281 < Back to Research Top Published Date 21/10/2010 Metamorphosis of Borrelia burgdorferi organisms-RNA, lipid and protein composition in context with the spirochete’s shape Journal Journal of Basic Microbiology Citation J Basic Microbiol. 2010 Dec;50 Suppl 1:S5-17 DOI doi: 10.1002/jobm.201000074 Authors Al-Robaiy S, Dihazi H, Kacza J, Seeger J, Schiller J, Huster D, Knauer J, Straubinger RK Abstract Borrelia burgdorferi, the agent of Lyme borreliosis, has the ability to undergo morphological transformation from a motile spirochetal to non-motile spherical shape when it encounters unfavorable conditions. However, little information is available on the mechanism that enables the bacterium to change its shape and whether major components of the cells--nucleic acids, proteins, lipids--are possibly modified during the process. Deducing from investigations utilizing electron microscopy, it seems that shape alteration begins with membrane budding followed by folding of the protoplasmatic cylinder inside the outer surface membrane. Scanning electron microscopy confirmed that a deficiency in producing functioning periplasmic flagella did not hinder sphere formation. Further, it was shown that the spirochetes' and spheres' lipid compositions were indistinguishable. Neither phosphatidylcholine nor phosphatidylglycerol were altered by the structural transformation. In addition, no changes in differential protein expression were detected during this process. However, minimal degradation of RNA and a reduced antigen-antibody binding activity were observed with advanced age of the spheres. The results of our comparisons and the failure to generate mutants lacking the ability to convert to spheres suggest that the metamorphosis of B. burgdorferi results in a conditional reconstruction of the outer membrane. The spheres, which appear to be more resistant to unfavorable conditions and exhibit reduced immune reactivity when compared to spirochetes, might allow the B. burgdorferi to escape complete clearance and possibly ensure long-term survival in the host. URL Previous https://www.ncbi.nlm.nih.gov/pubmed/20967786 No Review Needed? Next

201 < Back to Research Top Published Date 17/11/2014 Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013 Journal Bulletin of the World Health Organization Citation Bull World Health Organ. 2015 Jan 1; 93(1): 19-28 DOI 10.2471/BLT.14.139790 Authors Oza S, Lawn J.E, Hogan D.R, Mathers C, Cousens S.N Abstract Objective To estimate cause-of-death distributions in the early (0–6 days of age) and late (7–27 days of age) neonatal periods, for 194 countries between 2000 and 2013. Methods For 65 countries with high-quality vital registration, we used each country’s observed early and late neonatal proportional cause distributions. For the remaining 129 countries, we used multinomial logistic models to estimate these distributions. For countries with low child mortality we used vital registration data as inputs and for countries with high child mortality we used neonatal cause-of-death distribution data from studies in similar settings. We applied cause-specific proportions to neonatal death estimates from the United Nations Inter-agency Group for Child Mortality Estimation, by country and year, to estimate cause-specific risks and numbers of deaths. Findings Over time, neonatal deaths decreased for most causes. Of the 2.8 million neonatal deaths in 2013, 0.99 million deaths (uncertainty range: 0.70–1.31) were estimated to be caused by preterm birth complications, 0.64 million (uncertainty range: 0.46–0.84) by intrapartum complications and 0.43 million (uncertainty range: 0.22–0.66) by sepsis and other severe infections. Preterm birth (40.8%) and intrapartum complications (27.0%) accounted for most early neonatal deaths while infections caused nearly half of late neonatal deaths. Preterm birth complications were the leading cause of death in all regions of the world. Conclusion The neonatal cause-of-death distribution differs between the early and late periods and varies with neonatal mortality rate level. To reduce neonatal deaths, effective interventions to address these causes must be incorporated into policy decisions. URL Previous https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271684/ No Review Needed? Next

181 < Back to Research Top Published Date 01/12/2015 A study on the association between infectious burden and Alzheimer's disease Journal European Journal of Neurology Citation Eur J Neurol. 2015 Dec;22(12):1519-25 DOI 10.1111/ene.12477 Authors Bu XL, Yao XQ, Jiao SS, Zeng F, Liu YH, Xiang Y, Liang CR, Wang QH, Wang X, Cao HY, Yi X, Deng B, Liu CH, Xu J, Zhang LL, Gao CY, Xu ZQ, Zhang M, Wang L, Tan XL, Xu X, Zhou HD, Wang YJ Abstract BACKGROUND AND PURPOSE: Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between infectious burden (IB) and Alzheimer's disease (AD) was examined. METHODS: Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme-linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens. RESULTS: Seropositivities toward zero-two, three and four-five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini-Mental State Examination scores were negatively correlated with IB in all cases. Serum beta-amyloid protein (Aβ) levels (i.e. Aβ40, Aβ42 and total Aβ) and inflammatory cytokines (i.e. interferon-γ, tumor necrosis factor α, interleukin-1β and interleukin-6) in individuals exposed to four-five infectiouspathogens were significantly higher than those exposed to zero-two or three pathogens. CONCLUSIONS: IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD. URL Previous https://onlinelibrary.wiley.com/doi/full/10.1111/ene.12477 No Review Needed? Next

221 < Back to Research Top Published Date 27/03/2014 Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey Journal PeerJ Citation PeerJ. 2014 Mar 27;2:e322 DOI 10.7717/peerj.322 Authors Johnson L, Wilcox S, Mankoff J, Stricker RB Abstract OVERVIEW: The Centers for Disease Control and Prevention (CDC) health-related quality of life (HRQoL) indicators are widely used in the general population to determine the burden of disease, identify health needs, and direct public health policy. These indicators also allow the burden of illness to be compared across different diseases. Although Lyme disease has recently been acknowledged as a major health threat in the USA with more than 300,000 new cases per year, no comprehensive assessment of the health burden of this tickborne disease is available. This study assesses the HRQoL of patients with chronic Lyme disease (CLD) and compares the severity of CLD to other chronic conditions. METHODS: Of 5,357 subjects who responded to an online survey, 3,090 were selected for the study. Respondents were characterized as having CLD if they were clinically diagnosed with Lyme disease and had persisting symptoms lasting more than 6 months following antibiotic treatment. HRQoL of CLD patients was assessed using the CDC 9-item metric. The HRQoL analysis for CLD was compared to published analyses for the general population and other chronic illnesses using standard statistical methods. RESULTS: Compared to the general population and patients with other chronic diseases reviewed here, patients with CLD reported significantly lower health quality status, more bad mental and physical health days, a significant symptom disease burden, and greater activity limitations. They also reported impairment in their ability to work, increased utilization of healthcare services, and greater out of pocket medical costs. CONCLUSIONS: CLD patients have significantly impaired HRQoL and greater healthcare utilization compared to the general population and patients with other chronic diseases. The heavy burden of illness associated with CLD highlights the need for earlier diagnosis and innovative treatment approaches that may reduce the burden of illness and concomitant costs posed by this illness. URL Previous https://peerj.com/articles/322 No Review Needed? Next

107 < Back to Research Top Published Date 16/05/2019 Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters Journal Parasites & Vectors Citation Parasit Vectors. 2019 May 16;12(1):237 DOI 10.1186/s13071-019-3495-7 Authors Rudenko N, Golovchenko M, Kybicova K, Vancova M Abstract The survival of spirochetes from the Borrelia burgdorferi (sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation. Both subpopulations represent the cells in different physiological states. "Dormancy" and "persistence" do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of "persisters" substituted the originally-used term "survivors", referring to the small bacterial population of Staphylococcus that survived killing by penicillin. The phenomenonof persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics. Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients? URL Previous https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3495-7 No Review Needed? Next

123 < Back to Research Top Published Date 04/01/2019 The economic burden of Lyme disease and the cost-effectiveness of Lyme disease interventions: A scoping review Journal PLoS One Citation PLoS One. 2019; 14(1): e0210280 DOI 10.1371/journal.pone.0210280 Authors Mac S, da Silva SR, Sander B Abstract INTRODUCTION: While Lyme disease (LD) is mostly treatable, misdiagnosed or untreated LD can result in debilitating sequelae and excessive healthcare usage. The objective of this review was to characterize the body of literature on the economic burden of Lyme disease (LD) and the cost-effectiveness of LD interventions, such as antibiotic treatment and vaccination. METHODS: We followed Joanna Briggs Institute scoping review methodologies. We systematically searched terms related to LD, economic evaluations, costs, and cost-effectiveness in Medline, Embase, PsycInfo, Cochrane Library, and the grey literature up to November 2017. We included primary economic evaluations conducted in North America and Europe, reporting LD-related costs or cost-effectiveness of human interventions. Two reviewers screened articles and charted data independently. Costs were standardized to 2017 United States dollars (USD). RESULTS: We screened 923 articles, and included 10 cost-effectiveness analyses (CEA) and 11 cost analyses (CA). Three CEAs concluded LD vaccination was likely cost-effective only in endemic areas (probability of infection ?1%). However, LD vaccination is not currently available as an intervention in the US or Europe. Six studies assessed economic burden from a societal perspective and estimated significant annual national economic impact of: 735,550 USD for Scotland (0.14 USD per capita, population = 5.40M), 142,562 USD in Sweden (0.014 USD per capita, 9.96M), 40.88M USD in Germany (0.51 USD per capita, 80.59M), 23.12M USD in the Netherlands (1.36 USD per capita, 17.08M), and up to 786M USD in the US (2.41 USD per capita, 326.63M). CONCLUSIONS: Lyme disease imposes an economic burden that could be considered significant in the US and other developed countries to justify further research efforts in disease control and management. Societal costs for Lyme disease can be equally impactful as healthcare costs, but are not fully understood. Economic literature from countries with historically high incidence rates or increasing rates of Lyme disease are limited, and can be useful for future justification of resource allocation. URL Previous https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210280 No Review Needed? Next

21 < Back to Research Top Published Date 01/02/2021 A murine model of Lyme disease demonstrates that Borrelia burgdorferi colonizes the dura mater and induces inflammation in the central nervous system Journal PLoS Pathogen Citation 17(2):e1009256 DOI 10.1371/journal.ppat.1009256 Authors Casselli T, Divan A, Vomhof-DeKrey EE, Tourand Y, Pecoraro HL, Brissette CA Abstract Lyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Inbred laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in joints and heart, however similar studies are lacking in the CNS of these animals. A tractable animal model for investigating host-Borrelia interactions in the CNS is key to understanding the mechanisms of CNS pathogenesis. Therefore, we characterized the kinetics of B. burgdorferi colonization and associated immune responses in the CNS of mice during early and subacute infection. Using fluorescence-immunohistochemistry, intravital microscopy, bacterial culture, and quantitative PCR, we found B. burgdorferi routinely colonized the dura mater of C3H mice, with peak spirochete burden at day 7 post-infection. Dura mater colonization was observed for several Lyme disease agents including B. burgdorferi, B. garinii, and B. mayonii. RNA-sequencing and quantitative RT-PCR showed that B. burgdorferi infection was associated with increased expression of inflammatory cytokines and a robust interferon (IFN) response in the dura mater. Histopathologic changes including leukocytic infiltrates and vascular changes were also observed in the meninges of infected animals. In contrast to the meninges, we did not detect B. burgdorferi, infiltrating leukocytes, or large-scale changes in cytokine profiles in the cerebral cortex or hippocampus during infection; however, both brain regions demonstrated similar changes in expression of IFN-stimulated genes as observed in peripheral tissues and meninges. Taken together, B. burgdorferi is capable of colonizing the meninges in laboratory mice, and induces localized inflammation similar to peripheral tissues. A sterile IFN response in the absence of B. burgdorferi or inflammatory cytokines is unique to the brain parenchyma, and provides insight into the potential mechanisms of CNS pathology associated with this important pathogen. URL Previous https://pubmed.ncbi.nlm.nih.gov/33524035/ No Review Needed? Next

280 < Back to Research Top Published Date 01/12/2010 Lyme disease diagnosis and treatment: lessons from the AIDS epidemic Journal Minerva Medica Citation Minerva Med. 2010 Dec;101(6):419-25 DOI Authors Stricker RB, Johnson L Abstract Lyme disease is a controversial tick-borne illness that is estimated to be four times more common than AIDS in the United States. This paper outlines the challenges overcome in the healthcare response to human immunodeficiency virus (HIV) infection, the development of sensitive laboratory tests for the AIDS virus, and the promotion of long-term combination antimicrobial regimens to effectively treat HIV disease. We suggest that similar challenges need to be overcome before the chronic form of Lyme disease can be successfully treated. Currently, diagnosis and treatment of Lyme disease is hindered by the lack of a uniform case definition that adequately reflects the clinical presentation of the disease, poor laboratory test sensitivity, and high treatment failure rates using short-term monotherapy. Consequently the optimal treatment for patients with persistent symptoms of Lyme disease remains undefined. Although antibiotic monotherapy has been successful in treating early Lyme disease, the use of combination antibiotic therapy modelled on HIV treatment appears to be more effective for patients with persistent symptoms of tick-borne infection. Resolution of the controversy surrounding Lyme disease should lead to improved diagnosisand treatment modelled on the approach to HIV disease. URL Previous https://www.ncbi.nlm.nih.gov/pubmed/21196901 No Review Needed? Next

198 < Back to Research Top Published Date 29/12/2014 Borrelia burgdorferi promotes the establishment of Babesia microti in the northeastern United States Journal PLoS One Citation PLoS One. 2014 Dec 29;9(12):e115494 DOI 10.1371/journal.pone.0115494 Authors Dunn JM, Krause PJ, Davis S, Vannier EG, Fitzpatrick MC, Rollend L, Belperron AA, States SL, Stacey A, Bockenstedt LK, Fish D, Diuk-Wasser MA Abstract Babesia microti and Borrelia burgdorferi, the respective causative agents of human babesiosis and Lyme disease, are maintained in their enzootic cycles by the blacklegged tick (Ixodes scapularis) and use the white-footed mouse (Peromyscus leucopus) as primary reservoir host. The geographic range of both pathogens has expanded in the United States, but the spread of babesiosis has lagged behind that of Lyme disease. Several studies have estimated the basic reproduction number (R0) for B. microti to be below the threshold for persistence (<1), a finding that is inconsistent with the persistence and geographic expansion of this pathogen. We tested the hypothesis that host coinfection with B. burgdorferi increases the likelihood of B. microti transmission and establishment in new areas. We fed I. scapularis larva on P. leucopus mice that had been infected in the laboratory with B. microti and/or B. burgdorferi. We observed that coinfection in mice increases the frequency of B. microti infected ticks. To identify the ecological variables that would increase the probability of B. microti establishment in the field, we integrated our laboratory data with field data on tick burden and feeding activity in an R0 model. Our model predicts that high prevalence of B. burgdorferi infected mice lowers the ecological threshold for B. microti establishment, especially at sites where larval burden on P. leucopus is lower and where larvae feed simultaneously or soon after nymphs infect mice, when most of the transmission enhancement due to coinfection occurs. Our studies suggest that B. burgdorferi contributes to the emergence and expansion of B. microti and provides a model to predict the ecological factors that are sufficient for emergence of B. microti in the wild. URL Previous https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115494 No Review Needed? Next

210 < Back to Research Top Published Date 01/08/2014 Broad-range survey of tick-borne pathogens in Southern Germany reveals a high prevalence of Babesia microti and a diversity of other tick-borne pathogens Journal Vector-Borne and Zoonotic Diseases Citation Vector Borne Zoonotic Dis. 2014 Aug;14(8):584-91 DOI 10.1089/vbz.2013.1498 Authors Eshoo MW, Crowder CD, Carolan HE, Rounds MA, Ecker DJ, Haag H, Mothes B, Nolte O Abstract Ticks harbor numerous pathogens of significance to human and animal health. A better understanding of the pathogens carried by ticks in a given geographic area can alert health care providers of specific health risks leading to better diagnosis and treatments. In this study, we tested 226 Ixodes ricinis ticks from Southern Germany using a broad-range PCR and electrospray ionization mass spectrometry assay (PCR/ESI-MS) designed to identify tick-borne bacterial and protozoan pathogens in a single test. We found 21.2% of the ticks tested carried Borrelia burgdorferi sensu lato consisting of diverse genospecies; a surprisingly high percentage of ticks were infected with Babesia microti (3.5%). Other organisms found included Borrelia miyamotoi, Rickettsia helvetica, Rickettsia monacensis, and Anaplasma phagocytophilum. Of further significance was our finding that more than 7% of ticks were infected with more than one pathogen or putative pathogen. URL Previous https://www.liebertpub.com/doi/full/10.1089/vbz.2013.1498 No Review Needed? Next

5 < Back to Research Top Published Date 06/07/2021 In vitro efficacy of antibiotics against different Borrelia isolates Journal Acta Microbiologica Immunologica Hungarica Citation 10.1556/030.2021.0144 DOI 10.1556/030.2021.0144 Authors Veinovic G, Cakic S, Mihaljica D, Sukara R, Ruzic-Sabljic E, Tomanovic S Abstract In the present study, the effectiveness of six antimicrobial agents have been tested against 24 borrelia strains isolated from Ixodes ricinus ticks (11 Borrelia lusitaniae, eight Borrelia afzelii, three Borrelia garinii and two Borrelia valaisiana) and one B. lusitaniae strain isolated from human skin. The minimum inhibitory concentration range of antimicrobial agents was as follows: amoxicillin, 0.125-2 mg/L; doxycycline, 0.125-1 mg/L, ceftriaxone, 0.016-0.063 mg/L; cefuroxime, 0.063-1 mg/L; azithromycin, 0.0017-0.11 mg/L; amikacin 32-512 mg/L. Potentially pathogenic B. lusitaniae and B. valaisiana species were more susceptible to amoxicillin and azithromycin than pathogenic B. afzelii and B. garinii (P < 0.05); B. garinii, B. lusitaniae and B. valaisiana were more susceptible to doxycycline than B. afzelii (P < 0.05) while all species showed same susceptibility to ceftriaxone and cefuroxime (P > 0.05). This study is the first report on in vitro susceptibility of isolates from Serbia to antimicrobial agents and the first report on susceptibility of larger number of isolates of potentially pathogenic species B. lusitaniae. We showed that antimicrobial agents in vitro inhibit growth of borrelia strains very effectively, indicating the potential of their equally beneficial use in the treatment of Lyme borreliosis. Keywords: Borrelia; Lyme borreliosis; antimicrobial agents; in vitro susceptibility; treatment. URL Previous https://pubmed.ncbi.nlm.nih.gov/34232906/ No Review Needed? Next