| 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. |
- Berge, Andreas, et al.
(författare)
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Non-betahemolytic streptococcal bacteremia, cardiac implantable electronic device, endocarditis, extraction, and outcome; a population-based retrospective cohort study
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Ingår i: Infection. - 0300-8126.
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Tidskriftsartikel (refereegranskat)abstract
- PurposePatients with non-beta-hemolytic streptococcal bacteremia (NBHSB) are at risk of infective endocarditis (IE). Patients with cardiac implantable electronic device (CIED) have been described to have an increased risk of IE. The aim of the study was to describe a population-based cohort of patients with NBHSB and CIED and variables associated with IE and recurrent NBHSB.MethodsAll episodes with NBHSB in blood culture from 2015 to 2018 in a population of 1.3 million inhabitants were collected from the Clinical Microbiology Laboratory, Lund, Sweden. Through medical records, patients with CIED during NBHSB were identified and clinical data were collected. Patients were followed 365 days after NBHSB.ResultsEighty-five episodes in 79 patients with CIED and NBHSB constituted the cohort. Eight patients (10%) were diagnosed with definite IE during the first episode, five of whom also had heart valve prosthesis (HVP). In 39 patients (49%) transesophageal echocardiography (TEE) was performed of which six indicated IE. Four patients had the CIED extracted. Twenty-four patients did not survive (30%) the study period. Four patients had a recurrent infection with NBHSB with the same species, three of whom had HVP and had been evaluated with TEE with a negative result during the first episode and diagnosed with IE during the recurrency.ConclusionThe study did not find a high risk of IE in patients with NBHSB and CIED. Most cases of IE were in conjunction with a simultaneous HVP. A management algorithm is suggested.
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Bläckberg, Anna, et al.
(författare)
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Erysipelas, a large retrospective study of aetiology and clinical presentation.
- 2015
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Erysipelas is a common and severe infection where the aetiology and optimal management is not well-studied. Here, we investigate the clinical features, bacteriological aetiology, and treatment of erysipelas.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- Bläckberg, Anna, et al.
(författare)
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Infective endocarditis due to Streptococcus dysgalactiae: clinical presentation and microbiological features
- 2018
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 0934-9723 .- 1435-4373. ; 37:12, s. 2261-2272
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of infective endocarditis (IE) caused by Streptococcus dysgalactiae (SD) is limited. This study aimed to identify the clinical and microbiological features of SD-caused IE and to investigate any possible synergy between penicillin and gentamicin on SD isolates. Cases of IE 2008-2016 due to SD reported to the Swedish Registry of Infective Endocarditis (SRIE) were identified. Isolates were emm typed and synergy between antibiotics was determined in time-kill experiments. Medical records were reviewed and SD-cases were compared to cases of IE due to other pathogens reported to the SRIE. Fifty cases of SD-caused IE were confirmed. emm types stC74a, stG62647, and stG643 were most commonly encountered. The patients had a median age of 74years (range 38-93) and were significantly older compared to patients with Staphylococcus aureus-caused IE, (65years (p=0.003)). The median time to diagnosis from symptom onset was 1day for patients with SD-caused IE which was less compared to patients with IE due to the other pathogens (2-15days). Embolization was seen in 46% and the in-hospital mortality was 8%. Etest-based methods did not indicate any synergy between penicillin and gentamicin whereas synergy was noted for four out of nine isolates applying time-kill assays. This is the largest study of SD-caused IE, a condition with an acute onset predominantly affecting elderly people. Synergy between penicillin and gentamicin against some SD isolates was distinguished but the potential benefit of this must be weighed against the risk of aminoglycoside side effects.
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| 11. |
- 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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| 12. |
- 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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| 13. |
- 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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| 14. |
- Bläckberg, Anna, et al.
(författare)
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Time to positivity of blood cultures in bloodstream infections with Streptococcus dysgalactiae and association with outcome
- 2023
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:5, s. 333-339
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Tidskriftsartikel (refereegranskat)abstract
- PurposeInvasive infections with Streptococcus dysgalactiae predominantly occur in persons of older age with substantial morbidity and mortality. Time to positivity from blood cultures (TTP) has been shown to be a prognostic indicator in bloodstream infections caused by other beta-haemolytic streptococci. This study aimed to determine any possible association between TTP and outcome in invasive infections due to S. dysgalactiae.Materials and methodsEpisodes of S. dysgalactiae bacteraemia, that occurred during 2015–2018 in the Region of Skåne, Sweden, were identified through the laboratory database and retrospectively studied. Any association with TTP and the primary outcome, death within 30 days and the development of sepsis or disease deterioration within 48 hours from blood culturing as secondary outcomes were investigated.ResultsAmong the 287 episodes of S. dysgalactiae bacteraemia, 30-day mortality rate was 10% (n = 30). Median TTP was 9.3 h (interquartile range 8.0–10.3 h). Median TTP was statistically significantly shorter in patients who died within 30 days compared to surviving patients (7.7 vs 9.3 h, p = .001, Mann–Whitney U test). Short TTP(≤ 7.9 h) was still associated with 30-day mortality when adjusting for age, (OR 4.4, 95% CI 1.6–12.2, p = .004). Associations between secondary outcomes and levels of TTP were not observed.ConclusionTTP may be an important prognostic indicator for 30-day mortality in patients with bloodstream infections due to S. dysgalactiae.
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| 15. |
- Böös, Malin, et al.
(författare)
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Who should record surgical complications? : Results from a third-party assessment of complications after radical cystectomy
- 2019
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Ingår i: Scandinavian journal of urology. - : Informa Healthcare. - 2168-1805 .- 2168-1813. ; 53:5, s. 339-343
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Tidskriftsartikel (refereegranskat)abstract
- Objective: In Sweden complications after radical cystectomy have been reported to the nationwide population-based Swedish Cystectomy Registry since 2011. Here, validation of the reporting was assessed in two healthcare regions.Materials and methods: Complications were ascertained from patient records by a third party not involved in the care delivered to 429 randomly selected patients from 949 who had undergone radical cystectomy since 2011 in four hospitals. Without knowledge of the outcome in the primary registration, post-operative complications within 90 days post-operatively were assessed by an independent review of patient charts, and the results were compared with the primary reports in the Swedish Cystectomy Registry.Results: The third-party assessment identified post-operative complications in 310 patients (72%). Low-grade complications (Clavien-Dindo I-II) were noted in 110 (26%) of the patients in the primary registration, but increased to 182 (42%) in the validation (p < 0.00001). High-grade complications (Clavien-Dindo III-V) were reported in 113 (26%) patients in the primary registration, but in 128 (30%) of the patients in the validation (p = 0.02). According to the third-party assessment, 18 patients (4%) had Clavien-Dindo grade IV complications and 12 (3%) died within 90 days of surgery (Clavien-Dindo grade V); corresponding values in the primary registration were 15 (3%) and 9 (2%), respectively. The readmission rate within 90 days increased from 27 to 32% in the validation (p < 0.00001).Conclusions: Compared with registry data, third-party assessment revealed more complications and readmissions after radical cystectomy. Hence such evaluation may improve the validity of reported complication data.
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| 16. |
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| 17. |
- Chao, Yashuan, et al.
(författare)
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Distinct phenotypes of platelet, monocyte, and neutrophil activation occur during the acute and convalescent phase of COVID-19
- 2021
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 32:8, s. 1092-1102
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 has spread rapidly worldwide, causing the COVID-19 pandemic. Platelet activation and platelet-leukocyte complex formation are proposed to contribute to disease progression. Here, we report platelet and leukocyte activation during acute and convalescent COVID-19 in patients recruited between May-July 2020. Blood samples were analyzed by flow cytometry and ELISA using paired comparison between inclusion (day 0) and 28 days later. The majority of patients were mildly or moderately ill with significantly higher cytokine levels (IL-6 and IL-10) on day 0 as compared with day 28. Platelet activation and granule release were significantly higher on day 0 compared with day 28, as determined by ADP- or thrombin-induced surface CD62P expression, baseline released CD62P, and thrombin-induced platelet-monocyte complex formation. Monocyte activation and procoagulant status at baseline and post activation were heterogeneous but generally lower on day 0 compared with day 28. Baseline and thrombin- or fMLF-induced neutrophil activation and procoagulant status were significantly lower on day 0 compared with day 28. We demonstrate that during the acute phase of COVID-19 compared with the convalescent phase, platelets are more responsive while neutrophils are less responsive. COVID-19 is associated with thromboembolic events where platelet activation and interaction with leukocytes may play an important role.
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| 18. |
- De Marinis, Yang, et al.
(författare)
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Serology assessment of antibody response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test
- 2020
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Ingår i: Infection Ecology and Epidemiology. - : Informa UK Limited. - 2000-8686. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n = 45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. The total IgM and IgG detection is 63% in patients with <2 weeks from disease onset; 85% in non-hospitalized patients with >2 weeks disease duration; and 91% in hospitalized patients with >2 weeks disease duration. We also compared different blood sample types and suggest a higher sensitivity by serum/plasma over whole blood. Test specificity was determined to be 97% on 69 sera/plasma samples collected between 2016-2018. Our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our results support that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.
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| 19. |
- de Neergaard, Therese, et al.
(författare)
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Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies
- 2022
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Ingår i: Microbiology spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced ( emm118, emm85, and two emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.
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| 20. |
- Kahn, Fredrik, et al.
(författare)
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Heparin-Binding Protein As A Prognostic Biomarker of Sepsis and Disease Severity at The Emergency Department
- 2019
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Ingår i: Shock. - 1540-0514. ; 52:6, s. 135-135
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Rapid and early detection of patients at risk to develop sepsis remains demanding. Heparin-binding protein (HBP) has previously demonstrated good prognostic properties in detecting organ dysfunction among patients with suspected infections. This study aimed to evaluate the plasma-levels of HBP as a prognostic biomarker for infection-induced organ dysfunction among patients seeking medical attention at the emergency department.DESIGN: Prospective, international multicenter, convenience sample study SETTING:: Four general emergency departments at academic centers in Sweden, Switzerland and Canada.PATIENTS: All emergency encounters among adults where one of the following criteria were fulfilled: a) respiratory rate >25 breaths per minute; b) heart rate >120 beats per minute; c) altered mental status; d) systolic blood pressure <100 mm Hg; e) oxygen saturation <90% without oxygen; f) oxygen saturation <93% with oxygen; g) reported oxygen saturation <90%.INTERVENTION: None MEASUREMENTS AND MAIN RESULTS:: A total of 524 ED patients were prospectively enrolled, of these 236 (45%) were eventually adjudicated to have a non-infectious disease. Three hundred forty-seven patients (66%) had or developed organ dysfunction within 72 hours, 54 patients (10%) were admitted to an intensive care unit (ICU), and 23 patients (4%) died within 72 hours. For the primary outcome, detection of infected-related organ dysfunction within 72 hours, the AUC for HBP was 0.73 (95% C.I. 0.68-0.78) among all patients and 0.82 (95% C.I. 0.76-0.87) among patients confidently adjudicated to either infection or no infection. Against the secondary outcome, infection leading to admittance to the ICU, death or a persistent high SOFA-score due to an infection (SOFA-score ≥5 at 12-24 hours) HBP had an AUC of 0.87 (95% C.I. 0.79-0.95) among all patients and 0.88 (95% C.I. 0.77-0.99) among patients confidently adjudicated to either infection or non-infection.CONCLUSIONS: Among patients at the emergency department, HBP demonstrated good prognostic and discriminatory properties in detecting the most severely ill patients with infection.
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| 21. |
- Kidd-Ljunggren, Karin, et al.
(författare)
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High levels of hepatitis B virus DNA in body fluids from chronic carriers.
- 2006
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 64:4, s. 352-357
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Tidskriftsartikel (refereegranskat)abstract
- infection with hepatitis B virus (HBV) is a major global health problem. Transmission is mainly blood-borne, although the route of infection during horizontal transmission in childhood is unclear. Nosocomial outbreaks of HBV have been widely reported, but have mainly focused on blood-borne transmission. There is Limited knowledge of the viral Load Levels in other body fluids. In the present study, chronic HBV carriers were tested for the presence of HBV DNA in serum, saliva, nasopharyngeal fluid, urine and tears by means of qualitative and quantitative polymerase chain reaction (PCR) methods. Twenty-five patients who were positive for HBV DNA with both PCRs were included. Low titres in real-time PCR corresponded with weak bands in the qualitative assay. HBV DNA was found in two urine samples, 10 saliva samples, five nasopharyngeal, swabs and in tear fluid from four patients. One highly viraemic HBeAg-positive carrier with serum HBV DNA Levels of 7 x 10(9) genome copies had high copy numbers detected in both saliva and nasopharyngeal fluid. These results demonstrate that highly viraemic HBV carriers may have high titres of HBV DNA in other body fluids. This has particular importance for infection control programmes and regulations, underlining the importance of aiming towards regular HBV DNA testing and thus infectivity assessment of chronic carriers in order to prevent transmission. (c) 2006 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
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| 22. |
- Lind, Anna Karin, et al.
(författare)
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Health-related quality of life prior to and 1 year after radical cystectomy evaluated with FACT-G and FACT-VCI questionnaires
- 2023
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Ingår i: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 58:1, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate health-related quality of life (HRQoL) before and 1 year after radical cystectomy in relation to age and gender.METHODS: This prospective study involves 112 men and 40 women with bladder cancer treated with radical cystectomy between 2015 and 2018. HRQoL was assessed preoperatively and 1 year post-surgery through Functional Assessment of Cancer Therapy Scale - General (FACT-G) and Functional Assessment of Cancer Therapy Scale - Vanderbilt Cystectomy Index (FACT-VCI) questionnaires. The median age of the 152 patients was 71.5 years.RESULTS: Preoperatively, emotional and functional well-being were negatively affected. Physical, emotional and functional well-being presented higher values 1 year after surgery compared to before radical cystectomy, that is, better HRQoL. Social well-being showed a reduction, especially regarding closeness to partner and support from family. Men and women were equally satisfied with their sex life before radical cystectomy, but less so 1 year after, where men were less satisfied compared to women. Additionally, one out of five patients reported that they had to limit their physical activities, were afraid of being far from a toilet and were dissatisfied with their body appearance after surgery.CONCLUSIONS: Recovery regarding HRQoL was ongoing 1 year after radical cystectomy. Patients recovered in three out of four dimensions of HRQoL, but social well-being was still negatively affected 1 year after treatment. Sexual function after radical cystectomy was exceedingly limited for both men and women. An individual sexual rehabilitation plan involving the couple with special intention to encourage intimacy, might not only improve sexual life but also have a positive effect on social well-being as a consequence.
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| 23. |
- Lindberg, Helena, et al.
(författare)
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Performance of the 2023 Duke-ISCVID diagnostic criteria for infective endocarditis in relation to the modified Duke criteria and to clinical management- reanalysis of retrospective bacteremia cohorts
- 2024
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Ingår i: Clinical Infectious Diseases. - 1537-6591. ; 78:4, s. 956-963
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRevised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE-treatment.MethodsWe reanalyzed patient cohorts with Stapylococcus aureus, Staphylococcus lugdunensis, non-beta-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis and HACEK bacteremia. Episodes were classified as definite, possible or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, PET-CT and cardiac implanted elect-ronical devices. To calculate sensitivity, patients treated as IE were considered as having IE.ResultsIn 4050 episodes of bacteremia, the modified Duke criteria criteria assigned 307episodes (7.6%) as definite IE, 1190 episodes (29%) as possible IE and 2553 episodes (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE and eleven of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE.ConclusionsThe Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible group while keeping or improving sensitivity.
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| 24. |
- Ljungquist, Oskar, et al.
(författare)
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A population-based study of the appearances of enteric Campylobacter and non-typhoidal Salmonella infections on computed tomography
- 2024
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Ingår i: Annals of Medicine. - 1365-2060. ; 56:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSwift identification and diagnosis of gastrointestinal infections are crucial for prompt treatment, prevention of complications, and reduction of the risk of hospital transmission. The radiological appearance on computed tomography could potentially provide important clues to the etiology of gastrointestinal infections. We aimed to describe features based on computed tomography of patients diagnosed with Campylobacter, Salmonella or Shigella infections in South Sweden.MethodsThis was a retrospective observational population-based cohort study conducted between 2019 and 2022 in Skåne, southern Sweden, a region populated by 1.4 million people. Using data from the Department of Clinical Microbiology combined with data from the Department of Radiology, we identified all patients who underwent computed tomography of the abdomen CTA two days before and up to seven days after sampling due to the suspicion of Campylobacter, Salmonella or Shigella during the study period.ResultsA total of 215 CTAs scans performed on 213 patients during the study period were included in the study. The median age of included patients was 45 years (range 11–86 years), and 54% (114/213) of the patients were women. Of the 215 CTAs, 80% (n = 172) had been performed due to Campylobacter and 20% (n = 43) due to Salmonella enteritis. CTA was not performed for any individual diagnosed with Shigella during the study period. There were no statistically significant differences in the radiological presentation of Campylobacter and Salmonella infections.ConclusionThe most common location of Campylobacter and Salmonella infections was the cecum, followed by the ascending colon. Enteric wall edema, contrast loading of the affected mucosa, and enteric fat stranding are typical features of both infections. The CTA characteristics of Campylobacter and Salmonella are similar, and cannot be used to reliably differentiate between different infectious etiologies.
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| 25. |
- Odeberg, Görel, et al.
(författare)
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Infection or Contamination with Rothia, Kocuria, Arthrobacter and Pseudoglutamicibacter — a Retrospective Observational Study of Non-Micrococcus Micrococcaceae in the Clinic
- 2023
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 1098-660X .- 0095-1137. ; 61:4, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Rothia, Kocuria, Arthrobacter, and Pseudoglutamicibacter are bacterial species within the family Micrococcaeae. Knowledge of human infections due to these bacteria is limited. This study aimed to examine features of infections caused by non-Micrococcus Micrococcaeae (NMM). Findings of NMM from blood cultures and other sterile cultures from 2012 to 2021 were identified from the records of the Department of Clinical Microbiology in Region Skåne, Lund, Sweden. Medical records were retrospectively reviewed. True infection was defined as having signs of infection, no other more likely pathogen, and no other focal infection, together with two positive blood cultures or one positive blood culture and an intravascular device. A total of 197 patients with findings of NMM in blood cultures were included. Among adult patients with bacteremia, 29 patients (22%) were considered to have a true infection. Adults with true infection were significantly more likely to have malignancy (69%), leukopenia (62%), and treatment with chemotherapeutics (66%) compared to patients with contaminated samples (24%, 3%, and 8%, respectively) (P
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| 26. |
- Sunnerhagen, Torgny, et al.
(författare)
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Campylobacter infections with and without bacteraemia- a comparative retrospective population-based study
- 2024
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Ingår i: Open Forum Infectious Diseases. - 2328-8957. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBacteraemia with species in the genus Campylobacter is rare, and knowledge of the disease course in comparison to Campylobacter enteritis is limited.MethodsThis is a retrospective population-based study. Episodes of Campylobacter bacteraemia, and Campylobacter enteritis with a concurrent negative blood culture, that occurred between 2015 and 2022 in southern Sweden were identified through the laboratory database. Medical records were reviewed and clinical features between patients with bacteraemic Campylobacter infections were compared with patients with Campylobacter spp. found in faeces.ResultsA total of 29 bacteraemic infections with Campylobacter and 119 patients with Campylobacter spp. found in faeces were included. Patients with Campylobacter bacteraemia were statistically significantly older compared to patients with only enteritis (72 years, IQR 58-62 years, and 58 years, IQR 33-67 years, respectively, p < 0.0001). Eleven patients with bacteraemia developed sepsis within 48 hours from blood culturing and no patient died within 30 days from hospital admission.ConclusionsCampylobacter bacteraemia is rare and occurs mainly in the elderly with co-morbidities. In comparison to Campylobacter infections limited to the gastrointestinal tract, patients with bacteraemic Campylobacter infections are older and seem more prone to develop sepsis. Classical gastroenteritis symptoms in bacteraemic patients with Campylobacter may be absent.
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| 27. |
- Svensson, Emma, et al.
(författare)
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Increasing incidence of pyogenic liver abscess in Southern Sweden : a population-based study from 2011 to 2020
- 2023
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:6, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pyogenic liver abscess (PLA) is a rare but potentially life-threatening disease, and estimates suggest a gradual increase in the incidence during the last decades. The primary aim of this study was to report the incidence, trend and aetiology of PLA during a decade in Southern Sweden.METHODS: This was a population-based observational cohort study between 2011 and 2020 in Skåne, Southern Sweden. Data were retrieved from the Swedish National Board of Health and Welfare for all individuals diagnosed with liver abscess (K750) according to ICD-10 (International Statistical Classification of Diseases, 10th revision).RESULTS: A total of 456 episodes of PLA occurred in 364 patients during the study period. The median age of the first PLA episode was 71 years (range 3-97) and 57% (n = 206) were men. The mean incidence of all patients was 3.4/100,000 person-years (range 1.8-5.2). The incidence increased almost three times, from 1.8/100,000 person-years in 2011 to 5.2/100,000 person-years in 2020. Streptococcus species, Escherichia coli and Klebsiella species accounted for the vast majority of both mono- and polymicrobial findings in both blood and local abscess cultures. 16s rDNA added information about aetiology in 37% of episodes.CONCLUSION: The incidence of PLA increased during the study period, and Streptococcus spp., Klebsiella spp. and E. coli dominated both blood and local cultures. Despite antimicrobial therapy, pathogens could be found in local abscess cultures several weeks into treatment. Increased use of 16s rDNA in the management of PLA could be beneficial.
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