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Eckman E, Clausen D, Herdt A, et al.
AbstractBackgroundDemonstration of intrathecal production of Borrelia-specific antibodies (ITAb) is considered the most specific diagnostic marker of Lyme neuroborreliosis (LNB). Limitations include delayed detectabilty in early infection and continued presence long after successful treatment. Markers of active inflammation – increased CSF leukocytes, protein and CXCL13 – provide nonspecific markers of active infection. To assess the utility of CSF CXCL13, we measured its concentration in 132 patients with a broad spectrum of neuroinflammatory disorders, including LNB.MethodsCSF CXCL13 was measured by immunoassay. Spearman’s rank correlation test was performed to explore its relationship to conventional markers of neuroinflammation and Borrelia-specific ITAb production.ResultsIn non-LNB neuroinflammatory disorders, CSF CXCL13 elevation correlated with CSF IgG synthesis and leukocyte count. In LNB, CXCL13 concentration was far greater than expected from overall CSF IgG synthesis, and correlated with Borrelia-specific ITAb synthesis. Median CSF CXCL13 concentration in ITAb-positive LNB patients was >500 times greater than in any other group.ConclusionsIntrathecal CXCL13 and IgG production are closely inter-related. CXCL13 is disproportionately increased in “definite LNB,” defined as having demonstrable Borrelia-specific ITAb, but not “probable LNB,” without ITAb. This disproportionate increase may help identify patients with very early infection, those with active vs. treated LNB, or help differentiate ITAb-defined active LNB from other neuroinflammatory disorders. However, its reported specificity is closely related to the diagnostic requirement for ITAb. It may add little specificity to the demonstration of a pleocytosis or increased overall or specific IgG production in the CSF.
Thompson, C., Mason, C., Parrilla, S., Ouyang, Z.
Borrelia burgdorferi encodes a functional homolog of canonical Lon protease termed Lon-2. In addition, B. burgdorferi encodes a second Lon homolog called Lon-1. Recent studies suggest that Lon-1 may function differently from the prototypical Lon protease. However, the function of Lon-1 in B. burgdorferi biology remains virtually unknown. Particularly, the contribution of Lon-1 to B. burgdorferi fitness and infection remains hitherto unexplored. Herein, we show that Lon-1 plays a critical role in the infection of B. burgdorferi in a mammalian host. We found that lon-1 was highly expressed during animal infection, implying an important function of this protein in bacterial infection. We further generated a lon-1 deletion mutant and an isogenic complemented strain. Relative to that of the wild-type strain, the infectivity of the mutant was severely attenuated in a murine infection model. Our data also showed that the mutant displayed growth defects in regular BSK-II medium. Furthermore, bacterial resistance to osmotic stress was markedly reduced when lon-1 was inactivated. When exposed to tert-butyl hydroperoxide, survival of the lon-1 mutant was impaired. In addition, production of several virulence factors such as BosR, RpoS, and OspC was elevated in the mutant. These phenotypes were restored when lon-1 mutation was complemented. Finally, we created a lon-1(S714A) mutant and found that this mutant failed to infect mice, suggesting that the proteolytic activity of Lon-1 is essential for bacterial infection. Taken together, these results demonstrate that Lon-1 is required by B. burgdorferi to infect animal hosts and to cope with environmental stresses.
V. Muigg et al.
Marcinkiewicz, A. L., Lieknina, I., Yang, X., Lederman, P. L., Hart, T. M., Yates, J., Chen, W.-H., Bottazzi, M. E., Mantis, N. J., Kraiczy, P., Pal, U., Tars, K., Lin, Y.-P.
The spirochete Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding. We found that the sera from CspZ-YA-vaccinated mice more efficiently eliminated spirochetes and blocked CspZ FH-binding activity than sera from CspZ-immunized mice. We also found vaccination with CspZ, but not CspZ-YA, triggered the production of anti-FH antibodies, justifying CspZ-YA as a LD vaccine candidate. The mechanistic and efficacy information derived from this study provides insights into the development of a CspZ-based LD vaccine.
Ruiyan Zhang, Ting Gong, Teng Chen, Ning Zhang, Faming Miao, Qi Chen, Ye Feng, Lu Ji, Jinghui Zhao
We read with interest the recently published article titled "Seroprevalence of Lyme borreliosis in Finland 50 years ago" .We applaud the authors for studyingthe Lyme borreliosis (LB) seroprevalence in Finland in the 1960s and 1970s through evaluation of IgG against Borrelia burgdorferiin historical serum samples. Despite its scientific and comprehensive, some technical issues should be discussed.
Strle K, Strle F.
Lyme borreliosisoutcomeposttreatment Lyme disease symptomsBorrelia burgdorferi sensu latobiomarkers
Quentin Bernard, Antoine Grillon, Cédric Lenormand, Laurence Ehret-Sabatier, Nathalie Boulanger
The skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence.
Cuellar, J., Astrand, M., Elovaara, H., Pietikäinen, A., Siren, S., Liljeblad, A., Guedez, G., Salminen, T. A., Hytönen, J.
Borrelia burgdorferi sensu lato (sl), the causative agent of the tick-borne Lyme borreliosis (LB), has a limited metabolic capacity and needs to acquire nutrients, such as amino acids, fatty acids, and nucleic acids, from the host environment. Using X-ray crystallography, liquid chromatography-mass spectrometry, microscale thermophoresis, and cellular localization studies, we show that Basic membrane protein D (BmpD) is a periplasmic substrate-binding protein of an ABC transporter system binding to purine nucleosides. Nucleosides are essential for bacterial survival in the host organism and these studies suggest a key role for BmpD in the purine salvage pathway of B. burgdorferi sl. As B. burgdorferi sl lacks the enzymes required for de novo purine synthesis, BmpD may play a vital role in ensuring access to the purines needed for sustaining an infection in the host. Further, we show that although human LB patients develop anti-BmpD antibodies, immunization of mice with BmpD does not confer protection against B. burgdorferi sl infection.
Nayak, A., Schüler, W., Seidel, S., Gomez, I., Meinke, A., Comstedt, P., Lundberg, U.
The development of vaccines for prevention of diseases caused by pathogenic species can encounter major obstacles if high sequence diversity is observed between individual strains. Therefore, the development might be restricted either to conserved antigens, which often are rare, or to multivalent vaccines, which renders the production more costly and cumbersome. In light of this complexity, we applied a structure-based surface shaping approach for the development of a Lyme borreliosis (LB) vaccine suitable for the USA and Europe. The surface of the C-terminal fragment of outer surface protein A (OspA) was divided into distinct regions mainly based on binding sites of monoclonal antibodies. In order to target the six clinically most relevant OspA serotypes (ST) in a single protein, exposed amino acids of the individual regions were exchanged to corresponding amino acids of a chosen OspA serotype. Six chimeric proteins were constructed and based on their immunogenicity four of these chimeras were tested in mouse challenge models. Significant protection could be demonstrated for all four proteins following challenge with infected ticks (OspA ST1, OspA ST2, and OspA ST4), as well as with in vitro grown spirochetes (OspA ST1 and OspA ST5). Two of the chimeric proteins were linked to form a fusion protein, which provided significant protection against in vitro grown spirochetes (OspA ST1) and infected ticks (OspA ST2). This article presents the proof-of-concept study for a multivalent OspA vaccine targeting a wide range of pathogenic LB Borrelia species with a single recombinant antigen for prevention of Lyme borreliosis.
Célia Scherelle Boumbanda Koyo, Sandrine Lydie Oyegue-Liabagui, Oleg Mediannikov, Sébastien Cortaredona, Lady Charlene Kouna, Didier Raoult, Jean Bernard Lekana-Douki and Florence Fenollar
The epidemiology of febrile illness etiologies is under-explored in resource-poor settings. Establishing a local repertory of microorganisms circulating in blood of febrile and afebrile people is important for physicians. Blood was collected from 428 febrile and 88 afebrile children in Makokou (Gabon) and analyzed using polymerase chain reaction. Plasmodium spp. were the pathogens, which were most detected in febrile children (69.6%; 298/428) and in afebrile children (31.8%; 28/88) (P < 0.0001). Plasmodium falciparum was the most prevalent species in both febrile and afebrile children (66.8% and 27.3%, respectively). No differences were observed between febrile and afebrile children for Plasmodium malariae and Plasmodium ovale (8.2% versus 10.2% and 3.3% versus 3.4%, respectively). Triple infection with P. falciparum, P. malariae, and P. ovale was also detected in 1% of febrile children (4/428). Filariasis due to Mansonella perstans was detected in 10 febrile patients (2.3%), whereas Loa loa was detected in both febrile and afebrile children (1.4% and 2.3%, respectively). Bacterial DNA was detected in only 4.4% (19/428) of febrile children, including 13 (68.4%) who were coinfected with at least one Plasmodium species. These were Haemophilus influenzae (1.6%, 7/428), Streptococcus pneumoniae and Staphylococcus aureus (1.2%, 5/428), and Rickettsia felis (0.9%, 4/428). Coxiella burnetii, Bartonella spp., Borrelia spp., Tropheryma whipplei, Anaplasma spp., Leptospira spp., Streptococcus pyogenes, and Salmonella spp. were not detected. This study also highlights the over-prescription and the overuse of antibiotics and antimalarials. Overall, malaria remains a major health problem in Makokou. Malaria control measures must be reconsidered in this region.
Ndeye Safietou Fall, Nafissatou Diagne, Oleg Mediannikov, Florence Fenollar, Philippe Parola, Cheikh Sokhna, Didier Raoult, Jean-Christophe Lagier
Kristin Boardman, Kyle Rosenke, David Safronetz, Heinz Feldmann and Tom G. Schwan
African multimammate rats, Mastomys natalensis, are widely distributed in sub-Saharan Africa and live in close association with humans. In West Africa, numerous field studies have shown these animals may be naturally infected with the relapsing fever spirochete Borrelia crocidurae, the primary cause of tick-borne relapsing fever in this region of the continent. However, naturally infected individual rats have never been examined over time; therefore, the true host competency of these rats for this spirochete is unknown. Therefore, using animals from an established laboratory colony of M. natalensis, rats were experimentally infected with B. crocidurae and their blood examined to 28 days postinoculation. These animals were highly susceptible to infection and displayed prolonged and cyclic spirochetemias. Our results demonstrate these peridomestic rodents are likely competent hosts for infecting argasid tick vectors and play a primary role in the enzootic cycle for B. crocidurae in West Africa.
International Liver Congress (ILC) 2020
15.04.2020 - 19.04.2020
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020
18.04.2020 - 21.04.2020
DSI årsmøde 2020 (aflyst)
Hindsgavl Slot, Middelfart
1.05.2020 - 2.05.2020
Kursus i rejsemedicin 2020
Statens Serum Institut
4.05.2020 - 6.05.2020
5.05.2020 - 7.05.2020
COVID-19 retningslinje (2020)
National handlingsplan for antibiotika til mennesker (2017)
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
A real-world evaluation of a Case-Based Reasoning algorithm to support antimicrobial prescribing decisions in acute care
4.04.2020Clinical Infectious Diseases Advance Access
Open versus endovascular repair of aortic aneurysms
COVID-19 will not leave behind refugees and migrants
Redefining vulnerability in the era of COVID-19
The COVID-19 pandemic in the USA: what might we expect?
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Hvad mener Professor Lars Østergaard om artiklen"Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial."?
Hvad synes Professor Thomas Benfield om"Oral versus Intravenous Antibiotics for Bone and Joint Infection."?
Hvorfor anbefaler Professor Niels Obel artiklen"Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis."?
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