Papers by Raymond Dattwyler
Lyme Disease and Relapsing Fever Spirochetes: Genomics, Molecular Biology, Host Interactions and Disease Pathogenesis, 2021
Emerging Topics in Artificial Intelligence 2020, 2020
We report a point-of-care (POC) assay and neural network-based diagnostic algorithm for Lyme Dise... more We report a point-of-care (POC) assay and neural network-based diagnostic algorithm for Lyme Disease (LD). A paper-based test in a vertical flow format detects 16 different IgM and IgG LD-specific antibodies in serum using a mobile phone reader and automated image processing to quantify its colorimetric signals. The multiplexed information is then input into a trained neural-network which infers a positive or negative result for LD. The assay and diagnostic decision algorithm were validated through fully-blinded testing of human serum samples yielding an area-under-the-curve (AUC), sensitivity, and specificity of 0.950, 90.5%, and 87.0% respectively, outperforming previous Lyme POC tests.
Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene. Series A: Medical Microbiology, Infectious Diseases, Virology, Parasitology, 1986
Although some manifestations of Lyme disease may be secondary to the presence of B. burgdorferi, ... more Although some manifestations of Lyme disease may be secondary to the presence of B. burgdorferi, the immune system appears to play a significant role in the clinical manifestations of the disease. The humoral response is well characterized, however the cellular response remains poorly defined. To further define cellular immunity in Lyme disease, the responses of lymphocytes from patients with active Lyme disease were assessed to Con a, PHA, PWM, tetanus toxoid, and whole live B. burgdorferi. In addition, the natural killer cell (NK) function of these patients was assayed. As compared to the controls the lymphocyte response to Con A was reduced and the response to PHA was increased. There was a significant proliferative response to B. burgdorferi in all patients with no response in the controls. The responses to PWM and tetanus toxoid were not different in the two groups. NK cell function in the patients with active disease was reduced as compared to the normal controls and patient's who were not clinically active. We conclude that there is a significant alteration in cellular immunity in active LD consistent with a defect in the induction of suppressor cells leading to a vigorous humoral response.
Journal of chemotherapy (Florence, Italy), 1989
Research in Microbiology, 1993
Muscle & Nerve, 1989
Neurophysiologic evidence of median nerve entrapment in the carpal tunnel was present in 25% of p... more Neurophysiologic evidence of median nerve entrapment in the carpal tunnel was present in 25% of patients with late Lyme borreliosis. Sixty-eight of 76 consecutive, prospectively studied patients with late Lyme underwent neurophysiologic testing. Nineteen reported intermittent hand paresthesias; 17 had neurophysiologically confirmed carpal tunnel syndrome. This was not consistently associated with clinically apparent wrist arthritis or with neurophysiologically evident peripheral neuropathy. We conclude that a significant proportion of patients with late Lyme borreliosis develop carpal tunnel syndrome.
The Lancet Infectious Diseases, 2012
Ang CW, Notermans DW, Hommes M, Simoons-Smit, Herremans T. Large diff erences between test strate... more Ang CW, Notermans DW, Hommes M, Simoons-Smit, Herremans T. Large diff erences between test strategies for the detection of anti-Borrelia antibodies are revealed by comparing eight ELISAs and fi ve immunoblots.
The Lancet, 1990
Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis 72 a... more Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis 72 adults with erythema migrans (early Lyme borreliosis) were enrolled in a randomised prospective trial comparing amoxycillin 500 mg plus probenecid 500 mg three times a day with doxycycline 100 mg twice a day for 21 days. These antibiotic regimens were chosen because of the known in-vitro sensitivity of Borrelia burgdorferi, the antibiotic tissue penetration, the pharmacokinetics of the drugs, and because the organism can disseminate early in the course of infection. 72 patients were evaluable (35 in the doxycycline group and 37 in the amoxycillin/probenecid group). The two regimens were equally effective for treatment of erythema migrans. Mild fatigue or arthralgia were the only post-treatment complaints, which resolved within 6 months. None of the patients needed further antibiotic treatment for Lyme borreliosis.
Journal of Medical Ethics, 2010
Journal of Infectious Diseases, 1987
... In spirochetal infections, such as syphillis, it has been demonstrated that such near-constan... more ... In spirochetal infections, such as syphillis, it has been demonstrated that such near-constant antibiotic levels are preferable because these slowly multiplying organisms may regenerate during the time that the antimicrobial concen ... RJ Dattwyler, JJ Halperin, H. Pass, BJ Luft ...
The Journal of Infectious Diseases, 2007
To the Editor-The recent article by Yrjänäinen et al. [1] adds to the list of publications on Lym... more To the Editor-The recent article by Yrjänäinen et al. [1] adds to the list of publications on Lyme borreliosis in which the results do not strongly support the conclusion. The authors demonstrated that B. burgdorferi could be isolated from more mice in each of the groups that received ceftriaxone and anti-tumor necrosis factor-␣ (anti-TNF-␣), compared with the group that received antibiotic therapy alone, but the differences were not significant in either experiment and thus could have been a chance event. For example, in the experiment using the B. burgdorferi sensu stricto N40 strain, simultaneous treatment with anti-TNF-␣ plus ceftriaxone resulted in 2 of 9 mice with cultures that were positive for the organism, compared with 0 of 10 mice that received ceftriaxone alone (P ϭ .21, by the Fisher exact test). Therapy with anti-TNF-␣ 4 weeks after administration of ceftriaxone resulted in 3 of 10 mice with cultures positive for the organism, compared with 0 of 10 mice that received ceftriaxone alone (P ϭ .21). Even if one combines both anti-TNF-␣ groups and compares that group with the group that received ceftriaxone alone, the difference was not significant (5 of 19 vs. 0 of 10 mice with cultures positive for B. burgdorferi s.s. N40; P ϭ .13). Irrespective of treatment with anti-TNF-␣, 5 (17.2%) of 29 mice infected with B. burgdorferi s.s. N40 and treated with ceftriaxone remained culture positive. This rate of positivity is remarkably similar to that found in an
Arthritis & Rheumatism, 1987
We describe the clinical courses of 5 patients with Lyme disease who developed significant late c... more We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migrans with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.
Archives of Internal Medicine, 2001
Background: The present recommendation for the serologic diagnosis of Lyme disease is a 2-tier pr... more Background: The present recommendation for the serologic diagnosis of Lyme disease is a 2-tier process in which a serum sample with a positive or equivocal result by an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay is then followed by supplemental testing by Western blot. Our laboratory has developed recombinant chimeric proteins composed of key Borrelia epitopes. These novel antigens are consistent and are easily standardized. Methods: We adapted these recombinant proteins into a new immunochromatographic format that can be used as a highly sensitive and specific first-tier assay that can be used to replace the ELISA or immunofluorescent assay. Results: This rapid test was equally sensitive (PϾ.05) and more specific (PϽ.05) than a frequently used commercial whole cell ELISA. The overall clinical accuracy achieved on agreement studies among 3 Lyme research laboratories on clinically defined serum panels was shown to be statistically equivalent to the commercial ELISA. The assay can detect anti-Borrelia burgdorferi antibodies in either serum or whole blood. Conclusion: This sensitive and specific rapid assay, which is suited for the physician's office, streamlines the 2-tier system by allowing the physician to determine if a Western blot is necessary at the time of the initial office visit.
Annals of the New York Academy of Sciences, 1988
Annals of the New York Academy of Sciences, 1988
... RAYMOND J. DATTWYLER, DAVID J. VOLKMAN, JOHN J. HALPERIN, BENJAMIN J. LUFT, JOANNE THOMAS, AN... more ... RAYMOND J. DATTWYLER, DAVID J. VOLKMAN, JOHN J. HALPERIN, BENJAMIN J. LUFT, JOANNE THOMAS, AND MARC G. GOLIGHTLY State University of New York at Stony Brook School of Medicine Stony Brook, New York I1 794 ... Louis, MO). ...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 7, 2017
The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing proto... more The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination. Nevertheless, 2-tiered testing with immunoblotting remains the benchmark for evaluation of new methods or approaches. Next-generation serologic assays, prepared with recombinant proteins or synthetic peptides, and alternative testing protocols, can now overcome or circumvent many of these past drawbacks. This article descr...
npj Vaccines
The expansion of Lyme borreliosis endemic areas and the corresponding increase of disease inciden... more The expansion of Lyme borreliosis endemic areas and the corresponding increase of disease incidence have opened the possibility for greater acceptance of a vaccine. In this perspective article, we discuss the discovery of outer surface protein A (OspA) ofB. burgdorferi, and the subsequent pre-clinical testing and clinical trials of a recombinant OspA vaccine for human Lyme disease. We also discuss in detail the open public hearings of the FDA Lyme disease vaccine advisory panel held in 1998 where concerns of molecular mimicry induced autoimmunity to native OspA were raised, the limitations of those studies, and the current modifications of recombinant OspA to develop a multivalent subunit vaccine for Lyme disease.
Journal of Clinical Microbiology, 2000
Current serologic Lyme disease tests use whole borrelia cells as the source of antigen. These ass... more Current serologic Lyme disease tests use whole borrelia cells as the source of antigen. These assays are difficult to standardize and to optimize for sensitivity and specificity. To help solve these problems, we constructed a library of recombinant chimeric proteins composed of portions of key antigens of Borrelia burgdorferi . These proteins were then used to develop an enzyme-linked immunosorbent assay. We compared our assay with the most sensitive of three whole-cell borrelia assays. We found that the recombinant assay could detect antibodies significantly better from early Lyme disease sera ( P < 0.05), and had the same sensitivity for late Lyme disease sera, as the most sensitive whole-cell borrelia assay. On potentially cross-reactive sera, the recombinant assay was more specific, but not significantly so, than the best whole-cell borrelia assay. Optimization of the recombinant assay offers the potential for a significant improvement in both sensitivity and specificity.
Diagnostic Microbiology and Infectious Disease, 2017
Uploads
Papers by Raymond Dattwyler