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Latest Research on Lyme Disease
     
Expert Rev Anti Infect Ther. 2008 Apr;6(2):241-50.
Management of Lyme disease.
Corapi KM, Gupta S, Liang MH.
Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. kricorapi@rcsi.ie

It has been 30 years since Lyme disease was first described in a cohort of patients from Connecticut. An understanding of disease transmission, clinical manifestations and prevention strategies has been established. With the number of new cases increasing each year, it is important that clinicians are aware of the available treatment options. Most patients respond well to a course of treatment with a recommended antibiotic; however, for those patients who develop post-Lyme disease syndrome, the management is unclear. This review provides an overview of Lyme disease and the recommended treatment options available to physicians.

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Epidemiol Infect. 2008 Mar 6;:1-5 [Epub ahead of print]
Neuroborreliosis in the South West of England.
Lovett JK, Evans PH, O'Connell S, Gutowski NJ.
Southampton General Hospital, Southampton, UK.

SUMMARYAlthough Lyme borreliosis is increasingly diagnosed in the United Kingdom, few systematic studies have been performed there. UK data suggest that the commonest complications are neurological, but inadequate information exists about their nature and the incidence of late neuroborreliosis. Local data are necessary because clinical presentations may show geographical variation. This study aimed to provide data on clinical manifestations in an area of South West England and to estimate treatment delay. We reviewed clinical records of 88 patients in the Royal Devon and Exeter Hospital catchment area who had positive Borrelia antibody tests during a 5-year period. Fifty-six (64%) reported tick bites. The commonest presentations were erythema migrans (65%) and arthralgia/myalgia (27%). However, 22 patients (25%) had neurological symptoms other than headache alone. Fourteen had facial palsy, eight had confusion/drowsiness, four had meningism, five had radiculopathy, two had sixth nerve palsies, and two had peripheral neuropathies. No late, progressive or atypical neurological syndromes were found. Neurological manifestations were generally predictable and usually included either (or all) of meningoencephalitis, facial palsy or radiculopathy.

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J Am Acad Dermatol. 2008 Feb 11 [Epub ahead of print]
Insect repellents: Historical perspectives and new developments.
Katz TM, Miller JH, Hebert AA.
Department of Dermatology, University of Texas at Houston, Houston, Texas.

Arthropod bites remain a major cause of patient morbidity. These bites can cause local or systemic effects that may be infectious or inflammatory in nature. Arthropods, notably insects and arachnids, are vectors of potentially serious ailments including malaria, West Nile virus, dengue, and Lyme disease. Measures to curtail the impact of insect bites are important in the worldwide public health effort to safely protect patients and prevent the spread of disease. The history of insect repellent (IR) lends insight into some of the current scientific strategies behind newer products. Active ingredients of currently available IRs include N,N-diethyl-3-methylbenzamide (DEET), botanicals, citronella, and, the newest agent, picaridin. Currently, the Environmental Protection Agency's registered IR ingredients approved for application to the skin include DEET, picaridin, MGK-326, MGK-264, IR3535, oil of citronella, and oil of lemon eucalyptus. DEET has reigned as the most efficacious and broadly used IR for the last 6 decades, with a strong safety record and excellent protection against ticks, mosquitoes, and other arthropods. Newer agents, like picaridin and natural products such as oil of lemon eucalyptus are becoming increasingly popular because of their low toxicity, comparable efficacy, and customer approval. Various characteristics and individual product advantages may lead physicians to recommend one agent over another.

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Emerg Infect Dis. 2008 Feb;14(2):210-6.
Effectiveness of personal protective measures to prevent Lyme disease.
Vázquez M, Muehlenbein C, Cartter M, Hayes EB, Ertel S, Shapiro ED.
Yale University School of Medicine, New Haven, Connecticut, USA. marietta.vazquez@yale.edu

After the manufacture of Lyme vaccine was discontinued in 2002, strategies to prevent Lyme disease (LD) have focused on personal protective measures. Effectiveness of these measures has not been conclusively demonstrated. The aim of our case-control study was to assess the effectiveness of personal preventive measures in a highly disease-endemic area. Case-patients were persons with LD reported to Connecticut's Department of Public Health and classified as having definite, possible, or unlikely LD. Age-matched controls without LD were identified. Study participants were interviewed to assess the practice of preventive measures and to obtain information on occupational and recreational risk factors. Use of protective clothing was 40% effective; routine use of tick repellents on skin or clothing was 20% effective. Checking one's body for ticks and spraying property with acaricides were not effective. We concluded that use of protective clothing and of tick repellents (on skin o
r clothing) are effective in preventing LD.

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Adv Exp Med Biol. 2008;609:185-95.
Lyme disease.
Shapiro ED.
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA. Eugene.Shapiro@Yale.edu

We now have more than 30 years of solid, scientific research about Lyme disease, a relatively common, vector-borne illness in parts of the United States and of Europe. Although there is still widespread misunderstanding of and misinformation about the disease among the lay public, its clinical manifestations as well as how to diagnose and to treat it are now well understood. In the vast majority of cases simple treatment with a relatively short course of orally administered antimicrobials results in long-term cure with no adverse sequelae.

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Annu Rev Entomol. 2008;53:323-43.
Prevention of tick-borne diseases.
Piesman J, Eisen L.
Division of Vector-Borne Infectious Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA. jfp2@cdc.gov

Tick-borne diseases are on the rise. Lyme borreliosis is prevalent throughout the Northern Hemisphere, and the same Ixodes tick species transmitting the etiologic agents of this disease also serve as vectors of pathogens causing human babesiosis, human granulocytic anaplasmosis, and tick-borne encephalitis. Recently, several novel agents of rickettsial diseases have been described. Despite an explosion of knowledge in the fields of tick biology, genetics, molecular biology, and immunology, transitional research leading to widely applied public health measures to combat tick-borne diseases has not been successful. Except for the vaccine against tick-borne encephalitis virus, and a brief campaign to reduce this disease in the former Soviet Union through widespread application of DDT, success stories in the fight against tick-borne diseases are lacking. Both new approaches to tick and pathogen control and novel ways of translating research findings into practical control measures are needed to prevent tick-borne diseases in the twenty-first century.

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Med Hypotheses. 2007 Nov 1 [Epub ahead of print]
The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders.
Bransfield RC, Wulfman JS, Harvey WT, Usman AI.
Department of Psychiatry, Riverview Medical Center, 225 State Route 35, Red Bank, NJ, United States.

Chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading to increased vulnerability for developing autism spectrum disorders. A dysfunctional synergism with other predisposing and contributing factors may contribute to autism spectrum disorders by provoking innate and adaptive immune reactions to cause and perpetuate effects in susceptible individuals that result in inflammation, molecular mimicry, kynurenine pathway changes, increased quinolinic acid and decreased serotonin, oxidative stress, mitochondrial dysfunction and excitotoxicity that impair the development of the amygdala and other neural structures and neural networks resulting in a partial Klüver-Bucy Syndrome and other deficits resulting in autism spectrum disorders and/or exacerbating autism spectrum disorders from other causes throughout life. Support for this hypothesis includes multiple cases of mothers with Lyme disease and children with autism spectrum disorders; fetal neurological abnormalities associated with tick-borne diseases; similarities between tick-borne diseases and autism spectrum disorder regarding symptoms, pathophysiology, immune reactivity, temporal lobe pathology, and brain imaging data; positive reactivity in several studies with autistic spectrum disorder patients for Borrelia burgdorferi (22%, 26% and 20-30%) and 58% for mycoplasma; similar geographic distribution and improvement in autistic symptoms from antibiotic treatment. It is imperative to research these and all possible causes of autism spectrum disorders in order to prevent every preventable case and treat every treatable case until this disease has been eliminated from humanity.

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J Emerg Med. 2007 Oct 16 [Epub ahead of print]
An Update on the Diagnosis and Treatment of Early Lyme Disease: "Focusing on the Bull's Eye, You May Miss the Mark"
Stonehouse A, Studdiford JS, Henry CA.
Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

To confidently diagnose and treat Lyme disease, the clinician must first understand the natural history of this disease, especially its protean early manifestations. Emergency physicians, primary care physicians, and other providers need to be vigilant in terms of the timely recognition of erythema migrans (EM), the unique marker of early localized stage 1 disease. The classic EM, originally described as a slowly expanding bull's eye lesion, is now recognized to be present in only the minority of cases (9%); the dominant morphologic lesion of EM is now recognized to be the diffusely homogenous red plaque or patch, which occurs in over 50% of cases. This update will define the current morphologic features of early Lyme disease, the indication for serologic studies, and the most recent treatment guidelines, including therapeutic pitfalls.

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Neurology. 2007 Oct 10 [Epub ahead of print]
A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.
Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackeim HA.
From the Department of Psychiatry (B.A.F., J.G.K., K.M.C., E.P., I.S., J.C., H.A.S.), Department of Biostatistics (E.P.), Department of Neurology (C.B.B.), Department of Medicine (E.D., J.D.), and New York State Psychiatric Institute (B.A.F., J.G.K., K.M.C., E.P., I.S., J.C., H.A.S.), Columbia University, New York; and Department of Cell and Molecular Biology, University of Rhode Island, Kingston (D.R.N.).

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across
six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

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Clin Infect Dis. 2007 Oct 15;45(8):1032-8. Epub 2007 Sep 11.
Reinfection in patients with Lyme disease.
Nadelman RB, Wormser GP.
Division of Infectious Diseases, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. robert_nadelman@nymc.edu

Lyme disease is the most common tick-borne infection in the United States and Europe. A surprising number of patients experience a subsequent episode of Lyme disease after the first episode has resolved. Reinfection has been well-documented only after successfully treated early infection (nearly always erythema migrans) and can often be recognized clinically by the development of a repeat episode of erythema migrans occurring at a different location on the skin during months when the principal tick vectors are abundant in the environment. Limited data suggest that the clinical and laboratory manifestations of reinfection in patients with Lyme disease with erythema migrans are not very different from those of initial infection. Patients with recurrent infections afford an opportunity to study the role of the immune response in this illness. Because patients with early Lyme disease continue to remain at high risk for reinfection, this population should be targeted for education about prevention of Lyme disease.

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Med Mal Infect. 2007 July - August;37(7-8):394-409. Epub 2007 Aug 21.
[Microbiological and pharmacological data useful for the treatment of Lyme disease. Treatment and follow up of early Lyme disease (erythema migrans).]
[Article in French]
Martinot M.
Service de médecine interne et rhumatologie, centre hospitalier Louis-Pasteur, 39, avenue de la Liberté, 68000 Colmar, France.

The aim of this review was first to analyze the microbiological and pharmacological criteria used to choose a treatment for Lyme disease. The determination of Borrelia burgdorferi sensu lato susceptibility to antibiotics is difficult, especially because of the lack of standardization in the methods used. In vitro data is helpful to determine Lyme treatment but discrepancies between in vitro and in vivo results highlight the need to confirm this data by clinical trials. The second part is an analysis of the literature made to evaluate the current strategies of treatment and follow up of early Lyme disease characterized by erythema migrans (EM). beta-lactams (penicillin G and V, amoxicillin, cefuroxime axetil, ceftriaxone), tetracyclines (doxycycline), and macrolides (mainly azithromycin) are the drugs most frequently used during clinical trials. The comparison between treatments is difficult because of the lack of reliable clinical and biological criteria to identify complete recovery. However the prognosis of treated EM is good in most trials. If a clinical follow-up remains necessary after the treatment of an EM, prolonged antibody production among asymptomatic patients reduces the interest of a serological follow-up.

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Med Mal Infect. 2007 July - August;37(7-8):368-380. Epub 2007 Aug 17.
[Treatment and follow up of disseminated and late Lyme disease.]
[Article in French]
Mohseni Zadeh M.
Service de médecine interne et de maladies infectieuses et tropicales, hôpital civil, 1, place de l'Hôpital, BP 426, 67091 Strasbourg cedex, France.

The aim of this review was to analyze the current strategies of treatment and follow-up of disseminated and late Lyme borreliosis. A comprehensive search was performed using the Medline database. Only relevant reviews, expert guidelines and randomized controlled clinical trials were selected and, if necessary, open trials. Major drugs used in these studies were amoxicillin, doxycycline, penicillin G, and ceftriaxone. Oral administration of antibiotics was preferred in Lyme arthritis whereas parenteral drugs were mostly used in neuroborreliosis. The treatment duration usually ranged from 14 to 30 days. Prolonged antibiotic courses recommended by some authors in post-Lyme syndromes were not validated by several randomized placebo controlled studies. Follow up patterns were analyzed in order to determine possible prognosis parameters allowing to distinguish active Borrelia burgdorferi infection from a sequel of infection.

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Med Mal Infect. 2007 July - August;37(7-8):422-434. Epub 2007 Aug 14.
[Lyme arthritis, Lyme carditis and other presentations potentially associated to Lyme disease.]
[Article in French]
Begon E.
Service de dermatologie, centre hospitalier général René-Dubos, 6, avenue de l'Île-de-France, BP 79, 95303 Cergy-Pontoise cedex, France.

Lyme disease or Lyme borreliosis is the most common tick-transmitted disease in the Northern hemisphere and is caused by Borrelia burgdorferi spirochetes. Lyme disease commonly begins with a characteristic skin lesion, erythema migrans. Weeks or months later, the patients may have neurologic, joint, or cardiac abnormalities. Some patients may still present persistent deep fatigue and various unspecific symptoms after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease", or "post-Lyme disease syndrome". The first French National Consensus Conference on Lyme Disease was the reason to review all aspects of articular and cardiac manifestations of Lyme disease after a synthesis of recent literature. The involvement of Borrelia species in chronic Lyme disease and other pathologies is discussed.

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Med Mal Infect. 2007 July - August;37(7-8):511-517. Epub 2007 Jul 16.
[Cardiac involvement in Lyme disease.]
[Article in French]
Lamaison D.
Service de cardiologie, CHU, place Henri-Dunant, 63000 Clermont-Ferrand, France.

Cardiac manifestations of Lyme Borreliosis are relatively infrequent, occurring within weeks after the infectious tick bite (median of 21 days), and resulting at this stage from a direct borrelial infection of the myocardium, as indicated by reports of spirochete isolation from pericardium and myocardium. They may persist or appear in the late, tertiary phase of the illness, being then more likely due to infection-triggered autoimmunity. Lyme carditis typically presents with a fluctuating degree of atrioventricular block that spontaneously resolves in several days. Rarely, myocarditis may occur with or without pericardial involvement, in patients presenting with chest pain, ST depression or T wave inversion, mimicking an acute myocardial infarction, and various arrhythmias are reported, as well as pericardial effusion or heart failure. A complete recovery is usually observed, spontaneous or after antibiotherapy. Severe myocarditis or Pericarditis leading to death is exceptional. The diagnosis of Lyme carditis is based on the same association of clinical and laboratory features as in Lyme disease without cardiac involvement. But the occurrence of conduction disturbances in healthy young people suggests screening for other criteria of Lyme disease. The management of Lyme carditis does not differ from the treatment of Lyme disease without carditis and is mainly based upon the use of doxycycline or ceftriaxone.

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Clin Infect Dis. 2007 Jul 15;45(2):149-57. Epub 2007 Jun 5. Comment on:
Clin Infect Dis. 2007 Jul 15;45(2):143-8.
Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with lyme disease.
Stricker RB.
International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com

BACKGROUND: Controversy exists regarding the diagnosis and treatment of Lyme disease. Patients with persistent symptoms after standard (2-4-week) antibiotic therapy for this tickborne illness have been denied further antibiotic treatment as a result of the perception that long-term infection with the Lyme spirochete, Borrelia burgdorferi, and associated tickborne pathogens is rare or nonexistent. METHODS: I review the pathophysiology of B. burgdorferi infection and the peer-reviewed literature on diagnostic Lyme disease testing, standard treatment results, and coinfection with tickborne agents, such as Babesia, Anaplasma, Ehrlichia, and Bartonella species. I also examine uncontrolled and controlled trials of prolonged antibiotic therapy in patients with persistent symptoms of Lyme disease. RESULTS: The complex "stealth" pathology of B. burgdorferi allows the spirochete to invade diverse tissues, elude the immune response, and establish long-term infection. Commercial testing
for Lyme disease is highly specific but relatively insensitive, especially during the later stages of disease. Numerous studies have documented the failure of standard antibiotic therapy in patients with Lyme disease. Previous uncontrolled trials and recent placebo-controlled trials suggest that prolonged antibiotic therapy (duration, >4 weeks) may be beneficial for patients with persistent Lyme disease symptoms. Tickborne coinfections may increase the severity and duration of infection with B. burgdorferi. CONCLUSIONS: Prolonged antibiotic therapy may be useful and justifiable in patients with persistent symptoms of Lyme disease and coinfection with tickborne agents.

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Clin Infect Dis. 2007 Jul 15;45(2):143-8. Epub 2007 Jun 5. Comment in:
Clin Infect Dis. 2007 Jul 15;45(2):149-57.
Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease.
Auwaerter PG.
Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. pauwaert@jhmi.edu

It is not well understood why some patients develop a subjective syndrome that includes considerable fatigue, musculoskeletal aches, and neurocognitive dysfunction after receiving standard antibiotic courses for the treatment of Lyme disease. Some practitioners use the term "chronic Lyme disease" and order prolonged courses of oral and parenteral antibiotics, believing that persistent infection with Borrelia burgdorferi is responsible. However, well-performed prospective studies have found neither evidence of chronic infection nor a benefit worthy of long-term antibiotic therapy for these patients. Such extended antibiotic therapy poses hazards and cannot be viewed as acceptable. The term "chronic Lyme disease" should be discarded as misleading; rather, the term "post-Lyme disease syndrome" better reflects the postinfectious nature of this condition. Further research is necessary to understand possible mechanisms of these chronic symptoms following Lyme disease as well as to
find effective therapies.

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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.

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Curr Opin Pediatr. 2007 Jun;19(3):275-80.
Lyme disease update.
Hoppa E, Bachur R.
Division of Emergency Medicine, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA. Eric.hoppa@childrens.harvard.edu

PURPOSE OF REVIEW: Lyme disease is endemic to areas in both Europe and the United States and the incidence is increasing. Despite published guidelines, controversy persists about its diagnosis and management in patients who do not meet strict diagnostic criteria. This review summarizes important recently published studies and recommendations for the diagnosis and management of Lyme disease. RECENT FINDINGS: Recent comprehensive guidelines have been published for the diagnosis and management of pediatric Lyme disease. In addition, recent studies may help physicians differentiate between Lyme and aseptic meningitis, as well as show the poor sensitivity of cerebrospinal fluid polymerase chain reaction. Controversy continues about the diagnosis and management of "chronic Lyme disease", despite the current medical literature. Recently published studies in the US have also better described southern tick-associated rash illness, an entity that may present a similar clinical picture to Lyme disease. Guidelines have also been published on the management and diagnosis of other tick-borne illnesses often seen as co-infections with Lyme disease. Finally, case reports have been published describing new cardiac manifestations associated with Lyme disease. SUMMARY: Controversies persist about the diagnosis and management of Lyme disease. Recently published guidelines and primary research can aid clinicians in diagnosing Lyme properly.

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J Dtsch Dermatol Ges. 2007 May;5(5):406-14.
Lyme borreliosis—an update.
[Article in English, German]
Aberer E.
Klinik für Dermatologie, Medizinische Universität Graz, Graz, Austria. elisabeth.aberer@meduni-graz.at

Lyme borreliosis is the most common tick-borne, infectious disease in the northern hemisphere. Disease manifestations in the United States and Europe vary as a result of geographic distribution of different species within the genospecies Borrelia burgdorferi sensu lato, which in turn are host-specific. Certain toxigenic B. burgdorferi strains cause early disseminated disease. The ability of Borrelial organisms to break down the extracellular matrix also promotes dissemination. B. burgdorferi are eliminated by complement-mediated lysis and by T and B cell activity of the specific immune response. Yet, B. burgdorferi can evade humoral immunity by means of type of protective mechanism by which it adheres to the proteoglycan decorin in the joints and skin. A further factor in the persistence of the pathogen is altered antigen expression. Re-infection usually occurs with a different strain, although repeated infection with the same strain is also possible after a certain period of latency. New developments in serologic testing include the use of recombinant native antigen as well as antigens produced in vivo such as VlsE (variable major protein-like sequence, expressed) or decorin-binding protein A. Diagnosis continues to be complicated by seropositivity of healthy individuals, the persistence of antibodies after therapy, and a lacking humoral immune response in patients with erythema migrans.

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Health Educ Behav. 2007 Apr 27; [Epub ahead of print]
A Controlled Trial of a Novel Primary Prevention for Lyme Disease and Other Tick-Borne Illnesses.
Daltroy LH, Phillips C, Lew R, Wright E, Shadick NA, Liang MH.
Brigham and Women's Hospital, Harvard Medical School, Harvard School of Public Health, Boston, Massachusetts.

To evaluate a theory-based educational program to prevent Lyme disease and other tick-borne illnesses (TBI), a randomized controlled trial of an educational program was delivered to ferry passengers traveling to an endemic area in southeastern Massachusetts. Rates of TBI and precautionary and tick check behaviors were measured over three summers in 30,164 passengers. There were lower rates of TBI among participants receiving TBI education compared with control participants receiving bicycle safety education (relative risk [RR] = 0.79) and a 60% reduction in risk among those receiving TBI education who visited Nantucket Island for more than 2 weeks compared to control participants (RR = 0.41,95% confidence intervals = 0.18 to 0.95, p < .038). TBI-educated participants were also significantly more likely to take precautions (use repellent, protective clothing, limit time in tick areas) and check themselves for ticks. The study demonstrates that a theory-based Lyme disease prevention program can increase precautionary behavior and result in a significant reduction in TBI.

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Med Mal Infect. 2007 Apr 3; [Epub ahead of print]
[Antibiotherapy for early localized Lyme disease.]
[Article in French]
Monsel G, Canestri A, Caumes E.
Service des maladies infectieuses et tropicales, groupe hospitalier de la Pitie-Salpetriere, Assistance publique-hopitaux de Paris, 47-83, boulevard de l'hopital, 75651 Paris cedex 13, France.

OBJECTIVE: The aim of this article is to provide clinicians with guidelines for the antibiotherapy of early-localized Lyme disease. The outcome measures are the clearance of erythema migrans and associated symptoms of early localized Lyme disease and the prevention rate of late complications, with a low risk of adverse effects. Design. The reviewed studies were selected by Medline with the keywords: "erythema migrans, treatment". Sixteen studies comparing treatment or duration of treatment were analyzed. RESULTS: Amoxicillin, doxycycline, and cefuroxim axetil are equally efficacious for early-localized Lyme disease. Azithromycin is an alternative. Most patients respond completely and less than 10% fail to respond. All antibiotics are associated with a low frequency of adverse effects, with the exception of Jarisch Herxheimer reaction which occurs in about 15% of the patients. CONCLUSIONS: We recommend treating adults with amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (100 mg bid) for 14 days (erythema migrans) to 21 days (early localized Lyme disease with associated symptoms). For children, we recommend amoxicillin (50 mg/kg/day in 3 intakes) or doxycycline (4 mg/kg/day in 2 intakes, maximum 100 mg/dose) above 8 years of age. Cefuroxim axetil (500 mg twice daily for adults or 30 mg/kg/day in 2 intakes, maximum 500 mg/dose, for children), and azithromycin (500 mg/day for adults and 20 mg/kg/day for children for 7-10 days) are second line treatment.

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Med Mal Infect. 2007 Apr 2; [Epub ahead of print]
[Lyme disease: basis for treatment strategy, primary preventive care and secondary preventive care.]
[Article in French]
Guy N.
Service de neurologie, CHU de Clermont-Ferrand, BP 69, 63003 Clermont-Ferrand cedex 01, France.

Lyme disease is the most common tick borne disease and is caused by Borrelia burgdorferi sensu lato. Ticks of the genus Ixodes are the vectors that transmit the infection to host mammals in endemic foci. Ixodes is infected by Borrelia at larval stage when it feeds on infected mammals. Man is an occasional host. The infection risk is linked to interaction between human and the natural environment. Strategies for prevention are closely related to the enzootic cycle of the Ixodes tick. Environmental measures to reduced tick density or host mammals are expensive, need to be repeated annually and cannot be applied to large areas. The primary prevention could be reduced to personal preventive measures such as reducing the amount of exposed skin and frequent checking for ticks. The risk of Lyme disease transmission after a tick bite is relatively low, and remains under 4%. The transmission rate depends on the duration of feeding. A rapide tick removal with fine tweezers or preferably special forceps and disinfection of the bite site appear to be the best technique. The absence of scientific evidence, and the risk of adverse events does not lead to recommending antimicrobial prophylaxis. Follow-up and educating the patients on the disease, clinical manifestation, and later primary prevention should be undertaken.

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Med Mal Infect. 2007 Mar 29; [Epub ahead of print]
[Lyme disease: prophylaxis after tick bite.]
[Article in French]
Patey O.
Service des maladies infectieuses et tropicales, groupe etudes epidemiologique et prophylactique, CHI de Villeneuve-Saint-Georges, 94195 Villeneuve-Saint-Georges, France.

Lyme disease is a bacterial infection caused by Borrelia burgdorferi, which is transmitted by infected ticks. The transmission depends on several factors, especially on the duration of the tick's presence in the host body (the nymph which is smaller than the adults and thus less visible, is in this case the most frequently involved) and on whether the tick is infected or not. The interpretation of results in the few available studies is made difficult by the lack of information obtained (due to difficulty to collect information and examination costs). The comparison is made even more difficult by the difference between Borrelia ticks species in various regions. Today, the best methods are preventive: protective clothing, tick repellents, checking and removal of ticks after a journey in an endemic zone, and in case of tick bite, regular examination of the bite site during the following weeks in order to initiate an early curative treatment if ECM is diagnosed. The currently available data seems to be insufficient to suggest systematic antimicrobial prophylaxis in case of tick bite.

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Med Mal Infect. 2007 Mar 19; [Epub ahead of print]
[Ocular manifestations of Lyme disease.]
[Article in French]
Bodaghi B.
Service d'ophtalmologie, universite Paris-VI, CHU de la Pitie-Salpetriere, 47-83, boulevard de l'Hopital, 75651 Paris cedex 13, France.

Despite the wide spectrum of clinical entities, eye involvement remains a rare event in patients with Lyme borreliosis. Most of ocular manifestations occur during the late phase of the disease. The infection needs to be considered along with more conventional causes of ocular inflammation, particularly in regions where Lyme disease is common. The pathogenesis of this condition remains controversial. Direct ocular infection and a delayed hypersensitivity mechanism may be involved at different disease stages. Uveitis and optic neuritis are the most common ocular complications. Serological testing lacks sensitivity and specificity. In atypical cases, ocular fluids sampling and analysis may be proposed. PCR seems to be an interesting diagnostic tool, allowing genotypic analysis. In the majority of cases, therapeutic strategy should be based on the association of antibiotics and corticosteroids. A new course of antibiotics may be prescribed to patients with chronic or relapsing inflammation due to bacterial persistence in ocular tissues.

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Med Mal Infect. 2007 Mar 15; [Epub ahead of print]
[What primary prevention should be used to prevent Lyme disease?]
[Article in French]
Boulanger N.
Service de physiopathologie et antibiologie microbiennes, EA 3432: physiopathologie des interactions hotes-bacteries, faculte de pharmacie de Strasbourg, universite Louis-Pasteur, 74, route du Rhin, BP 60024, 67401 Illkirch cedex, France.

Arthropod-borne diseases are a real public health problem. One of these, Lyme disease, is a bacterial infection due to Borrelia spp., transmitted by a hard tick, Ixodes spp.. The infection is particularly prevalent in the Northern Hemisphere and primary prevention relies on the use of repellents for cloth impregnation (pyrethroids) or for skin application (DEET). Pyrethroids and DEET are the two most studied repellents. The concentration of the active principle is essential to get a real repellent efficiency. The most efficient are: DEET at 30-50%, picaridin or KBR3023 at 20%, citriodiol at 30-50%, and IR35/35 at 20-35%. These molecules may induce adverse-effects. Considered for some time as cosmetics, a new European regulation now defines these molecules as biocides.

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Med Mal Infect. 2007 Mar 8; [Epub ahead of print]
[Neurologic and psychiatric manifestations of Lyme disease.]
[Article in French]
Blanc F; GEBLY.
Departement de neurologie, hopitaux universitaires de Strasbourg, 1, place de l'Hopital, 67091 Strasbourg, France.

The neurological and psychiatric manifestations of Borrelia burgdorferi sensu lato are so numerous that Borrelia is also called the "new great imitator". Thus knowing about the multiple clinical aspects of neuroborreliosis is necessary for the clinician. We reviewed literature for "classical" neuroborreliosis such as acute meningoradiculitis or chronicle encephalomyelitis, but also for encephalitis, myelitis, polyneuritis, radiculitis and more controversial disorders such as chronic neurological disorders, ischemic and hemorrhagic stroke, and motor neuron disease. We specified every time on which basis each disorder was attributed to Lyme disease, particularly if European or American criteria were met. Every part of the nervous system can be involved: from central to peripheral nervous system, and even muscles. In endemic areas, Lyme serology must be assessed in case of unexplained neurological or psychiatric disorder. In case of positive serology, CSF assessment with intrathecal anti-Borrelia antibody index will be more efficient to prove the diagnosis.

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Curr Treat Options Neurol. 2007 Mar;9(2):93-100.
Diagnosis and treatment of the neuromuscular manifestations of lyme disease.
Halperin JJ.
John J. Halperin, MD Atlantic Neuroscience Institute and New York University School of Medicine, Overlook Hospital, 99 Beauvoir Avenue, Summit, NJ 07902, USA. john.halperin@atlantichealth.org.

Although estimates vary, the nervous system appears to be involved in 10% to 15% of patients infected with Borrelia burgdorferi. The resulting disorders, known collectively as neuroborreliosis or nervous system Lyme disease, generally respond well to antimicrobial therapy. Definitive treatment of nervous system infection typically consists of 2 to 4 weeks of parenteral ceftriaxone, cefotaxime, or high-dose penicillin (Class III). However, numerous European studies have shown that oral doxycycline is equally effective in patients with Lyme meningitis and cranial neuritis (Class II and III). This may be equally valid in patients infected with the strains prevalent in the United States, but this remains to be established.

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Nat Clin Pract Rheumatol. 2007 Jan;3(1):20-5.
Strategies for primary and secondary prevention of Lyme disease.
Corapi KM, White MI, Phillips CB, Daltroy LH, Shadick NA, Liang MH.
Royal College of Surgeons in Ireland. kricorapi@rcsi.ie

Lyme disease (borreliosis) incidence continues to increase despite a growing knowledge of primary and secondary prevention strategies. Primary prevention aims to reduce the risk of tick exposure and thereby decrease the incidence of new Lyme disease cases. Secondary prevention targets the development of disease or reduces disease severity among people who have been bitten by infected ticks. Numerous prevention strategies are available, and although they vary in cost, acceptability and effectiveness, uptake has been universally poor. Research in areas where Lyme disease is endemic has demonstrated that despite adequate knowledge about its symptoms and transmission, many people do not perform behaviors to reduce their risk of infection. New prevention strategies should aim to increase people's confidence in their ability to carry out preventive behaviors, raise awareness of desirable outcomes, and aid in the realization that the necessary skills and resources are available for preventive measures to be taken. In this article we evaluate the prevention and treatment strategies for Lyme disease, and discuss how these strategies can be implemented effectively. As many patients with Lyme disease develop arthritis and are referred to rheumatologists it is important that these health-care providers can educate patients about disease-prevention strategies.

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Am J Trop Med Hyg. 2006 Dec;75(6):1090-4.
Reinfection and relapse in early Lyme disease.
Krause PJ, Foley DT, Burke GS, Christianson D, Closter L, Spielman A; Tick-Borne Disease Study Group.
Department of Pediatrics, Connecticut Children's Medical Center and the University of Connecticut School of Medicine, Hartford, CT 06106, USA. Pkrause@ccmckids.org

To determine whether recurrent episodes of appropriately treated Lyme disease are caused by reinfection or relapse, we monitored pertinent clinical manifestations and serology of residents of an endemic site each year for 14 years. Of 253 episodes of early Lyme disease recorded among 213 residents, we observed 40 recurrent episodes. Virtually all included an erythema migrans (EM) rash that appeared at body sites that differed from those of the initial rash, no subjects produced detectable levels of specific antibody between sequential episodes, all episodes occurred a year or more after the initial EM episode, and all occurred during late spring and early summer. People experiencing recurrent episodes tended to have frequent contact with vector ticks. Prompt administration of standard antibiotic therapy for early Lyme disease reliably eliminates persistent infection and prevents relapse.

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Clin Dermatol. 2006 Nov-Dec;24(6):509-20.
Diagnosis, treatment, and prognosis of erythema migrans and Lyme arthritis.
Feder HM Jr, Abeles M, Bernstein M, Whitaker-Worth D, Grant-Kels JM.
Division of Infectious Diseases, University of Connecticut Health Center, Farmington, CT 06030, USA. feder@nso2.uchc.edu

Most patients with erythema migrans, the pathognomonic rash of Lyme disease, do not recall a deer tick bite. The rash is classically 5 to 68 cm of annular homogenous erythema (59%), central erythema (30%), central clearing (9%), or central purpura (2%). Serologic testing is not indicated for patients with erythema migrans, because initially, the result is usually negative. Successful treatment of a patient with erythema migrans can be accomplished with 20 days of oral doxycycline, amoxicillin, or cefuroxime axetil. Patients with Lyme arthritis usually present with a mildly painful swollen knee. Patients with Lyme arthritis have markedly positive serology and can usually be successfully treated with 28 days of oral doxycycline or amoxicillin. Some patients may have persistent effusion despite 4 to 8 weeks of antibiotics and may need synovectomy. Persistent effusion is not due to persistent infection. Antibiotic therapy for more than 8 weeks for patients with Lyme disease is not indicated. Chronic Lyme disease due to antibiotic resistant infection has not been demonstrated.
 

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