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Uva-DARE (Digital Academic Repository) UvA-DARE (Digital Academic Repository) Molecular characterization of the lyme disease spirochetes Borrelia burgdorferi sensu lato Wang, G. Publication date 1999 Link to publication Citation for published version (APA): Wang, G. (1999). Molecular characterization of the lyme disease spirochetes Borrelia burgdorferi sensu lato. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:03 Oct 2021 Captée MOLECULAR TYPING OF BORRE LIA BURGDORFERI SENSU LATO: TAXONOMIC, EPIDEMIOLOGICAL AND CLINICAL IMPLICATIONS Guiqing Wang1, Alje P. van Dam', Ira Schwartz2, and Jacob Dankert' Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands, and Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, U.SA. Clinical Microbiology Reviews, submitted Chapter 2 SUMMARY Borrelia burgdorferi sensu lato, the bacterium that causes human Lyme borreliosis (LB), has been cultured from various biological and geographic sources worldwide since its first discovery in 1982. Early studies have demonstrated that isolates of B. burgdorferi sensu lato are genetically and phenotypically divergent. Thus, various molecular approaches were developed and used to determine the phenotypic and genetic heterogeneity within the LB related spirochetes, and their potential association with distinct clinical syndromes. These methods include i) serotyping; ii) multilocus enzyme electrophoresis; iii) DNA-DNA relatedness analysis; iv) rRNA gene restriction analysis (ribotyping); v) pulsed-field gel electrophoresis; vi) plasmid fingerprinting; vii) randomly amplified polymorphic DNA fingerprinting analysis; viii) species-specific PCR and PCR-based restriction fragment length polymorphism (RFLP) analysis, and ix) DNA sequence analysis. On the basis of 5S-23S rRNA intergenic spacer RFLP and DNA-DNA hybridization, ten different Borrelia species have been described within the B. burgdorferi sensu lato complex: B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, Borrelia japonica, Borrelia andersonii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia tanukii, Borrelia turdi and B. bissettii sp. nov.. To date, only B. burgdorferi sensu stricto, B. garinii, and B. afzelii are known to be responsible for causing human disease. B. burgdorferi sensu stricto is present in both North America and Europe, whereas B. garinii and B. afzelii are widely distributed in Eurasia. B. bissettii sp. nov. may represent the fourth Borrelia species for causing human LB since strains with similarity of genetic and phenotypic characteristics to this species have been cultured from patients in Europe. Several studies suggest that different Borrelia species are associated with distinct clinical manifestations of LB. Infection with B. burgdorferi sensu stricto is more commonly associated with arthritis, B. garinii with neuroborreliosis, and B. afzelii with acrodermatitis chronica atrophicans. In addition, Borrelia species are differentially distributed worldwide, and may be maintained through different transmission cycles in nature. In this paper, the molecular methods used for typing of B. burgdorferi sensu lato are reviewed. The current taxonomie status of B. burgdorferi sensu lato and its epidemiological and clinical implications, especially correlation between the variable clinical presentations and the infecting Borrelia species, are discussed in detail. INTRODUCTION Lyme borreliosis (LB), or Lyme disease represents a new global public health problem ( 18). It is now the most common vector-borne disease in North America (42, 233) and Eurasia (168, 285). In the United States, more than 100,000 LB cases have been reported from 47 states from 1982 through 1996, with more than 16,000 cases in 1996 (42). It is estimated that annually about 50,000 cases occur in Europe (168). In 1982, the bacterium that causes LB was firstly isolated by Dr. Willy Burgdorfer from the hard tick Ixodes dammini collected in Long Island, New York (35). The isolate was subsequently identified as a new species of the genus Borrelia and was named Borrelia burgdorferi in 1984 (108). Since then, hundreds of B. burgdorferi isolates have been cultured worldwide from various geographic regions and biological sources, including Ixodes ticks, their reservoir hosts and specimens from patients with Molecular Typing of B. burgdorferi Sensu Lato different clinical syndromes. Molecular analysis has indicated that these B. burgdorferi isolates are genetically and phenotypically divergent. A closely related cluster containing several tick-borne Borrelia species and genomic groups associated with LB has been defined (16, 38, 68, 108, 113, 122, 139, 195, 261). The term 'B. burgdorferi sensu lato' is now collectively used to refer to all Borrelia isolates within this cluster, and to distinguish it from the species 'B. burgdorferi sensu stricto' (strict sense of B. burgdorferi) (222). Like other Borrelia, B. burgdorferi sensu lato is a spiral-shaped, gram-negative bacterium with 7 to 11 periplasmic flagellae. It varies from 10 to 30 (im in length and 0.2 to 5 jam in width (20). The genome of the type strain B. burgdorferi sensu stricto B31 contains a linear chromosome of 910,725 bp with an average G+C of 28.6%, and 21 plasmids (9 circular, 12 linear) with a combined size of approximately 613,000 bp (65). The G+C content of plasmid DNA ranges from 23.1% to 32.3% (65). Human infection due to B. burgdorferi sensu lato may involve multiple organs or tissues, resulting in skin, cardiac, neurological and musculoskeletal disorders. Lyme Table 1. Major cl^m Staged Clinical features North America" Eurasia I Early local infection Erythema migrans, EM Common (60-90%)(44'79) Common (-77%)(25) Systemic symptoms Common (>50%)(l57)e Uncommon (<3 8%)(241,e II Early disseminated Infection Common (>18%)(,57)e Unusual (6%)(24,) e Multiple EM Common (10-20%) (44'79) Common (16-80%) (25'43) (9U73)/ Neuroborreliosis, NB 3_21%(44.79,f 37-61% (797 1119 mo f Meningoradiculitis 2_17%(44.79)f 4 27°/ - ' > Meningitis 0.5-10% (44'79) 0.5.4% («,i73) Carditis Rare Well documented (3%)(25) Borrelial lymphocytoma III Late Lyme borreliosis Lyme arthritis Common(51-57%)(44'238)g Uncommon (-7%)(25) ACA Rare Well documented (3%)(25) Peripheral neuropathy 30-70% late NB(90)(44)f 40-63% ACA patients (117) CNS involvement Well documented (89) <9%NB(173)f (90) Encephalomyelitis rare (0.1%) 4_60/o(9..173)f Meningencephalitis 9%(h) { 0.5-4% (9U73)f a. Stages of the clinical features were according to Steere (232); b. EM: erythema migrans; ACA: acrodermatitis chronica atrophicans; NB: neuroborreliosis; CNS: central nervous system.; c. Data were mainly based on an earlier report of CDC on LB surveillance from 1984 to 1986 (44) and a population-based study in children in Southern Connecticut (79), except for that indicated specifically; d. Data were mainly based on a population-based study in Southern Sweden (25), except for that indicated specifically; e. Data were based on 76 American (157) and 231 European culture-confirmed patients with EM (241); f. NB patients were used as denominator to calculate the relative prevalence. European data were based on data from 330 NB cases from Germany (173) and 176 NB cases from Denmark (91); g A recent population-based study showed that only 7% of children with LB developed Lyme arthritis (79). About 10% of patients with Lyme arthritis may develop chronic antibiotic treatment-resistant arthritis (87). 19 Chapter 2 disease (232) was described as a new clinical entity in 1977 because of a geographic clustering of children with rheumatoid-like arthritis in Lyme, Connecticut (235, 236, 237). Retrospective analysis revealed that many of the clinical manifestations of LB had been separately recorded by European clinicians since the end of 19th century (264). Table 1 lists the spectrum of the major clinical manifestations of human LB in North America and Eurasia. It has been shown that multiple EM and Lyme arthritis are more common in the United States than in Europe, whereas neuroborreliosis has more frequently occurred in European patients, especially in children with LB (25, 43, 44, 79, 173). Borrelial lymophocytoma and acrodematitis chronica atrophicans (ACA) are well documented in European LB patients, but are rarely recognized among LB patients in the United States (188, 231). In general, the clincial manifestations of LB shows many features in common with syphilis. As a result of its protean clinical manifestations, LB was described as the new 'greater imitator' of various human diseases (174). Numerous studies indicate that the B. burgdorferi sensu lato
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