Dr. James Schaller, MD
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New Jersey Lyme Disease

  1. J Econ Entomol. 2009 Dec;102(6):2316-24.

    Ability of two natural products, nootkatone and carvacrol, to suppress Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) in a Lyme disease endemic area of New Jersey.

    Dolan MC, Jordan RA, Schulze TL, Schulze CJ, Manning MC, Ruffolo D, Schmidt JP, Piesman J, Karchesy JJ.

    Division of Vector-Borne Infectious Diseases, National Center for Zoonotic, Vector-Borne and Enteric Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA. mcd4@cdc.gov

    We evaluated the ability of the natural, plant-derived acaricides nootkatone and carvacrol to suppress Ixodes scapularis Say and Amblyomma americanum (L.) (Acari: Ixodidae). Aqueous formulations of 1 and 5% nootkatone applied by backpack sprayer to the forest litter layer completely suppressed I. scapularis nymphs through 2 d. Thereafter, the level of reduction gradually declined to < or =50% at 28 d postapplication. Against A. americanum nymphs, 1% nootkatone was less effective, but at a 5% concentration, the level of control was similar or greater to that observed with I. scapularis through 21 d postapplication. Initial applications of 0.05% carvacrol were ineffective, but a 5% carvacrol formulation completely suppressed nymphs of both species through 2 d and resulted in significant reduction in I. scapularis and A. americanum nymphs through 28 and 14 d postapplication, respectively. Backpack sprayer applications of 5% nootkatone to the shrub and litter layers resulted in 100% control of I. scapularis adults through 6 d, but the level of reduction declined to 71.5% at 28 d postapplication. By contrast, high-pressure applications of 2% nootkatone to the litter layer resulted in 96.2-100% suppression of both I. scapularis and A. americanum nymphs through 42 d, whereas much lower control was obtained from the same formulation applied by backpack sprayer. Backpack sprayer application of a 3.1% nootkatone nanoemulsion resulted in 97.5-98.9 and 99.3-100% reduction in I. scapularis and A. americanum nymphs, respectively, at 1 d postapplication. Between 7 d and 35 d postapplication, the level of control varied between 57.1% and 92.5% for I. scapularis and between 78.5 and 97.1% for A. americanum nymphs. The ability of natural products to quickly suppress and maintain significant control of populations of these medically important ticks at relatively low concentrations may represent a future alternative to the use of conventional synthetic acaricides.

    PMID: 20069863 [PubMed - indexed for MEDLINE]

  2. Vaccine. 2009 Dec 9;27(52):7322-5. Epub 2009 Oct 4.

    Small fiber neuropathy following vaccination for rabies, varicella or Lyme disease.

    Souayah N, Ajroud-Driss S, Sander HW, Brannagan TH, Hays AP, Chin RL.

    Department of Neurology, New Jersey Medical School, 90 Bergen Street, DOC 8100, Newark, NJ 07103, United States. souayani@umdnj.edu

    Neuropathy following vaccination has been reported; however, biopsy-confirmed small fiber neuropathy has not been described. We report five patients who developed paresthesias within one day to two months following vaccination for rabies, varicella zoster, or Lyme disease. On examination, there was mild sensory loss in distal extremities, preserved strength, normal or minimally abnormal electrodiagnostic findings, and decreased epidermal nerve fiber densities per skin biopsy. Empiric immunomodulatory therapy was tried in two patients and was ineffective. All patients' symptoms have improved, but persist. We conclude that an acute or subacute, post-vaccination small fiber neuropathy may occur and follow a chronic course.

    PMID: 19808027 [PubMed - indexed for MEDLINE]

  3. J Med Entomol. 2009 Sep;46(5):1025-9.

    Precipitation and temperature as predictors of the local abundance of Ixodes scapularis (Acari: Ixodidae) nymphs.

    Schulze TL, Jordan RA, Schulze CJ, Hung RW.

    Division of Epidemiology, Environmental and Occupational Health, New Jersey, Department of Health and Senior Services, PO Box 369, Trenton, NJ 08625, USA.

    Populations of Ixodes scapularis Say nymphs were surveyed at a Lyme disease- endemic area for 8 consecutive yr (1998-2005) to characterize annual changes in abundance. Precipitation and temperature were also monitored over the period 1998-2004 to determine their potential value as predictors of tick abundance. Although both parameters showed annual variation, no statistical differences in the annual abundance of I. scapularis nymphs were observed over the 8-yr period. Our results suggest that precipitation and temperature were not predictive of the abundance of I. scapularis nymphs.

    PMID: 19769032 [PubMed - indexed for MEDLINE]

  4. Am J Med. 2009 Sep;122(9):843-50.

    Psychiatric comorbidity and other psychological factors in patients with "chronic Lyme disease".

    Hassett AL, Radvanski DC, Buyske S, Savage SV, Sigal LH.

    Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA. a.hassett@umdnj.edu

    BACKGROUND: There is no evidence of current or previous Borrelia burgdorferi infection in most patients evaluated at university-based Lyme disease referral centers. Instead, psychological factors likely exacerbate the persistent diffuse symptoms or "Chronic Multisymptom Illness" (CMI) incorrectly ascribed to an ongoing chronic infection with B. burgdorferi. The objective of this study was to assess the medical and psychiatric status of such patients and compare these findings to those from patients without CMI. METHODS: There were 240 consecutive patients who underwent medical evaluation and were screened for clinical disorders (eg, depression and anxiety) with diagnoses confirmed by structured clinical interviews at an academic Lyme disease referral center in New Jersey. Personality disorders, catastrophizing, and negative and positive affect also were evaluated, and all factors were compared between groups and with functional outcomes. RESULTS: Of our sample, 60.4% had symptoms that could not be explained by current Lyme disease or another medical condition other than CMI. After adjusting for age and sex, clinical disorders were more common in CMI than in the comparison group (P <.001, odds ratio 3.54, 95% confidence interval, 1.97-6.55), but personality disorders were not significantly more common. CMI patients had higher negative affect, lower positive affect, and a greater tendency to catastrophize pain (P <.001) than did the comparison group. Except for personality disorders, all psychological factors were related to worse functioning. Our explanatory model based on these factors was confirmed. CONCLUSIONS: Psychiatric comorbidity and other psychological factors are prominent in the presentation and outcome of some patients who inaccurately ascribe longstanding symptoms to "chronic Lyme disease."

    PMCID: PMC2751626 [Available on 2010/9/1] PMID: 19699380 [PubMed - indexed for MEDLINE]

  5. Vector Borne Zoonotic Dis. 2009 Aug;9(4):389-400.

    Effectiveness of the 4-Poster passive topical treatment device in the control of Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) in New Jersey.

    Schulze TL, Jordan RA, Hung RW, Schulze CJ.

    Terry L. Schulze, Ph.D., Inc., Perrineville, New Jersey, USA.

    Twenty-five "4-Poster" feeders were placed throughout a 5.2 km(2) study area within a secured military facility situated in a hyperendemic area for Lyme disease in central Monmouth County, New Jersey. Calculated levels of control, relative to untreated areas, peaked at 82.7%, 77.3%, and 94.2% for of host-seeking Ixodes scapularis Say larvae, nymphs, and adults, respectively, within 5 years of deployment. Control of host-seeking Amblyomma americanum (L.) peaked at 99.2%, 89.5%, and 96.9% for larvae, nymphs, and adults, respectively, during the treatment period. Tick burdens on hunter-killed deer were significantly reduced on deer harvested from the treatment area and on deer that had consumed bait corn. Populations of subadult I. scapularis and A. americanum demonstrated some rebound effect following the removal of 4-Posters, but treatment area tick populations remained lower than control area populations 2 years following withdrawal of the 4-Posters. However, control of I. scapularis adults declined to 20.7% by the third fall activity period following removal of the 4-Posters. The posttreatment phase of the study was of insufficient duration to evaluate continued population rebound of adults and subadults during subsequent activity periods.

    PMID: 19650733 [PubMed - indexed for MEDLINE]

  6. Vector Borne Zoonotic Dis. 2009 Aug;9(4):365-70.

    The United States Department Of Agriculture Northeast Area-wide Tick Control Project: history and protocol.

    Pound JM, Miller JA, George JE, Fish D.

    Knipling-Bushland U.S. Livestock Insects Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Kerrville, Texas 78028-9184, USA. mat.pound@ars.usda.gov

    The Northeast Area-wide Tick Control Project (NEATCP) was funded by the United States Department of Agriculture (USDA) as a large-scale cooperative demonstration project of the USDA-Agricultural Research Service (ARS)-patented 4-Poster tick control technology (Pound et al. 1994) involving the USDA-ARS and a consortium of universities, state agencies, and a consulting firm at research locations in the five states of Connecticut (CT), Maryland (MD), New Jersey (NJ), New York (NY), and Rhode Island (RI). The stated objective of the project was "A community-based field trial of ARS-patented tick control technology designed to reduce the risk of Lyme disease in northeastern states." Here we relate the rationale and history of the technology, a chronological listing of events leading to implementation of the project, the original protocol for selecting treatment, and control sites, and protocols for deployment of treatments, sampling, assays, data analyses, and estimates of efficacy.

    PMID: 19650730 [PubMed - indexed for MEDLINE]

  7. BMC Microbiol. 2009 Feb 24;9:43.

    Detection and quantification of Lyme spirochetes using sensitive and specific molecular beacon probes.

    Saidac DS, Marras SA, Parveen N.

    Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103-3535, USA. dianasaidac@hotmail.com

    BACKGROUND: Lyme disease, caused by Borrelia burgdorferi, affects a large number of people in both the USA and Europe. The mouse is a natural host for this spirochete and is widely used as a model system to study Lyme pathogenesis mechanisms. Since disease manifestations often depend upon the spirochete burden in a particular tissue, it is critical to accurately measure the bacterial number in infected tissues. The current methods either lack sensitivity and specificity (SYBR Green), or require independent analysis of samples in parallel to quantitate host and bacterial DNA (TaqMan). We have developed a novel molecular beacon-based convenient multiplex real-time quantitative PCR assay to identify and detect small numbers of B. burgdorferi in infected mouse tissues. RESULTS: We show here that molecular beacons are effective, sensitive and specific probes for detecting and estimating wide-ranging numbers of B. burgdorferi in the presence of mouse DNA. In our assays, the spirochete recA and the mouse nidogen gene amplicons were detected simultaneously using molecular beacons labeled with different fluorophores. We further validated the application of these probes by quantifying the wild-type strain and bgp-defective mutant of B. burgdorferi. The bgp-defective mutant shows a ten-fold reduction in the level of spirochetes present in various tissues. CONCLUSION: The high sensitivity and specificity of molecular beacons makes them superior probes for the detection of small numbers of B. burgdorferi. Furthermore, the use of molecular beacons can be expanded for the simultaneous detection and quantification of multiple pathogens in the infected hosts, including humans, and in the arthropod vectors.

    PMCID: PMC2670302 PMID: 19239692 [PubMed - indexed for MEDLINE]

  8. Arthritis Rheum. 2008 Dec 15;59(12):1742-9.

    Role of psychiatric comorbidity in chronic Lyme disease.

    Hassett AL, Radvanski DC, Buyske S, Savage SV, Gara M, Escobar JI, Sigal LH.

    University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA. a.hassett@umdnj.edu

    OBJECTIVE: To evaluate the prevalence and role of psychiatric comorbidity and other psychological factors in patients with chronic Lyme disease (CLD). METHODS: We assessed 159 patients drawn from a cohort of 240 patients evaluated at an academic Lyme disease referral center. Patients were screened for common axis I psychiatric disorders (e.g., depressive and anxiety disorders); structured clinical interviews confirmed diagnoses. Axis II personality disorders, functional status, and traits like negative and positive affect and pain catastrophizing were also evaluated. A physician blind to psychiatric assessment results performed a medical evaluation. Two groups of CLD patients (those with post-Lyme disease syndrome and those with medically unexplained symptoms attributed to Lyme disease but without Borrelia burgdorferi infection) were compared with 2 groups of patients without CLD (patients recovered from Lyme disease and those with an identifiable medical condition explaining symptoms attributed to Lyme disease). RESULTS: After adjusting for age and sex, axis I psychiatric disorders were more common in CLD patients than in comparison patients (P = 0.02, odds ratio 2.64, 95% confidence interval 1.30-5.35), but personality disorders were not. Patients with CLD had higher negative affect, lower positive affect, and a greater tendency to catastrophize pain (P < 0.001) than comparison patients. All psychological factors except personality disorders were related to level of functioning. A predictive model based on these psychological variables was confirmed. Fibromyalgia was diagnosed in 46.8% of CLD patients. CONCLUSION: Psychiatric comorbidity and other psychological factors distinguished CLD patients from other patients commonly seen in Lyme disease referral centers, and were related to poor functional outcomes.

    PMID: 19035409 [PubMed - indexed for MEDLINE]

  9. Ecology. 2008 Oct;89(10):2841-9.

    Impact of host community composition on Lyme disease risk.

    LoGiudice K, Duerr ST, Newhouse MJ, Schmidt KA, Killilea ME, Ostfeld RS.

    Department of Biological Sciences, Union College, Schenectady, New York 12308, USA. logiudik@union.edu

    The drivers of variable disease risk in complex multi-host disease systems have proved very difficult to identify. Here we test a model that explains the entomological risk of Lyme disease (LD) in terms of host community composition. The model was parameterized in a continuous forest tract at the Cary Institute of Ecosystem Studies (formerly the Institute of Ecosystem Studies) in New York State, U.S.A. We report the results of continuing longitudinal observations (10 years) at the Cary Institute, and of a shorter-term study conducted in forest fragments in LD endemic areas of Connecticut, New Jersey, and New York, USA. Model predictions were significantly correlated with the observed nymphal infection prevalence (NIP) in both studies, although the relationship was stronger in the longer-term Cary Institute study. Species richness was negatively, albeit weakly, correlated with NIP (logistic regression), and there was no relationship between the Shannon diversity index (H') and NIP. Although these results suggest that LD risk is in fact dependent on host diversity, the relationship relies explicitly on the identities and frequencies of host species such that conventional uses of the term biodiversity (i.e., richness, evenness, H') are less appropriate than are metrics that include species identity. This underscores the importance of constructing interaction webs for vertebrates and exploring the direct and indirect effects of anthropogenic stressors on host community composition.

    PMID: 18959321 [PubMed - indexed for MEDLINE]

  10. MMWR Surveill Summ. 2008 Oct 3;57(10):1-9.

    Surveillance for Lyme disease--United States, 1992-2006.

    Bacon RM, Kugeler KJ, Mead PS; Centers for Disease Control and Prevention (CDC).

    Division of Vector-Borne Infectious Diseases, National Center for Zoonotic Vector-Borne and Enteric Diseases, Fort Collins, CO 80521, USA.

    PROBLEM/CONDITION: Lyme disease is a multisystem disease that occurs in North America, Europe, and Asia. In the United States, the etiologic agent is Borrelia burgdorferi sensu stricto, a spirochete transmitted to humans by infected Ixodes scapularis and I. pacificus ticks. The majority of patients with Lyme disease develop a characteristic rash, erythema migrans (EM), accompanied by symptoms of fever, malaise, fatigue, headache, myalgia, or arthralgia. Other manifestations of infection can include arthritis, carditis, and neurologic deficits. Lyme disease can be treated successfully with standard antibiotic regimens. REPORTING PERIOD: 1992--2006. DESCRIPTION OF SYSTEM: U.S. health departments report cases of Lyme disease voluntarily to CDC as part of the National Notifiable Disease Surveillance System. Variables collected include patient age, sex, race, county and state of residence, date of illness onset, and reported signs and symptoms. RESULTS: During 1992--2006, a total of 248,074 cases of Lyme disease were reported to CDC by health departments in the 50 states, the District of Columbia, and U.S. territories; the annual count increased 101%, from 9,908 cases in 1992 to 19,931 cases in 2006. During this 15-year period, 93% of cases were reported from 10 states (Connecticut, Delaware, Massachusetts, Maryland, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). Incidence was highest among children aged 5--14 years, and 53% of all reported cases occurred among males. More than 65% of patients with EM had illness onset in June and July, compared with 37% of patients with arthritis. INTERPRETATION: Lyme disease is the most commonly reported vectorborne illness in the United States. The geographic distribution of cases is highly focused, with the majority of reported cases occurring in the northeastern and north-central states. During 1992--2006, the number of reported cases more than doubled. A disproportionate increasing trend was observed in children and in young males compared with other demographic groups. PUBLIC HEALTH ACTION: The results presented in this report underscore the continued emergence of Lyme disease and the need for tick avoidance and early treatment interventions. Public health practitioners can use the data presented in this report to target prevention campaigns to populations with increasing incidence (i.e., children and young males).

    PMID: 18830214 [PubMed - indexed for MEDLINE]

  11. MMWR Morb Mortal Wkly Rep. 2008 Jan 18;57(2):42-5.

    Effect of electronic laboratory reporting on the burden of lyme disease surveillance--New Jersey, 2001-2006.

    Centers for Disease Control and Prevention (CDC).

    Lyme disease (LD) is a vector-borne illness caused by the spirochete Borrelia burgdorferi and transmitted in the United States by blacklegged ticks (Ixodes spp.). LD is most commonly found in the northeastern, mid-Atlantic, and north-central regions of the United States. In 2005, New Jersey reported 38.6 LD cases per 100,000 population, the third-highest incidence in the United States after Delaware and Connecticut. Since 1980, New Jersey has mandated that health-care providers and clinical laboratories report all LD cases to local health departments, which investigate these reports to confirm that they meet the national surveillance case definition. Reports from health-care providers typically include exposure and clinical information needed for case confirmation. In contrast, reports from laboratories do not contain exposure and clinical information, and local health departments must follow up with health-care providers to obtain the missing information needed to confirm a case for surveillance purposes. In 2002, New Jersey expanded its paper-based laboratory reporting system to include electronic laboratory-reporting (ELR) for all laboratory-reportable diseases. During the next 4 years, New Jersey's local health departments noted that the number of ELR reports for LD and the time needed to handle them had begun to impede the departments' abilities to address other public health priorities. In 2006, to assess these concerns, the New Jersey Department of Health and Senior Services evaluated the state's LD surveillance system. This report summarizes the results of that evaluation, which determined that during 2001-2004, the total annual number of LD reports increased nearly fivefold (from 2,460 in 2001 to 11,957 in 2004), but confirmed reports increased only 18% (from 2,371 in 2001 to 2,791 in 2004). ELR represented 51% of reports received during 2001-2006, but only 29% were confirmed upon investigation. These results illustrate the difficulties associated with ELR reporting of LD in New Jersey, especially the use of resources needed to address other public health problems. Other states with similar difficulties might need to reevaluate the resources used to confirm electronically reported LD and other notifiable diseases.

    PMID: 18199968 [PubMed - indexed for MEDLINE]

  12. J Med Entomol. 2007 Sep;44(5):752-7.

    Effects of reduced deer density on the abundance of Ixodes scapularis (Acari: Ixodidae) and Lyme disease incidence in a northern New Jersey endemic area.

    Jordan RA, Schulze TL, Jahn MB.

    Freehold Area Health Department, 1 Municipal Plaza, Freehold, NJ 07728, USA. rajordanphd@msn.com

    We monitored the abundance of Ixodes scapularis Say (Acari: Ixodidae) and the Lyme disease incidence rate after the incremental removal of white-tailed deer, Odocoileus virginianus Zimmermann, within a suburban residential area to determine whether there was a measurable decrease in the abundance of ticks due to deer removal and whether the reduction in ticks resulted in a reduction in the incidence rate within the human population. After three seasons, the estimated deer population was reduced by 46.7%, from the 2002 postfawning estimate of 2,899 deer (45.6 deer per km2) to a 2005 estimate of 1,540 deer (24.3 deer per km2). There was no apparent effect of the deer culling program on numbers of questing I. scapularis subadults in the culling areas, and the overall numbers of host-seeking ticks in the culling areas seemed to increase in the second year of the program. The Lyme disease incidence rate generated by both passive and active surveillance systems showed no clear trend among years, and it did not seem to vary with declining deer density. Given the resources required to mount and maintain a community-based program of sufficient magnitude to effectively reduce vector tick density in ecologically open situations where there are few impediments to deer movement, it may be that deer reduction, although serving other community goals, is unlikely to be a primary means of tick control by itself. However, in concert with other tick control interventions, such programs may provide one aspect of a successful community effort to reduce the abundance of vector ticks.

    PMID: 17915504 [PubMed - indexed for MEDLINE]

  13. MMWR Morb Mortal Wkly Rep. 2007 Jun 15;56(23):573-6.

    Lyme disease--United States, 2003-2005.

    Centers for Disease Control and Prevention (CDC).

    Lyme disease is caused by the spirochete Borrelia burgdorferi and is transmitted to humans by the bite of infected blacklegged ticks (Ixodes spp.). Early manifestations of infection include fever, headache, fatigue, and a characteristic skin rash called erythema migrans. Left untreated, late manifestations involving the joints, heart, and nervous system can occur. A Healthy People 2010 objective (14-8) is to reduce the annual incidence of Lyme disease to 9.7 new cases per 100,000 population in 10 reference states where the disease is endemic (Connecticut, Delaware, Maryland, Massachusetts, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin). This report summarizes surveillance data for 64,382 Lyme disease cases reported to CDC during 2003-2005, of which 59,770 cases (93%) were reported from the 10 reference states. The average annual rate in these 10 reference states for the 3-year period (29.2 cases per 100,000 population) was approximately three times the Healthy People 2010 target. Persons living in Lyme disease--endemic areas can take steps to reduce their risk for infection, including daily self-examination for ticks, selective use of acaricides and tick repellents, use of landscaping practices that reduce tick populations in yards and play areas, and avoidance of tick-infested areas.

    PMID: 17568368 [PubMed - indexed for MEDLINE]

  14. Lancet Neurol. 2007 Jun;6(6):544-52.

    Lyme neuroborreliosis: infection, immunity, and inflammation.

    Pachner AR, Steiner I.

    Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. pachner@umdnj.edu

    Comment in: Lancet Neurol. 2007 Sep;6(9):756-7; author reply 757. Lancet Neurol. 2008 Jan;7(1):25; author reply 25.

    Lyme neuroborreliosis (LNB), the neurological manifestation of systemic infection with the complex spirochaete Borrelia burgdorferi, can pose a challenge for practising neurologists. This Review is a summary of clinical presentation, diagnosis, and therapy, as well as of recent advances in our understanding of LNB. Many new insights have been gained through work in experimental models of the disease. An appreciation of the genetic heterogeneity of the causative pathogen has helped clinicians in their understanding of the diverse presentations of LNB.

    PMID: 17509489 [PubMed - indexed for MEDLINE]

  15. J Med Entomol. 2006 Nov;43(6):1269-75.

    Relative abundance and prevalence of selected Borrelia infections in Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) from publicly owned lands in Monmouth County, New Jersey.

    Schulze TL, Jordan RA, Healy SP, Roegner VE, Meddis M, Jahn MB, Guthrie DL Sr.

    Freehold Area Health Department, 1 Municipal Plaza, Freehold, NJ 07728, USA. tlschulze@monmouth.com

    To evaluate their potential importance in the transmission of ixodid tick-borne borrelioses in Monmouth County, NJ, we collected host-seeking Ixodes scapularis Say and Amblyomma americanum (L.) (Acari: Ixodidae) adults and nymphs to determine relative encounter frequencies and the infection prevalence of selected Borrelia spp. in their respective tick vectors. We also reviewed records of all ticks submitted for identification by the public in Monmouth County during 2001-2005. Relative abundance of the two species varied markedly among sites. Adult encounter frequencies for the two species were similar; however, A. americanum nymphs were encountered 3 times more frequently than I. scapularis nymphs. Of 435 ticks submitted by the public, 50.1 and 38.9% were I. scapularis and A. americanum, respectively. However, during May through August, the peak Lyme disease transmission season in New Jersey, significantly more submitted ticks were A. americanum (55.9%), compared with I. scapularis (34.1%). Polymerase chain reaction analysis of 94 1. scapularis and 103 A. americanum adults yielded infection prevalences of 31.9% for B. burgdorferi and 5.8% for B. lonestari, respectively. Although the infection prevalence of B. burgdorferi in I. scapularis was considerably higher than the infection prevalence of B. lonestari in A. americanum, the higher encounter frequencies for A. americanum compared with I. scapularis observed in this and other studies may result in increased risk of acquiring exposure to A. americanum-transmitted pathogens. The potential public health implications of these results are discussed.

    PMID: 17162963 [PubMed - indexed for MEDLINE]

  16. Wien Klin Wochenschr. 2006 Nov;118(21-22):653-8.

    The mammalian host response to borrelia infection.

    Cadavid D.

    Department of Neurology and Neuroscience and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. cadavidi@umdnj.edu

    Tick-borne relapsing fever (RF) and Lyme disease (LD) are spirochetal infections of humans caused by different Borrelia species in endemic areas throughout the world. Our laboratory is studying the response of mammalian hosts to borrelia infection in RF and LD. For this, we use mice and non-human primates infected with B. burgdorferi sensu stricto strain N40 (N40) and the Oz1 strain of Borrelia turicatae (Bt), agents of LD and RF in North America, respectively. Our results have revealed that outbred non-human primates are significantly less susceptible than outbred mice to persistent infection with N40. In contrast, the majority of mice inoculated with the RF agent B. turicatae clear the infection, with the notable exception of residual brain or blood infection in up to 25% of cases. Little if any tissue injury occurs in immunocompetent animals with either LD or RF. In contrast, impairment of specific antibody production results in significant tissue injury, most notably in the heart, in both LD and RF. The inflammatory infiltrate is rich in plasma cells, activated macrophages and T cells, and there is significant deposition of antibody and complement, including membrane attack complex, in inflamed tissues and spirochetes. Significant loss of cardiomyocytes with apoptosis and caspase activation was observed in the heart of immunosuppressed non-human primates infected with N40 and in B cell-deficient mice infected with B. turicatae. Unlike the heart, the brain of B cell-deficient mice infected with B. turicatae showed prominent microglial activation but no detectable tissue injury. Tissues from immunosuppressed non-human primates infected with N40 produce large amounts of immunoglobulin and the B cell chemokine CXCL13, both of which significantly correlate with the spirochetal load. We conclude that the main response of mammalian hosts in LD and RF is the production of specific antibody to clear the infection. Failure of this response leads to persistent infection, which can lead to tissue injury, most notably in the heart.

    PMID: 17160603 [PubMed - indexed for MEDLINE]

  17. J Clin Rheumatol. 2003 Apr;9(2):77-87.

    Evidence for disseminated Mycoplasma fermentans in New Jersey residents with antecedent tick attachment and subsequent musculoskeletal symptoms.

    Eskow E, Adelson ME, Rao RV, Mordechai E.

    Hunterdon Medical Center, Flemington, NJ, USA.

    Mycoplasma species are one of nature's most abundant groups of microbes. These bacteria inhabit a wide diversity of insect, plant, and animal species, including humans. Certain mycoplasma species have been identified in blood-sucking arthropods, including Ixodes ticks. Frequent human exposure to this genus of ticks led us to explore the possibility of tick-mediated transmission of these bacteria. We evaluated 7 residents of central New Jersey who developed fatigue, musculoskeletal symptoms, and cognitive disturbance after tick attachment. All 7 of these patients lacked both serological evidence and erythema migrans skin lesions characteristic of Lyme disease. We were able to amplify and quantitate Mycoplasma fermentans-specific DNA from their peripheral blood lymphocytes. After antimicrobial therapy, symptoms subsided, and M. fermentans DNA could no longer be detected in their blood specimens. These findings suggest that a subset of disseminated M. fermentans infections may be a vector-mediated process in humans and should be considered in patients with puzzling musculoskeletal presentations.

    PMID: 17041434 [PubMed]

  18. Infect Immun. 2006 Nov;74(11):6408-18. Epub 2006 Aug 28.

    Interaction of a neurotropic strain of Borrelia turicatae with the cerebral microcirculation system.

    Sethi N, Sondey M, Bai Y, Kim KS, Cadavid D.

    Department of Neurology and Neuroscience, Center for the Study of Emerging Pathogens, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, MSB H506, Newark, NJ 07103, USA.

    Relapsing fever (RF) is a spirochetal infection characterized by relapses of a febrile illness and spirochetemia due to the sequential appearance and disappearance of isogenic serotypes in the blood. The only difference between isogenic serotypes is the variable major outer membrane lipoprotein. In the absence of specific antibody, established serotypes cause persistent infection. Studies in our laboratory indicate that another consequence of serotype switching in RF is a change in neuroinvasiveness. As the next step to elucidate this phenomenon, we studied the interaction of the neurotropic Oz1 strain of the RF agent Borrelia turicatae with the cerebral microcirculation. During persistent infection of antibody-deficient mice, we found that serotype 1 entered the brain in larger numbers and caused more severe cerebral microgliosis than isogenic serotype 2. Microscopic examination revealed binding of B. turicatae to brain microvascular endothelial cells in vivo. In vitro we found that B. turicatae associated with brain microvascular endothelial cells (BMEC) significantly more than with fibroblasts or arachnoidal cells. The binding was completely eliminated by pretreatment of BMEC with proteinase K. Using transwell chambers with BMEC barriers, we found that serotype 1 crossed into the lower compartment significantly better than serotype 2. Heat killing significantly reduced BMEC crossing but not binding. We concluded that the interaction of B. turicatae with the cerebral microcirculation involves both binding and crossing brain microvascular endothelial cells, with significant differences among isogenic serotypes.

    PMCID: PMC1695479 PMID: 16940140 [PubMed - indexed for MEDLINE]

  19. J Med Entomol. 2006 Jul;43(4):762-73.

    Distribution and characterization of Borrelia burgdorferi isolates from Ixodes scapularis and presence in mammalian hosts in Ontario, Canada.

    Morshed MG, Scott JD, Fernando K, Geddes G, McNabb A, Mak S, Durden LA.

    Laboratory Services, BC Centre for Disease Control, 655 West 12th Ave., Vancouver, British Columbia, Canada V5Z 4R4. mmorshed@interchange.ubc.ca

    The blacklegged tick, Ixodes scapularis Say (Acari: Ixodidae), has a wide geographical distribution in Ontario, Canada, with a detected range extending at least as far north as the 50th parallel. Our data of 591 adult I. scapularis submissions collected from domestic animals (canines, felines, and equines) and humans during a 10-yr period (1993-2002) discloses a monthly questing activity in Ontario that peaks in May and October. The Lyme disease spirochete Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner was detected in 12.9% of I. scapularis adults collected from domestic hosts with no history of out-of-province travel or exposure at a Lyme disease endemic area. Fifty-three isolates of B. burgdorferi were confirmed positive with polymerase chain reaction by targeting the rrf (5S)-rrl (23S) gene. Using DNA sequencing of the ribosomal species-specific rrf (5S) -rrl (23S) intergenic spacer region, all isolates belong to the pathogenic genospecies B. burgdorferi sensu stricto (s.s.). Nucleotide sequence analysis of a 218- to 220-bp amplicon fragment exhibits six cluster patterns and, collectively, these isolates branch into four phylogenetic cluster groups for both untraveled, mammalian hosts and those with travel to the northeastern United States (New Jersey and New York). Four of five geographic regions in Ontario had strain variants consisting of three different genomic cluster groups. Overall, our molecular characterization of B. burgdorferi s.s. shows genetic heterogeneity within Ontario and displays a connecting link to common strains from Lyme disease endemic areas in the northeastern United States. Moreover, our findings of B. burgdorferi in I. scapularis reveal that people and domestic animals may be exposed to Lyme disease vector ticks, which have wide-ranging distribution in eastern and central Canada.

    PMID: 16892637 [PubMed - indexed for MEDLINE]

  20. PLoS Med. 2006 Jun;3(6):e231.

    Sacred cows and sympathetic squirrels: the importance of biological diversity to human health.

    Dobson A, Cattadori I, Holt RD, Ostfeld RS, Keesing F, Krichbaum K, Rohr JR, Perkins SE, Hudson PJ.

    Department of Ecology, Evolution, and Biology, Princeton University, Princeton, New Jersey, USA. dobber@princeton.edu

    PMCID: PMC1472550 PMID: 16729846 [PubMed - indexed for MEDLINE]

  21. Infect Immun. 2006 May;74(5):3016-20.

    Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice.

    Parveen N, Cornell KA, Bono JL, Chamberland C, Rosa P, Leong JM.

    Department of Microbiology and Molecular Genetics, ICPH Building, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103-2714, USA. Parveeni@umdnj.edu

    Bgp, one of the surface-localized glycosaminoglycan-binding proteins of the Lyme disease spirochete, Borrelia burgdorferi, exhibited nucleosidase activity. Infection of SCID mice with B. burgdorferi strain N40 mutants harboring a targeted insertion in bgp and apparently retaining all endogenous plasmids revealed that Bgp is not essential for colonization of immunocompromised mice.

    PMCID: PMC1459710 PMID: 16622242 [PubMed - indexed for MEDLINE]

  22. Int J Med Microbiol. 2006 May;296 Suppl 40:17-22. Epub 2006 Mar 9.

    Strategies for reducing the risk of Lyme borreliosis in North America.

    Piesman J.

    Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, PO Box 2087, Ft. Collins, CO 80522, USA. jpiesman@cdc.gov

    The incidence of Lyme borreliosis continues to increase in the United States. In 1991, when Lyme borreliosis first became a nationally reportable disease to the Centers for Disease Control and Prevention (CDC), a total of 9470 cases were reported; in contrast, by 2002 a total of 23,763 cases were reported, >2.5x the total in 1991. Area-wide acaricides can be highly effective in killing nymphal Ixodes scapularis, with >95% of nymphs killed in studies using cyfluthrin, deltamethrin, or carbaryl. The majority of residents living in households within the area hyperendemic for Lyme borreliosis will not, however, consider the use of area-wide acaricides. A survey of communities in 4 states (Connecticut, Massachusetts, New Jersey, New York) demonstrated that <25% of the populace have used area-wide acaricides on their own property. In searching for alternative methods of reducing Lyme borreliosis risk, host-targeted methods have been proven to be effective. Newly developed methods include the use of acaricides applied to deer feeder stations. This method is called the 4-poster method and has been shown in trials to reduce populations of nymphal I. scapularis by 69%. In addition, rodent-targeted bait boxes containing fipronil have been shown to eliminate ticks on mice and negatively impact the population of questing I. scapularis and reduce the proportion of these ticks infected with Borrelia burgdorferi sensu stricto. Host eradication can also be utilized. On Monhegan Island, Maine, white-tailed deer were totally eradicated from the island from 1999 to 2000. By 2004, no immature I. scapularis could be found on rodents on Monhegan Island. Landscape management practices can also be utilized to reduce the risk of Lyme borreliosis as can personal protection procedures including regular tick checks. These practices have been nicely summarized in a new Tick Management Handbook produced by Dr. Kirby C. Stafford III with the Connecticut Agricultural Experiment Station. Although there is no magic bullet available to completely eliminate the risk of Lyme borreliosis from large geographic areas, the use of Integrated Pest Management (IPM) practices holds the prospect for reducing and managing Lyme borreliosis risk in the future.

    PMID: 16524769 [PubMed - indexed for MEDLINE]

  23. J Med Entomol. 2005 Nov;42(6):1057-62.

    Three multiplex assays for detection of Borrelia burgdorferi sensu lato and Borrelia miyamotoi sensu lato in field-collected Ixodes nymphs in North America.

    Ullmann AJ, Gabitzsch ES, Schulze TL, Zeidner NS, Piesman J.

    Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.

    Two hundred fifty New Jersey field-collected Ixodes scapularis Say ticks and 17 Colorado Ixodes spinipalpis Hadwen & Nuttall ticks were tested using three separate multiplex real-time polymerase chain reaction (PCR) assays. One assay targets the rrs-rrlA IGS region of Borrelia spp. to detect Borrelia burgdorferi sensu lato (s.l.) and Borrelia miyamotoi s.l. The second assay targets the ospA region of B. burgdorferi s.l. to detect B. burgdorferi sensu stricto (s.s.), Borrelia bissettii, and Borrelia andersonii. The final assay targets the glpQ region of B. miyamotoi s.l. to differentiate B. miyamotoi LB-2001 and Borrelia lonestari. A testing scheme combining these tests yielded 18% of tested I. scapularis ticks surveyed from New Jersey positive for B. burgdorferi s.s., 3.2% I. scapularis ticks positive for B. miyamotoi LB-2001, and 41.2% I. spinipalpis ticks positive for B. bissettii surveyed from Colorado.

    PMID: 16465748 [PubMed - indexed for MEDLINE]

  24. J Med Entomol. 2005 Nov;42(6):966-73.

    Host associations of Ixodes scapularis (Acari: Ixodidae) in residential and natural settings in a Lyme disease-endemic area in New Jersey.

    Schulze TL, Jordan RA, Schulze CJ.

    Division of Epidemiology, Environmental and Occupational Health, New Jersey Department of Health and Senior Services, Trenton 08625, USA.

    We live-trapped small mammals and flagged vegetation within wooded natural and residential landscapes to examine how any observed differences in small mammal species composition may influence Ixodes scapularis Say burdens and the abundance of host-seeking ticks. Two years of live trapping showed that Eastern chipmunks, Tamias striatus, were captured with significantly greater frequency in some residential areas than white-footed mice, Peromyscus leucopus, whereas the proportion of white-footed mouse captures was higher or similar to chipmunk captures in the undeveloped natural areas. Both mice and chipmunks seemed to adapt well to managed residential landscapes, with residential sites yielding similar or significantly greater numbers of captures compared with undeveloped sites. In areas where chipmunk captures outnumbered mice, larval tick burdens on mice were either higher or no different than in areas where few or no chipmunks were captured, in contrast to previous studies suggesting that alternate hosts should reduce larval burdens on mice. Chipmunks apparently play an important role in the Lyme disease transmission cycle in these residential settings.

    PMID: 16465736 [PubMed - indexed for MEDLINE]

  25. Vector Borne Zoonotic Dis. 2005 Winter;5(4):383-9.

    Distribution of borreliae among ticks collected from eastern states.

    Taft SC, Miller MK, Wright SM.

    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, USA.

    Lyme disease is the most commonly reported vector-borne disease in the United States and is transmitted by Borrelia burgdorferi-infected Ixodes species. The disease is typically characterized by an erythema migrans (EM) rash at the site of tick feeding. EM rashes have also been associated with feeding by Amblyomma americanum ticks despite evidence suggesting that they are incompetent vectors for Lyme disease. In 1996, a Borrelia organism only recently cultivated in the laboratory was described in A. americanum ticks and designated B. lonestari. This Borrelia is believed to be the etiologic agent of a novel Lyme-like disease, southern tick associated rash illness (STARI). This study examined ticks collected from eight eastern states to evaluate the epidemiology of B. lonestari, B. burgdorferi, and their tick hosts. Three hundred individual or small pool samples were evaluated from tick genera that included Amblyomma, Ixodes, and Dermacentor. DNA was extracted following tick homogenization and the polymerase chain reaction (PCR) was performed using primers derived from the flagellin gene that amplify sequences from both B. burgdorferi and B. lonestari. Species specific digoxigenin labeled probes were designed and used to differentiate between B. burgdorferi and B. lonestari. Borrelia DNA was detected in approximately 10% of the A. americanum and I. scapularis tick samples, but none was present in any of the Dermacentor samples tested. Positive samples were detected in ticks collected from Kentucky, Maryland, Massachusetts, New Jersey, New York, and Virginia. This is the first known report of B. lonestari from Massachusetts and New York and the first detection in I. scapularis. This suggests that B. lonestari and its putative association with STARI may be more widespread than previously thought.

    PMID: 16417434 [PubMed - indexed for MEDLINE]

  26. J Neuroimmunol. 2006 Apr;173(1-2):56-68. Epub 2006 Jan 4.

    Intrathecal antibody production in a mouse model of Lyme neuroborreliosis.

    Li L, Narayan K, Pak E, Pachner AR.

    Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S. Orange Ave., Newark, NJ 07103, USA.

    Intrathecal antibody (ITAb) production is a common feature of neurological diseases, yet very little is known about its mechanisms. Because ITAb is prominent in human Lyme neuroborreliosis (LNB), in the present study we established a mouse model of LNB to study ITAb production. We injected different strains of Borrelia burgdorferi into a variety of mouse strains by the intracerebral (i.c.) route to develop the model. Spirochetal infection and ITAb production were identified by complementary methods. This study demonstrates that the mouse model of LNB can be utilized to test hypotheses related to the mechanisms of ITAb production.

    PMID: 16387369 [PubMed - indexed for MEDLINE]

  27. Infect Immun. 2005 Nov;73(11):7669-76.

    Cardiac apoptosis in severe relapsing fever borreliosis.

    Londoño D, Bai Y, Zückert WR, Gelderblom H, Cadavid D.

    Department of Neurology and Neuroscience and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, MSB H506, Newark, NJ 07103, USA.

    Previous studies revealed that the heart suffers significant injury during experimental Lyme and relapsing fever borreliosis when the immune response is impaired (D. Cadavid, Y. Bai, E. Hodzic, K. Narayan, S. W. Barthold, and A. R. Pachner, Lab. Investig. 84:1439-1450, 2004; D. Cadavid, T. O'Neill, H. Schaefer, and A. R. Pachner, Lab. Investig. 80:1043-1054, 2000; and D. Cadavid, D. D. Thomas, R. Crawley, and A. G. Barbour, J. Exp. Med. 179:631-642, 1994). To investigate cardiac injury in borrelia carditis, we used antibody-deficient mice persistently infected with isogenic serotypes of the relapsing fever agent Borrelia turicatae. We studied infection in hearts 1 to 2 months after inoculation by TaqMan reverse transcription-PCR and immunohistochemistry (IHC) and inflammation by hematoxylin and eosin and trichrome staining, IHC, and in situ hybridization (ISH). We studied apoptosis by terminal transferase-mediated DNA nick end labeling assay and measured expression of apoptotic molecules by RNase protection assay, immunofluorescence, and immunoblot. All antibody-deficient mice, but none of the immunocompetent controls, developed persistent infection of the heart. Antibody-deficient mice infected with serotype 2 had more severe cardiac infection and injury than serotype 1-infected mice. The injury was more severe around the base of the heart and pericardium, corresponding to sites of marked infiltration by activated macrophages and upregulation of interleukin-6 (IL-6). Infected hearts showed evidence of apoptosis of macrophages and cardiomyocytes as well as significant upregulation of caspases, most notably caspase-1. We conclude that persistent infection with relapsing fever borrelias causes significant loss of cardiomyocytes associated with prominent infiltration by activated macrophages, upregulation of IL-6, induction of caspase-1, and apoptosis.

    PMCID: PMC1273893 PMID: 16239571 [PubMed - indexed for MEDLINE]

  28. Int J Epidemiol. 2005 Dec;34(6):1345-7. Epub 2005 Sep 2.

    Commentary: 'What's in a name? That which we call a rose by any other name would smell as sweet.' Shakespeare W. Romeo and Juliet, II, ii(47-48).

    Sigal LH, Hassett AL.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. leonard.sigal@bms.com

    Comment on: Int J Epidemiol. 2005 Dec;34(6):1340-5.

    PMID: 16143662 [PubMed - indexed for MEDLINE]

  29. J Med Entomol. 2005 May;42(3):450-6.

    Relative encounter frequencies and prevalence of selected Borrelia, Ehrlichia, and Anaplasma infections in Amblyomma americanum and Ixodes scapularis (Acari: Ixodidae) ticks from central New Jersey.

    Schulze TL, Jordan RA, Schulze CJ, Mixson T, Papero M.

    Freehold Area Health Department, Municipal Plaza, Schanck Rd., Freehold, NJ 07728, USA.

    To evaluate their relative importance in tick-borne disease transmission in New Jersey, host-seeking Amblyomma americanum (L.) and Ixodes scapularis Say adults and nymphs were collected during spring activity periods in 2003 and 2004 to determine relative frequencies at which these ticks were encountered from an area known to be hyperendemic for Lyme disease. Although similar numbers of the two species were encountered during early spring of both years, A. americanum were encountered more often later in the season and exhibited a longer activity period than I. scapularis. A. americanum nymphs were collected at frequencies between 2.6 and 7.3 times higher than I. scapularis nymphs. Polymerase chain reaction (PCR) analysis of 121 A. americanum adults yielded infection prevalences of 9.1% for Borrelia lonestari, 12.3% for Ehrlichia chaffeenensis, and 8.2% for E. ewingii, and coinfection prevalences of 4.1% for E. chaffeensis/E. ewingii and 0.8% for E. chaffeensis/B. lonestari. Infection prevalences in 147 I. scapularis adults were 50.3% for B. burgdorferi, 6.1% for Anaplasma (Ehrlichia) phagocytophilum, and 1.4% for a recently described novel Borrelia species, whereas the coinfection prevalences were 2.7% for B. burgdorferi/A. phagocytophilum, 0.7% for B. burgdorferi/novel Borrelia, and 0.7% for A. phagocytophilum/novel Borrelia. The B. burgdorferi infection prevalence in I. scapularis was considerably higher than that in A. americanum. However, the higher A. americanum encounter frequencies compared with I. scapularis may result in increased risk of acquiring exposure to A. americanum-transmitted pathogens. The potential public health implications of these results are discussed.

    PMID: 15962799 [PubMed - indexed for MEDLINE]

  30. Ann Neurol. 2005 Jun;57(6):813-23.

    The nervous system as ectopic germinal center: CXCL13 and IgG in lyme neuroborreliosis.

    Narayan K, Dail D, Li L, Cadavid D, Amrute S, Fitzgerald-Bocarsly P, Pachner AR.

    University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.

    Lyme neuroborreliosis (LNB) is a chronic infection in which B-cell activation, plasma cell infiltration, and enhanced Ig production in infected tissue are prominent feature. However, little is known about how B cells and plasma cells invade and persist in target organs. To assess this issue, we developed real-time PCR measurements of IgG and CXCL13 production. We used these RNA assays and specific enzyme-linked immunosorbent assays for protein and demonstrated that human peripheral blood mononuclear cells (PBMCs), stimulated by Borrelia burgdorferi sonicate, produced CXCL13 and IgG. Magnetic separation of PBMC populations and flow cytometry showed that CXCL13 is produced by dendritic cells. We then measure the expression of CXCL13 and IgG in tissues and correlated the expression of these host genes with spirochetal load. We also measured expression of dbpA and BBK32, two spirochetal genes important in chronic infection. There was a strong correlation between host immune response gene expression (CXCL13 and IgG) and spirochetal load. Immunohistochemistry of infected nonhuman primates tissue confirmed that CXCL13 is expressed in the nervous system. We conclude that persistent production of CXCL13 and IgG within infected tissue, two characteristics of ectopic germinal centers, are definitive features of LNB.

    PMID: 15929033 [PubMed - indexed for MEDLINE]

  31. J Clin Microbiol. 2005 Feb;43(2):850-6.

    Evidence of Borrelia autoimmunity-induced component of Lyme carditis and arthritis.

    Raveche ES, Schutzer SE, Fernandes H, Bateman H, McCarthy BA, Nickell SP, Cunningham MW.

    Department of Pathology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, 185 S. Orange Ave., Newark, NJ 07103, USA.

    We investigated the possibility that manifestations of Lyme disease in certain hosts, such as arthritis and carditis, may be autoimmunity mediated due to molecular mimicry between the bacterium Borrelia burgdorferi and self-components. We first compared amino acid sequences of Streptococcus pyogenes M protein, a known inducer of antibodies that are cross-reactive with myosin, and B. burgdorferi and found significant homologies with OspA protein. We found that S. pyogenes M5-specific antibodies and sera from B. burgdorferi-infected mice reacted with both myosin and B. burgdorferi proteins by Western blots and enzyme-linked immunosorbent assay. To investigate the relationship between self-reactivity and the response to B. burgdorferi, NZB mice, models of autoimmunity, were infected. NZB mice infected with B. burgdorferi developed higher degrees of joint swelling and higher anti-B. burgdorferi immunoglobulin M cross-reactive responses than other strains with identical major histocompatibility complex (DBA/2 and BALB/c). These studies reveal immunological cross-reactivity and suggest that B. burgdorferi may share common epitopes which mimic self-proteins. These implications could be important for certain autoimmunity-susceptible individuals or animals who become infected with B. burgdorferi.

    PMCID: PMC548028 PMID: 15695691 [PubMed - indexed for MEDLINE]

  32. Curr Treat Options Neurol. 2005 Mar;7(2):167-170.

    The Therapy of Lyme Neuroborreliosis.

    Pachner AR.

    Department of Neurology, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA. pachner@umdnj.edu.

    The challenge for the neurologist in the treatment of Lyme neuroborreliosis is not in the treatment per se, but in the diagnosis. Neurological manifestations of Lyme disease can present in many forms, and diagnostic techniques which detect the spirochete directly; the culture or polymerase chain reaction of the spirochete in cerebrospinal fluid, are of disappointingly low yield. Therefore, the diagnosis is frequently not easy. After the diagnosis is made, antibiotic therapy is straightforward; Lyme neuroborreliosis should be treated with at least 2 weeks of antibiotics. In the United States, intravenous therapy with ceftriaxone or penicillin for 2 weeks is the standard, whereas in Europe oral doxycycline therapy is commonly administered. Either is effective, and my choice of therapy generally depends on the patient. Many patients have symptoms which continue after antibiotic therapy referable to persistent inflammation, and, for those patients, I will commonly prescribe nonsteroidal anti-inflammatory medications.

    PMID: 15676120 [PubMed - as supplied by publisher]

  33. Lab Invest. 2004 Nov;84(11):1439-50.

    Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi.

    Cadavid D, Bai Y, Hodzic E, Narayan K, Barthold SW, Pachner AR.

    Department of Neurology and Neuroscience, UMDNJ-New Jersey Medical School, Newark, NJ, USA. Cadavidi@umdnj.edu

    To investigate cardiac involvement in the non-human primate (NHP) model of Lyme disease, we inoculated 39 adult Macaca mulatta with Borrelia burgdorferi sensu stricto strains N40 (BbN40) by needle (N=22, 14 immunocompetent (IC), seven permanently immunosuppressed (IS), and four transiently immunosuppressed (TISP)) or by tick-bite (N=4, all TISP) or strain 297 (Bb297) by needle (N=2 IS), or with B. garinii strains Pbi (N=4, 2 TISP and 2 IS), 793 (N=2, TISP) or Pli (N=2, TISP). Five uninfected NHPs were used as controls. Infection and inflammation was studied in the hearts and the aorta removed at necropsy 2-32 months after inoculation by (1) H&E and trichrome-staining; (2) immunohistochemistry and digital image analysis; (3) Western blot densitometry; and (4) TaqMan RT-PCR. All NHPs inoculated with BbN40 became infected and showed carditis at necropsy. The predominant cells were T cells, plasma cells, and macrophages. There was increased IgG and IgM in the heart independent of immunosuppression. The B-cell chemokine BLC was significantly increased in IS-NHPs. There was increased deposition of the complement membrane attack complex (MAC) in TISP and IS-NHPs. The spirochetal load was very high in all BbN40-inoculated IS-NHPs but minimal if any in IC or TISP NHPs. Double-immunostaining revealed that many spirochetes in the heart of BbN40-IS NHPs had MAC on their membranes. We conclude that carditis in NHPs infected with B. burgdorferi is frequent and can persist for years but is mild unless they are immunosupressed.

    PMID: 15448708 [PubMed - indexed for MEDLINE]

  34. Ann Neurol. 2004 Sep;56(3):361-70.

    Genotype determines phenotype in experimental Lyme borreliosis.

    Pachner AR, Dail D, Bai Y, Sondey M, Pak L, Narayan K, Cadavid D.

    University of Medicine and Dentristry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA. pachner@umdnj.edu

    Borrelia burgdorferi sensu lato, the causative organism of Lyme borreliosis, is a heterogeneous group of spirochetes, consisting of at least three pathogenic species. To test the hypothesis that the genetic heterogeneity is the reason for the clinical differences, we investigated whether the experimental disease induced by European isolates is different from that induced by American isolates. Two American isolates of species B. burgdorferi sensu stricto were compared with three European isolates, two of species B. garinii, and one of species B. afzelii. The patterns of infection, immunity, and inflammation induced by the different species was distinctive. Inflammatory cells and levels of antibody in B. garinii- and B. afzelii-infected animals were lower than in B. burgdorferi s.s.-infected animals, whereas levels of spirochetal infection in the skin and nervous system were higher in the former group of animals. These data demonstrate that B. burgdorferi s.s. strains are more infective and inflammatory, whereas B. garinii and B. afzelii strains can survive the adaptive immune response to a greater degree and persist at greater numbers in the skin and nervous system. The results explain to a large extent the disparities between LNB in humans in the United States and Europe.

    PMID: 15349863 [PubMed - indexed for MEDLINE]

  35. Lab Invest. 2004 Feb;84(2):160-72.

    Spinal cord involvement in the nonhuman primate model of Lyme disease.

    Bai Y, Narayan K, Dail D, Sondey M, Hodzic E, Barthold SW, Pachner AR, Cadavid D.

    Department of Neurology and Neuroscience, and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.

    Lyme borreliosis is a multisystemic disease caused by infection with various genospecies of the spirochete Borrelia burgdorferi. The organs most often affected are the skin, joints, the heart, and the central and peripheral nervous systems. Multiple neurological complications can occur, including aseptic meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and peripheral neuropathy. To investigate spinal cord involvement in the nonhuman primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta with B. burgdorferi sensu strictu strains N40 by needle (N=9) or by tick (N=4) or 297 by needle (N=2), or with B. burgdorferi genospecies garinii strains Pbi (N=4), 793 (N=2), or Pli (N=4) by needle. Immunosuppression either transiently (TISP) or permanently (IS) was used to facilitate establishment of infection. Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and eosin staining was used to study inflammation, and immunohistochemistry and digital image analysis to measure inflammation and localize spirochetes. The spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord parenchyma itself. T cells and plasma cells were the predominant inflammatory cells. Significantly increased amounts of IgG, IgM, and C1q were found in inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma. C1q mRNA expression was significantly increased in inflamed spinal cord. This is the first comprehensive study of spinal cord involvement in Lyme borreliosis.

    PMID: 14688796 [PubMed - indexed for MEDLINE]

  36. J Med Entomol. 2003 Jul;40(4):555-8.

    Prevalence of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Ixodes scapularis (Acari: Ixodidae) adults in New Jersey, 2000-2001.

    Schulze TL, Jordan RA, Hung RW, Puelle RS, Markowski D, Chomsky MS.

    New Jersey Department of Health and Senior Services, P.O. Box 369, Trenton, NJ 08625, USA. tlschulze@monmouth.com

    Using polymerase chain reaction, we analyzed 529 Ixodes scapularis Say adults collected from 16 of New Jersey's 21 counties for the presence of Borrelia burgdorferi, the etiological agent of Lyme disease. Overall, 261 (49.3%) were positive. B. burgdorferi was detected in ticks obtained from each county and from 53 of the 58 (93.1%) municipalities surveyed. The observed statewide prevalence in New Jersey is similar to those reported from other northeastern and mid-Atlantic states.

    PMID: 14680126 [PubMed - indexed for MEDLINE]

  37. Infect Immun. 2003 Dec;71(12):7087-98.

    Infection and inflammation in skeletal muscle from nonhuman primates infected with different genospecies of the Lyme disease spirochete Borrelia burgdorferi.

    Cadavid D, Bai Y, Dail D, Hurd M, Narayan K, Hodzic E, Barthold SW, Pachner AR.

    Department of Neuroscience, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA. Cadavidi@umdnj.edu

    Lyme borreliosis is a multisystemic disease caused by various genospecies of the spirochete Borrelia burgdorferi. To investigate muscle involvement in the nonhuman primate (NHP) model of Lyme disease, 16 adult Macaca mulatta animals inoculated with strain N40 of B. burgdorferi sensu strictu by syringe or by tick bite or with strain Pbi of B. burgdorferi genospecies garinii by syringe were studied. Animals were necropsied while immunosuppressed on day 50 (two animals each inoculated with B. burgdorferi N40 by syringe and with B. garinii Pbi by syringe) or on day 90, 40 days after immunosuppression had been discontinued (four animals each inoculated with strain N40 by syringe, with strain N40 by tick bite, and with strain Pbi by syringe). Skeletal muscles removed at necropsy were studied by (i) microscopic examination of hematoxylin-eosin-stained sections for inflammation and tissue injury; (ii) immunohistochemical and digital image analyses for antibody and complement deposition and cellular inflammation; (iii) Western blot densitometry for the presence of antibodies; and (iv) reverse transcription-PCR for measurement of the spirochetal load or C1q (the first component of the complement cascade) synthesis. The results showed that N40 was more infectious for NHPs than Pbi. NHPs inoculated with N40 but not with Pbi developed myositis. The inflammation in skeletal muscle was more severe in NHPs inoculated with N40 by syringe than in those inoculated by tick bite. The predominant cells in the inflammatory infiltrate were T cells and plasma cells. The deposition of antibody and complement in inflamed muscles from N40-inoculated NHPs was significantly higher than that in Pbi-inoculated NHPs. The spirochetal load was very high in the two N40-inoculated NHPs examined while they were immunosuppressed but decreased to minimal levels in the NHPs when immunocompetence was restored. We conclude that myositis can be a prominent feature of Lyme borreliosis depending on the infecting organism and host immune status.

    PMCID: PMC308929 PMID: 14638799 [PubMed - indexed for MEDLINE]

  38. Appl Environ Microbiol. 2003 Aug;69(8):4561-5.

    Real-time PCR for simultaneous detection and quantification of Borrelia burgdorferi in field-collected Ixodes scapularis ticks from the Northeastern United States.

    Wang G, Liveris D, Brei B, Wu H, Falco RC, Fish D, Schwartz I.

    Department of Microbiology and Immunology. Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.

    The density of spirochetes in field-collected or experimentally infected ticks is estimated mainly by assays based on microscopy. In this study, a real-time quantitative PCR (qPCR) protocol targeting the Borrelia burgdorferi-specific recA gene was adapted for use with a Lightcycler for rapid detection and quantification of the Lyme disease spirochete, B. burgdorferi, in field-collected Ixodes scapularis ticks. The sensitivity of qPCR for detection of B. burgdorferi DNA in infected ticks was comparable to that of a well-established nested PCR targeting the 16S-23S rRNA spacer. Of the 498 I. scapularis ticks collected from four northeastern states (Rhode Island, Connecticut, New York, and New Jersey), 91 of 438 (20.7%) nymphal ticks and 15 of 60 (25.0%) adult ticks were positive by qPCR assay. The number of spirochetes in individual ticks varied from 25 to 197,200 with a mean of 1,964 spirochetes per nymphal tick and a mean of 5,351 spirochetes per adult tick. No significant differences were found in the mean numbers of spirochetes counted either in nymphal ticks collected at different locations in these four states (P = 0.23 by one-way analysis of variance test) or in ticks infected with the three distinct ribosomal spacer restriction fragment length polymorphism types of B. burgdorferi (P = 0.39). A high degree of spirochete aggregation among infected ticks (variance-to-mean ratio of 24,877; moment estimate of k = 0.279) was observed. From the frequency distribution data and previously published transmission studies, we estimated that a minimum of 300 organisms may be required in a host-seeking nymphal tick to be able to transmit infection to mice while feeding on mice. These data indicate that real-time qPCR is a reliable approach for simultaneous detection and quantification of B. burgdorferi infection in field-collected ticks and can be used for ecological and epidemiological surveillance of Lyme disease spirochetes.

    PMCID: PMC169074 PMID: 12902243 [PubMed - indexed for MEDLINE]

  39. Vector Borne Zoonotic Dis. 2002 Winter;2(4):265-73.

    Epidemiology and impact of coinfections acquired from Ixodes ticks.

    Belongia EA.

    Epidemiology Research Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, USA. belongia.edward@mcrf.mfldclin.edu

    Ixodes scapularis and other ticks in the Ixodes ricinus complex may transmit multiple pathogens, but research on coinfections has been limited. Coinfections occur with varying frequency in ticks, but single infections are more common than dual infections. The proportion of I. scapularis or I. ricinus ticks coinfected with both Borrelia burgdorferi sensu lato and Anaplasma phagocytophila is generally low, ranging from < 1% to 6% in six geographic areas. A higher prevalence of tick coinfection (26%) has been reported in Westchester County, New York. Genetic variants of the human disease-causing strain of A. phagocytophila are present in some tick populations, and they may affect the risk of coinfection or clinical illness. The proportion of Ixodes ticks coinfected with B. burgdorferi and Babesia microti has ranged from 2% in New Jersey to 19% on Nantucket Island, Massachusetts. In humans, cross-sectional seroprevalence studies have found markers of dual infection in 9-26% of patients with a tick-borne infection, but such studies often fail to distinguish simultaneous coinfection from sequential infections. Several studies have prospectively assessed the occurrence of acute coinfection. Among patients with a confirmed tick-borne infection, coinfection rates as high as 39% have been reported. The most commonly recognized coinfection in most of the eastern United States is Lyme borreliosis (LB) and babesiosis, accounting for approximately 80% of coinfections. LB and human granulocytic ehrlichiosis coinfections are less common, occurring in 3-15% of patients with a tick-borne infection in Connecticut or Wisconsin. Studies of clinical outcomes suggest that patients with acute Babesia coinfection have more severe symptoms and a longer duration of illness than patients with LB alone, but the risk of spirochete dissemination is similar. Coinfections can modify the immune response and alter the severity of arthritis in animal models. Future coinfection research should focus on long-term clinical outcomes, the role of genetic variants, immunologic effects, and the potential role of Bartonella species as tick-borne pathogens.

    PMID: 12804168 [PubMed - indexed for MEDLINE]

  40. J Mol Microbiol Biotechnol. 2003;5(3):167-71.

    Early OspA immune complex formation in animal models of Lyme disease.

    Schutzer SE, Luan J.

    Department of Medicine, Division of Allergy and Immunology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA. schutzer@umdnj.edu

    Infection with Borrelia burgdorferi, the cause of Lyme disease, has been accompanied by a puzzling delayed antibody (Ab) response to B. burgdorferi antigens (Ags) including the abundant organism-specific outer surface proteins, such as the 31-kD OspA. In humans the response to nonspecific B. burgdorferi Ags has required 3-6 weeks. The response to OspA has rarely been detected by conventional methodology until months after infection, despite demonstrable T cell reactivity. Tick inoculation and low-dose intradermal inoculation animal models have been characterized by a comparable response to OspA. Using more sensitive biotin-avidin immunoblots and immune complex (IC) dissociation techniques, we demonstrated in humans that Ab to OspA is formed early but may remain at low levels or bound in IC. To see if this was a universal biologic response, animal models were analyzed by these methods. The results with mice, monkeys and rabbits show that IC Ab to OspA may be detected at the onset of infection. The data suggest that these animal models may be used to understand the immune response to B. burgdorferi and the pathogenesis of Lyme disease. With attention to unique B. burgdorferi Ags, these results are likely to have both clinical and diagnostic importance. Copyright 2003 S. Karger AG, Basel

    PMID: 12766346 [PubMed - indexed for MEDLINE]

  41. Vector Borne Zoonotic Dis. 2001 Spring;1(1):21-34.

    A relapsing fever group spirochete transmitted by Ixodes scapularis ticks.

    Scoles GA, Papero M, Beati L, Fish D.

    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034, USA.

    A species of Borrelia spirochetes previously unknown from North America has been found to be transmitted by Ixodes scapularis ticks. Infected ticks are positive for Borrelia spp. by DFA test but negative for Borrelia burgdorferi by polymerase chain reaction (PCR) using species-specific primers for 16S rDNA, outer surface protein A, outer surface protein C, and flagellin genes. A 1,347-bp portion of 16S rDNA was amplified from a pool of infected nymphs, sequenced, and compared with the homologous fragment from 26 other species of Borrelia. The analysis showed 4.6% pairwise difference from B. burgdorferi, with the closest relative being Borrelia miyamotoi (99.3% similarity) reported from Ixodes persulcatus in Japan. Phylogenetic analysis showed the unknown Borrelia to cluster with relapsing fever group spirochetes rather than with Lyme disease spirochetes. A 764-bp fragment of the flagellin gene was also compared with the homologous fragment from 24 other Borrelia species. The flagellin sequence of B. burgdorferi was 19.5% different from the unknown Borrelia and showed 98.6% similarity with B. miyamotoi. A pair of PCR primers specifically designed to amplify a 219-bp fragment of the flagellin gene from this spirochete was used to survey field-collected I. scapularis nymphs from five northeastern states (Connecticut, Rhode Island, New York, New Jersey, and Maryland). Positive results were obtained in 1.9-2.5% of 712 nymphs sampled from four states but in none of 162 ticks collected from Maryland. Transovarial transmission was demonstrated by PCR of larval progeny from infected females with filial infection rates ranging from 6% to 73%. Transstadial passage occurred from larvae through adults. Vertebrate infection was demonstrated by feeding infected nymphs on Peromyscus leucopus mice and recovering the organism from uninfected xenodiagnostic larvae fed 7-21 days later. Considering the frequency of contact between I. scapularis and humans, further work is needed to determine the potential public health significance of yet another zoonotic agent transmitted by this tick species.

    PMID: 12653133 [PubMed - indexed for MEDLINE]

  42. Cytokine. 2002 Sep 21;19(6):297-307.

    Increased expression of B-lymphocyte chemoattractant, but not pro-inflammatory cytokines, in muscle tissue in rhesus chronic Lyme borreliosis.

    Pachner AR, Dail D, Narayan K, Dutta K, Cadavid D.

    Department of Neurosciences, University of Medicine and Dentistry of New Jersey--New Jersey Medical School, Newark, NJ 07103, USA.

    Inflammation in skeletal muscle is a consistent feature of Lyme borreliosis, both in the human disease and experimental models. This study had two goals: to evaluate the expression of selected pro-inflammatory and chemokine genes in skeletal muscle in the Rhesus model of Lyme disease, and to identify unexpected cytokine genes involved in Lyme myositis. Two different techniques for measuring cytokine messenger RNA (mRNA) levels were used to achieve these goals: gene expression microarrays and. real-time RT-PCR (Taqman). Muscle from necropsies and biopsies were used, and were obtained from both infected and uninfected non-human primates (NHPs). Although many cytokines were found expressed in muscle tissue, pro-inflammatory cytokines commonly associated with inflammation were not consistently upregulated in infected muscles relative to uninfected muscles. However, B-lymphocyte chemoattractant (BLC), a chemokine implicated in the trafficking of B-cells into tissue, was increased in expression. This study is the first to extensively characterize cytokine gene expression in chronically inflamed tissue in Lyme borreliosis.

    PMID: 12421572 [PubMed - indexed for MEDLINE]

  43. Clin Diagn Lab Immunol. 2002 Nov;9(6):1348-55.

    Humoral immune response associated with lyme borreliosis in nonhuman primates: analysis by immunoblotting and enzyme-linked immunosorbent assay with sonicates or recombinant proteins.

    Pachner AR, Dail D, Li L, Gurey L, Feng S, Hodzic E, Barthold S.

    Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA. pachner@umdnj.edu

    The immune response to Borrelia burgdorferi, the causative agent of Lyme disease, is complex. We studied the immunoglobulin M (IgM) and IgG antibody response to N40Br, a sensu stricto strain, in the rhesus macaque(nonhuman primate [NHP]) model of infection to identify the spirochetal protein targets of specific antibody. Antigens used in enzyme-linked immunosorbent assays were whole-cell sonicates of the spirochete and recombinant proteins of B. burgdorferi. Immunoblotting with a commercially available strip and subsequent quantitative densitometry of the bands were also used. Sera from four different groups of NHPs were used: immunocompetent, transiently immunosuppressed, extended immunosuppressed, and uninfected. In immunocompetent and transiently immunosuppressed NHPs, there was a strong IgM and IgG response. Major proteins for the early IgM response were P39 and P41 and recombinant BmpA and OspC. Major proteins for the later IgG response were P39, P41, P18, P60, P66, and recombinant BmpA and DbpA. There was no significant response in the NHPs to recombinant OspA or to Arp, a 37-kDa protein that elicits an antibody response during infection in mice. Most antibody responses, except for that to DbpA, were markedly diminished by prolonged dexamethasone treatment. This study supports the hypothesis that recombinant proteins may provide a useful adjunct to current diagnostic testing for Lyme borreliosis.

    PMCID: PMC130097 PMID: 12414773 [PubMed - indexed for MEDLINE]

  44. Environ Health Perspect. 2002 Aug;110 Suppl 4:607-11.

    Contributions of societal and geographical environments to "chronic Lyme disease": the psychopathogenesis and aporology of a new "medically unexplained symptoms" syndrome.

    Sigal LH, Hassett AL.

    Division of Rheumatology and Connective Tissue Research, Department of Medicine, Lyme Disease Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA. sigallh@umdnj.edu

    Comment in: Environ Health Perspect. 2003 Feb;111(2):A77; author reply A77. Environ Health Perspect. 2003 Feb;111(2):A76; author reply A77.

    Lyme disease is a relatively well-described infectious disease with multisystem manifestations. Because of confusion over conflicting reports, anxiety related to vulnerability to disease, and sensationalized and inaccurate lay media coverage, a new syndrome, "chronic Lyme disease," has become established. Chronic Lyme disease is the most recent in a continuing series of "medically unexplained symptoms" syndromes. These syndromes, such as fibromyalgia, chronic fatigue syndrome, and multiple chemical sensitivity, meet the need for a societally and morally acceptable explanation for ill-defined symptoms in the absence of objective physical and laboratory findings. We describe factors involved in the psychopathogenesis of chronic Lyme disease and focus on the confusion and insecurity these patients feel, which gives rise to an inability to adequately formulate and articulate their health concerns and to deal adequately with their medical needs, a state of disorganization termed aporia.

    PMCID: PMC1241213 PMID: 12194894 [PubMed - indexed for MEDLINE]

  45. Acta Paediatr Taiwan. 2002 May-Jun;43(3):162-5.

    Lyme disease in childhood: report of one case.

    Chung YC, Tsai HY, Shih CM, Chao LL, Lin RY.

    Department of Pediatrics, Taipei Municipal Ho-Ping Hospital, Taiwan. tsaichristina@yahoo.com

    We report a pediatric patient of Lyme disease in Taiwan, confirmed by laboratory tests. An 8-year-old overseas Chinese girl from New Jersey, USA, visited our dermatological clinic with joint pain and multiple expanding annular erythema rashes (measured up to 17x10 cm) for three days. Lyme disease was diagnosed by the presence of the antibody against Borrelia burgdorferi. The skin lesions and arthralgia were resolved after amoxicillin treatment, and she got well in the following one year. This presented work tries to remind physicians to be aware of Lyme disease in Taiwan, particularly for children or young people with recurrent expanding annular skin rashes and chronic arthralgia of undetermined causes.

    PMID: 12148968 [PubMed - indexed for MEDLINE]

  46. Vet Ther. 2002 Spring;3(1):64-71.

    Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs.

    Endris RG, Cooke D, Amodie D, Sweeney DL, Katz TL.

    Schering-Plough Animal Health Corp., Union, New Jersey 07083, USA.

    Two topically applied spot-on products used for flea and tick control on dogs, 65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe. Eighteen dogs were evenly and randomly allocated to the following treatments: 1) 65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical application of the assigned product in accordance with product label directions on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for 2 hours to 50 unfed, adult ticks in a cage with a carpet that covered approximately 70% of the floor area. After the exposure period, dogs were removed from the cages and live and dead ticks were counted on the dogs and in the cages. The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated with 65% permethrin (P <.0001 versus controls and selamectin), compared with 10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9% repellency for selamectin (P >.05 versus controls).

    PMID: 12050829 [PubMed - indexed for MEDLINE]

  47. Cell Mol Neurobiol. 2001 Oct;21(5):477-95.

    H9724, a monoclonal antibody to Borrelia burgdorferi's flagellin, binds to heat shock protein 60 (HSP60) within live neuroblastoma cells: a potential role for HSP60 in peptide hormone signaling and in an autoimmune pathogenesis of the neuropathy of Lyme disease.

    Sigal LH, Williams S, Soltys B, Gupta R.

    Department of Medicine, Robert Wood Johnson Medical School. University of Medicine and Dentistry of New Jersey, USA. sigallh@umdnj.edu

    Although Borrelia burgdorferi, the causative agent of Lyme disease, is found at the site of many disease manifestations, local infection may not explain all its features. B. burgdorferi's flagellin cross-reacts with a component of human peripheral nerve axon, previously identified as heat shock protein 60 (HSP60). The cross-reacting epitopes are bound by a monoclonal antibody to B. burgdorferi's flagellin, H9724. Addition of H9724 to neuroblastoma cell cultures blocks in vitro spontaneous and peptide growth-factor-stimulated neuritogenesis. Withdrawal of H9724 allows return to normal growth and differentiation. Using electron microscopy, immunoprecipitation and immunoblotting, and FACS analysis we sought to identify the site of binding of H9724, with the starting hypotheses that the binding was intracellular and not identical to the binding site of II-13, a monoclonal anti-HSP60 antibody. The current studies show that H9724 binds to an intracellular target in cultured cells with negligible, if any, surface binding. We previously showed that sera from patients with neurological manifestations of Lyme disease bound to human axons in a pattern identical to H9724's binding; these same sera also bind to an intracellular neuroblastoma cell target. II-13 binds to a different HSP60 epitope than H9724: II-13 does not modify cellular function in vitro. As predicted, II-13 bound to mitochondria, in a pattern of cellular binding very different from H9724, which bound in a scattered cytoplasmic, nonorganelle-related pattern. H9724's effect is the first evidence that HSP60 may play a role in peptide-hormone-receptor function and demonstrates the modulatory potential of a monoclonal antibody on living cells.

    PMID: 11860186 [PubMed - indexed for MEDLINE]

  48. Immunol Rev. 2001 Oct;183:186-204.

    The rhesus model of Lyme neuroborreliosis.

    Pachner AR, Gelderblom H, Cadavid D.

    Neurosciences, UMDNJ - New Jersey Medical School, Newark, NJ, USA.

    Erratum in: Immunol Rev. 2002 Sep;187:139.

    Similarity of pathology and disease progression make the non-human primate (NHP) model of Lyme neuroborreliosis appropriate and valuable. In the NHP model of Lyme neuroborreliosis, spirochetal density in the nervous system and other tissues has been measured by polymerase chain reaction and correlated to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid and to inflammation in tissues. Despite the demonstrable presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, only minor inflammation of the central nervous system occurs, though inflammation can be demonstrated in other tissues. Infected animals also develop anti-Borrelia burgdorferi antibody in the serum, although increased amplitude of antibody is not predictive of higher levels of infection. The NHP model continues to provide important insight into the disease process in humans.

    PMID: 11782257 [PubMed - indexed for MEDLINE]

  49. Arch Neurol. 2001 Sep;58(9):1357-63.

    Concurrent infection of the central nervous system by Borrelia burgdorferi and Bartonella henselae: evidence for a novel tick-borne disease complex.

    Eskow E, Rao RV, Mordechai E.

    Hunterdon Medical Center, Flemington, NJ, USA.

    Comment in: Arch Neurol. 2001 Sep;58(9):1345-7.

    OBJECTIVES: To investigate Bartonella henselae as a potential human tick-borne pathogen and to evaluate its role as a coinfecting agent of the central nervous system in the presence of neuroborreliosis. DESIGN: Case report study. SETTING: A primary health care center in Flemington, NJ, and the Department of Research and Development at Medical Diagnostic Laboratories LLC in Mt Laurel, NJ. SUBJECTS: Two male patients (aged 14 and 36 years) and 2 female patients (aged 15 and 30 years, respectively) with a history of tick bites and Lyme disease. MAIN OUTCOME MEASURES: Laboratory and diagnostic findings before and after antimicrobial therapy. RESULTS: Patients residing in a Lyme-endemic area of New Jersey with ongoing symptoms attributed to chronic Lyme disease were evaluated for possible coinfection with Bartonella species. Elevated levels of B henselae-specific antibodies were found in these patients using the immunofluorescent assay. Bartonella henselae-specific DNA was detected in their blood. None of these patients exhibited the clinical characteristics of cat-scratch disease. Findings of cerebrospinal fluid analysis revealed the presence of both B henselae- and Borrelia burgdorferi-specific DNA. Bartonella henselae-specific DNA was also detected in live deer ticks obtained from the households of 2 of these patients. CONCLUSIONS: Our data implicate B henselae as a potential human tick-borne pathogen. Patients with a history of neuroborreliosis who have incomplete resolution of symptoms should be evaluated for B henselae infection.

    PMID: 11559306 [PubMed - indexed for MEDLINE]

  50. Ann Neurol. 2001 Sep;50(3):330-8.

    Central and peripheral nervous system infection, immunity, and inflammation in the NHP model of Lyme borreliosis.

    Pachner AR, Cadavid D, Shu G, Dail D, Pachner S, Hodzic E, Barthold SW.

    Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark 07103, USA. pachner@umdnj.edu

    The relationship between chronic infection, antispirochetal immunity, and inflammation is unknown in Lyme neuroborreliosis. In the nonhuman primate model of Lyme neuroborreliosis, we measured spirochetal density in the nervous system and other tissues by polymerase chain reaction and correlated these values to anti-Borrelia burgdorferi antibody in the serum and cerebrospinal fluid, and to inflammation in tissues. Despite substantial presence of Borrelia burgdorferi, the causative agent of Lyme borreliosis, in the central nervous system, only minor inflammation was present there, though skeletal and cardiac muscle, which contained similar levels of spirochete, were highly inflamed. Anti-Borrelia burgdoferi antibody was present in the cerebrospinal fluid but was not selectively concentrated. All infected animals developed anti-Borrelia burgdorferi antibody in the serum, but increased amplitude of antibody was not predictive of higher levels of infection. These data demonstrate that Lyme neuroborreliosis is a persistent infection, that spirochetal presence is a necessary but not sufficient condition for inflammation, and that antibody measured in serum may not predict the severity of infection.

    PMID: 11558789 [PubMed - indexed for MEDLINE]

  51. J Clin Microbiol. 2001 Sep;39(9):3213-21.

    Use of serum immune complexes in a new test that accurately confirms early Lyme disease and active infection with Borrelia burgdorferi.

    Brunner M, Sigal LH.

    Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

    The present recommendation for serologic confirmation of Lyme disease (LD) calls for immunoblotting in support of positive or equivocal ELISA. Borrelia burgdorferi releases large quantities of proteins, suggesting that specific antibodies in serum might be trapped in immune complexes (ICs), rendering the antibodies undetectable by standard assays using unmodified serum. Production of ICs requires ongoing antigen production, so persistence of IC might be a marker of ongoing or persisting infection. We developed an immunoglobulin M (IgM) capture assay (EMIBA) measuring IC-derived IgM antibodies and tested it using three well-defined LD populations (from an academic LD referral center, a well-described Centers for Disease Control and Prevention (CDC) serum bank, and a group of erythema migrans patients from whose skin lesions B. burgdorferi was grown) and controls (non-Lyme arthritis inflammatory joint disease, syphilis, multiple sclerosis, and nondisease subjects from a region where LD is endemic, perhaps the most relevant comparison group of all). Previous studies demonstrated that specific antigen-antibody complexes in the sera of patients with LD could be precipitated by polyethylene glycol and could then be disrupted with maintenance of the immunoreactivity of the released antibodies, that specific anti-B. burgdorferi IgM was concentrated in ICs, and that occasionally IgM to specific B. burgdorferi antigens was found in the IC but not in unprocessed serum. EMIBA compared favorably with commercial and CDC flagellin-enhanced enzyme-linked immunosorbent assays and other assays in confirming the diagnosis of LD. EMIBA confirmed early B. burgdorferi infection more accurately than the comparator assays. In addition, EMIBA more accurately differentiated seropositivity in patients with active ongoing infection from seroreactivity persisting long after clinically successful antibiotic therapy; i.e., EMIBA identified seroreactivity indicating a clinical circumstance requiring antibiotic therapy. Thus, EMIBA is a promising new assay for accurate serologic confirmation of early and/or active LD.

    PMCID: PMC88321 PMID: 11526153 [PubMed - indexed for MEDLINE]

  52. Hosp Pract (Minneap). 2001 Jul 15;36(7):31-2, 35-7, 41-2, 47.

    Lyme disease: a clinical update.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    With adequate attention to specifics and details, the diagnosis and management of Lyme disease are usually relatively straight-forward. Still, there can be subtleties--for instance, in determining precisely what pathogen a tick bite transmitted, whether a patient's arthralgia is truly Lyme arthritis, or whether "positive" serologies represent refractory Lyme disease.

    PMID: 11446598 [PubMed - indexed for MEDLINE]

  53. Infect Immun. 2001 May;69(5):3389-97.

    Isogenic serotypes of Borrelia turicatae show different localization in the brain and skin of mice.

    Cadavid D, Pachner AR, Estanislao L, Patalapati R, Barbour AG.

    Department of Neuroscience, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA. cadavida@umdnj.edu

    Mice with severe combined immunodeficiency (scid mice) and infected with the relapsing fever agent Borrelia turicatae develop manifestations that resemble those of disseminated Lyme disease. We have characterized two isogenic serotypes, A and B, which differ in their variable small proteins (Vsps) and disease manifestations. Serotype A but not serotype B was cultured from the brain during early infection, and serotype B caused more severe arthritis, myocarditis, and vestibular dysfunction than serotype A. Here we compared the localization and number of spirochetes and the severity of inflammation in scid mice, using immunostained and hematoxylin-and-eosin-stained coronal sections of decalcified heads. Spirochetes in the brain localized predominantly to the leptomeninges, and those in peripheral tissues localized mainly to the extracellular matrix. There were significantly more serotype A than B spirochetes in the leptomeninges and more serotype B than A spirochetes in the skin. The first tissue where spirochetes were observed outside the vasculature was the dura mater. Inflammation was more severe in the skin than in the brain. VspA, VspB, and the periplasmic flagellin protein were expressed in all tissues examined. These findings indicate that isogenic but antigenically distinct Borrelia serotypes can have marked differences in their localization in tissues.

    PMCID: PMC98298 PMID: 11292762 [PubMed - indexed for MEDLINE]

  54. Clin Diagn Lab Immunol. 2001 Mar;8(2):225-32.

    Lyme borreliosis in rhesus macaques: effects of corticosteroids on spirochetal load and isotype switching of anti-borrelia burgdorferi antibody.

    Pachner AR, Amemiya K, Bartlett M, Schaefer H, Reddy K, Zhang WF.

    Department of Neurosciences, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S. Orange St., Newark, NJ 07103, USA. pachner@umdnj.edu

    Experimental Borrelia burgdorferi infection of rhesus monkeys is an excellent model of Lyme disease and closely parallels the infection in humans. Little is known about the interaction of host immunity with the spirochete in patients with chronic infection. We hypothesized that rapid development of anti-B. burgdorferi antibody in immunocompetent nonhuman primates (NHPs) is the major determinant of the reduction of the spirochetal load in Lyme borreliosis. This hypothesis was tested by measurement of the spirochetal load by PCR in association with characterization of the anti-B. burgdorferi humoral immune response in immunocompetent NHPs versus that in corticosteroid-treated NHPs. Although anti-B. burgdorferi immunoglobulin G (IgG) antibody was effectively inhibited in dexamethasone (Dex)-treated NHPs, anti-B. burgdorferi IgM antibody levels continued to rise after the first month and reached levels in excess of IgM levels in immunocompetent NHPs. This vigorous production of anti-B. burgdorferi IgM antibodies was also studied in vitro by measurement of antibody produced by B. burgdorferi-stimulated peripheral blood mononuclear cells. Despite these high IgM antispirochetal antibodies in Dex-treated NHPs, spirochetal loads were much higher in these animals. These data indicate that Dex treatment results in interference with isotype switching in this model and provide evidence that anti-B. burgdorferi IgG antibody is much more effective than IgM antibody in decreasing the spirochetal load in infected animals.

    PMCID: PMC96041 PMID: 11238200 [PubMed - indexed for MEDLINE]

  55. Allergy Asthma Proc. 2001 Jan-Feb;22(1):29-31.

    The role of the allergist in Lyme disease.

    Schutzer SE, Coyle PK, Chen D.

    Department of Medicine, Division of Allergy, Immunology, and Rheumatology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA.

    The allergist may frequently be involved with cases of Lyme disease. There are at least three reasons for this. First, the major symptom is often a rash that brings into the differential diagnosis several diseases that the allergist is likely to have expertise in; therefore, the allergist's role as a diagnostician is very important. The second reason is that the Borrelia burgdorferi (Bb) infection is treated with antibiotics and the patients may frequently develop reactions that may be immune-mediated. The allergist's expertise in diagnosis and management of allergic reactions is important. The third reason is that there is no established laboratory diagnostic test so that the clinician must use the existing tests, most often serologic, with their limitations, in the context of a history and physical. The allergist as an immunologist can be very helpful in the proper interpretation of the test results. The differential of the rash and the immune response to the infecting agent is described.

    PMID: 11227914 [PubMed - indexed for MEDLINE]

  56. Cleve Clin J Med. 2000 Dec;67(12):873-4.

    Should speculations about immune-mediated adverse effects of Lyme disease vaccine deter us from giving it?

    Sigal L.

    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.

    PMID: 11127980 [PubMed - indexed for MEDLINE]

  57. J Intraven Nurs. 2000 Jan-Feb;23(1):15-20.

    Controversies in the treatment and management of Lyme disease.

    Connolly-Taylor B.

    Promptcare/Transworld Inc. in Clark, New Jersey, USA.

    Lyme disease is an infection caused by the bite of the deer tick. It is the most common vector-transmitted disease in the United States. Past treatment practices included the administration of oral and/or i.v. antibiotics. Today the question is "to treat or not to treat." The etiology, signs and symptoms, and current treatments and management of Lyme disease and its associated somatic complaints are discussed.

    PMID: 11013529 [PubMed - indexed for MEDLINE]

  58. JAMA. 2000 Aug 9;284(6):695-6.

    Serologic testing for lyme disease

    Schutzer SE, Holland B, Reid P, Coyle PK.

    University of Medicine and Dentistry of New Jersey, Newark.

    PMID: 10927775 [PubMed - as supplied by publisher]

  59. J Infect Dis. 2000 Aug;182(2):534-9. Epub 2000 Jul 28.

    Immune complexes from serum of patients with lyme disease contain Borrelia burgdorferi antigen and antigen-specific antibodies: potential use for improved testing.

    Brunner M, Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. brunnemimickey08903@yahoo.com.

    We report sequestration of specific IgM anti-Borrelia burgdorferi (Bb) and Bb antigens within immune complexes (ICs) isolated from serum of patients with Lyme disease (LD). The relative enrichment in specific IgM measured by ELISA was apparent, even after correcting for differences in total IgM concentration in serum versus ICs. Immunoblot demonstrated that ICs contained antibodies against specific Bb proteins, whereas reactivity was absent or significantly lessened in unprocessed serum. This is the first study to show ICs containing Bb antigen identified by immunoblot with anti-Bb monoclonal antibody. ICs may be a useful source of antigen and antibody for development of more-accurate testing for LD.

    PMID: 10915085 [PubMed - indexed for MEDLINE]

  60. Lab Invest. 2000 Jul;80(7):1043-54.

    Localization of Borrelia burgdorferi in the nervous system and other organs in a nonhuman primate model of lyme disease.

    Cadavid D, O'Neill T, Schaefer H, Pachner AR.

    Department of Neuroscience, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA.

    Lyme borreliosis is caused by infection with the spirochete Borrelia burgdorferi. Nonhuman primates inoculated with the N40 strain of B. burgdorferi develop infection of multiple tissues, including the central (CNS) and peripheral nervous system. In immunocompetent nonhuman primates, spirochetes are present in low numbers in tissues. For this reason, it has been difficult to study their localization and changes in expression of surface proteins. To further investigate this, we inoculated four immunosuppressed adult Macaca mulatta with 1 million spirochetes of the N40 strain of B. burgdorferi, and compared them with three infected immunocompetent animals and two uninfected controls. The brain, spinal cord, peripheral nerves, skeletal muscle, heart, and bladder were obtained at necropsy 4 months later. The spirochetal tissue load was first studied by polymerase chain reaction (PCR)-ELISA of the outer surface protein A (ospA) gene. Immunohistochemistry was used to study the localization and numbers of spirochetes in tissues and the expression of spirochetal proteins and to characterize the inflammatory response. Hematoxylin and eosin and trichrome stains were used to study inflammation and tissue injury. The results showed that the number of spirochetes was significantly higher in immunosuppressed animals. B. burgdorferi in the CNS localized to the leptomeninges, nerve roots, and dorsal root ganglia, but not to the parenchyma. Outside of the CNS, B. burgdorferi localized to endoneurium and to connective tissues of peripheral nerves, skeletal muscle, heart, aorta, and bladder. Although ospA, ospB, ospC, and flagellin were present at the time of inoculation, only flagellin was expressed by spirochetes in tissues 4 months later. Significant inflammation occurred only in the heart, and only immunosuppressed animals had cardiac fiber degeneration and necrosis. Plasma cells were abundant in inflammatory foci of steroid-treated animals. We concluded that B. burgdorferi has a tropism for the meninges in the CNS and for connective tissues elsewhere in the body.

    PMID: 10908149 [PubMed - indexed for MEDLINE]

  61. J Neuroophthalmol. 1999 Dec;19(4):263-73.

    Annual update of systemic disease--1999: emerging and re-emerging infections (part I).

    Frohman L, Lama P.

    Department of Ophthalmology, UMD-New Jersey Medical School, Newark, New Jersey, USA.

    PMID: 10608682 [PubMed - indexed for MEDLINE]

  62. JAMA. 1999 Nov 24;282(20):1942-6.

    Borrelia burgdorferi-specific immune complexes in acute Lyme disease.

    Schutzer SE, Coyle PK, Reid P, Holland B.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103, USA. schutzer@umdnj.edu

    Erratum in: JAMA 2000 Oct 25;284(16):2059.

    Comment in: JAMA. 2000 Aug 9;284(6):695-6.

    CONTEXT: Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection. OBJECTIVE: To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD. DESIGN, SETTING, AND PATIENTS: Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for Disease Control and Prevention surveillance criteria for LD and 145 healthy and other disease controls conducted over 8 years. Tests were performed blinded. MAIN OUTCOME MEASURE: Detection of B. burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot. RESULTS: The B. burgdorferi immune complexes were found in 25 of 26 patients with early seronegative erythema migrans (EM) LD; 105 of 107 patients with seropositive EM LD; 6 of 10 samples that were seronegative [corrected] with culture-positive EM; 0 of 12 patients who were treated and recovered from LD; and 13 of 13 patients with neurologic LD without EM. Among 147 controls, B. burgdorferi immune complex was found in 0 of 50 healthy individuals; 0 of 40 patients with persistent fatigue; 0 of 7 individuals with frequent tick exposure; and 2 of 50 patients with other diseases. CONCLUSION: These data suggest that B. burgdorferi immune complex formation is a common process in active LD. Analysis of the B. burgdorferi immune complexes by a simple technique has the potential to support or exclude a diagnosis of early as well as active LD infection.

    PMID: 10580460 [PubMed - indexed for MEDLINE]

  63. J Clin Rheumatol. 1999 Dec;5(6):360-2.

    Molecular biology and immunology for clinicians, 10 cytokines-1.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics & Microbiology, Lyme Disease Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. sigallh@umdnj.edu

    PMID: 19078431 [PubMed]

  64. Rheum Dis Clin North Am. 1999 Nov;25(4):861-81, viii.

    Antibiotics for the treatment of rheumatologic syndromes.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA. sigallh@umdnj.edu

    Design of rational therapy depends on knowledge of the causes of the disease, which is knowledge often lacking in rheumatology. There have been theories of infectious causes of many rheumatologic diseases but no proof. The seductive possibility of an infectious etiology has led to the use of antibiotics for treating these diseases. This article reviews the effectiveness of antibiotics against rheumatologic syndromes, including rheumatoid arthritis and Lyme disease.

    PMID: 10573763 [PubMed - indexed for MEDLINE]

  65. Neurology. 1999 Oct 12;53(6):1340-1.

    Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome.

    Schutzer SE, Natelson BH.

    Department of Medicine, University of Medicine and Dentistry, New Jersey Medical School, Newark 07103, USA. schutzer@umdnj.edu

    Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue, contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients and controls were nonreactive. Centers for Disease Control and Prevention-defined CFS patients lacking antecedent signs of Lyme disease--erythema migrans, Bell's palsy, or large joint arthritis--are not likely to have laboratory evidence of Bb infection.

    PMID: 10522896 [PubMed - indexed for MEDLINE]

  66. J Clin Rheumatol. 1999 Oct;5(5):293-296.

    Molecular Biology and Immunology for Clinicians, 9 Pathogenesis of Autoimmunity-Molecular Mimicry.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics & Microbiology, Lyme Disease Center; Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

    The immune system generally does an excellent job of differentiating between self and non-self. In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no longer leaves self alone; this is auto-immunity-the defense system attacks self. In studying these exceptions, some aspects of the magnificent complexity of the immune system and of the molecular biology of life become apparent.Given that evolutionary processes build on prior experience and mechanisms, it is not surprising that human cells have much in common with yeast, and bacteria molecules found in lower organisms resemble, sometimes quite closely, homologous molecules in human cells. Microbes contain molecules resembling those used by mammalian cells, perhaps because some pathogens use or subvert mammalian systems. These similarities may be sufficient to interfere with the immune system's ability to discern between self and non-self. Thus, the immune response to certain components of pathogens may recognize the host, a phenomenon called molecular mimicry. This mechanism may be involved in the pathogenesis of rheumatologic and other immune-mediated diseases.

    PMID: 19078412 [PubMed - as supplied by publisher]

  67. J Vector Ecol. 1999 Jun;24(1):91-8.

    Geographic survey of vector ticks (Ixodes scapularis and Ixodes pacificus) for infection with the Lyme disease spirochete, Borrelia burgdorferi.

    Piesman J, Clark KL, Dolan MC, Happ CM, Burkot TR.

    Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Dept. Health and Human Services, Ft. Collins, CO 80522, USA.

    Populations of adult Ixodes scapularis and Ixodes pacificus, the two principal vectors of Lyme disease spirochetes in the United States, were collected from 17 sites in 12 states. Female ticks were fed on experimental rabbits; ticks and rabbits were subsequently examined for infection with Borrelia burgdorferi. Fourteen rabbits were exposed to I. scapularis ticks from the northeastern states of Connecticut, New York, New Jersey, and Maryland; all 14 rabbits became infected with B. burgdorferi. A total of 165/226 (73%) of these northeastern ticks was infected. Similarly, ticks from the midwestern states of Michigan, Wisconsin, and Minnesota transmitted infection to all three exposed rabbits; 29/51 (57%) of these midwestern I. scapularis were infected. In marked contrast, none of the 12 rabbits exposed to I. scapularis ticks from the southeastern states of South Carolina, Georgia, Florida, and Mississippi acquired infection with B. burgdorferi, and 0/284 (0%) of these ticks contained spirochetes. Four rabbits were exposed to I. pacificus collected from one location in California; 2/4 of these rabbits acquired infection and 2/57 (4%) of the I. pacificus were infected with B. burgdorferi. The antigenic profiles of all 58 strains tested were consistent with an identity of B. burgdorferi sensu lato. The availability of a human Lyme disease vaccine adds urgency to our efforts to calculate the ecological transmission risk throughout the United States, as an aid to the judicious use of such a vaccine.

    PMID: 10436883 [PubMed - indexed for MEDLINE]

  68. Bull Rheum Dis. 1999 Apr;48(4):1-4.

    Lyme disease and the Lyme disease vaccines.

    Sigal LH.

    University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA.

    Both OspA vaccines, with or without adjuvant, are effective and safe. People must receive repeated doses of the vaccine, however, to receive effective protection. If the vaccines are to be part of a Lyme disease prevention strategy, doctors and patients must pay attention to booster shot timing. Maximum public health benefit can be achieved only if the Lyme disease vaccines are integrated into broad individual and community-based efforts to prevent Lyme disease and other tick-borne diseases. Only people at significant risk of contracting Lyme disease should consider vaccination, and vaccination should merely complement--not replace--personal precautions for avoiding tick bites.

    PMID: 10418202 [PubMed - indexed for MEDLINE]

  69. Compr Ther. 1999 Apr;25(4):228-38.

    Management of Lyme arthritis.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    Musculoskeletal complaints and findings can be features of Lyme disease and can occur following treatment. Only with a good understanding of the pathogenesis of these problems can further evaluation and a proper therapeutic scheme be developed.

    PMID: 10349093 [PubMed - indexed for MEDLINE]

  70. J Med Entomol. 1998 Nov;35(6):1025-8.

    Air temperature and relative humidity effects on behavioral activity of blacklegged tick (Acari: Ixodidae) nymphs in New Jersey.

    Vail SG, Smith G.

    Department of Biology, William Paterson University, Wayne, NJ 07470, USA.

    Air-temperature and relative humidity data were used to explain variation in behavioral activity of Ixodes scapularis Say nymphs. We estimated behavioral activity as the residual variation in drag-sample data after seasonal changes in population density were removed by regression. The seasonal decline in drag samples between June and August 1995 on field plots at Morristown National Historical Park, NJ, can be described by a simple negative exponential function. Residuals around a fitted exponential were significantly correlated with temperature and with relative humidity measured at the leaf-litter surface, and explained 34 and 44% of the variance, respectively. Multiple regression on temperature and relative humidity explained 51% of the variance. These regressions estimated the explanatory power of microclimate, independent of seasonal correlations, and might provide a basis for day-to-day prediction of human exposure to Lyme disease.

    PMID: 9835697 [PubMed - indexed for MEDLINE]

  71. N Engl J Med. 1998 Jul 23;339(4):216-22.

    A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

    Sigal LH, Zahradnik JM, Lavin P, Patella SJ, Bryant G, Haselby R, Hilton E, Kunkel M, Adler-Klein D, Doherty T, Evans J, Molloy PJ, Seidner AL, Sabetta JR, Simon HJ, Klempner MS, Mays J, Marks D, Malawista SE.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.

    Erratum in: N Engl J Med 1998 Aug 20;339(8):571.

    Comment in: N Engl J Med. 1998 Nov 26;339(22):1638-9. N Engl J Med. 1998 Jul 23;339(4):263-4. N Engl J Med. 1998 Nov 26;339(22):1637; author reply 1638-9.

    BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

    PMID: 9673299 [PubMed - indexed for MEDLINE]

  72. Rheum Dis Clin North Am. 1998 May;24(2):323-51.

    Musculoskeletal manifestations of Lyme arthritis.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    Lyme disease is a treatable and curable infectious disease that can be diagnosed with relative confidence with attention to the details of the syndrome and proper use of serologic testing to confirm the clinical diagnosis. Lyme disease should not be a "diagnosis of exclusion," made on the basis of isolated serologic reactivity or because of the presence of symptoms compatible with Lyme disease. The pathogenesis of chronic complaints following infection with B. burgdorferi is often unclear, but such persistent complaints should not automatically be ascribed to ongoing infection. There is no proven role for long-term antibiotics or combination regimens.

    PMID: 9606762 [PubMed - indexed for MEDLINE]

  73. J Med Entomol. 1998 Jan;35(1):64-70.

    Comparison of Ixodes scapularis (Acari: Ixodidae) populations and their habitats in established and emerging Lyme disease areas in New Jersey.

    Schulze TL, Jordan RA, Hung RW.

    Division of Communicable Diseases, New Jersey Department of Health and Senior Services, Trenton 08625, USA.

    Hunterdon Country, New Jersey, experienced a significant increase in the number of Lyme disease cases during 1990-1995, accounting for 21.2% of all New Jersey cases. This study compares the relative abundance of Ixodes scapularis Say in similar habitats in Hunterdon County, an emerging Lyme disease area, and Monmouth County, where Lyme disease has been established for well over a decade. The extent to which differences in habitat physiognomy could explain differences in tick populations, and consequently Lyme disease case rates, is addressed. Ticks were surveyed and vegetation measurements made in 4 habitat types at 1 site in each county. I. scapularis was 7 times more abundant in Monmouth County than in the Hunterdon County site, and the distribution of all life stages among habitats differed significantly between sites. The greater numbers of subadult ticks at the Monmouth County site was attributed to greater shrub cover and litter depth which created more favorable microclimatic conditions for tick survival. However, the overall physiognomy of the different vegetation types at the sites studied in Monmouth and Hunterdon counties was remarkably similar and did not appear to explain differences in tick abundance. Until further research clarifies microscale differences between habitats, the differences in the case rates between the counties appear to be more likely the result of reporting artifact.

    PMID: 9542347 [PubMed - indexed for MEDLINE]

  74. J Clin Microbiol. 1998 Apr;36(4):1074-80.

    Immunoglobulin M capture assay for serologic confirmation of early Lyme disease: analysis of immune complexes with biotinylated Borrelia burgdorferi sonicate enhanced with flagellin peptide epitope.

    Brunner M, Stein S, Mitchell PD, Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA.

    We previously reported on the efficacy of the enzyme-linked immunoglobulin M capture immune complex (IC) biotinylated antigen assay (EMIBA) for the seroconfirmation of early Lyme disease and active infection with Borrelia burgdorferi. In earlier work we identified non-cross-reacting epitopes of a number of B. burgdorferi proteins, including flagellin. We now report on an improvement in the performance of EMIBA with the addition of a biotinylated form of a synthetic non-cross-reacting immunodominant flagellin peptide to the biotinylated B. burgdorferi B31 sonicate antigen source with the avidin-biotinylated peroxidase complex detection system used in our recently developed indirect IgM-capture immune complex-based assay (EMIBA). As in our previous studies, the enzyme-linked immunosorbent assay (ELISA) reactivities of antibodies liberated from circulating ICs (by EMIBA) were compared with those of antibodies in unprocessed serum (antibodies found free in the serum, thus as an IgM-capture ELISA, but not EMIBA, because the antibodies were not liberated from ICs), the sample usually used in standard ELISAs and Western blot assays. The addition of the flagellin epitope enhanced the ELISA signal obtained with untreated sera from many Lyme disease patients but not from healthy controls. In tests with both free antibodies and ICs, with or without the addition of the flagellin epitope to the sonicate, we found the most advantageous combination was IC as the source of antibodies and sonicate plus the flagellin epitope as the antigen. In a blinded study of sera obtained from patients with early and later-phase Lyme disease, EMIBA with the enhanced antigenic preparation compared favorably with other serologic assays, especially for the confirmation of early disease.

    PMCID: PMC104692 PMID: 9542940 [PubMed - indexed for MEDLINE]

  75. J N J Dent Assoc. 1998 Winter;69(1):19, 21, 62-3 passim.

    Lyme disease awareness for the New Jersey dentist. A survey of orofacial and headache complaints associated with Lyme disease.

    Heir GM, Fein LA.

    Department of Oral Pathology, Biology and Diagnostic Services, UMDNJ, USA.

    The incidence of Lyme disease is increasing in New Jersey. In 1996, 2,190 cases were reported, representing an increase of 487 cases from the 1,703 reported in 1995 [Table 1]. Symptoms associated with Lyme disease include headache and facial pain that often mimics dental pathology and temporomandibular disorders. Patients with complaints of vague, non-specific dental, facial or head pain, who present with a multisystemic, multi-treatment history, are suspect. This article discusses Lyme disease in New Jersey and the clinical presentation of Lyme disease that the dental practitioner may encounter. A summary of data is provided which was collected from 120 patients diagnosed with laboratory confirmed Lyme disease. The most common orofacial, head and dental complaints seen in the Lyme disease patient are reviewed. This information will hopefully aid in establishing a diagnosis and appropriate referral where indicated.

    PMID: 9584762 [PubMed - indexed for MEDLINE]

  76. Am J Epidemiol. 1998 Feb 15;147(4):391-7.

    Emergence of Lyme disease in Hunterdon County, New Jersey, 1993: a case-control study of risk factors and evaluation of reporting patterns.

    Orloski KA, Campbell GL, Genese CA, Beckley JW, Schriefer ME, Spitalny KC, Dennis DT.

    Bacterial Zoonoses Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.

    Reported cases of Lyme disease in Hunterdon County, New Jersey, increased almost 200% from 75 (67/100,000 population) in 1992 to 216 (193/100,000 population) in 1993. For evaluation of risk factors for Lyme disease and for determination of the cause of this increase, a case-control study was conducted, and the reporting practices of physicians' offices were evaluated. For cases reported in 1993, age and sex distribution, month of disease onset, and proportion of cases with erythema migrans rash were within expected limits. Analysis of age-matched case-control data showed that rural residence; clearing periresidential brush during spring and summer months; and the presence of rock walls, woods, deer, or a bird feeder on residential property were associated with incident Lyme disease. A review of physician reporting patterns suggested that the increase in reported cases in 1993 was due to improved reporting as well as to an increase in the numbers of patients diagnosed with Lyme disease. In addition, substantial underreporting of Lyme disease by physicians' offices was found.

    PMID: 9508107 [PubMed - indexed for MEDLINE]

  77. Emerg Infect Dis. 1998 Jan-Mar;4(1):97-9.

    Prevalence of tick-borne pathogens in Ixodes scapularis in a rural New Jersey County.

    Varde S, Beckley J, Schwartz I.

    New York Medical College, Valhalla, New York, USA.

    To assess the potential risk for other tick-borne diseases, we collected 100 adult Ixodes scapularis in Hunterdon County, a rapidly developing rural county in Lyme disease endemic western New Jersey. We tested the ticks by polymerase chain reaction for Borrelia burgdorferi, Babesia microti, and the rickettsial agent of human granulocytic ehrlichiosis (HGE). Fifty-five ticks were infected with at least one of the three pathogens: 43 with B. burgdorferi, five with B. microti, and 17 with the HGE agent. Ten ticks were coinfected with two of the pathogens. The results suggest that county residents are at considerable risk for infection by a tick-borne pathogen after an I. scapularis bite.

    PMCID: PMC2627663 PMID: 9452402 [PubMed - indexed for MEDLINE]

  78. Arthritis Rheum. 1998 Feb;41(2):195-204.

    Pitfalls in the diagnosis and management of Lyme disease.

    Sigal LH.

    University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA.

    PMID: 9485077 [PubMed - indexed for MEDLINE]

  79. J Emerg Nurs. 1997 Dec;23(6):525-9.

    Pericarditis as a manifestation of Lyme disease.

    Briant C, Roye K, Kutscher AH Jr.

    Emergency Department, Hunterdon Medical Center, Flemington, New Jersey, USA.

    PMID: 9460386 [PubMed - indexed for MEDLINE]

  80. J Clin Rheumatol. 1998 Feb;4(1):22-27.

    Molecular Biology and Immunology for Clinicians, 7: The Humoral Immune Response (Continued).

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Lyme Disease Center; Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

    The humoral immune response elicits the production of immunoglobulins of different structures and biologic functions. These differences are intrinsic to the various classes (isotypes), subclasses, and allotypes of the antibodies made. The binding of antibodies to their respective specific antigens occurs because of physicochemical interactions between tertiary structures of the antibody and the target epitope. Understanding the nature of these interactions allows one to better understand binding affinity and the ability of an antibody made as part of a specific response to one antigen to bind to other, even unrelated, antigens. This ability of an antibody made during the immune response to an infection to bind to different antigens provides the plasticity needed to provide protection from different related or unrelated pathogens.Thus, antibodies made during the response to one adenovirus may be of assistance in the response to infection with a second adenovirus. Cross-reactivity between molecules in and on disparate organisms, e.g., different Gram-negative bacilli, is common; heat-shock proteins and flagellins are very similar and broadly cross-reactive. Antibodies made to one bacterium can be the basis of immune protection from another.The affinity of an antibody for its specific antigen is enhanced during the secondary immune response, because the interaction of the antigen with surface immunoglobulin on memory cells selects the production of antibodies with a "better fit" for the target antigen.In a previous article in this series, on the humoral immune response, we reviewed much of the basic terminology of immunology (epitopes, paratopes, etc.), and described many of the characteristics of antigens and immunoglobulins. In this article we proceed with a description of the various immunoglobulin classes (also known as isotypes) and some of their functional characteristics.

    PMID: 19078239 [PubMed - as supplied by publisher]

  81. Infect Dis Clin North Am. 1997 Dec;11(4):803-12.

    The potential for clinical guidelines to impact appropriate antimicrobial agent use.

    Gross PA.

    Department of Internal Medicine, Hackensack University Medical Center, New Jersey, USA.

    Practice guidelines can help clinicians and microbiologists improve the quality and efficiency of health care. Numerous areas are in need of guideline development and development of quality improvement programs. These areas include antibiotic control, duration of antibiotic administration, use of narrowest spectrum, least toxic, lowest cost-effective antibiotic, use of rapid diagnostic tests, management of outpatient intravenous antibiotics, antibiotic prophylaxis for surgery, switching from intravenous to oral antibiotics, antibiotic selection for special situations, diagnosis of Lyme disease, and several other topics. IDSA, SHEA, CDC, NIH, and other organizations are cooperating to develop these guidelines.

    PMID: 9421701 [PubMed - indexed for MEDLINE]

  82. J Clin Rheumatol. 1997 Dec;3(6):361-367.

    Molecular Biology and Immunology for Clinicians 6: Antibodies and Antigens: Terminology, Structures, and the Humoral Immune Response.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Lyme Disease Center; Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Brunswick, New Jersey.

    The immune response that protects us from pathogens and malignancy is directed at the individual constituent molecules of the invading cells, a response specific for discrete sections of each of these molecules. A unique language is used to describe these individual targets, called epitopes or antigenic determinants. Understanding this language is necessary to better appreciate the character of the challenge and the nature, efficiency, and evolution of the response. As we determine the immune mechanisms of many diseases, e.g., autoimmunity due to molecular mimicry, it is crucial that physicians be able to interpret the immunological literature.Proper interpretation of serological testing, e.g., the use of Western blot to confirm/corroborate less specific tests like ELISA, depends in part on a full understanding of how the specificity of antibodies are determined. Novel therapeutic strategies, e.g., use of intravenous gammaglobulin to alter immune control networks, are being developed; only with an appreciation of the humoral immune response can the clinician make use of these new approaches that seek to manipulate the immune system. The terminology used in defining antigens, the molecules that are the target of the immune response, and the structure of immunoglobulins, and how these structures determine and influence function, are reviewed. This paper serves as a start, a "jumping off" point, for further description of the immune response in later papers in this series.To be successfully immersed in or introduced to immunology, it is important to "speak the language." So, consider this a refresher course, not to recall high school Spanish but medical school immunology.

    PMID: 19078228 [PubMed - as supplied by publisher]

  83. J Clin Invest. 1997 Aug 15;100(4):763-7.

    Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

    Schutzer SE, Coyle PK, Krupp LB, Deng Z, Belman AL, Dattwyler R, Luft BJ.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA. schutzer@umdnj.edu

    Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease.

    PMCID: PMC508246 PMID: 9259573 [PubMed - indexed for MEDLINE]

  84. Am Fam Physician. 1997 Aug;56(2):427-36, 439-40.

    Recognition and management of Lyme disease.

    Verdon ME, Sigal LH.

    Hunterdon Medical Center Family Practice Residency Hunterdon Medical Center, Flemington, New Jersey, USA.

    Lyme disease, the most common tick-borne illness in the United States, has an annual incidence of 0.5 percent in endemic areas. It most commonly occurs in the Northeast and upper Midwest, in areas that encourage and harbor the deer tick. The tick transmits an infection of the spirochete Borrelia burgdorferi that typically manifests as a localized skin lesion, erythema migrans. Rarely, Lyme disease manifests as localized arthritis, heart block or disease of the nervous system. Lyme disease is a clinical diagnosis, and laboratory tests should only be used to clarify diagnostic issues. The current standard for laboratory diagnosis includes a two-step approach using an initial immunoassay with a confirmatory Western blot. Treatment includes 10 to 21 days of oral doxycycline in nonpregnant adults or a similar course of amoxicillin in children or pregnant women. Overdiagnosis and overtreatment of Lyme disease have become common.

    PMID: 9262524 [PubMed - indexed for MEDLINE]

  85. J Clin Rheumatol. 1997 Jun;3(3):135-139.

    Molecular Biology and Immunology for Clinicians DNA Polymerase and the Polymerase Chain Reaction.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Lyme Disease Center; Division of Rheumatology and Connective. Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Brunswick. New Jersey.

    By using enzymes that underlie the molecular mechanisms of normal cell function, scientists have advanced the molecular biology of research and diagnostic testing. Normal cells divide and in so doing must accurately replicate their DNA; one of the enzymes crucial in making exact copies of DNA is DNA polymerase, which is at the heart of the polymerase chain reaction. This technique allows one to make billions or trillions of copies from a single molecule of DNA in a few hours, levels of DNA easily detectable by techniques described earlier in this series. The polymerase chain reaction can be used for clinical testing, e.g., identification of DNA derived from a micro-organism. Also, one can clone DNA in large quantities and then determine the specific nucleotide sequences. This then allows one to study the DNA of certain proteins in individuals with a specific disease process and how these DNA sequences differ from those in unaffected people. With this new technology, we can identify the following: variant collagens that underlie familial osteoarthritis; the presence of the DNA of micro-organisms, such as Ureaplasma and Chlamydia, at the site of inflammatory joint diseases, establishing the infectious nature of the synovitis; different human leukocyte antigen (HLA)-B27 alleles that predispose patients to the development of the seronegative spondylarthropathies; and characteristics of different HLA class II molecules that may yield insights into antigen presentation and its role in the pathogenesis of rheumatoid arthritis.

    PMID: 19078169 [PubMed - as supplied by publisher]

  86. Infect Immun. 1997 May;65(5):1722-8.

    A monoclonal antibody to Borrelia burgdorferi flagellin modifies neuroblastoma cell neuritogenesis in vitro: a possible role for autoimmunity in the neuropathy of Lyme disease.

    Sigal LH, Williams S.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903, USA.

    Although Borrelia burgdorferi is found at the site of many manifestations of Lyme disease, local infection may not explain all features of the disease. Previous work has demonstrated that the organism's flagellin cross-reacts with a component of human peripheral nerve axon, heat shock protein 60. The cross-reacting epitope is identified by a single anti-B. burgdorferi flagellin monoclonal antibody, H9724. We now report that the spontaneous and peptide growth factor-stimulated in vitro neuritogenesis of SK-N-SH neuroblastoma cells and other neural tumor cell lines is suppressed by H9724. In contrast, changes induced by exposure of these cells to optimal and suboptimal concentrations of cyclic AMP, phorbol ester, or retinoic acid are not affected by H9724. H9724 does not decrease cell viability or the ability of the cells to anchor to the culture plate or extracellular matrix and does not block nerve growth factor binding to the cells. These findings are compatible with the premise that antiaxonal antibodies formed during the immune response to B. burgdorferi flagellin might modify axonal function in vivo and play a role in the pathogenesis of neurologic features of Lyme disease. A humoral immune response predicated on molecular mimicry could explain persistent or ongoing neurologic dysfunction occurring after elimination of the organism by appropriate antibiotic therapy.

    PMCID: PMC175205 PMID: 9125553 [PubMed - indexed for MEDLINE]

  87. Dent Clin North Am. 1997 Apr;41(2):243-58.

    Differentiation of orofacial pain related to Lyme disease from other dental and facial pain disorders.

    Heir GM.

    Department of Oral Pathology, Biology and Diagnostic Sciences, University of Medicine and Dentistry, New Jersey Dental School, Newark, USA.

    The diagnostic process for the orofacial pain patient is often perplexing. Compounding the process of solving a diagnostic mystery is the multiplicity of etiologic factors. The propensity for Lyme disease to present with symptoms mimicking dental and temporomandibular disorders makes the task even more complex. It is hoped that the reader is cognizant of the fact that a pathologic process of dental structures--the teeth and their attachments to the mandible and maxilla, the temporomandibular joints, masticatory musculature, and vascular supply and sensory innervation of the oromandibular anatomy--may also be the source of facial pain. Although unique, similar complaints may also be manifestations of other causes, including pain associated with Lyme disease. The informed and fastidious clinician does not overlook these possibilities when evaluating the headache and facial pain patient. The clinician should be equipped with the knowledge and minimal armamentarium to evaluate the patient appropriately. To paraphrase from Sherlock Holmes, we must first eliminate the impossible, whatever is left is the truth, no matter how unlikely. A differential diagnosis must be achieved based on clinical experience, unbiased observations, and probability.

    PMID: 9142482 [PubMed - indexed for MEDLINE]

  88. Arch Intern Med. 1997 Mar 24;157(6):697, 700.

    Lyme disease: public education key to appropriate care.

    Nahass RG, Herman DJ, Hirsh EJ.

    Comment on: Arch Intern Med. 1996 Jul 22;156(14):1493-500.

    PMID: 9080925 [PubMed - indexed for MEDLINE]

  89. Semin Neurol. 1997 Mar;17(1):63-8.

    Immunologic mechanisms in Lyme neuroborreliosis: the potential role of autoimmunity and molecular mimicry.

    Sigal LH.

    Department of Medicine and Disease Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.

    Most of the clinical manifestations of Lyme disease are due to the local presence of the causative agent, Borrelia burgdorferi, in the affected tissues. However, the precise means of tissue damage are not well understood and there is no proof that the organism, live or dead, is always present. An understanding of the complex interaction between the organism, the immune response elicited by the organism, and the host can explain manifestations of the disease and persistence of symptoms and signs after the antibiotic-induced death of the organism. It is possible that dead spirochetes, or fragments thereof may persist and act as a focus of ongoing inflammation. Different immunogenetic types may predispose to different immunologic responses, with distinct clinical outcomes. Vascular changes induced by the infection, either by local infection or the effects of cytokines on the vessel wall, may underlie tissue pathology. Finally, the immune response to B. burgdorferi may elicit the production of antibodies capable of recognizing and damaging or modifying normal host tissues. Only by establishing the mechanisms causing tissue damage in Lyme disease can rational therapeutic strategies be developed. Only by understanding these mechanisms can physicians and patients interpret clinical responses to therapy and accurately appreciate the clinical prognosis.

    PMID: 9166962 [PubMed - indexed for MEDLINE]

  90. J Clin Rheumatol. 1997 Feb;3(1):28-34.

    Molecular Biology and Immunology for Clinicians.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Lyme Disease Center; Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

    After tissue injury, homeostatic mechanisms attempt to repair the damage. Local changes in the vasculature allow inflammatory cells to exit to deal with pathogens and take part in healing. Cytokines produced locally can cause systemic changes: fever, leukocytosis, transfer of amino acids from muscles to the liver, and increased glucocorticoid levels. A complicated blend of cytokines, including interleukins 1 and 6 and tumor necrosis factor, modulate patterns of hepatic protein synthesis. Changes in the production of metabolism-related enzymes occur, serving to provide fuel for the body and increase protein glycosylation. Also, there is an increase in synthesis of certain proteins exported from the liver, including components of the coagulation, complement, kinin, and fibrinolytic systems, all involved in the inflammatory response. Different inflammatory conditions elicit different responses; the types of proteins and the pattern of glycosylation may vary. Serum levels of heavy metals, including iron, copper, and zinc, change during inflammation because of altered levels of relevant transport or storage proteins.It is not clear what purpose is served by some of these changes. Many of the proteins are immunomodulatory, but some "functions" may be merely in vitro artifacts. What is clear, however, is that measurement of the protein known as C-reactive protein and of the erythrocyte sedimentation rate may provide markers of inflammation and measures of the response of certain inflammatory diseases to therapy.

    PMID: 19078114 [PubMed - as supplied by publisher]

  91. J Med Entomol. 1996 Nov;33(6):963-70.

    Seasonal and long-term variations in abundance of adult Ixodes scapularis (Acari:Ixodidae) in different coastal plain habitats of New Jersey.

    Schulze TL, Jordan RA.

    New Jersey Department of Health, Environmental and Occupational Health Services, Trenton 08625, USA.

    Fifteen sites in 4 different vegetation types in a Lyme disease endemic area were surveyed during times of peak tick activity in fall of 1982, 1984, and 1992, and subsequent spring activity periods to determine seasonal and year-to-year differences in habitat use by the blacklegged tick, Ixodes scapularis Say. Populations of I. scapularis adults varied significantly among the 3 yr surveyed, although this variability tended to be more pronounced in fall. I. scapularis adults were consistently more abundant in the fall than spring. Significant seasonal and year-to-year differences in adult populations were observed between and within vegetation types. However, the variability in habitat use was generally lower in spring compared with fall. In most of the surveys, the 5 sites yielding the greatest number of adults were represented by 3 or 4 of the vegetation types. Explanations for this variability and implications for tick surveillance and reducing risk of Lyme disease transmission are discussed.

    PMID: 8961647 [PubMed - indexed for MEDLINE]

  92. J Clin Rheumatol. 1996 Aug;2(4):209-214.

    Molecular Biology and Immunology for Clinicians.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Microbiology, Lyme Disease Center, Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

    Electrophoresis is a technique that allows the separation of charged molecules within a mixture into individual components. This represents a very powerful tool in research but has come into its own as a component of serologic testing. Western (immuno-) blot analysis takes advantage of the protein separation accomplished by a particular type of electrophoresis, called sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), to identify antibodies to individual components of cells, be they mammalian or microbial. The specificity of this kind of testing allows more rigorous testing to be done. Western blot analysis has become a "gold standard" in certain clinical circumstances and is used to corroborate equivocal or positive ELISA results in a number of diseases, Lyme disease and HIV infection being but two examples.

    PMID: 19078067 [PubMed - as supplied by publisher]

  93. Arch Intern Med. 1996 Jul 22;156(14):1493-500.

    The Lyme disease controversy. Social and financial costs of misdiagnosis and mismanagement.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA.

    Comment in: Arch Intern Med. 1997 Mar 24;157(6):697, 700. Arch Intern Med. 1997 Mar 24;157(6):697, 700. Arch Intern Med. 1997 Apr 14;157(7):817-8.

    Since it was first described, Lyme disease has emerged as a major public health concern, complicated by an emerging body of beliefs often at odds with scientifically established facts. Disagreement between the belief systems has led to confusion and anxiety, resulting in an alternative, but unproved, approach to management. When Lyme disease is incorrectly diagnosed, the debility related to the true, underlying problems remains unaddressed. The financial cost of the overdiagnosis and overtreatment of Lyme disease includes expenses related to testing and therapy and those of side effects and toxic effects of these treatments. Harder to estimate are the emotional costs to society of incorrectly burdening patients with the diagnosis of a chronic, incurable illness, with attendant assumption of a sick role and a disabled self-image. Better education is a major component of the solution to the problems of misdiagnosis and mistreatment of Lyme disease.

    PMID: 8687256 [PubMed - indexed for MEDLINE]

  94. J Clin Rheumatol. 1996 Jun;2(3):141-146.

    Molecular Biology and Immunology for Clinicians.

    Sigal LH.

    Department of Medicine, Department of Pediatrics, Department of Molecular Genetics and Micrcrobiology. Lyme Disease Center, and Division of Rheumatology and Connective Tissue Research, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

    Enzyme-linked immunosorbent assay (ELISA) represents a quick, reproducible, and easy assay that allows a single technician to measure antibodies to a defined target in a large number of samples. Obviously, its limitations must be included in the interpretation of results. Specifically, false negativity and false positivity are common problems, and the mechanisms underlying these phenomena must be understood before ELISA results can be incorporated into the clinical decision-making process. In many diseases, e.g., Lyme disease and human immunodeficiency virus (HIV) infection, Western blot analysis is necessary to corroborate the ELISA reactivity, to differentiate between true positive and false positive results, and occasionally to determine whether equivocal ELISA results are of any significance. ELISA has revolutionized the practice of medicine related to certain diseases, and its applications will doubtless expand. However, ELISA and all serologic techniques measure only the immune response to an infection, not the presence of the infectious agent itself, which can be detected by culture, immunohistochemical staining, and polymerase chain reaction (the subject of an upcoming article in this series).

    PMID: 19078049 [PubMed - as supplied by publisher]

  95. Bioconjug Chem. 1996 May-Jun;7(3):338-42.

    Presentation of peptide antigens as albumin conjugates for use in detection of serum antibodies by enzyme-linked immunosorbent assay.

    Yu Z, Carter JM, Huang SY, Lackland H, Sigal LH, Stein S.

    Center for Advanced Biotechnology and Medicine, Piscataway, New Jersey 08854, USA.

    The use of linear peptides as antigens for detection of serum antibodies has been studied using a sequence of the Borrelia burgdorferi protein, flagellin, and Lyme disease sera as a model. It was found that a novel presentation of the peptide as a hapten on the carrier protein, bovine serum albumin, in the enzyme-linked immunosorbent assay format can be successfully applied to distinguish between Lyme disease and control sera.

    PMID: 8816957 [PubMed - indexed for MEDLINE]

  96. J Infect Dis. 1996 Feb;173(2):403-9.

    Identification of an uncultivable Borrelia species in the hard tick Amblyomma americanum: possible agent of a Lyme disease-like illness.

    Barbour AG, Maupin GO, Teltow GJ, Carter CJ, Piesman J.

    Department of Microbiology, University of Texas Health Science Center, San Antonio 78284, USA.

    Bites from the hard tick Amblyomma americanum are associated with a Lyme disease-like illness in the southern United States. To identify possible etiologic agents for this disorder, A. americanum ticks were collected in Missouri, Texas, New Jersey, and New York and examined microscopically. Uncultivable spirochetes were present in approximately 2% of the ticks. Borrelia genus-specific oligonucleotides for the flagellin and 16S rRNA genes were used for amplification of DNA. Products were obtained from ticks containing spirochetes by microscopy but not from spirochete-negative ticks. Sequences of partial genes from spirochetes in Texas and New Jersey ticks differed by only 2 of 641 nucleotides for flagellin and 2 of 1336 nucleotides for 16S rRNA. Phylogenetic analysis showed that the spirochete was a Borrelia species distinct from previously characterized members of this genus, including Borrelia burgdorferi. Gene amplification could be used to detect these spirochetes in ticks and possible mammalian hosts.

    PMID: 8568302 [PubMed - indexed for MEDLINE]

  97. J Orofac Pain. 1996 Winter;10(1):74-86.

    Lyme disease: considerations for dentistry.

    Heir GM, Fein LA.

    TMD and Orofacial Pain Center, University of Medicine and Dentistry, New Jersey Dental School, Newark, USA.

    Although Lyme disease has spread rapidly and it is difficult to diagnose, a review of the dental literature does not reveal many references to this illness. Dental practitioners must be aware of the systemic effects of this often multiorgan disorder. Its clinical manifestations may include facial and dental pain, facial nerve palsy, headache, temporomandibular joint pain, and masticatory muscle pain. The effects precipitated when performing dental procedures on a patient with Lyme disease must also be considered. This study discusses the epidemiology and diagnosis of Lyme disease, its prevention, and factors to consider when making a differential diagnosis. Dental care of the patient with Lyme disease and currently available treatments also are considered. Three case reports are presented.

    PMID: 8995919 [PubMed - indexed for MEDLINE]

  98. N J Med. 1996 Jan;93(1):35-7.

    Recording occupational Lyme disease in New Jersey.

    Budnick LD.

    UMDNJ-New Jersey Medical School, Newark 07103-2714, USA.

    PMID: 8927298 [PubMed - indexed for MEDLINE]

  99. Bull Rheum Dis. 1995 Dec;44(8):1-3.

    Pseudo-Lyme disease.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, USA.

    PMID: 8528435 [PubMed - indexed for MEDLINE]

  100. Clin Infect Dis. 1995 Oct;21(4):910-4.

    Human granulocytic ehrlichiosis in Connecticut: report of a fatal case.

    Hardalo CJ, Quagliarello V, Dumler JS.

    Department of Internal Medicine, Morristown Memorial Hospital, New Jersey, USA.

    We report a case of granulocytic ehrlichiosis in a 71-year-old man who presented with an acute febrile illness and subsequently developed multisystem organ dysfunction and sudden severe anemia with thrombocytopenia requiring intensive care, mechanical ventilation, hemodialysis, and transfusions. The diagnosis was suspected on the fifth hospital day after a peripheral blood smear was examined; intracytoplasmic inclusion bodies were present in granulocytes only. Results of serological tests of acute and convalescent sera confirmed the diagnosis of granulocytic ehrlichiosis. We discuss the features of this case that were similar to those of published case reports as well as the course and outcome of treatment. This, to our knowledge, represents to first documented case of human granulocytic ehrlichiosis to occur outside the Upper Midwest. Because of the possible epidemiological association of Ehrlichia species with the deer tick Ixodes scapularis (dammini), this case raises additional concern for clinicians and patients in regions where Lyme disease is endemic.

    PMID: 8645839 [PubMed - indexed for MEDLINE]

  101. N J Med. 1995 Sep;92(9):601-3.

    Tick bite victims and their environment: the risk of Lyme disease.

    Smith-Fiola DC, Hallman WK.

    Rutgers University, Cook College, Department of Human Ecology, New Brunswick, NJ 08903-0231, USA.

    The authors surveyed 308 New Jersey tick bite victims. Education concerning landscape ecology, wildlife control, tick and wildlife habitat reduction, tick control using acaricides, and how to keep pets tick-free is especially needed to reduce human exposure to tick bites and Lyme disease.

    PMID: 7566679 [PubMed - indexed for MEDLINE]

  102. Pa Med. 1995 Jun;98(6):37.

    Lyme disease: debilitating, yet preventable.

    Hernandez R.

    Lyme Care Center, Whippany, New Jersey, USA.

    PMID: 7567043 [PubMed - indexed for MEDLINE]

  103. Am J Med. 1995 Apr 24;98(4A):74S-78S.

    Anxiety and persistence of Lyme disease.

    Sigal LH.

    Division of Rheumatology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    Lyme disease has become a major concern in endemic areas, in large measure because of fears that it does not respond to current antibiotic regimens. This anxiety has led to the use of untested drugs and longer courses of therapy than have been demonstrated to be necessary, with attendant increase in cost and toxicity. Concern about the lack of response to such therapy has convinced many patients that they have a permanent disease, with profound effects on their lives and those of their families. A better understanding of the natural history of Lyme disease and of possible causes for persisting symptoms other than active infection is needed to optimize management of such patients. Most symptoms persisting after adequate therapy can be explained by a small number of pathogenic mechanisms, only one of which is ongoing infection. Individualization of care and prudent analysis are crucial if overdiagnosis and overtreatment of Lyme disease are to be avoided.

    PMID: 7726196 [PubMed - indexed for MEDLINE]

  104. Am J Med. 1995 Apr 24;98(4A):25S-28S; discussion 28S-29S.

    Early disseminated Lyme disease: cardiac manifestations.

    Sigal LH.

    Division of Rheumatology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    The cardiac features of Lyme disease usually occur within weeks to months of the infecting tick bite; the result may be disruption of the conduction system, leading to heart block and muscle dysfunction, causing a mild myopericarditis. Lyme carditis is usually mild, although permanent heart block and a few fatalities claimed to be due to Lyme carditis have been reported, the latter usually with poor documentation. In general, Lyme carditis is treatable and curable with antibiotic regimens in current use. Recent reports have suggested that Lyme disease may be a cause of chronic congestive cardiomyopathy. Lyme carditis should be considered in the proper clinical setting with appropriate use of diagnostic tests, recalling that patients with carditis early in Lyme disease may be seronegative and that all patients who are seropositive do not necessarily have Lyme disease.

    PMID: 7726189 [PubMed - indexed for MEDLINE]

  105. Arthritis Rheum. 1995 Apr;38(4):565-9.

    Summary of the Sixth International Conference on Lyme Borreliosis.

    Sigal LH.

    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    PMID: 7718012 [PubMed - indexed for MEDLINE]

  106. Antimicrob Agents Chemother. 1995 Mar;39(3):661-7.

    Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans.

    Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, Wisniewski M, Collins JJ.

    Lyme Disease Center for South Jersey, Absecon, New Jersey, USA.

    A randomized, multicenter, investigator-blinded clinical trial was undertaken in order to compare the efficacies of cefuroxime axetil and doxycycline in the treatment of patients with Lyme disease associated with erythema migrans. A total of 232 patients with physician-documented erythema migrans were treated orally for 20 days with either cefuroxime axetil, 500 mg twice daily (119 patients), or doxycycline, 100 mg three times daily (113 patients), and clinical evaluations were conducted during treatment (8 to 12 days) and at 1 to 5 days and 1, 3, 6, 9, and 12 months posttreatment. Patients were assessed as to the resolution of erythema migrans and of the signs and symptoms related to early Lyme disease as well as to the prevention of late Lyme disease. A satisfactory clinical outcome (success or improvement) was achieved in 90 of 100 (90%) evaluable patients treated with cefuroxime axetil and in 89 of 94 (95%) patients treated with doxycycline (difference, -5%; 95% confidence interval, -12 to 3%). Patients with paresthesia, arthralgia, or irritability at enrollment were at higher risk for an unsatisfactory clinical outcome at 1 month posttreatment. Of the patients with satisfactory outcomes at 1 month posttreatment who were evaluable at 1 year posttreatment, a satisfactory outcome was achieved in 62 of 65 (95%) and in 53 of 53 (100%) patients treated with cefuroxime axetil and doxycycline, respectively (difference, -5%; 95% confidence interval, -10 to 4%). Twenty-eight percent of patients treated with doxycycline and 17% of those treated with cefuroxime axetil had one or more drug-related adverse events (P = 0.041). Doxycycline was associated with more photosensitivity reactions (6% compared with 0% for patients treated with cefuroxime axetil; P=0.006), and cefuroxime axetil was associated with more cases of diarrhea (5% compared with 0% for patients treated with doxycycline; P=0.030). Jarisch-Herxheimer reactions occurred in 12% of the patients in each treatment group. In summary, cefuroxime axetil is well tolerated and appears to be equally as effective as doxycycline in the treatment of early Lyme disease and in preventing the subsequent development of late Lyme disease.

    PMCID: PMC162601 PMID: 7793869 [PubMed - indexed for MEDLINE]

  107. J Infect Dis. 1995 Feb;171(2):356-61.

    Biliary complications in the treatment of unsubstantiated Lyme disease.

    Ettestad PJ, Campbell GL, Welbel SF, Genese CA, Spitalny KC, Marchetti CM, Dennis DT.

    Bacterial Zoonoses Branch, Centers for Disease Control and Prevention (CDC), Fort Collins, Colorado.

    Comment in: J Infect Dis. 1995 Feb;171(2):423-4.

    Treatment of unsubstantiated Lyme disease has led to serious complications in some cases. Two case-control studies, based on information in clinical records of patients discharged with a diagnosis of Lyme disease during 1990-1992, were conducted at a central New Jersey hospital. Twenty-five patients with biliary disease were identified, and 52 controls were selected from 1352 patients with suspected Lyme disease. Only 3% of 71 evaluatable subjects met the study criteria for disseminated Lyme disease. Patients with biliary disease were more likely than were antibiotic controls to have received ceftriaxone and more likely than ceftriaxone controls to have received a daily ceftriaxone dose > or = 40 mg/kg and to be < or = 18 years old. Fourteen of 25 biliary case-patients underwent cholecystectomy; all had histopathologic evidence of cholecystitis and 12 had gallstones. Thus, treatment of unsubstantiated diagnoses of Lyme disease is associated with biliary complications.

    PMID: 7844372 [PubMed - indexed for MEDLINE]

  108. Rheum Dis Clin North Am. 1995 Feb;21(1):217-30.

    Management of Lyme disease refractory to antibiotic therapy.

    Sigal LH.

    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.

    Lyme disease has become a major public health problem. One result of this anxiety is over-diagnosis and over-treatment in many endemic and near-to-endemic areas. The diagnosis of Lyme disease is often made solely on the basis of often misinterpreted serologic tests. Therefore, a major reason for inadequate response to antibiotic therapy is initial misdiagnosis. Persisting inflammation and tissue damage following treated Lyme disease does occur but is probably an uncommon cause of refractory symptoms and long-term debility post-Lyme disease.

    PMID: 7732170 [PubMed - indexed for MEDLINE]

  109. J Med Entomol. 1995 Jan;32(1):66-70.

    Seasonal activity of nymphal Ixodes scapularis (Acari: Ixodidae) in different habitats in New Jersey.

    Lord CC.

    Department of Ecology and Evolutionary Biology, Princeton University, NJ 08544-1003.

    Activity patterns of nymphal Ixodes scapularis Say were compared between habitat types (dominant tree types: mixed deciduous, oak, white pine, red cedar, sassafras, and spicebush). Both the time of peak abundance and the relative abundance of questing nymphs at the peak were compared. Several smoothing algorithms were tested with the data to determine if they could be used to estimate the time of peak abundance more accurately. Determination of the time of peak abundance using the raw data or simple moving averages was susceptible to outliers. Weighted averages were less susceptible to outliers. The seasonal pattern of nymphal abundance was similar in all habitat types. Variation in the time of peak abundance between habitats was low. Peak densities were lower in deciduous habitats (0.24 +/- 0.05 nymphs per square meter) than in nondeciduous habitats (0.85 +/- 0.15 nymphs per square meter); this could have resulted from higher host use of the nondeciduous areas. These data suggest that there are differences in the population dynamics of nymphs found in different habitats.

    PMID: 7869344 [PubMed - indexed for MEDLINE]

  110. Clin Pediatr (Phila). 1994 Nov;33(11):663-8.

    The overdiagnosis of Lyme disease in children residing in an endemic area.

    Rose CD, Fawcett PT, Gibney KM, Doughty RA.

    Division of Rheumatology, Alfred I. duPont Institute, Wilmington, Delaware 19899.

    The medical records of 227 children ages 1 to 19 years referred to the Lyme disease pediatric clinic over a 32-month period since May 1990 were reviewed. Clinico-serologic criteria for a positive diagnosis were applied. One hundred thirty-eight of 227 referred children did not fulfill those criteria and became the study population. Four subsets of patients emerged: (1) 54 patients with predominantly subjective symptoms; (2) 52 patients with objective evidence for an alternative diagnosis; (3) eight patients who had documented infection in the past and continued with symptoms after antibiotic treatment; and (4) 24 patients with a history of tick attachment or prenatal/family history of Lyme disease. Serologic testing data from commercial laboratories were available for the 54 children from the "predominantly subjective" group; 50% were negative, and 50% were borderline or positive. Ninety-two percent of these patients were negative at retesting by our enzyme-linked immunosorbent assay (ELISA) and 100% were negative by Western blot. Fifty-seven percent of these patients had received treatment prior to our evaluation. Children residing in an endemic area who present with vague symptoms are being diagnosed with and treated for Lyme disease without clinical or serologic documentation. In addition, fear in the lay community may be inducing doctors to diagnose Lyme disease in patients with symptoms that may be suggestive of an alternative diagnosis.

    PMID: 7859425 [PubMed - indexed for MEDLINE]

  111. Ear Nose Throat J. 1994 Nov;73(11):824-9.

    Lyme disease: a review for the otolaryngologist.

    Goldfarb D, Sataloff RT.

    Department of Otolaryngology-Head and Neck Surgery, Medical Center at Princeton, New Jersey 08540.

    Lyme disease is an important consideration in the differential diagnosis of patients seen by the otolaryngologist. Facial paralysis is the most common sign. The otolaryngologist may also see patients with temporal mandibular joint pain, cervical lymphadenopathy, facial pain, headache, tinnitis, vertigo, decreased hearing, otalgia and sore throat. The incidence is increasing and known to be endemic to certain areas of the United States and abroad. This paper reviews the various ways Lyme disease appears to the otolaryngologist. Three cases along with a discussion including epidemiology, vector, animal host relationship, clinical manifestations and pathophysiology are included. The literature is reviewed and the treatment discussed.

    PMID: 7828475 [PubMed - indexed for MEDLINE]

  112. Pediatrics. 1994 Aug;94(2 Pt 1):185-9.

    Cognitive effects of Lyme disease in children.

    Adams WV, Rose CD, Eppes SC, Klein JD.

    Department of Pediatrics, Alfred I. duPont Institute, Jefferson Medical College, Wilmington, DE 19899.

    OBJECTIVE: To measure possible cognitive sequelae of Lyme disease (LD) within a pediatric population. DESIGN: Prospective, blinded, controlled study of cognitive skills in children who had been treated for LD. SETTING: A children's hospital in an area endemic for LD. PATIENTS: Forty-one children with strictly defined LD were compared with 14 control children who had subacute rheumatological diseases, and with 23 healthy sibling controls. OUTCOME MEASURES: Neuropsychologic measures were administered to each child to assess the following cognitive areas: IQ information processing speed, fine-motor dexterity, novel-problem solving and executive functioning, short-term and intermediate memory, and the ability to acquire new learning. Predisease and postdisease academic achievement test scores were also gathered. Impressions from parents concerning the disease's subsequent impact were also obtained. RESULTS: No differences between LD and control groups were found for any of the numerous neuropsychologic measures. Analyses also failed to show differences between LD patients grouped with respect to the presence or absence of known neurologic involvement, disease stage, duration of symptoms before therapy, or type of antibiotic treatment. No predisease versus post-disease difference in academic performance was found. No perceived long-term deterioration in cognitive, social, or personality areas was reported by parents. CONCLUSION: Children appropriately treated for LD have an excellent prognosis for unimpaired cognitive functioning.

    PMID: 8036071 [PubMed - indexed for MEDLINE]

  113. J Clin Invest. 1994 Jul;94(1):454-7.

    Early and specific antibody response to OspA in Lyme Disease.

    Schutzer SE, Coyle PK, Dunn JJ, Luft BJ, Brunner M.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.

    Borrelia burgdorferi (Bb), the cause of Lyme disease, has appeared not to evoke a detectable specific antibody response in humans until long after infection. This delayed response has been a biologic puzzle and has hampered early diagnosis. Antibody to the abundant organism-specific outer surface proteins, such as the 31-kD OspA, has rarely been detected less than 6 mo after infection. Antibody to a less organism-specific 41-kD flagellin protein, sharing common determinants with other bacteria and thus limiting its diagnostic potential, may appear after 4 to 6 wks. To investigate our hypothesis that specific antibody to OspA may actually be formed early but remain at low levels or bound in immune complexes, we analyzed serum samples from patients with concurrent erythema migrans (EM). This is the earliest sign of Lyme disease and occurs in 60-70% of patients, generally 4-14 d after infection. We used less conventional but more sensitive methods: biotin-avidin Western blots and immune complex dissociation techniques. Antibody specificity was confirmed with recombinant OspA. Specific complexed antibody to whole Bb and recombinant OspA was detected in 10 of 11 of the EM patients compared to 0 of 20 endemic area controls. IgM was the predominant isotype to OspA in these EM patients. Free IgM to OspA was found in half the EM cases. IgM to OspA was also detected in 10 of 10 European patients with EM who also had reactive T cells to recombinant OspA. In conclusion a specific antibody response to OspA occurs early in Lyme disease. This is likely to have diagnostic implications.

    PMCID: PMC296331 PMID: 8040289 [PubMed - indexed for MEDLINE]

  114. Pediatr Neurol. 1994 Jul;11(1):41-3.

    Childhood neurologic disorders and Lyme disease during pregnancy.

    Gerber MA, Zalneraitis EL.

    Department of Pediatrics, University of Connecticut Health Center, Farmington 06030-1515.

    To determine the prevalence of clinically significant nervous system disease attributable to transplacental transmission of Borrelia burgdorferi, we surveyed neurologists in areas of the United States in which Lyme disease is endemic (i.e., Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota). Overall, 162 of the 176 (92%) pediatric neurologists contacted responded to the survey with a range of 90-100% in the different geographic areas. One pediatric neurologist was following 3 children who were labeled as having "congenital Lyme disease," but none of the 3 met our case definition. None of the other pediatric neurologists surveyed had ever seen a child whose mother had been diagnosed as having Lyme disease during pregnancy. Similarly, none of the 37 adult neurologists in Connecticut surveyed had ever seen a child whose mother had been diagnosed as having had Lyme disease during pregnancy. We conclude that congenital neuroborreliosis is either not occurring or is occurring at an extremely low rate in areas endemic for Lyme disease.

    PMID: 7986291 [PubMed - indexed for MEDLINE]

  115. J Med Entomol. 1994 Mar;31(2):206-11.

    Suppression of Ixodes scapularis (Acari: Ixodidae) nymphs in a large residential community.

    Schulze TL, Jordan RA, Vasvary LM, Chomsky MS, Shaw DC, Meddis MA, Taylor RC, Piesman J.

    Division of Epidemiology, Occupational and Environmental Health, New Jersey State Department of Health, Trenton 08625.

    To determine the feasibility of suppressing Ixodes scapularis Say populations in a large, hyperendemic residential community, several rates of granular carbaryl were applied by ground and air to the shrub layer and wooded buffers of a forested residential community during the peak activity period of nymphs. Granular carbaryl significantly reduced the abundance of I. scapularis nymphs on Peromyscus leucopus Raphinesque. Control nymphal ticks ranged between 70.0 and 90.3%. The use of properly timed acaricide applications to I. scapularis habitat within residential communities can provide an effective means of reducing exposure to I. scapularis nymphs, which are chiefly responsible for transmitting Borrelia burgdorferi to humans.

    PMID: 8189411 [PubMed - indexed for MEDLINE]

  116. Am J Epidemiol. 1994 Mar 1;139(5):504-12.

    Longitudinal study of Borrelia burgdorferi infection in New Jersey outdoor workers, 1988-1991.

    Schwartz BS, Goldstein MD, Childs JE.

    Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.

    From 1988 to 1991, annual questionnaires and serosurveys were performed in a cohort of outdoor workers in New Jersey at high risk for Lyme disease to 1) evaluate temporal trends in seroprevalence and seroconversion of antibody to Borrelia burgdorferi; 2) identify risk factors for B. burgdorferi seroconversion during these years; and 3) examine associations between such seroconversion in 1989-1990 and anti-tick saliva antibody (ATSA, a biologic marker of tick exposure) seropositivity in 1990. A total of 1,519 workers participated in at least 1 year of the study. Lyme disease seroprevalence and seroconversion increased from 1988 to 1990 and then decreased in 1991. Years at residence, rural residence, and a history of medical problems were observed to be risk factors for seroconversion from 1988 to 1991. An interaction between pet ownership and rural residence was observed in that rural residents were only at an elevated risk if they owned pets. B. burgdorferi seroconversion from 1989 to 1990 was associated with ATSA seropositivity in 1990; in subjects reporting low tick exposure, the odds ratio was 8.2 (95% confidence interval 1.5-44.7). Associations between ATSA and B. burgdorferi serologic status suggested that educational programs may have contributed to the decline in Lyme seroprevalence and seroconversion in 1991.

    PMID: 8154474 [PubMed - indexed for MEDLINE]

  117. Arthritis Rheum. 1994 Jan;37(1):10-4.

    Summary of the Fifth International Congress on Lyme Borreliosis.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey.

    PMID: 7907474 [PubMed - indexed for MEDLINE]

  118. Am J Public Health. 1993 Dec;83(12):1746-8.

    Antibodies to Borrelia burgdorferi and tick salivary gland proteins in New Jersey outdoor workers.

    Schwartz BS, Goldstein MD, Childs JE.

    Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Md.

    In 1990, a second cross-sectional study of outdoor workers (n = 758) at high risk for Lyme disease was conducted. A questionnaire was administered, and antibodies to Borrelia burgdorferi and tick salivary gland proteins (antitick saliva antibody, a biologic marker of tick exposure) were assayed by enzyme-linked immunosorbent assay. The statewide Lyme disease seroprevalence increased from 8.1% in 1988 to 18.7% in 1990. Antitick saliva antibody seropositivity varied by county and was associated with measures of self-reported tick exposure. The data suggested that the prevalence of B. burgdorferi infection increased in New Jersey outdoor workers from 1988 to 1990.

    PMCID: PMC1694949 PMID: 8259808 [PubMed - indexed for MEDLINE]

  119. Arthritis Rheum. 1993 Nov;36(11):1493-500.

    "Chronic Lyme disease" as the incorrect diagnosis in patients with fibromyalgia.

    Hsu VM, Patella SJ, Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019.

    Comment in: Arthritis Rheum. 1993 Nov;36(11):1489-92.

    OBJECTIVE: To evaluate a large number of patients referred with persistent symptoms thought to represent chronic Lyme disease. METHODS: We retrospectively reviewed the charts of nearly 800 patients referred with persisting nonspecific musculoskeletal and/or neurologic symptoms thought to represent chronic Lyme disease. RESULTS: Seventy-seven patients were found to have fibromyalgia, not ongoing Lyme disease, as the explanation of their chronic symptoms. Many had received multiple courses of antibiotic therapy for symptoms of fibromyalgia mistakenly attributed to chronic Lyme disease. No patient reported permanent and/or total resolution of fibromyalgia symptoms following antibiotic therapy. Appropriate therapy for fibromyalgia in those who remained compliant, however, was often effective in improving some if not all of the chronic symptoms. CONCLUSION: Fibromyalgia is a treatable and potentially curable disorder, and should be considered in the evaluation of patients with "refractory Lyme disease."

    PMID: 8240427 [PubMed - indexed for MEDLINE]

  120. Cutis. 1993 Sep;52(3):169-70.

    Lyme disease: the evolution of erythema chronicum migrans into acrodermatitis chronica atrophicans.

    Patmas MA.

    Community Medical Center, Toms River, New Jersey.

    Erythema chronicum migrans and acrodermatitis chronica atrophicans are both recognized to be lesions associated with Lyme disease, although they are thought to be distinct entities. In this paper, the clear evolution of erythema chronicum migrans into acrodermatitis chronica atrophicans is demonstrated.

    PMID: 8243101 [PubMed - indexed for MEDLINE]

  121. J Infect Dis. 1993 Jun;167(6):1372-8.

    Cross-reactivity between Borrelia burgdorferi flagellin and a human axonal 64,000 molecular weight protein.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019.

    The serum of patients with Lyme neurologic disease contain antibodies that bind to human axonal antigens that cross-react with Borrelia burgdorferi. The sera also bind to SK-N-SH neuroblastoma cells, especially the neuritic processes of these cells. H9724, a murine IgG monoclonal antibody to B. burgdorferi flagellin, binds to an SK-N-SH cell protein of approximately 64,000 apparent molecular weight (M(r)). H9724 immunoprecipitates a protein of the same M(r) (p64) from the cells and from a delipidated preparation of human peripheral nerve. The Lyme disease patient sera that bind to human axons and SK-N-SH cells also bind to the immunoprecipitated p64. Immunologic cross-reactivity between borrelial and human axonal proteins may be involved in the immunopathogenesis of Lyme neurologic disease.

    PMID: 8501326 [PubMed - indexed for MEDLINE]

  122. Ann Clin Lab Sci. 1993 May-Jun;23(3):221-9.

    Serological responses in Lyme disease: the influence of sex, age, and environment.

    Fidelus-Gort R, Gilmour RW, Kashatus WC.

    SmithKline Beecham Clinical Laboratories, Norristown, PA 19403.

    In the laboratory, the serodiagnosis of Lyme disease is a difficult decision, especially in early disease. The variability in the immune response to the Borrelia burgdorferi spirochete and the lack of specificity and sensitivity of commercial assays for the detection of antibodies in early disease have contributed to the difficulty of serodiagnosis. This study examines the serological data of over 20,000 serum specimens submitted for enzyme linked immunosorbent assay (ELISA) and/or Western Blot analysis to detect IgM and IgG antibodies to the Lyme spirochete. These samples were submitted to SmithKline Beecham Clinical Laboratories in Philadelphia from the five state region of New York, Pennsylvania, New Jersey, Delaware, and Massachusetts. These areas of the northeastern United States are considered endemic for infestation with the Borrelia burgdorferi spirochete and its vector, the deer tick. Samples were examined by positivity rate for ELISA and/or Western Blot Analysis (WBA). Specimens were broken down by age (greater than or equal to 13 years and less than 12 years) sex (male versus female), State (NY, NJ, PA, DE, MA), and by month of submission. Using the established criteria of the manufacturers for a positive response, these studies demonstrate an overall positivity rate for ELISA testing at 5.2 percent, while WBA alone had a positivity rate of 1.6 percent. Specimens examined by both ELISA and WBA had a positivity rate of 1.0 percent. Females > or = 13 years of age had the highest positivity rate of 8.5 percent on ELISA testing, while females < or = 12 years gave a positive reaction in 2.6 percent of the samples.(ABSTRACT TRUNCATED AT 250 WORDS)

    PMID: 8323257 [PubMed - indexed for MEDLINE]

  123. JAMA. 1993 Feb 24;269(8):979-80.

    From the Centers for Disease Control and Prevention. Ceftriaxone-associated biliary complications of treatment of suspected disseminated Lyme disease--New Jersey, 1990-1992.

    [No authors listed]

    PMID: 8429594 [PubMed - indexed for MEDLINE]

  124. Rheum Dis Clin North Am. 1993 Feb;19(1):79-93.

    Lyme disease: testing and treatment. Who should be tested and treated for Lyme disease and how?

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick.

    LD can mimic a number of other disease, and vice versa. It is imperative that clinicians understand LD and be able to use serologic diagnostic techniques appropriately. LD is not a diagnosis that can be made on the basis of serologic testing. By this is meant that vague symptoms plus a positive serologic test do not assure that the patient has LD. On the other hand, a patient with ECM or other manifestations of LD may still be seronegative. In addition, therapy for LD must be tailored to the clinical problems of the individual patient. Especially in patients with chronic or persisting complaints, it is important to be precise in making the correct diagnosis and in understanding the underlying pathogenetic mechanisms at work so that an appropriate and ultimately successful therapeutic plan can be made.

    PMID: 8356262 [PubMed - indexed for MEDLINE]

  125. MMWR Morb Mortal Wkly Rep. 1993 Jan 22;42(2):39-42.

    Ceftriaxone-associated biliary complications of treatment of suspected disseminated Lyme disease--New Jersey, 1990-1992.

    Centers for Disease Control and Prevention (CDC).

    Lyme disease (LD) is endemic in Monmouth and Ocean counties, New Jersey (1). In June 1992, CDC and the New Jersey Department of Health (NJDOH) conducted a telephone survey in both counties of 65 schoolchildren who required home instruction because of suspected LD to determine the public health impact of the disease. Most children had received prolonged and repeated courses of oral antimicrobials and/or home intravenous infusion of antimicrobials; 79% had been hospitalized for treatment of suspected LD or management of treatment complications, most notably drug-induced symptoms of gallbladder disease occurring in patients receiving ceftriaxone (Rocephin), and bloodstream infections associated with intravenous catheters. To determine the characteristics of and treatment complications for patients hospitalized for treatment of LD, a computerized search of hospital discharge data in New Jersey was performed; nearly 30% of all hospitalizations for LD during 1990-1991 were at a regional hospital serving Monmouth and Ocean counties. This report presents findings of an analysis of patients admitted to that hospital for treatment of LD.

    PMID: 8419791 [PubMed - indexed for MEDLINE]

  126. Pediatrics. 1992 Oct;90(4):523-8.

    Lyme arthritis as the incorrect diagnosis in pediatric and adolescent fibromyalgia.

    Sigal LH, Patella SJ.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick.

    In areas endemic for Lyme disease there is increasing concern and anxiety about possible chronic and untreatable manifestations of the disease. The authors have diagnosed fibromyalgia in many patients with chronic musculoskeletal complaints in whom chronic Lyme arthritis had previously been diagnosed as the cause of their joint pains. Fibromyalgia is a common disorder, causing arthralgia (not true arthritis), fatigue, and debility. The repeated and/or long-term antibiotic therapy prescribed for "chronic Lyme disease" is not successful in curing the symptoms of fibromyalgia. Especially in areas where anxiety about Lyme disease is great, it is important to be careful in diagnosing chronic Lyme disease. Fibromyalgia is a potentially treatable and curable cause of chronic complaints and should be considered in the differential diagnosis of "refractory Lyme arthritis."

    PMID: 1408503 [PubMed - indexed for MEDLINE]

  127. J Med Entomol. 1992 May;29(3):544-7.

    Effectiveness of an aerial application of carbaryl in controlling Ixodes dammini (Acari: Ixodidae) adults in a high-use recreational area in New Jersey.

    Schulze TL, Taylor GC, Vasvary LM, Simmons W, Jordan RA.

    Division of Epidemiology and Communicable Disease Control, New Jersey State Department of Health, Trenton 08625.

    Lyme disease risk reduction through the control of the principal tick vector, Ixodes dammini Spielman, Clifford, Piesman & Corwin, has become a major issue facing public health agencies in many endemic states. Where large tracts of land are involved, established methods of I. dammini control are impractical. An aerial application of carbaryl directed against fall populations of I. dammini adults resulted in 93.8% control after 96 h. Control persisted through the following spring. The usefulness of aerial applications may be limited to areas where logistic constraints obviate the use of conventional ground applications.

    PMID: 1625304 [PubMed - indexed for MEDLINE]

  128. Am Fam Physician. 1992 May;45(5):2151-6.

    Diagnosing Lyme disease.

    Schutzer SE.

    University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark.

    The incidence of Lyme disease is increasing, and the disease is spreading geographically. Prompt diagnosis requires recognition of characteristic signs and symptoms of infection with the spirochete Borrelia burgdorferi. In more than half of cases, erythema migrans is the earliest sign of Lyme disease. Although less frequently seen than erythema migrans, peripheral neuropathy of the seventh cranial nerve is another important sign. Tests for Lyme disease await refinement, but laboratory evaluation can be helpful when Lyme disease is suspected.

    PMID: 1575110 [PubMed - indexed for MEDLINE]

  129. Drugs. 1992 May;43(5):683-99.

    Current recommendations for the treatment of Lyme disease.

    Sigal LH.

    Lyme Disease Center, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick.

    Lyme disease is a multisystem inflammatory disease caused by infection with Borrelia burgdorferi. Soon after the tick bite which transmits the infection, the pathognomonic skin rash erythema chronicum migrans occurs in 50 to 70% of patients, often with associated symptoms resembling a 'summer cold' or viral infection. Therapy for this stage of disease consists of 3 to 4 weeks of oral therapy. The agents currently used are: amoxicillin (500 mg 3 or 4 times daily) with or without probenecid 500 mg 3 times daily, doxycycline (100 mg twice daily), or tetracycline (500 mg 4 times daily). Longer duration therapy has never been evaluated and therefore is not currently indicated. Even patients with severe early manifestations of Lyme disease should be treated orally. Later features of Lyme disease include carditis and neurological disease, which can occur days to approximately 9 months after the onset of illness, and arthritis and neurological disease which can occur weeks to years after the onset of the illness. Treatment at this stage is with 2 to 3 weeks of intravenous antibiotics, currently cefotaxime (3 g every 12 hours), ceftriaxone (1 g every 12 hours or 2 g every day) and benzylpenicillin (14 g in divided doses). There is no evidence that longer duration therapy is indicated or more efficacious. The exception to this suggestion is the patient with isolated facial seventh cranial nerve palsy; if such a patient has no other signs or symptoms to suggest Lyme disease and has normal spinal fluid, oral therapy is usually sufficient, although some physicians will give concomitant corticosteroids to hasten the resolution of the palsy. Of major consequence to the practitioner and patient is the possibility that persistent symptoms (e.g. fibromyalgia) may be caused by a process which is no longer antibiotic-sensitive. Special care in the management of so-called 'chronic Lyme disease' is crucial lest the clinician prescribes prolonged or unending courses of antibiotics for such noninfectious problems.

    PMID: 1379147 [PubMed - indexed for MEDLINE]

  130. Am J Epidemiol. 1991 Jul 1;134(1):86-95.

    Anti-tick saliva antibody: a biologic marker of tick exposure that is a risk factor for Lyme disease seropositivity.

    Schwartz BS, Ford DP, Childs JE, Rothman N, Thomas RJ.

    Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.

    Anti-tick saliva antibody (ATSA) has potential as a biologic marker of exposure to tick bites. In 1989, we conducted a cross-sectional study of 304 outdoor workers in Monmouth County, New Jersey, to evaluate associations between self-reported tick exposure, ATSA status, and Lyme disease antibody status. ATSA levels 1) were correlated with an index of tick exposure on the basis of three self-reported measures of tick exposure and outdoor hours worked per week (p = 0.01); 2) were consistently higher in pet owners compared with persons without pets (p = 0.03); and 3) when examined by duration since last tick bite, peaked at 3-5 weeks after tick bite and then declined (p = 0.06). ATSA levels dichotomized at the 75th percentile (approximately two standard deviations above the mean ATSA optical density of 25 subjects who denied recent tick exposure) were associated with self-reported tick exposure: adjusted odds ratios for high ATSA levels were 4.2 (95% confidence interval (CI) 0.9-18.9) for moderate (versus none) tick exposure and 5.8 (95% CI 1.2-27.2) for high (versus none) tick exposure. Finally, high ATSA levels were associated with Lyme disease seropositivity, with an adjusted odds ratio of 3.2 (95% CI 1.3-7.6). The data suggest that ATSA is a biologic marker of tick exposure that is a risk factor for Lyme disease seropositivity.

    PMID: 1853864 [PubMed - indexed for MEDLINE]

  131. MMWR Morb Mortal Wkly Rep. 1991 Jun 28;40(25):417-21.

    Lyme disease surveillance--United States, 1989-1990.

    Centers for Disease Control (CDC).

    Surveillance for Lyme disease (LD) was initiated by CDC in 1982 (1), and in January 1991, LD became nationally reportable (2). Forty-six states reported cases in 1989 and 1990 (Figure 1), but the occurrence in nature of the causative bacterium, Borrelia burgdorferi, has not been documented in all of these states. From 1982 through 1989, the annual reported number of cases of LD increased 18-fold (from 497 to 8803, respectively) and from 1986 through 1989, nearly doubled each year (Figure 2). The provisional total of 7997 cases for 1990 suggests a plateau in this trend of rapid annual increase. This report summarizes surveillance of LD during 1990 in Connecticut, Georgia, Michigan, Missouri, New Jersey, and Wisconsin.

    PMID: 2046649 [PubMed - indexed for MEDLINE]

  132. Am J Public Health. 1991 Jun;81(6):714-8.

    Lyme disease: a proposed ecological index to assess areas of risk in the northeastern United States.

    Schulze TL, Taylor RC, Taylor GC, Bosler EM.

    Division of Epidemiology and Disease Control, New Jersey State Department of Health, Trenton 08625.

    BACKGROUND: Recent public awareness has resulted in a demand for information about ways to reduce the risk of acquiring Lyme disease. METHODS: Twenty-two school properties and recreational areas within a Lyme disease endemic area of central Monmouth County, New Jersey were evaluated for risk of transmission using an ecological index on the suitability, amount, and access to Ixodes dammini habitat by target human populations and the abundance of infected adult ticks. RESULTS: The characterization of tick habitat accurately predicted the elimination of 11 sites from concern. Of the remaining 11 sites, six were classified high risk and five as moderate risk. On-site tick surveys identified infected I. dammini adults at only four sites (three risk; one moderate risk). CONCLUSIONS: These results indicate that the use of selected ecological parameters provides a cost-effective method to rapidly identify areas at risk for Lyme disease transmission.

    PMCID: PMC1405152 PMID: 2029039 [PubMed - indexed for MEDLINE]

  133. Cutis. 1991 Apr;47(4):267-8.

    Lyme disease during pregnancy.

    Schutzer SE, Janniger CK, Schwartz RA.

    Department of Allergy and Immunology, New Jersey Medical School, Newark 07103-2714.

    Lyme disease, caused by infection with Borrelia burgdorferi, can affect those exposed to a vector tick. Pregnant women are no exception, and such infection places the fetus at risk. It is particularly important to recognize the disease early so that effective therapy may be instituted. Although the present patient had a favorable outcome, not all do. Clinical diagnosis is especially important since conventional laboratory tests may be inadequate or require lengthy periods of time before a positive result occurs. The dermatologic sign of Lyme disease, erythema migrans, although occurring in only 50 percent of cases, is likely to be the most important diagnostic sign.

    PMID: 2070648 [PubMed - indexed for MEDLINE]

  134. Cutis. 1991 Apr;47(4):229-30, 232.

    Diagnosing Lyme disease: often simple, often difficult.

    Schutzer SE, Schwartz RA.

    Department of Medicine, UMDNJ-New Jersey Medical School, Newark 07103.

    Lyme disease has as its hallmark erythema migrans. However, it is only present in about one half of the patients who contract this disease. In its absence, the diagnosis of Lyme disease may be difficult. It depends upon a compatible history of exposure and clinical signs and symptoms together with positive results of serologic testing. Unfortunately, seronegativity for antibody to the pathogen may occur both during the first six weeks of infection and be chronic due to the reactive antibody being bound in immune complexes. The selective use of new diagnostic tests may be required to confirm the diagnosis. These tests include assays for antibody or antigen analysis of immune complex components, as well as polymerase chain reactions.

    PMID: 2070642 [PubMed - indexed for MEDLINE]

  135. Arthritis Rheum. 1991 Mar;34(3):367-70.

    Summary of the fourth international symposium on Lyme borreliosis.

    Sigal LH.

    Department of Medicine, University of Medicine and Dentistry of New Jersey, New Brunswick.

    PMID: 2003859 [PubMed - indexed for MEDLINE]

  136. JAMA. 1991 Jan 16;265(3):317-8.

    From the Centers for Disease Control. Imported malaria associated with malariotherapy of Lyme disease--New Jersey.

    [No authors listed]

    PMID: 1984528 [PubMed - indexed for MEDLINE]

  137. Annu Rev Public Health. 1991;12:85-109.

    Lyme disease: a multifocal worldwide epidemic.

    Sigal LH, Curran AS.

    Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.

    PMID: 2049148 [PubMed - indexed for MEDLINE]

  138. Milbank Q. 1991;69(1):79-112.

    Lyme disease: the social construction of a new disease and its social consequences.

    Aronowitz RA.

    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Camden.

    American medical researchers who investigated Lyme disease in the 1970s conceived of the disorder as a categorically new entity. Other interpretations emphasizing the continuities between Lyme disease and its epidemiological antecedents, nevertheless, were possible. Clinicians, patients, and advocacy groups continue to contest the character, significance, and appropriate treatment of Lyme disease. Highly publicized discussions among the interested parties reflect American society's ongoing concern with new legitimating diagnoses, personal responsibility for acute and chronic disease, and the authority of science.

    PMID: 2034186 [PubMed - indexed for MEDLINE]

  139. MMWR Morb Mortal Wkly Rep. 1990 Dec 7;39(48):873-5.

    Imported malaria associated with malariotherapy of Lyme disease--New Jersey.

    Centers for Disease Control (CDC).

    PMID: 2123017 [PubMed - indexed for MEDLINE]

  140. Am J Public Health. 1990 Oct;80(10):1225-9.

    Lyme disease in New Jersey outdoor workers: a statewide survey of seroprevalence and tick exposure.

    Goldstein MD, Schwartz BS, Friedmann C, Maccarillo B, Borbi M, Tuccillo R.

    Center for Occupational Medicine, New Jersey Department of Environmental Protection, Trenton.

    To evaluate the spread of Lyme disease in New Jersey, we conducted a statewide cross-sectional study of Lyme disease seroprevalence in a high-risk occupational group of outdoor employees. Of the 689 employees who participated in the study, 39 (5.7 percent) were positive for antibody to B. burgdorferi, the causative agent of Lyme disease. Seroprevalence varied markedly by county; unexpectedly high seroprevalence rates were found in several northern counties (Sussex, Hudson, and Hunterdon). Furthermore, some southern counties (Atlantic, Cape May, and Ocean) with large tick populations (as measured by self-reported exposure to ticks) had low seroprevalence rates which were inversely correlated with self-reported preventive practices. These data suggest that lyme disease, as measured by seroprevalence of antibody to B. burgdorferi, may be spreading beyond the southern portion of the state where it had been previously well documented and that preventive behaviors may play an important role in minimizing the risk of the disease.

    PMCID: PMC1404838 PMID: 2400034 [PubMed - indexed for MEDLINE]

  141. N J Med. 1990 Jul;87(7):579-84.

    Lyme disease in New Jersey.

    Goldoft MJ, Schulze TL, Parkin WE, Gunn RA.

    New Jersey State Department of Health, Division of Epidemiology, Trenton 08625-0360.

    Lyme disease is a spirochetal infection endemic throughout New Jersey. Case reports from 1984 through 1986 suggest different high-risk groups and different disease severity than had been observed in earlier cases in the state. Both sexes now appear equally at risk, while younger age groups, particularly children less than ten years old, appear to be at increased risk. Mild disease is usual, although classic rheumatologic and neurologic complications can occur. Informal surveys suggest Lyme disease is under-reported by a factor of five- to tenfold in New Jersey. Early recognition by physician and patient is necessary for prompt treatment to reduce complications.

    PMID: 2385371 [PubMed - indexed for MEDLINE]

  142. Am J Epidemiol. 1990 Jul;132(1):58-66.

    Anti-tick antibodies: an epidemiologic tool in Lyme disease research.

    Schwartz BS, Ribeiro JM, Goldstein MD.

    Department of Medicine, University of Pennsylvania, Philadelphia.

    In 1988, antibodies to arthropod (Ixodes dammini, Dermacentor variabilis, and Aedes aegypti) salivary gland proteins and to Borrelia burgdorferi were measured by enzyme-linked immunosorbent assay in 53 high-risk outdoor workers from the New Jersey Department of Environmental Protection. Lyme disease seropositives had significantly higher anti-I. dammini antibody levels than seronegative controls (p = 0.006). Anti-B. burgdorferi antibody (enzyme-linked immunosorbent assay) and anti-I. dammini antibody titers were highly correlated in these workers (r = 0.49, p = 0.0002). Quantitative self-reported tick exposure (tick bites in the past year) and anti-I. dammini antibody titers were significantly correlated (r = 0.27, p = 0.05), and persons without tick exposure had lower anti-I. dammini antibody levels (p = 0.009) than persons with known exposure. A second serum sample obtained 3 months after the first after a period of decreased tick exposure (the winter) revealed that the anti-I. dammini antibody levels had significantly declined (p = 0.0004). Additional experiments revealed that the antibody was not completely specific for I. dammini but was relatively specific for the two tick species examined compared with A. aegypti. The data hold promise that this antibody may be a useful tool in Lyme disease research as a biologic marker of tick exposure.

    PMID: 2356814 [PubMed - indexed for MEDLINE]

  143. Am J Med. 1990 Jun;88(6):577-81.

    Summary of the first 100 patients seen at a Lyme disease referral center.

    Sigal LH.

    Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019.

    PURPOSE AND PATIENTS AND METHODS: Lyme disease is a major clinical problem in a number of endemic areas in the United States. In areas where anxiety about the disease is high, patients and physicians often ascribe clinical concerns to Lyme disease. Incorrect diagnosis often leads to unnecessary antibiotic treatment (often prolonged or repeated intravenous therapy). This report summarizes the cases of the first 100 patients referred to the Lyme Disease Center at Robert Wood Johnson Medical School. RESULTS: In only 37 of the patients referred was Lyme disease, either current or preceding, the explanation for the complaints. Many of the patients had another definable arthropathy. Twenty-five of the patients had fibromyalgia, which has not previously been reported in Lyme disease. Three of these patients had active Lyme disease at the time of evaluation, and 17 had a history suggesting preceding Lyme disease. Approximately half of the 91 courses of antibiotic therapy given to these 100 patients before referral were probably unwarranted. CONCLUSIONS: Anxiety about possible late manifestations of Lyme disease has made Lyme disease a "diagnosis of exclusion" in many endemic areas. Persistence of mild to moderate symptoms after adequate therapy and misdiagnosis of fibromyalgia and fatigue may incorrectly suggest persistence of infection, leading to further antibiotic therapy. Attention to patient anxiety and increased awareness of these musculoskeletal problems after therapy should decrease unnecessary therapy of previously treated Lyme disease.

    PMID: 2346158 [PubMed - indexed for MEDLINE]

  144. Am J Epidemiol. 1990 May;131(5):877-85.

    Lyme disease in outdoor workers: risk factors, preventive measures, and tick removal methods.

    Schwartz BS, Goldstein MD.

    Department of Medicine, University of Pennsylvania, Philadelphia.

    Comment in: Am J Epidemiol. 1991 Apr 1;133(7):754-5.

    A statewide cross-sectional study of risk factors for seropositivity for antibody to Borrelia burgdorferi in outdoor workers in New Jersey was performed in September and October 1988. The crude odds ratio associated with exposure to ticks on the primary state job was 2.2 (95% confidence interval (CI) 0.7-9.0). After adjustment for multiple confounding variables with logistic regression, the adjusted occupational tick exposure odds ratio was 5.1 (95% CI 1.1-23.6). Additional analyses revealed that any use of insect repellent or antibiotics may have decreased the risk of Lyme disease in these workers (adjusted odds ratios for not using insect repellent or antibiotics were 2.0 (95% CI 1.0-4.0) and 2.3 (95% CI 0.8-6.7), respectively). These data suggest that Lyme disease is a hazard of outdoor work and that increased recognition of this fact will be necessary to prevent Lyme disease in these workers.

    PMID: 2321630 [PubMed - indexed for MEDLINE]

  145. J Am Vet Med Assoc. 1990 Apr 15;196(8):1255-8.

    Serologic survey for Borrelia burgdorferi antibody in horses referred to a mid-Atlantic veterinary teaching hospital.

    Bernard WV, Cohen D, Bosler E, Zamos D.

    Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square 19348.

    Blood samples obtained from 13 of 100 (13%) and 6 of 91 (7%) horses at the George D. Widener Hospital for Large Animals in the months of June and October, respectively, had antibody to Borrelia burgdorferi as determined by ELISA. Horses from the states of New York, Maryland, Delaware, New Jersey, and Pennsylvania were seropositive for B burgdorferi. The frequency of antibody response in horses from New Jersey was greater (P less than 0.05) than the frequency of antibody response in horses from Pennsylvania or that of horses from the other states combined. Statistically significant difference was not found when a comparison was made between horses with serotiter and open diagnosis of neurologic or musculoskeletal disease and horses with negative serotest results and open diagnosis of neurologic or musculoskeletal disease.

    PMID: 2332371 [PubMed - indexed for MEDLINE]

  146. Arch Intern Med. 1990 Apr;150(4):761-3.

    Serologic tests for Lyme disease. Interlaboratory variability.

    Luger SW, Krauss E.

    Department of Pathology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway.

    Comment in: Arch Intern Med. 1990 Apr;150(4):732-3. Arch Intern Med. 1991 Apr;151(4):815-6.

    The serologic test for the detection of antibodies to Borrelia burgdorferi is the most frequently used laboratory method for the diagnosis of Lyme disease. However, the insensitivity of the assays and the interlaboratory variability are frequent problems. To determine the extent of this variability, one aliquot of serum from each of nine patients with a history of Lyme disease was sent to nine reference laboratories, including national, university, state, and local hospital laboratories. A second aliquot of the original serum was submitted 2 weeks later. Wide variability among laboratories was observed, ranging from a university laboratory that detected antibody to B burgdorferi (IgG or IgM) in 18 of 18 specimens, to a state laboratory that detected antibody in only 8 of 18 specimens. Detection of IgM specific antibodies showed similar variability (range, 2 to 10 of 18). There were eight instances of a fourfold or greater change in titer between the aliquots sent 2 weeks apart, although only three of these were an increase in titer. These results indicate the need for standardization of the assays and the availability of national reference material. It is recommended that the results of serologic testing should not be relied on as the sole criteria in making the diagnosis of Lyme disease.

    PMID: 2183731 [PubMed - indexed for MEDLINE]

  147. Lancet. 1990 Feb 10;335(8685):312-5.

    Sequestration of antibody to Borrelia burgdorferi in immune complexes in seronegative Lyme disease.

    Schutzer SE, Coyle PK, Belman AL, Golightly MG, Drulle J.

    Department of Medicine, University of Medicine and Dentistry-New Jersey Medical School, Newark 07103.

    To find out whether apparent seronegativity in patients strongly suspected of having Lyme disease can be due to sequestration of antibodies in immune complexes, such complexes were isolated and tested for antibody to Borrelia burgdorferi. In a blinded analysis the antibody was detected in all 10 seronegative Lyme disease patients with erythema chronicum migrans (ECM), in none of 19 patients with other diseases, and in 4 of 12 seronegative patients who probably had Lyme disease but had no ECM. These findings were confirmed by western blot, which also showed that immune complex dissociation liberated mainly antibody reactive to the 41 kD antigen and sometimes antibody to an approximate 30 kD antigen. Complexed B burgdorferi antibody was also found in 21 of 22 (95%) of seropositive patients with active disease, 3 additional seronegative but cell mediated immune reactive patients, and 3 other seronegative patients who eventually became seropositive. Apparent B burgdorferi seronegativity in serum immune complexes may thus be due to sequestration of antibody in immune complexes.

    PMID: 1967770 [PubMed - indexed for MEDLINE]

  148. JAMA. 1989 Dec 22-29;262(24):3431-4.

    Antibody testing in Lyme disease. A comparison of results in four laboratories.

    Schwartz BS, Goldstein MD, Ribeiro JM, Schulze TL, Shahied SI.

    Section of General Internal Medicine, University of Pennsylvania, Philadelphia.

    Comment in: JAMA. 1990 Aug 8;264(6):692-3. JAMA. 1989 Dec 22-29;262(24):3464-5.

    To evaluate the interlaboratory and intralaboratory agreement in the performance of Lyme disease serological testing, we sent serum specimens from 132 outdoor workers in New Jersey to as many as four independent laboratories. These included one state department of health laboratory, one large commercial laboratory, and two research laboratories. The measurement of agreement employed, the kappa statistic, ranged from .45 to .53 among the four laboratories and from .50 to .54 within the commercial laboratory. These values represent low levels of agreement. The data suggest that Lyme disease serological testing procedures should be standardized so that Lyme disease test results are more comparable between laboratories.

    PMID: 2685383 [PubMed - indexed for MEDLINE]

  149. Rev Infect Dis. 1989 Sep-Oct;11 Suppl 6:S1435-41.

    Lyme disease surveillance in the United States, 1983-1986.

    Ciesielski CA, Markowitz LE, Horsley R, Hightower AW, Russell H, Broome CV.

    Epidemiology Section, Centers for Disease Control, Atlanta, Georgia 30333.

    During 1983-1986, 5,016 cases of Lyme disease were reported to the Centers for Disease Control. Cases were acquired in 31 states; however, 86% of the cases were acquired in seven states: Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota. For 63% of patients the disease began in summer; 52% recalled a tick bite. Erythema chronicum migrans (ECM) occurred in 91% of the patients; arthritis, in 57%; neurologic complications, in 18%; and cardiac manifestations, in 10%. When serum samples were obtained greater than or equal to 21 days after onset of symptoms, 14% (6 of 42) with ECM alone and 19% (17 of 89) with complicated Lyme disease (ECM plus organ-system involvement) had positive serologic tests. Antimicrobial therapy did not appear to affect serologic response. Lyme disease is now the most commonly reported tick-borne illness in the United States and has been reported from 32 states since 1980. Physicians nationwide need to be familiar with the protean signs and symptoms associated with Lyme disease and with the limitations of current serologic techniques in diagnosing early illness.

    PMID: 2682955 [PubMed - indexed for MEDLINE]

  150. Conn Med. 1989 Jun;53(6):324-6.

    National surveillance of Lyme disease, 1987-1988.

    Tsai TF, Bailey RE, Moore PS.

    In 1987 and 1988, 6876 Lyme disease cases from 43 states were reported to the Centers for Disease Control. The 4507 cases reported in 1988 was nearly double the case number reported in 1987, and ninefold the number reported in 1982, when a systematic system of national surveillance was established. The average annual incidence of reported Lyme disease in the United States in 1987-1988 was 1.4/100,000. New York led the nation in reported cases in 1988 with 57% of the cases reported nationally. Eight states, New York, New Jersey, Pennsylvania, Connecticut, Massachusetts, Rhode Island, Wisconsin, and Minnesota, reported 92% of the nation's cases. The state reporting the highest incidence rate in 1987-88 was Rhode Island, with 9.9 cases/100,000. Regionally, incidence rates were highest in Northeastern and Mid-Atlantic states, intermediate in North Central and Pacific states, lower in the Southeast, and lowest in the Great Plains and Mountains states. The seven remaining states in which Lyme disease has not been transmitted all lie west of the 100th meridian.

    PMID: 2758820 [PubMed - indexed for MEDLINE]

  151. J Infect Dis. 1989 Mar;159(3):562-8.

    An outbreak of ehrlichiosis in members of an Army Reserve unit exposed to ticks.

    Petersen LR, Sawyer LA, Fishbein DB, Kelley PW, Thomas RJ, Magnarelli LA, Redus M, Dawson JE.

    Division of Field Services, Centers for Disease Control, Atlanta 30333.

    An outbreak of unexplained illness occurred in members of an army reserve unit after field training in an area of New Jersey endemic for Lyme disease. Nine (12%) of the 74 who attended the exercise had serological evidence of Ehrlichia infection, defined as a single rise in titer of antibody to Ehrlichia canis greater than or equal to 1:160 four weeks after training. Two reservists with early serum samples had documented seroconversion, defined by a four-fold or greater increase in titer of antibody to E. canis, with a peak titer of greater than or equal to 1:160. Reservists with serological evidence of Ehrlichia infection were more than three times as likely to report arthralgia, myalgia, headache, appetite loss, nausea, eye pain, and abdominal pain than the other reservists. No reservist with serological evidence of Ehrlichia infection was hospitalized and most had minimal or no symptoms. This outbreak of ehrlichiosis suggests that the usual symptoms of Ehrlichia infection are milder than previously reported and that ehrlichiosis must be considered in symptomatic persons with recent tick exposure.

    PMID: 2915168 [PubMed - indexed for MEDLINE]

  152. Arthritis Rheum. 1988 Nov;31(11):1384-9.

    Synovial fluid eosinophilia in Lyme disease.

    Kay J, Eichenfield AH, Athreya BH, Doughty RA, Schumacher HR Jr.

    Pediatric Rheumatology Center, Children's Seashore House, Philadelphia, Pennsylvania.

    We describe three 14-year-old boys who developed synovial fluid eosinophilia associated with Lyme disease. One patient, with arthritis that began in 1975, had the first documented case of Lyme disease in New Jersey. Lyme disease should be considered when eosinophilia is noted on analysis of synovial fluid from patients with undiagnosed arthritis.

    PMID: 3056421 [PubMed - indexed for MEDLINE]

  153. Ann N Y Acad Sci. 1988;539:283-8.

    The geographic distribution of Lyme disease in the United States.

    Ciesielski CA, Markowitz LE, Horsley R, Hightower AW, Russell H, Broome CV.

    Epidemiology Section, Division of Bacterial Diseases, Centers for Disease Control, Atlanta, Georgia 30333.

    In 1982, national surveillance for Lyme disease was established by the Centers for Disease Control to monitor trends and determine endemic geographic areas. Initially, the endemic areas corresponded to the known distribution of Ixodes dammini, a five-state area of the northeastern seaboard (New York, New Jersey, Connecticut, Rhode Island, and Massachusetts) and Wisconsin and Minnesota. Increasing numbers of cases have been reported outside these areas, however, 86% of the provisional 5731 cases reported to CDC were acquired in these seven states. The number of reported cases increased from 491 in 1982 to approximately 1500 per year in 1984-1986, making Lyme disease the most commonly reported tick-borne illness in the United States. The apparently widening distribution of Lyme disease indicates that physicians in all regions of the country should be familiar with its signs and symptoms. Investigations of the vector in areas endemic for Lyme disease where Ixodes ticks are not found are warranted.

    PMID: 3190099 [PubMed - indexed for MEDLINE]

  154. Ann N Y Acad Sci. 1988;539:244-57.

    Epidemiologic studies of Lyme disease in horses and their public health significance.

    Cohen D, Bosler EM, Bernard W, Meirs D 2nd, Eisner R, Schulze TL.

    University of Pennsylvania Veterinary School, Philadelphia 19348.

    A serologic survey of horses in the New Jersey-Pennsylvania area demonstrated that about 10% (6.2-14.2%) have significant levels of serum antibody to Borrelia burgdorferi. However, in a highly endemic area of central New Jersey, up to 60% of the mares and yearlings samples on one farm were seropositive. In 1983, sera from this same farm exhibited only 12% positives in mares and 35% positives in yearlings. Longitudinal studies of paired sera obtained from individual yearlings over a 6-month period in 1985 showed that 34% of them declined during the period. A new clinical syndrome associated with this farm has been observed in 1985-87. In 1985 only an edema of the legs and a dermatitis were noted, in 19.2% of the foals. There was a clustering of cases on one site, where one peer group of foals was sequestered after weaning, which suggested a point source of infection other than arthropods. In 1986, 14.6% of the foals were affected, four of them with arthritis, two of which resisted antibiotic treatment for over several months' time. Experimental infection of a pony with triturated B. burgdorferi infected tick material indicated low specific antibody levels starting about the ninth day that continued for a 3-week period. When this animal was challenged 6 months later with primary B. burgdorferi cultures, a rapid and significant booster effect was evidenced within 4 days.

    PMID: 3190097 [PubMed - indexed for MEDLINE]

  155. Ann N Y Acad Sci. 1988;539:204-11.

    Vector tick populations and Lyme disease. A summary of control strategies.

    Schulze TL, Parkin WE, Bosler EM.

    New Jersey State Department of Health, Trenton 08625.

    Although many aspects of Lyme disease have been intensely studied for over a decade, little research has been directed toward control of the principal tick vector, Ixodes dammini. Ecological and epidemiological investigations have provided not only an ample understanding of tick biology and behavior, they have also identified the types of areas at risk for disease transmission. The advantages and limitations of previous attempts to control I. dammini by host reduction, habitat modification, and acaricide applications have been discussed in relation to overall control strategies for high-risk areas, and an integrated approach to control proposed.

    PMID: 3190092 [PubMed - indexed for MEDLINE]

  156. J Med Entomol. 1987 Jul;24(4):420-4.

    Effectiveness of two insecticides in controlling Ixodes dammini (Acari: Ixodidae) following an outbreak of Lyme disease in New Jersey.

    Schulze TL, McDevitt WM, Parkin WE, Shisler JK.

    PMID: 3114494 [PubMed - indexed for MEDLINE]

  157. Zentralbl Bakteriol Mikrobiol Hyg A. 1987 Feb;263(3):427-34.

    Prevalence of canine Lyme disease from an endemic area as determined by serosurvey.

    Schulze TL, Bosler EM, Shisler JK, Ware IC, Lakat MF, Parkin WE.

    From August 1984 through February 1985, 423 dogs from 43 municipalities in 7 New Jersey counties were evaluated for the presence of antibodies to the Lyme disease spirochete (Borrelia burgdorferi). Of these dogs, 34.7% with no apparent clinical symptoms were serologically reactive (IFA greater than or equal to 1:64); titers in this study ranged from non-reactive to 1:2048. Ninety percent of the dogs surveyed had a current vaccination status to Leptospira interrogans serovars canicola and icterohaemorhagiae. Dogs vaccinated to leptospirosis elicited homologous antibody titers of less than or equal to 1:16 and, therefore, did not interfere with interpretation of antibody levels to B. burgdorferi. Effects of age, degree of outdoor activity, travel history, and location of residence were evaluated. The use of serosurveys of dogs as a tool for Lyme disease surveillance is discussed.

    PMID: 3591094 [PubMed - indexed for MEDLINE]

  158. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):72-8.

    Comparison of rates of infection by the Lyme disease spirochete in selected populations of Ixodes dammini and Amblyomma americanum (Acari: Ixodidae).

    Schulze TL, Lakat MF, Parkin WE, Shisler JK, Charette DJ, Bosler EM.

    At a major endemic focus in New Jersey, 50% of 290 adult Ixodes dammini collected in the fall of 1984 were infected with the Lyme disease spirochete (Borrelia burgdorferi), which was statistically higher than the rate found in the 202 adult ticks (39.6%) examined during the spring. Neither sex nor site of collection within the focus significantly affected the infection rate. The observed infection rates were similar to those reported in endemic areas of New York and Connecticut. Borrelia burgdorferi also infected all active stages of Amblyomma americanum ticks. Rates of infection were 5.4% in adults (n = 467) and 3.4% in nymphs (n = 289); 15.6% of clusters of unengorged larvae harbored B. burgdorferi, suggesting transovarial passage of the spirochete. Comparison of the rates of infection in I. dammini and A. americanum and their potential impact on Lyme disease transmission is discussed.

    PMID: 3577494 [PubMed - indexed for MEDLINE]

  159. Zentralbl Bakteriol Mikrobiol Hyg A. 1986 Dec;263(1-2):65-71.

    Evolution of a focus of Lyme disease.

    Schulze TL, Shisler JK, Bosler EM, Lakat MF, Parkin WE.

    Epidemiological investigations were initiated in 1984 when significant Lyme disease activity was observed within a 5-km radius of an area previously used as a non-endemic control site for Lyme disease research in New Jersey. Through 1983, collections of Ixodes dammini from vegetation and feral rodents were infrequent and no human cases were identified within a 16-km radius of the control site. In 1984, 4 human cases and 3 serologically reactive canines (greater than or equal to 1:512) were recognized within the area and adult I. dammini populations were over 3-fold greater than those at our primary study location where Lyme disease has been endemic since 1981. Using darkfield microscopy, 53.4% of adult I. dammini were infected with Borrelia burgdorferi as compared to 50.0% of adults collected during the same period at the known endemic study site. These data indicate that a focus of Lyme disease has recently become established at the previously non-endemic control site and that the establishment of new foci may occur more rapidly than once thought.

    PMID: 3577493 [PubMed - indexed for MEDLINE]

  160. J Med Entomol. 1986 Jan 24;23(1):105-9.

    Seasonal abundance and hosts of Ixodes dammini (Acari: Ixodidae) and other ixodid ticks from an endemic Lyme disease focus in New Jersey, USA.

    Schulze TL, Bowen GS, Lakat MF, Parkin WE, Shisler JK.

    PMID: 3950921 [PubMed - indexed for MEDLINE]

  161. J Am Vet Med Assoc. 1985 May 1;186(9):960-4.

    Arthritis caused by Borrelia burgdorferi in dogs.

    Kornblatt AN, Urband PH, Steere AC.

    From October 1982 to May 1984, we studied 34 dogs from the Lyme, Conn area that had a history of tick exposure and lameness associated with pain, warmth, and/or swelling in one or more joints. Large numbers of polymorphonuclear leukocytes were seen in Giemsa-stained smears of synovial fluid from 9 dogs, and spirochetes (Borrelia burgdorferi) were found in 1 sample by darkfield microscopy and immunoperoxidase techniques. The geometric mean antibody titer to B burgdorferi in the 34 dogs was 1:2,700, compared with 1:285 in 43 clinically normal dogs from the same area (P less than 0.0001) and 1:50 in 29 dogs from an area in New Jersey that is not endemic for human Lyme disease (P less than 0.00001). We concluded that B burgdorferi in dogs may cause arthritis similar to that in human Lyme disease.

    PMID: 3997648 [PubMed - indexed for MEDLINE]

  162. J Med Entomol. 1985 Jan 18;22(1):88-93.

    The role of adult Ixodes dammini (Acari: Ixodidae) in the transmission of Lyme disease in New Jersey, USA.

    Schulze TL, Bowen GS, Lakat MF, Parkin WE, Shisler JK.

    PMID: 3981553 [PubMed - indexed for MEDLINE]

  163. Am J Epidemiol. 1984 Sep;120(3):387-94.

    A focus of Lyme disease in Monmouth County, New Jersey.

    Bowen GS, Schulze TL, Hayne C, Parkin WE.

    An endemic focus of Lyme disease is present in Colt's Neck, Howell, Freehold, and Wall Townships in Monmouth County, New Jersey. Cases of Lyme disease have occurred in this area from 1978 to 1982. Fifty-seven of the 117 persons (49%) who acquired their infection in New Jersey from 1978 to 1982 live or work in these four townships, whose population of 82,491 is only 1.1% of the population of the entire state. Thirty persons who contracted Lyme disease were exposed to ticks at the Naval Weapons Station, Earle, which is located within Colt's Neck and Howell Townships. The annual incidence rate for persons stationed at or working on this military facility in 1981 and 1982 was about 1%. At Naval Weapons Station, Earle, persons working outdoors in 1981-1982 were at higher risk than those working indoors.

    PMID: 6475916 [PubMed - indexed for MEDLINE]

  164. Yale J Biol Med. 1984 Jul-Aug;57(4):661-8.

    Lyme disease in New Jersey, 1978-1982.

    Bowen GS, Schulze TL, Parkin WL.

    From 1978 to 1982, 117 cases of Lyme disease were reported in New Jersey. The number of cases increased each year from four in 1978 and 1979 to 56 in 1982. Forty-eight percent of cases occurred in a four-township area in central Monmouth County. The proportion of cases with arthritis decreased in 1982 because of early antibiotic treatment and better reporting of milder cases. The proportion of cases with positive serology increased with severity of the clinical syndrome. About 25 percent of patients had exposure to ticks because of occupations that required outdoor activities. Lyme disease is a growing public health problem in New Jersey.

    PMCID: PMC2590043 PMID: 6393614 [PubMed - indexed for MEDLINE]

  165. Yale J Biol Med. 1984 Jul-Aug;57(4):669-75.

    Geographical distribution and density of Ixodes dammini (Acari: Ixodidae) and relationship to Lyme disease transmission in New Jersey.

    Schulze TL, Bowen GS, Lakat MF, Parkin WE, Shisler JK.

    As part of continuing studies of Lyme disease, deer were surveyed during three hunting seasons in 1981 to obtain information on geographic distribution and density of I. dammini in New Jersey. I. dammini occurred throughout central and southern New Jersey. Four deer management zones (DMZs) were shown to have high tick densities. Geographical distribution and density data were independently regressed against 25 environmental and physical factors. Elevation was shown to be the most important factor in explaining the variability in both I. dammini distribution and density. Lyme disease cases were closely associated with the distribution of I. dammini and 57.3 percent of 117 Lyme disease cases occurred in the four DMZs previously identified as having the highest tick density.

    PMCID: PMC2590025 PMID: 6334941 [PubMed - indexed for MEDLINE]

  166. Science. 1984 May 11;224(4649):601-3.

    Amblyomma americanum: a potential vector of Lyme disease in New Jersey.

    Schulze TL, Bowen GS, Bosler EM, Lakat MF, Parkin WE, Altman R, Ormiston BG, Shisler JK.

    Amblyomma americanum is a likely secondary vector of Lyme disease in New Jersey. Ticks of this species were removed from the site of the characteristic skin lesion known as erythema chronicum migrans on two patients with the disease, and the Lyme disease spirochete was isolated from nymphs and adults of this species. That A. americanum is a potential vector is supported by its similarities to Ixodes dammini, the known tick vector, in seasonal distribution and host utilization. The extensive range of A. americanum may have great implications for potential Lyme disease transmission outside known endemic areas.

    PMID: 6710158 [PubMed - indexed for MEDLINE]

  167. JAMA. 1984 May 4;251(17):2236-40.

    Clinical manifestations and descriptive epidemiology of Lyme disease in New Jersey, 1978 to 1982.

    Bowen GS, Griffin M, Hayne C, Slade J, Schulze TL, Parkin W.

    Clinical manifestations and epidemiologic characteristics of 117 cases (31 children and 86 adults) of Lyme disease in New Jersey from 1978 to 1982 are summarized. The male-female sex ratio was 1.9:1. An endemic focus in Monmouth County has been recognized. Erythema chronicum migrans was present in 93% of cases and was the only clinical manifestation in 25% of patients. Nonspecific febrile syndrome, in addition to erythema chronicum migrans, was present in 45% of cases; 26% had arthritis. The proportion of cases with arthritis in 1982 (7/56) was less than for 1978 to 1981 (24/61) probably because of better recognition of milder cases by physicians and earlier antibiotic treatment, which may have reduced late complications. Meningitis (10%) and cranial nerve palsies (8%) were the most frequent neurological manifestations. As medical personnel and the public become more aware of the disease, Lyme disease is being recognized with increased frequency in central and southern New Jersey.

    PMID: 6708273 [PubMed - indexed for MEDLINE]

  168. J Med Soc N J. 1982 Jun;79(6):496-500.

    Lyme disease in New Jersey: a cluster of 4 cases and 13 sporadic cases.

    Slade JD, Lenz PR.

    PMID: 6956739 [PubMed - indexed for MEDLINE]

  169. J Med Soc N J. 1981 Jun;78(6):469-70.

    A case of "Lyme Disease" acquired in New Jersey.

    Ward LL.

    PMID: 6942167 [PubMed - indexed for MEDLINE]

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