NEW JERSEY LYME DISEASE, BABESIA, ERLICHIA AND BARTONELLA AND TREATMENT
PART TWO
A REVIEW OF MAJOR STUDIES
Recently a troubled and agitated New Jersey pseudo expert in Lyme disease seemed to report no interest in treating Babesia, and since her old protocols were questionable anyway, I suppose it was just as well. Others are treating her failures. She had one tool and one way to treat. In 2008 this is 1990's medicine. I believe one must read very widely, and just because past IV treatment has helped some patients does not mean one tool is the only option in the tool box.
So let's look at a small sample of the PUBLISHED DATA on New Jersey. But as real researchers and seasoned clinicians know, the best information is not even published yet. This is one reason to have expert clinicians and researchers to be close and talking back and forth. I recall one article I wrote for the Journal of the American Medical Association which was accepted and yet was not published for a year. In tick and flea-infection science at this time, a year is 10 years.
Here are some sample material relating only to New Jersey Lyme Disease
- 1: 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]
- 2: 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.
Publication Types:
PMID: 17915504 [PubMed - in process]
- 3: MMWR Morb Mortal Wkly Rep. 2007 Jun 15;56(23):573-6.
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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]
- 4: Lancet Neurol. 2007 Jun;6(6):544-52.
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: infection, immunity, and inflammation.
Pachner AR, Steiner I.
Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA. pachner@umdnj.edu
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.
Publication Types:
PMID: 17509489 [PubMed - indexed for MEDLINE]
- 5: 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.
Publication Types:
PMID: 17162963 [PubMed - indexed for MEDLINE]
- 6: 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.
Publication Types:
PMID: 17160603 [PubMed - indexed for MEDLINE]
- 7: 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]
- 8: 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.
Publication Types:
PMID: 16940140 [PubMed - indexed for MEDLINE]PMCID: PMC1695479
- 9: 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.
Publication Types:
PMID: 16892637 [PubMed - indexed for MEDLINE]
- 10: 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
Publication Types:- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
PMID: 16729846 [PubMed - indexed for MEDLINE]PMCID: PMC1472550
- 11: Infect Immun. 2006 May;74(5):3016-20.
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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.
Publication Types:
PMID: 16622242 [PubMed - indexed for MEDLINE]PMCID: PMC1459710
- 12: 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.
Publication Types:
PMID: 16524769 [PubMed - indexed for MEDLINE]
- 13: 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.
Publication Types:
PMID: 16465748 [PubMed - indexed for MEDLINE]
- 14: 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.
Publication Types:
PMID: 16465736 [PubMed - indexed for MEDLINE]
- 15: 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.
Publication Types:
PMID: 16417434 [PubMed - indexed for MEDLINE]
- 16: J Neuroimmunol. 2006 Apr;173(1-2):56-68. Epub 2006 Jan 4.
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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.
Publication Types:
PMID: 16387369 [PubMed - indexed for MEDLINE]
- 17: Int J Epidemiol. 2005 Dec;34(6):1345-7. Epub 2005 Sep 2.
Comment on:
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
Publication Types:
PMID: 16143662 [PubMed - indexed for MEDLINE]
- 18: 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.
Publication Types:
PMID: 15962799 [PubMed - indexed for MEDLINE]
- 19: 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.
Publication Types:
PMID: 15929033 [PubMed - indexed for MEDLINE]
- 20: 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.
Publication Types:- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
PMID: 15695691 [PubMed - indexed for MEDLINE]PMCID: PMC548028
- 21: 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]
- 22: 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.
Publication Types:
PMID: 15448708 [PubMed - indexed for MEDLINE]
- 23: Ann Neurol. 2004 Sep;56(3):361-70.
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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.
Publication Types:
PMID: 15349863 [PubMed - indexed for MEDLINE]
- 24: Lab Invest. 2004 Feb;84(2):160-72.
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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.
Publication Types:
PMID: 14688796 [PubMed - indexed for MEDLINE]
- 25: 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.
Publication Types:
PMID: 14680126 [PubMed - indexed for MEDLINE]
- 26: Infect Immun. 2003 Dec;71(12):7087-98.
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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