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R B Nadelman

Publications and source records attributed to R B Nadelman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Estimation of the incidence of Lyme disease.

The incidence of Lyme disease in most endemic areas is unknown but will be an important factor in determining the cost-effectiveness of Lyme disease vaccines in those areas. The authors developed a deterministic model with nine components to estimate the frequency of Ixodes scapularis tick bites and the resulting incidence of Lyme disease in residents of endemic areas. For each component, best point estimates and plausible ranges of values were based on the published literature, unpublished data, expert opinion, or a combination of the above. By using the mean, crude, annual total of 3,827 Lyme disease cases reported from the endemic county of Westchester, New York, in 1991-1994, a mean of 178,889 I. scapularis bites (20.4 per 100 person-years) and a mean of 10,632 incident Lyme disease cases (1.2 per 100 person-years) were estimated to have occurred per year. Results of a sensitivity analysis that used two different methods suggested that this deterministic model is reasonably robust. In conclusion, according to this model, the incidence of Lyme disease in Westchester County is several-fold higher than suggested by the current passive reporting system.

Animals↗
PubMed1998

Lyme borreliosis.

Lyme borreliosis (Lyme disease) is often said to be associated with "protean" manifestations, a reference to the ancient god Proteus, who could assume many forms and thus elude his pursuers. This legendary quality has clouded our understanding of Lyme borreliosis by giving Borrelia burgdorferi infection a mythical aura of its own. This review shows that this illness, while incompletely understood, is far more palpable than Proteus and is (in most cases) much more readily subdued. The clinical presentations of Lyme borreliosis do differ in North America and Eurasia, possibly due to the differing pathogenicity of distinct genospecies of Borrelia burgdorferi. The most common manifestation, however, in both continents is erythema migrans. Diagnosis should rest on a careful history and objective clinical findings, supported by appropriately chosen laboratory tests. Reports of coinfection with other tick-borne diseases should prompt a fresh look at Lyme borreliosis. Assertions about "protean manifestations" of B burgdorferi infection should be reappraised. Advances in laboratory techniques are welcome but culture remains the gold standard for the diagnosis--and no laboratory test result should substitute for careful clinical observation and critical analysis.

Anti-Bacterial Agents↗
PubMed1998

Improving the yield of blood cultures for patients with early Lyme disease.

This study was designed to improve the recovery of Borrelia burgdorferi from blood. With the techniques used, B. burgdorferi could be recovered from the blood of approximately 25% of patients with early Lyme disease associated with erythema migrans. Serum was a better source of culture material than whole blood. The volume of blood cultured correlated directly with yield, particularly for patients with a single erythema migrans lesion.

Adult↗
PubMed1997

Cellular changes and induction of apoptosis in human promyelocytic HL-60 cells infected with the agent of human granulocytic ehrlichiosis (HGE).

Human granulocytic ehrlichiosis (HGE) is an emerging and occasionally fatal human infectious disease whose pathogenesis is largely unknown. Goodman et al. (1) recently described the successful cultivation of the HGE infectious agent in human promyelocytic HL-60 leukemic cells. It was reported in the same study that infectivity invariably led to host cell death, although the mechanism by which HGE infection triggers cellular self-destruction is as yet undetermined. In this communication, we show that in vitro passage of HGE pathogen-infected blood elicits a significantly dysfunctional G1-to-S transition. Moreover, we provide evidence that the cytopathic properties of the HGE pathogen are attributed to its ability to induce apoptosis in host HL-60 cells. Determination of specific protein expression changes by Western blot analysis showed that HGE infection resulted in reduced expression of PCNA and pRB, both of which play a role in cell cycling. Moreover, the steady state level of bcl-2, which protects eukaryotic cells against apoptosis, is suppressed by exposure to the HGE agent. These results suggest that this pathogen HGE induces apoptosis in HL-60 cells by a mechanism involving the shut-off of multiple cell cycle and apoptosis regulatory events.

Apoptosis↗
PubMed1997

Inhibition of efficient polymerase chain reaction amplification of Borrelia burgdorferi DNA in blood-fed ticks.

Polymerase chain reaction (PCR) analysis is a widely used method for detection of Borrelia burgdorferi DNA in biological specimens, including ticks. Studies have demonstrated that substances present in mammalian blood can inhibit PCR amplification. This would limit the utility of PCR for determination of B. burgdorferi infection in engorged ticks that have taken a blood meal from a human or other animal host. To systematically assess the potential for such inhibition, nymphal Ixodes scapularis, which had acquired B. burgdorferi as larvae, were fed on rats. These engorged ticks were lysed in standard PCR lysis buffer and aliquots were subjected to PCR analysis; 0 of 56 were PCR positive. An equivalent cohort of unfed (unengorged) ticks had an infection rate of 19% (11 of 57) as determined by identical PCR analysis (P = 0.0006, by Fisher's exact test). When lysates from the engorged ticks were spiked with the 500 prelysed B. burgdorferi, none of the samples yielded a positive PCR signal, indicating the presence of inhibitory substances. Consistent with this observation, PCR amplification of the original engorged tick lysates after extraction with a DNA extraction kit, resulted in detection of B. burgdorferi DNA in 13 specimens (23%). Furthermore, when 500 prelysed B. burgdorferi were added to the treated extracts, all samples (56 of 56) were PCR positive. Thus, extraction resulted in removal of inhibitors of PCR amplification present in unprocessed engorged tick lysates. Furthermore, additional titration experiments showed that some inhibitory substances may also be present in unfed ticks, although this inhibition does not completely prevent detection of B. burgdorferi DNA in unprocessed lysates. This study clearly demonstrates that inhibitors of PCR amplification are present in engorged ticks and prevent accurate determination of B. burgdorferi infection rates by this method unless steps are taken to remove such inhibitors.

Animals↗
PubMed1997

Screening for Lyme disease in hospitalized psychiatric patients: prospective serosurvey in an endemic area.

BACKGROUND: Nervous system involvement in Lyme disease may mimic certain psychiatric disorders. We studied whether it is worthwhile to conduct routine screening of psychiatric inpatients for serologic evidence of Lyme disease. METHODS: Between March 1988 and June 1989, we prospectively screened sera for Lyme disease from adults admitted to an acute care psychiatric hospital in Westchester County. New York, an area in which this infection is endemic. Of all cases of Lyme disease reported to the U.S. Public Health Service in 1988, 16% originated in Westchester County. The prevalence in healthy blood donors from this area were reported to be 0.7%. Sera were tested by fluorescent immunoassay alone (90%) or fluorescent immunoassay plus enzyme-linked immunosorbent assay (10%). RESULTS: Sera from only 1 of 517 patients demonstrated antibodies to Borrelia burgdorferi, the etiologic agent of Lyme disease (0.2% [95% CI, 0.0% to 1.1%]). This patient had a nonreactive Western blot, which suggested a false-positive antibody test. CONCLUSIONS: We cannot presently recommend routine serologic screening for Lyme disease for adult psychiatric inpatients, even in areas of the United States where this illness is endemic.

Adult↗
PubMed1996

Accuracy of IgM immunoblotting to confirm the clinical diagnosis of early Lyme disease.

BACKGROUND: A 2-test approach for the serologic diagnosis of Lyme disease has recently been proposed. A positive or equivocal result on a first-stage test (eg, an enzyme immunoassay) is followed by a Western immunoblot test. For a sample to be considered seropositive for Lyme disease, the immunoblot result must be positive. OBJECTIVES: To assess the accuracy of IgM immunoblotting for detection of early Lyme disease and to establish interpretative criteria for a commercially available immunoblot assay. METHODS: Serum samples from 44 patients with erythema migrans were tested by an IgM immunoblot assay. All patients were culture-positive for Borrelia burgdorferi. Serum samples from 2 different control groups were also tested. Interpretative criteria were developed using receiver operating characteristic curves. RESULTS: The presence of any 2 IgM bands was found to be the optimal criterion for a positive test result, and in patients with illness of less than 7 days' duration, this was significantly more sensitive than the criterion of any 2 of the 3 specific bands defined by the Centers for Disease Control and Prevention/Association of State and Territorial Public Health Laboratory Directors Lyme Disease Workgroup (P < .05). Specificity of the criterion of any 2 bands was 100% for 1 group of controls but only 96% for the more clinically relevant control group; this small difference had a large impact on the positive predictive value in populations at low risk for Lyme disease. CONCLUSIONS: Using a commercially available immunoblot test kit, the presence of any 2 IgM bands is proposed as a positive result. The predictive value of a positive IgM immunoblot result, however, is poor in patients with minimal clinical evidence for Lyme disease.

Humans↗
PubMed1996

Liver function in early Lyme disease.

To evaluate the frequency, pattern, and severity of liver function test abnormalities in patients with Lyme disease associated with erythema migrans (EM), 115 individuals with no other identifiable cause for liver function test abnormalities who presented with EM between July 1990 and September 1993 were prospectively evaluated. For individuals with abnormal liver function tests, common causes of hepatitis, including hepatitis A, B, and C, were excluded. A local control group was used for comparison. Forty-six (40%) patients had at least one liver test abnormality, and 31 (27%) had more than 1 abnormality compared with 19 (19%) and 4 (4%) of controls, respectively (P < .01 for each comparison). gamma-Glutamyl transpeptidase (28%) and alanine transaminase (ALT) (27%) were the most frequently elevated liver function tests among Lyme disease patients. Anorexia, nausea, or vomiting was reported by 30% of patients, but did not occur more frequently in patients with elevated liver function tests compared with those with normal values. Patients with early disseminated Lyme disease were more likely to have elevated liver function studies (66%) compared with patients with localized disease (34%) (P = .002). After antibiotic treatment, elevated liver function tests improved or resolved in most patients. Liver function test abnormalities are common in patients with EM but were mild, most often not associated with symptoms, and improved or resolved by 3 weeks after the onset of antibiotic therapy in most patients.

Adult↗
PubMed1996

Efficacy of antibiotic prophylaxis for prevention of Lyme disease.

OBJECTIVE: To determine if antibiotic prophylaxis following a dear tick bite is effective in reducing the risk of developing Lyme disease. DESIGN: Meta-analysis of published trials. DATA IDENTIFICATION: Clinical trials were identified by a computerised literature search of MEDLINE and by an assessment of the bibliographies of published studies. STUDY SELECTION: Trials were included in the analysis if their patients were randomly allocated to a treatment or control group, enrolled within 72 hours following an Ixodes tick bite, and had no clinical evidence of Lyme disease at enrollment. Three trials were selected for review after inclusion criteria were applied. DATA EXTRACTION: Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, and number of adverse events in each arm of therapy. RESULTS OF DATA SYNTHESIS: Among the 600 patients with Ixodes tick bites, the rate of infection in the placebo group was 1.4%. In contrast, patients who received antibiotic prophylaxis had a 0% infection rate. The pooled odds ratio, comparing prophylaxis to placebo, was 0.0 (95% confidence interval 0.0, 1.5) (p = .12). CONCLUSIONS: The available evidence to date suggests that the routine use of antibiotic prophylaxis for the prevention of Lyme disease remains uncertain. Meta-analysis of the controlled trials failed to establish definitive treatment efficacy owing to the small sample size of the combined trials and the low rates of infection following a deer tick bite. A larger randomized trial is needed to demonstrate definitively that prophylaxis is more effective than placebo in reducing the risk of early Lyme disease in endemic areas.

Amoxicillin↗
PubMed1996

The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans.

BACKGROUND: The diagnosis of erythema migrans (EM), the characteristic rash of early Lyme borreliosis, is based primarily on its clinical appearance since it often occurs prior to the development of a specific antibody response. Other skin disorders, however, may be confused with EM. METHODS: Between June 1991 and September 1993, a prospective study was conducted at the Lyme Disease Diagnostic Center of the Westchester County Medical Center to isolate Borrelia burgdorferi systematically from patients with Em, and to characterize the clinical manifestations of patients with culture-documented infection. Skin biopsies and/or needle aspirates of the advancing margin of primary lesions, and blood specimens from adult patients were cultured for B burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. RESULTS: B burgdorferi was recovered from 79 patients (49 [62%] males) ranging in age from 16 to 76 years old (mean, 43 +/- 14 years old). Maximum EM diameter (mean, 16 +/- 10 cm; range, 6-73 cm) was a function of EM duration (mean 6.7 +/- 6.4 days; range, 1-39 days) (correlation coefficient = 0.7; P < 0.001). Twenty (25%) patients had noted a tick bite at the site of the primary lesion a mean of 10 days (range, 1-27 days) before onset. Multiple EM lesions (range, 2-70) were present in 14 (18%) patients. Systemic symptoms were present at the time of culture in 54 patients (68%) including fatigue (54%), arthralgia (44%), myalgia (44%), headache, (42%), fever and/or chills (39%), stiff neck (35%), and anorexia (26%). Thirty-three patients (42%) had at least one objective finding on physical examination in addition to EM, including 18 (23%) with localized lymphadenopathy, 13 (16%) with fever (t > or = 37.8 degrees C), seven (9%) with tender neck flexion, six (8%) with joint tenderness, and 1 each with joint swelling, nuchal rigidity, and facial nerve palsy. No patient had new electrocardiogram evidence of atrioventricular block. Liver function assays were abnormally elevated in 37% of patients. Thirty-four percent of patients were seropositive by enzyme-linked immunosorbent assay at presentation. Most others rapidly seroconverted so that 69 of 78 evaluable patients (88%) were seropositive at some point during the first month after diagnosis. CONCLUSIONS: We describe the largest group of culture-positive patients with EM from the United States to date. Although systemic symptoms were present in most patients, objective evidence of advanced disease was uncommon. Our patients with culture-confirmed EM were less sick than those described in the days before culture confirmation was possible. The ability to isolate B burgdorferi from lesional skin of large numbers of patients with EM should make culture-positive patients the standard by which to define manifestations of early Lyme borreliosis associated with this rash. Microbiologic documentation of Lyme borreliosis will help delineate the manifestations of this illness, and should form the framework for research directed at pathophysiology, diagnosis, treatment, and prevention.

Adolescent↗
PubMed1996

Evolution of the serologic response to Borrelia burgdorferi in treated patients with culture-confirmed erythema migrans.

We investigated the appearance and evolution of immunoglobulin M (IgM) and IgG antibodies to Borrelia burgdorferi in 46 patients with culture-proven erythema migrans (EM). All patients received antimicrobial treatment and were prospectively evaluated for up to 1 year. A total of 257 serially collected serum samples were tested by commercial IgG-IgM enzyme-linked immunosorbent assay and separate IgM and IgG immunoblots (IBs). At the baseline, 33% of the patients had a positive ELISA result and 43% of the patients had a positive IgM IB result by using the criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors for the interpretation of IB results. Positive serology at the baseline and the rate of seroconversion correlated directly with disease duration and/or evidence of dissemination prior to treatment. At days 8 to 14 after the baseline, 91% of patients had a positive ELISA result and/or IgM IB result. Peak IgM antibody levels were seen at this time in patients with localized or disseminated disease. The most frequent IgM bands at the baseline and the peak were of 24 kDa (OspC), 41 kDa, and 37 kDa. Although 89% of the patients developed IgG antibodies as determined at a follow-up examination, only 22% were positive by the IgG IB criteria of the Centers for Disease Control and Prevention-Association of State and Territorial Public Health Laboratory Directors. The persistence of antibodies was directly related to disease duration and/or dissemination prior to treatment. Since IgM antibodies to the 24- and 41-kDa antigens remained detectable for long periods, 38% of IgM IBs were still positive at 1 year postbaseline. IgM to antigens of 39, 58, 60, 66, or 93 kDa, conversely, were most often seen in sera obtained within 1 month postbaseline. Their presence may be of assistance in confirming a recent infection with B. burgdorferi in individuals living in areas where Lyme disease is endemic.

Antibodies, Bacterial↗
PubMed1995

Erythema migrans and early Lyme disease.

Erythema migrans (EM) must be distinguished from other entities including streptococcal and staphylococcal cellulitis, hypersensitivity reactions to arthropod bites, plant dermatitis, tinea, and granuloma annulare. Although EM lesions may be pruritic or painful, these complaints are generally mild. Central clearing may be absent in > 50% of patients. Multiple lesions, formerly present in 50% of U.S. patients, now occur in approximately 20%. EM develops days to 1 month after a tick bite (median 7-10 days), and lesion diameter increases with duration. Most patients have associated complaints, with fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), and fever and/or chills (39%) being the most common. Respiratory and gastrointestinal complaints are infrequent. Symptoms may begin prior to the onset of, concomitant with, or after resolution of the rash. The incidence of viral-like illness due to Lyme disease without EM is unknown. Antibodies to Borrelia burgdorferi are absent in up to 50% of patients at presentation, with initial seropositivity most likely in those with EM of longer duration. The vast majority of patients will become seropositive within the first month of illness, even with treatment. Although there is evidence that B. burgdorferi can spread to the blood and central nervous system soon after onset of infection, oral therapy is highly effective in preventing objective extracutaneous complications of Lyme disease. The most appropriate choice, route of administration, and duration of therapy require further study. Because of variations in the etiologic agent between North America and Europe, comparisons of disease manifestations, treatment, and prognosis of Lyme disease must be made cautiously.

Borrelia burgdorferi Group↗