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SAVE THE DATE!
2014 Lyme & Tick-Borne Diseases:
Medical, Neuropsychiatric & Public Health Implications

Providence Downtown Marriott

Providence, RI

May 3-4, 2014



Recent Lyme & TBD Abstracts

 

Anesthesia. 2012, 67, 180–183, doi:10.1111/j.1365-2044.2011.06941.x

Spinal anaesthesia for caesarean delivery in a parturient with babesiosis
and Lyme disease
P. Sultan, C. Green, E. Riley and B. Carvalho.

Specialist Registrar, University College London Hospital, London, UK. Community Physician, Greenoaks Medical Center, PC Los Altos, CA. Associate Professor of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA

SUMMARY
We present a case of a parturient with babesiosis and Lyme disease who was scheduled for elective caesarean section. The caesarean section was performed under spinal anaesthesia, and the patient had a coronary artery dissection 4 days postoperatively. Neuraxial anaesthesia and possible mechanisms for the coronary artery dissection in a patient with babesiosis and Lyme disease are discussed.

Babesiosis is a tick-borne infectious disease caused by intraerythrocyte protozoa, that has many clinical features similar to malaria [1, 2]. An increasing number of cases are occurring in endemic parts of North Eastern USA [3]. Lyme borreliosis is caused by the spirochete Borrelia burgdorferi sensu lato, and is the most common human tick-borne disease in the northern hemisphere. The prevalence of Lyme borreliosis is estimated to be 20–100 cases per 100 000 population in the USA, and about 100–130 cases per
100 000 in Europe [4, 5]. The Centers for Disease Control and Prevention (CDC) reported 28 921 Lyme disease cases in 2008, and estimated that this may only represent 10% of the actual number of cases. To our knowledge, there have been no reports describing neuraxial anaesthesia in patients with either Lyme disease or babesiosis. We present the anaesthetic management of an obstetric patient with both babesiosis and Lyme disease who presented for elective caesarean section, and consider possible mechanisms for the coronary artery dissection that occurred postoperatively.

CASE REPORT
A 34-year-old primigravida, with a singleton pregnancy, presented for obstetric care at 20 weeks’ gestation. The patient’s clinical history of babesiosis began abruptly seven years previously with symptoms of fever, sore throat and a viral-like syndrome, followed by sweats, periodic rigours and chills, weakness, fatigue and severe nausea; all of these symptoms were not responsive to treatment. The patient reported several tick bites since childhood, and after an extensive investigation for chronic fatigue, she tested positive to Babesia WA-1 species (titre 1:1280) in 2005, and also showed evidence of exposure to Borrelia burgdorferi. The laboratory diagnosis of Babesia duncani (then WA-1 babesia) was further established by a fivefold titre change (from 1:1280 in 2005 to < 1:40 in 2008). Following a further tick bite in 2007, an increase in IgM titres from 1:40 to 1:160, and positive FISH (fluorescent in
situ hybridisation) to babesia species suggested active infection caused by a new exposure. Consequently, between 2007 and 2009 the patient required prolonged treatments of atovoquone, azithromycin and malarone, each treatment lasting several weeks to months. Before conception, laboratory evidence of babesiosis had resolved, and the patient’s symptoms had improved. She had a previous history of Herxheimer–Jarisch reaction, a reaction caused by endotoxins released into the body when bacteria are destroyed by antibiotic treatment, following azithromycin and penicillin therapy. Her other past medical history included adrenal insufficiency, which had been diagnosed during surgery for

removal of uterine polyps. The aetiology for adrenal insufficiency was never established but subsequently the patient had been prescribed long term fludrocortisone and hydrocortisone therapy. The patient also reported a history of a herniated L4-5 disc, osteoporosis and hypothyroidism; she was currently euthyroid on levothyroxine therapy. She had no known cardiac risk factors or family history of
cardiac disease or Ehlers-Danlos syndrome. A normal echocardiogram and thyroid function tests had been reported at twelve weeks’ gestation. During pregnancy, her symptoms of malaise and fatigue
worsened and she had recurrence of night sweats during her second trimester. Piroplasm, fluorescent in situ hybridisation to babesia species, and RNA and babesia duncani titres tests were unchanged compared to previous results. These symptoms gradually improved but did not resolve during her third trimester. She was admitted to the labour ward at 39 weeks’ gestation for elective caesarean section for maternal request. On admission her weight was 87 kg and her height was 1.73 m (BMI 29 kg.m)2). An ultrasound of the abdomen revealed an anterior placenta with no anomalies. Laboratory tests performed on the day before surgery were normal and included a haemoglobin level of 13.1 g.dl)1, white cell count of 10.1 · 109.l)1, platelet count of 232 · 109.l)1, activated partial thromboplastin time
(APTT) 26.9 s, prothrombin time (PT) 12.0 s and international normalised ratio (INR) 0.9. The haemoglobin, white cell and platelet counts were stable throughout pregnancy. She was apyrexial (36.5 C) and her vital signs were normal on the day of surgery. A 18-G peripheral intravenous cannula was sited, and the patient received 10 mg metoclopramide, 50 mg ranitidine, 100 mg hydrocortisone and 1 g cefazolin, intravenously. With the patient in a sitting position, spinal anaesthesia was performed with a 25-G Whitacre needle. A total of 1.6 ml 0.75% hyperbaric bupivacaine with 10 lg fentanyl and 200 lg preservative-free morphine was injected intrathecally. The patient was then placed into the supine
position with a left lateral tilt. A sensory level to the T3 dermatome was recorded using pinprick sensation. A total of 1 mg phenylephrine was given intravenously for the treatment of hypotension in order to maintain blood pressure at the patient’s baseline throughout surgery. The patient’s oxygen saturation remained ‡ 97% throughout the peripartum period. Surgery proceeded uneventfully and a
healthy infant with Apgar scores of 9 and 9, at 1 and 5 min, respectively, was delivered. The patient required a total of 150 lg fentanyl intravenously in the last 30 min of the procedure for breakthrough discomfort; the total duration of surgery was 55 min. Estimated surgical blood loss was
800 ml, and the patient received 500 ml Hespan (6% hetastarch in 0.9% sodium chloride; B.Braun Medical Inc., Bethlehem, PA) and 2 l Hartmann’s solution. Following delivery, an initial bolus of 2 IU oxytocin followed by an infusion (20 IU in 1 l Hartmann’s solution at 125 ml.h)1) was administered. No neurological complications or postpartum haemorrhage occurred following surgery. The patient’s postpartum haemoglobin and haematocrit on the fourth postoperative day were 11.7 g.dl.)1 and 0.35,
respectively. The patient’s postpartum course was uneventful until the fourth postoperative day, when she suddenly developed severe substernal pain radiating to her left arm and jaw, associated with  palpitations and shortness of breath. The pain lasted for 2 h before gradually resolving.
The initial ECG showed subtle ST depression in leads II and III, with subtle ST elevation in lead I. Blood tests included a creatine kinase of 1081 U.l)1, a CK-MB 62.5 ng.ml)1 and a troponin level of 15.2 lg.l)1. A bedside echocardiogram demonstrated apical akinesis with moderate-severe hypokinesis of the distal septal and anterior wall and a hyperdynamic base. There was a normal left ventricular size with overall ejection fraction at the lower limits of normal, mild aortic regurgitation, mild tricuspid regurgitation and a trace of mitral regurgitation, and the right ventricular systolic pressure was estimated at 35 mmHg. She was provisionally diagnosed with a non-ST elevation myocardial infarction and was subsequently transferred to the cardiac catheterisation laboratory for further management, following a bolus dose of intravenous heparin. Urgent angiography revealed evidence of dissection in the proximal obtuse marginal branch of the left circumflex artery. The dissection was not flow limiting (Thrombolysis In Myocardial Infarction grade three flow) within this vessel. There was no evidence of coronary dissection elsewhere and due to her stable haemodynamics, revascularisation was not indicated. She was   admitted to the coronary care unit for further medical management and was discharged from hospital seven days after her caesarean section.


PLoS ONE. 2012 Jan;7(1):e29914.doi:10.1371/journal.pone.0022914

Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection    
StMonica E. Embers, Stephen W. Barthold, Juan T. Borda, Lisa Bowers, Lara Doyle, Emir Hodzic, Mary B. Jacobs, Nicole R. Hasenkampf, Dale S. Martin, Sukanya Narasimhan, Katherine M. Phillippi-Falkenstein, Jeanette E. Purcell, Marion S. Ratterree, Mario T. Philipp.

Divisions of Bacteriology & Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, Comparative Pathology, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, Veterinary Medicine, Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana, United States of America, Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California Davis, Davis, California, United States of America, Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America

The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferiand a portion received aggressive antibiotic therapy 4–6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis), culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone) in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.

 

Go to the ABSTRACT Archive



Clin Infect Dis. 2011 Sep;53(6):541-7.

Two-Tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay.
Branda JA, Linskey K, Kim YA, Steere AC, Ferraro MJ.

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. branda.john@mgh.harvard.edu

BACKGROUND:

Lyme disease (LD) antibody testing currently involves a 2-tiered algorithm with a whole-cell sonicate (WCS) enzyme immunoassay (EIA), followed by IgM/IgG Western immunoblots. A single EIA using the C6 peptide of the Borrelia burgdorferi variable-major protein-like sequence expressed lipoprotein provides similar or better sensitivity but less specificity, compared with standard 2-tiered testing. Here, we investigated an alternative 2-tiered strategy, in which the first step remained a WCS EIA, but immunoblotting was replaced by a C6 EIA.

METHODS:

We determined the sensitivity of the 3 testing strategies with use of 91 serum samples from research study patients with LD and 78 serum samples from patients with LD whose samples were submitted to our hospital's clinical laboratory. Specificity was measured using 54 patients with other illnesses and 1246 healthy subjects from areas where the infection is endemic and nonendemic.

RESULTS:

The 2-EIA algorithm in early LD had similar sensitivity as C6 testing alone, and both strategies had better sensitivity than did standard 2-tiered testing (61% and 64%, respectively, vs 48%; P = .03 and P = .008). For late disease, all 3 strategies had 100% sensitivity. The specificity of the 2-EIA algorithm was equal to that of standard 2-tiered testing, and both 2-tiered strategies were more specific than C6 testing alone (for both, 99.5% vs 98.4%; P = .01). The positive predictive value of the 2-EIA algorithm was 70%, compared with 66% for standard 2-tiered testing and 43% for the C6 EIA alone.

CONCLUSIONS:

The 2-EIA strategy matched the individual strengths of the C6 EIA and Western blotting, without the drawbacks. The 2 EIAs provided sensitivity comparable to that of the C6 EIA but maintained the specificity of standard 2-tiered testing.

the disease.


 

Am J Pathol. 2011 Jun;178(6):2726-39.

Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease.
Strle K, Jones KL, Drouin EE, Li X, Steere AC.

Division of Rheumatology, Allergy and Immunology, the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Evidence is emerging for differential pathogenicity among Borrelia burgdorferi genotypes in the United States. By using two linked genotyping systems, ribosomal RNA intergenic spacer type (RST) and outer surface protein C (OspC), we studied the inflammatory potential of B. burgdorferi genotypes in cells and patients with erythema migrans or Lyme arthritis. When macrophages were stimulated with 10 isolates of each RST1, RST2, or RST3 strain, RST1 (OspC type A)-stimulated cells expressed significantly higher levels of IL-6, IL-8, chemokine ligand (CCL) 3, CCL4, tumor necrosis factor, and IL-1β, factors associated with innate immune responses. In peripheral blood mononuclear cells, RST1 strains again stimulated significantly higher levels of these mediators. Moreover, compared with RST2, RST1 isolates induced significantly more interferon (IFN)-α, IFN-γ, and CXCL10, which are needed for adaptive immune responses; however, OspC type I (RST3) approached RST1 (OspC type A) in stimulating these adaptive immune mediators. Similarly, serum samples from patients with erythema migrans who were infected with the RST1 genotype had significantly higher levels of almost all of these mediators, including exceptionally high levels of IFN-γ-inducible chemokines, CCL2, CXCL9, and CXCL10; and this pronounced inflammatory response was associated with more symptomatic infection. Differences among genotypes were not as great in patients with Lyme arthritis, but those infected with RST1 strains more often had antibiotic-refractory arthritis. Thus, the B. burgdorferi RST1 (OspC type A) genotype, followed by the RST3 (OspC type I) genotype, causes greater inflammation and more severe disease, establishing a link between spirochetal virulence and host inflammation.

Arthritis Rheum. 2011 May 17. doi: 10.1002/art.30384. [Epub ahead of print]

Burden and viability of Borrelia burgdorferi in skin or joints, of patients with erythema migrans or lyme arthritis.
Li X, McHugh G, Damle N, Sikand VK, Glickstein L, Steere AC.

Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts; Nitin Damle, MD. South County Internal Medicine, Wakefield RI, and Vijay Sikand, MD, Lawrence and Memorial Hospital, New London, CT.

OBJECTIVE.: To determine Borrelia burgdorferi burden and viability in skin and joints in patients with Lyme disease. METHODS.: Standard and quantitative PCR techniques were used to detect B. burgdorferi DNA in skin samples of 90 patients with erythema migrans (EM) and in synovial fluid (SF) or synovial tissue from 63 patients with Lyme arthritis (LA). QPCR determinations of B. burgdorferi DNA, mRNA and rRNA were made in 10 EM and 11 SF samples. RESULTS.: EM lesions in most patients had positive PCR results for B. burgdorferi DNA, and the majority of LA patients, a late disease manifestation, also had positive results in pre-treatment SF samples. In patients with antibiotic-refractory arthritis, positive PCR results persisted for as long as 11 months, but positive results in the post-antibiotic period did not correlate with relapse or subsequent duration of arthritis, and at synovectomy, all results in synovial tissue were negative. B. burgdorferi mRNA, a marker of spirochetal viability, was detected in 8 of 10 EM samples, but in none of 11 SF samples, even when obtained prior to antibiotics. Moreover, the median ratio of spirochetal rRNA to DNA, a measure of ribosomal activity, was 160 in the 10 EM samples, but only 0.15 in the 3 SF samples with positive results. CONCLUSION.: B. burgdorferi in EM lesions were active and viable, whereas those in SF were moribund or dead at any time point. Thus, detection of B. burgdorferi DNA in SF is not a reliable test of active joint infection in Lyme disease.

Clin Vaccine Immunol. 2011 May;18(5):767-71. Epub 2011 Mar 16.

Anti-Borrelia burgdorferi Antibody Profile in Post-Lyme Disease Syndrome.
Chandra A, Wormser GP, Marques AR, Latov N, Alaedini A.

Department of Medicine, Columbia University Medical Center, 1130 Saint Nicholas Ave., Room 937, New York, NY 10032. aa819@columbia.edu.

Patients with post-Lyme disease syndrome (PLDS) report persistent symptoms of pain, fatigue, and/or concentration and memory disturbances despite antibiotic treatment for Lyme borreliosis. The etiopathogenesis of these symptoms remains unknown and no effective therapies have been identified. We sought to examine the antiborrelia antibody profile in affected patients with the aim of finding clues to the mechanism of the syndrome and its relationship to the original spirochetal infection. Serum specimens from 54 borrelia-seropositive PLDS patients were examined for antibodies to Borrelia burgdorferi proteins p18, p25, p28, p30, p31, p34, p39, p41, p45, p58, p66, p93, and VlsE by automated immunoblotting and software-assisted band analysis. The presence of serum antibodies to the 31-kDa band was further investigated by examination of reactivity against purified recombinant OspA protein. Control specimens included sera from 14 borrelia-seropositive individuals with a history of early localized or disseminated Lyme disease who were symptom free (post-Lyme healthy group), as well as 20 healthy individuals without serologic evidence or history of Lyme disease. In comparison to the post-Lyme healthy group, higher frequencies of antibodies to p28 (P < 0.05), p30 (P < 0.05), p31 (P < 0.0001), and p34 (P < 0.05) proteins were found in the PLDS group. Assessment of antibody reactivity to recombinant OspA confirmed the presence of elevated levels in PLDS patients (P < 0.005). The described antiborrelia antibody profile in PLDS offers clues about the course of the antecedent infection in affected patients, which may be useful for understanding the pathogenic mechanism of the disease.


Clin Vaccine Immunol. 2011 May;18(5):851-9. Epub 2011 Mar 2.

Multiplex Immunoassay for Lyme Disease Using VlsE1-IgG and pepC10-IgM Antibodies: Improving Test Performance through Bioinformatics.
Porwancher RB, Hagerty CG, Fan J, Landsberg L, Johnson BJ, Kopnitsky M, Steere AC, Kulas K, Wong SJ.

Infectious Disease Consultants, PC, 1245 Whitehorse-Mercerville Road, Suite 411, Mercerville, NJ 08619. porwancher@aol.com.

The Centers for Disease Control and Prevention currently recommends a 2-tier serologic approach to Lyme disease laboratory diagnosis, comprised of an initial serum enzyme immunoassay (EIA) for antibody to Borrelia burgdorferi followed by supplementary IgG and IgM Western blotting of EIA-positive or -equivocal samples. Western blot accuracy is limited by subjective interpretation of weakly positive bands, false-positive IgM immunoblots, and low sensitivity for detection of early disease. We developed an objective alternative second-tier immunoassay using a multiplex microsphere system that measures VlsE1-IgG and pepC10-IgM antibodies simultaneously in the same sample. Our study population comprised 79 patients with early acute Lyme disease, 82 patients with early-convalescent-phase disease, 47 patients with stage II and III disease, 34 patients post-antibiotic treatment, and 794 controls. A bioinformatic technique called partial receiver-operator characteristic (ROC) regression was used to combine individual antibody levels into a single diagnostic score with a single cutoff; this technique enhances test performance when a high specificity is required (e.g., ≥95%). Compared to Western blotting, the multiplex assay was equally specific (95.6%) but 20.7% more sensitive for early-convalescent-phase disease (89.0% versus 68.3%, respectively; 95% confidence interval [95% CI] for difference, 12.1% to 30.9%) and 12.5% more sensitive overall (75.0% versus 62.5%, respectively; 95% CI for difference, 8.1% to 17.1%). As a second-tier test, a multiplex assay for VlsE1-IgG and pepC10-IgM antibodies performed as well as or better than Western blotting for Lyme disease diagnosis. Prospective validation studies appear to be warranted.


J Clin Microbiol. 2011 May;49(5):2027-30. Epub 2011 Mar 2.

Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid.
van Burgel ND, Bakels F, Kroes AC, van Dam AP.

Department of Medical Microbiology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, Netherlands. N.D.van_Burgel@LUMC.nl

CXCL13 in cerebrospinal fluid (CSF) could be an important component for diagnosing Lyme neuroborreliosis (LNB). Levels of intrathecal CXCL13 were determined for 58 LNB patients and 210 controls; sensitivity was 88% and specificity was 89% (cutoff, 250 pg of CXCL13/ml of CSF). Elevated levels of CXCL13 can aid in the diagnosis of LNB, but levels should be interpreted with care.


Infection. 2011 Apr 27. [Epub ahead of print]

Oral antibiotic treatment and long-term outcomes of Lyme facial nerve palsy.
Kowalski TJ, Berth WL, Mathiason MA, Agger WA.

Section of Infectious Disease, Gundersen Lutheran Health System, 1900 South Avenue, C04-001, La Crosse, WI, 54601, USA, TJKowals@gundluth.org.

PURPOSE:
To study the long-term functional outcomes of patients with Lyme facial nerve palsy treated with oral antibiotics.

METHODS:
We conducted a retrospective double-cohort study involving patients with Lyme facial nerve palsy treated with oral antibiotics matched to three controls with early localized Lyme disease. Chart review was completed and an SF-36 health questionnaire and standardized symptom questionnaire administered.

RESULTS:
Lyme facial nerve palsy patients were treated with oral antibiotics for a median duration of 21 days (range 7-30 days). Only three patients underwent lumbar puncture and each demonstrated lymphocytic pleocytosis. Fourteen of 15 patients with Lyme facial nerve palsy completely regained nerve function. The long-term outcomes were similar between patients with Lyme facial nerve palsy and controls after a median follow-up duration of 4.6 years. Patients with Lyme facial nerve palsy had significantly higher reported rates of fatigue (60%) than controls (27%) (p = 0.019), but similar energy and vitality scores on the SF-36 questionnaire (55.0 vs. 58.4, p = 0.621). SF-36 social functioning domain scores were significantly lower in patients with Lyme facial nerve palsy (77.5) than in controls (88.6) (p = 0.044). There were no other significant differences noted between the two cohorts.

CONCLUSIONS:
For patients with Lyme facial nerve palsy in North America, treatment with oral doxycycline appears to be an effective therapeutic strategy.



J Neuroinflammation. 2011 Apr 20;8:36.

Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study.
Henningsson AJ, Tjernberg I, Malmvall BE, Forsberg P, Ernerudh J.

Department of Infectious Diseases, Ryhov County Hospital, Jönköping, Sweden. anna.henningsson.jonsson@lj.se

BACKGROUND:
Previous studies indicate that successful resolution of Lyme neuroborreliosis (NB) is associated with a strong T helper (Th) 1-type cytokine response in the cerebrospinal fluid (CSF) followed by a down-regulating Th2 response, whereas the role of the recently discovered Th17 cytokine response is unknown.

METHODS:
To investigate the relative contribution of different Th associated cytokine/chemokine responses, we used a multiple bead array to measure the levels of CXCL10 (Th1 marker), CCL22 (Th2 marker), IL-17 (Th17 marker) and CXCL8 (general inflammation marker), in serum and in CSF from untreated patients with confirmed NB (n = 133), and non-NB patients (n = 96), and related the findings to clinical data. Samples from patients with possible early NB (n = 15) and possible late NB (n = 19) were also analysed, as well as samples from an additional control group with orthopaedic patients (n = 17), where CSF was obtained at spinal anaesthesia.

RESULTS:
The most prominent differences across groups were found in the CSF. IL-17 was elevated in CSF in 49% of the patients with confirmed NB, but was not detectable in the other groups. Patients with confirmed NB and possible early NB had significantly higher CSF levels of CXCL10, CCL22 and CXCL8 compared to both the non-NB group and the control group (p < 0.0001 for all comparisons). Patients in the early NB group, showing a short duration of symptoms, had lower CCL22 levels in CSF than did the confirmed NB group (p < 0.0001). Furthermore, patients within the confirmed NB group showing a duration of symptoms <2 weeks, tended to have lower CCL22 levels in CSF than did those with longer symptom duration (p = 0.023). Cytokine/chemokine levels were not correlated with clinical parameters or to levels of anti-Borrelia-antibodies.

CONCLUSION:
Our results support the notion that early NB is dominated by a Th1-type response, eventually accompanied by a Th2 response. Interestingly, IL-17 was increased exclusively in CSF from patients with confirmed NB, suggesting a hitherto unknown role for Th17 in NB. However, for conclusive evidence, future prospective studies are needed.

 


Eur J Neurol. 2011 Apr;18(4):547-55. doi: 10.1111/j.1468-1331.2010.03229.x. Epub 2010 Oct 27.

The diagnostic spectrum in patients with suspected chronic Lyme neuroborreliosis--the experience from one year of a university hospital's Lyme neuroborreliosis outpatients clinic.
Djukic M, Schmidt-Samoa C, Nau R, von Steinbüchel N, Eiffert H, Schmidt H.

Department of Neurology, University of Goettingen, Goettingen, Germany.

BACKGROUND AND PURPOSE:
Studies addressing the diagnostic relevance of anti-Borrelia burgdorferi (BB) serum antibodies in patients with non-specific symptoms and suspected chronic Lyme neuroborreliosis (LNB) are scarce.

METHODS:
In this study, we enrolled within 1 year 122 patients with suspected chronic LNB. One hundred and fourteen patients had previously tested positive for BB. All patients had previously received antibiotic treatment. Each patient received a clinical examination and measurement of BB-specific antibodies. The diagnosis of neuroborreliosis was made according to the national guidelines of the German Society of Neurology. Nine patients had acute borreliosis. One of the nine met the criteria of acute LNB. Of the remaining 113 patients, 85 patients underwent a lumbar puncture. Ten seronegative subjects without lumbar puncture were also considered. In 61.8% of these 95 patients the quality of life, of sleep, mood, and anxiety were assessed.

RESULTS:
Of 95 patients, 25.3% had symptoms without a somatic cause or evidence of borreliosis, 38.9% had a well-defined illness unrelated to BB infection, and 29.5% suffered from symptoms without a detectable somatic cause, displaying antibodies against BB. Six patients were grouped as post-LNB syndrome. Most common symptoms in all categories were arthralgia, myalgia, dysaesthesia, depressive mood and chronic fatigue.

CONCLUSION:
Patients with persistent symptoms with elevated serum antibodies against BB but without signs of cerebrospinal fluid inflammation require further diagnostic examinations to exclude ongoing infection and to avoid co-infections and other treatable conditions (e.g. autoimmune diseases). One patient with acute LNB, who was treated with ceftriaxone for 3 weeks suffered from LNB with new headaches and persistent symptoms 6 months later. These data should encourage further studies with new experimental parameters.



Neurology. 2011 Mar 22;76(12):1051-8.

A prospective study on the role of CXCL13 in Lyme neuroborreliosis.
Schmidt C, Plate A, Angele B, Pfister HW, Wick M, Koedel U, Rupprecht TA.

Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.

BACKGROUND:
The definite diagnosis of acute Lyme neuroborreliosis (LNB) requires detection of an increased Borrelia burgdorferi-specific antibody index (AI). The B burgdorferi AI, however, is negative in up to 20% of patients with early LNB and can remain elevated for years after adequate therapy; both of these factors can make the diagnosis difficult. Recent retrospective studies suggested the chemokine CXCL13 as a potential biomarker for LNB. To evaluate its diagnostic value, we conducted a prospective study.

METHODS:
From March 2008 to August 2009, CSF and serum samples from all patients in whom a B burgdorferi-specific AI was requested (n=692) and CSF analysis revealed CSF pleocytosis (n=192) were included in the study. Because of the low number of patients with untreated LNB, 13 additional retrospectively selected samples of patients with untreated LNB were added. CXCL13 concentrations were measured by ELISA and receiver operating characteristic curves were generated.

RESULTS:
CSF CXCL13 was highly elevated in all patients with untreated acute LNB (mean=15,149 pg/mL) compared with that in the patients without LNB (mean=247 pg/mL). At a cutoff of 1,229 pg/mL, the sensitivity of CXCL13 was 94.1%, which is higher than the AI (85.7%). Only 7 patients (5 with a CNS lymphoma and 2 with bacterial meningitis) had a CXCL13 level above the cutoff, resulting in a specificity equal to the AI of 96.1%.

CONCLUSIONS:
CXCL13 shows high sensitivity and specificity for acute, untreated LNB. This novel marker appears to be helpful in clinically atypical cases and, in particular, in early stages of the disease when the B burgdorferi AI is (still) negative.



Vector Borne Zoonotic Dis. 2011 Mar 11. [Epub ahead of print].

Pilot Study Assessing the Effectiveness of Long-Lasting Permethrin-Impregnated Clothing for the Prevention of Tick Bites.
Vaughn MF, Meshnick SR.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina.

Abstract Introduction: Tick-borne diseases such as Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis are a significant concern for many thousands of workers who have frequent and unavoidable exposure to tick-infested habitats. Many North Carolina state employees with outdoor occupations report multiple tick bites each year, indicating that existing tick preventive strategies may be underutilized or ineffective. Treatment of clothing with permethrin, a nontoxic chemical with insecticidal, knockdown, and repellent properties, is highly effective against ticks. However, most permethrin products must be reapplied after several washings to maintain insecticidal activity. Recently, a factory-based method for long-lasting permethrin impregnation of clothing has been developed by Insect Shield, Inc., that allows clothing to retain insecticidal activity for over 70 washes. Methods: A nonrandomized open label pilot study was conducted to determine the effectiveness of Insect Shield-treated clothing for the prevention of tick bites among 16 outdoor workers from the North Carolina Division of Water Quality under actual field conditions. Participants completed questionnaires at the start of follow-up (March, 2008) and at the end of follow-up (September, 2008), and tick bites and outdoor work hours were reported on weekly tick bite logs for the entire follow-up period. Results: Subjects wearing Insect Shield-treated clothing had a 93% reduction (p < 0.0001) in the total incidence of tick bites compared to subjects using standard tick bite prevention measures. Conclusion: This study provides preliminary evidence that long-lasting permethrin-impregnated clothing may be highly effective against tick bites.

Clin Vaccine Immunol. 2011 Mar;18(3):406-13. Epub 2010 Dec 22.

BBK07 immunodominant peptides as serodiagnostic markers of Lyme disease.
Coleman AS, Rossmann E, Yang X, Song H, Lamichhane CM, Iyer R, Schwartz I, Pal U.


Department of Veterinary Medicine, Building 795, Room 1341, University of Maryland, College Park, MD 20742, USA.


Lyme disease (LD) is a tick-borne infection caused by the bacterial pathogen Borrelia burgdorferi. Current diagnostic tests mostly use borrelial lysates or select antigens to detect serum antibodies against B. burgdorferi. These immunoassays are not entirely effective, especially for detection of early infection. We have recently characterized an in vivo-induced antigen, BBK07, as a serodiagnostic marker for LD. We now report that in a line blot assay, recombinant BBK07 protein-based detection is 90% sensitive and nearly 100% specific against B. burgdorferi infection in humans. Using an overlapping peptide library of 23 peptides encompassing full-length BBK07, we identified the immunodominant epitopes of BBK07 during human infection. We show that a select combination of amino-terminal peptides significantly enhanced BBK07-based diagnostic accuracy compared to that with the full-length protein. Although in enzyme-linked immunosorbent assay (ELISA) studies BBK07 peptides had overall lower sensitivity than established serodiagnostic peptides, such as the VlsE peptide C6 and OspC peptide pepC10, for the detection of early human LD, a subset of serum samples that failed to recognize either VlsE or OspC peptides were preferentially reactive to BBK07 peptides. These results highlight the fact that BBK07 peptides could be useful to complement the efficacy of VlsE and OspC peptide-based serodiagnostic assays. Finally, using a panel of canine sera, we show that BBK07 peptide is also effective for LD diagnosis in infected dogs. Together, our data show that peptides from the B. burgdorferi surface protein BBK07 are highly specific and sensitive serodiagnostic markers, and we suggest their future use in LD diagnostic assays.


Mol Cell Proteomics. 2011 Mar;10(3):M110.002477. Epub 2010 Nov 16.

Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis.
Seward RJ, Drouin EE, Steere AC, Costello CE.

Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts 02118, USA.

Disease-associated HLA-DR molecules, which may present autoantigens, constitute the greatest genetic risk factor for rheumatoid arthritis (RA) and antibiotic-refractory Lyme arthritis (LA). The peptides presented by HLA-DR molecules in synovia have not previously been defined. Using tandem mass spectrometry, rigorous database searches, and manual spectral interpretation, we identified 1,427 HLA-DR-presented peptides (220-464 per patient) from the synovia of four patients, two diagnosed with RA and two diagnosed with LA. The peptides were derived from 166 source proteins, including a wide range of intracellular and plasma proteins. A few epitopes were found only in RA or LA patients. However, two patients with different diseases who had the same HLA allele had the largest number of epitopes in common. In one RA patient, peptides were identified as originating from source proteins that have been reported to undergo citrullination under other circumstances, yet neither this post-translational modification nor anti-cyclic citrullinated peptide antibodies were detected. Instead, peptides with the post-translational modification of S-cysteinylation were identified. We conclude that a wide range of proteins enter the HLA-DR pathway of antigen-presenting cells in the patients' synovial tissue, and their HLA-DR genotype, not the disease type, appears to be the primary determinant of their HLA-DR-peptide repertoire. New insights into the naturally presented HLA-DR epitope repertoire in target tissues may allow the identification of pathogenic T cell epitopes, and this could lead to innovative therapeutic interventions.


J Bone Joint Surg Am. 2011 Feb 2;93(3):252-60.

Lyme arthritis in children presenting with joint effusions.
Milewski MD, Cruz AI Jr, Miller CP, Peterson AT, Smith BG.


Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06520-8071, USA. mdmilewski@gmail.com


BACKGROUND:
The present study was designed to evaluate the prevalence of Lyme arthritis in children who had a joint aspiration at a tertiary care children's hospital in an endemic area and to identify clinical factors useful to differentiate Lyme arthritis from septic arthritis at the time of the initial presentation.

METHODS:
The records of all children with an age of eighteen years or less who were managed with aspiration for joint effusions at our institution from 1992 to 2009 were reviewed. Data collection included a review of aspirates; an analysis of cell count, culture results, and hematological inflammatory markers; and a review of surgical intervention.

RESULTS:
A total of 506 joint aspirations were analyzed. One hundred and fifteen aspirations were excluded. In the remaining group of 391 patients, 123 (31%) were subsequently diagnosed with Lyme arthritis. Fifty-one patients had culture-positive septic arthritis. The two cohorts were significantly different in terms of the presence of a fever of >101.5°F (>40.6°C) at the time of presentation, the refusal to bear weight, the peripheral white blood-cell count, and joint fluid cell count. The erythrocyte sedimentation rate and the C-reactive protein level were not significantly different between the two cohorts. Multivariate analysis demonstrated that refusal to bear weight was the strongest predictor of the diagnosis of septic arthritis over Lyme arthritis.

CONCLUSIONS:
For any child presenting with a joint effusion in a Lyme-endemic area of the Northeastern United States, the likely prevalence of Lyme arthritis is 31% overall and 45% in the presence of knee effusion. Children with joint effusions resulting from Lyme disease are more likely to have knee involvement, a lower peripheral white blood-cell count, and a lower joint fluid cell count, and they are less likely to have fever or complete refusal to bear weight, when compared with children with septic arthritis.


Cardiol J. 2011;18(1):63-6.

Postural orthostatic tachycardia syndrome following Lyme disease.
Kanjwal K, Karabin B, Kanjwal Y, Grubb BP.


Section of Electrophysiology, Division of Cardiology, Department of Medicine,The University of Toledo Medical Center, Toledo, USA.


BACKGROUND:
A subgroup of patients suffering from Lyme disease (LD) may initially respond to antibiotics only to later develop a syndrome of fatigue, joint pain and cognitive dysfunction referred to as 'post treatment LD syndrome'. We report on a series of patients who developed autonomic dysfunction in the form of postural orthostatic tachycardia syndrome (POTS).

METHODS:
All of the patients in this report had suffered from LD in the past and were successfully treated with antibiotics. All patients were apparently well, until years later when they presented with fatigue, cognitive dysfunction and orthostatic intolerance. These patients were diagnosed with POTS on the basis of clinical features and results of the tilt table (HUTT) testing.

RESULTS:
Five patients (all women), aged 22-44 years, were identified for inclusion in this study. These patients developed symptoms of fatigue, cognitive dysfunction, orthostatic palpitations and either near syncope or frank syncope. The debilitating nature of these symptoms had resulted in lost of the employment or inability to attend school. Three patients were also suffering from migraine, two from anxiety and depression and one from hypertension. All patients demonstrated a good response to the employed treatment. Four of the five were able to engage in their activities of daily living and either resumed employment or returned to school.

CONCLUSIONS:
In an appropriate clinical setting, evaluation for POTS in patients suffering from post LD syndrome may lead to early recognition and treatment, with subsequent improvement in symptoms of orthostatic intolerance.


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