Lyme Disease
Introduction
Lyme disease was named in 1977 when arthritis was observed in a cluster of children in and around Lyme, Connecticut. Other clinical symptoms and environmental conditions suggested that this was an infections disease probably transmitted by an arthropod. Further investigation revealed that Lyme disease is caused by the bacterium, Borrelia burgdorferi. These bacteria are are helical shaped bacteria about 10-25(mu)m long. They are transmitted to humans by the bite of infected deer ticks and cause more than 16,000 infections in the United States each year.
Vector: Black-legged ticks (Ixodes scapularis) are responsible for transmitting Lyme disease bacteria to humans in the north eastern and north-centra) United States. On the Pacific Coast, the bacteria are transmitted to humans by the western black-legged tick (Ixodes pacificus). Ixodes ticks are much smaller than common dog and cattle ticks. In their larval and nymphal stages, they are no bigger than a pinhead. Ticks feed by inserting their mouths into the skin of a host and slowly take in blood. Ixodes ticks are most likely to transmit infection after feeding for two or more days.
Risk: In the United States, Lyme disease is mostly localized to states in the northeastern, mid- Atlantic, and upper north-centra) regions, and to several counties in northwestern California. In 1999, 16,273 cases of Lyme disease were reported to the Centers for Disease Control and Prevention (CDC). Ninety-two percent of these were from the states of Connecticut, Rhode Island, New York, Pennsylvania, Delaware, New Jersey, Maryland, Massachusetts, and Wisconsin.
Individuals who live or work in residential areas surrounded by tick-infected woods or overgrown brush are at risk of getting Lyme disease. Persons who work or play in their yard, participate in recreational activities away from home such as hiking, camping, fishing and hunting, or engage in outdoor occupations, such as landscaping, brush clearing, forestry, and wildlife and parks management in endemic areas may also be at risk of getting Lyme disease.
Prevention and Treatment: It is important to remember that prevention measures can be effective in reducing your exposure to infected ticks, and most patients can be successfully treated with antibiotic therapy when diagnosed in the early stages of Lyme disease. Visit the links below for more information on the following topics:
History of Lyme Disease: Early in the 20th century, European physicians observed patients witti a red, slowly expanding rash (called erythema migrans or EM), associated this rash with the bite of ticks, and postulated that it was caused by a tick-borne bacterium. Then in the 1940s, similar tick-borne illness was described that often began with EM and developed into multi-system ill- ness. Later that decade, spirochete-like structures were observed in skin specimens leading to the use of penicillin for treatment.
Aware of these findings, a physician in Wisconsin diagnosed a patient with EM and successfully treated it with penicillin in 1969. In the mid 1970s, physicians observed clusters of children with arthritis in and around Lyme, Connecticut. Other clinical symptoms and environmental conditions suggested that this was a distinct illness probably transmitted by an arthropod. Researchers linked the presence of EM rasti lesions to preceding tick bites and determined that early treatment with penicillin not only shortened the duration of EM hut also reduced the risk of subsequent arthritis.
In 1982, spirochetes were identified in the midgut of the adult deer tick, Ixodes dammini (referred herein by its original name, the black-legged tick, Ixodes scapularis) and given the name Borrelia burgdorferi. Finally, conclusive evidence that Borrelia burgdorferi caused Lyme discase came in 1984 when spirochetes were cultured from the blood of patients with EM, from the rasti lesion itself, and from the cerebrospinal fluid of a patient with meningo-encephalitis and history of prior EM. CDC began surveillance for Lyme disease in 1982 and the Council of State and Territoria) Epidemiologists (CSTE) designated Lyme disease as a nationally notifiable disease in January 1991.
Symptoms
Lyme disease most often presents witti a characteristic "bull's-eye" rasti, erythema migrans, accompanied by non specific symptoms such as fever, malaise, fatigue, headache, muscle aches (myalgia), and joint aches (arthralgia). The incubation period from infection to onset of erythema migrans is typically 7 to 14 days but may be as short as 3 days and as long as 30 days. Some infected individuals have no recognized illness (asymptomatic infection determined by serological testing), or manifest only non-specific symptoms such as fever, headache, fatigue, and myalgia. Lyme disease spirochetes disseminate from the site of the tick bite by cutaneous, lymphatic and blood borne routes. The signs of early disseminated infection usually occur days to weeks after the appearance of a solitary erythema migrans lesion. In addition to multiple (secondary) erythema migrans lesions, early disseminated infection may be manifest as disease of the nervous system, the musculoskeletal system, or the heart. Early neurological manifestations include lymphocytic meningitis, cranial neuropathy (especially facial nerve palsy), and radiculoneuritis. Musculoskeletal manifestations may include migratory joint and muscle pains witti or without objective signs of joint swelling. Cardiac manifestations are rare but may include myocarditis and transient atrioventricular blocks of varying degree. Borrelia burgdorferi infection in the untreated or inadequately treated patient may progress to late disseminated disease weeks to mouths after infection. The most common objective manifestation of late disseminated Lyme disease is intermittent swelling and pain of one or a few joints, usually large, weight-bearing joints such as the knee. Some patients develop chronic axonal polyneuropathy, or encephalopathy, the latter usually manifested by cognitive disorders, sleep disturbance, fatigue, and personality changes. Infrequently, Lyme discase morbidity may be severe, chronic, and disabling. An ill-defined post-Lyme disease syndrome occurs in some persons following treatment for Lyme disease. Lyme discase is rarely, if ever, fatal.
Diagnosis
The diagnosis of Lyme disease is based primarily on clinical findings, and it is often appropriate to treat patients with early disease solely on the basis of objective signs and a known exposure. Serologic testing may, however, provide valuable supportive diagnostic information in patients with endemic exposure and objective clinical findings that suggest later stage disseminated Lyme disease. When serologic testing is indicated, CDC recommends testing initially with a sensitive first test, either an enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test, followed by testing with the more specific Western immunoblot (WB) test to corroborate equivocal or positive results obtained witti the first test. Although antibiotic treatment in early localized disease may blunt or abrogate the antibody response, patients with early disseminated or late-stage disease usually have strong serological reactivity and demonstrate expanded WB immunoglobulin G (IgG) banding patterns to diagnose Borrelia burgdorferi antigens. Antibodies often persist for months or years following successfully treated or untreated infection. Thus, sero reactivity alone cannot be used as a marker of active disease. Neither positive serologic test results nor a history of previous Lyme disease assures that an individual has protective immunity. Repeated infection with Borrelia burgdorferi has been documented. Borrelia burgdorferi can be cultured from 80% or more of biopsy specimens taken from early erythema migrans lesions. However, the diagnostic usefulness of this procedure is limited because of the need for a special bacteriologic medium (modified Barbour-Stoenner-Kelly medium) and protracted observation of cultures. Polymerase chain reaction (PCR) has been used to amplify genomic DNA of B. burgdorferi in skin, blood, cerobro-spinal fluid, and synovial fluid, but PCR has not been standardized for routine diagnosis of Lyme disease.
Other Tick-Borne Diseases
Southern Tick-Associated Rash Illness Babesiosis
Ehrlichiosis
Rocky Mountain Spotted Fever
Bacterium
Cultivation: The spirochete isolated from ticks and humans was described as Borrelia burgdorferi by Johnson, et al. in 1984. Borrelia burgdorferi can be cultivated from their arthropod vectors or vertebrate hosts in a modified Kelly medium called BSK (BarbourStoenner-Kelly). Borrelia from ticks and from the blood, skin, and cerebrospinal fluid of Lyme disease patients have been successfully cultivated in BSK. BSK solidified with 1.3% agarose allows the production of colonies from single organisms. Borrelia burgdorferi grows slowly as compared to most bacteria. Each spirochete divides into two cells after 12 to 24 hours of elongation. Although the organism can be cultured in media, continuous passage may result in biological changes resulting in a population quite different from their naturally occurring ancestors.
Human disease: The type of Borrelia infectiog humans in the U.S. is designated Borrelia burgdorferi sensu stricto. Borrelia burgdorferi sensu strico and two related Borrelia, Borrelia garinii and Borrelia afzelii also cause Lyme disease in Europe. In Asia, only Borrelia garinii and Borrelia afzelii cause Lyme disease in humans. Evidence is accumulating that these closely related, hut different, spirochetes are associated with somewhat different disease expressions. Arthritis appears to occur more frequently following infection with Borrelia burgdorferi sensu stricto; neurological manifestations are more common in infections with Borrelia garinii; and cutaneous manifestations occur more frequently in association with Borrelia afzelii infection.
Structure
Borrelia, including Borrelia burgdorferi, are flexible helical cells comprised of a protoplasmic cylinder surrounded by a cell membrane, 7 to 11 periplasmic flagella, and an outer membrane that is loosely associated with the underlying structures. The DNA sequence of B. burgdorferi type strain B31 was published in 1997 and contains a 950 kilobase linear chromosome, 9 linear plasmids, and 12 circular plasmids. The outer membrane of Borrelia burgdorferi and other Borrelia is unique in that genes encoding its proteins are located on linear plasmids; these extrachromasomal genes determine the antigenic identity of these organisms and presumably help the bacteria adapt and survive in ticks and different mammalian hosts.
Vector Ecology
Lyme disease is spread by the bite of ticks of the genus Ixodes that are infected witti Borrelia burgdorferi. For Lyme disease to exist in an area, at least three closely interrelated elements must be present in nature: (1) the Lyme disease bacteria B. burgdorferi (2) Ixodes ticks that can transmit the bacteria, and (3) mammals such as mice and deer to provide a blood meal for the ticks through their various life stages.
Picture of the type of forested area that could be a habitat for ticks.
Tick Habitat
In the United States, ticks of the genus Ixodes serve as the competent vectors for transmitting the Lyme disease bacteria, Borrelia burgdorferi to humans. Ixodes ticks can be found in temperate regions with high relative humidity at ground level. Known as die deer tick or black-legged tick, Ixodes scapularis is responsible for transmitting bacteria to humans in the northeastem and northcentral United States. In eastern states, ticks are associated with deciduous forest and habitat containing leaf litter. Leaf lifter provides a moist cover from wind, snow, and other elements. Importantly, research demonstrates that tick populations are reduced 72100% when leaf litter is removed. In the north-central states, I. scapularis is generally found in heavily wooded areas often surrounded by broad tracts of land cleared for agriculture. On the Pacific Coast, the bacteria are transmitted to humans by the western black-legged tick (Ixodes pacificus) and habitats are more diverse. Here, ticks have been collected in habitats witti forest, north coastal scrub, high brush, and open grasslands. Coastal tick populations thrive in areas of high rainfall, but ticks are also found at inland locations.
Life cycle of the deer tick
Knowing the complex life cycle of Ixodes ticks is important in understanding the risk of acquiring Lyme disease and in finding ways to reduce this risk. For this example, we will describe the two year life cycle of an I. scapularis deer tick located in a northeastern state. Life cycles may vary slightly for other ticks located in different regions of North America.
71e life cycle requires 2 years to complete. Adult female ticks lay eggs on the ground in early spring. By summer, eggs hatch into larvae. Larvae feed on mice, other small mammals, deer, and birds in the late summer and early famolt into nymphs, and then are dormant (inactive) until the next spring. Nymphs feed on rodents, small mammals, birds and humans in the late spring and summer and molt into adults in the fall. In die fall and early spring, adult ticks feed and mate on large mammals (especially deer) and bite humans. The adult female ticks then drop off these animals and lay eggs in spring, completing a 2-year life cycle.
Natural reservoirs
Ticks, small rodents, and other non-human vertebrate animals all serve as natural reservoirs for Borrelia burgdorferi. This means that the Lyme disease bacteria can live and grow within these hosts without causing them to die. Larvae and nymph ticks typically become infected with the Lyme disease spirochete, B. burgdorferi, when they feed on small animals that carry the bacteria in spring and summer. The bacteria remain in a tick as it changes from larva to nymph or from nymph to adult in late summer or early fall. Infected nymphs bite and transmit Borrelia burgdorferi bacteria to other small rodents, mammals, and humans, all in the course of their normal feeding behavior.
Transmission to Humans
Research in the eastem United States has indicated that, for the most part, nymphal ticks transmit Lyme disease bacteria to humans from May to July. Feeding nymphs are rarely noticed because of their small size, and thus have ample time to feed on humans. Tïck-to-human transmission of the Lyme disease bacteria usually occurs after approximately 2 or more days of feeding. Although tick larvae are smaller than nymphs, they rarely, if ever, carry Borrelia burgdorferi at the time of feeding and are not important in the transmission of Lyme disease to humans. Adult ticks can transmit the disease, but since they are larger and more likely to be removed from a person's body within a few hours, they are less likely than nymphs to have sufficient time to transmit the infection. As expected, few cases of Lyme disease are reported in the cooler months of the year, when adult Ixodes ticks are most active. National Lyme disease risk map with four categories of risk.
Ticks search for host animals from the tips of grasses, shrubs, and leaf litter and transfer to animals or persons that brush against vegetation. They only crawl, not fly or jump. Ticks can attach to any part of the human body but often crawl to the more hidden areas to feed such as the groin or armpit and often where clothing is tight. They feed on blood by inserting their mouths into the skin of a host animal. T heir bodies slowly enlarge with blood as they feed over several days.
Picture of people enjoying the outdoors in a spot where risk of exposure to ticks may be greatest. Campers, hikers, outdoor workers, and others who frequent wooded, brushy, and grassy places are commonly exposed to ticks, and this may be important in the transmission of Lyme disease in some areas. Because new homes are often built in wooded areas, transmission of Lyme discase near homes has become an important problem in some areas of the United States. The risk of exposure to ticks is greatest in the woods and garden fringe areas of properties, but ticks may also be carried into lawns and gardens by animals.
There is no evidence that a person can get Lyme disease from the air, food or water, from sexual contact, or by handling wild or domestic animals. There is no convincing evidence that Lyme disease can be transmitted by insects such as mosquitoes, flies, or fleas. Lyme disease infection from a blood transfusion or other contact with infected blood or urine has never been documented.
Literature Lyme disease
Adam T, Gossmann GS, Rasiah C, et al. Phenotypic and genotypic analysis of Borrelia burgdorferi isolates from various sources. Infect Immun. 99;59:2579-255.
Anderson JF, Johnson RC, Magnarelli LA, Hyde FW, and Myers JE. Prevalence of Borrelia burgdorferi and Babesia microti in mice on islands inhabited by white-tailed deer. Applied and Environmental Microbiology 97;53:92-94.
Apperson CS, Levine JF, Evans TL, Braswell A, and Heller J. Relative utilization of reptiles and rodents as hosts by immature Ixodes scapularis (Acari: Ixodidae) in the coastal plain of North Carolina, USA. Experimental and Applied Acarology 993;7:79- 73.
Balmelli T, Piffaretti JC. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato. Res Microbiol. 995 May;4(4):329-340.
Baranton G, Postic D, Saint-Girons I, et al. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and Group V54 associated with Lyme borreliosis. Int J Syst Bacteriol. 99;42:37-33.
Barbour AG. Lyme Disease: The Cause, the Cure, the Controversy. 99. The Johns Hopkins University Press, Baltimore, MD. Barbour AG, and Hayes SF. Biology of Borrelia species. Microbiol Rev. 9;50:3-400. Barbour AG, Restrepo BI. Antigenic variation in vector-borne pathogens. Emerg Infect Dis. 2000;(5):449-457.
Benach JL, Bosler EM, Hanrahan JP, et al. Spirochetes isolated from the blood of two patients with Lyme disease. N Engl J Med. 93;30:740-742.
Berger BW, Johnson RC, Kodner C, Coleman L. Cultivation of Borrelia burgdorferi from erythema migrans lesions and perilesional skin. J Clin Microbiol 992;30:359-3.
Brettschneider S, Bruckbauser H, Klugbauer K, Hofmann H. Diagnostic value of PCR for detection of Borrelia burgdorferi in skin biopsy and urine samples from patients with skin borreliosis. J Clin Microbiol 99;3:25-25.
Bujak DI, Weinstein A, Dornbush RL. Clinical and neurocognitive features of the post Lyme syndrome. J Rheumatol 99;23:392- 397.
Burgdorfer W. How the discovery of Borrelia burgdorferi came about. Clin Dermatol. 993 Jul-Sep;(3):335-33.
Burgdorfer WA, Barbour AG, Hayes SF, et al. Lyme disease - a tick-borne spirochetosis? Science. 92;2:37-39.
Burgdorfer W. How the discovery of Borrelia burgdorferi came about. Clin Dermatol. 993 Jul-Sep;(3):335-33.
Burgdorfer W, Schwan TG. Borrelia in Murray PR (ed):Manual of Clinical Microbiology 7th Ed. American Society for Microbiology Press.
Burkot TR, Clover JR, Happ CM, DeBess E, and Maupin GO. Isolation of Borrelia burgdorferi from Neotoma fuscipes, Peromyscus maniculatus, Peromyscus boylii, and Ixodes pacificus in Oregon. American Journal of Tropical Medicine and Hygiene 999;0:453-457.
van Dam AP, Kuiper H, Vos K, Widjojokusumo A, de Jongh BM, Spanjaard L, Ramselaar AC, Kramer MD, Dankert J. Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis. Clin Infect Dis. 993 Oct;7(4):70-77.
Daniels TJ, and Fish D. Effect of deer exclusion on the abundance of immature Ixodes scapularis (Acari: Ixodidae) parasitizing small and medium-sized mammals. Journal of Medical Entomology 995;32:5-.
Dennis DT. Lyme disease. Dermatology Clinics 995;3:537-55.
Dennis DT. Epidemiology, ecology, and prevention of Lyme disease. in Rahn DW, Evans J eds. Lyme disease. Philadelphia, PA: American College of Physicians, 99;7-34.
Dennis DT, Nekomoto TS, Victor JC, Paul WS, Piesman J. Reported distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the United States. Journal of Medical Entomology 99;35:29-3.
des Vignes F, Piesman J, Heffernan R, Schulze TL, Stafford III KC, and Fish D. Effect of tick removal on transmission of Borrelia burgdorferi and Ehrlichia phagocytophila by Ixodes scapularis nymphs. Journal of Infectious Diseases 200;3:773-77.
Dister SW, Fish D, Bros SM, Frank DH, and Wood BL. Landscape characterization of peridomestic risk for Lyme disease using satellite imagery. American Journal of Tropical Medicine and Hygiene 997;57:7-92.
Dressler F, Whelan JA, Reinhart BN, Steere AC. Western blotting in the serodiagnosis of Lyme disease. J Infect Dis 993;7:392- 400.
Duffy DC, Campbell SR, Clark D, Dimotta, and Gurney S. Ixodes scapularis (Acari: Ixodidae) deer tick mesoscale populations in natural areas: effects of deer, area, and location. Journal of Medical Entomology 994;3:52-5.
Falco RC, Fish D, and Piesman J. Duration of tick bites in a Lyme disease-endemic area. American Journal of Epidemiology 99;43:7-92.
Falco RC, McKenna DF, Daniels TJ, Nadelman RB, Nowakowski J, Fish D, and Wormser GP. Temporal relation between
Ixodes scapularis abundance and risk of Lyme disease associated with erythema migrans. American Journal of Epidemiology 999;49:77-77.
Fikrig E, Feng W, Aversa J, Schoen RT, Flavell RA. Differential expression of Borrelia burgdorferi genes during erythema migrans and Lyme arthritis. J infect Dis. 99;3():2-290.
Fraser CM, Casjens, Huang WM, et al. Genomic sequence of a Lyme disease spirochete, Borrelia burgdorferi. Nature. 997;390:50-5.
Hellerstrom S. Erythema chronicum migrans Afzelius with meningitis. Southern Med J. 950;43:330-335.
Johnson, BJ, Robbins KE, Bailey RE, et al. Serodiagnosis of Lyme disease: accuracy of a two-step approach using a flagella-based ELISA and immunoblotting. J Infect Dis 99;74:34-353.
Johnson RC, Schmid GP, Hyde FW, et al. Borrelia burgdorferi sp. nov.: etiologic agent of Lyme disease. Int J Sys Bacteriol. 94;34:49-497.
Jonsson M, Noppa L, Barbour AG. Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins. Infect Immun. 992;0:45-53.
Kitron U, and Kazmierczak JJ. Spatial analysis of the distribution of Lyme disease in Wisconsin. American Journal of
Plant seminar, Part 2, 24-25 May 2002, © HAU, Stichting Alonnissos
4Epidemiology 997;45:55-5.
Lane RS, Manweiler SA, Stubbs HA, et al. Risk factors for Lyme disease in a small rural community in northern California. American Journal of Epidemiology 992;3:35-3.
Lane RS, Piesman J, Burgdorfer W. Lyme borreliosis: relation of its causative agent to its vectors and hosts in North America and Europe. Annual Review of Entomology 99;3:57-09.
Li XL, Peavey CA, and Lane RS. Density and spatial distribution of Ixodes pacificus (Acari: Ixodidae) in two recreational areas in north coastal California. American Journal of Tropical Medicine and Hygiene 2000;2:45-422.
Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 990;323:43-444. Mannelli A, Kitron U, Jones CJ, and Slajchert TL. Influence of season and habitat on Ixodes scapularis infestation on white-footed mice in northwestern Illinois. Journal of Parasitology 994;0:03-042.
Marques AR, Stock F, Gill V. Evaluation of a new culture medium for Borrelia burgdorferi. J Clin Microbiol. 2000 Nov;3():4239-424.Gaudino EA, Coyle PK, Krupp LB. Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences. Arch Neurol 997;54:372-37.
Mather TN, Wilson ML, Moore SI, Ribeiro JMC, and Spielman A. Comparing the relative potential of rodents as reservoirs of the Lyme disease spirochete (Borrelia burgdorferi). American Journal of Epidemiology 99;30:43-50.
Maupin GO, Fish D, Zultowsky J, Campos EG, and Piesman J. Landscape ecology of Lyme disease in a residential area of Westchester County, New York. American Journal of Epidemiology 99;33:05-3.
Nadelman RB and Wormser GP. Lyme borreliosis. Lancet. 99;352:557-55.
Nadelman RB, Pavia CS, Magnarelli LA, Wormser GP. Isolation of Borrelia burgdorferi from the blood of seven patients with Lyme disease. Am J Med. 990 Jan;():2-2.
Nocton JJ, Dressler F, Rutledge BJ, et al. Detection of Borrelia burgdorferi by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. N Engl J Med 994;44:203-207.
Nowakowski J, Schwartz I, Nadelman RB, et al. Culture-confirmed infection and reinfection with Borrelia burgdorferi. Ann Intern Med 997;27:30-32.
Olson CA, Cupp EW, Luckhart S, Ribeiro JMC, and Levy C. Occurrence of Ixodes pacificus (Parasitoformes: Ixodidae) in Arizona. Journal of Medical Entomology 992;29:00-02.
Orloski KA, Hayes EB, Campbell GL, Dennis DT. Surveillance for Lyme disease--United States, 992-99. Mor Mortal Wkly Rep CDC Surveill Summ. 2000 Apr 2;49(3):-.
Piesman J, Mather TN, Donahue JG, Levine J, Campbell JD, Karakashian SJ, and Spielman A. Comparative prevalence of Babesia microti and Borrelia burgdorferi in four populations of Ixodes dammini in eastern Massachusetts. Acta Tropica 9;43:23-270. Piesman J, Maupin GO, Campos EG, and Happ CM. Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method. Journal of Infectious Diseases 99;3:95-97. Pinger RR, Timmons L, and Karris K. Spread of Ixodes scapularis (Acari: Ixodidae) in Indiana: Collections of adults in 99-994 and description of a Borrelia burgdorferi-infected population. Journal of Medical Entomology 99;33:52-55.
Pollack RJ, Telford SR 3rd, Spielman A. Standardization of medium for culturing Lyme disease spirochetes. J Clin Microbiol.
993 May;3(5):25-255.Rahn DW. Natural history of Lyme disease. In: Rahn DW, Evans J, eds. Lyme disease, Philadelphia: American College of Physicians, 99;35-4.
Preac-Mursic V, Wilske B, Reinhardt S. Culture of Borrelia burgdorferi on six solid media. Eur J Clin Microbiol Infect Dis. 99 Dec;0(2):07-079.
Rahn DW, Evans J eds. Lyme Disease. 99. American College of Physicians, Philadelphia, PA.
Rosa PA, Schwan TG. Molecular biology of Borrelia burgdorferi In Coyle PK (ed): Lyme Disease. Chicago: Mosby-Year Book, Inc.; 993:-7.
Rosa PA. Microbiology of Borrelia burgdorferi. Semin Neurol. 997 Mar;7():5-0.
Scrimenti RJ. Erythema chronicum migrans. Arch Dermatol. 970;02:04-05.
Schulze TL, Jordan RA, and Hung RW. Suppresion of subadult Ixodes scapularis (Acari: Ixodidae) following removal of leaf litter. Journal of Medical Entomology 995;32:730-733.
Shadick NA, Phillips CB, Logigian EL, et al. The long-term clinical outcomes of Lyme disease. Ann Intern Med 994;2:50-57. Skare JT, Foley DM, Hernandez SR, Moore DC, Blanco DR, Miller JN, Lovett MA. Cloning and molecular characterization of plasmid-encoding antigens of Borrelia burgdorferi. Infect Immun 999;(9):4407-447.
Smith Jr. RP, Rand PW, Lacombe EH, Telford, III SR, Rich SM, Piesman J, and Spielman A. Norway rats as reservoir hosts for Lyme disease spirochetes on Monhegan Island, Maine. Journal of Infectious Diseases 993;:7-9.
Sood SK, Salzman MB, Johnson BJ, Happ CM, Feig K, Carmody L, Rubin LG, Hilton E, Piesman J. Duration of tick attach-
ment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. Journal of Infectious Diseases 997 Apr;75(4):99-999.
Sood SK, Salzman MB, Johnson BJ, Happ CM, Feig K, Carmody L, Rubin LG, Hilton E, Piesman J. Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis. 997 Apr;75(4):99-999. Spielman A, Levine JF, and Wilson ML. Vectorial capacity of North American Ixodes ticks. Yale Journal of Biology and Medicine 94;57:507-53.
Stafford III, KC. Reduced abundance of Ixodes scapularis (Acari: Ixodidae) with exclusion of deer by electric fencing. Journal of Medical Entomology 993;30:9-99.
Stafford III, KC. Survival of immature Ixodes scapularis (Acari: Ixodidae) at different relative humidities. Journal of Medical Entomology 994;3:30-34.
Stafford III, KC, Bladen VC, and Magnarelli LA. Ticks (Acari: Ixodidae) infesting wild birds (Aves) and white-footed mice in Lyme, CT. Journal of Medical Entomology 995;32:453-4.
Stafford KC, Magnarelli LA. Spatial and temporal patterns of Ixodes scapularis (Acari:Ixodidae) in southeastern Connecticut. Journal of Medical Entomology 993;30:72-77.
Steere, AC. Medical Progress: Lyme Disease. New England J Med. 99;32(9):5-59.
Plant seminar, Part 2, 24-25 May 2002, © HAU, Stichting Alonnissos
47
Steere AC. Lyme disease. N Engl J Med. 99 Aug 3;32(9):5-59.
Steere AC. Lyme disease. N Engl J Med. 200 Jul 2;345(2):5-25.
Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochetal etiology of Lyme disease. N Engl J Med. 93;30:733-740.
Steere AC, Levin RE, Molloy PJ et al. Treatment of Lyme arthritis. Arthritis Rheum 994;37:7-.
Steere AC, Malawista SE, Hardin JA, et al. Erythema chronicum migrans and Lyme arthritis: the enlarging clinical spectrum. Ann Intern Med. 977;:5-9.
Steere AC, Malawista SE, Newman JH, et al. Antibiotic therapy in Lyme disease. Ann Intern Med. 90;93:-.
Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum. 977;20:7-7.
Tugwell P, Dennis DT, Weinstein A, et al. Clinical guideline 2: laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 997; 27:09-23.
Wang G, van Dam AP, Schwartz I, Dankert J. Molecular typing of Borrelia burgdorferi sensu lato: taxonomic, epidemiological, and clinical implications99 Oct;2(4):33-53.
Westrom DR, Lane RS, and Anderson JR. Ixodes pacificus (Acari: Ixodidae): population dynamics and distribution on Columbian black-tailed deer (Odocoileus hemionus columbianus). Journal of Medical Entomology 95;22:507-5.
Wilson ML. Distribution and abundance of Ixodes scapularis (Acari:Ixodidae) in North America: ecological processes and spatial analysis. Journal of Medical Entomology 99;35:44-457.