Pull the Thread: Finding Tick-Borne Illness in Complex Chronic Patients

Why Broadening the Differential Matters in Complex Chronic Illness

Patients with complex, chronic presentations rarely arrive with a single clear diagnosis. More often, they carry a collection of labels, fibromyalgia, dysautonomia, mast cell activation syndrome, postural orthostatic tachycardia syndrome, or post viral syndrome, that describe a pattern of symptoms without explaining what is driving them. In this session, Dr. Cramer describes a shift in approach: instead of narrowing the differential quickly to a single unifying diagnosis, she starts by ruling everything in and asking what combination of factors could produce this presentation.

Dr. Cramer describes health and disease as a continuum rather than two separate states, and uses the image of a sweater: it does not matter where a clinician and patient start pulling, since the sweater is knit from a single thread and pulling any part of it begins to unravel the whole pattern of inflammation. She also frames chronic illness as the result of multiple cumulative hits to a person’s health rather than a single cause, and recommends stabilizing and quieting inflammation first, then following the immune system’s response to decide what to address next.

What This Means for Clinical Practice

A patient’s most recent diagnosis may be accurate without being complete. Holding multiple possible contributors in mind at once, rather than searching for one unifying explanation, creates room to consider vector-borne pathogen presence as one thread worth pulling alongside other contributors such as environmental exposures or hormonal changes.

Building the Patient History: What to Listen For

Dr. Cramer places significant weight on the patient interview itself. Key elements of that history include the following:

           Where and when the patient first stopped feeling well, and what the circumstances were at the time.

           A timeline of inflammatory events, head injuries, major infections, COVID-19, hormonal shifts, mapped for a pattern of cumulative insults                rather than a single trigger. 

           Exposure risk, including pets, outdoor work, travel, and time spent in regions where tick-borne illness is endemic. Most patients with                          tick-borne illness do not recall a specific bite, and the absence of that memory is not evidence that no exposure occurred.  

          Unusual clusters of symptoms that do not track with a single system, for example joint pain in a young person paired with fatigue, facial                  or sinus symptoms, and normal labs that do not explain the presentation.

Dr. Cramer also recommends starting from what she calls the pillars of health: whether the patient can move their body well, whether they can eat without digestive issues, how they sleep and whether they feel restored, whether they feel socially connected (she flags loneliness as a vital sign), and whether there are addictive or repetitive patterns or environmental stressors at play. She frames the approach as assuming the patient in front of her has crafted a carefully balanced life in response to what they have lived through, and asks why, rather than assuming the balance itself is the problem.

For providers who want a more structured starting point, validated symptom burden and quality of life questionnaires, such as the GSQ-30, HMQ, MSQ, SF-36, and PROMIS-10, can help surface clinical suspicion in patients who continue to plateau on other protocols. These tools are not diagnostic on their own, but they provide a structured way to flag a patient worth a closer look [13].

What This Means for Testing

Normal labs paired with a patient who still feels significantly unwell is, in Dr. Cramer’s framing, a signal to order direct detection testing, not a reason for reassurance. As Galaxy’s own clinical team frames it, a provider does not need certainty before ordering, only enough clinical suspicion to ask the question differently.

The three cases below are drawn from Dr. Cramer’s practice and from Galaxy’s own de-identified, provider-consented case documentation. They illustrate a diagnostic pattern. They are not typical or guaranteed results, and every testing decision still requires individual clinical judgment.

Case One: When the Labs Look Good and the Patient Does Not

A woman in her late thirties presented with several years of waxing and waning visual disturbances, including episodes of tunnel vision and blurring, along with severe fatigue and heaviness in her limbs, facial pain, pins and needles sensations, jaw and TMJ discomfort, anxiety, photosensitivity, recurrent sinus infections, brain fog, heavy periods, and weight gain. She had been diagnosed with acute Lyme disease several years earlier and treated with a six-week course of antibiotics, without full resolution of her symptoms. Her history included years spent working as an outdoor educator in a tick-endemic region, regularly leading children on outdoor trips.

Given that exposure history and the unusual symptom cluster, Dr. Cramer ordered a BBB Direct Detect dPCR on a single draw. The result was positive for

Bartonella, detected through Galaxy’s enhanced BBB Direct Detect dPCR methodology [16]. Dr. Cramer notes that her standard labs remained largely unremarkable throughout, which she views as more suspicious, not less, when a patient’s symptom burden is this significant. A clinician the patient had seen previously did not view the result as clinically significant; the patient sought a second opinion and began treatment.

Following treatment, the patient’s brain fog, fatigue, and visual symptoms began improving within weeks. The treatment approach described in Galaxy’s own campaign materials for this case named specific antimicrobial and adjunct agents; this blog generalizes that detail to a categorical description, an extended, multi-agent course targeting the pathogen and biofilm burden, per Galaxy’s standing rule against publishing named treatment protocols on client-facing content.

What This Means for Testing

A positive result on a single draw, paired with a symptom cluster and exposure history that fit, was treated as clinically significant even though an earlier clinician had dismissed it. Normal-looking standard labs alongside a significant symptom burden are themselves a signal to look further, not a reason to stop. Bartonella has been documented in patients with neurological and neurocognitive symptoms similar to this presentation [1].

Case Two: When the Diagnosis Has a Name But the Treatment Is Not Working

A woman in her late forties presented with fatigue and joint pain severe enough that she described feeling like she was falling apart, along with hormonal and menstrual cycle changes, weight gain, and intermittent brain fog. She had previously been diagnosed with psoriatic arthritis despite the absence of skin manifestations or positive autoimmune antibodies, and a biologic medication targeting that diagnosis produced no improvement. She had no known arthropod bite or prior vector-borne disease testing.

Dr. Cramer notes three things that made her question the existing diagnosis: the patient’s age, since a woman in her forties should have decades of physiologic reserve ahead of her rather than describing herself as falling apart; the fact that joint pain is a symptom, not proof that a specific diagnostic label is correct; and a hormonal picture that, in Dr. Cramer’s clinical experience, is common in vector-borne illness. Rheumatic symptoms in the absence of a confirmed autoimmune driver have separately been documented in patients with Bartonella bacteremia in Lyme-endemic regions [14].

Dr. Cramer ordered a triple draw BBB Direct Detect dPCR alongside a Bartonella IgG Detect IFA. Two partitions on the B2 triple-draw sample returned positive for Bartonella by dPCR, and the IFA came back reactive across all four Bartonella species Galaxy’s panel covers, with titers of 1:64 or greater for each [16]. A Lyme Borrelia Direct Detect run alongside the panel came back negative, narrowing the finding specifically to Bartonella rather than a broader co-infection. Direct detection and serology together indicated pathogen presence even in the absence of a known exposure event.

Treatment led to substantial improvement. As with Case One, the specific agents named in Galaxy’s internal campaign materials have been generalized here to an extended, multi-agent approach addressing the pathogen and biofilm burden, consistent with the standing rule against publishing named treatment protocols in client-facing content.

What This Means for Testing

A symptom cluster that does not fit a prior diagnosis, combined with a lack of response to that diagnosis’s standard treatment, is a reasonable trigger to broaden testing even without a known history of tick or vector exposure. When direct detection and serology agree, as they did here, the combined result removes a meaningful amount of diagnostic ambiguity.

Case Three: When the Patient Has Stopped Believing There Is an Answer

A woman in her seventies arrived with an extensive history of prior diagnoses, including osteoarthritis and chronic migraines, alongside chronic fatigue, complex chronic pain consistent with fibromyalgia, low energy, dysbiosis, and neuropsychiatric symptoms including depression and social isolation. She had been managing symptoms for decades, and that history had been compounded by dismissal from prior providers and skepticism from her own family about whether there was a root cause at all.

The patient initially declined further testing. Dr. Cramer worked for over a year to build the relationship and trust needed before she agreed to a triple draw BBB Direct Detect dPCR alongside a Lyme Borrelia Direct Detect urine antigen test. The Bartonella IgG Detect IFA came back non-reactive across all four species, and no dPCR partitions were positive, meaning Bartonella was not detected by either method. The Lyme Borrelia Direct Detect, however, was positive on the triple draw.

A single draw retest six months later confirmed the Lyme Borrelia Direct Detect result again, and the patient showed measurable neurological improvement on treatment. Dr. Cramer notes that patients who have accumulated many prior diagnoses over a long period may not immediately register a new finding as meaningfully different from the others, but describes this patient’s reaction as relief rather than fear, since after decades of being told nothing definitive was wrong, a result that pointed to something detectable changed how she related to her own symptoms [16].

What This Means for Clinical Practice

A label like fibromyalgia describes a symptom cluster, not a root cause, and a negative result on one platform, here Bartonella serology and dPCR, does not mean vector-borne illness is off the table. In this case, the urine antigen test, not blood-based testing, was the differentiating result, which underscores why matching the right direct detection method to the pathogen in question matters.

What Standard Testing Can Miss

Several biological features of Borrelia, Bartonella, and Babesia make them difficult to catch with standard testing alone. Standard antibody testing measures whether the immune system has responded to a pathogen, not whether the pathogen is present at the time of testing, and that response can be delayed, variable, or blunted in some patients. Borrelia associated with Lyme disease disseminates from the bloodstream into tissue relatively quickly [4], and experimental research has documented rapid clearance from the blood circulation [5]. This is why Galaxy’s Lyme Borrelia Direct Detect urine antigen test, rather than blood-based PCR, is the more appropriate direct detection method for Borrelia. It detects OspA antigen directly in urine and does not depend on the antibody response, which means it can identify Lyme before or during seroconversion [3].

Bartonella presents a related but distinct challenge. It is an intracellular pathogen capable of persisting inside endothelial cells, red blood cells, and macrophages, compartments that limit the immune system’s access to it [11]. It has evolved several mechanisms to evade the immune system, including variation of its surface proteins and modulation of the host immune response, which allow it to persist at low levels for extended periods [12]. Because it can also be difficult to recover directly from blood, Galaxy’s BBB Direct Detect dPCR includes a proprietary enrichment culture step, developed specifically to support Bartonella growth [8], before the molecular testing step using dPCR [6]. Galaxy’s BBB Direct Detect dPCR is designed to detect Bartonella, Babesia, and Borrelia DNA [7]. Serial sampling over a multi-day collection period has been associated with improved detection sensitivity [9]. Galaxy’s own data show patients are 2.5 times more likely to test positive on a triple draw, three separate draws collected across roughly a week, than on a single draw, which is why the triple draw is often the preferred approach when clinical suspicion remains high [13].

Serology adds a further limitation worth naming directly: when standard commercial Bartonella serology is ordered at all, it is often limited to a single species, Bartonella henselae, the species most associated with cat scratch disease. Galaxy’s Bartonella IgG Detect IFA instead covers four of the most clinically relevant North American species, using slides prepared from strain-specific clinical isolates rather than laboratory-adapted reference strains, which Galaxy positions as a more clinically representative antigen target. A prior negative single-species serology result does not rule out Bartonella on that basis alone [13].

Chronic fatigue and neurological symptom presentations, similar to those described in the cases above, have specifically been documented in patients with Bartonella and Babesia DNA detected through enrichment blood culture methods[10], and Bartonella bacteremia has separately been documented in patients with neurological and neurocognitive dysfunction [1], and studied in association with psychiatric presentations including psychosis [2]. This is part of why a broad symptom cluster, not only classic joint or skin findings, is a reasonable basis for considering direct detection testing.

None of this means a negative result should be dismissed or reflexively retested. It means a negative result reflects the biology of these pathogens as much as it reflects the test itself, and should be treated as a data point rather than a final verdict, particularly when the clinical picture still points toward vector-borne disease, as in Case Three above.

How Galaxy’s Three Core Tests Compare

A positive result on any of these platforms indicates pathogen presence or immune exposure and supports moving forward with clinical correlation. A negative result is a data point, not a verdict [16].

What This Means for Clinical Practice

Serology and direct detection answer different clinical questions. Serology indicates whether the immune system has encountered the pathogen, while direct detection indicates whether pathogen DNA or antigen is present in the specific sample tested. Used together, and interpreted alongside the patient’s full history, they provide a more complete picture than either used alone.