Patch testing with palladium and aluminium, epidemiological and experimental studies

AbstractThe aim of this thesis was to investigate the prevalence and significance of contact allergy to palladium from a Swedish perspective. Our initial findings made it necessary to also explore the importance of the metal aluminium used in test chamber systems and the effect of aluminium chloride (Al-Cl) in patch test preparations. A retrospective study (study I), with 18,306 patch test results obtained from 1995-2016 showed that the prevalence of contact allergy to palladium is following that of nickel. After the introduction of the EU Nickel Directive in 2001, there was a significant decrease in contact allergy to sodium tetrachloropalladate (Na-PdCl), palladium chloride (Pd-Cl), and nickel sulphate (Ni) among younger females, age six to 30 years. Regression analysis revealed that women with contact allergy to Ni were approximately 36 times more likely to have contact allergy to Pd-Cl compared to females with no allergy to Ni.The prevalence of isolated palladium (Pd) allergy in the whole study population (men and women) was 1.4% and remained stable from 1995 to 2016. In study II, Na-PdCl showed less variability in patch test results, compared to Pd-Cl. When re-testing the same 15 participants with known contact allergy to Ni, Na-PdCl, and Pd-Cl, a seasonal variation was seen. In wintertime, there were significantly higher summarised test scores compared to in late summertime for the three metal salts Pd-Cl, Na-PdCl, and Ni.A retrospective study (study III) showed that the use of Finn Chambers in patients with contact allergy to aluminium could be a risk for false-positive patch test reactions to Na-PdCl and Pd-Cl. No such risk was seen in patients tested with Finn Chamber Aqua. In study IV, the use of Al-Cl in test preparations with Ni seemed to increase the sensitivity for detecting Ni allergy. When adding 30.0% Al-Cl to Ni 15.0% aqua, the sensitivity increased to 91% from 50.0% in Ni 5.0% in petrolatum. This increase in sensitivity was only seen when adding Al-Cl to Ni and was not seen when adding Al-Cl to methylisothiazolinone and to fragrance mix I

Can interventions that aim to decrease Lyme disease hazard at non-domestic sites be effective without negatively affecting ecosystem health? A systematic review protocol

Background Lyme disease (LD) is the most commonly reported, broadly distributed vector-borne disease of the northern temperate zone. It is transmitted by ticks and, if untreated, can cause skin, cardiac, nervous system and musculoskeletal disease. The distribution and incidence of LD is increasing across much of North America and Western Europe. Interventions to decrease exposure to LD hazard by encouraging behavioural change have low acceptance in high risk groups, and a safe, effective human LD vaccine is not presently available. As a result, habitat level interventions to decrease LD hazard itself (i.e. levels of infected ticks) have been proposed. However, some interventions may potentially negatively affect ecosystem health, and consequentially be neither desirable, nor politically feasible. This systematic review will catalogue interventions that aim to reduce LD hazard at non-domestic sites, and examine the evidence supporting those which are unlikely to negatively affect ecosystem health. Methods The review will be carried out in two steps. First, a screening and cataloguing stage will be conducted to identify and characterise interventions to decrease LD hazard at non-domestic sites. Secondly, the subset of interventions identified during cataloguing as unlikely to negatively affect ecosystem health will be investigated. In the screening and cataloguing step literature will be collected through database searching using pre-chosen search strings, hand-searching key journals and reviewing the websites of public health bodies. Further references will be identified by contacting stakeholders and researchers. Article screening and assessment of the likely effects of interventions on ecosystem health will be carried out independently by two reviewers. A third reviewer will be consulted if disagreements arise. The cataloguing step results will be presented in tables. Study quality will then be assessed independently by two reviewers, using adapted versions of established tools developed in healthcare research. These results will be presented in a narrative synthesis alongside tables. Though a full meta-analysis is not expected to be possible, if sub-groups of studies are sufficiently similar to compare, a partial meta-analysis will be carried out

Patch testing with aluminium Finn Chambers could give false-positive reactions in patients with contact allergy to aluminium

Background Earlier laboratory studies have shown that sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride trigger the release of aluminium (Al) from Finn Chambers (FC). Objectives To investigate whether aluminium realease from FC could influence the diagnostic outcome of patch testing with FC. Method A retrospective analysis of patch test results from 2010 to 2019 was performed. A two-sided Fisher\u27s exact test was used to calculate any overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Results A total of 5446 patients had been tested with FC during the study period. There was a significant overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Patients with a strong Al allergy had significantly higher amounts of concomitant reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride compared to patients with weak Al allergy. These results were not seen for patients tested with Finn Chambers AQUA. Conclusion In patients with contact allergy to Al, patch testing with Finn chambers could give false-positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride

Pseudomonas aeruginosa vaccine identified by the AI-immunology™ platform improves outcomes in a murine biofilm lung infection model

The Gram-negative opportunistic bacterial pathogen, Pseudomonas aeruginosa is considered by WHO as a “priority pathogen” for which new antibacterial strategies are urgently needed due to antimicrobial resistance development. In addition, P. aeruginosa is a cause of difficult to treat chronic infections due to its ability to form biofilms. Therefore, pseudomonal vaccines have been proposed as alternative strategies to combat these infections for the last 50 years, however, no vaccines are available on the market for human use. The aim of this study was to investigate the capacity of a vaccine composed of seven antigens, identified using EDEN™ (Efficacy Discriminative Educated Network) - a proteome-wide in silico antigen prediction model within AI-Immunology™ platform - in improving outcomes in a murine model of chronic P. aeruginosa lung infection. The primary endpoint was quantitative bacteriology (Colony forming units - CFU) in the lungs of immunized animals compared to control animals. The secondary endpoints were clinical signs (a clinical score), body temperature and weight loss. Mice immunized with the heptavalent combination vaccine had a significantly 1.2 log10 lower lung CFU compared to the control group. Furthermore, the vaccinated mice presented significantly fewer clinical signs of infection, had less reduction in body temperature and weight loss as, compared to control mice. There was a statistically significant correlation between the lung bacteriology and secondary endpoints. Antibodies against all seven antigens were measured by ELISA confirming their immunogenicity. The encouraging results obtained in this, and previous studies provide a proof-of-concept that EDEN™ is a useful tool in identifying vaccine antigens against P. aeruginosa and possibly other problematic pathogens.</p

Complex Population Structure of Lyme Borreliosis Group Spirochete Borrelia garinii in Subarctic Eurasia

Borrelia garinii, a causative agent of Lyme borreliosis in Europe and Asia, is naturally maintained in marine and terrestrial enzootic cycles, which primarily involve birds, including seabirds and migratory passerines. These bird groups associate with, correspondingly, Ixodes uriae and Ixodes ricinus ticks, of which the latter species may bite and transmit the infection to humans. Studies of the overlap between these two natural cycles of B. garinii have been limited, in part due to the absence of representative collections of this spirochete's samples, as well as of the lack of reliable measure of the genetic heterogeneity of its strains. As a prerequisite for understanding the epidemiological correlates of the complex maintenance of B. garinii, the present study sought to assess the diversity and phylogenetic relationships of this species' strains from its natural hosts and patients with Lyme borreliosis from subarctic Eurasia. We used sequence typing of the partial rrs-rrl intergenic spacer (IGS) of archived and prospective samples of B. garinii from I. uriae ticks collected predominantly on Commander Islands in North Pacific, as well as on the islands in northern Sweden and arctic Norway. We also typed B. garinii samples from patients with Lyme borreliosis and I. ricinus ticks infesting migratory birds in southern Sweden, or found questing in selected sites on the islands in the Baltic Sea and Lithuania. Fifty-two (68%) of 77 B. garinii samples representing wide geographical range and associated with I. ricinus and infection of humans contributed 12 (60%) of total 20 identified IGS variants. In contrast, the remaining 25 (32%) samples recovered from I. uriae ticks from a few islands accounted for as many as 10 (50%) IGS types, suggesting greater local diversity of B. garinii maintained by seabirds and their ticks. Two IGS variants of the spirochete in common for both tick species were found in I. ricinus larvae from migratory birds, an indication that B. garinii strains are exchanged between different ecological niches. Notably, B. garinii variants associated with I. uriae ticks were found in each of the six clusters, representing two phylogenetic lineages of this species identified among the studied samples. Our findings suggest that B. garinii in subarctic Eurasia comprises two partially overlapping populations with different levels of genetic heterogeneity, presumably, due to distinctive selective pressures on the spirochete in its marine and terrestrial enzootic cycles

Habitat properties are key drivers of Borrelia burgdorferi (s.l.) prevalence in Ixodes ricinus populations of deciduous forest fragments

Background: The tick Ixodes ricinus has considerable impact on the health of humans and other terrestrial animals because it transmits several tick-borne pathogens (TBPs) such as B. burgdorferi (sensu lato), which causes Lyme borreliosis (LB). Small forest patches of agricultural landscapes provide many ecosystem services and also the disservice of LB risk. Biotic interactions and environmental filtering shape tick host communities distinctively between specific regions of Europe, which makes evaluating the dilution effect hypothesis and its influence across various scales challenging. Latitude, macroclimate, landscape and habitat properties drive both hosts and ticks and are comparable metrics across Europe. Therefore, we instead assess these environmental drivers as indicators and determine their respective roles for the prevalence of B. burgdorferi in I. ricinus. Methods: We sampled I. ricinus and measured environmental properties of macroclimate, landscape and habitat quality of forest patches in agricultural landscapes along a European macroclimatic gradient. We used linear mixed models to determine significant drivers and their relative importance for nymphal and adult B. burgdorferi prevalence. We suggest a new prevalence index, which is pool-size independent. Results: During summer months, our prevalence index varied between 0 and 0.4 per forest patch, indicating a low to moderate disservice. Habitat properties exerted a fourfold larger influence on B. burgdorferi prevalence than macroclimate and landscape properties combined. Increasingly available ecotone habitat of focal forest patches diluted and edge density at landscape scale amplified B. burgdorferi prevalence. Indicators of habitat attractiveness for tick hosts (food resources and shelter) were the most important predictors within habitat patches. More diverse and abundant macro- and microhabitat had a diluting effect, as it presumably diversifies the niches for tick-hosts and decreases the probability of contact between ticks and their hosts and hence the transmission likelihood.[br/] Conclusions: Diluting effects of more diverse habitat patches would pose another reason to maintain or restore high biodiversity in forest patches of rural landscapes. We suggest classifying habitat patches by their regulating services as dilution and amplification habitat, which predominantly either decrease or increase B. burgdorferi prevalence at local and landscape scale and hence LB risk. Particular emphasis on promoting LB-diluting properties should be put on the management of those habitats that are frequently used by humans. In the light of these findings, climate change may be of little concern for LB risk at local scales, but this should be evaluated further

Borrelia burgdorferi sensu lato in Ixodes ricinus ticks collected from migratory birds in Southern Norway

<p>Abstract</p> <p>Background</p> <p><it>Borrelia burgdorferi </it>sensu lato (s.l.) are the causative agent for Lyme borreliosis (LB), the most common tick-borne disease in the northern hemisphere. Birds are considered important in the global dispersal of ticks and tick-borne pathogens through their migration. The present study is the first description of <it>B. burgdorferi </it>prevalence and genotypes in <it>Ixodes ricinus </it>ticks feeding on birds during spring and autumn migration in Norway.</p> <p>Methods</p> <p>6538 migratory birds were captured and examined for ticks at Lista Bird Observatory during the spring and the autumn migration in 2008. 822 immature <it>I. ricinus </it>ticks were collected from 215 infested birds. Ticks were investigated for infection with <it>B. burgdorferi </it>s.l. by real-time PCR amplification of the 16S rRNA gene, and <it>B. burgdorferi </it>s.l. were thereafter genotyped by melting curve analysis after real-time PCR amplification of the <it>hbb </it>gene, or by direct sequencing of the PCR amplicon generated from the <it>rrs </it>(16S)-<it>rrl </it>(23S) intergenetic spacer.</p> <p>Results</p> <p><it>B. burgdorferi </it>s.l. were detected in 4.4% of the ticks. The most prevalent <it>B. burgdorferi </it>genospecies identified were <it>B. garinii </it>(77.8%), followed by <it>B.valaisiana </it>(11.1%), <it>B. afzelii </it>(8.3%) and <it>B. burgdorferi </it>sensu stricto (2.8%).</p> <p>Conclusion</p> <p>Infection rate in ticks and genospecies composition were similar in spring and autumn migration, however, the prevalence of ticks on birds was higher during spring migration. The study supports the notion that birds are important in the dispersal of ticks, and that they may be partly responsible for the heterogeneous distribution of <it>B. burgdorferi </it>s.l. in Europe.</p

Ведение беременных с преэклампсией в женской консультации

ЖЕНЩИНЫ БЕРЕМЕННЫЕБЕРЕМЕННОСТЬБЕРЕМЕННОСТИ ОСЛОЖНЕНИЯГИПЕРТЕНЗИЯ, ВЫЗВАННАЯ БЕРЕМЕННОСТЬЮ /ПРОФПРЕЭКЛАМПСИЯГЕСТОЗЖЕНСКИЕ КОНСУЛЬТАЦИ

Migratory Passerine Birds as Reservoirs of Lyme Borreliosis in Europe

Birds host vector ticks and Borrelia species and vary in effectiveness as reservoirs