Can Ticks Be Used to Test for Infection? Xenodiagnosis for Lyme Disease
Most Lyme disease tests look for antibodies, not the bacteria itself. Xenodiagnosis takes a very different approach: using uninfected larval ticks as a research tool to look for evidence of Borrelia burgdorferi in humans.
Xenodiagnosis: Using Ticks to Test for Lyme Disease
“Xenodiagnosis was positive for B. burgdorferi DNA in a patient with erythema migrans early during therapy and in a patient with PTLDS [post-treatment Lyme disease syndrome],” writes Marques from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. However, there was not enough evidence to conclude that viable spirochetes were present in either patient.
Researchers have long used ticks to study infection in animals. “Xenodiagnosis has long been used in Lyme disease research to provide definitive evidence of a host’s infection status,” explain Turk and colleagues in Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans.
Marques’ study was the first clinical study to use Ixodes scapularis larval ticks for xenodiagnosis of B. burgdorferi infection in humans.
How the Tick Testing Method Works
The method was described in the journal Methods of Molecular Biology. The larval ticks used in the study were uninfected.
“Specific pathogen-free I. scapularis larval ticks were obtained from Dr. Sam Telford from a laboratory-maintained tick colony at Tufts Veterinary School,” Turk states.
These larval ticks were tested and found to be free of B. burgdorferi, Babesia, Anaplasma phagocytophilum, Borrelia miyamotoi, Bartonella, Rickettsia, deer tick virus, orbiviruses, Francisella tularensis, spirochetes, and alphaproteobacteria.
The larvae were placed on the subject with a wooden toothpick, and an adhesive dressing was used to hold them in place during feeding.
Patient Instructions for Xenodiagnosis
Participants were instructed to keep the dressing in place for 4 to 6 days and not to remove or disturb it during the study period.
They were advised not to scratch the site if itching occurred. Oral diphenhydramine could be used if needed.
When showering, the dressing was to be covered with AquaGuard, then gently dried afterward. Participants were also told to avoid aerobic activity or heavy perspiration and to check the dressing daily to ensure all edges remained sealed.
What If a Tick Escapes?
The authors emphasized that an escaped tick posed minimal risk.
Ixodes ticks require high humidity and would not be expected to survive indoors for more than 1 to 2 days. Unfed ticks were uninfected, and fed ticks were not expected to feed again for another 3 to 6 months.
Current Status and Limitations
The authors point out that “xenodiagnosis using Ixodes ticks in humans remains an experimental method and must be performed under an approved clinical research protocol.”
This is not a test available for routine clinical use. It remains a research tool designed to explore infection status in situations where standard testing may be limited. For more on these limitations, see Lyme disease testing and diagnosis.
The fact that xenodiagnosis detected B. burgdorferi DNA in both an early Lyme disease patient and a patient with PTLDS raises important questions. However, detection of DNA alone does not prove the presence of viable, culturable bacteria.
Why This Method Matters for Research
Xenodiagnosis offers a different way to study persistent infection. Standard serologic testing detects antibodies, not active bacteria. PCR may miss low-level infection, and culture remains difficult for Borrelia burgdorferi.
By allowing uninfected larval ticks to feed on patients, investigators can ask whether spirochetes are present and accessible to feeding ticks—even when other tests are negative.
The positive xenodiagnosis finding in a patient with PTLDS is especially noteworthy because it suggests that spirochetal material may persist after standard antibiotic treatment in at least some cases. For broader discussion of this question, see Post-Treatment Lyme Disease Syndrome (PTLDS).
Frequently Asked Questions
What is xenodiagnosis for Lyme disease?
Xenodiagnosis is an experimental method in which uninfected larval ticks feed on a patient and are later tested for Borrelia burgdorferi DNA. It is used in research, not routine clinical care.
Is tick testing for Lyme disease available to patients?
No. Xenodiagnosis remains an experimental research method and is not available for routine diagnostic use.
How accurate is xenodiagnosis?
Xenodiagnosis detected B. burgdorferi DNA in selected patients, but DNA detection does not confirm viable bacteria.
What if the tick escapes during testing?
The risk is considered minimal. The ticks used were uninfected, and Ixodes ticks do not survive well indoors.
Does xenodiagnosis prove persistent infection after treatment?
Not definitively. It suggests that bacterial DNA may still be present, but it does not prove viable organisms or establish the cause of symptoms.
Clinical Takeaway
Xenodiagnosis is an experimental research method that highlights both the complexity of Lyme disease testing and the limitations of standard diagnostics. Its value lies less in immediate clinical use and more in what it reveals: negative routine tests do not necessarily exclude the possibility of persistent spirochetal material in some patients.
Related Reading
References
- Marques A, et al. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clin Infect Dis. 2014;58(7):937-945.
- Turk SP, Williams C, Marques A. Xenodiagnosis Using Ixodes scapularis Larval Ticks in Humans. Methods Mol Biol. 2018;1690:337-346.
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
My understanding is that tick attachment induces some previously present borrelia spirochetes to migrate to the attachment site. Has anyone considered using uninfected lab ticks to increase tissue PCR yield?
I am not familiar with the migration of spirochetes. There can be an more aggressive immune response if there was a previous infection. I am not not all that thrilled letting ticks bite you as part of the diagnostic test.
“However, there wasn’t enough evidence to conclude that viable spirochetes were present in either patient.” How is it possible to say that? It is totally illogical. If the tick got Lyme, then the Lyme bacteria can only have come from the patient.
The authors were hedging. They implied that the spirochetes may not be viable if transmitted to another person. But who would want to place the infected tick on another person.