Lyme borreliosis: diagnostics, treatment and the role of healthcare services

Lyme borreliosis (LB) is the most common tick-borne disease in Europe, caused by spirochete Borrelia burgdorferi sensu lato. Approximately 3–16% of patients with B. burgdorferi infection develop neurological symptoms, leading to a disease called Lyme neuroborreliosis (LNB). Serological response in LB may take several weeks, which complicates the diagnostics in early LNB. The chemokine CXCL13 is a promising biomarker, the concentration of which starts to rise in acute LNB before intrathecal production of B. burgdorferi–specific antibodies begins. In Finland, LNB has been treated with a 3-week course of intravenous ceftriaxone. The aims of this study were to specify the manifestations of LNB in Finland, investigate the role of CXCL13 as a tool in the LNB diagnostics, compare oral doxycycline to intravenous ceftriaxone in the treatment of LNB, study the diagnostic accuracy of suspected LB with the most typical differential diagnoses, and evaluate the use of antibiotics and healthcare services in patients with suspected LB. The most typical signs and symptoms of LNB were painful meningoradiculitis, facial nerve palsy, Garin-Bujadoux-Bannwarth syndrome, headache and unspecific neck-shoulder pain. Cerebrospinal fluid CXCL13 concentration was elevated in the acute phase of infection and decreased rapidly after treatment. LNB patients who received doxycycline improved equally well as patients with ceftriaxone treatment. LB was unlikely in half of the patients with suspected LB. The most typical conditions causing the symptoms in patients with unlikely LB were of musculoskeletal, neurological, psychological and functional origin. Patients with unlikely LB used more healthcare services than patients with definite, probable or possible LB. Antimicrobial utilization did not differ among the groups of differing LB certainty. In conclusion, our results support the clinical use of CXCL13 in the diagnostics of LNB, and oral doxycycline in the treatment of LNB. Additionally, because various conditions may be confused with LB, physicians must pay attention to differential diagnostics of LB to avoid unnecessary antibiotic treatments and treatment delays.Lymen borrelioosi: diagnostiikka, hoito ja terveydenhuollon palvelujen käyttö Lymen borrelioosi (LB) on tavallisin puutiaisvälitteinen sairaus Euroopassa. Sen aiheuttaa spirokeetta Borrelia burgdorferi sensu lato. Noin 3–16 %:lle potilaista kehittyy neurologisia oireita, jolloin sairautta kutsutaan Lymen neuroborrelioosiksi (LNB). Serologisen vasteen kehittyminen voi kestää viikkoja, mikä vaikeuttaa alkuvaiheen LNB:n diagnostiikkaa. Kemokiini CXCL13 on lupaava merkkiaine, jonka pitoisuus alkaa nousta akuutissa LNB:ssä ennen aivokalvojen sisäisen vastaainemuodostuksen alkamista. Suomessa LNB on hoidettu kolmen viikon kestoisella suonensisäisellä keftriaksonihoidolla. Tämän tutkimuksen tavoitteina oli täsmentää LNB:n ilmenemismuotoja Suomessa, tutkia CXCL13 hyödyllisyyttä LNB diagnostiikassa, verrata suun kautta otettavaa doksisykliiniä keftriaksoniin LNB:n hoidossa, tutkia epäillyn LB:n todennäköisyyttä ja tyypillisimpiä erotusdiagnooseja, sekä arvioida antibioottien ja terveyspalvelujen käyttöä potilailla, joilla epäillään LB:a. LNB-potilaiden yleisimmät oireet ja löydökset olivat kivulias hermojuurten tulehdus, kasvohermohalvaus, Garin-Bujadoux-Bannwarthin oireyhtymä, päänsärky ja epäspesifinen niska-hartiaseudun kipu. Aivo-selkäydinnesteen CXCL13 pitoisuus oli kohonnut akuutissa infektiossa ja väheni nopeasti hoidon jälkeen. Doksisykliinillä hoidetut LNB-potilaat paranivat yhtä hyvin kuin keftriaksonihoidon saaneet potilaat. LB oli epätodennäköinen puolella potilaista, joilla sairautta epäiltiin. Näillä potilailla oireiden taustalla oli useimmiten tuki- ja liikuntaelimistön ongelmia tai neurologisia, psykiatrisia tai toiminnallisia sairauksia. Potilaat, joilla LB osoittautui epätodennäköiseksi, käyttivät terveydenhuollon palveluja enemmän kuin potilaat, joiden LB-diagnoosi oli varma, todennäköinen tai mahdollinen. Mikrobilääkkeiden kulutuksessa ei ollut eroa näiden ryhmien välillä

Hajautetun reaktiivisen ohjelmoinnin haasteet

Tiivistelmä. Hajautetun arkkitehtuurin ja reaktiiviseen ohjelmointiin yhdistäminen luo monenlaisia haasteita sovelluksen toiminnan tason takaamiselle. Eri komponenttien pitää pystyä esittämään jaettua tilaa yhtäpitävästi ja tiedon kulkua niiden välillä pitää pystyä koordinoimaan. Reaktiivisen arvojen topologisen päivitysjärjestyksen skaalautuminen hajautettuihin ympäristöihin on rajallista. Virheiden todennäköisyys kasvaa, kun komponenttien pitää kommunikoida verkon yli. Verkkohäiriöt voivat katkaista tai hidastaa kommunikaatiokanavia. Yksittäisten komponenttien joutuessa vikatilaan, pitäisi muiden osata reagoida siihen. Tämä tutkielma selvitti minkälaisia haasteita liittyy hajautettuun reaktiiviseen ohjelmointiin. Se tehtiin kirjallisuuskatsauksena, jonka tulosten pohjalta nämä keskeiset haasteet luokiteltiin kuuteen aihealueeseen. Nämä ovat tiedon toisintaminen, tapahtumaohjautuvuus, topologinen päivitysjärjestys, virheet, verkkohäiriöt ja osittaiset häiriöt

Suspicion of Lyme borreliosis in patients referred to an infectious diseases clinic : what did the patients really have?

Objective: To evaluate the conditions behind the symptoms in patients with suspected Lyme borreliosis (LB) who were referred to an infectious diseases clinic. Methods: In this retrospective, population-based study, we collected data from the medical records of all patients referred for infectious disease consultations in 2013 due to presumed LB from a population of 1.58 million. The patients were classified according to the certainty of LB on the basis of their symptoms, signs and laboratory results. Data on the outcomes and subsequent alternative diagnoses during the 4-year follow-up period were reviewed from all of the available patient records from public, private and occupational healthcare providers. Results: A total of 256 patients (16/100 000) were referred as a result of suspicion of LB; 30 (12%) of 256 were classified with definite, 36 (14%) with probable and 65 (25%) with possible LB. LB was unlikely in 121 (47%) patients. A novel diagnosis was discovered in the background symptoms in 73 (29%) of pa-tients. Previously diagnosed comorbidities caused at least some of the symptoms in 48 (19%) patients. Other explanations for symptoms were found in 81 (67%) of 121 of unlikely and 22 (34%) of 65 of possible LB patients. The spectrum of conditions behind the symptoms was quite broad and most often were musculoskeletal, neurological, psychological or functional disorders. Conclusions: LB was unlikely in half of the patients with presumed LB. In most cases the patients had other conditions that explained their symptoms. Elisa Kortela, Clin Microbiol Infect 2021;27:1022 (c) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area - a population-based registry study

Background Male sex predicts case-fatality in SARS-CoV-2 (COVID-19) - a phenomenon linked to systemic inflammation. We compared sex-related associations of inflammation parameters and outcome in a population-based setting with low case-fatality prior to wide use of immunosuppressives. Methods A population-based quality registry with laboratory-confirmed COVID-19 cases of specialized hospitals of the Capital Province of Finland were analysed to compare inflammatory parameters by sex during the first COVID-19 wave February-June 2020. Results Altogether, 585 hospitalized patients (54% males) were included. Males required more often intensive care unit (ICU) treatment (26.9 vs. 17.5%) and had higher 90-d case-fatality (14.9 vs. 7.8%) compared with females. Highest association with case-fatality in males was seen for high neutrophil counts (median; interquartile range) (8.70; 7.10-9.10 vs. 5.60; 3.90-7.80) (E9/l), low monocyte (0.50; 0.20-1.50 vs. 0.70; 0.50-0.90) (E9/l) and lymphocyte (0.90; 0.70-1.40 vs. 1.50; 1.10-2.00) (E9/l) counts, and high levels of d-dimer (3.80; 1.80-5.30 vs. 1.10; 0.60-2.75) (mg/l) and C-reactive protein (CRP) (190; 85.5-290 vs. 77.0; 49.0-94.0) (mg/l). In females, low lymphocyte (0.95; interquartile range 0.60-1.28 vs. 1.50; 1.10-2.00) (E9/l) and thrombocyte counts (196; 132-285 vs. 325; 244-464) (E9/l) and high CRP values (95.0; 62.0-256 vs. 66.0; 42.5-89.0) (mg/l) were associated with case-fatality. In multivariable analysis for males, lymphocyte cut-off 0.85 (E9/l) (OR 0.02; 95% CI 0.002-0.260), d-dimer cut-off 1.15 (mg/l) (OR 7.29; 1.01-52.6) and CRP cut-off 110 (mg/l) (OR 15.4; 1.87-127) were independently associated with case-fatality. In female multivariable analysis, CRP cut-off 81 (mg/l) (OR 7.32; 1.44-37.2) was the only inflammatory parameter associated with case-fatality. Conclusions COVID-19 results in higher inflammation parameter levels in male vs. female patients irrespective of outcome. This study suggests that low lymphocyte, high d-dimer and high CRP cut-off values may serve as potential markers for risk stratification in male patients.Peer reviewe

Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis

Publisher Copyright: © 2022 The Author(s)We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63, 3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.Peer reviewe

C6 peptide enzyme immunoassay in Lyme borreliosis serology

The cut-off values used in C6 peptide-based enzyme immunoassay (EIA), a widely used test in Lyme borreliosis (LB) serology, have not been thoroughly analysed. The objective of the study was to examine the performance of the C6 EIA, and to determine optimal cut-off values for the test. The analysed data contained results of 1368 serum samples. C6 EIA index values were compared statistically with the immunoblot (IB) test results. The identified cut-off values were further tested in a well-defined LB patient cohort. Cut-off value 1.6 appeared to be optimal when C6 EIA was used as a stand-alone test. When using C6 EIA as the first-tier test, the optimal cut-off values were 0.9 and 2.4 for negative and positive results. When C6 EIA was used as a second-tier test, samples yielding C6 index values >= 3.0 could be considered positive. The identified cut-off values had also a high sensitivity to identify seropositivity among definite LB patients. The identified cut-off values refine the role of C6 EIA in LB serology. Importantly, the use of C6 EIA leads to a reduction in the number of samples that need to be analysed using an IB, thus also reducing the costs. Two alternative workflows for LB serology including the C6 EIA are suggested.Peer reviewe

Neuroborrelioosin oireet, diagnostiikka ja hoito

Vertaisarvioitu. English summary.• Neuroborrelioosin yleisimmät oireet ja löydökset ovat kivulias meningoradikuliitti, ¬kasvohermohalvaus ja lymfosytaarinen meningiitti. • Oireisto ilmaantuu yleensä muutaman viikon kuluessa infektion alusta. • Diagnostiikka perustuu kliinisen kuvan lisäksi seerumin borreliavasta-aineisiin sekä ¬aivo-selkäydinneste¬löydöksiin. • Neuroborrelioosi voidaan hoitaa 2–4 viikon doksisykliinihoidolla suun kautta tai 2–3 viikon ¬suonensisäisellä keftriaksonihoidolla.Peer reviewe

Neuroborrelioosin oireet, diagnostiikka ja hoito

Neuroborrelioosin yleisimmät oireet ja löydökset ovat kivulias meningoradikuliitti, ­kasvohermohalvaus ja lymfosytaarinen meningiitti.Oireisto ilmaantuu yleensä muutaman viikon kuluessa infektion alusta.Diagnostiikka perustuu kliinisen kuvan lisäksi seerumin borreliavasta-aineisiin sekä ­aivo-selkäydinneste­löydöksiin.Neuroborrelioosi voidaan hoitaa 2–4 viikon doksisykliinihoidolla suun kautta tai 2–3 viikon ­suonensisäisellä keftriaksonihoidolla.</p

Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis

We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63,3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.</p

Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples

Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, Lubeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.Peer reviewe