| 1. |
- Eimer, Johannes, et al.
(författare)
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Spiroplasma ixodetis Infections in Immunocompetent and Immunosuppressed Patients after Tick Exposure, Sweden
- 2022
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 28:8, s. 1681-1685
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Tidskriftsartikel (refereegranskat)abstract
- We report 2 cases of Spiroplasma ixodetis infection in an immunocompetent patient and an immunocompromised patient who had frequent tick exposure. Fever, thrombocytopenia, and increased liver aminotransferase levels raised the suspicion of anaplasmosis, but 16S rRNA PCR and Sanger sequencing yielded a diagnosis of spiroplasmosis. Both patients recovered after doxycycline treatment.
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| 2. |
- Aberšek, Nina, et al.
(författare)
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Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study
- 2022
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Ingår i: European Journal of Obstetrics & Gynecology and Reproductive Biology. - : Elsevier BV. - 1872-7654 .- 0301-2115. ; 272, s. 24-29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study design: Seventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. Results: Women with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. Conclusions: Calprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.
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| 3. |
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| 4. |
- Dadgar, A., et al.
(författare)
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Fever of unknown origin in a multiple sclerosis patient on immunomodulatory therapy was due to neoehrlichiosis
- 2017
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Ingår i: Läkartidningen. - 0023-7205. ; 114:38
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Tidskriftsartikel (refereegranskat)abstract
- The emerging tick-borne bacterium Candidatus Neoehrlichia mikurensis is the etiologic agent of neoehrlichiosis, a febrile illness that may be accompanied by vascular complications. Severe cases of neoehrlichiosis have been described in patients with hematologic malignancies and systemic rheumatic diseases. We present the first case of neoehrlichiosis in a patient with multiple sclerosis undergoing rituximab therapy. © 2017, Swedish Medical Association. All rights reserved.
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| 5. |
- Darsalia, Vladimer, et al.
(författare)
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Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats
- 2012
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Ingår i: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 122:9-10, s. 473-483
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is a strong risk factor for premature and severe stroke. The GLP-IR (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto-Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 mu g/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2-4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-IR agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions.
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| 6. |
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| 7. |
- Grankvist, Anna
(författare)
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Candidatus Neoehrlichia mikurensis - a new agent of tick-borne infectious disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- “Candidatus Neoehrlichia mikurensis” (Ca. N. mikurensis) is a tick-borne bacterial pathogen that can cause disease particularly among immune compromised persons. This new infectious disease is called neoehrlichiosis. The clinical picture of neoehrlichios is characterized by fever, migrating pain, and vascular/thromboembolic complications. The bacterium received its name in 2004, after its discovery in ticks and rodents on the Japanese island of Mikura. This thesis have four main aims 1) Map this new infectious disease with respect to what types of patients that are afflicted, the clinical picture displayed by the patient categories, and the pattern of laboratory findings seen in infected patients. This is described in paper I; where clinical data of six patients participating in the “NEO-VÄST study” are described together with additional cases from Europe. 2) Determine if Ca. N. mikurensis is an opportunist that only afflicts immune compromised patients? In paper II we describe two immune competent patients who had raised levels of Ca. N. mikurensis DNA in the blood accompanied by a cytokine response for several months. The patients were diagnosed after PCR screening of plasma samples from 102 tick-bitten persons in Sweden who participated in the Tick-Borne Disease Study called STING. A PCR assay for clinical use was developed in this study and the cytokine levels were measured with multiplex technology. 3) Establish if Ca. N. mikurensis strains in Europe vary genetically. Paper III describes the development and use of a multilocus sequence analysis (MLSA) protocol to investigate the genetic diversity of clinical Ca. N. mikurensis strains in Europe. A low genetic diversity was seen among the strains, all of which were derived from immune compromised patients. Unexpectedly, Ehrlichia ruminantium was found to be the closest relative of Ca. N. mikurensis within the family of Anaplasmataceae. 4) Perform de novo whole-genome sequenc-ing of Ca. N. mikurensis to characterize the bacterium. In paper IV we determined the complete reference genome sequence of Ca. N. mikurensis, sequenced directly from the blood of three immune suppressed patients. We also compared these sequences with those of other whole-genome sequenced relatives of Ca. N. mikurensis. The sequencing strategy relied on library preparation using a new type of technology called 10X Chromium followed by Hiseq Illumina sequencing, sequence assembly and de novo annotation. Our studies have yielded more knowledge about this anonymous emerging pathogen but much remains to be resolved, the work continues!
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| 8. |
- Grankvist, Anna, et al.
(författare)
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Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2 Persons Bitten by Ticks, Sweden
- 2015
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 21:8, s. 1462-1465
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in 102 persons bitten by ticks in Sweden. Two infected women had erythematous rashes; 1 was co-infected with a Borrelia sp., and the other showed seroconversion for Anaplasma phagocytophilum. Both patients had increased levels of Neoehrlichia DNA and serum cytokines for several months.
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| 9. |
- Grankvist, Anna, et al.
(författare)
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Infections With the Tick-Borne Bacterium "Candidatus Neoehrlichia mikurensis" Mimic Noninfectious Conditions in Patients With B Cell Malignancies or Autoimmune Diseases
- 2014
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 58:12, s. 1716-1722
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Tidskriftsartikel (refereegranskat)abstract
- Background. Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. Methods.aEuro integral We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. Results.aEuro integral The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Conclusions.aEuro integral Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists.
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| 10. |
- Grankvist, Anna, et al.
(författare)
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Multi-locus sequence analysis (MLSA) of clinical "CandidatusNeoehrlichia mikurensis" strains from Europe.
- 2015
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 53:10, s. 3126-3132
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Tidskriftsartikel (refereegranskat)abstract
- CandidatusNeoehrlichia mikurensis is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of Neoehrlichia has been studied only by comparing 16S rRNA gene and groEL operon sequences. We describe the development and use of a multi-locus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinicalNeoehrlichiastrains in Europe and their relatedness to other species within the Anaplasmataceae family.Six genes were selected:ftsZ, clpB, gatB,lipA,groEL and 16SrRNA. Each MLSA locus was amplified by real-time PCR, and the PCR-products sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed Neoehrlichia infection from Sweden (n = 9), the Czech Republic (n = 2) and Germany (n = 1) were analyzed with the MLSA protocol.Threeof the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other.One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16SrRNA,ftsZ, gatB, and groEL.According to the MLSA, Neoehrlichia is most closely related to E. ruminantium, less so to A. phagocytophilum and least to Wolbachiaendosymbiont, among the Anaplasmataceae.To conclude, three sequence types of infectious Neoehrlichia wereidentified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
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