Winter activity of questing ticks (Ixodes ricinus and Dermacentor reticulatus) in Germany - Evidence from quasi-natural tick plots, field studies and a tick submission study.

Changing climatic conditions and other anthropogenic influences have altered tick distribution, abundance and seasonal activity over the last decades. In Germany, the two most important tick species are Ixodes ricinus and Dermacentor reticulatus, the latter of which has expanded its range across the country during the past three decades. While I. ricinus was rarely found during the colder months in the past, D. reticulatus is known to be active at lower temperatures. To quantify tick appearance during winter, specimens were monitored in quasi-natural tick plots three times a week. Additionally, the questing activities of these two tick species were observed throughout the year at nine field collection sites that were regularly sampled by the flagging method from April 2020 to April 2022. Furthermore, tick winter activity in terms of host infestation was analysed as part of a nationwide submission study from March 2020 to October 2021, in which veterinarians sent in ticks mainly collected from dogs and cats. All three study approaches showed a year-round activity of I. ricinus and D. reticulatus in Germany. During the winter months (December to February), on average 1.1% of the inserted I. ricinus specimens were observed at the tops of rods in the tick plots. The average questing activity of I. ricinus amounted to 2 ticks/100 m² (range: 1-17) in the flagging study, and 32.4% (211/651) of ticks found infesting dogs and cats during winter 2020/21 were I. ricinus. On average 14.7-20.0% of the inserted D. reticulatus specimens were observed at the tops of rods in the tick plots, while the average winter questing activity in the field study amounted to 23 specimens/100 m² (range: 0-62), and 49.8% (324/651) of all ticks collected from dogs and cats during winter 2020/21 were D. reticulatus. Additionally, the hedgehog tick Ixodes hexagonus was found to infest dogs and cats quite frequently during the winter months, accounting for 13.2% (86/651) of the collected ticks. A generalized linear mixed model identified significant correlations of D. reticulatus winter activity in quasi-natural plots with climatic variables. The combined study approaches confirmed a complementary main activity pattern of I. ricinus and D. reticulatus with climate change-driven winter activity of both species. Milder winters and a decrease of snowfall, and consequently high winter activity of D. reticulatus, among other factors, may have contributed to the rapid spread of this tick species throughout the country. Therefore, an effective year-round tick control is strongly recommended to not only efficiently protect dogs and cats with outdoor access from ticks and tick-borne pathogens (TBPs), but also to limit the further geographical spread of ticks and TBPs to so far non-endemic regions. Further measures, including information of the public, are necessary to protect both, humans and animals, in a One Health approach.

Distribution of the soft tick Carios vespertilionis in lowlands and low mountain regions of Germany.

In Germany, the knowledge about ticks infesting bats is limited, and is restricted only to a few studies, most of them dating back decades. To further improve our knowledge on ticks parasitising bats, healthy and sick bats in central Germany were examined for ticks. In total 519 larvae and one nymph of Carios vespertilionis were collected from nine bat species: Eptesicus nilssonii, Eptesicus serotinus, Myotis daubentonii, Myotis myotis, Nyctalus leisleri, Pipistrellus nathusii, Pipistrellus pygmaeus, Pipistrellus pipistrellus, and Vespertilio murinus. Either the presence of C. vespertilionis was new for some areas or it was confirmed in some federal states in central Germany. The infestation rate was mostly low (n = 1-5 larvae/bat). However, in two cases a high number of ticks was observed. The highest infestation of 97 C. vespertilionis larvae was recorded on one Parti-coloured bat (V. murinus).

Tick findings from subterranean environments in the Central German Uplands and Luxembourg reveal a predominance of male Ixodes hexagonus.

Questing ticks are usually collected by flagging or dragging. Mostly exophilic tick species are caught, such as Ixodes ricinus, the most common tick in Central Europe. In the present study, ticks collected from underground environments in the Grand Duchy of Luxembourg and in the Central German Uplands (Federal States of Hesse, Bavaria, Thuringia, Baden-Wuerttemberg, Rhineland-Palatinate, Saarland and Northrhine-Westphalia) were investigated. Six tick species were revealed among the 396 analyzed specimens: Ixodes ariadnae, Ixodes canisuga, Ixodes hexagonus, I. ricinus, Ixodes trianguliceps, and Dermacentor marginatus. Adults and immatures of I. hexagonus dominated the findings (57% of all specimens), especially in shelters acting as potential resting places of main hosts. Ixodes canisuga and I. trianguliceps were for the first time recorded in Luxembourg, and one nymph of the bat tick I. ariadnae represents only the second report for Germany. Collecting ticks in subterranean environments turned out to be a useful approach to increase knowledge about the occurrence of relatively rare tick species, including those that spend most of their lifetime on their hosts, but detach in such environmental settings.

Rickettsia spp. in ticks (Acari: Ixodidae) from wild birds: First detection of Candidatus Rickettsia vini in Hesse, Germany.

Tick-borne diseases are recognized as a growing public health concern and cause significant issues in humans and animals by serving as dispersal agents of ticks and their associated pathogens. Birds contribute to the spread of ticks and tick-borne diseases, with migratory birds playing a role in regional dispersal. Only a few studies have been carried out in Germany so far to investigate tick fauna on birds and the pathogens they harbour. In 2017 and 2018, we collected ticks from a total of 358 birds in the northern region of the Federal State of Hesse, Germany. Most ticks were Ixodes ricinus larvae and nymphs (95.4%). However, two ornithophilic species were also collected: Ixodes frontalis (larvae, nymphs and females) and Ixodes arboricola (larvae and nymphs). Ticks were tested individually or in pools, depending on the tick life stage and species for each bird host, in order to detect tick-borne encephalitis (TBE) virus and Rickettsia spp. All samples tested negative for TBE virus. Of 684 investigated tick pools, 162 tested positive for Rickettsia spp. by screening PCR. Of these, 117 carried Rickettsia helvetica detected by specific real-time PCR. The samples which were negative in the R. helvetica PCR were further investigated using five targets (gltA, 16S, ompA IV, ompB, 23S-5S intergenic spacer region) using multi locus sequence typing and phylogenetic analysis. The obtained sequences showed strong phylogenetic relationship to Candidatus Rickettsia vini, which is most closely related to R. japonica and R. heilongjiangensis, and occur in I. arboricola. Three more sequences were determined as R. helvetica in I. ricinus and I. frontalis. This is the first detection of Ca. R. vini in Germany and the first 23S-5S data published for Ca. R. vini, a useful target for Rickettsia species identification.

Long-Term Itching in a Tourist Following Bite by a Nymph of Dermacentor auratus (Acari: Ixodidae) in Cambodia.

The impact of tick bites during holidays in tropical countries is seldom reported. Here, we describe long-term skin alterations and itching experienced by a German tourist following the bite of a nymph of Dermacentor auratus Supino, 1897 in Cambodia. Tick infestation may be neglected by travelers. Therefore, careful travel history is necessary when travelers report a tick bite after spending holiday in tropical and subtropical countries.

The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis.

Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.

Stress (Takotsubo) Cardiomyopathy: A Review of Its Pathophysiology, Manifestations, and Factors That Affect Prognosis.

Stress (Takotsubo) cardiomyopathy (SC) is becoming an increasingly recognized syndrome, previously underdiagnosed due to its similar presentation to acute coronary syndrome (ACS). With advancements in imaging and diagnostic tools, our ability to recognize, diagnose and subsequently manage SC has advanced as well. Multiple diagnostic criteria have been created for the diagnosis of SC. While the diagnosis of SC does not always require imaging, advanced imaging can aid in the diagnosis of SC in unclear cases. However, due to the severity of ACS and the consequences of missing that diagnosis, SC is still typically a diagnosis of exclusion once ACS has been ruled out on cardiac catheterization. Our understanding of the pathogenesis of SC is still evolving. While catecholamine surges are widely believed to be the precipitating cause of SC, the exact mechanism for how catecholamine surges lead to ventricular dysfunction is still being debated. Understanding the mechanism behind ventricular dysfunction in SC can potentially provide the basis for treatment. Different stressors may lead to different variants of cardiomyopathy, with different portions of the ventricles affected. Treatment of SC is largely supportive and therefore should be tailored to the patient's individual needs based on the severity of presentation. Both the underlying stressor and the variant of SC affect time to recovery and mortality. Many patient factors can impact prognosis as well. Even after initial hospital discharge for SC, long-term risks do exist, including the risk for recurrent SC. Only angiotensin-converting enzyme inhibitors have been shown to reduce the recurrence of SC.

The Spatial Distribution of Dermacentor Ticks (Ixodidae) in Germany-Evidence of a Continuing Spread of Dermacentor reticulatus.

In Europe, two tick species of the genus Dermacentor occur, Dermacentor marginatus and Dermacentor reticulatus. When the spatial distribution of both species in Germany was studied comprehensively for the first time in 1976, D. marginatus populations were recorded along the Rhine and Main river valleys in southwestern Germany, while D. reticulatus was very rare. In the last 50 years, however, a considerable range expansion of D. reticulatus has been noted in several European countries. To assess the current distribution of Dermacentor spp. in Germany, citizens were asked to send in ticks suspected to belong to the genus Dermacentor or that were of "unusual" appearance. From February 2019 until February 2020, 3,902 Dermacentor ticks were received in total. Of those, 15.48% (604/3,902) were identified as D. marginatus and 84.24% (3,287/3,902) as D. reticulatus, while 11 specimens could not be identified to species level. The majority of D. reticulatus specimens was collected from dogs (1,212/2,535; 47.12%), while D. marginatus was mostly collected from horses (184/526; 34.98%). Our results confirm that the adults of both Dermacentor species are active all year round. D. reticulatus specimens were sent in from all federal states except the Free and Hanseatic City of Hamburg, while D. marginatus specimens were only received from locations in southwestern Germany. Overall, data obtained from this citizen-science study show that D. reticulatus has significantly expanded its range, especially in northern Germany. Regarding D. marginatus, new locations northwest of the previous range were detected, although the distribution has remained rather stable as compared to D. reticulatus. The spread of D. reticulatus, the vector of Babesia canis, is of major importance for veterinarians and dog owners in terms of canine babesiosis outbreaks or endemization in hitherto B. canis-free areas. Thus, veterinarians and veterinary students need to be informed about the new situation to be able to give adequate advice to dog owners on the extended D. reticulatus range and appropriate control measures.

Wellens' syndrome: a rare presentation after an endoscopic retrograde cholangiopancreatography.

Wellens' syndrome is a pattern of ECG changes typically seen in patients with unstable angina that has a high positive predictive value for critical left anterior descending coronary artery stenosis. Recognition of this syndrome can allow for intervention before the patient develops myocardial infarction. We report a case of Wellens' syndrome that was observed after an endoscopic retrograde cholangiopancreatography, which highlights risk factors that needs consideration in evaluating patients with these ECG findings after undergoing procedures even when asymptomatic.

Detection of Amblyomma mixtum (Acari: Ixodidae) in Germany on a Human Traveler Returning From Cuba.

The importation of exotic ticks to Germany on infested humans is rarely reported. Here we describe the detection of an Amblyomma mixtum nymph harboring Rickettsia amblyommatis by a tourist returning from a holiday trip to Cuba. Tick infestation may be neglected by tourists. Therefore, careful anamnesis and diagnosis should be carried out when tourists return from tropical and subtropical countries suffering from nonspecific symptoms, such as fever and malaise.

Morphological anomalies in Ixodes ricinus and Ixodes inopinatus collected from tick-borne encephalitis natural foci in Central Europe.

In 2015, 0.02% nymphs displayed anomalies (ectromely) out of the 6744 collected ticks as part of a tick-borne encephalitis program in Germany. In 2016, questing Ixodes ricinus (n = 14,527) and Ixodes inopinatus (n = 75) ticks were collected by flagging as part of a tick-borne encephalitis program in Germany, Slovakia and Denmark. A total of 278 (1.9%) out of 14,602 nymph and adult ticks showed morphological anomalies. The anomalies were divided into general anomalies (body asymmetry) and local anomalies (anomalies of appendages, malformation of capitulum, exoskeleton anomalies and anal groove deformation) with nymphs being the most affected life stage. Most important, leg atrophy was the most common anomaly (209 nymphs, 11 females and three males) followed by asymmetry (10 nymphs, five females and a male) and ectromely (nine nymphs). Two females and one male displayed multiple anomalies on legs, palps and exoskeleton. Anal groove deformation was observed in three females and three nymphs. In 2016, the frequency of anomalies in I. inopinatus was found five times higher (9.3%) than in I. ricinus (1.9%). This is the first report of anomaly (ectromely, leg atrophy, idiosoma deformation) in flagged I. inopinatus and the first report of schizomely in I. ricinus.

Polysaccharide conjugate vaccine protein carriers as a "neglected valency" - Potential and limitations.

The development of vaccines against polysaccharide-encapsulated pathogens (e.g. Haemophilus influenzae type b, pneumococci, meningococci) is challenging because polysaccharides do not elicit a strong and long-lasting immune response (i.e. T-cell independent). This can be overcome by conjugating the polysaccharide to a protein carrier (e.g. tetanus toxoid, cross-reacting material 197 [CRM]), which vastly improves the immune response and induces memory to the polysaccharide (T-cell dependent). Although it is well documented that protein carriers additionally induce an immune response against themselves, this potential "additional valency" has so far not been recognized. The only exception is for the protein D carrier (derived from non-typeable Haemophilus influenzae [NTHi]) used in a pneumococcal conjugate vaccine, which may have a beneficial impact on NTHi acute otitis media. In this review, we describe the immunogenicity of various protein carriers and discuss their potential dual function: as providers of T-cell helper epitopes and as protective antigens. If this "additional valency" could be proven to be protective, it may be possible to consider its potential effect on the number of required immunizations. We also describe the potential for positive or negative interference between conjugate vaccines using the same protein carriers, the resulting desire for novel carriers, and information on potential new carriers. The range of conjugate vaccines is ever expanding, with different carriers and methods of conjugation. We propose that new conjugate vaccine trials should assess immunogenicity to both the polysaccharide and carrier. Ultimately, this so-far "neglected valency" could be an exploitable characteristic of polysaccharide conjugate vaccines.

Vascular access placement in patients with chronic kidney disease Stages 4 and 5 attending an inner city nephrology clinic: a cohort study and survey of providers.

BACKGROUND: The majority of incident hemodialysis (HD) patients initiate dialysis via catheters. We sought to identify factors associated with initiating hemodialysis with a functioning arterio-venous (AV) access. METHODS: We conducted a retrospective chart review of all adult patients, age >18 years seeing a nephrologist with a diagnosis of CKD stage 4 or 5 during the study period between 06/01/2011 and 08/31/2013 to evaluate the placement of an AV access, initiation of dialysis and we conducted a survey of providers about the process. RESULTS: The 221 patients (56% female) in the study had median age of 66 years (interquartile range (IQR), 57-75) and were followed for a median of 1.26 years (IQR 0.6-1.68). At study entry, 81%had CKD stage 4 and 19% had CKD stage 5. By the end of study, 48 patients had initiated dialysis. Thirty-four of the patients started dialysis with a catheter (1 failed and 10 maturing AVFs), 9 with an AVF and 5 with an AVG. During the study period, 61 total AV accesses were placed (54 AVF and 7 AVG). A higher urinary protein/ creatinine ratio and a lower eGFR were associated with AV access placement and dialysis initiation. A greater number of nephrology visits were associated with AV access creation but not dialysis initiation. Hospitalizations and hospitalizations with an episode of acute kidney injury (AKI) were strongly associated with dialysis initiation (odds ratio (OR) 13.0 (95% confidence interval (CI) 2.3 to 73.3, p-value = 0.004) and OR 6.6 (95% CI 1.9 to 22.8, p-value = 0.003)). CONCLUSIONS: More frequent nephrology clinic visits for patients with a recent hospitalization may improve rates of placement of an AV access. A hospitalization with AKI is strongly associated with the need for dialysis initiation. Nephrologists may not be referring the correct patients to get an AV access surgery.

Factors contributing to the immunogenicity of meningococcal conjugate vaccines.

Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics.

Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates.

When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed.

Meningococcal serogroup Y disease in Europe: Continuation of high importance in some European regions in 2013.

Neisseria meningitidis or meningococcus is divided into 12 distinct serogroups of which A, B, C, W, X, and Y are medically most important and cause health problems in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Globally, serogroup A has been prevalent in the African "meningitis belt" whereas serogroup B and C have predominated in Europe. In a paper published earlier in this journal (1) , an increase in serogroup Y invasive meningococcal disease (IMD) in some European countries was reported based on the epidemiological data for 2010, 2011 and 2012. Here, we report additional data from 30 European countries indicating that high or increased serogroup Y disease levels have continued in 2013 in certain regions of Europe. In the Western and Central Europe, there were no major changes in the proportion of serogroup Y IMD cases in 2013 compared to 2012. In the Scandinavian countries, proportion of serogroup Y disease remained high, ranging from 26% to 51% in 2013. This was in contrast to Baltic, Eastern and most Southern European countries, where the proportion of serogroup Y IMD was low similarly to previous years. For the last 2 decades, the mean age of patients affected by serogroup Y was 41 y for 7 countries from which data was available and 50% of cases were in patients aged 45 to 88 y. The age distribution of serogroup Y was bimodal and did not change significantly despite the increase of the total number and the proportion of serogroup Y IMD in some European regions.

Meningococcal serogroup Y emergence in Europe: high importance in some European regions in 2012.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. (1)(,) (2) Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

Meningococcal serogroup Y emergence in Europe: update 2011.

Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W-135, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 from various European countries previously published in this journal. ( 1) Here, data is reported indicating that the emergence of serogroup Y continued in 2011 in various regions of Europe. The average age of persons affected by N. meningitidis serogroup Y seems to have decreased in some countries in comparison to the previous decade.

Increase of meningococcal serogroup Y cases in Europe: a reason for concern?

Neisseria meningitidis is differentiated into 12 distinct serogroups of which A, B, C, W-135, X and Y are medically most important and represent a major health problem in one or more parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. A sudden increase or decrease of IMD or meningococcal carriage may occur anywhere at any time. Recent epidemiological surveillance indicates an increase of serogroup Y IMD in some parts of Europe and data from various European countries are presented.

Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease.

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo(®)) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.