| 1. |
- Bengnér, Malin, et al.
(författare)
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Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
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Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
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| 2. |
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| 3. |
- Enkirch, Theresa, et al.
(författare)
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Molecular epidemiology of community- and hospital-associated Clostridioides difficile infections in Jönköping, Sweden, October 2017-March 2018
- 2022
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 130:11, s. 661-670
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Tidskriftsartikel (refereegranskat)abstract
- Clostridioides difficile infections (CDIs) in Sweden are mostly hospital-associated (HA) with limited knowledge regarding community-associated (CA) infections. Here, we investigated the molecular epidemiology of clinical isolates of CA-CDI and HA-CDI in a Swedish county. Data and isolates (n = 156) of CDI patients (n = 122) from Jonkoping county, October 2017-March 2018, were collected and classified as CA (without previous hospital care or onset <= 2 days after admission or >12 weeks after discharge from hospital) or HA (onset >3 days after hospital admission or within 4 weeks after discharge). Molecular characterization of isolates included PCR ribotyping (n = 156 isolates) and whole genome sequencing with single nucleotide polymorphisms (SNP) analysis (n = 53 isolates). We classified 47 patients (39%) as CA-CDI and 75 (61%) as HA-CDI. Between CA-CDI and HA-CDI patients, we observed no statistically significant differences regarding gender, age, 30-day mortality or recurrence. Ribotype 005 (RR 3.1; 95% CI: 1.79-5.24) and 020 (RR 2.5; 95% CI: 1.31-4.63) were significantly associated with CA-CDI. SNP analysis identified seven clusters (0-2 SNP difference) involving 17/53 isolates of both CA-CDI and HA-CDI. Molecular epidemiology differed between CA-CDI and HA-CDI and WGS analysis suggests transmission of CDI within and between hospitals and communities.
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| 4. |
- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 6. |
- 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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| 7. |
- Rezk, Francis, et al.
(författare)
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Healthcare professionals' experiences of being observed regarding hygiene routines: the Hawthorne effect in vascular surgery
- 2021
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Hawthorne Effect is the change in behaviour by subjects due to their awareness of being observed and is evident in both research and clinical settings as a result of various forms of observation. When the Hawthorne effect exists, it is short-lived, and likely leads to increased productivity, compliance, or adherence to standard protocols. This study is a qualitative component of an ongoing multicentre study, examining the role of Incisional Negative Pressure Wound Therapy after vascular surgery (INVIPS Trial). Here we examine the factors that influence hygiene and the role of the Hawthorne effect on the adherence of healthcare professionals to standard hygiene precautions.MethodsThis is a qualitative interview study, investigating how healthcare professionals perceive the observation regarding hygiene routines and their compliance with them. Seven semi-structured focus group interviews were conducted, each interview included a different staff category and one individual interview with a nurse from the Department for Communicable Disease Control. Additionally, a structured questionnaire interview was performed with environmental services staff. The results were analysed based on the inductive qualitative content analysis approach.ResultsThe analysis revealed four themes and 12 subthemes. Communication and hindering hierarchy were found to be crucial. Healthcare professionals sought more personal and direct feedback. All participants believed that there were routines that should be adhered to but did not know where to find information on them. Staff in the operating theatre were most meticulous in adhering to standard hygiene precautions. The need to give observers a clear mandate and support their work was identified. The staff had different opinions concerning the patient's awareness of the importance of hygiene following surgery. The INVIPS Trial had mediated the Hawthorne effect.ConclusionThe results of this study indicate that the themes identified, encompassing communication, behaviour, rules and routines, and work environment, influence the adherence of healthcare professionals to standard precautions to a considerable extent of which many factors could be mediated by a Hawthorne effect. It is important that managers within the healthcare system put into place an improved and sustainable hygiene care to reduce the rate of surgical site infections after vascular surgery.
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| 8. |
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| 9. |
- Strindhall, Jan, et al.
(författare)
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Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio
- 2016
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Ingår i: INFECTIOUS DISEASES. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 48:6, s. 436-442
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Tidskriftsartikel (refereegranskat)abstract
- Background Annual vaccination against influenza virus is generally recommended to elderly and chronically ill, but the relative importance of factors influencing the outcome is not fully understood. Methods In this study of 88 individuals all aged 69 years, the increase in haemagglutinin-inhibiting (HI) antibodies to trivalent inactivated influenza vaccine was correlated with HI titres before vaccination, prior vaccinations against influenza, cytomegalovirus serostatus and, as an estimate of immune risk profile, the ratio between CD4 + and CD8 + T cells. Results Vaccine responses were impaired by high pre-existing HI antibody titres. For influenza B repeated vaccinations and an inverse CD4/CD8 ratio had a negative impact on the vaccine response. Cytomegalovirus seropositivity had no apparent effect on HI titres before or after vaccination. Conclusions It is concluded that both pre-existing HI antibodies and previous vaccinations to influenza may influence the humoral response to influenza vaccination and that a CD4/CD8 ratio < 1 may indicate an impaired ability to respond to repeated antigenic stimulation.
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| 10. |
- Studahl, Marie, 1957, et al.
(författare)
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Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.
- 2013
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 73:2, s. 131-58
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Forskningsöversikt (refereegranskat)abstract
- Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.
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