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Xenodiagnosis for B. burgdorferi detection safe in humans
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Xenodiagnosis to detect Borrelia burgdorferi in humans was safe and well tolerated in the first human study of the procedure, according to researchers at Tufts University.
“This study establishes that xenodiagnosis can safely be used as a tool in patients with Lyme disease and has potential for furthering our knowledge of Borrelia biology in humans,” the researchers wrote in Clinical Infectious Diseases. “Future studies are necessary to determine the incidence of positive xenodiagnostic results for B. burgdorferi after antibiotic treatment, if these results represent viable organisms or remnants of infection, and whether these results can be related to ongoing symptoms in patients after therapy for Lyme disease.”
The study included 36 adults: 10 patients had high C6 antibody levels, 10 patients had post-treatment Lyme disease syndrome, five patients with erythema migrans after antibiotic therapy, one patient with erythema migrans during antibiotic therapy and 10 healthy volunteers. All of the patients had 25 to 30 pathogen-free Ixodes scapularis larval ticks placed over a 7 cm2 area, preferably where the disease was observed, with modified retention dressing. The ticks were collected 3 to 7 days after placement and tested for B. burgdorferi.
The procedure was well tolerated, and all of the patients completed the tick placement. Mild itching at the site was the most common adverse effect, which affected 58% of the patients for a median of 3 days. Seven patients underwent repeat xenodiagnosis, which was also well tolerated.
The engorged ticks were tested for B. burgdorferi by PCR, culture and/or isothermal amplification followed by PCR and electrospray ionization mass spectroscopy. Among 16 patients with post-treatment Lyme disease syndrome and/or high C6 antibody levels and among five patients who complete antibiotic treatment for erythema migrans, xenodiagnosis was negative. Xenodiagnosis was positive for B. burgdorferi DNA in two patients: one with erythema migrans early during therapy and in a patient with post-treatment Lyme disease syndrome, but there is not enough evidence to conclude the presence of viable spirochetes.
“An important caveat is that the number of tested xenodiagnostic ticks per participant in general was small, particularly in the early subjects,” the researchers wrote. “The number of engorged ticks tested for each individual is likely to be an important variable. The more engorged ticks tested, the larger the probability of detecting a positive.”
Disclosure: Three researchers are employed by Ibis Biosciences, the maker of the assays used in this study. Another researcher has received consulting fees from Immunetics and is a shareholder of Abbott.
Perspective
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Eugene Shapiro, MD
This is an interesting and important study. The applicability to humans of results of previous studies in which other animal species were used for xenodiagnosis is questionable. This is especially true for mice, which are natural reservoirs for B. burgdorferi. The bacteria clearly have evolved adaptations to help survive the reactions of such hosts. In the study of humans, no viable organisms were recovered from ticks that fed on any of the patients. DNA of the organism was found in only two instances, one of which was a patient treated for infection recently. The results will stimulate even more interest in assessing the duration that antigenic fragments of B. burgdorferi may survive after treatment, but provides no support for arguments that live organisms can survive, reproduce and produce disease long after antimicrobial treatment is completed.
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