| 1. |
- Bahnan, Wael, et al.
(författare)
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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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| 2. |
- Andersson, Tilde, et al.
(författare)
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Development of a Molecular Imprinting-Based Surface Plasmon Resonance Biosensor for Rapid and Sensitive Detection of Staphylococcus aureus Alpha Hemolysin From Human Serum
- 2020
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Stapylococcus aureus is a common infectious agent in e.g. sepsis, associated with both high mortality rates and severe long-term effects. The cytolytic protein α-hemolysin has repeatedly been shown to enhance the virulence of S. aureus. Combined with an unhindered spread of multi drug-resistant strains, this has triggered research into novel anti virulence (i.e. anti α-hemolysin) drugs. Their functionality will depend on our ability to identify infections that might be alleviated by such. We therefore saw a need for detection methods that could identify individuals suffering from S. aureus infections where α-hemolysin was a major determinant. Molecular imprinted polymers were subsequently prepared on gold coated sensor chips. Used in combination with a surface plasmon resonance biosensor, α-hemolysin could therethrough be quantified from septic blood samples (n = 9), without pre-culturing of the infectious agent. The biosensor recognized α-hemolysin with high affinity (KD = 2.75 x 10-7 M) and demonstrated a statistically significant difference (p < 0.0001) between the α-hemolysin response and potential sample contaminants. The detection scheme proved equally good, or better, when compared to antibody-based detection methods. This novel detection scheme constitutes a more rapid, economical, and user-friendly alternative to many methods currently in use. Heightening both reproducibility and sensitivity, molecular imprinting in combination with surface plasmon resonance (SPR)-technology could be a versatile new tool in clinical- and research-settings alike.
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| 3. |
- Bläckberg, Anna, et al.
(författare)
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A Population-Based Study of Unfavorable Prognostic Factors Associated With Pyogenic Liver Abscess
- 2023
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Ingår i: Open Forum Infectious Diseases. - 2328-8957. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPyogenic liver abscess (PLA) is a rare entity that is associated with substantial mortality and morbidity. Our objective was to investigate variables associated with mortality and subsequent PLA in patients diagnosed with PLA in southern Sweden.MethodsWe conducted a population-based observational study comprising all episodes of PLA that occurred between 2011 and 2020 in the county of Skåne, southern Sweden. The primary outcome was defined as all-cause 90-day mortality and the secondary outcome was defined as the occurrence of a subsequent PLA.ResultsA total of 452 episodes of PLA occurred in 360 patients during the study period. The 90-day mortality rate was 16% (n = 58) and the subsequent PLA rate was 20% (n = 92). In a multivariable logistic regression model, female sex (odds ratio [OR], 2.0 [95% confidence interval {CI}, 1.1–3.9]), malignancy (OR, 3.7 [95% CI, 1.9–7.1]), liver failure (OR, 6.3 [95% CI, 2.7–14.5]), and polymicrobial findings (OR, 3.8 [95% CI, 2.2–6.9]) were associated with death within 90 days (P < .05). Male sex (OR, 2.1 [95% CI, 1.2–3.6]), malignancy (OR, 2.1 [95% CI, 1.3–3.6]), age (64–74 years: OR, 2.5 [95% CI, 1.3–4.8]), and chronic liver disease (OR, 3.0 [95% CI, 1.4–6.5]) were associated with the risk of subsequent PLA (P ≤ .01).ConclusionsIdentifying different clinical variables associated with an unfavorable outcome may improve the management and treatment of patients with PLA and thus prevent the risk of death and subsequent PLA.
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| 4. |
- Bläckberg, Anna, et al.
(författare)
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Antibody kinetics and clinical course of COVID-19 a prospective observational study
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:3 March
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Tidskriftsartikel (refereegranskat)abstract
- Background Serological response and association to clinical manifestation is important for understanding the pathogenesis of COVID-19. Materials and methods A prospective observational study was conducted where antibody responses of IgG and IgA towards SARS-CoV-2 spike protein were studied over time in patients with COVID-19. Possible associations between antibody titers and outcome were analyzed. Results Forty patients with COVID-19, hospitalized at Skåne University hospital, Sweden, between April and June 2020 were included. IgG antibody responses were detected for all patients with the highest levels four weeks after COVID-19 diagnosis. Levels of IgA were generally higher at diagnosis and decreased towards baseline 4 weeks after confirmed COVID-19. Patients with severe COVID-19 had higher levels of antibodies directed against SARS-CoV- 2 spike protein compared with patients with mild disease. Conclusion IgG and IgA antibodies towards the spike protein follow different kinetics during COVID-19 and patients with severe disease develop higher antibody levels.
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| 5. |
- Bläckberg, Anna, et al.
(författare)
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Eubacterium bacteremia – a retrospective observational study of a seldom found anaerobic pathogen
- 2024
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Ingår i: Diagnostic Microbiology and Infectious Disease. - 1879-0070. ; 108:4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHuman infections due to Eubacterium are rare and knowledge of the condition is limited. This study aimed to describe clinical characteristics and outcome in patients with Eubacterium bacteremia.MethodsEpisodes of Eubacterium bacteremia were identified through the clinical microbiology laboratory in Lund, Sweden. Medical records were retrospectively reviewed. Blood isolates of Eubacterium were collected and antibiotic susceptibility testing was performed with agar dilution.ResultsSeventeen patients with Eubacterium bacteremia were identified of whom six had monomicrobial bacteremia. The incidence was 1.7 cases of Eubacterium bacteremia per million inhabitants and year. The median age was 67 years (interquartile range 63-79 years), and six patients had some form of malignancy. Most of the patients an abdominal focus of infection and the 30-day mortality was low (n=1).ConclusionsInvasive infections with Eubacterium have a low incidence. The condition has a low mortality and an abdominal focus of infection, and malignancy, is common.
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| 6. |
- Bläckberg, Anna, et al.
(författare)
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Infective endocarditis caused by HACEK group bacteria—a registry-based comparative study
- 2021
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 40:9, s. 1919-1924
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Tidskriftsartikel (refereegranskat)abstract
- Infective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low.
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| 7. |
- Bläckberg, Anna, et al.
(författare)
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Infective Endocarditis Due to Corynebacterium Species : Clinical Features and Antibiotic Resistance
- 2021
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Corynebacterium species are often dismissed as contaminants in blood cultures, but they can also cause infective endocarditis (IE), which is a severe condition. Antibiotic resistance of corynebacteria is increasing making treatment challenging. Reports on IE caused by Corynebacterium species are scarce and more knowledge is needed. Methods: Cases of IE caused by Corynebacterium species were identified through the Swedish Registry of Infective Endocarditis. Isolates were collected for species redetermination by matrix-assisted laser desorption ionization-time of flight and for antibiotic susceptibility testing using Etests. Results: Thirty episodes of IE due to Corynebacterium species were identified between 2008 and 2017. The median age of patients was 71 years (interquartile range, 60-76) and 77% were male. Corynebacterium striatum (n = 11) was the most common IE causing pathogen followed by Corynebacterium jeikeium (n = 5). Surgery was performed in 50% and in-hospital mortality rate was 13%. Patients with IE caused by Corynebacterium species were significantly more likely to have prosthetic valve endocarditis (70%), compared with patients with IE due to Staphylococcus aureus or non-beta-hemolytic streptococci (14% and 26%, respectively) (P <. 0001). Vancomycin was active towards all Corynebacterium isolates, whereas resistance towards penicillin G was common. Conclusions: Corynebacterium species cause IE, where prosthetic valves are mainly affected and surgery is often performed. Corynebacterium striatum is an important causative agent of IE within the genus. Antibiotic resistance of corynebacteria is relatively common but resistance towards vancomycin could not be detected in vitro.
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| 8. |
- Bläckberg, Anna
(författare)
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Interactions between β-haemolytic streptococci and the human host. Heart, skin and beyond.
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Group C and G streptococci (GCS/GGS) and group A streptococci (GAS) belong to β-haemolytic streptococci (BHS). GCS/GGS can further be species determined to S. dysgalactiae, whereas S. pyogenes are GAS. S. dysgalactiae and S. pyogenes cause similar diseases, (e.g., skin and soft tissue infections, erysipelas, bacteraemia, and infective endocarditis (IE)). Erysipelas often presents as a sharply demarcated oedematous erythema and often reoccurs in the same host. The diagnosis relies on the clinical presentation since cultures from blood and/or wounds often are negative. IE due to BHS is rare but is a challenging infection to treat. Combination therapy using a β-lactam and an aminoglycoside has been employed to treat the condition, but the evidence for synergy between the two antibiotics is weak. This thesis began investigating erysipelas and predominantly found GCS/GGS, but also GAS as important pathogens to erysipelas, (Paper I). To further investigate the disease panorama of GCS/GGS, the second study comprised cases of IE due to S. dysgalactiae from a nationwide registry. IE with S. dysgalactiae was found to have an acute onset of symptoms with substantial mortality and embolic event rate, (Paper II). Synergy between penicillin G and gentamicin was observed in some blood isolates of S. dysgalactiae. However, in most cases, penicillin G alone showed bactericidal action so strong, that any further killing action of gentamicin was difficult to detect. Recurrent infections with S. dysgalactiae, involving erysipelas but also bacteraemia, are common. The cell surface attached M protein is an important virulence determinant for the bacteria. There are different M proteins which render an antigenic diversity and facilitate the bacteria’s evasion of the host defence system. In a prospectively based study, type-specific antibodies were developed in convalescent serum from patients with prior bacteraemia with S. dysgalactiae, (Paper III). However, further analysis with bactericidal and phagocytosis assays could not establish that these evolved antibodies opsonised the bacteria or enhanced the killing of the bacteria. The quest for prognostic factors in bacteraemia with BHS is challenging. Time to positivity (TTP) from blood cultures may reflect bacterial concentration in blood and was identified as an independent prognostic factor for 30-day mortality in invasive infections due to both S. pyogenes and S. dysgalactiae respectively, (Paper IV and V). All things considered, this thesis highlights the clinical and microbiological aspects of infections caused by BHS and their interactions with the human host. Recurrent infections due to the bacteria are common, and a lack of development of opsonising antibodies may partially explain the presence of recurrent bacteraemia with S. dysgalactiae.
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| 9. |
- Bläckberg, Anna, et al.
(författare)
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Lack of Opsonic Antibody Responses to Invasive Infections With Streptococcus dysgalactiae
- 2021
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Streptococcus dysgalactiae can cause severe recurrent infections. This study aimed to investigate antibody responses following S. dysgalactiae bacteraemia and possible development of protective immunity. Materials and Methods: Patients with S. dysgalactiae bacteraemia in the county of Skåne between 2017 and 2018 were prospectively included. Acute and convalescent sera were obtained. All isolates were emm typed and enzyme-linked immunosorbent assay (ELISA) was utilised to analyse specific antibody responses to bacteria and antigens. Bactericidal- and phagocytosis assays were applied to further establish antibody function. Results: Sixteen patients with S. dysgalactiae bacteraemia were included of whom one had recurrent episodes of bacteraemia. Using ELISA with S. dysgalactiae isolates and mutants, development of IgG antibodies was demonstrated in few patients. Type-specific antibodies were demonstrated in one patient when recombinant M proteins as antigens, were applied. The type-specific serum mediated a small increase in phagocytosis but did not facilitate increased killing of the S. dysgalactiae isolate, carrying that M protein, in blood or by phagocytic cells. Conclusion: S. dysgalactiae bacteraemia sometimes results in increased levels of antibodies to the infecting pathogen. We did not find evidence that these antibodies are effectively opsonising. Apparent failure to produce opsonising antibodies might partially explain why S. dysgalactiae can cause recurrent invasive infections in the same host.
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| 10. |
- Bläckberg, Anna, et al.
(författare)
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Time to Blood Culture Positivity: An Independent Predictor of Mortality in Streptococcus Pyogenes Bacteremia
- 2022
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundStreptococcus pyogenes bacteremia is a severe condition with high mortality. Time to blood culture positivity (TTP) is known to predict the outcome in bacteremia with other pathogens. This study aimed to determine the association between TTP and outcome in S pyogenes bacteremia.MethodsThis retrospective observational cohort study comprised adults with S pyogenes bacteremia, identified through the laboratory database between 2015 and 2018, in the Region of Skåne, Sweden. Correlations between TTP and outcomes were investigated. Primary outcome was death within 30 days, and secondary outcomes were presence of sepsis or disease deterioration within the first 48 hours.ResultsA total of 347 episodes of S pyogenes bacteremia were identified, of which 61 were excluded, resulting in 286 included episodes. Median TTP was 10.4 (interquartile range, 8.4–11.4) hours. Thirty-day mortality was 10%. Median TTP was shorter in patients who died within 30 days compared to survivors (8.6 vs 10.4 hours; P < .001). In a multivariable logistic regression, shorter TTP was associated with 30-day mortality when adjusting for age, Charlson Comorbidity Index, and focus of infection (odds ratio, 3.7 [95% confidence interval, 1.2–11.3]; P = .02). There was no statistically significant difference in TTP between patients with sepsis within 48 hours and those who did not have sepsis. Additionally, there was no statistically significant difference in TTP between patients with disease deterioration compared to those who did not deteriorate.ConclusionsKnowledge on TTP might be a tool to determine the prognosis of a given patient with S pyogenes bacteremia.
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