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Biomedical subjects

R T Schoen

Publications and source records attributed to R T Schoen.

At least 19 recordsLinked to original sources
PubMed2000

The Lyme disease vaccine: conception, development, and implementation.

In the past 20 years, remarkable strides have been made toward understanding and preventing Lyme disease in humans. In December 1998, the U.S. Food and Drug Administration approved a recombinant outer surface protein A vaccine against Lyme disease (LYMErix, SmithKline Beecham, Philadelphia, Pennsylvania). The vaccine, which is derived from a lipidated outer surface protein of the causative spirochete Borrelia burgdorferi, is important because it may decrease the morbidity and financial costs associated with Lyme disease. Its mechanism is unique because it works inside the tick vector itself, preventing the human from becoming infected.

Animals↗
PubMed2000

Safety and immunogenicity profile of a recombinant outer-surface protein A Lyme disease vaccine: clinical trial of a 3-dose schedule at 0, 1, and 2 months.

OBJECTIVES: This study compared the tolerability of a Lyme disease vaccine administered intramuscularly at 0 and 1 months with that of a vaccine administered at 0, 1, and 2 months to determine (1) whether adding a third dose of vaccine 1 month after the second would affect the safety profile, and (2) whether a shortened vaccination schedule of 0, 1, and 2 months would provide an immune response similar to that obtained with vaccine administered at 0, 1, and 12 months. BACKGROUND: An efficacy trial of a Lyme disease vaccine had demonstrated safety and efficacy against definite (clinically manifested and laboratory-confirmed) Lyme disease after 3 doses at 0, 1, and 12 months and resulted in 90% of subjects having titers > or =1400 enzyme-linked immunosorbent assay units (EL.U)/mL (the proposed seroprotective level for 1 tick season). METHODS: This multicenter, open-label, prospective, randomized study assessed the safety and efficacy of different doses of a recombinant outer-surface protein A (OspA) vaccine in 956 volunteers aged 17 to 72 years from 3 Lyme disease-endemic sites. Blood samples were collected at months 0, 2, 3, 12, and 13 to assess total immunoglobulin-G anti-OspA titers. RESULTS: Most adverse events were transient and mild to moderate. The geometric mean antibody titer increased 2.8-fold from month 2 (1786 EL.U/mL to 4842 EL.U/mL), and approximately 90% of the volunteers had a titer > or =1400 and 99% had a titer > or =400 EL.U/mL (the mini- mum seroprotective level at any given time) after the third dose. An antibody kinetics model predicts that protection would last for a typical tick-transmission season. CONCLUSIONS: In volunteers aged 17 to 72 years, 3 doses of vaccine administered in 2 months was well tolerated, more immunogenic than 2 doses, and provided a higher probability of protection before exposure or travel to Lyme disease-endemic areas.

Adolescent↗
PubMed1999

Successful vaccination for Lyme disease: a novel mechanism.

Two vaccines are on the horizon for the prevention of Lyme disease, the most common vector-borne illness in the US and Europe. This review describes the pathogenesis and clinical illness of Lyme disease, as well as the sequence of events that led to the development of these novel vaccines. The results of the most recent Phase III human trials are reported.

Journal Article↗
PubMed1998

Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group.

BACKGROUND: The risk of acquiring Lyme disease is high in areas in which the disease is endemic, and the development of a safe and effective vaccine is therefore important. METHODS: We conducted a multicenter, double-blind, randomized trial involving 10,936 subjects who lived in areas of the United States in which Lyme disease is endemic. Participants received an injection of either recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant or placebo at enrollment and 1 and 12 months later. In cases of suspected Lyme disease, culture of skin lesions, polymerase-chain-reaction testing, or serologic testing was done. Serologic testing was performed 12 and 20 months after study entry to detect asymptomatic infections. RESULTS: In the first year, after two injections, 22 subjects in the vaccine group and 43 in the placebo group contracted definite Lyme disease (P=0.009); vaccine efficacy was 49 percent (95 percent confidence interval, 15 to 69 percent). In the second year, after the third injection, 16 vaccine recipients and 66 placebo recipients contracted definite Lyme disease (P<0.001); vaccine efficacy was 76 percent (95 percent confidence interval, 58 to 86 percent). The efficacy of the vaccine in preventing asymptomatic infection was 83 percent in the first year and 100 percent in the second year. Injection of the vaccine was associated with mild-to-moderate local or systemic reactions lasting a median of three days. CONCLUSIONS: Three injections of vaccine prevented most definite cases of Lyme disease or asymptomatic B. burgdorferi infection.

Adjuvants, Immunologic↗
PubMed1998

The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study.

BACKGROUND: The adverse consequences associated with overdiagnosis and overtreatment of Lyme disease, although previously recognized, have received inadequate attention. OBJECTIVE: To determine the use of health services and occurrence of treatment-related illness, disability, and distress among patients in whom Lyme disease is inappropriately diagnosed or treated. DESIGN: Observational cohort study. SETTING: University-based Lyme disease clinic. PARTICIPANTS: 209 patients with a presumptive diagnosis of Lyme disease previously assigned by referring physicians, the patients themselves, or both. MEASUREMENTS: Self-reported data, review of medical records, and standardized instruments were used to determine 1) use of health services in terms of number of outpatient visits, number of physicians seen, types of serologic tests, and days of antibiotic treatment; 2) occurrence of antibiotic-related adverse events; and 3) levels of disability, depression, and stress. RESULTS: Of the 209 patients, 44 (21%) met criteria for active Lyme disease, 40 (19%) had previous but not active Lyme disease, and 125 (60%) had no evidence of current or previous infection. In general, patients with active Lyme disease (who were not the focus of this study) had good outcomes. Patients with previous Lyme disease and patients with no evidence of Lyme disease used considerable health resources (median number of office visits, 11 and 7; median number of serologic tests, 4 and 4; and median days of antibiotic treatment, 75 and 42), had frequent minor adverse drug events (53% and 55%), reported significant disability (proportion of symptomatic days during which normal activities could not be performed, 16% and 18%), and had high rates of depression (38% and 42%) and stress (52% and 45%). CONCLUSIONS: Overdiagnosis and overtreatment of Lyme disease are associated with inappropriate use of health services, avoidable treatment-related illness, and substantial disability and distress.

Adult↗
PubMed1998

Differential expression of Borrelia burgdorferi genes during erythema migrans and Lyme arthritis.

Borrelia burgdorferi, the agent of Lyme disease, selectively expresses genes in the arthropod vector and mammalian host. Specific B. burgdorferi gene expression during human infection was examined in tissue specimens, using RNA-polymerase chain reaction, from 3 patients with Lyme disease. ospA was investigated because OspA is down-regulated by B. burgdorferi in ticks during engorgement and is a vaccine candidate in phase III clinical trials. p35 and p37 were also assessed because these genes are induced by spirochetes during murine Lyme borreliosis and play roles in protective immunity. p35 and p37 mRNA were detected in erythema migrans biopsy specimens from 2 patients and in the synovium of 1 patient with Lyme arthritis. ospA mRNA was not identified in any of these tissues. These data show that ospA is repressed while p35 and p37 are induced in human infection; these results are the first direct demonstration of differential B. burgdorferi gene expression during Lyme disease.

Adolescent↗
PubMed1997

Borrelia burgdorferi enzyme-linked immunosorbent assay for discrimination of OspA vaccination from spirochete infection.

Recombinant Lyme disease vaccines based on purified preparations of outer surface protein A (OspA) have been shown to be effective in preventing transmission of Borrelia burgdorferi in experimental animal models and are now being tested in humans. Since the most widely used screening tests for Lyme disease are based on a whole-cell sonicate of B. burgdorferi, serologic false positivity in vaccinated persons could result from reactivity to OspA within the antigen preparation. In order to avoid serologic false positivity in vaccinated subjects, we developed an immunoassay based on a low-passage-number, naturally occurring variant of B. burgdorferi which lacks the plasmid encoding OspA and OspB. The use of an antigen preparation derived from this organism provided sensitive and specific detection of B. burgdorferi seropositivity in experimental animals and in human Lyme disease cases. The OspA-B-negative enzyme-linked immunosorbent assay (ELISA) also appeared to be capable of discriminating the vaccinated state from vaccine failure and natural infection in experimental animals. Sera from human subjects participating in a vaccine trial gave false-positive results with an ELISA based on an OspA-containing strain, but no such reactivity was observed when the OspA-negative ELISA was used. We conclude that low-passage-number OspA-B-negative isolates in immunoassays may become useful for the immunologic discrimination of the vaccinated state, natural infection, and vaccine failure.

Antigens, Surface↗
PubMed1995

An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies.

Passive immunization with murine or human Abs to outer surface protein A (OspA) can protect mice against Borrelia burgdorferi, but OspA Abs elicited during natural infection in mice or humans are unable to clear the spirochete from the infected host. To examine Ab binding by OspA during the course of human infection, we amplified the operon encoding full-length ospA and ospB from synovial fluids of a patient with chronic Lyme arthritis, the first such recoveries from human material, at four separate time points over 4.5 mo, and expressed OspA in Escherichia coli. OspA mAbs that passively protected mice from infection did not bind one of the expressed OspAs, because of a deletion in ospA that resulted in a frame shift and premature stop codon near the carboxyl terminus. However, expressed OspA from a later synovial fluid sample did not contain this deletion. Thus, although altered forms of OspA, which potentially can influence host immune effectiveness, do occur in the human host, they cannot be the only factors responsible for microbial persistence.

Adolescent↗
PubMed1995

Safety and immunogenicity of an outer surface protein A vaccine in subjects with previous Lyme disease.

The safety and immunogenicity of a recombinant outer surface protein A (OspA) Lyme vaccine in patients previously diagnosed with Lyme disease was assessed in a dose-ranging, prospective study. Thirty healthy volunteers were consecutively assigned to receive three doses of 3, 10, or 30 micrograms of OspA vaccine at 0, 1, and 2 months. Subjects were seen 3 days after each vaccine dose and 1 month after completion of the three-dose schedule. Local side effects included soreness, induration, swelling, and redness. Transient systemic side effects occurred in 21 subjects, the majority of which (81%) were characterized as mild. Solicited symptoms included migratory mild arthralgias that lasted 24 h in 3 subjects. Side effects were not more evident after the second or third dose. Of the patients, 93% developed high-titer OspA antibodies. Thus, an OspA vaccine may be safe and immunogenic in patients with a history of Lyme disease.

Adult↗
PubMed1994

Identification of Lyme disease.

The identification of Lyme disease is an important, rewarding process. In early disease, the presence of EM, the geographic location of the patient, and the time of year are critical in assessing the likelihood of Lyme disease. Beyond this, it is important to have a high index of suspicion in early Lyme disease, because the rash may be atypical or absent, the early flu-like features can be nonspecific, and at this stage seroreactivity to B. burgdorferi may be lacking. Treatment is always with antibiotics and is highly successful. In late Lyme disease, the issues are different. Most individuals presenting with questions about late Lyme disease do not have the disorder. The clinician must recognize characteristic, objective disease manifestations such as oligoarthritis or chronic meningitis and avoid the diagnosis in individuals with "chronic fatigue" alone. Serologic testing is useful because few, if any, individuals with late Lyme disease will be seronegative. Serologic testing should not be indiscriminate, however, because false positives are common. Most patients with late Lyme disease are cured with antibiotics, but the response to successful treatment may be slow. In a minority of patients, there is a role for managing disease that cannot be cured (for example, anti-inflammatory medication, physical therapy, reassurance) as in other rheumatic diseases.

Diagnosis, Differential↗
PubMed1993

Lyme disease.

In 1992, reported Lyme disease cases increased, but the majority remained clustered in the northeast and midwest, and in California. The clinical syndromes associated with infection are better understood, and this information can calm public anxiety. The concept of fibromyalgia occurring after infection with Borrelia burgdorferi allows more appropriate treatment in late Lyme disease. The polymerase chain reaction is being applied to gain insights into the pathogenic mechanisms of Lyme disease. Progress has been made toward developing a vaccine through the use of animal models. Together, these advances provide clinicians with more confidence in the diagnosis and treatment of Lyme disease.

Diagnosis, Differential↗
PubMed1992

Epidemiology, clinical features, and diagnosis of Lyme disease.

Lyme disease is the most common vector-borne disease in the United States. Epidemiologic research has contributed to a better understanding of the factors involved in the geographic spread and increased incidence of the disease. Clinical features of Lyme disease, including skin, joint, cardiac, and neurologic involvement, are discussed here, along with recent studies that better characterize these clinical manifestations and more clearly define their immunopathogenesis. The diagnosis of Lyme disease is based on the clinical presentation. Laboratory testing may be helpful but has significant limitations, which we discuss in our review.

Humans↗
PubMed1991

Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy.

Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16 (80%) had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients (20%) had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.

Adolescent↗
PubMed1991

Pathogenesis, diagnosis, manifestations, and treatment of Lyme disease.

Progress in understanding the causation and immunopathogenesis of Lyme disease has continued in the past year. Only by studying the complex relationship between the infecting organism, Borrelia burgdorferi, and the host will improvements in therapy be possible. Physicians in the United States have evaluated large numbers of patients with late neurologic Lyme disease, and a more consistent clinical description of the North American experience is emerging. Laboratory diagnosis remains a problem. Improvements are being made in both the sensitivity and specificity of existing tests and also in the selection of appropriate patients by physicians. Both of these factors will improve predictive value.

Borrelia burgdorferi Group↗