Differentiating Lyme arthritis: a case-based review.

The incidence or prevalence of Lyme arthritis (LA) in Denmark is unknown and assumed very low. No published cases of polymerase chain reaction (PCR)-confirmed LA from Denmark exist. Clinically, LA does not differ from other rheumatic oligoarthritic disorders posing a differential diagnostic challenge. To review the incidence and prevalence of LA to our knowledge and to present a case series of PCR-confirmed LA cases from Denmark. We conducted a systematic literature review via MEDLINE and EMBASE to explore incidence and prevalence rates of LA. Additionally, we present six cases of patients diagnosed with LA in Denmark. Our literature review identified 23 studies reporting prevalence or incidence, yet only ten studies provided estimates ranging from 1.1 to 280/100.000 in the general population. Our case series identified six patients with LA from a localized region in Southern Denmark; all confirmed by Borrelia-specific real-time PCR from synovial fluid. The diagnostic delay was up to 38 months. All patients except one had a history of previous tick bites; none had erythema migrans lesions. All presented with recurrent arthritis in the knee joint, and two had arthritis in the wrist. The literature review showed an incidence of LA ranging from 1.1 to 15.8 per 100.000 in Europe. Our case series suggests a potentially higher prevalence of LA in Denmark than previously believed. Lack of tick exposure history, antibody assessments and test of Borrelia burgdorferi sensu lato DNA in synovial fluid might lead to misdiagnosed cases potentially explaining the assumed low incidence of LA in Denmark.

Neuroborreliosis interpreted as multiple sclerosis by MRI.

Lyme neuroborreliosis (LNB) is the most prevalent nervous system bacterial infection in Denmark. In a young man with LNB, brain MRI and cerebrospinal fluid (CSF) demonstrated findings compatible with multiple sclerosis. This case report underlines the requirement for testing for intrathecal Borrelia antibody production when the number of cells in the CSF is low or even normal. It also demonstrates the unchanged diagnostic delay of NBL observed during the last 20 years.

Tick-borne encephalitis.

Tick-borne encephalitis (TBE) is a viral tick-borne infection occurring in many parts of Europe and Asia as described in this review. Increasing TBE case numbers have been reported over recent decades. In Denmark the infection is rare (1-14 annual cases). The rise in TBE in Denmark is mainly driven by microfoci outside of Bornholm, primarily North Zealand. Clinical illness has a bi-phasic presentation: "summer-flu" which may be followed by a neuroinfection. No specific treatment exists, and mortality is less-than 1%. A considerable percentage of patients may experience neurological sequelae. TBE is preventable through vaccination.

Rickettsiosis in Denmark: A nation-wide survey.

Rickettsia helvetica has been reported at varying prevalences in Danish and other European Ixodes ricinus populations. Though apparently widespread and with reported cases of human infection, the significance of the bacteria as a threat to public health remains unclear. We present a nation-wide survey of rickettsia in ticks, roe deer and humans in Denmark. Ticks were collected by flagging and screened for presence of rickettsial DNA by polymerase chain reaction. Sera from roe deer, hunters, neuroborreliosis patients and blood donors were analyzed for presence of anti-R. helvetica and Rickettsia felis antibodies by immunofluorescence microscopy. The Rickettsia minimum infection rate in ticks was 4.9 % (367/973 pools positive, 7510 ticks in total), with 3.9 % in nymphs and 9.3 % in adults. Rickettsia helvetica accounted for 4.17 % and Rickettsia monacensis for 0.03 %, 0.6 % comprised non-differentiable rickettsial DNA. The prevalence of antibodies against R. helvetica was 2.8 % (9/319) in roe deer, while no hunters (n = 536) or blood donors (n = 181) were positive. The prevalence of anti-R. helvetica antibodies among Lyme neuroborreliosis patients was 6 % (3/47), where it co-occurred with Anaplasma phagocytophilum. Based on our study autochthonous rickettsiosis is of limited concern to the public health in Denmark, but our finding of R. monacensis for the first time in Denmark illustrates the dynamic nature of tick-borne pathogens, emphasizing that continuous surveillance is necessary.

Detection of Borrelia burgdorferi sensu lato DNA in cerebrospinal fluid samples following pre-enrichment culture.

Molecular methods for diagnosing Lyme neuroborreliosis (LNB) have shown suboptimal diagnostic sensitivities. The objective of this study was to improve the clinical sensitivity of PCR detection of Borrelia burgdorferi sensu lato spirochetes by inoculating cerebrospinal fluid (CSF) from patients suspected of LNB directly into culture medium at the time of lumbar puncture, with this pursuing enrichment of Borrelia spirochetes before PCR analysis. Adult patients with symptoms suggestive of LNB were prospectively enrolled at two hospitals in the Region of Southern Denmark. The CSF-culture samples were incubated for at least eight weeks. During this period, culture sample aliquots were analysed for the presence of Borrelia DNA by separate PCR protocols in two independent clinical laboratories. The included patients were diagnosed with definite (n=12) or possible (n=2) LNB, and non-LNB (n=171) based on clinical and paraclinical findings. Patients in the LNB and the non-LNB group had a median duration from symptom onset to lumbar puncture of 40 days (IQR [23-90] days) and 120 days (IQR [32-365] days), respectively. Pre-enrichment growth of Borrelia spirochetes was accomplished from three patients (21 %) in the LNB group. The positive culture samples were confirmed by both the digital droplet PCR and the real-time PCR methods employed. All CSF samples were PCR negative in the non-LNB group. The results of this study do not support the use of Borrelia-specific PCR as a general routine diagnostic tool in adults. Still, they suggest it may prove of additional value in selected patients with a limited time from symptom onset to sample collection.

No correlation between symptom duration and intrathecal production of IgM and/or IgG antibodies in Lyme neuroborreliosis - a retrospective cohort study in Denmark.

OBJECTIVES: In Europe, a definite diagnosis of Lyme neuroborreliosis (LNB) requires intrathecally produced Borrelia-specific antibodies. We aimed to examine if the time from symptom debut to lumbar puncture (LP) correlated with findings of intrathecal production of Borrelia-specific IgM and/or IgG antibodies in LNB METHODS: A retrospective study of 544 patients with a positive Borrelia burgdorferi antibody index (Bb-AI) analysed at the Department of Clinical Microbiology, Odense University Hospital, Denmark, between 01.01.1995 and 31.12.2020 RESULTS: The delay from symptom onset to LP for patients with positive Bb-AI IgM was 30 days (IQR 14-95 days), IgG 24 days (IQR 11-62), IgM+IgG 24 days (IQR 14-48), P = 0.098. Ninety-three patients had a second LP after median 125 days (IQR 28-432) and 25 had a third LP after median 282 days (IQR 64-539). Most patients (66.7%) did not convert from their initial intrathecal antibody finding. The prevalence of different clinical manifestations differed significantly between the three Bb-AI groups. CONCLUSIONS: Intrathecal Borrelia-specific antibody production did not follow the typical immune response of initial IgM production followed by IgG production. Diagnosis of LNB stage should not be based on the type of antibodies found in the cerebrospinal fluid.

An intervention in general practice to improve the management of Lyme borreliosis in Denmark.

BACKGROUND: Our objectives were to improve the following outcomes in patients with Lyme borreliosis (LB) through an educational intervention in general practice: (i) increase the number of hospital referrals on suspicion of LB, (ii) increase the number of cerebrospinal fluid (CSF) tests examined for Borrelia burgdorferi antibody index, (iii) decrease the number of serum-B. burgdorferi antibody tests ordered, (iv) shorten delay from symptom onset to hospital in Lyme neuroborreliosis (LNB) patients, (v) increase LB knowledge among general practitioners. METHODS: A prospective non-blinded non-randomized intervention trial on the island of Funen, Denmark. The intervention included oral and written education about LB and was carried out in areas with an LNB incidence ≥4.7/100.000 between 22 January 2019 and 7 May 2019. Results were compared between the intervention group (49 general practices) and the remaining general practices in Funen (71 practices) 2 years before and after the intervention. RESULTS: In the study period, 196 patients were referred on suspicion of LB, a 28.9% increase in the intervention group post-intervention, 59.5% increase in the control group (P = 0.47). The number of CSF-Borrelia-antibody index tests increased 20.8% in the intervention group, 18.0% in the control group (P = 0.68), while ordered serum-B. burgdorferi antibody tests declined 43.1% in the intervention group, 34.5% in the control group (P = 0.30). 25.1% had the presence of serum-B. burgdorferi antibodies. We found no difference in LNB pre-hospital delay before and after intervention or between groups (P = 0.21). The intervention group performed significantly better on a follow-up questionnaire (P = 0.02). CONCLUSION: We found an overall improvement in LB awareness and referrals among general practitioners but could not show any effect of the intervention on clinical outcomes of LNB.

Monitoring Temporal Trends in Internet Searches for "Ticks" across Europe by Google Trends: Tick-Human Interaction or General Interest?

Monitoring vector-human interaction is pivotal for assessing potential transmission rates of vector borne diseases and their associated public health impact. People often seek information following an insect bite in order to identify hematophagous arthropods, which in recent years often is done using Internet resources. Through this activity, a record of net searches is generated, which include information that reflect local human-arthropod interaction, e.g., for the common tick (Ixodes ricinus) in European countries. Such records could in principle provide low cost real-time monitoring data, if indeed Internet search activities adequately reflect tick-human interaction. We here explore Google Trends records for within-year and between-year trends, for four different Danish search terms for "tick(s)". We further assess the relationship between monthly search-frequencies and local weather conditions (temperatures and precipitation from 2007 to 2016) in nine European countries. Our findings point to significant limitations in the records due to changes in search-term preferences over the given years. However, the seasonal dynamics are comparable among search-terms. Moreover, the seasonal pattern in search terms vary across Europe in tune with changes in temperature and precipitation. We conclude that, the within-year variation for given search-terms provide credible information, which systematically vary with local weather patterns. We are not convinced that these records merely reflect general interest. It will, however, require a more in-depth analysis by researchers that have specific insight into local language practices to fully assess the strength and weaknesses of this approach.

Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study.

BACKGROUND: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. OBJECTIVES: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. DATA SOURCES: Medline, Embase, Scopus, Cochrane library. STUDY ELIGIBILITY CRITERIA: There was no discrimination on study type, time of publication or language. PARTICIPANTS: Review: All articles with definite LNB and confirmed/possible encephalitis. COHORT: LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis. METHODS: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. COHORT: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. RESULTS: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died. COHORT: Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died. CONCLUSIONS: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.

Evaluation of factors influencing tick bites and tick-borne infections: a longitudinal study.

BACKGROUND: Various tick-borne infections like borreliosis and rickettsiosis pose a health risk to humans in many parts of the world. We investigated seroprevalence of and seroconversion to Borrelia burgdorferi and Rickettsia spp. and relation to tick-bites, weather and clinical manifestations in Denmark. METHODS: Blood donors were enrolled at the Hospital of Southern Jutland in June-July with follow-up November-February of 2018 and 2019. Blood samples were collected, and a questionnaire regarding tick bites, potential exposures and symptoms was completed at each visit. Samples were tested for presence of IgM and IgG antibodies directed against B. burgdorferi and Rickettsia spp. using R. helvetica and R. felis as antigens. Data were examined for correlation between tick bites, serological results, potential exposures and symptoms. RESULTS: Two-hundred and fourteen (93 follow-ups) and 130 (38 follow-ups) blood donors were included in 2018 and 2019, respectively. The total borrelia seroconversion rate was 6.3% (CI 2.1-10.5), while the prevalence of IgM and IgG antibodies was 7.8% (CI 4.9-10.6) and 6.7% (CI 4-9.3), respectively. Seroconversion to Rickettsia spp. was detected in one participant. Tick bites and seroconversion were not significantly associated with the reported unspecific symptoms, but unspecific symptoms were common in the study population. There was no significant difference in number of tick bites or seroconversion/prevalence between seasons with highly alternating weather. CONCLUSIONS: Results suggest that weather conditions in an individual year have a limited impact. Anti-Borrelia-antibodies do not seem to persist in serum for several years. Rickettsiosis is of limited concern in Denmark.

Spatial and temporal patterns of Lyme Neuroborreliosis on Funen, Denmark from 1995-2014.

In Europe, Lyme neuroborreliosis (LNB) is the most severe manifestation of Lyme borreliosis and has recently been added to the communicable disease surveillance list for EU/EEA by the European Commission. In Northern Europe, LNB is primarily caused by the spirochete Borrelia garinii and transmitted by the tick Ixodes ricinus. This Danish observational epidemiologic case-control study includes every identified LNB patient (n = 401) on Funen, Denmark, from 1995-2014. We display spatial and temporal LNB incidence variation, seasonal distribution of cases and local spatial case clustering. Seasonal patterns show LNB symptom-onset peaking in July and a significant seasonal difference in number of cases (p < 0.01). We found no significant change in seasonality patterns over time when dividing the study period into 5-year intervals. We identified a significant local geographical hot-spot of cases with a relative risk of 2.44 (p = 0.013). Analysis revealed a significantly shorter distance to nearest forest for cases compared with controls (p < 0.001). We present a novel map of the focal geographical distribution of LNB cases in a high endemic borreliosis area. Continued studies of case clustering in the epidemiology of LNB are of key importance in guiding intervention strategies.

The predictive value of CXCL13 in suspected Lyme neuroborreliosis: a retrospective cross-sectional study.

The role of CXCL13 as a marker of Lyme neuroborreliosis (LNB) is under investigation, and CXCL13 is not part of routine diagnostics in suspicion of LNB. Our aim was to find the optimal cut-off value of CXCL13 for LNB in a Danish population and to investigate the role of CXCL13 both in early LNB and as a discriminatory marker between LNB and other neuroinflammatory disorders. We conducted a retrospective cross-sectional study including all patients with a cerebrospinal CXCL13 test performed at the Department of Clinical Immunology, Odense University Hospital, Denmark, between 1 January 2015 and 31 December 2018. We included 619 patients, of which 51 had definite LNB, 14 patients had possible LNB with neurological symptoms suggestive of LNB and pleocytosis but no intrathecal Borrelia antibodies, eight patients had prior LNB and 546 had no LNB. With an optimal CXCL13 cut-off of 49 ng/L we found a sensitivity of 100% and specificity of 94% (AUC 0.988, 95% CI 0.980-0.996) when patients treated with antibiotics prior to lumbar puncture were excluded (n = 130). All patients with possible LNB had a CXCL13 value above the cut-off value; 18/546 patients (3.3%) without LNB had a CXCL13 value ≥ 50 ng/L. While CXCL13 cannot be used as a stand-alone test, it can be used as a reliable additional marker in treatment-naive patients suspected of LNB. CXCL13 can be used to monitor treatment response in LNB patients.

Eosinophilic meningitis due to Angiostrongylus cantonensis in Europe.

OBJECTIVES: To describe and analyse the epidemiological and clinical characteristics of imported human angiostrongyliasis in Europe. METHODS: A systematic literature review of cases of human angiostrongyliasis in Europe was performed. Seven databases were searched. The epidemiological and clinical characteristics were extracted from included records and simple summary statistics were performed on extracted data. RESULTS: Twenty-two cases reported between 1988 and 2019 were identified. They were mainly from French Polynesia, Southeast Asia, and the Caribbean Islands. The dominant suspected mode of transmission was ingestion of prawns, shrimp, or salad. For patients with data, 90% had a history of headache, often lasting, and half had paresthesia. Eighty-nine percent had eosinophilia, 93% had cerebrospinal fluid (CSF) eosinophilia, and 92% had elevated CSF protein. Central nervous system (CNS) imaging was normal in most cases. Two-thirds received albendazole or mebendazole treatment, although this is not currently recommended. CONCLUSIONS: We have increased previous numbers to 22 reported cases in total since 1988. Angiostrongyliasis should generally be suspected in patients with a lasting headache who have returned from Southeast Asia, China, the Caribbean Islands, Australia, or French Polynesia, as well as parts of North America and Tenerife, Spain, although one autochthonous case from mainland Europe has also been reported. A dietary history should focus on prawns, shrimp, and salad, whilst also including slugs and snails and other paratenic hosts where relevant. The clinical diagnosis is supported by the presence of blood eosinophilia, CSF eosinophilia, and elevated CSF protein. A definitive laboratory diagnosis should be sought, and CNS imaging should be used to support, not to rule out the diagnosis. The most up-to-date evidence should always be consulted before initiating treatment. Current recommendations include analgesics, corticosteroids, and periodic removal of CSF for symptom relief, while antihelminthic treatment is debated.

Phylogenetic characterization of tick-borne encephalitis virus from Bornholm, Denmark.

The Danish island of Bornholm in the Baltic Sea has been known as a tick-borne encephalitis (TBE) natural focus for more than 60 years. TBE in humans is diagnosed on a regular basis either in inhabitants or tourists of the island. Other areas in Denmark have been suggested as possible risk areas of TBE. Despite the long-known endemicity on Bornholm and the possibility of the virus circulating in other areas, no data on the prevalences of TBE virus (TBEV) in ticks, or adequate molecular characterization and phylogenetic studies are available for the circulating TBEV strains. This study aimed to detect TBEV in ticks collected on the island of Bornholm and other possible risk areas, with the attempt to isolate the circulating viruses for molecular and phylogenetic analysis and confirm the presence of virus in the predicted risk areas. From 2014 to 2016, 9321 I. ricinus (nymphs, females, and males) were collected by flagging 31 locations in Denmark. The ticks were pooled and tested for TBEV by qPCR. The envelope gene of the detected TBE virus strains was amplified and sequenced by RT-PCR. After successful virus isolation, whole genome sequencing was performed. Phylogenetic analysis of the obtained sequences was done by the Maximum Likelihood method. One pool of 11 females and one pool of eight males from a total of 34 tick pools collected from the northwestern shore of lake Rubinsøen on Bornholm tested positive, resulting in a local estimated point prevalence of 0.6% [CI95% 0,1-1.85%] in this microfocus. We were not successful in confirming any other of the predicted TBEV-endemic areas. Alignment of the two complete E genes from Bornholm revealed identical sequences. Virus isolation and whole genome sequencing were succeeded from one of the positive samples. Phylogenetic analysis showed that the isolated virus had the closest phylogenetic relationship to TBEV sequences detected in Eastern and Central Europe.

Continued expansion of tick-borne pathogens: Tick-borne encephalitis virus complex and Anaplasma phagocytophilum in Denmark.

Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus within the tick-borne encephalitis (TBE) complex. The TBE complex is represented by both TBEV and louping ill virus (LIV) in Denmark. Anaplasma phagocytophilum is also transmitted by ticks and is believed to play an essential role in facilitating and aggravating LIV infection in sheep. This study aimed to describe the distribution of TBE complex viruses in Denmark, to establish the possible emergence of new foci and their association with the distribution of A. phagocytophilum. We performed a nationwide seroprevalence study of TBE complex viruses using roe deer (Capreolus capreolus) as sentinels and determined the prevalence of A. phagocytophilum in roe deer. Danish hunters obtained blood samples from roe deer during the hunting season of 2013-14. The samples were examined for TBEV-specific antibodies by virus neutralization tests (NT). A. phagocytophilum infection was assessed by specific real-time-PCR. The overall seroprevalence of the TBE complex viruses in roe deer was 6.9% (51/736). The positive samples were primarily obtained from a known TBE endemic foci and risk areas identified in previous sentinel studies. However, new TBE complex risk areas were also identified. The overall prevalence of A. phagocytophilum was 94.0% (173 PCR-positive of 184 roe deer), which is twice the rate observed ten years ago. These results point to an expansion of these tick-borne diseases geographically and within reservoir populations and, therefore, rationalize the use of sentinel models to monitor changes in transmission of tick-borne diseases and development of new risk areas. We found no association between TBE complex-positive roe deer and the prevalence of A. phagocytophilum, as almost all roe deer were infected. Based on our findings we encourage health care providers to be attentive to tick-borne illnesses such as TBE when treating patients with compatible symptoms.

Rickettsioses in Denmark: A retrospective survey of clinical features and travel history.

Rickettsia spp. can be found across the globe and cause disease of varying clinical severity, ranging from life-threatening infections with widespread vasculitis to milder, more localized presentations. Vector and, to some degree, reservoir are hematophagous arthropods, with most species harboured by ticks. In Denmark, rickettsiae are known as a cause of imported travel-related infections, but are also found endemically in ticks across the country. Data are, however, lacking on the geographical origin and clinical features of diagnosed cases. In this study, we have examined the travel history and clinical features of two groups of patients; 1) hospital-patients diagnosed with rickettsioses in the years 2010-2015 and 2) patients from primary health care (PHC) centers in Denmark having demonstrated anti-rickettsia antibodies in the years 2012-2015. The patients were identified using the Danish National Patient Registry (DNPR) and through the serological database at the State Serum Institute, where the laboratory diagnosis of rickettsioses is currently centralized. Data were collected for 86 hospital patients and 26 PHC center patients by reviewing hospital medical records and performing telephone interviews with PHC centers. Of the hospital patients, 91% (78/86) had a history of international travel 14 days prior to symptom start, with most having imported their infection from southern Africa, South Africa in particular (65%), and presenting with a clinical picture most compatible with African tick-bite fever caused by R. africae. Only two patients presented with a CRP > 100 mg/L and no mortalities were reported. At the PHC centers, most patients presented with mild flu-like symptoms and had an unknown (50%) or no history (19%) of international travel, raising the possibility of endemic rickettsioses. In view of our findings, rickettsioses do not appear to constitute a major public health problem in Denmark, with most cases being imported infections and potential endemic cases presenting as mild infections.

Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer.

Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe.

Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark.

BACKGROUND: Despite a well-described symptomatology, treatment delay and sequelae are common in patients with Lyme neuroborreliosis (LNB). The aim of this study was to contribute to the knowledge about the symptomatology and epidemiology of LNB. METHODS: We conducted a retrospective study of all LNB cases verified by a positive Borrelia intrathecal antibody index test performed at the Department of Microbiology, Odense University Hospital, Denmark, from 1995 through 2014. RESULTS: The study included 431 patients; 126 were children. The mean incidence was 4.7 per 100 000 inhabitants per year. The median delay from neurological symptom debut to first hospital contact was 20 days and significantly longer for patients with symptom debut in the winter/early spring. The most common clinical symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6% were admitted during their course of treatment. Serum Borrelia immunoglobulin M and immunoglobulin G at the time of positive Borrelia intrathecal antibody index test were negative in 67 patients (15.5%). We found a median treatment delay of 24 days, with no improvement in our 20-year study period. Residual symptoms following treatment were found in 28.1% of patients, and risk of residual symptoms was significantly associated with delay from symptom debut to initiation of treatment. CONCLUSIONS: The association between treatment delay and residual symptoms and the lack of improvement in treatment delay during the study period highlight the need for standardized diagnostic routines and a better follow-up for LNB patients. Our findings disprove that all patients with LNB develop positive serum Borrelia antibodies within 6 weeks after infection.

[Clinical manifestations, diagnosis and treatment of Lyme borreliosis].

Lyme borreliosis is an infection caused by the Borrelia burgdorferi sensu lato complex and transmitted by Ixodes ricinus ticks in Denmark. It can manifest itself in several different forms of which erythema migrans is the most common and is diagnosed by clinical assessment of the characteristic erythema. Laboratory support for the clinical diagnosis of other manifestations rests on the measurement of Borrelia-specific antibodies. Treatment is straight-forward with antibiotics such as penicillin. This paper reviews the clinical manifestations, diagnosis and treatment of this infection.