From the Clinical Trenches

Dear community,

As you all are aware, the treatment of patients suffering from tick-borne diseases can be quite complicated. However, a research article published in Antibiotics (June 2023) by Trouillas and Franck (1) offers an encouraging method for addressing the severe neurological symptoms associated with these diseases. They observed full recovery in seven out of ten patients with severe neurological Lyme disease, marked by paresis. Importantly, these patients stayed healthy even two years after recovery.

Patients in this study had been dealing with their illnesses for periods ranging from six months to seven years. None had been treated with antimicrobials. The researchers scrutinized several recognized, but under-researched, problems within the field.

Their findings contradicted the existing recommendation to treat neuroborreliosis with 21 days of a single drug, Ceftriaxone. Out of 16 treatment studies focused on patients with Neurologic Lyme, only 15 individuals could be diagnosed as having late-stage Lyme neuroborreliosis. Interestingly, studies employing long-term antibiotics showed better outcomes for patients (2,3,4).

A key aspect of their research was the consideration of patients suffering from multiple tick-borne diseases simultaneously, such as Borrelia, Babesia, Bartonella, and Anaplasma.

Patients were treated until their neurological symptoms disappeared. If symptoms recurred after a period of remission, treatment was resumed and continued until remission could again be achieved.

In line with this, the researchers treated patients for Lyme disease (Borreliosis) and other co-infections such as Babesiosis, Bartonellosis, and Anaplasmosis, if a patient’s symptoms and lab tests suggested the presence of these diseases. They used a combination of clinical judgment and lab testing to guide their treatment decisions. They also referred to studies suggesting the persistence of these infections, which justified the need for prolonged antimicrobial treatment.

Treatment continuation was decided based on the patient’s clinical response, emphasizing a patient-centric approach. The results were significant: seven out of ten patients regained their health, allowing them to resume societal and family roles, without previous discomfort. On average, treatment duration needed to achieve this was 25 months. This study represents a promising development in the management of severe tick-borne diseases, although more research is needed to validate and apply these findings more broadly.



Help us fund the Tick Bytes Clinical Data Repository

Patients who suffer with tick-borne diseases need faster research results that translate to meaningful clinical interventions and better outcomes. A solution to this is Invisible’s Tick Bytes Clinical Data Repository. This is an initiative to organize clinical information from the ten best tick-borne disease physicians across the nation within a privacy-protected database, enabling researchers to analyze and publish best practices for treating patients.

With this precision medicine approach, more quality evidence will reach physicians, insurers, and the government, leading to better patient outcomes, insurance coverage, and a deeper understanding of tick-borne diseases.

Based on prior work by Dr. Nevena Zubcevik and Dr. Charlotte Mao at the Dean Center for Tick Borne Illness in Boston, it’s anticipated that it will take 12 months for database set-up, and 24 months for data collection, analysis, and publication. To move forward, all we need is funding from people like you. Please help us launch this important initiative.


  1. Trouillas P, Franck M. Complete Remission in Paralytic Late Tick-Borne Neurological Disease Comprising Mixed Involvement of Borrelia, Babesia, Anaplasma, and Bartonella: Use of Long-Term Treatments with Antibiotics and Antiparasitics in a Series of 10 Cases. Antibiotics (Basel). 2023 Jun 7;12(6):1021. doi: 10.3390/antibiotics12061021. PMID: 37370340; PMCID: PMC10294829.
  2. Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999 Aug;180(2):377-83. PMID: 10395852  DOI: 10.1086/314860
  3. Oksi, J.; Kalimo, H.; Marttila, R.J.; MariamaÃàki, M.; Sonninen, P.; Nikoskelainen, J.; Villanen, M.K. Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain 1996, 119 Pt 6, 2143-2154.
  4. Fallon, B.A.; Keilp, J.G.; Corbera, K.M.; Petkova, E.; Britton, C.B.; Dwyer, E.; Slavov, I.; Cheng, J.; Dobkin, J.; Nelson, D.R.; et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008, 70, 992–1003. DOI:

Do I Have Lyme Disease? A Physician Offers Advice.

Christine Green, MD, is a Stanford-trained, board-certified family medicine physician with 30 years of experience treating patients with tick-borne illness. In this Q&A, she discusses common symptoms and the diagnostic process for Lyme disease and other tick-borne diseases.

Q: I’m achy and tired all the time. Could I have Lyme disease?

The answer is yes. When a patient comes into my clinic for the first time, I take down their clinical history. If I suspect tick-borne disease, I ask if they’ve been exposed to ticks or tick habitats. Have they observed any rashes? The typical Lyme rash expands and is ring-like, usually not itchy or painful. If it’s under a person’s hairline, between the toes, or on the back of the body, it may not be noticed. At least 21% of Lyme patients, and probably more than 50%, never see a tick or a rash.

Early Lyme patients present with flu-like symptoms. Tick bites and resulting symptoms often occur in the summer, but in my California practice, Lyme season may overlap with the fall/winter flu season, confusing the diagnostic picture.

Next, I do a complete physical exam, with an emphasis on neurological deficits, such as loss of balance, tremors, facial asymmetry (Bell’s Palsy), and asymmetric reflexes. Then, I ask about the progression of their symptoms over time. In the first few months of Lyme disease, patients often experience malaise, fatigue, mild-to-severe headaches, nerve pain or tingling in the hands or feet, all in a relapsing-remitting course. In other words, the symptoms wax and wane.

If Lyme is diagnosed four or more months after symptom onset, the picture of the disease is different and variable. The longer between infection and diagnosis, the higher likelihood that more bodily systems have been invaded. Late-stage patients tend to have peripheral nerve symptoms that come and go, and symptoms that migrate to joints, muscles and/or nerves. Most patients with late Lyme have encephalopathy, inflammation of the brain that reduces blood supply in some areas. It can manifest as sleep problems, memory issues, word-recall problems, or difficulty reading or carrying out executive functions, the mental processes that enable us to plan, focus, remember instructions, and juggle multiple activities. For instance, a person who organizes large events might find that they have trouble completing and sequencing tasks. Things that used to take minutes, take hours.

Patients can also experience cardiac symptoms, including irregular heartbeats, chest pain, or dizziness. These patients often come in misdiagnosed with old age, depression, anxiety, or hypochondriasis (preoccupation with an imagined illness). Another presentation of this disease is chronic pain. The pain can be widespread and migrate around the body. These patients often come in with a diagnosis of fibromyalgia or new onset migraine headache.

Q: What’s the best test for diagnosing Lyme disease?

First and foremost, Lyme disease, as with any disease, should be diagnosed based on a clinical history and physical exam, not by test results alone. It’s important to note that the complex, conservative two-tiered testing criteria for “CDC positive cases” was developed for disease-tracking only, and it shouldn’t be used by physicians as the sole criteria for diagnosis or denying treatment to patients. What’s more, not all Lyme tests are created equal. The major labs typically look for only one strain of Lyme bacteria, the B31 strain of Borrelia burgdorferi. I prefer using specialized labs that test for multiple Lyme strains. Three of the labs I use are MDL, Galaxy, and Igenex.

One tick can inject multiple species of disease-causing microbes in single blood meal, so, based on symptoms, I sometimes test for other tick-borne infections. If a patient has night sweats, shortness of breath, stabbing chest pains, or autonomic symptoms (dizziness, nausea, vertigo, flushing), I’ll test for babesia, a malaria-like red blood cell infection. For a pinprick rash on the extremities and/or severe illness, I’ll test for spotted fever. Bartonellosis can present in many ways, including neuropathy, or neuropsychiatric symptoms, such as panic attacks, rages, psychosis, and obsessive-compulsive disorders.

 Q: Once diagnosed, how should you treat Lyme disease?

Research over the last three decades suggests that Lyme bacteria have multiple ways of evading the human immune system and that treating acute Lyme with 21 days of antibiotics fails approximately a third of patients. For that reason, I treat in two phases. For early Lyme, I treat with four weeks of doxycycline, amoxicillin, or cefuroxime antibiotics. I follow this up with four more weeks of drugs that prevent and eradicate “persister” forms of the bacteria. The persisters are drug-tolerant and can revert to an active infection once the antibiotics are stopped.

I treat late Lyme patients with severe degenerative neurologic or rheumatologic cases aggressively. As noted above, the very sick patients frequently have a mixture of tick-borne infections. For these patients, I choose a combination of oral or, when needed, intravenous antibiotics that target the pathogens known to be present.

 Q: Can you cure chronic Lyme disease?

In my practice, I’ve helped many of my tick-borne disease patients return to full health. Every patient is unique, with different genetics, co-morbidities, and co-infections. To me, the important thing is to evaluate clinical response and not to cut off treatment at some arbitrary end point. I assess symptoms at the beginning of each visit, then treat until symptoms improve or resolve. For any patient who is ill for an extended time, after the illness is controlled, I initiate rehabilitation protocols to help the person feel normal again. A patient must become fit to fully recover from a protracted state of ill health.


For a checklist of common Lyme disease symptoms or to find an experienced tick-borne disease physician, visit the website.

To learn more about diagnosing and treating vector-borne diseases, watch Invisible International’s online, evidence-based physician medical education courses.