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Comparison of Erythema Migrans Caused by Borrelia burgdorferi and Borrelia garinii

Authors:
Franc Strle at Ljubljana University Medical Centre
Franc Strle
Eva Ruzic Sabljic at University of Ljubljana
Eva Ruzic Sabljic
Mateja Logar at University of Ljubljana
Mateja Logar
Vera Maraspin at Ljubljana University Medical Centre
Vera Maraspin
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Abstract

A comparison of patients with erythema migrans due to Borrelia garinii versus Borrelia burgdorferi has not been reported. One hundred nineteen patients from New York State with erythema migrans caused by B. burgdorferi were compared with 116 patients from Slovenia with erythema migrans due to B. garinii infection. Patients with B. garinii infection were older, more often reported a tick bite, and developed larger lesions (median largest diameter: 18 and 14  cm, respectively; p = 0.01) that more often had central clearing (61.2% compared with 35.3%; p < 0.0001). Patients infected with B. burgdorferi, however, more often had systemic symptoms (68.9% vs. 37.1%; p < 0.0001), including fatigue (p < 0.0001), arthralgia (p = 0.0003), myalgia (p < 0.0001), headache (p = 0.0008), fever and/or chills (p < 0.0001), and stiff neck (p < 0.0001), and more often had abnormal physical findings (57.1% compared with 11.2%; p < 0.0001), such as fever (p = 0.0002) or regional lymphadenopathy (p < 0.0001). There was a trend for more patients with B. burgdorferi infection to have multiple erythema migrans skin lesions (13.4% compared with 5.2%; p = 0.051), and among patients with multiple erythema migrans the number of lesions was greater in B. burgdorferi-infected patients (median: 5.5 compared with 2.0; p = 0.006). The results of the present study indicate that in patients with erythema migrans the clinical features vary according to whether infection is caused by B. garinii or B. burgdorferi.
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Comparison of Erythema Migrans
Caused by
Borrelia burgdorferi
and
Borrelia garinii
Franc Strle
Eva Ružić-Sabljić
Mateja Logar
Vera Maraspin
Stanka Lotrič-Furlan
Jože Cimperman
Katarina Ogrinc
Daša Stupica
Robert B. Nadelman
John Nowakowski
Gary P. Wormser
Address correspondence to:
Franc Strle
Department of Infectious Diseases
University Medical Center Ljubljana
Japljeva 2
1525 Ljubljana
Slovenia
E-mail:
franc.strle@kclj.si
Vector-Borne and Zoonotic Diseases
Vol. 11: Issue. 9: Pages. 1253-1258
(Issue publication date: September 2011)
DOI: 10.1089/vbz.2010.0230
Abstract
Background: A comparison of patients with
erythema migrans due to Borrelia garinii versus
Borrelia burgdorferi has not been reported.
Patients and Methods: One hundred nineteen
patients from New York State with erythema
migrans caused by B. burgdorferi were compared
with 116 patients from Slovenia with erythema
migrans due to B. garinii infection.
Results: Patients with B. garinii infection were
older, more often reported a tick bite, and
developed larger lesions (median largest
diameter: 18 and 14 cm, respectively; p=0.01)
that more often had central clearing (61.2%
compared with 35.3%; p<0.0001). Patients
infected with B. burgdorferi, however, more often
had systemic symptoms (68.9% vs. 37.1%;
p<0.0001), including fatigue (p<0.0001),
arthralgia (p=0.0003), myalgia (p<0.0001),
headache ( p=0.0008), fever and/or chills
(p<0.0001), and stiff neck (p<0.0001), and more
often had abnormal physical findings (57.1%
compared with 11.2%; p<0.0001), such as fever
(p=0.0002) or regional lymphadenopathy
(p<0.0001). There was a trend for more patients
with B. burgdorferi infection to have multiple
erythema migrans skin lesions (13.4% compared
with 5.2%; p=0.051), and among patients with
multiple erythema migrans the number of
lesions was greater in B. burgdorferi -infected
patients (median: 5.5 compared with 2.0;
p=0.006).
Comparison of Erythema Migrans
Caused by
Borrelia burgdorferi
and
Borrelia garinii
Franc Strle
Eva Ružić-Sabljić
Mateja Logar
Vera Maraspin
Stanka Lotrič-Furlan
Jože Cimperman
Katarina Ogrinc
Daša Stupica
Robert B. Nadelman
John Nowakowski
Gary P. Wormser
Address correspondence to:
Franc Strle
Department of Infectious Diseases
University Medical Center Ljubljana
Japljeva 2
1525 Ljubljana
Slovenia
E-mail:
franc.strle@kclj.si
Vector-Borne and Zoonotic Diseases
Vol. 11: Issue. 9: Pages. 1253-1258
(Issue publication date: September 2011)
DOI: 10.1089/vbz.2010.0230
Abstract
Background: A comparison of patients with
erythema migrans due to Borrelia garinii versus
Borrelia burgdorferi has not been reported.
Patients and Methods: One hundred nineteen
patients from New York State with erythema
migrans caused by B. burgdorferi were compared
with 116 patients from Slovenia with erythema
migrans due to B. garinii infection.
Results: Patients with B. garinii infection were
older, more often reported a tick bite, and
developed larger lesions (median largest
diameter: 18 and 14 cm, respectively; p=0.01)
that more often had central clearing (61.2%
compared with 35.3%; p<0.0001). Patients
infected with B. burgdorferi, however, more often
had systemic symptoms (68.9% vs. 37.1%;
p<0.0001), including fatigue (p<0.0001),
arthralgia (p=0.0003), myalgia (p<0.0001),
headache ( p=0.0008), fever and/or chills
(p<0.0001), and stiff neck (p<0.0001), and more
often had abnormal physical findings (57.1%
compared with 11.2%; p<0.0001), such as fever
(p=0.0002) or regional lymphadenopathy
(p<0.0001). There was a trend for more patients
with B. burgdorferi infection to have multiple
erythema migrans skin lesions (13.4% compared
with 5.2%; p=0.051), and among patients with
multiple erythema migrans the number of
lesions was greater in B. burgdorferi -infected
patients (median: 5.5 compared with 2.0;
p=0.006).
Comparison of Erythema Migrans
Caused by
Borrelia burgdorferi
and
Borrelia garinii
Franc Strle
Eva Ružić-Sabljić
Mateja Logar
Vera Maraspin
Stanka Lotrič-Furlan
Jože Cimperman
Katarina Ogrinc
Daša Stupica
Robert B. Nadelman
John Nowakowski
Gary P. Wormser
Address correspondence to:
Franc Strle
Department of Infectious Diseases
University Medical Center Ljubljana
Japljeva 2
1525 Ljubljana
Slovenia
E-mail:
franc.strle@kclj.si
Vector-Borne and Zoonotic Diseases
Vol. 11: Issue. 9: Pages. 1253-1258
(Issue publication date: September 2011)
DOI: 10.1089/vbz.2010.0230
Abstract
Background: A comparison of patients with
erythema migrans due to Borrelia garinii versus
Borrelia burgdorferi has not been reported.
Patients and Methods: One hundred nineteen
patients from New York State with erythema
migrans caused by B. burgdorferi were compared
with 116 patients from Slovenia with erythema
migrans due to B. garinii infection.
Results: Patients with B. garinii infection were
older, more often reported a tick bite, and
developed larger lesions (median largest
diameter: 18 and 14 cm, respectively; p=0.01)
that more often had central clearing (61.2%
compared with 35.3%; p<0.0001). Patients
infected with B. burgdorferi, however, more often
had systemic symptoms (68.9% vs. 37.1%;
p<0.0001), including fatigue (p<0.0001),
arthralgia (p=0.0003), myalgia (p<0.0001),
headache ( p=0.0008), fever and/or chills
(p<0.0001), and stiff neck (p<0.0001), and more
often had abnormal physical findings (57.1%
compared with 11.2%; p<0.0001), such as fever
(p=0.0002) or regional lymphadenopathy
(p<0.0001). There was a trend for more patients
with B. burgdorferi infection to have multiple
erythema migrans skin lesions (13.4% compared
with 5.2%; p=0.051), and among patients with
multiple erythema migrans the number of
lesions was greater in B. burgdorferi -infected
patients (median: 5.5 compared with 2.0;
p=0.006).
Comparison of Erythema Migrans
Caused by
Borrelia burgdorferi
and
Borrelia garinii
Franc Strle
Eva Ružić-Sabljić
Mateja Logar
Vera Maraspin
Stanka Lotrič-Furlan
Jože Cimperman
Katarina Ogrinc
Daša Stupica
Robert B. Nadelman
John Nowakowski
Gary P. Wormser
Address correspondence to:
Franc Strle
Department of Infectious Diseases
University Medical Center Ljubljana
Japljeva 2
1525 Ljubljana
Slovenia
E-mail:
franc.strle@kclj.si
Vector-Borne and Zoonotic Diseases
Vol. 11: Issue. 9: Pages. 1253-1258
(Issue publication date: September 2011)
DOI: 10.1089/vbz.2010.0230
Abstract
Background: A comparison of patients with
erythema migrans due to Borrelia garinii versus
Borrelia burgdorferi has not been reported.
Patients and Methods: One hundred nineteen
patients from New York State with erythema
migrans caused by B. burgdorferi were compared
with 116 patients from Slovenia with erythema
migrans due to B. garinii infection.
Results: Patients with B. garinii infection were
older, more often reported a tick bite, and
developed larger lesions (median largest
diameter: 18 and 14 cm, respectively; p=0.01)
that more often had central clearing (61.2%
compared with 35.3%; p<0.0001). Patients
infected with B. burgdorferi, however, more often
had systemic symptoms (68.9% vs. 37.1%;
p<0.0001), including fatigue (p<0.0001),
arthralgia (p=0.0003), myalgia (p<0.0001),
headache ( p=0.0008), fever and/or chills
(p<0.0001), and stiff neck (p<0.0001), and more
often had abnormal physical findings (57.1%
compared with 11.2%; p<0.0001), such as fever
(p=0.0002) or regional lymphadenopathy
(p<0.0001). There was a trend for more patients
with B. burgdorferi infection to have multiple
erythema migrans skin lesions (13.4% compared
with 5.2%; p=0.051), and among patients with
multiple erythema migrans the number of
lesions was greater in B. burgdorferi -infected
patients (median: 5.5 compared with 2.0;
p=0.006).
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Comparison of Erythema Migrans Caused by Borrelia burgdorferi and Borrelia garinii.pdf
Saved to Dropbox • Mar 29, 2016, 21:26
... Erythema migrans is the most common clinical manifestation of Lyme disease in the United States and Europe, occurring in >80% of patients in both geographic areas (2) 37%), multiple erythema migrans skin lesions (13% vs. 5% for both B. afzelii and B. garinii), and regional lymphadenopathy (29% vs. 8% or 3%) (8-10) ( Table 2). Erythema migrans lesions in patients acquiring the infection in the United States have a shorter incubation period from tick bite to lesion development and are less likely to have central clearing at the time of diagnosis (8)(9)(10). The frequency of central clearing at least partially depends on the duration of the erythema migrans lesion before the diagnosis, and the duration is on average longer in Europe than in the United States (8)(9)(10). ...
... Erythema migrans lesions in patients acquiring the infection in the United States have a shorter incubation period from tick bite to lesion development and are less likely to have central clearing at the time of diagnosis (8)(9)(10). The frequency of central clearing at least partially depends on the duration of the erythema migrans lesion before the diagnosis, and the duration is on average longer in Europe than in the United States (8)(9)(10). In Europe, the percentage of patients with multiple erythema migrans lesions is lower for adult patients than for children (8)(9)(10)(11), whereas in the United States, multiple erythema migrans lesions occur with similar frequency in adults and children (8,(12)(13)(14). ...
... The frequency of central clearing at least partially depends on the duration of the erythema migrans lesion before the diagnosis, and the duration is on average longer in Europe than in the United States (8)(9)(10). In Europe, the percentage of patients with multiple erythema migrans lesions is lower for adult patients than for children (8)(9)(10)(11), whereas in the United States, multiple erythema migrans lesions occur with similar frequency in adults and children (8,(12)(13)(14). Patients infected with B. mayonii, found in the Upper Midwest region of the United States, can exhibit multiple and very small erythema migrans lesions (6). ...
Comparison of Lyme Disease in the United States and Europe
Article
Full-text available
  • Aug 2021
Lyme disease, or Lyme borreliosis, is the most common tickborne disease in the United States and Europe. In both locations, Ixodes species ticks transmit the Borrelia burgdorferi sensu lato bacteria species responsible for causing the infection. The diversity of Borrelia species that cause human infection is greater in Europe; the 2 B. burgdorferi s.l. species collectively responsible for most infections in Europe, B. afzelii and B. garinii, are not found in the United States, where most infections are caused by B. burgdorferi sensu stricto. Strain differences seem to explain some of the variation in the clinical manifestations of Lyme disease, which are both minor and substantive, between the United States and Europe. Future studies should attempt to delineate the specific virulence factors of the different species of B. burgdorferi s.l. responsible for these variations in clinical features.
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... These differences were first appreciated by comparing the findings of several independent case series on the clinical and laboratory features of EM in Europe and in the US, and verified by studies providing direct comparisons of the clinical features of culture confirmed cases of EM in the US and Europe. In these latter studies, the etiologic agent causing the EM skin lesion was identified based on a positive skin culture for B. burgdorferi in the US, and for B. afzelii or B. garinii in Europe [4][5][6][7]. Thus, the observed regional differences in certain clinical and laboratory features of patients with EM have been interpreted to be due to the different causative agents on the two continents. ...
... The data from these reports suggest several differences in the presentation of EM between the two continents. However, direct comparisons of the clinical and laboratory characteristics of US EM patients with B. burgdorferi infection and European EM patients with B. afzelii or B. garinii infection are limited to only four reports [4][5][6][7]. All four reports are based on positive borrelia culture results from skin. ...
... These direct comparisons confirmed findings observed in the independent case series, providing further evidence that patients with EM in the US demonstrate certain clinical differences from patients with EM in Europe. The reported differences are that US patients with EM, compared with patients with EM in Europe, less often recall a preceding tick bite at the site of the EM skin lesion [4,6], have a shorter duration of the skin lesion until diagnosis [4][5][6][7], and the skin lesion less often has central clearing [4,6]. In addition, US patients with EM more frequently report fever and concomitant constitutional symptoms [4][5][6][7], more frequently have regional lymphadenopathy [4,6], and more often have multiple EM skin lesions [6]. ...
Are Differences in Presentation of Early Lyme Borreliosis in Europe and North America a Consequence of a More Frequent Spirochetemia in American Patients?
Article
Full-text available
  • Apr 2021
To assess whether differences in presentation between US and European patients with early Lyme borreliosis are due to the lower rate of spirochetemia in Europe, we compared multiple variables for patients with erythema migrans (EM), restricting the analysis to subjects with a positive blood culture at the time of presentation: 93 US patients infected with Borrelia burgdorferi versus 183 European patients infected with Borrelia afzelii (No = 144) or Borrelia garinii (No = 39). Compared to spirochetemic Slovenian EM patients infected with B. afzelii, US patients with a positive blood culture significantly less often recalled a preceding tick bite at the site of the EM skin lesion, had a shorter duration of EM prior to diagnosis and more often had multiple EM lesions, regional lymphadenopathy, constitutional symptoms, an increased ESR value, a low blood lymphocyte count and detectable borrelia antibodies in acute and convalescent phase blood samples. Similar differences were observed when US patients were compared to Slovenian patients with B. garinii infection, but not all reached statistical significance. The findings are comparable to those previously reported for the corresponding skin culture positive patients and do not support the hypothesis that a higher frequency of spirochetemia at the time of presentation in US patients with EM, compared with European EM patients, is the reason for the observed differences.
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... Pain or itchiness at the EM site are often present but typically described as mild in comparison to other skin conditions where they are more prominent [4,7]. The clinical presentation of EM has been shown to vary between US and European patient samples, likely as a result of discordance in primary infecting Borrelia genospecies [15,16]. ...
... As neither of these studies applied the same 5 cm entry criteria that we did, it is possible that differentiation to central clearing occurs very early and therefore we did not identify this trend. However, as noted by Strle et al. [16], other factors besides duration may influence the pathogenesis of central clearing. One such factor may be age, as we found that the odds of central clearing decreased 25% for every 10-year age increase. ...
... Our reported rates of itchiness and pain at the site of the EM are similar or somewhat higher than those reported by other US-based studies [17,33]. These rates may also be lower in US compared to European EM patients, particularly those infected with B. garinii [15,16]. ...
The presenting characteristics of erythema migrans vary by age, sex, duration, and body location
Article
Full-text available
  • Aug 2021
  • INFECTION
PurposeThe erythema migrans (EM) skin lesion is often the first clinical sign of Lyme disease. Significant variability in EM presenting characteristics such as shape, color, pattern, and homogeneity, has been reported. We studied associations between these presenting characteristics, as well as whether they were associated with age, sex, EM duration, body location, and initiation of antibiotics.Methods Two hundred and seventy one adult participants with early Lyme disease who had a physician-diagnosed EM skin lesion of ≥ 5 cm in diameter and ≤ 72 h of antibiotic treatment were enrolled. Participant demographics, clinical characteristics, and characteristics of their primary EM lesion were recorded.ResultsAfter adjusting for potential confounders, EM size increased along with increasing EM duration to a peak of 14 days. Male EM were found to be on average 2.18 cm larger than female EM. The odds of a red (vs blue/red) EM were 65% lower in males compared to females, and were over 3 times as high for EM found on the pelvis, torso, or arm compared to the leg. Age remained a significant predictor of central clearing in adjusted models; for every 10-year increase in age, the odds of central clearing decreased 25%.Conclusions Given that EM remains a clinical diagnosis, it is essential that both physicians and the general public are aware of its varied manifestations. Our findings suggest possible patterns within this variability, with implications for prompt diagnosis and treatment initiation, as well as an understanding of the clinical spectrum of EM.
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... Our study has shown that the majority of basic clinical and epidemiologic characteristics of EM before treatment with antibiotics were analogous in the two groups of women and consonant with previous findings in Slovenian patients with EM [35][36][37][38][39][40][41][42] and that the outcome after antibiotic treatment was excellent regardless of pregnancy. No subsequent objective manifestations of LB were established in either of the two groups, and the proportion of patients with symptoms at follow-up visits was even lower than found in other recent studies from Slovenia [37][38][39][40][41][42], possibly because only young, previously healthy patients were included in the present study. ...
... Our study has shown that the majority of basic clinical and epidemiologic characteristics of EM before treatment with antibiotics were analogous in the two groups of women and consonant with previous findings in Slovenian patients with EM [35][36][37][38][39][40][41][42] and that the outcome after antibiotic treatment was excellent regardless of pregnancy. No subsequent objective manifestations of LB were established in either of the two groups, and the proportion of patients with symptoms at follow-up visits was even lower than found in other recent studies from Slovenia [37][38][39][40][41][42], possibly because only young, previously healthy patients were included in the present study. ...
... Nevertheless, there were also several differences. We do not have a reliable explanation for the observation that the pregnant women less often had ring-like EM despite similar duration of the skin lesion before treatment, but we stress that the findings in our control group are in agreement with previous reports in Slovenian patients with EM [35][36][37][38][39][40][41][42]. Furthermore, the proportion of reported constitutional symptoms accompanying EM was lower in the pregnant women, indicating that the course of EM during pregnancy was milder than in the age-matched non-pregnant women ( Table 1, Figure 1), as also shown in previous reports on EM from the same region [35][36][37][38][39][40][41][42]. ...
Course and Outcome of Erythema Migrans in Pregnant Women
Article
Full-text available
  • Jul 2020
Information on Lyme borreliosis (LB) during pregnancy is limited. In the present study, the course and outcome of erythema migrans (EM) in 304 pregnant women, diagnosed in the period 1990–2015, was assessed and compared with that in age-matched non-pregnant women. The frequency of unfavorable outcome of pregnancies was also evaluated. The pregnant women reported constitutional symptoms less frequently than the non-pregnant women (22.4% vs. 37.2%, p < 0.001). Pregnant women diagnosed with EM later during pregnancy had a lower probability of reporting constitutional symptoms (odds ratio = 0.97 for 1-week difference in gestation week at diagnosis of EM, 95% CI: 0.94–0.99, p = 0.02). The outcome of pregnancy was unfavorable in 42/304 (13.8%) patients: preterm birth in 22/42 (52.4%), fetal/perinatal death in 10/42 (23.8%), and/or anomalies in 15/42 (35.7%). Several patients had potential explanation(s) for the unfavorable outcome. In conclusion, the course of early LB during pregnancy is milder than in age-matched non-pregnant women. The outcome of pregnancy with the treatment approach used in the present study (i.v. ceftriaxone 2 g once daily for 14 days) is favorable.
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... 69.4% of them had observed a tick bite shortly before the consultation. This figure is quite consistent with studies conducted in Europe on patients with EM (30,31). We observed that the notion of a tick bite having preceded the diagnosis was higher in the case of EM (79.5%) whereas it was statistically lower in the case of symptoms of the disseminated phase (54.4%). ...
... The Sentinel network observed it in 2020 (32). While for children, the majority of bites were located on the head, upper limbs and trunk, they were generally located on the lower limbs for adults, as already reported (31). ...
Case presentation and management of Lyme disease patients: a 9-year retrospective analysis in France
Article
Full-text available
  • Jan 2024
Introduction Lyme borreliosis (LB) is the most common vector disease in temperate countries of the northern hemisphere. It is caused by Borrelia burgdorferi sensu lato complex. Methods To study the case presentation of LB in France, we contacted about 700 physicians every year between 2003 and 2011. An anonymous questionnaire was established allowing the collection of 3,509 cases. The information collected was imported or directly entered into databases and allowed identifying variables that were validated in a multiple correspondence analysis (MCA). Results Sixty percent of the cases were confirmed, 10% were probable, 13.5% doubtful, 10.2% asymptomatic seropositive and 6.3% were negative. The clinical manifestations reported were cutaneous (63%), neurological (26%), articular (7%), ocular (1.9%) and cardiac (1.3%). Almost all patients were treated. When focusing more particularly on confirmed cases, our studies confirm that children have a distinct clinical presentation from adults. There is a gender effect on clinical presentation, with females presenting more often with erythema migrans or acrodermatitis chronica atrophicans than males, while males present more often with neurological signs or arthritis than females. Discussion This is the first time that a comprehensive study of suspected Lyme borreliosis cases has been conducted over several years in France. Although we were not able to follow the clinical course of patients after treatment, these results suggest the interest of refining the questionnaire and of following up a cohort of patients over a sufficiently long period to obtain more information on their fate according to different parameters.
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... The low sensitivity of borrelia blood cultures is probably an important reason that data on characteristics of patients with culture-confirmed hematogenous dissemination of borreliae in Europe are limited. Indeed, according to a PubMed literature search performed in November 2020 (and using the key words "borrelia" OR "Borrelia afzelii" OR "Borrelia garinii" AND "blood"), several studies on the isolation of B. afzelii or B. garinii from skin or cerebrospinal fluid with corresponding clinical data have been published [10][11][12][13][14][15][16][17][18]. However, no information on the pre-treatment characteristics or the post-treatment outcome of LB for patients with isolation of B. afzelii or B. garinii from blood has been reported. ...
Characteristics of spirochetemic patients with a solitary erythema migrans skin lesion in Europe
Article
Full-text available
Neither pre-treatment characteristics, nor the outcome after antibiotic therapy, have been reported for spirochetemic European patients with Lyme borreliosis. In the present study, patients with a solitary erythema migrans (EM) who had a positive blood culture for either Borrelia afzelii (n = 116) or Borrelia garinii (n = 37) were compared with age- and sex-matched patients who had a negative blood culture, but were culture positive for the corresponding Borrelia species from skin. Collectively, spirochetemic patients significantly more often recalled a tick bite at the site of the EM skin lesion, had a shorter time interval from the bite to the onset of EM, had a shorter duration of the skin lesion prior to diagnosis, and had a smaller EM skin lesion that was more often homogeneous in appearance. Similar results were found for the subset of spirochetemic patients infected with B. afzelii but not for those infected with B. garinii. However, patients with B. garinii bacteremia had faster-spreading and larger EM skin lesions, and more often reported itching at the site of the lesion than patients with B. afzelii bacteremia. Treatment failures were rare (7/306 patients, 2.3%) and were not associated with having spirochetemia or with which Borrelia species was causing the infection.
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... Regional lymphadenopathy is the most common physical finding associated with EM in both Europe and North America. Differences in EM and associated symptoms caused by B. garinii and B. afzelii also have been noted (Logar et al., 2004;Strle et al., 2011a). Patients with B. garinii had shorter incubation periods, faster evolution of their EM, and more symptomatic lesions (burning, itching, and pain) as well as modestly increased systemic symptomatology. ...
Lyme Disease in Humans
Article
  • Dec 2020
  • CURR ISSUES MOL BIOL
Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the Borrelia burgdorferi sensu lato complex. The ailment, widespread throughout the Northern Hemisphere, continues to increase globally due to multiple environmental factors, coupled with increased incursion of humans into habitats that harbor the spirochete. B. burgdorferi sensu lato is transmitted by ticks from the Ixodes ricinus complex. In North America, B. burgdorferi causes nearly all infections; in Europe, B. afzelii and B. garinii are most associated with human disease. The spirochete's unusual fragmented genome encodes a plethora of differentially expressed outer surface lipoproteins that play a seminal role in the bacterium's ability to sustain itself within its enzootic cycle and cause disease when transmitted to its incidental human host. Tissue damage and symptomatology (i.e., clinical manifestations) result from the inflammatory response elicited by the bacterium and its constituents. The deposition of spirochetes into human dermal tissue generates a local inflammatory response that manifests as erythema migrans (EM), the hallmark skin lesion. If treated appropriately and early, the prognosis is excellent. However, in untreated patients, the disease may present with a wide range of clinical manifestations, most commonly involving the central nervous system, joints, or heart. A small percentage (~10%) of patients may go on to develop a poorly defined fibromyalgia-like illness, post-treatment Lyme disease (PTLD) unresponsive to prolonged antimicrobial therapy. Below we integrate current knowledge regarding the ecologic, epidemiologic, microbiologic, and immunologic facets of Lyme disease into a conceptual framework that sheds light on the disorder that healthcare providers encounter.
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... This implies that patients and clinicians value the added certainty that laboratory work-up gives to the physician's clinical assessment. Laboratory testing may be especially relevant in situations where the LB diagnosis is not clear-cut, for example, when skin lesions do not resemble a typical EM, or if patients present with only generalized symptoms without a skin lesion [23,24]. Considering the improved diagnostic parameters of MTTT, serology may serve to aid in the diagnosis of these situations. ...
Diagnostic parameters of modified two-tier testing in European patients with early Lyme disease
Article
Full-text available
  • Nov 2020
  • EUR J CLIN MICROBIOL
Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing (STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7–82.9; specificity 96.1%, 95% CI 92.7–98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (p < 0.001), while maintaining comparable specificity (population controls p = 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.
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Prevalence of Lyme Disease and Relapsing Fever Borrelia spp. in Vectors, Animals, and Humans within a One Health Approach in Mediterranean Countries
Article
Full-text available
  • Jun 2024
The genus Borrelia has been divided into Borreliella spp., which can cause Lyme Disease (LD), and Borrelia spp., which can cause Relapsing Fever (RF). The distribution of genus Borrelia has broadened due to factors such as climate change, alterations in land use, and enhanced human and animal mobility. Consequently, there is an increasing necessity for a One Health strategy to identify the key components in the Borrelia transmission cycle by monitoring the humananimalenvironment interactions. The aim of this study is to summarize all accessible data to increase our understanding and provide a comprehensive overview of Borrelia distribution in the Mediterranean region. Databases including PubMed, Google Scholar, and Google were searched to determine the presence of Borreliella and Borrelia spp. in vectors, animals, and humans in countries around the Mediterranean Sea. A total of 3026 were identified and screened and after exclusion of papers that did not fulfill the including criteria, 429 were used. After examination of the available literature, it was revealed that various species associated with LD and RF are prevalent in vectors, animals, and humans in Mediterranean countries and should be monitored in order to effectively manage and prevent potential infections.
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Early Lyme Disease (Erythema Migrans) and Its Mimics (Southern Tick-Associated Rash Illness and Tick-Associated Rash Illness)
Article
  • Sep 2022
  • INFECT DIS CLIN N AM
Erythema migrans, an expanding erythematous skin lesion that develops days to weeks following an Ixodes species tick bite, is the most common clinical manifestation of Lyme disease. Presentations in the United States differ somewhat from that in Europe, presumably because of the different etiologic agents. Diagnosis is based on the appearance of the skin lesion, rather than on laboratory testing. After treatment with an appropriate oral antibiotic for 10 to 14 days, the prognosis is excellent. Two conditions that cause a similar skin lesion following a tick bite, but are of unknown cause, are Southern tick-associated rash illness in the United States and tick-associated rash illness in Japan.
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Surveillance for Lyme Disease — United States, 2008–2015
Article
Full-text available
  • Nov 2017
Problem/condition: Lyme disease is the most commonly reported vectorborne disease in the United States but is geographically focal. The majority of Lyme disease cases occur in the Northeast, mid-Atlantic, and upper Midwest regions. Lyme disease can cause varied clinical manifestations, including erythema migrans, arthritis, facial palsy, and carditis. Lyme disease occurs most commonly among children and older adults, with a slight predominance among males. Reporting period: 2008-2015. Description of system: Lyme disease has been a nationally notifiable condition in the United States since 1991. Possible Lyme disease cases are reported to local and state health departments by clinicians and laboratories. Health department staff conduct case investigations to classify cases according to the national surveillance case definition. Those that qualify as confirmed or probable cases of Lyme disease are reported to CDC through the National Notifiable Diseases Surveillance System. States with an average annual incidence during this reporting period of ≥10 confirmed Lyme disease cases per 100,000 population were classified as high incidence. States that share a border with those states or that are located between areas of high incidence were classified as neighboring states. All other states were classified as low incidence. Results: During 2008-2015, a total of 275,589 cases of Lyme disease were reported to CDC (208,834 confirmed and 66,755 probable). Although most cases continue to be reported from states with high incidence in the Northeast, mid-Atlantic, and upper Midwest regions, case counts in most of these states have remained stable or decreased during the reporting period. In contrast, case counts have increased in states that neighbor those with high incidence. Overall, demographic characteristics associated with confirmed cases were similar to those described previously, with a slight predominance among males and a bimodal age distribution with peaks among young children and older adults. Yet, among the subset of cases reported from states with low incidence, infection occurred more commonly among females and older adults. In addition, probable cases occurred more commonly among females and with a higher modal age than confirmed cases. Interpretation: Lyme disease continues to be the most commonly reported vectorborne disease in the United States. Although concentrated in historically high-incidence areas, the geographic distribution is expanding into neighboring states. The trend of stable to decreasing case counts in many states with high incidence could be a result of multiple factors, including actual stabilization of disease incidence or artifact due to modifications in reporting practices employed by some states to curtail the resource burden associated with Lyme disease surveillance. Public health action: This report highlights the continuing public health challenge of Lyme disease in states with high incidence and demonstrates its emergence in neighboring states that previously experienced few cases. Educational efforts should be directed accordingly to facilitate prevention, early diagnosis, and appropriate treatment. As Lyme disease emerges in neighboring states, clinical suspicion of Lyme disease in a patient should be based on local experience rather than incidence cutoffs used for surveillance purposes. A diagnosis of Lyme disease should be considered in patients with compatible clinical signs and a history of potential exposure to infected ticks, not only in states with high incidence but also in areas where Lyme disease is known to be emerging. These findings underscore the ongoing need to implement personal prevention practices routinely (e.g., application of insect repellent and inspection for and removal of ticks) and to develop other effective interventions.
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Borrelia burgdorferi Stimulates Macrophages to Secrete Higher Levels of Cytokines and Chemokines than Borrelia afzelii or Borrelia garinii
Article
Full-text available
  • Nov 2009
  • J INFECT DIS
To delineate the inflammatory potential of the 3 pathogenic species of Borrelia burgdorferi sensu lato, we stimulated monocyte-derived macrophages from healthy human donors with 10 isolates each of B. burgdorferi, Borrelia afzelii or Borrelia garinii recovered from erythema migrans skin lesions of patients with Lyme borreliosis from the United States or Slovenia. B. burgdorferi isolates from the United States induced macrophages to secrete significantly higher levels of interleukin (IL)-8, CCL3, CCL4, IL-6, IL-10, and tumor necrosis factor than B. garinii or B. afzelii isolates. Consistent with this response in cultured macrophages, chemokine and cytokine levels in serum samples of patients from whom the isolates were obtained were significantly greater in B. burgdorferi–infected patients than in B. afzelii– or B. garinii–infected patients. These results demonstrate in vitro and in vivo that B. burgdorferi has greater inflammatory potential than B. afzelii and B. garinii which may account in part for variations in the clinical manifestations of Lyme borreliosis
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Characteristics of Erythema migrans in Borrelia afzelii and Borrelia garinii Infections
Article
  • Feb 2003
Erythema migrans is the most common manifestation of stage I Lyme borreliosis. This study investigated the relation between the subspecies of Borrelia burgdorferi involved, the time of development and the appearance of the manifestation. The study comprised 33 cases of erythema migrans yielding B. burgdorferi sensu lato by culture of skin biopsy. The species was determined by polymerase chain reaction analysis of the cultivated spirochaetes. In 22 of the cases, B. afzelii was demonstrated, whereas 11 yielded growth of B. garinii. All 11 erythemas associated with B. garinii were homogeneous, whereas 20 of the 22 associated with B. afzelii were annular. The garinii erythemas developed more rapidly, and were generally larger than the afzelii erythemas. The observations call for comparison with other geographical areas with similar, and with different, borrelial infection spectra.
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Comparison of Post-Lyme Borreliosis Symptoms in Erythema Migrans Patients with Positive and Negative Borrelia burgdorferi Sensu Lato Skin Culture
Article
  • Nov 2010
  • VECTOR-BORNE ZOONOT
Limited data exist on differences of erythema migrans patients with either positive or negative Borrelia burgdorferi sensu lato skin culture. We analyzed 252 adult patients with erythema migrans in whom skin biopsy specimen was cultured for the presence of B. burgdorferi sensu lato. Evaluations of epidemiological, clinical, and microbiological findings were conducted at baseline, 14 days, 2, 6, and 12 months after treatment with either doxycycline or cefuroxime axetil. One hundred fifty-one (59.9%) patients had positive skin culture (86.9% B. afzelii, 8.0% B. garinii, 5.1% B. burgdorferi sensu stricto) and 101 (40.1%) had negative skin culture. Patients in the culture-positive and culture-negative groups were comparable for the basic demographic, epidemiological, clinical, and laboratory characteristics at presentation. Statistically significantly worse selected treatment outcome parameters in the culture-positive group compared with the culture-negative group were established during follow-up. Treatment failure was documented in two patients who were culture positive and in none in the culture-negative group. Although findings for the pretreatment characteristics were comparable between the erythema migrans skin culture-positive and culture-negative patients, some parameters indicate that borrelia skin culture positivity may predict a less-favorable treatment outcome.
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Diagnosis of early Lyme disease by polymerase chain reaction amplification or culture of skin biopsies from erythema migrans lesions
Article
  • Jan 1993
Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease.
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Erythema chronicum migrans Afzelius in Sweden. A study on 231 patients
Article
  • Jan 1987
  • Zentralbl Bakteriol Mikrobiol Hyg Med Microbiol Infect Dis Virol Paras
In order to describe the clinical manifestations of erythema chronicum migrans Afzelius (ECMA) in Sweden and to compare them with those in Lyme disease in the United States, 231 patients with ECMA were investigated. Although there are many similarities between the two disorders the findings also point to differences. The skin lesions were of longer duration (median 5-6 weeks) than those in Lyme disease but less often multiple (8%). General symptoms were found in about half of the patients with a short disease duration (less than or equal to 3 weeks), but were usually mild. Laboratory abnormalities were noted in only a minority of the cases. At the time of diagnosis none of the patients had spirochete-induced arthritis, but in three of them cardiac involvement was suspected. Among 16 untreated patients meningitis later developed in two patients and arthritis in one. Diagnostic procedures such as serologic testing and cultivation of spirochetes are discussed.
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Serological diagnosis of Erythema migrans disease and related disorders
Article
  • Sep 1984
An indirect immunofluorescence technique for the determination of antibodies against ixodid tick spirochetes is described. Differences in the reactivity between Ixodes ricinus spirochete and Ixodes dammini spirochete antigens were not observed. Cross-reacting antibodies against Treponema pallidum and Treponema phagedenis can be eliminated by quantitative absorption with T. phagedenis. Cross-reactions with leptospira were not observed by immunofluorescence. In the IgM test, false negative reactions caused by high-titered specific IgG antibodies or false positive reactions caused by rheumatoid factor occur. This can be avoided by testing the IgM fraction (19S-IgM-test) or using sera previously treated with anti-IgG serum. Significantly elevated antibody titers against ixodid tick spirochetes were observed in 45% of 44 cases with erythema migrans disease, in 72% of 29 cases of lymphocytic meningoradiculitis, in all of nine patients with acrodermatitis chronica atrophicans and in all of four investigated patients with lymphocytoma (lymphadenosis benigna cutis).
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Lyme Disease—A Tick-borne Spirochetosis?
Article
  • Jul 1982
A treponema-like spirochete was detected in and isolated from adult Ixodes dammini, the incriminated tick vector of Lyme disease. Causally related to the spirochetes may be long-lasting cutaneous lesions that appeared on New Zealand White rabbits 10 to 12 weeks after infected ticks fed on them. Samples of serum from patients with Lyme disease were shown by indirect immunofluorescence to contain antibodies to this agent. It is suggested that the newly discovered spirochete is involved in the etiology of Lyme disease.
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Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato
Article
  • Jun 1995
  • RES MICROBIOL
Borrelia burgdorferi sensu lato, the aetiological agent of Lyme disease, has been subdivided into three species: B. burgdorferi sensu stricto, B. garinii and B. afzelii. We and other authors have hypothesized an association between the three species of B. burgdorferi sensu lato and some of the different clinical manifestations of Lyme disease. In order to demonstrate this hypothesis, we analysed twenty-nine isolates cultured from patients with different symptoms. The method used was multilocus enzyme electrophoresis: twelve genetic loci were characterized on the basis of the electrophoretic mobility of their products, and twenty-eight distinctive allele profiles (electrophoretic types) were distinguished, among which mean genetic diversity per locus was 0.649. Cluster analysis of a matrix of genetic distances between paired electrophoretic types revealed three primary divisions separated at genetic distances greater than 0.7 and corresponding to the three species of B. burgdorferi sensu lato. Ten strains obtained from skin of patients with erythema chronicum migrans (the primary stage of the disease) were assigned to the three different species. All the six strains isolated from patients with acrodermatitis chronica atrophicans were of the species B. afzelii, which was not found to be associated with another chronic manifestation of Lyme disease. Arthritis was caused prevalently by B. burgdorferi sensu stricto, and neuroborreliosis by B. burgdorferi sensu stricto and B. garinii. In conclusion, our results confirm the association between some of the different chronic manifestations of the disease and the species of B. burgdorferi sensu lato.
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Different Genospecies of Borrelia burgdorferi Are Associated with Distinct Clinical Manifestations of Lyme Borreliosis
Article
  • Nov 1993
Borrelia burgdorferi sensu lato has been subdivided into three genospecies: B. burgdorferi sensu stricto, B. garinii, and B. burgdorferi group VS461. Sixty-eight isolates cultured from patients and 26 strains from ticks were characterized with use of SDS-PAGE, western blotting, and rRNA gene restriction analysis. Fifty-seven of 58 strains obtained from the skin of 70 patients who had erythema migrans or acrodermatitis chronica atrophicans were of group VS461, whereas the genotype of the remaining strain was unidentifiable. Of 10 strains cultured from CSF (n = 3) and skin (n = 7) of 20 patients with extracutaneous symptoms of Lyme borreliosis, nine were B. garinii and one was B. burgdorferi sensu stricto. Of these 20 patients, 17 had neuroborreliosis, one had arthritis and carditis, one had myalgia, and one had erythema and arthralgia. All 26 isolates from ticks were of group VS461. In conclusion, infections due to group VS461 and B. garinii are associated with cutaneous and extracutaneous symptoms, respectively. Our findings suggest that B. burgdorferi genotypes have different pathogenic potentials.
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