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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 100 000 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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