Clinical science

Resources

Biofilms, persisters, intracellular survival, immune evasion, MSIDS framework, key researchers, and peer-reviewed publications that inform LLMD-informed care.

The biology of persistence

Stealth microbes use multiple survival strategies that make chronic illness fundamentally different from acute infection.

Borrelia burgdorferi, Bartonella species, and Babesia species are not ordinary pathogens. They evolved to persist in hosts for long periods, evade immune clearance, and resist standard short-course antimicrobial treatment. Understanding these mechanisms is the first step toward effective LLMD-informed care.

Stealth microbe characteristics

Low-virulence microbes share common features that distinguish them from aggressive pathogens:

  • Low concentration in the body. Unlike fast-growing bacteria, stealth microbes exist in very low numbers even during active symptoms. Standard tests often miss them.
  • Slow growth. Borrelia divides every 12–24 hours (compared to every 20 minutes for Staphylococcus). This means antibiotics that target rapidly dividing cells are less effective.
  • Intracellular sanctuary. Borrelia, Bartonella, and Mycoplasma can live inside cells where most antibiotics cannot reach therapeutic concentrations.
  • Immune system manipulation. Stealth microbes can suppress, redirect, or hide from the immune response, creating a state of chronic immune dysfunction.
  • Polymicrobial burden. Chronic Lyme rarely involves Borrelia alone. Co-infections with Bartonella, Babesia, Mycoplasma, Anaplasma, Ehrlichia, and viral reactivation are common. Each adds to the immune load.

Biofilm formation

Biofilms are structured communities of microbes encased in a protective matrix. Dr. Eva Sapi and colleagues at the University of New Haven demonstrated that Borrelia burgdorferi forms biofilm-like colonies in vitro and in human tissue samples.

  • Protective matrix. Biofilms consist of an extracellular polymeric substance (EPS) made of polysaccharides, proteins, and DNA. This matrix blocks antibiotics and shields microbes from immune cells.
  • Resistance to treatment. Bacteria within biofilms can be up to 1,000 times more resistant to antibiotics than free-floating (planktonic) bacteria.
  • Persister cells. Within biofilms, a subpopulation of bacteria enters a dormant, non-dividing state called persisters. These cells survive antibiotic exposure and can repopulate the infection once treatment stops.
  • Clinical relevance. Sapi's research found Borrelia biofilm aggregates in skin tissue of Lyme patients years after initial infection, supporting the observation that the infection can persist despite antibiotic treatment.

Cyst forms and round bodies

When threatened by antibiotics or unfavorable conditions, Borrelia can transform into dormant cyst forms (also called round bodies or L-forms).

  • Rapid encystment. Research shows Borrelia can convert to cyst forms within hours of antibiotic exposure. The harder the immune system or antibiotics attack, the more microbes encyst.
  • Metabolic dormancy. Cyst forms have minimal metabolic activity, making them invisible to antibiotics that target cell-wall synthesis or protein production.
  • Reactivation. When antibiotics are withdrawn or immune function wavers, cysts can revert to active spirochete forms and resume infection.
  • Biofilm association. Cyst forms are often found within biofilm aggregates, creating a layered defense: an outer biofilm matrix shelters inner cyst forms that can seed relapse.

Intracellular survival

Multiple tick-borne pathogens have evolved to live inside host cells where the immune system and most antibiotics cannot reach them.

  • Borrelia: Once considered strictly extracellular, Borrelia has been found inside endothelial cells, fibroblasts, macrophages, and even neuronal cells. Intracellular location protects it from antibody-mediated clearance.
  • Bartonella: Bartonella species primarily infect endothelial cells (lining blood vessels) and erythrocytes (red blood cells). Inside red blood cells, Bartonella is shielded from the immune system and can persist for weeks to months.
  • Babesia: Babesia infects red blood cells directly. The intracellular location protects it from immune surveillance and creates a cycle of hemolysis, anemia, and relapsing fever.
  • Clinical implication: Effective treatment requires cell-penetrating antibiotics, prolonged dosing, or combination therapy that addresses both intracellular and extracellular populations.

Antigenic variation and immune evasion

Borrelia burgdorferi has a sophisticated system for changing its surface proteins, allowing it to stay ahead of the adaptive immune response.

  • VlsE system. Borrelia carries a genetic cassette system (vls) that can generate millions of different surface-protein variants. By the time the immune system produces antibodies against one surface protein, the microbe has already switched to a different variant.
  • Complement evasion. Borrelia binds host complement-regulatory proteins to its surface, effectively disguising itself as "self" and preventing the complement cascade from destroying it.
  • Cytokine manipulation. Stealth microbes can alter cytokine signaling to shift the immune response away from effective Th1-type clearance toward less effective Th2-type antibody responses.
  • Immune exhaustion. Chronic antigen exposure can lead to T-cell exhaustion, where immune cells lose their ability to respond effectively to the persistent infection.

Immune dysfunction and the MSIDS framework

Dr. Richard Horowitz's MSIDS (Multi-System Infectious Disease Syndrome) model explains why chronic Lyme is not simply a persistent infection but a multi-factorial illness.

  • 16-point map. The MSIDS model identifies 16 drivers of chronic illness: infections, immune dysfunction, inflammation, toxins, allergies, sleep disruption, hormones, nutrition, mitochondria, autonomic dysfunction, psychiatric symptoms, pain, deconditioning, social stress, genetic factors, and medication side effects.
  • Immune dysfunction. Stealth microbes disrupt immune function at multiple levels: they suppress natural killer (NK) cell activity (measured by CD57 count), alter cytokine balance, and induce regulatory T-cell responses that dampen effective clearance.
  • Inflammatory load. Even when microbes are suppressed, the inflammatory response can become self-sustaining. Cytokines, chemokines, and immune complexes continue to drive symptoms.
  • Clinical value. The MSIDS framework helps clinicians sequence treatment: stabilize immune function, reduce inflammation, address co-infections, and only then use advanced antimicrobial protocols.
Bartonella persistence

Bartonella is a master of immune evasion, using intracellular survival, biofilm formation, and vascular niches.

Bartonella species are among the most stealthy of tick-borne pathogens. Dr. Edward Breitschwerdt at North Carolina State University and Dr. Robert Mozayeni have advanced the clinical understanding of persistent Bartonella infection in humans.

Intracellular endothelial niche

Bartonella's primary survival strategy is infecting endothelial cells that line blood vessels.

  • Endothelial cell invasion. Bartonella uses a type IV secretion system to inject effector proteins into host cells, hijacking cellular machinery to create a protective niche.
  • Anti-apoptotic effect. Bartonella prevents infected endothelial cells from undergoing programmed cell death (apoptosis), ensuring long-term survival of its intracellular habitat.
  • Proliferative niche. Bartonella stimulates endothelial cell proliferation, creating vascular growths (bacillary angiomatosis in immunocompromised patients) that provide additional reservoir space.
  • Clinical clues. This vascular tropism explains hallmark Bartonella symptoms: blood-vessel inflammation, neurological symptoms from altered blood-brain barrier, and the characteristic streak-like skin lesions.

Erythrocyte infection

Bartonella is one of the few bacteria that can infect mature red blood cells.

  • Protected reservoir. Red blood cells have no nucleus, limited metabolic machinery, and no MHC molecules for antigen presentation. Inside RBCs, Bartonella is invisible to T-cell surveillance.
  • Prolonged bacteremia. Bartonella can survive inside RBCs for weeks to months, creating a persistent bloodstream reservoir that can seed relapsing infection.
  • Transmission relevance. This intra-erythrocytic niche facilitates transmission to biting arthropods (fleas, lice, ticks), maintaining the pathogen's lifecycle across hosts.
  • Testing implications. Standard blood tests may miss Bartonella when it is sequestered inside cells. Enrichment culture (such as Bartonella Alpha-Proteobacteria Growth Medium) and PCR of specific tissue types improve detection.

Biofilm and aggregation

Bartonella forms biofilm-like aggregates that contribute to treatment resistance.

  • Aggregative adherence. Bartonella produces surface proteins that cause bacterial cells to adhere to each other and to host cells, forming microcolonies with biofilm-like properties.
  • Persister cell formation. Within these aggregates, a subpopulation of Bartonella enters a metabolically dormant state that resists antibiotic killing.
  • Reservoir in tissues. Breitschwerdt's research has identified Bartonella DNA and viable organisms in tissue samples from patients with months to years of symptoms, even after antibiotic treatment.
  • Co-infection synergy. Bartonella frequently co-exists with Borrelia and Babesia. The presence of one can suppress immune clearance of the others, requiring multi-target treatment strategies.

Immune modulation

Bartonella actively manipulates the host immune response to ensure its survival.

  • Chemokine suppression. Bartonella downregulates chemokine production, reducing the recruitment of immune cells to infection sites.
  • Macrophage manipulation. Bartonella can survive inside macrophages by inhibiting phagosome-lysosome fusion and resisting oxidative killing.
  • Neuropsychiatric inflammation. Bartonella triggers inflammatory cytokine cascades that can affect brain function. The resulting neuropsychiatric symptoms (anxiety, rage, insomnia, intrusive thoughts) are increasingly recognized as a direct consequence of immune activation in the central nervous system.
  • Clinical persistence. Because Bartonella can hide in endothelial cells, RBCs, and tissue reservoirs, treatment often requires longer courses, combination therapy, and careful sequencing with other co-infection treatment.
Babesia persistence

Babesia is a red-blood-cell parasite that evades immune clearance through antigenic variation, species diversity, and intracellular sequestration.

Unlike Borrelia and Bartonella, Babesia is a protozoan parasite (closer to malaria). Its persistence mechanisms are distinct and require anti-parasitic treatment strategies.

Red blood cell infection cycle

Babesia's entire lifecycle revolves around infecting and destroying red blood cells.

  • Direct RBC invasion. Babesia merozoites use specialized surface proteins to bind and invade erythrocytes. Once inside, they multiply asexually, producing more merozoites that burst out and infect new RBCs.
  • Intracellular protection. Inside RBCs, Babesia is shielded from antibody-mediated immunity. The host immune system must rely on cell-mediated responses and splenic clearance of infected cells.
  • Hemolytic cycle. Each cycle of RBC rupture releases parasites, inflammatory debris, and hemoglobin breakdown products. This drives the characteristic symptoms: fever waves, sweats, anemia, jaundice, dark urine, and splenic stress.
  • Splenic sequestration. Infected RBCs can be sequestered in the spleen, creating a reservoir that is difficult to clear and contributing to relapsing symptoms.

Antigenic variation and relapsing pattern

Babesia, like malaria parasites, can change its surface antigens to evade immunity.

  • Variable surface antigens. Babesia expresses different surface protein variants over time, allowing it to stay ahead of antibody responses. This produces the classic relapsing-remitting fever pattern.
  • Strain diversity. Multiple Babesia species (B. microti, B. duncani, B. odocoilei, B. divergens, and others) and strains can infect humans, each with different drug sensitivity profiles.
  • Low-level persistence. Even after apparent clearance, low-level parasitemia can persist in the spleen and bone marrow, recrudescing when immune surveillance drops.
  • Drug resistance mechanisms. Babesia species vary in their sensitivity to standard anti-parasitic drugs (atovaquone, azithromycin, clindamycin, quinine). Resistant strains may require tafenoquine-based or combination salvage therapy.

Immune evasion and host factors

Babesia has multiple strategies for avoiding immune clearance, especially in vulnerable hosts.

  • Complement resistance. Babesia can resist complement-mediated lysis, allowing it to survive in the bloodstream between RBC infections.
  • Cytokine dysregulation. Babesia infection triggers a strong inflammatory response (TNF-alpha, IL-6, IL-1) that contributes to symptoms but does not reliably clear the parasite.
  • Asplenia risk. The spleen is critical for filtering infected RBCs. Patients without a spleen or with impaired splenic function are at high risk for severe, persistent, or life-threatening Babesia infection.
  • Immunocompromised persistence. In patients on immunosuppressive medications, with HIV, with cancer, or with other causes of immune dysfunction, Babesia can persist for months to years despite standard treatment.

Species-specific treatment challenges

Not all Babesia species respond to the same treatment, and species identification matters for clinical outcomes.

  • B. microti generally responds to standard atovaquone + azithromycin or clindamycin + quinine, but relapses occur in immunocompromised patients.
  • B. duncani (WA-1) is more treatment-tolerant and more likely to relapse after standard therapy. Horowitz's clinical experience suggests it may require tafenoquine-based combination approaches.
  • B. odocoilei is an emerging species associated with highly resistant presentations. Its human pathogenicity continues to be studied, and it may require specialized testing and multi-drug protocols.
  • Co-infection impact. Babesia often co-infects with Borrelia and Bartonella. The immune dysfunction caused by one pathogen can facilitate the persistence of the others, making comprehensive treatment essential.
Key researchers

The clinicians and scientists advancing LLMD-informed care.

These researchers have published peer-reviewed studies, clinical frameworks, and treatment approaches that help LLMDs understand persistent tick-borne illness. Their work informs LADA's educational content.

Richard I. Horowitz, MD

“Chronic Lyme disease is not just an infection — it is a multi-system illness with up to 16 overlapping drivers.”
How Can I Get Better? and Medical Detective Substack

Dr. Horowitz developed the MSIDS (Multi-System Infectious Disease Syndrome) model, which maps infections, immune dysfunction, inflammation, toxins, allergies, sleep, hormones, nutrition, mitochondria, dysautonomia, psychiatric symptoms, pain, and other factors. His published dapsone combination therapy (DDDCT/HDDCT) research with Dr. Brian Fallon and Dr. Freeman provides a clinician-supervised pathway for resistant Lyme and Bartonella. His 2025 Bartonella Substack series details diagnosis, treatment, and pulsing strategies. He practices in New York and publishes through the Medical Detective Substack platform.

Medical Detective Substack • Get Better clinical education

Eva Sapi, PhD

“Borrelia burgdorferi can form biofilm aggregates that resist antibiotics and host immune clearance.”
University of New Haven, Department of Biology and Environmental Science

Dr. Sapi's laboratory published landmark studies demonstrating that Borrelia burgdorferi forms biofilm-like colonies in vitro and in human tissue. Her research showed that Borrelia biofilm aggregates contain multiple morphological forms (spirochetes, round bodies, and cyst forms) embedded in a protective matrix. Her work provides the scientific foundation for biofilm-disruption strategies in LLMD care. She has also studied the effectiveness of herbal and enzymatic agents against Borrelia biofilms.

UNH Profile

Edward B. Breitschwerdt, DVM, DACVIM

“Bartonella species have co-evolved with mammalian hosts for millions of years, developing sophisticated mechanisms for intracellular persistence.”
North Carolina State University, College of Veterinary Medicine; Galaxy Diagnostics co-founder

Dr. Breitschwerdt is the world's leading researcher on Bartonella pathogenesis in humans and animals. His laboratory developed the Bartonella Alpha-Proteobacteria Growth Medium (BAPGM) enrichment culture method that improved detection of persistent Bartonella infections. His research has documented Bartonella DNA and viable organisms in patients with neuropsychiatric symptoms, chronic fatigue, and rheumatologic illness. He has published extensively on Bartonella's ability to infect endothelial cells and erythrocytes.

NCSU Profile • Galaxy Diagnostics

Robert Mozayeni, MD

“Bartonella infection is underdiagnosed and can present with primarily neuropsychiatric, vascular, or rheumatologic symptoms.”
Former chief of rheumatology, NIH; founder of the Bartonella Institute

Dr. Mozayeni was Chief of Rheumatology at the National Institutes of Health (NIH) and later became a leading clinical voice for Bartonella-aware medicine. He co-founded Galaxy Diagnostics and has written extensively on the clinical presentation of chronic Bartonella infection, including its vascular, neurologic, and neuropsychiatric manifestations. His clinical framework emphasizes species-specific evaluation, testing limitations, and the need for combination antimicrobial therapy under close monitoring.

Bartonella Institute

Brian A. Fallon, MD

“Persistent Lyme infection and associated co-infections require a research framework that accounts for biological complexity.”
Columbia University; author of Conquering Lyme Disease

Dr. Fallon directs the Lyme and Tick-Borne Diseases Research Center at Columbia University. He co-authored the 2023 retrospective chart review on dapsone combination therapy (DDDCT/HDDCT) with Horowitz and Freeman, published in Microorganisms. His research focuses on the neuropsychiatric manifestations of Lyme disease and the biological mechanisms of persistent infection. He advocates for rigorous clinical research that respects patient-reported outcomes.

Columbia Lyme Center

M. Freeman, DO, MPH

“Combination dapsone therapy can offer a path forward for patients who have not responded to standard approaches.”
Co-author, 2023 Dapsone Combination Therapy study

Dr. Freeman co-authored the 2023 Microorganisms paper on Double Dose Dapsone Combination Therapy (DDDCT) followed by High Dose Dapsone Combination Therapy (HDDCT) for chronic Lyme disease patients with Bartonella and other co-infections. The study reported that 76% of patients showed improvement, though careful patient selection, G6PD screening, CBC/CMP monitoring, and methemoglobin awareness are required. The research provides a clinician-supervised framework for advanced persister therapy.

Read the 2023 study

Kenneth Liegner, MD

“Tick-borne illness can persist in the body despite aggressive standard antibiotic treatment.”
Internal medicine; published on persistent Lyme and co-infection pathology

Dr. Liegner is a board-certified internist who has published on the pathology of persistent Lyme disease, including tissue evidence of ongoing infection after standard antibiotic courses. His clinical work emphasizes the importance of recognizing treatment failure, addressing co-infections, and using combination therapy under careful monitoring.

Kenneth B. Liegner publications on PubMed

Joseph J. Burrascano, MD

“A comprehensive, individualized approach is essential for patients with chronic tick-borne illness.”
Advanced Topics in Lyme Disease; co-author of The Beginner's Guide to Lyme Disease

Dr. Burrascano created one of the first comprehensive diagnostic and treatment guidelines for Lyme disease (the Burrascano Guidelines), which served as a clinical foundation for LLMDs before ILADS formalized its guidelines. His diagnostic hints document remains a widely used clinical resource for symptom pattern recognition, laboratory interpretation, and treatment sequencing.

LDA physician resources

William Rawls, MD

“As long as immune function is disrupted, suppressing microbes alone is rarely enough to restore wellness.”
Unlocking Lyme

Dr. Rawls is a physician who recovered from chronic Lyme disease using an integrative approach. His book Unlocking Lyme describes the three-phase therapy framework (restorative, symptomatic, heroic), the seven system disruptors, the role of stealth microbes and biofilms, and the importance of gut restoration, detoxification, and immune support. His work provides a practical recovery map that patients can discuss with their LLMD.

Unlocking Lyme

Neil Nathan, MD

“The sensitive patient requires a different approach: start low, go slow, and stabilize before treating.”
Toxic and Mold and Mycotoxins

Dr. Nathan is a leading voice in the treatment of sensitive patients with mold toxicity, mycotoxin illness, and complex chronic disease. His work emphasizes the need to stabilize MCAS, sleep, limbic system function, and autonomic regulation before pushing detoxification or antimicrobial therapy. His approach is widely used by LLMDs treating patients with medication and supplement intolerance.

Neil Nathan clinical education

Federal policy

HHS & ILADS Strategic Partnership (June 2026).

The U.S. Department of Health and Human Services (HHS) and ILADS announced a landmark strategic partnership to advance Lyme and chronic disease care. This represents the first federal-level collaboration between HHS and the Lyme-literate clinical community.

What the HHS-ILADS partnership means for patients

“Patients will be able to access ILADS' clinician locator tool, helping connect individuals and families with experienced providers and educational resources related to Lyme disease and associated chronic conditions.”
U.S. Department of Health and Human Services, June 2026

Under this directive, HHS will establish a portal integrating the ILADS provider search tool into federal health resources. This is a significant step toward federal recognition that Lyme-literate care pathways should be accessible to patients through official channels. Key implications:

  • Federal validation of ILADS-style clinical approaches for Lyme and tick-borne disease
  • Integration of the ILADS clinician locator into HHS patient resources
  • Joint educational initiatives for healthcare providers on Lyme and chronic illness care
  • Increased visibility and legitimacy for LLMD-informed care pathways

Read the full ILADS-HHS announcement

Why this matters for LADA's Canadian mission

As a Canada-registered non-profit, LADA views the HHS-ILADS partnership as a precedent for what Canadian health agencies could adopt. Federal recognition of Lyme-literate care in the United States strengthens the international case for ILADS-informed treatment access. LADA will advocate for similar integration of LLMD navigation tools within Canadian provincial health systems.

Key publications

Peer-reviewed research and clinical resources that inform LLMD care.

Key studies, clinical books, and research sites that support informed patient-clinician discussions.

Selected research studies and clinical publications

Publication Focus Link
Horowitz, Fallon, Freeman (2023) — Microorganisms DDDCT followed by HDDCT for chronic Lyme/PTLDS patients with Bartonella and co-infections Read paper
Sapi et al. (2012) — PLoS One Characterization of biofilm formation by Borrelia burgdorferi in vitro Read paper
Sapi et al. (2016) — Journal of Applied Microbiology Evaluation of herbal and antibiotic effectiveness against Borrelia burgdorferi biofilms Read paper
Breitschwerdt et al. (2009–2025) — Various journals Bartonella pathogenesis, BAPGM enrichment culture, persistent Bartonella infection in humans Galaxy Diagnostics research
Horowitz (2024–2025) — Medical Detective Substack Babesia series: species diversity, tafenoquine-based therapy, resistant cases Medical Detective
Horowitz (2025) — Medical Detective Substack Bartonella series: diagnosis, DDDCT, two-week pulsing strategy for resistant Bartonella Medical Detective
Kinderlehrer (2021) — Recovery From Lyme Disease Comprehensive patient resource on Lyme, co-infections, mold, and treatment approaches Dr. Kinderlehrer's site
Rawls (2017) — Unlocking Lyme Three-phase recovery framework, stealth microbes, biofilms, gut restoration, herbal protocols Unlocking Lyme
Fallon and Sotsky (2018) — Conquering Lyme Disease Patient-oriented guide to Lyme disease science, treatment decisions, and advocacy Columbia Lyme Center
Buhner (2013–2015) — Healing Lyme series Herbal protocols for Lyme, co-infections, biofilm, and immune support Available through major booksellers

Clinical frameworks and organizations

Lab testing resources

Specialty laboratories for Lyme, Bartonella, Babesia, Mycoplasma, and tick-borne disease testing.

Specialty laboratories can extend testing beyond the standard CDC two-tier screen. Most require a clinician order and should be interpreted with clinical context in mind.

Best-fit testing sources by infection

Infection or testing need Useful sources Testing methods to discuss
Lyme / Borrelia IGeneX, Galaxy Diagnostics, ArminLabs, Vibrant Wellness, MDL, Quest/LabCorp through standard clinicians Two-tier serology, expanded immunoblot, relapsing-fever Borrelia testing, PCR, urine antigen, tick testing, and paired clinical documentation.
Bartonella Galaxy Diagnostics, TLab, IGeneX, MDL, Vibrant Wellness, ArminLabs Species-aware IFA/serology, enrichment culture, digital PCR, FISH, blood imaging, and repeat sampling when bacteremia is intermittent.
Babesia IGeneX, TLab, Galaxy Diagnostics, MDL, Vibrant Wellness, hospital/public-health labs for acute cases Thin smear, PCR, FISH, IFA/serology, hemolysis labs, species-aware interpretation, and capillary smear discussion for suspected sequestering species.
Mycoplasma MDL, Vibrant Wellness, ArminLabs, Quest/LabCorp/Mayo/ARUP through a clinician PCR, IgG/IgM serology, respiratory panels, urogenital testing when relevant, and broader chronic-infection panels when symptoms overlap.
Other tick-borne diseases MDL, IGeneX, Vibrant Wellness, ArminLabs, state health departments, CDC-supported public-health testing Anaplasma/Ehrlichia PCR in the first week, paired rickettsial serology, relapsing-fever Borrelia testing, tularemia testing, Powassan/rare-virus public-health coordination.

MicrobiologyDX

Best for: MARCoNS and nares bacterial culture discussion in CIRS-informed care

  • Nares culture — bacterial culture for coagulase-negative Staphylococci and other organisms.
  • Antibiotic-susceptibility reporting — helps a prescriber understand resistance patterns if treatment is clinically appropriate.
  • Interpretation boundary — MARCoNS results do not diagnose fungal colonization, mold exposure, or mycotoxin illness by themselves.
  • Use alongside the LADA MARCoNS guide and a qualified clinician who can interpret colonization versus infection.

microbiologydx.com/marcons-testing

Read LADA's MARCoNS guide

Galaxy Diagnostics

Best for: Bartonella-first evaluation and stealth pathogen direct detection

  • Bartonella IFA Panel — covers 4 clinically relevant species including B. henselae, B. quintana, B. vinsonii, and B. koehlerae
  • BAPGM enrichment culture — proprietary Bartonella Alpha-Proteobacteria Growth Medium that improves detection of low-level or intracellular infection
  • Digital PCR and direct detection — clinician-directed testing for Bartonella, Babesia, and Borrelia when blood levels may be low or intermittent
  • Nanotrap® Urine Antigen Test — detects Borrelia burgdorferi OspA antigen in urine; useful to discuss when antibody testing is incomplete or discordant
  • Suspected Tick-Borne Bundle — combined direct-detection approach for Bartonella, Babesia, and Borrelia questions
  • Founded by Dr. Ed Breitschwerdt and Dr. Ricardo Maggi; based in Research Triangle Park, NC

galaxydx.com

IGeneX

Best for: Comprehensive Lyme and co-infection immunoblot testing

  • ImmunoBlot IgG/IgM — multi-species Borrelia immunoblot covering B. burgdorferi, B. afzelii, B. garinii, and other species including relapsing fever Borrelia
  • Bartonella IFA and FISH — species-specific Bartonella detection
  • Babesia FISH and IFA — detects B. microti, B. duncani, and B. divergens
  • Tick testing — send a removed tick for pathogen PCR panel
  • Ehrlichia, Anaplasma, Rickettsia panels — expanded co-infection screening
  • Best used with a clinician who can choose the right test category and interpret negative, indeterminate, and species-specific results.

igenex.com

TLab

Best for: Direct molecular imaging and FISH for difficult cases

  • RNA FISH molecular imaging — blood-based direct detection approach used for Bartonella, Babesia, and Borrelia questions.
  • High-resolution blood imaging — used by some clinicians to evaluate blood-film patterns, suspected biofilm material, and red-cell inclusions.
  • Babesia and Bartonella focus — especially relevant when symptoms strongly suggest infection but standard serology or venous smear is unrevealing.
  • Patients should work with a physician or qualified clinician for ordering, specimen handling, and interpretation.

tlabdx.com

Vibrant Wellness / Vibrant America

Best for: Broad tick-borne disease immunoblot and multiplex panels

  • Tickborne testing — broad provider-ordered panels covering Borrelia and co-infections such as Bartonella, Babesia, Ehrlichia, Anaplasma, Rickettsia, and other TBDs
  • Lyme ImmunoBlot — multi-band Borrelia immunoblot with expanded antigen coverage
  • Co-infection panels — separate or combined testing for Bartonella, Babesia, Mycoplasma, Chlamydia pneumoniae, EBV, CMV, HHV-6, and other chronic infection markers
  • Widely used by functional medicine and integrative practitioners for initial screening

vibrant-wellness.com/tests

ArminLabs

Best for: European tick-borne disease testing and specialized panels

  • EliSpot / iSpot cellular testing — measures T-cell immune response to Borrelia, Bartonella, Chlamydia, EBV, and other pathogens; useful to discuss when serology is negative but clinical suspicion is high
  • TickPlex and Borrelia immunoblot — European and North American Borrelia coverage, including broader Lyme and co-infection questions
  • CD57+ NK cell panel — natural killer cell count used by some LLMDs as an immune function marker
  • Co-infection serology — Bartonella, Babesia, Rickettsia, Ehrlichia, Anaplasma, Coxiella, Yersinia
  • Based in Augsburg, Germany; offers laboratory diagnostic consultation for doctors and naturopaths

arminlabs.com

DNA Connexions

Best for: non-invasive Lyme and co-infection PCR discussion

  • Lyme and Co-Infection Panel — PCR-based detection of Borrelia burgdorferi, Bartonella henselae, Babesia microti/duncani, and other co-infections from urine samples
  • Individual PCR tests — available for specific pathogens when only certain infections are suspected
  • Non-invasive collection can be useful when access to specialty blood draws is limited; interpretation should still be clinician-guided.

dnaconnexions.com

Fry Laboratories

Best for: specialized blood-smear/biofilm work when available

  • Biofilm detection — specialized testing for Borrelia and other microbial biofilms
  • Blood smear analysis — direct visualization of blood for Borrelia, Babesia, and other blood-borne pathogens
  • Status check required — patients and clinicians should confirm current specimen acceptance before planning testing; lab availability can change.
  • Based in Scottsdale, AZ

frylabs.com

MDL — Medical Diagnostic Laboratories

Best for: PCR-based vector-borne disease and Mycoplasma testing

  • Vector-borne PCR menu — molecular detection options for Borrelia, Bartonella, Babesia, Ehrlichia, Anaplasma, Rickettsia, and rarer TBDs.
  • Mycoplasma PCR menu — includes M. fermentans, M. pneumoniae, M. hominis, M. penetrans, and broader Mycoplasma testing.
  • Individual PCR and serology tests — useful for targeted testing when a specific infection is suspected.
  • Based in Hamilton, NJ; clinician ordering and insurance handling vary by plan.

mdlab.com/vector-borne

Standard reference labs

Best for: acute conventional workups, insurance documentation, and Mycoplasma respiratory testing

  • Quest, LabCorp, Mayo, ARUP — useful for standard Lyme two-tier testing, CBC/CMP/hemolysis markers, respiratory PCR panels, Mycoplasma pneumoniae testing, and routine safety labs.
  • Strength — easier insurance coverage and acceptance by conventional clinicians, urgent care, hospitals, and specialists.
  • Limitation — standard panels may miss early Lyme, relapsing-fever Borrelia, Bartonella, Babesia species diversity, and low-level or intermittent infections.

Quest • LabCorp • Mayo Clinic Labs • ARUP

Public health and state labs

Best for: rare, severe, acute, or reportable tick-borne infections

  • Use urgently when appropriate — Powassan virus, Heartland virus, Bourbon virus, RMSF/spotted fever rickettsioses, tularemia, ehrlichiosis/anaplasmosis clusters, and neurologic disease often need health-department coordination.
  • Timing matters — early PCR, paired acute/convalescent serology, CSF testing, or specialized viral testing may be needed.
  • Do not delay treatment — clinicians often treat high-risk suspected rickettsial/ehrlichial/anaplasma illness while tests are pending.

CDC tick-borne disease clinical resources

Important notes on testing

  • No single test definitively rules out Lyme disease or co-infections. Clinical diagnosis based on exposure history, symptom patterns, and treatment response remains essential.
  • Serology (antibody) tests detect immune response, not the pathogen itself. A negative antibody test can occur when the immune system is suppressed or infection is intracellular.
  • PCR/DNA tests can miss low-level or intermittent infection. Timing sample collection during symptom flares may improve detection.
  • Most specialty labs require a licensed clinician to order testing. Discuss options with an LLMD before ordering.
  • Costs vary widely. Some labs accept insurance; others are cash-pay. Check with the lab and your insurance provider before testing.
Patient advocacy

LADA's mission is navigation and education, not treatment.

Understanding biofilms and persisters helps patients have informed conversations with LLMDs. It does not replace medical supervision. Treatment decisions for persistent tick-borne illness belong with a licensed clinician who can monitor safety, interactions, and response.

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