| 1. |
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| 2. |
- Hesstvedt, Liv, et al.
(författare)
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Differences in epidemiology of candidaemia in the Nordic countries - what is to blame?
- 2017
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Ingår i: Mycoses. - : Wiley. - 1439-0507 .- 0933-7407. ; 60:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- National data from Denmark, Finland, Norway and Sweden demonstrate remarkable differences in candidaemia epidemiology. Only Denmark has reported a high incidence of 10 per 100000 inhabitants and a species shift towards increased C.glabrata candidaemias. The reasons for this development remain unclear. The aim of this study was to explore possible contributing factors for the differences in Candida epidemiology in the Nordic countries. We used public data from 2011 from Denmark, Finland, Norway and Sweden on epidemiology, demographics, health facilities, predisposing risk factors, consumption of antimicrobial drugs and fungicides in agricultural industry. Only the prevalence of haematological malignancies (P<0.001) was significantly higher in Denmark compared to the other Nordic countries. The antibacterial drug use of metronidazole, piperacillin-tazobactam, ciprofloxacin, colistin and carbapenems, and antifungal use of fluconazole in humans (P<0.001), were significantly higher in Denmark compared to the other Nordic countries (all P<0.001). Our findings suggest haematological malignancy, the use of certain antibacterial drugs and azoles in humans as possible contributing factors for the differences in Candida epidemiology. However, our results should be interpreted with caution due to the lack of long-term, case-specific data. Further studies are needed.
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| 3. |
- Johansson, Marcus, et al.
(författare)
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Significant variations in the seroprevalence of C6 ELISA antibodies in a highly endemic area for Lyme borreliosis: evaluation of age, sex and seasonal differences
- 2017
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY. - 0903-4641 .- 1600-0463. ; 125:5, s. 476-481
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to assess the seroprevalence of C6 ELISA antibodies in healthy blood donors in Kalmar County, Sweden, in relation to age, sex and time of year (peak season vs off season). In addition, we wanted to assess serological status over time in a group of C6 ELISA seropositive blood donors. Sera were collected from 273 (131 women, 142 men) blood donors in autumn 2011 and 300 (144 women, 156 men) in winter 2014. All sera were analysed in the C6 ELISA and the results were interpreted according to the manufacturers instructions. The seroprevalence was 22% (females 16%, males 28%) in 2011 and 24% (females 15%, males 33%) in 2014. The seroprevalence was significantly higher in males and increased with age. The highest seroprevalence was observed among elderly men, 60-70 years old (46% in 2011 and 52% in 2014). No significant difference was detected in seropositivity between the samples collected in winter and autumn. All (34/34) seropositive blood donors followed over time remained seropositive at follow-up after 22-29 months. C6 ELISA seroprevalence in healthy blood donors is high in Kalmar County, thereby reducing the specificity of a positive test result regarding the clinical diagnosis of Lyme borreliosis (LB). Although C6 seroprevalence appears not to be affected by seasonal sample time, it varies greatly with age and sex. A careful evaluation of pre-test probability is therefore of the utmost importance in the clinical diagnosis of LB, especially in elderly men. We suggest that colleagues in other endemic regions also consider initiating similar evaluations to optimize the laboratory and clinical diagnosis of LB in relation to age and sex.
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| 4. |
- Baunwall, Simon Mark Dahl, et al.
(författare)
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The use of Faecal Microbiota Transplantation (FMT) in Europe : A Europe-wide survey
- 2021
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.Methods: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.Findings: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.Interpretation: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.Funding: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).
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| 5. |
- Björkqvist, Olle, 1993-, et al.
(författare)
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Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection
- 2021
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.
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| 6. |
- Carlsson, Hanna, et al.
(författare)
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Cell-Mediated Proteomics, and Serological and Mucosal Humoral Immune Responses after Seasonal Influenza Immunization: Characterization of Serological Responders and Non-Responders
- 2024
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Ingår i: Vaccines. - : MDPI. - 2076-393X. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Immunization against influenza through vaccination is the most effective method with which to prevent infection. To assess protection after immunization, analysing humoral response with a hemagglutinin inhibition assay is the gold standard, but cell-mediated immune response has been shown to better correlate with protection in the elderly. Our aim was to explore the influenza-specific cell-mediated and mucosal humoral responses in serologically defined responders and non-responders. We analysed sera for total immunoglobulins (Ig) A, G, and M and nasal swab samples for influenza-specific IgA. Peripheral blood mononuclear cells were stimulated with trivalent influenza vaccine VaxiGripTetra, and supernatants were analysed for influenza-specific responses with the Olink Immune-Oncology panel using a proximity extension assay. We included 73 individuals, of which 69 completed the study with follow-up sampling at one and six months post-vaccination. Of the 73, 51 (70%) were found to be serological responders and 22 (30%) were non-responders. We did not find any significant differences in sex or mucosal humoral response between responders and non-responders; however, a higher IFN gamma/IL-10 ratio in individuals <= 65 years of age indicates an enhanced cell-mediated immune response in this age group. Characteristics of the non-responders were found to be higher levels of IgM, Granzyme B and Interleukin 12, and lower levels of C-X-C motif chemokine 13 compared with those of the responders. In conclusion, our results did not show any correlation between serological response and age. Furthermore, the majority of influenza-specific cell-mediated immune markers did not differ between responders and non-responders; the immune marker profile of the non-responders and its contribution to protection is of interest but needs to be further explored.
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| 7. |
- Crisci, Elisa, et al.
(författare)
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Complement opsonization promotes HSV-2 infection of human dendritic cells
- 2016
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Ingår i: Journal of Virology. - : American society of microbiology. - 0022-538X .- 1098-5514. ; 90:10, s. 4939-4950
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Tidskriftsartikel (refereegranskat)abstract
- Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.
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| 8. |
- Hagbom, Marie, et al.
(författare)
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Replication in Human Intestinal Enteroids of Infectious Norovirus from Vomit Samples
- 2021
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 27:8, s. 2212-2214
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Tidskriftsartikel (refereegranskat)abstract
- A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.
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| 9. |
- Jonsson, Nina, et al.
(författare)
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Aichi virus infection in elderly people in Sweden.
- 2012
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Ingår i: Archives of Virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 157:7, s. 1365-1369
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Tidskriftsartikel (refereegranskat)abstract
- Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.
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| 10. |
- Kalsum, Sadaf, 1977-
(författare)
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Characterizing phenotypes of Mycobacterium tuberculosis and exploring anti-mycobacterial compounds through high content screening
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB), an airborne disease and one of the top 10 causes of death globally, is caused by Mycobacterium tuberculosis (Mtb). Current standard therapy for TB treatment includes multiple drugs for a period of at least 6 months. The long therapy duration is to sterilize a small sub-population of drug-tolerant bacteria, a characteristic related to biofilm formation, which otherwise responsible for disease relapse. On the other hand, because of such a long treatment period, patient adherence to therapy becomes difficult, which results in the emergence of multidrug-resistant (MDR) or, in worst cases, extensively drug-resistant (XDR)-TB. TB is primarily a disease of lungs and alveolar macrophages are one of the first host cell types to encounter Mtb following aerosol transmission. A well-established role of macrophages in immune defense is phagocytosis, but recent studies also demonstrated that upon interaction with large aggregates of microbes or cord-forming mycobacterial species, macrophages could produce extracellular traps known as macrophage extracellular traps (METs). METs have a DNA backbone with embeds histones and could trap a wide range of microorganisms, but may or may not be able to kill them. Natural products are always a promising starting point for drug discovery because of their wide range of activity. A large number of world’s population is still using extracts from different parts of plants as the primary source of medicines against diseases including TB. Today much effort is being invested by academia in screening campaigns that allows for fast discovery of new active compounds. Thanks to the use of automated technology such as automated microscopy or automated image analysis (known as high content screening, HCS) phenotypic drug discovery has become easier to perform. Therefore, the identification of highly effective compounds to combat infectious diseases like TB can be facilitated by the use of host-pathogen assays at the early stages of drug screening studies.This thesis describes the characterization and antibiotic sensitivity of different phenotypes of Mtb namely planktonic, cord-forming and biofilm-producing phenotypes that arise due to different culture conditions. The culture of Mtb with a high percentage of a detergent (Tween-80) and standing condition promoted planktonic phenotype while a culture with a low amount of Tween-80 and more aeration due to shaking promoted cording and biofilm phenotypes. Primary human macrophages upon interaction with the shaken culture of wild-type Mtb died by releasing METs. Whereas, the shaken cultures of early secreted antigenic target-6 (ESAT-6), an important virulence factor of Mtb, deletion mutant strain could not induce MET formation showing that the cord formation is related to virulence. Moreover, the biofilm phenotype of Mtb is more tolerant to two first-line antibiotics isoniazid (INH) and rifampicin (RIF) as compared to cording and planktonic phenotypes which demand a search of more effective TB therapy. A screening campaign based on a whole-cell assay using different ethanolic crude extracts of many African plants lead to the discovery of a hit, i.e., a chloroform fraction of Khaya senegalensis bark, which showed non-significant inhibition of intracellular growth of a virulent strain of Mtb was selected for further purification and evaluation. Lastly, we have also developed and validated an HCS assay to explore new compounds against intracellular Mtb in human macrophages. INH and RIF, which were found most effective in our system were used in a combination as a positive control to calculate a Z’ factor value, which confirmed our assay to be suitable for HCS.In conclusion, this thesis not only highlights the biology of TB infection, but also discusses the development of a pathophysiologically relevant assay that can be used in the identification of novel compound(s) that has either direct anti-mycobacterial activity (antibiotic), acts by stimulating the host cell immune mechanisms (immunomodulator) or acts by counteracting virulence factors (virulence blocker).
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| 11. |
- Klingspor, L., et al.
(författare)
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Epidemiology of fungaemia in Sweden: A nationwide retrospective observational survey
- 2018
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Ingår i: Mycoses. - : Wiley. - 0933-7407 .- 1439-0507. ; 61:10, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates to identify the epidemiology and antifungal susceptibilities of Candida spp. among blood culture isolates in Sweden. MethodsThe study was a retrospective, observational nationwide laboratory-based surveillance for fungaemia and fungal meningitis and was conducted from September 2015 to August 2016. ResultsIn total, 488 Candida blood culture isolates were obtained from 471 patients (58% males). Compared to our previous study, the incidence of candidaemia has increased from 4.2/100000 (2005-2006) to 4.7/100000 population/year (2015-2016). The three most common Candida spp. isolated from blood cultures were Candida albicans (54.7%), Candida glabrata (19.7%) and species in the Candida parapsilosis complex (9.4%). Candida resistance to fluconazole was 2% in C.albicans and between 0% and 100%, in non-albicans species other than C.glabrata and C.krusei. Resistance to voriconazole was rare, except for C.glabrata, C.krusei and C.tropicalis. Resistance to anidulafungin was 3.8% while no Candida isolate was resistant to amphotericin B. ConclusionsWe report an overall increase in candidaemia but a minor decrease of C.albicans while C.glabrata and C.parapsilosis remain constant over this 10-year period.
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| 12. |
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| 13. |
- Larsson, Jenny, 1974-, et al.
(författare)
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Involvement of the ß2-integrin CD18 in apoptosis signal transduction in human neutrophils
- 2000
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1023-3830 .- 1420-908X. ; 49:9, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- Objective and design: To examine the hypothesis that an accelerated rate of neutrophil apoptosis occurs following β2-integrin activation, and further investigate the signal transduction pathways involved.Material: Human polymorphonuclear neutrophils.Treatment: Neutrophils were challenged with pansorbins coated with antibodies towards the β2-integrin subunit CD18 in a proportion of 1:100 with or without the inhibitors diphenylene iodonium (10 M), cytochalasin B (5 μg/ml), genistein (10 nM), herbimycin A (10 M) and Z-VAD-FMK (10 μM).Methods: Measurement of phosphatidylserine exposure and DNA fragmentation in flow cytometry and assessment of H2O2-production through spectrofluorometry. The results were analysed using Mann Whitney U test and Kruskal Wallis.Results: Pansorbins coated with antibodies to CD18 induce apoptosis in neutrophils (p < 0.01), and activate the production of reactive oxygen species (p < 0.01). Pre-treatment with the inhibitors have no effect on anti-CD18 induced apoptosis.Conclusion: Anti-CD18 pansorbins induce apoptosis in neutrophils through an alternative pathway not involving reactive oxygen species and independent of tyrosine phosphorylation, cytoskeletal reorganisation and caspases.
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| 14. |
- Larsson, Marie C., et al.
(författare)
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Rapid identification of pneumococci, enterococci, beta-haemolytic streptococci and S. aureus from positive blood cultures enabling early reports
- 2014
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 14:146
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The aim of this study was to evaluate diagnostic tests in order to introduce a diagnostic strategy to identify the most common gram-positive bacteria (pneumococci, enterococci, β-haemolytic streptococci and S. aureus) found in blood cultures within 6 hours after signalling growth.METHODS:The tube coagulase test was optimized and several latex agglutination tests were compared and evaluated before a validation period of 11 months was performed on consecutive positive blood culture patient samples from Kalmar County Hospital, Sweden.RESULTS:During the validation period 150 (91%) of a total of 166 gram-positive cocci (119 in clusters, 45 in chains or pairs and 2 undefined morphology) were correctly identified as S. aureus, CoNS, Pneumococci, Enterococci or group A streptococci (GAS), group B streptococci (GBS), group G streptococci (GGS) within 6 hours with a minimal increase in work-load and costs. The remaining samples (9%) were correctly identified during the next day. No samples were incorrectly grouped with this diagnostic strategy and no patient came to risk by early reporting.CONCLUSION:A simple strategy gives reliable and cost-effective reporting of >90% of the most common gram-positive cocci within 6 hours after a blood cultures become positive. The high specificity of the tests used makes preliminary reports reliable. The reports can be used to indicate the focus of infection and not the least, support faster administration of proper antimicrobial treatment for patients with serious bacterial infections.
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| 15. |
- Lindmark, Maria, 1972-, et al.
(författare)
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Synaptotagmin II could confer Ca(2+) sensitivity to phagocytosis in human neutrophils.
- 2002
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Ingår i: Biochimica et biophysica acta. - 0006-3002. ; 1590:1-3, s. 159-166
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Tidskriftsartikel (refereegranskat)abstract
- Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent processes. The calcium requirements vary between granule types, suggesting the presence of different calcium sensors. The synaptotagmins, a family of calcium-binding proteins, previously shown to participate in vesicle fusion and vesicle recycling in excitable cells, are putative calcium-sensors of exocytosis in excitable cells. In this study, we show that synaptotagmin II is present in human neutrophils and may participate in phagocytic and in exocytotic processes. In protein extracts from human neutrophils, we identified synaptotagmin II by Western blot as an 80 kDa protein. Subcellular fractionation revealed that synaptotagmin II was associated with the specific granules. In fMLP-stimulated cells, synaptotagmin II translocated to the plasma membrane. This correlated with the upregulation of complement receptor 3 (CR 3), reflecting the translocation of specific granules to the cell surface. Synaptotagmin II also translocated to the phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP-1 translocated in parallel but probably was located to another subcellular compartment than synaptotagmin II. Under calcium-reduced conditions, neither synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in neutrophils.
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| 16. |
- Löfgren, Ragnhild, et al.
(författare)
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CR3, FcγRIIA and FcγRIIIB induce activation of the respiratory burst in human neutrophils : the role of intracellular Ca2+, phospholipase D and tyrosine phosphorylation
- 1999
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889 .- 1879-2596. ; 1452:1, s. 46-59
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Tidskriftsartikel (refereegranskat)abstract
- Human neutrophils express two different types of phagocytic receptors, complement receptors (CR) and Fc receptors. In order to characterize the different signaling properties of each receptor we have used non-adherent human neutrophils and investigated CR3, FcγRIIA and FcγRIIIB for their signaling capacity. Selective activation of each receptor was achieved by coupling specific antibodies to heat-killed Staphylococcus aureus particles, Pansorbins, through their Fc moiety. Despite the fact that these particles are not phagocytosed, we show that addition of Pansorbins with anti-CD18 antibodies recognizing CR3 induced prominent signals leading to a respiratory burst. Stimulation with anti-FcγRIIIB Pansorbins induced about half of the response induced by anti-CR3 Pansorbins, whereas anti-FcγRIIA Pansorbins induced an even weaker signal. However, FcγRIIA induced strong phosphorylation of p72syk whereas FcγRIIIB induced only a very weak p72syk phosphorylation. During CR3 stimulation no tyrosine phosphorylation of p72syk was seen. Both phospholipase D and NADPH oxidase activities were dependent on intracellular calcium. This is in contrast to tyrosine phosphorylation of p72syk that occurred even in calcium-depleted cells, indicating that oxygen metabolism does not affect p72syk phosphorylation. Inhibitors of tyrosine phosphorylation blocked the respiratory burst induced by both FcγRIIA and FcγRIIIB as well as CR3. This shows that tyrosine phosphorylation of p72syk is an early signal in the cascade induced by FcγRIIA but not by CR3.
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| 17. |
- Magnusson, Cecilia, 1971-, et al.
(författare)
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Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality
- 2022
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Ingår i: Emerging Microbes & Infections. - : Taylor & Francis. - 2222-1751. ; 11:1, s. 850-859
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Tidskriftsartikel (refereegranskat)abstract
- This study describe a large nosocomial outbreak of Clostridioides difficile infections (CDI) dominated by ribotype (RT) 046 in a Swedish hospital. The aim of the present study was to examine the pathogenicity of this RT, explore epidemiological links by whole genome sequencing (WGS) and evaluate different interventions implemented to stop the outbreak. Clinical isolates (n= 366) collected during and after the outbreak were ribotyped and 246 isolates were subjected to WGS. Medical records of patients infected with the seven most common RTs were evaluated. RT046 was spread effectively throughout the hospital and was the most common among the 44 different RTs found (114/366 isolates). Infection with RT046 was associated with higher mortality compared to other strains (20.2% to 7.8%), although there were no differences in concomitant disease, age or antibiotic treatment. In order to control the outbreak, a number of measures were successfully implemented.
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| 18. |
- Nguyen, Minh Vu Chuong, et al.
(författare)
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Quinone compounds regulate the level of ROS production by the NADPH oxidase Nox4
- 2013
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Ingår i: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839. ; 85:11, s. 1644-1654
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Tidskriftsartikel (refereegranskat)abstract
- NADPH oxidase Nox4 is expressed in a wide range of tissues and plays a role in cellular signaling by providing reactive oxygen species (ROS) as intracellular messengers. Nox4 oxidase activity is thought to be constitutive and regulated at the transcriptional level; however, we challenge this point of view and suggest that specific quinone derivatives could modulate this activity. In fact, we demonstrated a significant stimulation of Nox4 activity by 4 quinone derivatives (AA-861, tBuBHQ tBuBQ and duroquinone) observed in 3 different cellular models, HEK293E, T-REx (TM), and chondrocyte cell lines. Our results indicate that the effect is specific toward Nox4 versus Nox2. Furthermore, we showed that NAD(P)H:quinone oxidoreductase (NQO1) may participate in this stimulation. Interestingly, Nox4 activity is also stimulated by reducing agents that possibly act by reducing the disulfide bridge (Cys226, Cys270) located in the extracellular E-loop of Nox4. Such model of Nox4 activity regulation could provide new insight into the understanding of the molecular mechanism of the electron transfer through the enzyme, i.e., its potential redox regulation, and could also define new therapeutic targets in diseases in which quinones and Nox4 are implicated.
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| 19. |
- Rondahl, E., et al.
(författare)
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The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer
- 2014
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 60:2, s. 172-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination. Objectives: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting. Study design: In the present study, known HCV RNA positive (n= 149) and negative (n= 149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination. Results: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33. IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low. Conclusions: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000. IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity. © 2014 The Authors.
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| 20. |
- Scheer, Vendela, et al.
(författare)
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Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure
- 2021
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Ingår i: Journal of shoulder and elbow surgery. - : MOSBY-ELSEVIER. - 1058-2746 .- 1532-6500. ; 30:6, s. 1316-1323
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Most surgical site infections after shoulder surgery are caused by Cutibacterium acnes. Topically applied benzoyl peroxide (BPO) has for years been used to decrease the skin load of C acnes in treatment of acne vulgaris. The purpose of this study was to examine this effect on bacterial colonization in patients subjected to elective shoulder surgery at different stages of the procedure. Methods: A total of 100 patients scheduled for primary elective open shoulder surgery were randomized to prepare either with BPO or according to local guidelines-with soap (control group). Four skin swabs were taken in a standardized manner at different times, before and after surgical skin preparation, 1 in dermis, and finally after the skin was sutured. Before skin incision, 5 punch biopsies (3 mm in diameter and maximum 4 mm deep) were retrieved spaced 2 cm apart in the planned skin incision. On culturing, quantification of C acnes was made by serial dilutions. Results: Men had a 5-fold higher amount of C acnes on untreated skin. Treatment with BPO considerably lowered this count (P = .0001 both before and after skin disinfection compared to the control group. This positive effect of BPO persisted until skin closure, the point at which some recolonization of C acnes had occurred, but to a higher degree in the control group (P = .040). Conclusion: Preoperative BPO treatment of the shoulder may be an effective method to decrease bacterial skin load of C acnes from skin incision until wound closure. (C) 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
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| 21. |
- Scheer, Vendela, 1967-
(författare)
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Perioperative Strategies to Prevent Surgical Site Infection After Shoulder Surgery
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden, about 18 000 patients undergo shoulder surgery each year. The current surgical site infection (SSI) rate after planned shoulder surgery is 0,3-5 %, which means that approximately 300 people are affected each year in Sweden. Treatment of deep SSIs always involves at least one reoperation followed by long-lasting treatment with antibiotics. In addition to pain and reduced mobility, an SSI can also have a negative effect on mental health. It is not possible to pinpoint exactly what causes an SSI. However, in today´s modern operating theatres with ultra clean air, tightly woven gowns, and surgical practice that strictly adheres to aseptic guidelines, SSIs after orthopaedic surgery are predominately caused by bacteria from the patient’s skin.The aim of this thesis was to evaluate perioperative strategies to prevent surgical site infection after shoulder surgery, focusing on bacterial burden on the skin. Cutibacterium acnes (C. acnes), a skin commensal, thrives in the sebaceous glands and causes most infections after shoulder surgery. Despite strict standardised preoperative preparation with 0.5% chlorhexidine solution in 70% ethanol, studies have shown that C. acnes are only partially eradicated. Topical treatment with benzoyl peroxide (BPO) over several months has been used to treat acne vulgaris for more than 50 years.In two randomised studies, we compared prophylactic topical treatment with BPO (applied five times over a period of 48 hours before surgery), with a control group with no BPO treatment. In the BPO group, the burden of C. acnes prior to incision and at the end of the surgery decreased significantly.When studying the effects of skin preparation, the technique and method used to capture the microbiome while maintaining the skin’s barrier, is crucial. In a pilot study, we developed a novel Pencil Eraser Swab-technique (PES) and compared this with two established swab techniques. The PES-technique was found to be significantly better, both in terms of sensitivity in detecting C. acnes and in quantification of viable bacteria.Following closure of a surgical incision, the wound is re-epithelialised within 24-72 hours. Choice of dressing is usually a question of personal preference and tradition rather than evidence based. The degree of colonisation of bacteria beneath wound dressings with different occlusive properties is not known. To investigate this, we compared three wound dressings of varying permeability on healthy skin. After 48 hours we found that recolonisation of bacteria was significantly higher beneath the semipermeable and occlusive wound dressings, than beneath the airy (gauze) dressing.Perioperative reduction of the bacterial burden on the skin is important in the fight against surgical site infection. A reliable technique to capture bacteria is essential when evaluating different methods.
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| 22. |
- Scheer, Vendela, 1967-, et al.
(författare)
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The pencil eraser swab technique to quantify Cutibacterium acnes on shoulder skin
- 2021
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Ingår i: Journal of Bone and Joint Infection. - Göttingen, Germany : Copernicus publications. - 2206-3552. ; 6:9, s. 451-456
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Cutibacterium acnes is the most common cause of postoperative infections in orthopaedic shoulder surgery and is hard to eradicate with current measures. Newer strategies focus on reducing bacterial load on the skin before surgery. Several previous studies have used a large number of both described and undescribed sampling techniques. The purpose of this study was to compare three previously described swab techniques to obtain bacterial cultures: Levine's (L) technique, the Z technique and the pencil eraser swab (PES) technique. Methods: Three consecutive skin swabs were collected from the right shoulder, on 15 healthy male volunteers, using Levine's technique, Z technique and PES technique from each participant. To determine the number of living bacteria, serial dilutions were made, and after culturing for 5 d, viable count (VC) was expressed as CFU/mL (with CFU representing colony-forming unit). Results: The PES technique yielded significantly higher VC than the two others. PES: median 3700 CFU/mL, L: 200 CFU/mL and Z: 220 CFU/mL ( p=0.003). There was no significant difference between the methods regarding the number of positive cultures. PES: 14/15, L: 11/15 and Z: 12/15. Conclusions: There is a need to harmonise sampling techniques of C. acnes in order to compare the efficacy of different measures to reduce the bacterial load on the skin before and during surgery. Of the three tested methods, the PES technique is simple and produces the highest bacterial counts.
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| 23. |
- Scheer, Vendela, et al.
(författare)
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Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes: a randomized study
- 2018
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Ingår i: Journal of shoulder and elbow surgery. - : MOSBY-ELSEVIER. - 1058-2746 .- 1532-6500. ; 27:6, s. 957-961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Propionibacterium acnes is a common cause of infection following shoulder surgery. Studies have shown that standard surgical preparation does not eradicate P acnes. The purpose of this study was to examine whether topical application of benzoyl peroxide (BPO) gel could decrease the presence of P acnes compared with todays standard treatment with chlorhexidine soap (CHS). We also investigated and compared the recolonization of the skin after surgical preparation and draping between the BPO- and CHS-treated groups. Methods: In this single-blinded nonsurgical study, 40 volunteers-24 men and 16 women-were randomized to preoperative topical treatment at home with either 5% BPO or 4% CHS on the left shoulder at the area of a deltopectoral approach. Four skin swabs from the area were taken in a standardized manner at different times: before and after topical treatment, after surgical skin preparation and sterile draping, and 120 minutes after draping. Results: Topical treatment with BPO significantly reduced the presence of P acnes measured as the number of colony-forming units on the skin after surgical preparation. P acnes was found in 1 of 20 subjects in the BPO group and 7 of 20 in the CHS group (P = .044). The results remained after 2 hours (P = .048). Conclusion: Topical preparation with BPO before shoulder surgery may be effective in reducing P acnes on the skin and preventing recolonization. Conclusion: Topical preparation with BPO before shoulder surgery may be effective in reducing P acnes on the skin and preventing recolonization. (C) 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
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| 24. |
- Serrander, Lena
(författare)
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Neutrophil phagocytosis and secretion : The role of calcium and the cytoskeleton
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neutrophils assure rapid removal of bacteria by a variety of processes. They crawl out of the vessels, phagocytose the bacteria and kill them by secretion of bactericidal substances and production of oxidative metabolites. The aims of this study were to investigate the signalling pathways during these processes, in particular i) how complement receptors mediate phagocytosis and NADPH~oxidase activity ii) the role of Ca2+ in secretion and the role of a Ca2+-dependent, actin-binding protein, _gelsolin, in neutrophil phagocytosis and secretion. Conventional biochemical methods, capacitance measurements of secretion with the patchclamp technique and visualisation with fluorescence microscopy techniques were used. We found that phospholipase D (PLD) is an early Ca2+-independent signal in complementmediated phagocytosis, preceding cytoskeletal rearrangements. We also demonstrated'that the NADPH-oxidase could be activated in situ to generate oxidative metabolites intracellularly after particle stimulation of complement receptors in the absence of phagocytosis. This permits cells to use oxidative metabolites for signalling and not only to kill bacteria. This activation involved the cytoskeleton and PLD. Whereas signalling during pha~ocytosis can occur independently of Ca2+, other neutrophil functions are highly Ca +-dependent. Investigating the relative importance of Ca2+-release from intracellular stores versus Ca2+ influx over the plasma membrane, we found that secretion of primary granules induced by fMLP is dependent on Ca2+ -influx. ci+-influx alone is not sufficient to induce secretion in neutrophils. A second synergistic signal is required. This missing signal was not PLD, PLC or tyrosine kinases, but involved a pertussis-sensitive 0-protein and PI3-kinase. When further investigating the role of Ca2+ in secretion, we found that secretion of different granules is regulated by different [Ca2+:J. Primary granules are secreted at 100 ~ Ca2+ whereas the other granules are secreted at 1.5-5 ~ ci+, suggesting two mechanisms involving different Ca2+ activated systems/sensor proteins. One sensor protein could be the Ca2+-dependent, actinbinding protein, gelsolin, which has earlier been shown to stimulate secretion in different celltypes. Secretion from gelsolin-deficient mouse neutrophils was nevertheless nonnal. Gelsolin was however found to be essential for !gO-mediated-, but not complement-induced phagocytosis. Activation of the oxidase and phagolysosorne-fusion was unaffected in gelsolin-deficient neutrophils. This suggests gelsolin to be a Ca2+ -sensor specifically for !gOmediated phagocytosis. !gO-mediated phagocytosis often leads to more efficient killing than complement-mediated phagocytosis. Gelsolin seems to be part of the machinery that distinguishes the two pathways of phagocytosis. The present data show that receptor mediated activation of neutrophil functions involves several signalling pathways. This allows selective modulation of the inflammatory response.
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| 25. |
- Serrander, Lena, et al.
(författare)
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Particles binding β2-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis
- 1999
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Ingår i: Biochimica et Biophysica Acta. Molecular Cell Research. - 0167-4889 .- 1879-2596. ; 1452:2, s. 133-144
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Tidskriftsartikel (refereegranskat)abstract
- Complement-opsonised particles are readily ingested by human neutrophils through a complement receptor-mediated process leading to phagolysosome fusion and production of oxidative metabolites. To investigate the complement receptor 3 (CR3)-associated signal system involved, cells were challenged with protein A-positive, heat-killed Staphylococcus aureus to which antibodies with specificity for the subunits of the β2-integrins, i.e. anti-CD11b (the α subunit of CR3) and anti-CD18 (the β subunit of CR3), were bound through their Fc moiety. Despite not being ingested by the neutrophils, the surface associated anti-CD18- and anti-CD11b-coated particles were able to activate the neutrophil NADPH-oxidase. Also anti-CD11a- (the α subunit of LFA-1) and to a lesser extent anti-CD11c- (the α subunit of CR4) coated particles were able to trigger the NADPH-oxidase. The NADPH-oxidase was activated without extracellular release of reactive oxygen species. The activity was inhibited by cytochalasin B, suggesting a necessary role for the cytoskeleton in the signalling pathway that activates the oxidase. We show that particle-mediated cross-linking of β2-integrins on the neutrophil surface initiates a signalling cascade, involving cytoskeletal rearrangements, leading to an activation of the NADPH-oxidase without phagosome formation or extracellular release of reactive oxygen species.
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| 26. |
- Serrander, Lena, et al.
(författare)
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Selective Inhibition of IgG-Mediated Phagocytosis in Gelsolin-Deficient Murine Neutrophils
- 2000
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 165:5, s. 2451-2457
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Tidskriftsartikel (refereegranskat)abstract
- Phagocytosis and the microbicidal functions of neutrophils require dynamic changes of the actin cytoskeleton. We have investigated the role of gelsolin, a calcium-dependent actin severing and capping protein, in peripheral blood neutrophils from gelsolin-null (Gsn−) mice. The phagocytosis of complement opsonized yeast was only minimally affected. In contrast, phagocytosis of IgG-opsonized yeast was reduced close to background level in Gsn− neutrophils. Thus, gelsolin is essential for efficient IgG- but not complement-mediated phagocytosis. Furthermore, attachment of IgG-opsonized yeast to Gsn− neutrophils was reduced (∼50%) but not to the same extent as ingestion (∼73%). This was not due to reduced surface expression of the Fcγ-receptor or its lateral mobility. This suggests that attachment and ingestion of IgG-opsonized yeast by murine neutrophils are actin-dependent and gelsolin is important for both steps in phagocytosis. We also investigated granule exocytosis and several steps in phagosome processing, namely the formation of actin around the phagosome, translocation of granules, and activation of the NADPH-oxidase. All these functions were normal in Gsn− neutrophils. Thus, the role of gelsolin is specific for IgG-mediated phagocytosis. Our data suggest that gelsolin is part of the molecular machinery that distinguishes complement and IgG-mediated phagocytosis. The latter requires a more dynamic reorganization of the cytoskeleton.
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| 27. |
- Simon, Rozalyn, 1979-, et al.
(författare)
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Magnetotactic bacteria from the human gut microbiome associated with orientation and navigation regions of the brain
- 2021
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Ingår i: Journal of Oceanology and Limnology. - : Springer Nature. - 2096-5508 .- 2523-3521. ; 39:6, s. 2044-2052
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Tidskriftsartikel (refereegranskat)abstract
- Magnetotactic bacteria (MTB), ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals. MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields. Similar magnetite deposits have been found throughout the tissues of the human brain, including brain regions associated with orientation such as the cerebellum and hippocampus, the origins of which remain unknown. Speculation over the role and source of MTB in humans, as well as any association with the brain, remain unanswered. We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions. We identified seven MTB in the human gut microbiome: Magnetococcus marinus, Magnetospira sp. QH-2, Magnetospirillum magneticum, Magnetospirillum sp. ME-1, Magnetospirillum sp. XM-1, Magnetospirillum gryphiswaldense, and Desulfovibrio magneticus. Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus (adjusted for total intracranial volume, uncorrected P<0.05). These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation. These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans. Further studies will be necessary to validate and elucidate the relationship between these bacteria, magnetite concentrations, and brain function.
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| 28. |
- Sundbom, Per, 1981-, et al.
(författare)
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Progressive multifocal leukoencephalopathy after heart transplantation: 4 years of clinically stable infection on low-dose immunosuppressive therapy
- 2017
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Ingår i: Oxford Medical Case Reports. - : Oxford Academic. - 2053-8855. ; 2017:2, s. 15-17
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Tidskriftsartikel (refereegranskat)abstract
- Progressive multifocal leukoencephalopathy (PML), caused by reactivation of JC-virus is a relatively rare complication seen in patients with compromised immune system. There are no evidence-based treatment available and prognosis is poor. Withdrawal of immunosuppressant can result in further neurological deterioration and for patients with solid organ transplantations, fatal graft rejection. We report a 52-year-old women that presented with seizures within 1 month after heart transplantation. Initial diagnosis was vascular disease. After clinical deterioration 10 months after transplantation, further examinations led to the diagnosis. Minimizing tacrolimus, to a concentration of 2 ng/ml, and extensive physical therapy has improved the physical capacity of the patient. The patient has now been clinically stable for 4 years and extended survival for 5 years. This case adds to the limited adult cases of PML within the population of heart transplant recipients and the need for increased awareness to minimize diagnosis delay.
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| 29. |
- Sundén, Birgitta, et al.
(författare)
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Real-time PCR detection of Human Herpesvirus 1-5 in patients lacking clinical signs of a viral CNS infection
- 2011
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 11:220
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Infections of the central nervous system (CNS) with herpes- or enterovirus can be self-limiting and benign, but occasionally result in severe and fatal disease. The polymerase chain reaction (PCR) has revolutionized the diagnostics of viral pathogens, and by multiple displacement amplification (MDA) prior to real-time PCR the sensitivity might be further enhanced. The aim of this study was to investigate if herpes- or enterovirus can be detected in cerebrospinal fluid (CSF) from patients without symptoms.METHODS:Cerebrospinal fluid (CSF) samples from 373 patients lacking typical symptoms of viral CNS infection were analysed by real-time PCR targeting herpesviruses or enteroviruses with or without prior MDA.RESULTS:In total, virus was detected in 17 patients (4%). Epstein-Barr virus (EBV) was most commonly detected, in general from patients with other conditions (e.g. infections, cerebral hemorrhage). MDA satisfactorily amplified viral DNA in the absence of human nucleic acids, but showed poor amplification capacity for viral DNA in CSF samples, and did not increase the sensitivity for herpes virus-detection with our methodology.CONCLUSIONS:Viral pathogens are rarely detected in CSF from patients without signs of CNS infection, supporting the view that real-time PCR is a highly specific method to detect symptomatic CNS-infection caused by these viruses. However, EBV may be subclinically reactivated due to other pathological conditions in the CNS.
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| 30. |
- Sune, Dan, et al.
(författare)
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Optimization of 16S rRNA gene analysis for use in the diagnostic clinical microbiology service
- 2020
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Ingår i: Journal of Microbiological Methods. - : ELSEVIER. - 0167-7012 .- 1872-8359. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- Broad-range amplification and sequencing of the 16S rRNA gene, directly from clinical samples, is a method that potentially allows detection of any cultivable or non-cultivable bacteria. However, the method is prone to false positive results due to PCR contamination. Another concern is the human DNA abundance compared to bacterial DNA in samples from sterile sites. Those factors may decrease the sensitivity and specificity of the assay and can complicate the analysis and interpretation of the results. The objective of this prospective study was to try to avoid the most common pitfalls, mentioned above, and develop a molecular 16S assay with a high clinical sensitivity and specificity. Fifty-six consecutive tissue samples from patients with suspected deep infections were extracted by 3 different DNA-extraction methods; two based on a principle of bacterial DNA enrichment, and one conventional DNA extraction method. We compared three primer pairs, including both conventional and DPO principle, targeting different variable regions of the 16S rRNA gene. Results from routine tissue culture were used as reference. Clinical data was recorded from patient charts and analyzed in parallel. Of a total of 56 samples, collected from 39 patients, 70% (39 samples) were assessed as true infections by analysis of clinical data. Bacterial enrichment extraction increased sensitivity from 54% to 72%. The 2 sets of primer pairs defining region V1-V3 and V3-V4, showed similar sensitivity, but DPO-primers resulted in better specificity, i.e. less contaminations. The primer pairs covering V1-V8 show significantly lower sensitivity (p amp;lt; .001) than V1-V3 and V3-V4. Optimizing extraction protocols and choice of primers can increase the sensitivity and specificity of a molecular 16S-analysis, rendering a valuable complement to tissue culture.
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| 31. |
- Vandesande, Helena, et al.
(författare)
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Saffold virus infection in elderly people with acute gastroenteritis in Sweden
- 2021
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 93:6, s. 3980-3984
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Tidskriftsartikel (refereegranskat)abstract
- Viral gastroenteritis is a major source of morbidity and mortality, predominantly caused by so-called NOROAD viruses (norovirus, rotavirus, and adenovirus). In approximately one third of all cases, however, the exact etiology is unknown. The in 2007 discovered human cardiovirus Saffold virus (SAFV) may prove to be a plausible candidate to explain this diagnostic gap. This virus, a member of the Picornaviridae family which is closely related to the murine viruses Theiler's murine encephalomyelitis virus and Theravirus, is a widespread pathogen and causes infection early in life. Screening of 238 fecal or vomitus samples obtained from NOROAD-negative, elderly patients with acute gastroenteritis at the University Hospital of Linköping showed that SAFV is present in low abundance (4.6%). Phylogenetic analysis of the VP1 gene revealed a Swedish isolate belonging to the highly common and in Europe widespread SAFV-3 genotype. This genotype is also related to previously reported Asian strains. This study describes the first molecular typing of a Swedish SAFV isolate and is the first report to document the circulation of SAFV among elderly people. The pathogenicity of SAFV is, as of yet, still under debate; further studies are necessary to determine its role in the development of disease.
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| 32. |
- Åkerlund, Anna, et al.
(författare)
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EUCAST rapid antimicrobial susceptibility testing (RAST) in blood cultures : validation in 55 European laboratories
- 2020
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 75:11, s. 3230-3238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: When bloodstream infections are caused by resistant bacteria, rapid antimicrobial susceptibility testing (RAST) is important for adjustment of therapy. The EUCAST RAST method, directly from positive blood cultures, was validated in a multi-laboratory study in Europe.METHODS: RAST was performed in 40 laboratories in northern Europe (NE) and 15 in southern Europe (SE) from clinical blood cultures positive for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus or Streptococcus pneumoniae. Categorical results at 4, 6 and 8 h of incubation were compared with results for EUCAST standard 16-20 h disc diffusion. The method, preliminary breakpoints and the performance of the laboratories were evaluated.RESULTS: The total number of isolates was 833/318 in NE/SE. The number of zone diameters that could be read (88%, 96% and 99%) and interpreted (70%, 81% and 85%) increased with incubation time (4, 6 and 8 h). The categorical agreement was acceptable, with total error rates in NE/SE of 2.4%/4.9% at 4 h, 1.1%/3.5% at 6 h and 1.1%/3.3% at 8 h. False susceptibility at 4, 6 and 8 h of incubation was below 0.3% and 1.1% in NE and SE, respectively, and the corresponding percentages for false resistance were below 1.9% and 2.8%. After fine-tuning breakpoints, more zones could be interpreted (73%, 89% and 93%), with only marginally affected error rates.CONCLUSIONS: The EUCAST RAST method can be implemented in routine laboratories without major investments. It provides reliable antimicrobial susceptibility testing results for relevant bloodstream infection pathogens after 4-6 h of incubation.
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| 33. |
- Åkerlund, Anna, et al.
(författare)
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Short incubation of disc diffusion for Streptococcus pneumoniae and Haemophilus influenzae to reduce time to susceptibility report
- 2023
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 78:10, s. 2563-2571
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Tidskriftsartikel (refereegranskat)abstract
- Background Rapidly instituted antimicrobial therapy is important in severe infections, and reduced time to the antimicrobial susceptibility testing (AST) report is thus of importance. Disc diffusion (DD) is a cheap, rapidly adaptable, flexible and comprehensive method for phenotypic AST. Previous studies have shown that early reading of inhibition zones for non-fastidious species is possible.Objectives To evaluate zone reading after short incubation of DD in Haemophilus influenzae (n = 73) and Streptococcus pneumoniae (n = 112).Methods The readability was evaluated and susceptibility interpretation (SIR) was performed, using the EUCAST 18 & PLUSMN; 2 h incubation breakpoint table (version 12.0), after 6 and 8 h of incubation. Categorical agreement (CA) and error rates were calculated using standard DD and broth microdilution as reference.Results The proportion of readable zones in H. influenzae was 19% (6 h) and 89% (8 h). The CA was 98% after 8 h. The corresponding readability in S. pneumoniae was 63%/98% and CA was 95%/97% after 6 and 8 h, respectively. Early reading of the screening discs (benzylpenicillin 1 unit in H. influenzae and oxacillin 1 & mu;g in S. pneumoniae) correctly identified 18/22 of the H. influenzae isolates and all the readable S. pneumoniae isolates with reduced & beta;-lactam susceptibility. For non-& beta;-lactam agents, very major errors were most common for quinolones in S. pneumoniae. Introduction of areas of technical uncertainty (ATUs) reduced the error rate to & LE;1.1%.Conclusions We conclude that shortened incubation is feasible for H. influenzae and S. pneumoniae. To reduce the risk of false categorization a buffer zone (i.e. ATU) near the breakpoints must be used.
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| 34. |
- Åkerlund, Anna, et al.
(författare)
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Svarstiderna kan kortas vid mikrobiologisk diagnostik av sepsis: Bättre öppettider på laboratorier och aktiv rådgivning ger snabbare terapi
- 2015
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112:7
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Tidskriftsartikel (refereegranskat)abstract
- Snabbt insatt adekvat antibiotikabehandling är livräddande vid allvarliga bakteriella infektioner. Snabb mikrobiologisk diagnostik krävs i och med ökande antibiotikaresistens och kommer att ge medicinska vinster.En enkät till landets mikrobiologiska laboratorier visar på stora skillnader avseende tillgänglighet, snabbhet och kommunikation med svarsmottagande enhet vad gäller positiva blododlingar.För snabbare svar krävs att mikrobiologiska laboratorier erbjuder mer generösa öppettider, effektivare transportsystem och patientnära blododlingsinkubatorer samt tidig och aktiv rådgivning till behandlande läkare.n/a
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| 35. |
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