate results, it is better to use a laboratory that meets regulatory standards, such as CE marking and COFRAC accreditation.

What is the prozone reaction in syphilis testing?

The prozone reaction is a problem with non-treponemal tests like VDRL or RPR. In up to 2% of patients with secondary syphilis, extremely high antibody levels inhibit the antigen-antibody reaction, causing weakly positive, doubtful, or even negative results. Diluting the sample reveals the true titer.

How is relapsing fever diagnosed?

Relapsing fever bacteria do appear in the blood during fever episodes. The usual method is microscopy of a Giemsa-stained blood smear or thick drop. PCR is also available and shows better sensitivity than microscopy. Serology is often negative during early episodes, so it is mainly a retrospective tool.

Is it legal or safe to use a veterinary laboratory for human Lyme testing?

Since May 30, 2013, veterinary laboratories in France are not allowed to perform human biological tests. Results from such laboratories are not validated for human diagnosis, and the quality of tests performed outside accredited facilities cannot be guaranteed. Patients should only use accredited human diagnostic laboratories.

Source Information

Original Article Title: Médecine et maladies infectieuses 49 (2019) 102–111

DOI: 10.1016/j.medmal.2019.01.009

Authors: Carole Eldin, Benoit Jaulhac, Oleg Mediannikov, Jean-Pierre Arzouni, Didier Raoult

Journal: Médecine et maladies infectieuses, Volume 49, 2019, pages 102–111

Publication Details: Received October 26, 2018; Accepted January 21, 2019; Available online February 11, 2019. DOI: 10.1016/j.medmal.2019.01.009

Affiliations: The authors are affiliated with IRD, AP–HM, VITROME, IHU-Méditerranée Infection, Aix-Marseille Université (Marseille, France); the National Reference Center for Borrelia, Strasbourg University Hospitals (Strasbourg, France); and the Plateforme de sérologie bactérienne, IHU-Méditerranée Infection.

This patient-friendly article is based on peer-reviewed research originally published in a scientific journal. While every effort has been made to accurately represent the findings, this article is intended for educational purposes and does not constitute medical advice. Patients with concerns about Lyme disease, relapsing fever, syphilis, or leptospirosis should consult a qualified healthcare professional.

Note: The original article also covered leptospirosis, which was mentioned in its abstract and introduction. The section on leptospirosis diagnostics was not included in the source text provided for this translation.