Human seroprevalence of antibodies to tick-borne microbes in southern Norway

The tick Ixodes ricinus is widespread along the coastline of southern Norway, but data on human exposure to tick-borne microbes are scarce. We aimed to assess the seroprevalence of IgG antibodies to various tick-borne microbes in the general adult population living in a Norwegian municipality where ticks are abundant. Søgne is a coastline municipality in the southernmost part of Norway, and has a high density of ticks. All individuals aged 18-69 years with residential address in Søgne municipality (n = 7424) were invited to give a blood sample and answer a questionnaire. Blood samples from 3568 individuals were available for analysis. All samples were analyzed for IgG antibodies to Borrelia burgdorferi sensu lato (Bbsl), and around 1500 samples for IgG antibodies to other tick-borne microbes. Serum IgG antibodies to Bbsl were present in 22.0% (785/3568) of the tested samples, tick-borne encephalitis virus (TBEV) in 3.1% (45/1453), Anaplasma phagocytophilum in 11.0% (159/1452), Babesia microti in 2.1% (33/1537), Bartonella henselae/B. quintana in 0.1% (2/1451) and Rickettsia helvetica/R. conorii in 4.2% (60/1445). Serum IgG antibodies to A. phagocytophilum and R. helvetica/R. conorii were significantly more prevalent (p = 0.010 and p = 0.016, respectively) among individuals with serum IgG antibodies to Bbsl than among individuals without. In conclusion, our study showed a high exposure to Bbsl in the general adult population living in a coastline municipality in the southernmost part of Norway. The population is also exposed to A. phagocytophilum, R. helvetica/R. conorii, B. microti and TBEV, but very rarely B. henselae/B. quintana.acceptedVersio

Emerging tick-borne pathogens in the Nordic countries:A clinical and laboratory follow-up study of high-risk tick-bitten individuals

Despite the presence of several microorganisms, other than Borrelia burgdorferi sensu lato (Bbsl) and TBE virus, in Ixodes ricinus ticks from the Nordic countries, data is lacking on their pathogenic potential in humans. In this study, we wanted to investigate the aetiology and clinical manifestations of tick-transmitted infections in individuals seeking medical care following a tick-bite. The sampling frame was participants of a large-scale, prospective, multi-centre, follow-up study of tick-bitten volunteers recruited in Sweden, Finland and Norway in the years 2007-2015. Participants who sought medical care during the three-month follow-up period and from whom blood samples were collected during this healthcare visit (n=92) were tested, using PCR, for exposure to spotted fever group (SFG) Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Moreover, 86 of these individuals had two serum samples, collected three months apart, tested serologically for six tick-borne microorganisms. The selected organisms-Bbsl, SFG rickettsiae, Anaplasma phagocytophilum, TBE virus, Babesia microti and Bartonella henselae-have all been detected in field-collected ticks from the Nordic countries. Medical records were reviewed and questionnaires were completed to determine clinical manifestations. We found Lyme borreliosis to be the most common tick-transmitted infection as seen in 46 (54%) of the 86 participants with available medical records. Among the 86 participants with paired sera, serological or molecular evidence of recent exposure to other microorganisms than Bbsl could be demonstrated in eight (9%). Five participants (6%) exhibited serological evidence of recent concomitant exposure to more than one tick-borne microorganism. Clinical presentations were mild with one exception (TBE). In conclusion, our data suggest a low risk of infection with tick-borne microorganisms, other than Bbsl, in immunocompetent tick-bitten persons from the examined regions, a low occurrence of co-infection and mostly mild or no overt clinical signs of infection in immunocompetent persons exposed to the studied agents.Funding Agencies|EUEuropean Union (EU) [20200422]; Swedish Research Council Branch of MedicineSwedish Research Council [K2008-58X-14631-06-3]; Medical Research Council of Southeast Sweden; County Council of Ostergotland [LIO-56191]; Independent Research Fund Denmark [8020-00344B]; Wilhelm and Else Stockmann Foundation; Foundation for Aland Medical Research of the Aland Culture Foundation</p

MHC Class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete.: MHC Class II tetramers

International audienceSelective expansion and activation of a very small number of antigen-specific CD4(+) T cells is a remarkable and essential property of the adaptive immune response. Antigen-specific T cells were until recently identified only indirectly by functional assays, such as antigen-induced cytokine secretion and proliferation. The advent of MHC Class II tetramers has added a pivotal tool to our research armamentarium, allowing the definition of allo- and autoimmune responses in deeper detail. Rare antigen-specific CD4(+) cells can now be selectively identified, isolated and characterized. The same tetramer reagents also provide a new mean of stimulating T cells, more closely reproducing the MHC-peptide/TCR interaction. This property allows the use of tetramers to direct T cells toward the more desirable outcome, that is, activation (in malignancies and infectious diseases) or Th2/T regulatory cell deviation, anergy and deletion (in autoimmune diseases). These experimental approaches hold promise for diagnostic, prognostic and therapeutic applications

Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs

The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3–17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4–67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs

Transepithelial Transport and Enzymatic Detoxification of Gluten in Gluten-Sensitive Rhesus Macaques

In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness

Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules

Celiac disease is caused by an abnormal intestinal T-cell response to gluten proteins of wheat, barley and rye. Over the last few years, a number of gluten T-cell epitopes restricted by celiac disease associated HLA-DQ molecules have been characterized. In this work, we give an overview of these epitopes and suggest a comprehensive, new nomenclature

HLA-DRB1-DQB1 Haplotypes Confer Susceptibility and Resistance to Multiple Sclerosis in Sardinia

Introduction: Genetic predisposition to multiple sclerosis (MS) in Sardinia (Italy) has been associated with five DRB1*-DQB1* haplotypes of the human leukocyte antigen (HLA). Given the complexity of these associations, an in-depth re-analysis was performed with the specific aims of confirming the haplotype associations; establishing the independence of the associated haplotypes; and assessing patients ’ genotypic risk of developing MS. Methods and Results: A transmission disequilibrium test (TDT) of the DRB1*-DQB1 * haplotypes in 943 trio families

Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Prøveforstyrrelse: effekt av lagring på siltig leire fra Skien

Kontroll på elementer som fører til påvirkning av egenskaper til jordprøver er viktig innen geoteknikk. De fleste geotekniske beregninger og vurderinger baserer seg på parametere fra laboratorieundersøkelser utført på prøver hentet fra områder hvor ulike arbeid er prosjektert. Prøveforstyrrelse i laboratorieprøver kan medføre konservative eller liberale tolkninger av resultater som er usikre. Dette kan resultere i at grunnforholdene blir vurdert å være svakere enn det som er riktig. Ofte kan dette føre til økte kostnader for arbeidene som er prosjektert. I motsatt fall kan beregningen føre til at grunnen er mer usikker enn det som antas. Dette kan ha alvorlige sikkerhetskonsekvenser om arbeider på grunnen feildimensjoneres. Denne oppgaven ser på effekten av lagring ved ulik temperatur på siltig leire fra Skien. Litteraturstudiet viser at forventet effekt av lagring vil være redusert stivhet i materiale, skjærstyrke, prekonsolideringstrykk, omrørt skjærstyrke og sensitivitet. Årsaker til forringet kvalitet av lagrede prøver er migrasjon av porevæske, inntørking, oksidasjon, andre kjemiske reaksjoner, temperatur og fuktighetsforandringer. Det har vært benyttet miniblokkprøver i forsøkene. Prøvene er hentet fra ulik dybde i nærliggende boreserier fra Mælagata i Skien. Tre blokker er undersøkt i prosjektet. En har vært lagret i kjølerom (5C) og to i romtemperatur (20C). En ekstra blokk ble undersøkt fordi resultatene fra første blokk lagret ved 20C ikke var tilfredsstillende. Det har blitt utført fire treaksialforsøk (CAUc), 10 ødometerforsøk (CRS), fem omrørte konusforsøk, seks hydrometeranalyser og Atterbergs grenser er avgjort for fem utvalg. Det er i tillegg utført utvidet analyse av vanninnhold i seks snitt fra to av blokkene. Diskusjon rundt effekt av lagring ved ulik temperatur og grad av prøveforstyrrelse er basert på de samlede resultatene fra disse forsøkene. Visuell inspeksjon og hydrometeranalyser har vist at materialet i studien var av heterogen karakter. Det ble påvist siltig leire og leirig silt over svært små avstander innad i blokkprøver. Det ble også avdekket område med leire. Stor variasjon i type material har ført til at resultatene fra ødometerforsøk har vist svært ulik oppførsel og derfor er usikre. Vanninnholdet i den første blokken (oppbevart ved 20C) var hele 11% lavere enn i blokk nummer to (oppbevart ved 5C).Dette førte til at prøveresultater i de ulike analyser var lite egnet til sammenligning. Det ble derfor åpnet en ny prøve som var lagret i 20C. Vanninnholdet i denne var tilnærmet likt vanninnholdet i blokkprøven lagret i 5C. Undersøkelse av disse blokkene kunne benyttes for å vurdere prøveforstyrrelse etter lagring ved ulike temperaturer. Prøvemateriale lagret ved 5C viste seg å være lite forstyrret. Treaksialforsøk har gitt en udrenert skjærstyrke på 44,7kPa og en omrørt skjærstyrke fra omrørt konus test på 0,8kPa. Tilsvarende verdier for prøve undersøkt samme dag som prøvetaking var 45,0kPa og 0,3kPa. Noe økning i omrørt skjærstyrke skyldes trolig migrasjon av porevæske. Vellykkede ødometerforsøk fra blokkprøven lagret ved 5C viser en klar og tydelig p c-oppførsel og et tydelig fall i ødometermodul i overgangen mellom overkonsolidert og normalkonsolidert område. Prøvemateriale lagret ved 20C viser tydelige tegn på prøveforstyrrelse. Klassifisering av prøvekvalitet basert på volumtøyning og poretallsforhold ved konsolidering viser at kvaliteten er forringet. Resultat fra treaksial test viser en reduksjon av udrenert skjærstyrke på hele 30%, og resultater fra ødometerforsøk viser en kraftig reduksjon i prekonsolideringstrykk. Ødometer med prøve hentet fra øverst i miniblokkprøven viser et materiale med tilnærmet normalkonsolidert oppførsel. Utvidet analyse av vanninnhold viser at det er stor grad av porevæskemigrajon uavhengig av lagringstemperatur. Prøve lagret ved 20C har tørket ut i ytterkant av prøven, mens det er indikasjoner på at porevann migrerer innover i prøven for prøve lagret ved 5C. Prøvene viser en tendens til høyere vanninnhold midtveis inn til midten av prøven enn i selve sentrum. Arbeidet viser at lagring av prøve uten kjøling påvirker prøvens egenskaper i tråd med det som er avdekket i litteraturstudier. Lagring av prøve ved 5C bevarer derimot mye av prøvens opprinnelige materialeegenskaper. Det anbefales derfor å oppbevare prøver kjølig for å få gode prøvesvar etter lagring. Undersøkelsen som ble gjort vurderte prøve som hadde vært lagret i 550 dager. Det er også observert at prøveforstyrrelse er størst i toppen av begge prøvene