scholarly journals Impact of Genotypic Variation of Borrelia burgdorferi Sensu Stricto on Kinetics of Dissemination and Severity of Disease in C3H/HeJ Mice

2001 ◽  
Vol 69 (7) ◽  
pp. 4303-4312 ◽  
Author(s):  
Guiqing Wang ◽  
Caroline Ojaimi ◽  
Radha Iyer ◽  
Victoria Saksenberg ◽  
Steve A. McClain ◽  
...  

ABSTRACT Various genotypes of Borrelia burgdorferi sensu stricto have been previously identified among a large collection of isolates cultured from patients with Lyme disease in the United States. Furthermore, association of specific genotypes with hematogenous dissemination early in the disease course has been observed. The present study assessed kinetics of spirochete dissemination and disease severity in C3H/HeJ mice infected with two different genotypes ofB. burgdorferi. Spirochete load in plasma and ear and other tissue samples of infected mice was measured by quantitative PCR, and these data were compared to those obtained by culture and histopathologic analysis. In mice infected with isolate BL206 (a type 1 strain), the peak number of spirochetes was observed in plasma between day 4 and 7, in heart and ear tissue on day 14, and in joints on day 28 postinoculation. There was a correlation between the peak number of spirochetes in plasma on day 4 or 7 and that in ear biopsy and joint specimens on day 14. By contrast, spirochete burdens in plasma of mice infected with isolate B356 (a type 3 strain) were 16- and 5-fold lower than those of BL206-infected mice on days 7 and 14 of infection, respectively. Similarly, approximately 6- and 13-fold fewer spirochetes were detected in the heart tissues of B356-infected mice compared to BL206-infected mice. Histopathologically, severe arthritis and aortitis were noted only in mice infected with isolate BL206. Spirochete dissemination and disease severity vary significantly in mice infected with distinct genotypes of B. burgdorferi, suggesting that genotypic differences in the infecting spirochetes play a key role in the pathogenesis and development of clinical disease.

2020 ◽  
Vol 57 (3) ◽  
pp. 715-727 ◽  
Author(s):  
Holly Gaff ◽  
Rebecca J Eisen ◽  
Lars Eisen ◽  
Robyn Nadolny ◽  
Jenna Bjork ◽  
...  

Abstract Lyme disease is the most commonly reported vector-borne disease in the United States, and the number of cases reported each year continues to rise. The complex nature of the relationships between the pathogen (Borrelia burgdorferi sensu stricto), the tick vector (Ixodes scapularis Say), multiple vertebrate hosts, and numerous environmental factors creates challenges for understanding and predicting tick population and pathogen transmission dynamics. LYMESIM is a mechanistic model developed in the late 1990s to simulate the life-history of I. scapularis and transmission dynamics of B. burgdorferi s.s. Here we present LYMESIM 2.0, a modernized version of LYMESIM, that includes several modifications to enhance the biological realism of the model and to generate outcomes that are more readily measured under field conditions. The model is tested for three geographically distinct locations in New York, Minnesota, and Virginia. Model-simulated timing and densities of questing nymphs, infected nymphs, and abundances of nymphs feeding on hosts are consistent with field observations and reports for these locations. Sensitivity analysis highlighted the importance of temperature in host finding for the density of nymphs, the importance of transmission from small mammals to ticks on the density of infected nymphs, and temperature-related tick survival for both density of nymphs and infected nymphs. A key challenge for accurate modeling of these metrics is the need for regionally representative inputs for host populations and their fluctuations. LYMESIM 2.0 is a useful public health tool that downstream can be used to evaluate tick control interventions and can be adapted for other ticks and pathogens.


2012 ◽  
Vol 19 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Bettina Wagner ◽  
Heather Freer ◽  
Alicia Rollins ◽  
David Garcia-Tapia ◽  
Hollis N. Erb ◽  
...  

ABSTRACTLyme disease in the United States is caused byBorrelia burgdorferisensu stricto, which is transmitted to mammals by infected ticks.Borreliaspirochetes differentially express immunogenic outer surface proteins (Osp). Our aim was to evaluate antibody responses to Osp antigens to aid the diagnosis of early infection and the management of Lyme disease. We analyzed antibody responses during the first 3 months after the experimental infection of dogs using a novel multiplex assay. Results were compared to those obtained with two commercial assays detecting C6 antigen. Multiplex analysis identified antibodies to OspC and C6 as early as 3 weeks postinfection (p.i.) and those to OspF by 5 weeks p.i. Antibodies to C6 and OspF increased throughout the study, while antibodies to OspC peaked between 7 and 11 weeks p.i. and declined thereafter. A short-term antibody response to OspA was observed in 3/8 experimentally infected dogs on day 21 p.i. Quant C6 enzyme-linked immunosorbent assay (ELISA) results matched multiplex results during the first 7 weeks p.i.; however, antibody levels subsequently declined by up to 29%. Immune responses then were analyzed in sera from 125 client-owned dogs and revealed high agreement between antibodies to OspF and C6 as robust markers for infection. Results from canine patient sera supported that OspC is an early infection marker and antibodies to OspC decline over time. The onset and decline of antibody responses toB. burgdorferiOsp antigens and C6 reflect their differential expression during infection. They provide valuable tools to determine the stage of infection, treatment outcomes, and vaccination status in dogs.


Author(s):  
Julia E Poje ◽  
Jose F Azevedo ◽  
Nisha Nair ◽  
Kurayi Mahachi ◽  
Lexi E Frank ◽  
...  

Abstract Lyme disease, caused by Borrelia burgdorferi sensu stricto and most commonly transmitted by Ixodes scapularis Say (Ixodida: Ixodidae), is the most common tick-borne disease in Maryland. Because B. burgdorferi s.s. is maintained in enzootic cycles among wild mice (Peromyscus spp) and Ixodes spp ticks, differing patterns of parasitism of ticks on mice could impact the infection prevalence with B. burgdorferi. We determined the infection prevalence of Peromyscus spp as well as questing and partially engorged nymphal ticks collected at six sites on private land in five counties in Maryland from May to August 2020. Questing nymph infection prevalence (NIP) was 14%. We trapped 1258 mice and collected 554 ticks and 413 ear tissue samples. The prevalence of infested Peromyscus spp varied based on host age and sex, with older and male mice more likely to be infested. We detected a significant difference amongst the proportion of attached Ixodes and the location of trapping. Similarly, the prevalence of B. burgdorferi infected Peromyscus spp mice varied between locations (average mouse infection prevalence was 40%), with the highest prevalence in locations where Ixodes were the most commonly found ticks. The B. burgdorferi infection prevalence in partially engorged I. scapularis nymphs retrieved from Peromyscus spp was ~36% which lends further support to the host infection prevalence. Local differences in distribution of infected vectors and reservoirs are important factors to consider when planning interventions to reduce Lyme disease risk.


2017 ◽  
Vol 5 (28) ◽  
Author(s):  
Gabriele Margos ◽  
Sabrina Hepner ◽  
Christoph Mang ◽  
Andreas Sing ◽  
Bernhard Liebl ◽  
...  

ABSTRACT Borrelia burgdorferi sensu stricto is a causative agent of human Lyme borreliosis in the United States and Europe. We report here the completed genome sequences of strain B31 isolated from a tick in the United States and two closely related strains from Europe, PAli and PAbe, which were isolated from patients with erythema migrans and neuroborreliosis, respectively.


2009 ◽  
Vol 16 (11) ◽  
pp. 1546-1562 ◽  
Author(s):  
Inke Krupka ◽  
Jens Knauer ◽  
Leif Lorentzen ◽  
Thomas P. O'Connor ◽  
Jill Saucier ◽  
...  

ABSTRACTThe diversity of Lyme-borreliosis-inducingBorreliaspecies in Europe set high standards for the use of serodiagnostic test systems in terms of specificity and sensitivity. In the United States, the one-step C6antibody test system based on the invariable domain IR6 of the VlsE molecule has been established as a successful diagnostic tool for testing canine samples. However, only a limited set of data are available regarding the antigenicity of the C6peptides in an experimental murine model and sensitivity of the test regarding EuropeanBorreliaspecies. In order to investigate antibody reactions induced by these spirochetes, a total of 142 C3H/HeN mice were inoculated withBorrelia burgdorferisensu stricto N40,B. gariniiPBi, two isolates ofB. afzelii,B. spielmaniiA14S,B. valaisianaRio6,B. valaisianaVS116, orB. lusitaniae. Infection of the mice was documented utilizing tissue culture and PCR. The IR6 sequences ofB. burgdorferisensu stricto B31,B. gariniiIP90, and twoB. afzeliiACAI strains have been used to synthesize and test additional C6peptides. Compared to the well-established two-tiered test system, the results indicate that single C6peptides derived fromB. burgdorferisensu stricto andB. gariniican be used in an enzyme-linked immunosorbent assay-based technique to detect murine antibodies induced by either agent. Little is known about the prevalence or pathogenicity of theB. afzeliistrains in mammalian hosts, but our experimental data indicate differences in the C6peptide test sensitivity for the detection of antibodies induced by different strains or isolates ofB. afzelii.


2009 ◽  
Vol 78 (1) ◽  
pp. 138-144 ◽  
Author(s):  
Sarojini Adusumilli ◽  
Carmen J. Booth ◽  
Juan Anguita ◽  
Erol Fikrig

ABSTRACT Lyme disease is the most common tick-borne illness in the United States. In this paper we explore the contribution of Ixodes scapularis ticks to the pathogenicity of Borrelia burgdorferi in mice. Previously we demonstrated that an isolate of B. burgdorferi sensu stricto (designated N40), passaged 75 times in vitro (N40-75), was infectious but was no longer able to cause arthritis and carditis in C3H mice. We now show that N40-75 spirochetes can readily colonize I. scapularis and multiply during tick engorgement. Remarkably, tick-transmitted N40-75 spirochetes cause disease in mice. N40-75 spirochetes isolated from these animals also retained their pathogenicity when subsequently administered to mice via syringe inoculation. Array analysis revealed that several genes associated with virulence, including bba25, bba65, bba66, bbj09, and bbk32, had higher expression levels in the tick-passaged N40-75 spirochete. These data suggest that transmission of a high-passage attenuated isolate of B. burgdorferi by the arthropod vector results in the generation of spirochetes that have enhanced pathogenesis in mice.


2014 ◽  
Vol 81 (4) ◽  
pp. 1309-1318 ◽  
Author(s):  
S. Mechai ◽  
G. Margos ◽  
E. J. Feil ◽  
L. R. Lindsay ◽  
N. H. Ogden

ABSTRACTLyme disease, caused by the bacteriumBorrelia burgdorferisensu stricto, is an emerging zoonotic disease in Canada and is vectored by the blacklegged tick,Ixodes scapularis. Here we used Bayesian analyses of sequence types (STs), determined by multilocus sequence typing (MLST), to investigate the phylogeography ofB. burgdorferipopulations in southern Canada and the United States by analyzing MLST data from 564B. burgdorferi-positive samples collected during surveillance. A total of 107 Canadian samples from field sites were characterized as part of this study, and these data were combined with existing MLST data for samples from the United States and Canada. Only 17% of STs were common between both countries, while 49% occurred only in the United States, and 34% occurred only in Canada. However, STs in southeastern Ontario and southwestern Quebec were typically identical to those in the northeastern United States, suggesting a recent introduction into this region from the United States. In contrast, STs in other locations in Canada (the Maritimes; Long Point, Ontario; and southeastern Manitoba) were frequently unique to those locations but were putative descendants of STs previously found in the United States. The picture in Canada is consistent with relatively recent introductions from multiple refugial populations in the United States. These data thus point to a geographic pattern of populations ofB. burgdorferiin North America that may be more complex than simply comprising northeastern, midwestern, and Californian groups. We speculate that this reflects the complex ecology and spatial distribution of key reservoir hosts.


2019 ◽  
Vol 57 (1) ◽  
pp. 273-280 ◽  
Author(s):  
Alison E Simmons ◽  
Anna B Manges ◽  
Tashi Bharathan ◽  
Shannon L Tepe ◽  
Sara E McBride ◽  
...  

Abstract Lyme disease is the most commonly reported vector-borne illness and sixth most commonly reported notifiable infectious disease in the United States. The majority of cases occur in the Northeast and upper-Midwest, and the number and geographic distribution of cases is steadily increasing. The blacklegged tick (Ixodes scapularis Say) is the principal vector of the Lyme disease spirochete (Borrelia burgdorferi sensu stricto) in eastern North America. Although Lyme disease risk has been studied in residential and recreational settings across rural to urban landscapes including metropolitan areas, risk within U.S. cities has not been adequately evaluated despite the presence of natural and undeveloped public parkland where visitors could be exposed to B. burgdorferi-infected I. scapularis. We studied the occurrence of I. scapularis and infection prevalence of B. burgdorferi in four insular regional parks within the city of Pittsburgh to assess Lyme disease risk of exposure to infected adults and nymphs. We found that the density of I. scapularis adults (1.16 ± 0.21 ticks/100 m2) and nymphs (3.42 ± 0.45 ticks/100 m2), infection prevalence of B. burgdorferi in adults (51.9%) and nymphs (19.3%), and density of infected adults (0.60 ticks/100 m2) and nymphs (0.66 ticks/100 m2) are as high in these city parks as nonurban residential and recreational areas in the highly endemic coastal Northeast. These findings emphasize the need to reconsider, assess, and manage Lyme disease risk in greenspaces within cities, especially in high Lyme disease incidence states.


2001 ◽  
Vol 8 (2) ◽  
pp. 376-384 ◽  
Author(s):  
A. G. Bretz ◽  
K. Ryffel ◽  
P. Hutter ◽  
E. Dayer ◽  
O. Péter

ABSTRACT Borrelia burgdorferi, the agent of Lyme borreliosis, is genetically more heterogeneous than previously thought. In Europe five genospecies have been described from the original B. burgdorferi sensu lato (sl): B. burgdorferi sensu stricto (ss), B. garinii, B. afzelii, B. lusitaniae, and B. valaisiana. In the United States, B. burgdorferi ss as well as B. bissettii in California and B. andersonii on the East Coast were differentiated. In Asia, B. japonica has been identified along, with B. garinii, B. afzelii, and B. valaisiana. In order to evaluate sensitivity and specificity of four species-specific monoclonal antibodies, we analyzed 210 B. burgdorferi sl isolates belonging to eight genospecies by immunoblot and confirmed genospecies by restriction fragment length polymorphism (RFLP) of rrf (5S)-rrl (23S) intergenic spacer amplicon. Monoclonal antibody H3TS had 100% sensitivity for 55 B. burgdorferi ss isolates but showed reactivity with all four isolates belonging to B. bissetii. Monoclonal antibody I 17.3 showed 100% specificity and sensitivity for 45 B. afzelii isolates. Monoclonal antibody D6 was 100% specific forB. garinii but missed 1 of 64 isolates (98.5% sensitivity). Monoclonal antibody A116k was 100% specific forB. valaisiana but was unreactive with 4 of 24 isolates (83.5% sensitivity). Genetic analysis correlated well with results of reactivity and confirmed efficacy of the phenotypic typing of these antibodies. Some isolates showed atypical RFLP. Therefore, both phenotypic and genotypic analyses are needed to characterize newBorrelia isolates.


2007 ◽  
Vol 15 (3) ◽  
pp. 484-491 ◽  
Author(s):  
Peter Kraiczy ◽  
Annekatrin Seling ◽  
Catherine A. Brissette ◽  
Evelyn Rossmann ◽  
Klaus-Peter Hunfeld ◽  
...  

ABSTRACT Serological diagnosis of Lyme disease may be complicated by antigenic differences between infecting organisms and those used as test references. Accordingly, it would be helpful to include antigens whose sequences are well conserved by a broad range of Lyme disease spirochetes. In the present study, line blot analyses were performed using recombinant complement regulator-acquiring surface protein 2 (BbCRASP-2) from Borrelia burgdorferi sensu stricto strain B31 and serum samples from human Lyme disease patients from throughout the United States and Germany. The results indicated that a large proportion of the patients had produced antibodies recognizing recombinant BbCRASP-2. In addition, Lyme disease spirochetes isolated from across North America and Europe were found to contain genes encoding proteins with high degrees of similarity to the B. burgdorferi type strain B31 BbCRASP-2, consistent with the high percentage of serologically positive patients. These data indicate that BbCRASP-2 may be valuable for use in a widely effective serological assay.


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