Utilizing two Borrelia bavariensis isolates naturally lacking the PFam54 gene array to elucidate the roles of PFam54-encoded proteins

Lyme borreliosis is the most common vector-borne disease in the Northern hemisphere, caused by spirochetes belonging to the Borrelia burgdorferi sensu lato ( Bb sl) species complex which are transmitted by ixodid ticks. Bb sl species produce a family of proteins on the linear plasmid 54 (PFam54), some of which confer the functions of cell adhesion and inactivation of complement, the first line of host defense. However, the impact of PFam54 in promoting Bb sl pathogenesis remains unclear because of the hurdles to simultaneously knock out all PFam54 proteins in a spirochete. Here, we describe two Borrelia bavariensis ( Bbav ) strains, PBN and PNi, isolated from patients naturally lacking PFam54 but maintaining the rest of the genome with greater than 95% identity to the reference Bbav strain PBi. We found that PBN and PNi less efficiently survive in human serum than PBi. Such defects were restored by introducing two Bbav PFam54 recombinant proteins, BGA66 and BGA71, confirming the role of these proteins in providing complement evasion of Bbav . Further, we found that all three strains remain detectable in various murine tissues 21 days post subcutaneous infection, supporting the non-essential role of Bbav PFam54 in promoting spirochete persistence. This study identified and utilized isolates deficient in PFam54 to associate the defects with the absence of these proteins, building the foundation to further study the role of each PFam54 protein in contributing to Bb sl pathogenesis. Importance To establish infections, Lyme borreliae utilize various means to overcome the host’s immune system. Proteins encoded by the PFam54 gene array play a role for spirochete survival in vitro and in vivo . Moreover, this gene array has been described in all currently available Lyme borreliae genomes. By investigating the first two Borrelia bavariensis isolates naturally lacking the entire PFam54 gene array, we showed that both patient isolates display an increased susceptibility to human serum, which can be rescued in the presence of two PFam54 recombinant proteins. However, both isolates remain infectious to mice after intradermal inoculation suggesting the non-essential role of PFam54 during long-term but may differ slightly in the colonization of specific tissues. Furthermore, these isolates show high genomic similarity to type-strain PBi (>95%) and could be used in future studies investigating the role of each PFam54 protein in Lyme borreliosis pathogenesis.

Meteorological and climatic variables predict the phenology of Ixodes ricinus nymphs activity in France, accounting for habitat heterogeneity

Ixodes ricinus ticks (Acari: Ixodidae) are the most important vector for Lyme borreliosis in Europe. As environmental and climate changes might affect the distribution and activity of tick populations, this study aimed to determine the effects of environmental factors, i.e., meteorological, bioclimatic, and habitat characteristics on questing activity of I. ricinus nymphs across diverse climatic types in France over an 8-year period. Questing activity was observed using a repeated removal sampling design with a cloth-dragging technique in 11 sampling sites from 7 tick observatories from 2014 to 2021 at approximately 1-month intervals, involving 631 sampling campaigns. Three phenological patterns were observed, potentially following a climatic gradient. The mixed-effects negative binomial regression revealed that observed nymph counts were driven by different interval-average meteorological variables, including one-month average temperature, previous-season average temperature, and half-year average minimum relative humidity. The interaction effects indicated that the phenology in colder climates peaked differently from that of warmer climates. Also, the land cover characteristics that support the highest baseline abundance were moderate forest fragmentation with transition borders with agricultural areas. Finally, our model could potentially be used to predict seasonal human-tick exposure risks in France that could contribute to mitigating Lyme borreliosis risks.

Lyme Borreliosis as Cause of Myocarditis: A Case Report and a Review of the Literature

lyme borreliosis (LB) is the most common tick-born disease in the Northern Hemisphere. During early disseminated Lyme disease, cardiac manifestation can occur. including acute conduction disorders, atrioventricular block, acute myopericarditis or left ventricular dysfunction and rarely cardiomegaly or fatal pericarditis. We report a case of a patient with isolated Lyme myocarditis manifested by acute heart failure with atrial fibrillation and review of the literature on the subject. The interested of this case report is to show the need to acquire the reflex to think about a lyme carditis when patients in endemic areas come to attention with cardiovasculair symtoms, even in the absence of others concurerenr clinical manifestations of early lyme disease.

Persistent Anti- Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context

The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis.

Association between statin use and clinical course, microbiologic characteristics, and long-term outcome of early Lyme borreliosis. A post hoc analysis of prospective clinical trials of adult patients with erythema migrans

Background Statins were shown to inhibit borrelial growth in vitro and promote clearance of spirochetes in a murine model of Lyme borreliosis (LB). We investigated the impact of statin use in patients with early LB. Methods In this post-hoc analysis, the association between statin use and clinical and microbiologic characteristics was investigated in 1520 adult patients with early LB manifesting as erythema migrans (EM), enrolled prospectively in several clinical trials between June 2006 and October 2019 at a single-center university hospital. Patients were assessed at enrollment and followed for 12 months. Results Statin users were older than patients not using statins, but statin use was not associated with Borrelia seropositivity rate, Borrelia skin culture positivity rate, or disease severity as assessed by erythema size or the presence of LB-associated symptoms. The time to resolution of EM was comparable in both groups. The odds for incomplete recovery decreased with time from enrollment, were higher in women, in patients with multiple EM, and in those reporting LB-associated symptoms at enrollment, but were unaffected by statin use. Conclusion Statin use was not associated with clinical and microbiologic characteristics or long-term outcome in early LB.

Spatial and temporal distribution patterns of tick-borne diseases (Tick-borne Encephalitis and Lyme Borreliosis) in Germany

Background In the face of ongoing climate warming, vector-borne diseases are expected to increase in Europe, including tick-borne diseases (TBD). The most abundant tick-borne diseases in Germany are Tick-Borne Encephalitis (TBE) and Lyme Borreliosis (LB), with Ixodes ricinus as the main vector. Methods In this study, we display and compare the spatial and temporal patterns of reported cases of human TBE and LB in relation to some associated factors. The comparison may help with the interpretation of observed spatial and temporal patterns. Results The spatial patterns of reported TBE cases show a clear and consistent pattern over the years, with many cases in the south and only few and isolated cases in the north of Germany. The identification of spatial patterns of LB disease cases is more difficult due to the different reporting practices in the individual federal states. Temporal patterns strongly fluctuate between years, and are relatively synchronized between both diseases, suggesting common driving factors. Based on our results we found no evidence that weather conditions affect the prevalence of both diseases. Both diseases show a gender bias with LB bing more commonly diagnosed in females, contrary to TBE being more commonly diagnosed in males. Conclusion For a further investigation of of the underlying driving factors and their interrelations, longer time series as well as standardised reporting and surveillance system would be required.

Seroprevalence of antibodies against Borrelia burgdorferi sensu lato in healthy blood donors in Romania: an update

Background The Borrelia burgdorferi sensu lato (s.l.) genogroup is the causative agent responsible for Lyme borreliosis, a common tick-borne infectious disease in some temperate regions of the Northern Hemisphere. In humans, the clinical manifestations of Lyme borreliosis vary from dermatological infection to severe systemic manifestations. In Romania, data on the seroprevalence of Lyme borreliosis and associated risk factors are scarce and outdated, as the only seroprevalence study with a large dataset was published more than 20 years ago. Therefore, the aim of the present study was to evaluate the seroprevalence for Borrelia burgdorferi s.l. in healthy blood donors from six Romanian counties and identify the associated risk factors. Methods The study was conducted among 1200 healthy blood donors aged between 18 and 65 years during November 2019 and September 2020 from six counties in the northwestern and central parts of Romania. A two-tiered testing strategy was applied. Positive and equivocal immunoenzymatic test results for IgG and IgM antibodies were further confirmed by Western blot. Results Serum samples from 20% of the blood donors had positive or equivocal IgG and IgM ELISA index values. In total, 2.3% of the serum samples for IgG and 1.8% for IgM were positive by Western blot. The seroprevalence for both antibodies varied between 1.5% (Satu-Mare) and 6.5% (Bistrița-Năsăud) in the six counties investigated. The highest seroprevalence was observed in men (4.7%), in blood donors performing their professional activities outdoors (4.2%), and in those aged ≥ 56 years (8%). Conclusions These findings confirm the presence of specific IgG and IgM antibodies to B. burgdorferi s.l. among healthy blood donors from Romania. Furthermore, potential risk factors, such as gender, age, and behavior, associated with the presence of positive B. burgdorferi s.l. antibodies among healthy blood donors were identified. Graphical Abstract

Climate change impacts on ticks and tick-borne infections

Evidence climate change is impacting ticks and tick-borne infections is generally lacking. This is primarily because, in most parts of the world, there are no long-term and replicated data on the distribution and abundance of tick populations, and the prevalence and incidence of tick-borne infections. Notable exceptions exist, as in Canada where the northeastern advance of Ixodes scapularis and Lyme borreliosis in the USA prompted the establishment of tick and associated disease surveillance. As a result, the past 30 years recorded the encroachment and spread of I. scapularis and Lyme borreliosis across much of Canada concomitant with a 2-3 °C increase in land surface temperature. A similar northerly advance of I. ricinus [and associated Lyme borreliosis and tick-borne encephalitis (TBE)] has been recorded in northern Europe together with expansion of this species’ range to higher altitudes in Central Europe and the Greater Alpine Region, again concomitant with rising temperatures. Changes in tick species composition are being recorded, with increases in more heat tolerant phenotypes (such as Rhipicephalus microplus in Africa), while exotic species, such as Haemaphysalis longicornis and Hyalomma marginatum, are becoming established in the USA and Southern Europe, respectively. In the next 50 years these trends are likely to continue, whereas, at the southern extremities of temperate species’ ranges, diseases such as Lyme borreliosis and TBE may become less prevalent. Where socioeconomic conditions link livestock with livelihoods, as in Pakistan and much of Africa, a One Health approach is needed to tackling ticks and tick-borne infections under the increasing challenges presented by climate change.