http://cid.oxfordjournals.org/content/e ... 42.extractClin Infect Dis. (2014) doi: 10.1093/cid/cit939 First published online: February 11, 2014
Xenodiagnosis to Detect Borrelia burgdorferi Infection: A First-in-Human Study
Adriana Marques 1,
Sam R. Telford III 2,
Siu-Ping Turk 1,
Erin Chung 3,
Carla Williams 4,
Kenneth Dardick 5,
Peter J. Krause 6,
Christina Brandeburg 3,
Christopher D. Crowder 7,
Heather E. Carolan 7,
Mark W. Eshoo 7,
Pamela A. Shaw 8, and
Linden T. Hu 3
- Author Affiliations
1 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
2 Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University
3 Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
4 SAIC-Frederick, Inc, NCI-Frederick, Frederick, Maryland
5 Mansfield Family Practice, Storrs
6 Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale School of Medicine, New Haven, Connecticut
7 Ibis Biosciences, Inc., a subsidiary of Abbott Company, Carlsbad, California;
8 Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Correspondence: Linden Hu, MD, Tufts Medical Center, 800 Washington St, Box 41, Boston, MA 02111 (lhu@tuftsmedicalcenter.org).
Presented in part: 2013 International Conference on Lyme Borreliosis and other Tick Borne Diseases, Boston, Massachusetts, 18–21 August 2013. Poster B040.
Abstract
Background.
Animal studies suggest that Borrelia burgdorferi, the agent of Lyme disease, may persist after antibiotic therapy and can be detected by various means including xenodiagnosis using the natural tick vector (Ixodes scapularis). No convincing evidence exists for the persistence of viable spirochetes after recommended courses of antibiotic therapy in humans. We determined the safety of using I. scapularis larvae for the xenodiagnosis of B. burgdorferi infection in humans.
Methods.
Laboratory-reared larval I. scapularis ticks were placed on 36 subjects and allowed to feed to repletion. Ticks were tested for B. burgdorferi by polymerase chain reaction (PCR), culture, and/or isothermal amplification followed by PCR and electrospray ionization mass spectroscopy. In addition, attempts were made to infect immunodeficient mice by tick bite or inoculation of tick contents. Xenodiagnosis was repeated in 7 individuals.
Results.
Xenodiagnosis was well tolerated with no severe adverse events. The most common adverse event was mild itching at the tick attachment site. Xenodiagnosis was negative in 16 patients with posttreatment Lyme disease syndrome (PTLDS) and/or high C6 antibody levels and in 5 patients after completing antibiotic therapy for erythema migrans. Xenodiagnosis was positive for B. burgdorferi DNA in a patient with erythema migrans early during therapy and in a patient with PTLDS. There is insufficient evidence, however, to conclude that viable spirochetes were present in either patient.
Conclusions.
Xenodiagnosis using Ixodes scapularis larvae was safe and well tolerated. Further studies are needed to determine the sensitivity of xenodiagnosis in patients with Lyme disease and the significance of a positive result.
Clinical Trials Registration. NCT01143558.
It's a shame the extract doesn't include anything about xenodiagnoses itself. I guess we'll have to rely on notes from someone with access to the full article to better understand the title. *Clin Infect Dis. (2014) doi: 10.1093/cid/cit942 First published online: February 11, 2014
Xenodiagnosis for Posttreatment Lyme Disease Syndrome: Resolving the Conundrum or Adding to It?
Linda K. Bockenstedt 1 and
Justin D. Radolf 2
- Author Affiliations
1 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
2 Department of Medicine, University of Connecticut Health Center, Farmington
Correspondence: Linda K. Bockenstedt, MD, Section of Rheumatology, Yale University School of Medicine, PO Box 208031, New Haven, CT 06520-8031 (linda.bockenstedt@yale.edu).
The first reports of Lyme disease in Connecticut in the mid-1970s, followed by the discovery of its tick-borne etiologic agent, Borrelia burgdorferi, in 1983, has spawned one of the longest controversies in the history of biomedical research [1]. Whereas some clinical signs, such as the hallmark skin lesion erythema migrans (EM), can be explained by the inflammatory response elicited by spirochetes, other features remain enigmatic. Impressive generalized symptomatology can accompany EM and last for weeks to months following therapy and resolution of clinical signs. A minority of people (<10%) continue to experience fatigue, musculoskeletal pain, and/or cognitive dysfunction, a condition called posttreatment Lyme disease syndrome (PTLDS) [2]. The issue at the heart of the current, often acrimonious debate is whether persistent infection drives protracted symptomatology.
Four randomized, placebo-controlled trials have evaluated whether extended courses of antimicrobials ameliorate symptoms, ostensibly by eliminating persistent organisms [3–5]. The first 2 trials enrolled seropositive subjects with a previous episode of Lyme disease and seronegative subjects with physician-documented EM [3]. These were the most rigorous, as they evaluated therapeutic responses in a large number of subjects and also sought evidence of infection in blood and cerebrospinal fluid using culture and polymerase chain reaction (PCR). The treatment regimen (1 month of intravenous ceftriaxone followed by 2 months of oral doxycycline) was selected because both agents have good tissue penetration (including the central nervous system) and well-documented in vitro and in vivo activity against B. burgdorferi. The results of the intervention were clear: No evidence was obtained for persistent spirochetes, and antimicrobials provided no benefit over placebo. The remaining 2 trials showed either a similar lack of efficacy after 10 weeks of ceftriaxone [4 …
By the way, there's a thread from 2011 about xenodiagnosis for Lyme disease in case anyone is interested in that earlier discussion:
http://www.lymeneteurope.org/forum/view ... f=5&t=3387
Edited to add:
* The blogger Relative Risk has provided notes from the full article. I've posted them below (on page 2 of this thread).
