Can Lyme Disease Be Present Even When Tests Are Negative?
But the infection may still be there.
And in some cases—it can be cultured.
Seronegative Lyme disease occurs when patients have symptoms of Lyme disease but test negative on standard antibody tests.
In a study by Rudenko and colleagues, researchers were able to culture live Borrelia burgdorferi from patients who were seronegative and had already received antibiotic treatment. :contentReference[oaicite:1]{index=1}
Clinical implication: a negative test does not always rule out infection.
Can Borrelia Burgdorferi Be Cultured?
Yes—but it is difficult.
Researchers used a modified Kelly-Pettenkofer medium rather than standard BSK-H medium to successfully grow the bacteria.
Positive cultures were confirmed using:
- PCR amplification
- DNA sequencing
- Multilocus sequence analysis
- Electron microscopy
Key finding: live Borrelia was recovered even after prolonged antibiotic treatment.
Live Borrelia was cultured from patients who tested negative.
What Symptoms Did These Patients Have?
The patients did not present with classic Lyme disease.
Instead, they had a wide range of symptoms:
- Headache and dizziness
- Muscle and joint pain
- Numbness and tingling
- Fatigue and sleep problems
- Shortness of breath
- Anxiety and depression
Clinical pattern: symptoms were multisystem and often atypical.
What About Borrelia Bissettii?
The study also identified Borrelia bissettii-like strains.
This strain has been detected in:
- Human serum samples in Europe
- Cardiac tissue in Lyme patients
- Tick populations in North America
Clinical insight: Lyme-like illness may be caused by more than one Borrelia species.
Why These Cases Are Often Missed
According to the authors, these patients would not typically be studied because:
- The region is not considered highly endemic
- Patients were seronegative
- They had already received antibiotics
Clinical gap: current diagnostic frameworks may miss these cases.
What This Means for Diagnosis
Seronegative Lyme disease remains a clinical challenge.
This study suggests:
- Standard testing may miss active infection
- Borrelia may persist despite treatment
- Culture-based detection, while difficult, is possible
Clinical takeaway: diagnosis should not rely on testing alone when symptoms and exposure history are consistent.
Final Thought
Lyme disease cannot always be ruled out by a negative test.
The ability to culture Borrelia in seronegative patients highlights the limitations of current diagnostic approaches.
Key question: Could persistent symptoms reflect infection even when tests are negative?
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Dr. Cameron,
I used to see you back in 2013 when I contracted Lyme and Babesia. In 2016 I contacted you because I was to undergo a hysterectomy, which I had 4/22/16. I’ve been sick with all sorts of symptoms, have been recently diagnosed with urinary retention, and a rectocele. I often have the chills. I am wondering if my Lyme and Babesia flared up due to surgery. I also have tailbone pain; had impar ganglion injection for that; it didn’t work too well.
My last test for Lyme was by a pcp and she said that it existed but in small quantity. She did not test for babesia.
What should I do? I feel sickly, nauseated, tired, and have chills all the time (in this warm weather (May 2017).
These doctors don’t understand any of this and shrug it off to depression. Of course I am depressed, who wouldn’t be with all these symptoms. If I can find a friend to take me to see you again, do you think something can be prescribed to help me? Thank you.
We are sorry to hear you are ill. Stress due to illness does not help. It is hard to tell without seeing you if there is anything we can offer. In the meantime, work with your doctors.
I have lived in East Tennessee my entire life. I was misdiagnosed for over a decade until last year when a new rheumatologist who ran a panel of auto immune disease tests. He referred me to an infectious disease Dr who had treated tick born illnesses. I was diagnosed with Neuro Lyme. I have had a picc line for over a year. I have been on iv rocephin daily. The few times I went off the antibiotics, all my symptoms came back with a vengeance. When the official from the Tn department of health spoke with me, he stated that he wasn’t counting my case as an official case of Lyme. When I asked why not, he wouldn’t give me an answer, except we don’t have the white footed mouse in Tn…I am living proof that chronic Lyme disease does exist. It has destroyed my body, my mind, and lively hood. I guarantee if I were tested again, Lyme would still be present.
Janice, I am so sorry to hear this story! Mine is similar. It is sadthat chronic lyme does exist and the CDC does bot want the truth to come out about thus and thats the scariest part, besides you, me and many more have to suffer with this illlness daily! I am curently immobilized from pain and herniated disc from lymes and sever neuro damage. I have done antibiotic treatment for over a year and lots of hebal supplemnets & natural cures and recent blood test show ligher levels than when i originally got diagnosed a little over year ago. I feel for you and hope you get some relief. My prayers are with you. Stefany T.
I also live in east tn. and begote being diagnosed a rheumatologist screwed me up worse with IV steroids and steroid injections. Finally found Dr in NYC, he said my case was so difficult because of the strroids.
Treatment for a tick borne illness has been successful for many despite steroids.