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Biomedical subjects

G P Wormser

Publications and source records attributed to G P Wormser.

At least 19 recordsLinked to original sources
PubMed2001

Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques.

Recently, a number of refinements in diagnostic modalities for detection of Borrelia burgdorferi infection have been developed. These include large-volume blood cultures, quantitative polymerase chain reaction (PCR) techniques, and 2-stage serologic testing. In the present study, we compared 6 diagnostic modalities in 47 adult patients who had a clinical diagnosis of erythema migrans. Quantitative PCR on skin biopsy-derived material was the most sensitive diagnostic method (80.9%), followed by 2-stage serologic testing of convalescent-phase samples (66.0%), conventional nested PCR (63.8%), skin culture (51.1%), blood culture (44.7%), and serologic testing of acute-phase samples (40.4%). Results of all assays were negative for 3 patients (6.4%). We conclude that the clinical diagnosis of erythema migrans is highly accurate in an area where B. burgdorferi is endemic if it is made by experienced health care personnel, but some patients with this diagnosis may not have B. burgdorferi infection. No single diagnostic modality is suitable for detection of B. burgdorferi in every patient with erythema migrans.

Biopsy↗
PubMed2001

Dexamethasone inhibits CD4 T cell deletion mediated by macrophages from human immunodeficiency virus-infected persons.

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.

Adult↗
PubMed2001

A first-tier rapid assay for the serodiagnosis of Borrelia burgdorferi infection.

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 (P>.05) and more specific (P<.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.

Antibodies, Bacterial↗
PubMed2001

Yield of large-volume blood cultures in patients with early Lyme disease.

To improve yield, 6 3-mL plasma cultures (18 mL total) were established for adult patients with early Lyme disease associated with erythema migrans. Borrelia burgdorferi was recovered from the blood of 22 (44.0%) of 50 evaluable patients. The recovery rate per plasma culture and the frequency of positive results for plasma cultures for individual patients were consistent with a level of spirochetemia of approximately 0.1 cultivable cell/mL of whole blood. Our findings suggest that, if further improvements in the yield of blood cultures are possible, they probably will depend on enhancing the sensitivity of the culture method rather than increasing the volume of material cultured.

Bacteremia↗
PubMed2001

Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite.

BACKGROUND: It is unclear whether antimicrobial treatment after an Ixodes scapularis tick bite will prevent Lyme disease. METHODS: In an area of New York where Lyme disease is hyperendemic we conducted a randomized, double-blind, placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in 482 subjects who had removed attached I. scapularis ticks from their bodies within the previous 72 hours. At base line, three weeks, and six weeks, subjects were interviewed and examined, and serum antibody tests were performed, along with blood cultures for Borrelia burgdorferi. Entomologists confirmed the species of the ticks and classified them according to sex, stage, and degree of engorgement. RESULTS: Erythema migrans developed at the site of the tick bite in a significantly smaller proportion of the subjects in the doxycycline group than of those in the placebo group (1 of 235 subjects [0.4 percent] vs. 8 of 247 subjects [3.2 percent], P<0.04). The efficacy of treatment was 87 percent (95 percent confidence interval, 25 to 98 percent). Objective extracutaneous signs of Lyme disease did not develop in any subject, and there were no asymptomatic seroconversions. Treatment with doxycycline was associated with more frequent adverse effects (in 30.1 percent of subjects, as compared with 11.1 percent of those assigned to placebo; P<0.001), primarily nausea (15.4 percent vs. 2.6 percent) and vomiting (5.8 percent vs. 1.3 percent). Erythema migrans developed more frequently after untreated bites from nymphal ticks than after bites from adult female ticks (8 of 142 bites [5.6 percent] vs. 0 of 97 bites [0 percent], P=0.02) and particularly after bites from nymphal ticks that were at least partially engorged with blood (8 of 81 bites [9.9 percent], as compared with 0 of 59 bites from unfed, or flat, nymphal ticks [0 percent]; P=0.02). CONCLUSIONS: A single 200-mg dose of doxycycline given within 72 hours after an I. scapularis tick bite can prevent the development of Lyme disease.

Adolescent↗
PubMed2001

Borrelia lonestari infection after a bite by an Amblyomma americanum tick.

Erythematous rashes that are suggestive of early Lyme disease have been associated with the bite of Amblyomma americanum ticks, particularly in the southern United States. However, Borrelia burgdorferi, the causative agent of Lyme disease, has not been cultured from skin biopsy specimens from these patients, and diagnostic serum antibodies usually have not been found. Borrelia lonestari sp nov, an uncultured spirochete, has been detected in A. americanum ticks by DNA amplification techniques, but its role in human illness is unknown. We observed erythema migrans in a patient with an attached A. americanum tick. DNA amplification of the flagellin gene flaB produced B. lonestari sequences from the skin of the patient that were identical to those found in the attached tick. B. lonestari is a probable cause of erythema migrans in humans.

Aged↗
PubMed2001

Serial measurements of hematologic counts during the active phase of human granulocytic ehrlichiosis.

To describe the changes that occur in blood count parameters during the natural course of human granulocytic ehrlichiosis, we designed a retrospective cross-sectional case study of 144 patients with human granulocytic ehrlichiosis and matched controls who had a different acute febrile illness. Patients from New York State and the upper Midwest were evaluated from June 1990 through December 1998. Routine complete blood counts and manual differential leukocyte counts of peripheral blood were performed on blood samples that were collected during the active illness, and values were recorded until the day of treatment with an active antibiotic drug. Thrombocytopenia was observed more frequently than was leukopenia, and the risk of having ehrlichiosis varied inversely with the granulocyte count and the platelet count. Patients with ehrlichiosis displayed relative and absolute lymphopenia and had a significant increase in band neutrophil counts during the first week of illness. Knowledge of characteristic complete blood count patterns that occur during active ehrlichiosis may help clinicians to identify patients who should be evaluated specifically for ehrlichiosis and who should receive empiric antibiotic treatment with doxycycline.

Acute-Phase Reaction↗
PubMed2001

Impact of color blindness on recognition of blood in body fluids.

BACKGROUND: Color blindness is a common hereditary X-linked disorder. OBJECTIVE: To investigate whether color blindness affects the ability to detect the presence of blood in body fluids. METHODS: Ten color-blind subjects and 20 sex- and age-matched control subjects were shown 94 photographs of stool, urine, or sputum. Frank blood was present in 57 (61%) of the photographs. Surveys were done to determine if board-certified internists had ever considered whether color blindness would affect detection of blood and whether an inquiry on color blindness was included in their standard medical interview. RESULTS: Color-blind subjects were significantly less able to identify correctly whether pictures of body fluids showed blood compared with non-color-blind controls (P =.001); the lowest rate of correct identifications occurred with pictures of stool (median of 26 [70%] of 37 for color-blind subjects vs 36.5 [99%] of 37 for controls; P<.001). The more severely color-blind subjects were significantly less accurate than those with less severe color deficiency (P =.009). Only 2 (10%) of the 21 physicians had ever considered the possibility that color blindness might affect the ability of patients to detect blood, and none routinely asked their patients about color blindness. CONCLUSIONS: Color blindness impairs recognition of blood in body fluids. Color-blind individuals and their health care providers need to be made aware of this limitation.

Adult↗
PubMed2001

Asymptomatic Borrelia burgdorferi infection.

Little is known about the natural history of asymptomatic Borrelia burgdorferi infection. Our analysis of the asymptomatic infections diagnosed serologically in a recent OspA vaccine trial conducted in the United States (N Engl J Med 1998;339: 209-215), suggests that the natural history of this event is more benign than that reported for untreated patients with erythema migrans (Ann Intern Med 1987;107: 725-731). We hypothesize that this is due either to incorrect diagnosis since the specificity of the serologic criteria used to diagnose asymptomatic infection in the vaccine study is unknown, or to infection with non-pathogenic strains of B. burgdorferi. Increasing evidence indicates that the invasive potential of strains of B. burgdorferi varies according to the specific subtype. Theoretically, a serologic testing method could be devised which would distinguish infection with invasive versus non-invasive strains of B. burgdorferi, and allow testing of the second hypothesis.

Bacterial Vaccines↗
PubMed2001

Costs and savings associated with infection control measures that reduced transmission of vancomycin-resistant enterococci in an endemic setting.

OBJECTIVE: To determine the costs and savings of a 15-component infection control program that reduced transmission of vancomycin-resistant enterococci (VRE) in an endemic setting. DESIGN: Evaluation of costs and savings, using historical control data. SETTING: Adult oncology unit of a 650-bed hospital. PARTICIPANTS: Patients with leukemia, lymphoma, and solid tumors, excluding bone marrow transplant recipients. METHODS: Costs and savings with estimated ranges were calculated. Excess length of stay (LOS) associated with VRE bloodstream infection (BSI) was determined by matching VRE BSI patients with VRE-negative patients by oncology diagnosis. Differences in LOS between the matched groups were evaluated using a mixed-effect analysis of variance linear-regression model. RESULTS: The cost of enhanced infection control strategies for 1 year was $116,515. VRE BSI was associated with an increased LOS of 13.7 days. The savings associated with fewer VRE BSI ($123,081), fewer patients with VRE colonization ($2,755), and reductions in antimicrobial use ($179,997) totaled $305,833. Estimated ranges of costs and savings for enhanced infection control strategies were $97,939 to $148,883 for costs and $271,531 to $421,461 for savings. CONCLUSION: The net savings due to enhanced infection control strategies for 1 year was $189,318. Estimates suggest that these strategies would be cost-beneficial for hospital units where the number of patients with VRE BSI is at least six to nine patients per year or if the savings from fewer VRE BSI patients in combination with decreased antimicrobial use equalled $100,000 to $150,000 per year.

Adult↗
PubMed2001

Antimicrobial susceptibility of Ehrlichia phagocytophila.

Human granulocytic ehrlichiosis is a recently described disease caused by an obligate intracellular gram-negative organism recently named Ehrlichia phagocytophila. To expand our knowledge of the susceptibility of E. phagocytophila, we tested six New York State isolates for susceptibility to 12 antimicrobials using an HL-60 cell culture system. All of the isolates were susceptible to doxycycline (MIC, < or =0.125 microg/ml; minimum bactericidal concentration [MBC], 0.125 to 0.5 microg/ml), rifampin (MIC, < or =0.125 microg/ml; MBC, < or =0.125 microg/ml), ofloxacin (MIC, < or =2 microg/ml; MBC, < or =2 microg/ml), levofloxacin (MIC, < or =1 microg/ml; MBC, < or =1 microg/ml), and trovafloxacin (MIC, < or =0.032 microg/ml; MBC, < or =0.032 microg/ml). Isolates were uniformly resistant to amoxicillin, ceftriaxone, erythromycin, azithromycin, clarithromycin, and amikacin. For one strain, the MBC of chloramphenicol was < or =8 microg/ml. These data suggest that quinolone antibiotics and rifampin may be alternative agents for patients with intolerance to tetracyclines.

Anti-Bacterial Agents↗
PubMed2001

Efficacy of an evernimicin (SCH27899) in vitro and in an animal model of Lyme disease.

The MICs of evernimicin at which 90% of Borrelia burgdorferi patient isolates were inhibited ranged from 0.1 to 0.5 microg/ml. Evernimicin was as effective as ceftriaxone against B. burgdorferi in a murine model of experimental Lyme disease. As assessed by culturing the urinary bladders of infected C3H mice, no live Borrelia isolates were recoverable following antibiotic treatment.

Aminoglycosides↗
PubMed2001

Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice.

Various genotypes of Borrelia burgdorferi sensu stricto have been previously identified among a large collection of isolates cultured from patients with Lyme disease in the United States. Furthermore, association of specific genotypes with hematogenous dissemination early in the disease course has been observed. The present study assessed kinetics of spirochete dissemination and disease severity in C3H/HeJ mice infected with two different genotypes of B. burgdorferi. Spirochete load in plasma and ear and other tissue samples of infected mice was measured by quantitative PCR, and these data were compared to those obtained by culture and histopathologic analysis. In mice infected with isolate BL206 (a type 1 strain), the peak number of spirochetes was observed in plasma between day 4 and 7, in heart and ear tissue on day 14, and in joints on day 28 postinoculation. There was a correlation between the peak number of spirochetes in plasma on day 4 or 7 and that in ear biopsy and joint specimens on day 14. By contrast, spirochete burdens in plasma of mice infected with isolate B356 (a type 3 strain) were 16- and 5-fold lower than those of BL206-infected mice on days 7 and 14 of infection, respectively. Similarly, approximately 6- and 13-fold fewer spirochetes were detected in the heart tissues of B356-infected mice compared to BL206-infected mice. Histopathologically, severe arthritis and aortitis were noted only in mice infected with isolate BL206. Spirochete dissemination and disease severity vary significantly in mice infected with distinct genotypes of B. burgdorferi, suggesting that genotypic differences in the infecting spirochetes play a key role in the pathogenesis and development of clinical disease.

Animals↗
PubMed2001

Western blot analysis of sera reactive to human monocytic ehrlichiosis and human granulocytic ehrlichiosis agents.

Laboratory diagnosis of human ehrlichioses is routinely made by an indirect immunofluorescence assay (IFA) using cultured ehrlichia-infected whole cells as antigen. Concern has been raised that incorrect diagnoses of human monocytic ehrlichiosis (HME) or human granulocytic ehrlichiosis (HGE) may be made on the basis of serologic cross-reactivity between Ehrlichia chaffeensis and the agent of HGE. The present study examined whether two recombinant major outer membrane proteins, rP30 and rP44, that were previously shown to be sensitive and specific serodiagnostic antigens for HME and HGE, respectively, could be used to discriminate IFA dually reacting sera. Thirteen dually IFA-reactive sera, three sera that were IFA positive only with E. chaffeensis, and three sera that were IFA positive only with the HGE agent were examined by Western immunoblot analysis using purified whole organisms and recombinant proteins as antigens. All 16 E. chaffeensis IFA-positive sera reacted with rP30. However, none of these sera reacted with rP44, regardless of IFA reactivity with the HGE agent. The three HGE-agent-only IFA-positive sera reacted only with rP44, not with rP30. Western immunoblotting using purified E. chaffeensis and the HGE agent as antigens suggested that heat shock and other proteins, but not major outer membrane proteins, cross-react between the two organisms. Therefore, Western immunoblot analysis using rP44 and rP30 may be useful in discriminating dually HME and HGE IFA-reactive sera.

Antibodies, Bacterial↗
PubMed2001

Characterization of Borrelia burgdorferi isolated from erythema migrans lesions: interrelationship of three molecular typing methods.

Genetic diversity among Borrelia burgdorferi isolates recovered from the skin of Lyme disease patients was assessed by ribosomal DNA (rDNA) spacer restriction fragment length polymorphism analysis, genomic restriction site polymorphism analysis, and plasmid content analysis. There was a significant association between the three rDNA spacer types, the six pulsed-field gel types, and plasmid content (P < 0.001). The association between distinct chromosomal and plasmid markers implies a clonal origin for each genotype.

Adult↗
PubMed2000

Failure of treatment with cephalexin for Lyme disease.

CONTEXT: Lyme disease typically presents with a skin lesion called erythema migrans (EM), which though often distinctive in appearance may be confused with cellulitis. The first-generation cephalosporin, cephalexin monohydrate, is effective for treating bacterial cellulitis but has not been recommended or studied for treating Lyme disease because of poor in vitro activity. OBJECTIVE: To describe the outcome of patients with EM who were treated with cephalexin. PATIENTS AND METHODS: Patients presenting with EM to the Lyme Disease Diagnostic Center in Westchester, NY (May 1992-September 1997). A 2-mm punch biopsy specimen of the leading edge of the EM lesion and/or blood was cultured for Borrelia burgdorferi. RESULTS: Eleven (2.8%) of 393 study patients had been initially treated with cephalexin prior to our evaluation; 9 (82%) were originally diagnosed with cellulitis. Cephalexin was administered for 8.6 days (range, 2-21 days) prior to presentation. All 11 patients had clinical evidence of disease progression, including 8 whose rash enlarged, 2 who developed seventh-nerve palsy (1 with new EM lesions), and 1 who developed new EM lesions. Borrelia burgdorferi grew in cultures from 5 patients despite a mean of 9.8 days of treatment with cephalexin (range, 5-21 days). CONCLUSION: Cephalexin should not be used to treat early Lyme disease and should be prescribed with caution during the summer months for patients believed to have cellulitis in locations where Lyme disease is endemic.

Adult↗
PubMed2000

An indirect hemagglutination antibody test to detect antibodies to Borrelia burgdorferi in patients with Lyme disease.

An indirect hemagglutination antibody (IHA) test was evaluated for its ability to detect borrelial antibodies in serum samples from patients with Lyme disease. The key test reagent developed for this antibody detection system was tannic acid-treated and glutaraldehyde-fixed sheep red blood cells (SRBC) containing Borrelia burgdorferi (Bb) antigens attached to the outer surface of the SRBC. In order to establish suitable cut-off titers, initial specificity and sensitivity measurements were made using sera from 100 anonymous healthy volunteers and 30 additional pre-determined samples known to be non-reactive or reactive for Lyme disease or syphilis. These results were compared with those obtained using a commercially available ELISA. At titers >/=64, the IHA test had a combined 98% specificity and 100% sensitivity for these 130 serum samples, 30 of which were known positives or negatives, whereas the ELISA was less specific (93%) and much less sensitive (80%). Subsequent testing was performed on sera from 65 patients with the erythema migrans (EM) rash and 20 patients with early disseminated (cardiac/neurologic) symptoms or with Lyme arthritis. At initial presentation, 46-48% of the EM patients had IHA reactivity, with titers >/=128, while 42% were positive in the ELISA. Follow-up testing performed on these EM patients, 8-12 days after receiving antibiotic treatment, revealed that Bb antibodies were detected best by the IHA test (83-86% reactive) relative to the ELISA (81% reactive). Bb antibodies were readily detectable on all of the serum samples from the early disseminated and late stage Lyme disease cases in both assay systems. Based on these results and because of its technical and interpretive simplicity, the IHA test should be considered as a useful and convenient alternative for the serological analysis of Bb infections.

Antibodies, Bacterial↗