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In recent years, awareness of coinfections has increased as synergistic or antagonistic effects on interacting bacteria have been observed. To date, several reports on coinfections of ticks with Rickettsia and Borrelia spp. are available. However, associations are rarely described and studies are based on rather low sample sizes. In the present study, coinfections of Ixodes ricinus with these pathogens were investigated by determining their association in a meta -analysis. A total of 5079 tick samples examined for Rickettsia and Borrelia spp. via probe-based quantitative real-time PCR in previous prevalence studies or as submitted diagnostic material were included. In Borrelia -positive ticks, genospecies were determined by Reverse Line Blot. Determination of bacterial loads resulted in an increase between developmental tick stages with highest mean bacterial loads in female ticks (7.96 × 10 4 in Borrelia single-infected, 4.87 × 10 5 in Rickettsia single-infected and 3.22 × 10 5 in Borrelia - Rickettsia coinfected females). The determined Borrelia - Rickettsia tick coinfection rate was 12.3% (626/5079) with a significant difference to the expected coinfection rate of 9.0% (457/5079). A significant slight association as well as correlation between Borrelia and Rickettsia were determined. In addition, a significant interrelation of the bacterial load in coinfected ticks was shown. At the level of Borrelia genospecies, significant weak associations with Rickettsia spp. were detected for B. afzelii , B. garinii/bavariensis , B. valaisiana and B. lusitaniae . The positive association provides evidence for interactions between Borrelia and Rickettsia spp. in the tick vector, presumably resulting in higher bacterial replication rates in the tick vector and possibly the reservoir host. However, coinfection may impact the vector negatively as indicated by an absent increase in coinfection rates from nymphs to adults. Future studies are needed to investigate the underlying mechanisms of the positive association in ticks and possible associations in the vertebrate host as well as the potential influence of environmental factors. [ABSTRACT FROM AUTHOR]

Lyme borreliosis, caused by Borrelia burgdorferi sensu lato (s.l.) spirochaetes, is the most common tick-borne disease (TBD) in the Northern Hemisphere. Rising incidences indicate that its epidemiology may be affected by global changes. Therefore, the current study aimed to assess changes in tick infection rates with Borrelia spp. over a 15-year monitoring period in the city of Hanover, Germany, as a follow-up to previous prevalence studies (years 2005, 2010 and 2015). To assess the epidemiological risk, ticks of the Ixodes ricinus/inopinatus -complex were sampled from April to October 2020 by the flagging method at 10 frequently visited recreation areas in Hanover. Analysis by quantitative real-time PCR of 2100 individual ticks revealed an overall Borrelia prevalence of 25.5% (535/2100). Regarding different tick developmental stages, nymphs showed a significantly lower Borrelia prevalence (18.4% [193/1050]) than adult ticks (32.6% [342/1050]). Comparison with previous years revealed a stable total Borrelia prevalence along with consistent infection rates in the different developmental stages over the 15-year monitoring period. Borrelia species differentiation by Reverse Line Blot was successful in 67.3% of positive ticks collected in 2020, with B. afzelii being the dominating species (59.2% of the differentiated infections), besides B. burgdorferi sensu stricto (s.s.), B. garinii, B. valaisiana, B. spielmanii, B. bavariensis and B. bissettiae and the relapsing fever spirochaete B. miyamotoi. Additionally, the proportion of infections attributed to B. afzelii showed a significant increase in 2020 compared to 2005 and 2015 (59.2% vs. 37.6% and 32.0% of successfully differentiated infections, respectively). Coinfections with Anaplasma phagocytophilum and Rickettsia spp. stayed stable comparing 2020 with previous years. Therefore, although changes in the Borrelia prevalence in questing ticks were not observed throughout the 15-year monitoring period, shifts in Borrelia species distribution may alter the epidemiological risk. [ABSTRACT FROM AUTHOR]

Lyme borreliosis caused by spirochaetes of the Borrelia burgdorferi sensu lato (s.l.) complex is the most common tick-borne disease in Europe. In addition, the relapsing-fever spirochaete Borrelia miyamotoi , which has been associated with febrile illness and meningoencephalitis in immunocompromised persons, is present in Europe. This study investigated Borrelia prevalence and species distribution in ticks removed from humans and sent as diagnostic material to the Institute for Parasitology, University of Veterinary Medicine Hannover, in 2013-2017. A probe-based real-time PCR was carried out and Borrelia -positive samples were subjected to species determination by reverse line blot (RLB), including a B. miyamotoi -specific probe. The overall Borrelia -infection rate as determined by real-time PCR was 20.02 % (510/2547, 95 % CI: 18.48–21.63 %), with annual prevalences ranging from 17.17 % (90/524, 95 % CI: 14.04–20.68 %) in 2014 to 24.12 % (96/398, 95 % CI: 19.99–28.63 %) in 2015. In total, 271/475 (57.1 %) positive samples available for RLB were successfully differentiated. Borrelia afzelii was detected in 30.53 % of cases (145/475, 95 % CI: 26.41–34.89), followed by B. garinii/B. bavariensis (13.26 % [63/475], 95 % CI: 10.34–16.65). Borrelia valaisiana occurred in 5.89 % (28/475, 95 % CI: 3.95–8.41), B. spielmanii in 4.63 % (22/475, 95 % CI: 2.93–6.93), B. burgdorferi sensu stricto (s.s.)/ B. carolinensis in 2.32 % (11/475, 95 % CI: 1.16–4.11), B. lusitaniae in 0.63 % (3/475, 95 % CI: 0.13–1.83) and B. bisettiae in 0.42 % (2/475, 95 % CI: 0.05–1.51) of positive ticks. Borrelia kurtenbachii was not detected, while B. miyamotoi was identified in 7.37 % (35/475, 95 % CI: 5.19–10.10) of real-time PCR-positive samples. Sanger sequencing of B. garinii/B. bavariensis -positive ticks revealed that the majority were B. garinii -infections (50/52 successfully amplified samples), while only 2 ticks were infected with B. bavariensis. Furthermore, 6/12 B. burgdorferi s.s./ B. carolinensis -positive samples could be differentiated; all of them were identified as B. burgdorferi sensu stricto. Thirty-nine ticks (8.21 %, 95 % CI: 5.90–11.05) were coinfected with two different species. Comparison of the species distribution between ticks removed from humans in 2015 and questing ticks collected in the same year and the same area revealed a significantly higher B. afzelii -prevalence in diagnostic tick samples than in questing ticks, confirming previous observations. The obtained data indicate that Borrelia prevalence fluctuated in the same range as observed in a previous study, analysing the period from 2006 to 2012. Detection of B. miyamotoi in 7.37 % of Borrelia -positive samples points to the fact that clinicians should be aware of this pathogen as a differential diagnosis in cases of febrile illness. [ABSTRACT FROM AUTHOR]

Malaria represents a major cause of death from infectious disease. Hemozoin is a Plasmodium -derived product that contributes to progression of cerebral malaria. However, there is a gap of knowledge regarding how hemozoin is recognized by innate immunity. Myeloid C-type lectin receptors (CLRs) encompass a family of carbohydrate-binding receptors that act as pattern recognition receptors in innate immunity. In the present study, we identify the CLR CLEC12A as a receptor for hemozoin. Dendritic cell-T cell co-culture assays indicate that the CLEC12A/hemozoin interaction enhances CD8+ T cell cross-priming. Using the Plasmodium berghei Antwerpen-Kasapa (ANKA) mouse model of experimental cerebral malaria (ECM), we find that CLEC12A deficiency protects mice from ECM, illustrated by reduced ECM incidence and ameliorated clinical symptoms. In conclusion, we identify CLEC12A as an innate sensor of plasmodial hemozoin. • CLEC12A recognizes plasmodial hemozoin • The CLEC12A/hemozoin interaction enhances CD8+ T cell cross-priming in vitro • CLEC12A−/− mice are protected from experimental cerebral malaria Raulf et al. demonstrate that CLEC12A recognizes plasmodial hemozoin and is involved in the development of experimental cerebral malaria (ECM). In vivo studies show a reduction in ECM in CLEC12A−/− mice that is accompanied by a decrease in the frequency of brain-sequestered granzyme B-expressing T cells. [ABSTRACT FROM AUTHOR]