| 1. |
- Dalin, Frida, 1984-, et al.
(author)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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In: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Journal article (peer-reviewed)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 2. |
- Lagerqvist, Carina, et al.
(author)
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Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age
- 2008
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In: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 47:4, s. 428-35
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS: Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.
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| 3. |
- Ziegler, Ingrid, 1976-, et al.
(author)
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Quantitative data from the SeptiFast real-time PCR is associated with disease severity in patients with sepsis
- 2014
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In: BMC Infectious Diseases. - London : BioMed Central. - 1471-2334. ; 14:1
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Journal article (peer-reviewed)abstract
- Background: The commercial test, SeptiFast, is designed to detect DNA from bacterial and fungal pathogens in whole blood. The method has been found to be specific with a high rule-in value for the early detection of septic patients. The software automatically provides information about the identified pathogen, without quantification of the pathogen. However, it is possible to manually derive Crossing point (Cp) values, i.e. the PCR cycle at which DNA is significantly amplified. The aim of this study was to find out whether Cp values correlate to disease severity.Methods: We used a study cohort of patients with positive results from SeptiFast tests for bacteria from a recent study which included patients with suspected sepsis in the Emergency department. Cp values were compared with disease severity, classified as severe sepsis/septic shock or non-severe sepsis, according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine.Results: Ninety-four patients were included. The prevalence of severe sepsis/septic shock in the study was 29%. SeptiFast positive tests from patients with severe sepsis/septic shock had significantly lower Cp values compared with those from patients with non-severe sepsis, median 16.9 (range: 7.3 - 24.3) versus 20.9 (range: 8.5 - 25.0), p < 0.001. Positive predictive values from the SeptiFast test for identifying severe sepsis/septic shock were 34% at Cp cut-off <25.0, 35% at Cp cut-off <22.5, 50% at Cp cut-off <20.0, and 73% at Cp cut-off <17.5. Patients with a positive Septifast test with a Cp value <17.5 had significantly more severe sepsis/septic shock (73% versus 15%, p < 0.001), were more often admitted to the Intensive Care Unit (23% versus 4%, p = 0.016), had positive blood culture (BC) more frequently (100% versus 32%, p < 0.001) and had longer hospital stays (median 19.5 [range: 4 - 78] days versus 5 [range: 0 - 75] days, p < 0.001) compared with those with a Cp value >17.5.Conclusions: Our results suggest that introducing quantitative data to the SeptiFast test could be of value in assessing sepsis severity. Moreover, such data might also be useful in predicting a positive BC result.
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| 4. |
- Abdeldaim, Guma M. K., et al.
(author)
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Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction
- 2009
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In: Diagnostic microbiology and infectious disease. - : Elsevier. - 0732-8893 .- 1879-0070. ; 64:4, s. 366-373
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Journal article (peer-reviewed)abstract
- A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 104 DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.
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| 5. |
- Abdeldaim, Guma M. K., et al.
(author)
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Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia
- 2013
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In: Diagnostic microbiology and infectious disease. - : Elsevier. - 0732-8893 .- 1879-0070. ; 76:2, s. 141-146
-
Journal article (peer-reviewed)abstract
- A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions.
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| 6. |
- Abdeldaim, Guma M. K., et al.
(author)
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Toward a quantitative DNA-based definition of pneumococcal pneumonia : a comparison of Streptococcus pneumoniae target genes, with special reference to the Spn9802 fragment
- 2008
-
In: Diagnostic microbiology and infectious disease. - : Elsevier BV. - 0732-8893 .- 1879-0070. ; 60:2, s. 143-150
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Journal article (peer-reviewed)abstract
- The current shift from phenotypically toward genotypically based microbial diagnosis is not unproblematic. A novel quantitative real-time polymerase chain reaction (PCR) assay based on the Spn9802 DNA fragment was therefore developed for detection of Streptococcus pneumoniae. Out of 44 bacterial species, only S. pneumoniae and Streptococcus pseudopneumoniae were positive in Spn9802 PCR. In an evaluation on nasopharyngeal aspirates from 166 patients with community-acquired pneumonia, the assay was positive in 49 of 50 culture-positive cases. Of 19 culture-negative but Spn9802 PCR-positive cases, 12 were confirmed as S. pneumoniae by rnpB sequence analysis. With an expanded reference standard, including culture and rnpB sequencing, Spn9802 had a sensitivity of 94% and a specificity of 98%. A cutoff for clinically significant positivity was 10(4) DNA copies/mL, giving 71% sensitivity and 100% specificity. In conclusion, Spn9802 real-time PCR is highly sensitive and specific. The quantification it provides enables differentiation between pneumococcal pathogenicity and commensalism.
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| 7. |
- Abdeldaim, Guma, et al.
(author)
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Usefulness of real-time PCR for lytA, ply, and Spn9802 on plasma samples for the diagnosis of pneumococcal pneumonia
- 2010
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 16:8, s. 1135-1141
-
Journal article (peer-reviewed)abstract
- In the present study, we evaluated rapid real-time PCR assays for ply, Spn9802, and lytA applied to plasma samples for the detection of Streptococcus pneumoniae in patients with community-acquired pneumonia (CAP). In a prospective study of CAP aetiology, an EDTA plasma sample was collected together with blood culture in 92 adult CAP patients and 91 adult controls. Among the 92 CAP patients, lytA PCR was positive in eight (9%), Spn9802 PCR was positive in 11 (12%) and ply PCR was positive in 19 (21%) cases. Of 91 controls, the ply PCR was positive in eight cases (9%), but no positive cases were noted by Spn9802 or lytA PCRs. Ten CAP patients had pneumococcal bacteraemia. Compared to blood culture, PCR for lytA, Spn9802 and ply had sensitivities of 70% (7/10), 60% (6/10) and 70% (7/10), and specificities of 96% (79/82), 94% (77/82) and 85% (70/82) respectively. With blood culture and/or culture of representative sputum, and/or urinary antigen detection, S. pneumoniae was identified in 31 CAP patients. Compared to these tests in combination, PCR for lytA, Spn9802 and ply showed sensitivities of 26% (8/31), 32% (10/31) and 42% (13/31), and specificities of 100% (61/61), 98% (60/61) and 90% (55/61) respectively. We conclude that Spn9802 and lytA PCRs may be useful for the rapid detection of bacteraemic pneumococcal pneumonia, whereas ply PCR is not specific enough for routine use and blood PCR with small plasma volumes is not useful for the detection of nonbacteraemic pneumococcal pneumonia.
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| 8. |
- Almroth, Gabriel, et al.
(author)
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Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders
- 2006
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In: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 111:3, s. 339-352
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Journal article (peer-reviewed)abstract
- Background: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce.Design: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients).Results: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönlein's purpura had elevated IgA-antibodies to tissue transglutaminase.Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I). One patient with chronic glomerulnephritis also had Marsh I.Conclusions: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.
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| 9. |
- Backman, Anders, et al.
(author)
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Evaluation of an extended diagnostic PCR assay for detection and verification of the common causes of bacterial meningitis in CSF and other biological samples
- 1999
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In: Molecular and Cellular Probes. - : Elsevier BV. - 0890-8508 .- 1096-1194. ; 13:1, s. 49-60
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Journal article (peer-reviewed)abstract
- A seminested polymerase chain reaction (PCR)-based diagnostic assay was evaluated for detection and verification of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Steptococcus agalactiae and Listeria monocytogenes in cerebrospinal fluid (CSF) and other biological samples. A general bacterial amplicon from the 16S rRNA gene was amplified in a first step, and species-specific regions in a second. The detection level was 4 fg DNA/reaction, corresponding to about one bacterial genome per reaction tube. Sample preparations (Dynabeads DNA DIRECT kit) were assayed from 140 bacterial strains suspended in saline. In CSF the detection level for bacteria was 103 CFU ml-1 for N. meningitidis, H. influenzae and S. pneumoniae, 104 CFU ml-1 for Escherichia coli and 105 CFU ml-1 for S. agalactiae and L. monocytogenes. The detection levels for these bacteria were the same in the other tested biological samples, like blood with or without culture media. Clinical CSF samples were evaluated from 71 patients with proven bacterial meningitis, as were 61 CSF samples from individuals without bacterial meningitis. The diagnostic sensitivity of the assay in detecting bacteria in general was 0.97, and for the specific species in the clinical CSF samples 0.87-0.94. The specificity was 1.0 for detecting bacteria in general. Some cross-reactions were noted within the streptococcus group. The PCR results were verified by banding patterns of HaeIII digested PCR products.
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| 10. |
- Berglund, Torsten, et al.
(author)
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One year of Neisseria gonorrhoeae isolates in Sweden : the prevalence study of antibiotic susceptibility shows relation to the geographic area of exposure
- 2002
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In: International Journal of STD and AIDS (London). - : SAGE Publications. - 0956-4624 .- 1758-1052. ; 13:2, s. 109-114
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Journal article (peer-reviewed)abstract
- The aim of this study was to compare epidemiological data with antibiotic susceptibility patterns, so as to characterize the risk of infection with a highly resistant Neisseria gonorrhoeae strain. N. gonorrhoeae strains isolated in Sweden from February 1998 through January 1999 were tested for antibiotic susceptibility. Epidemiological data were received from each clinician reporting a case of gonorrhoea and these data were linked to the N. gonorrhoeae strains. A total of 348 N. gonorrhoeae isolates, representing 89% of all Swedish cases diagnosed during the 12-month period, were tested for antibiotic susceptibility. Of all isolates, 24% were β-lactamase-producing, and 18% had decreased susceptibility to ciprofloxacin (MIC>0.064 mg/l). All isolates were fully susceptible to ceftriaxone and spectinomycin. More than 99% of the isolates were fully susceptible to azithromycin. The antibiotic susceptibility varied with the places where patients were exposed to infection. When exposed in Asia, 63% of the isolates showed reduced susceptibility to ciprofloxacin, compared with 0-8.5% of the isolates from patients exposed in other places (RR=8.5, P<0.001). Ciprofloxacin cannot be recommended as the first choice of treatment if the place of exposure was in Asia.
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| 11. |
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| 12. |
- Bäckman, Anders, et al.
(author)
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Complete Sequence of a β-Lactamase-Encoding Plasmid in Neisseria meningitidis
- 2000
-
In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 44:1, s. 210-212
-
Journal article (peer-reviewed)abstract
- Identical β-lactamase-encoding (TEM-1) plasmids were found in two different clinical Neisseria meningitidis strains. They were completely sequenced (5,597 bp) and designated pAB6. The plasmid is almost identical to Neisseria gonorrhoeae plasmid pJD5 (5,599 kb) and may have been picked up from a gonococcus in vivo.
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| 13. |
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| 14. |
- Clarke, S. C., et al.
(author)
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Analysis of PorA variable region 3 in meningococci : implications for vaccine policy?
- 2003
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In: Vaccine. - 0264-410X .- 1873-2518. ; 21:19-20, s. 2468-2473
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Journal article (peer-reviewed)abstract
- Outer membrane protein (OMP) vaccines are being developed against Neisseria meningitidis serogroup B which may provide protection against common circulating serotypes and serosubtypes in some countries. However, limited data is available in Europe from genosubtyping meningococci. We therefore undertook a retrospective analysis of the three main variable regions, VR1, VR2 as well as VR3, of the porA gene from N. meningitidis isolated from different countries, mainly from Scotland and Sweden. Analysis of this gene showed that, amongst 226 strains studied, there were a total of 78 different strains. No new VR1 or VR2 alleles were found but five new VR3 alleles are described. Our data indicates the importance of analysing the VR3 region of PorA in addition to VR1 and VR2 and also highlights, in general terms, the need for genosubtyping meningococci. Such analyses have major implications for the design of new meningococcal vaccines.
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| 15. |
- Dahle, Charlotte, 1956-, et al.
(author)
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Methods of choice for diagnostic antinuclear antibody (ANA) screening : Benefit of adding antigen-specific assays to immunofluorescence microscopy
- 2004
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 22:3, s. 241-248
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Journal article (peer-reviewed)abstract
- Objectives. To evaluate and compare the performances of three enzyme-immunoassays (EIAs) and a double radial immunodiffusion (DRID) test in addition to immunofluorescence (IF) microscopy for routine laboratory screening of patient sera sent for antinuclear antibody (ANA) analysis. Methods. 3079 consecutive patient sera sent for routine testing of ANA were analysed by IF microscopy on HEp-2 cells (IF-ANA), three different ANA-EIAs, and a DRID test for antibodies against extractable nuclear antigens. The IF-ANA and DRID tests were regarded as reference methods. Results. By IF-ANA and/or DRID, 375 sera (12%) turned out ANA-positive. A further 171 sera (6%) were positive by EIA, but could not be confirmed either by IF microscopy or DRID. 32 of the 375 ANA-positive (9%) sera were negative by IF microscopy, but had precipitating antibodies against Ro/SS-A (52 and/or 60 kD). Conclusions. Different assays for ANA analysis give overlapping results to a certain extent, but are by no means interchangeable. Thus, different ANA tests reflect different aspects of these autoantibodies. The diagnostic utility of ANA testing still mainly refers to IF-microscopy and precipitin tests. IF-ANA should not be abandoned as the golden standard in clinical routine, until diagnostic and classification criteria for systemic lupus erythematosus and other systemic inflammatory autoimmune diseases have been revised. However, in addition we strongly advocate that a specific test for anti-Ro/SS-A antibodies is always included.
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| 16. |
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| 17. |
- Eliasson, Henrik, et al.
(author)
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Kinetics of the immune response associated with tularemia : comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test
- 2008
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In: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 15:8, s. 1238-1243
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Journal article (peer-reviewed)abstract
- We have developed and evaluated a novel and simplified whole-blood lymphocyte stimulation assay that focuses on the measurement of gamma interferon after 24 h of stimulation with whole-cell tularemia antigen and a tularemia enzyme-linked immunosorbent assay (ELISA) based on highly purified lipopolysaccharide antigen. Comparison of the kinetics of the two assays and those of the traditional tube agglutination test shows that the cellular immune response can be detected earlier by the lymphocyte stimulation assay. This test already shows a high proportion of positive results during the first week after the onset of the disease, may be applicable in everyday laboratory practice, and has the potential of changing routine diagnostics for tularemia. The new ELISA has a high sensitivity and becomes positive to a high degree during the second week of disease.
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| 18. |
- Erlandsson, Ann, 1968-, et al.
(author)
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Quantification of Bordetella pertussis in clinical samples by colorimetric detection of competitive PCR products
- 1998
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : John Wiley & Sons. - 0903-4641 .- 1600-0463. ; 106:7-12, s. 1041-1048
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Journal article (peer-reviewed)abstract
- Quantification of microorganisms is an important part of the normal diagnostic work of a clinical microbiology laboratory. Traditionally the diagnosis of pertussis is subject to a yes or no approach with no quantitative dimension. This can, however, be of interest as a factor when judging the risk of a patient spreading the bacterium and as a research tool. The aim of the present study was to develop a PCR-based quantitative assay for Bordetella pertussis DNA in clinical nasopharyngeal aspirates by combining a quantitative PCR with a colorimetric detection principle, DIANA (detection of immobilised amplified nucleic acid). A competitor to the PCR target sequence in IS-481, containing a lac-operator, was constructed and calibrated, and a test protocol prepared. A total of 46 clinical nasopharyngeal aspirates, previously diagnosed using a standard nested PCR assay and quantified by culture, were analysed by the quantitative PCR. The method showed acceptable precision and accuracy considering that it estimates the total number of bacterial genomes while culture detects viable bacteria. Recognised advantages were the simple colorimetric detection, the inborn indication of a working PCR assay, and the possibility of obtaining results even when partial inhibition of the PCR assay was seen. In addition, the quantitative PCR result can be obtained within one day compared to 3–10 days for culture. The present results and the qualities of the quantitative PCR suggest that this assay will be a useful complement in routine diagnostics and in research.
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| 19. |
- Falk, Lars, et al.
(author)
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Genotyping of Chlamydia trachomatis would improve contact tracing
- 2003
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In: Sexually Transmitted Diseases. - : Ovid Technologies (Wolters Kluwer Health). - 0148-5717 .- 1537-4521. ; 30:3, s. 205-210
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Journal article (peer-reviewed)abstract
- Background: The reported number of genital Chlamydia trachomatis infections has increased 15% annually since 1997 in Sweden. Inaccurate partner notification might be one reason.Goal: The goals were to determine if genotyping of C trachomatis would improve partner notification and to study the duration of infection.Study Design: Sexual networks were constructed. C trachomatis isolates from 231 individuals attending the Örebro STD clinic during 1 year were typed by sequencing of the omp1 gene.Results: All individuals were traced and diagnoses were established in 30 of 161 networks. More than one genotype was seen in seven networks. The mean duration of C trachomatis infection in each network was calculated to be 23 weeks.Conclusion: Genotyping could be a useful tool in partner notification when there are discrepant or uncommon genotypes. Limited clinic catchment areas create information difficulties that obstruct accurate contact tracing.
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| 20. |
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| 21. |
- Forsum, Urban, 1946-, et al.
(author)
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Methods in molecular biology
- 2004
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Book (other academic/artistic)abstract
- An accessible introduction to how genomics has and will provide novel methods for bacterial investigation and advance our understanding and knowledge of bacterial pathogenicity. The authors critically evaluate the applications of genomics to diagnostic bacteriology, highlighting both current and likely future uses, describing real-time PCR methods, and outlining the promise of microarrays in clinical bacteriology. Their discussion examines in detail genomic approaches to antibacterial discovery, the nature of pathogenicity, the discovery of new pathogens, the exploration of the concept of clonality in bacteria, and bacterial taxonomics.
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| 22. |
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| 23. |
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| 24. |
- Garpenholt, Ö., et al.
(author)
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Invasive disease due to Haemophilus influenzae type b during the first six years of general vaccination of Swedish children
- 2000
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227 .- 0000-0000. ; 89:4, s. 471-474
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Journal article (peer-reviewed)abstract
- Since 1992-93 vaccination against Haemophilus influenzae type b (Hib) has been included in the general Swedish childhood vaccination programme. The aim of the present study is to describe the epidemiology, identify and describe vaccine failures and calculate vaccine effectiveness during the first 6 y after introduction of vaccination against Hib. Laboratory reports of blood and cerebrospinal isolates to the Swedish Institute for Infectious Disease Control were used as the source for identifying the patients. Additional information was subsequently obtained from physicians and parents of children who had developed the disease during the study period. Vaccine failures were identified and vaccine effectiveness calculated. During the study period, 152 cases of invasive H. influenzae were identified in the age group 0-14 y. During the 6-y period, 6 true vaccine failures, 6 apparent vaccine failures and 1 possible vaccine failure were found in nearly two million vaccinated child-years. The effectiveness of the Hib vaccination in the birth cohort of children 1993 to 1997 in Sweden was calculated to be 96.1% (95% confidence interval 94.2-97.5). The study supports earlier studies from several countries that conjugated Hib vaccination introduced in general childhood vaccination programs is effective and substantially decreases suffering from invasive Hib diseases.
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| 25. |
- Garpenholt, Örjan, et al.
(author)
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The impact of Haemophilus influenzae type b vaccination in Sweden
- 1996
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In: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 28:2, s. 165-169
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Journal article (peer-reviewed)abstract
- The number of patients with meningitis and bacteremia due to Haemophilus influenzae was studied in Sweden over the period 1987-1994. Conjugated H. influenzae type b vaccines were introduced in Sweden in 1992, and all children born after December 31, 1992, were offered vaccination free of charge. A rapid decline of H. influenzae meningitis and bacteraemia was observed in the autumn of 1993, when the expected peak incidence failed to appear. In the prevaccination period 1987-1991, the average annual incidence (cases/100,000) was 34.4 in children aged 0-4 years. In 1994, the annual incidence fell to 3.5. No significant decline was observed in older children or adults. There was a 92% reduction in the number of meningitis cases and an 83% reduction in cases of bacteraemia. A similar decline was noted in 2 regions which followed different strategies for the introduction of the vaccination programme.
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| 26. |
- Gharizadeh, Baback, et al.
(author)
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Multiple group-specific sequencing primers for reliable and rapid DNA sequencing
- 2003
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In: Molecular and Cellular Probes. - 0890-8508 .- 1096-1194. ; 17:4, s. 203-210
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Journal article (peer-reviewed)abstract
- Pyrosequencing™ technology is a bioluminometric DNA sequencing method that employs a cascade of four enzymes to deliver sequence signals. To date this technology has been limited to the sequencing of short stretches of DNA. As an improvement to this technique, we have introduced a bacterial group-specific, multiple sequencing primer approach that circumvents sequencing of less informative semi-conservative regions of the 16S rRNA gene. This new approach is suitable for challenging templates, improving sequence data quality, avoiding sequencing of non-specific amplification products, lessening sequencing time, and moreover, this strategy should open the way for many new applications in the future. The group-specific, multiple sequencing primers can be applied in the Sanger dideoxy sequencing method as well. In addition, we have improved the chemistry of the Pyrosequencing system enabling sequencing of longer stretches of DNA, which allows numerous new applications.
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| 27. |
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| 28. |
- Hadad, Ronza, 1984-, et al.
(author)
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Novel meningococcal 4CMenB vaccine antigens : prevalence and polymorphisms of the encoding genes in Neisseria gonorrhoeae
- 2012
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In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 120:9, s. 750-760
-
Journal article (peer-reviewed)abstract
- The first cross-protective Neisseria meningitidis vaccine (focus on serogroup B), the protein-based 4 component meningococcus serogroup B (4CMenB), includes the New Zealand outer membrane vesicle and three main genome-derived neisserial antigens (GNAs). These GNAs are fHbp (fused to GNA2091), NHBA (fused to GNA1030) and NadA. In this study, the prevalence and polymorphisms of the nucleotide and amino acid sequences of the 4CMenB antigens in a temporally and geographically diverse collection of N. gonorrhoeae isolates (n similar to=similar to 111) were investigated. All the examined GNA genes, except the nadA gene, were present in all gonococcal isolates. However, 25 isolates contained premature stop codons in the fHbp gene and/or the nhba gene, resulting in truncated proteins. Compared with the 4CMenB antigen sequences in reference strain MC58, the gonococcal strains displayed 67.095.4% and 60.994.9% identity in nucleotide sequence and amino acid sequence, respectively, in the equivalent GNA antigens. The absence of NadA, lack of universal expression of fHbp and NHBA and the uncertainty regarding the surface exposure of fHbp as well as the function of NHBA in N. gonorrhoeae will likely limit the use of the identical 4CMenB antigens in a gonococcal vaccine. However, possible cross-immunity of 4CMenB with gonococci and expression and function of the equivalent gonococcal GNAs, as well as of more appropriate GNAs for a gonococcal vaccine, need to be further examined.
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| 29. |
- Hanson, Lars A, et al.
(author)
-
Immune system modulation by human milk.
- 2002
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In: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 503, s. 99-106
-
Journal article (peer-reviewed)
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| 30. |
- Hansson, L. Å., et al.
(author)
-
The immunological role of breast feeding
- 2001
-
In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 12:s14, s. 15-19
-
Journal article (peer-reviewed)
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| 31. |
- Hedberg, Sara Thulin, et al.
(author)
-
Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006 : phenotypic and genotypic perspectives
- 2009
-
In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 53:4, s. 1561-1566
-
Journal article (peer-reviewed)abstract
- Up-to-date information regarding the antibiotic susceptibility of Neisseria meningitidis strains from African countries is highly limited. Our aim was to comprehensively describe the antibiotic susceptibilities of a selection of N. meningitidis isolates recovered between 2000 and 2006 from 18 African countries, mainly those within the meningitis belt. Susceptibilities to 11 antibiotics were determined using Etest for 137 N. meningitidis isolates (stringently selected from 693 available isolates). The isolates were also characterized by serogrouping, multilocus sequence typing, genosubtyping, and penA allele identification. All N. meningitidis isolates were susceptible to ceftriaxone, chloramphenicol, and ciprofloxacin. No isolate produced beta-lactamase. Only three isolates (2%) displayed reduced susceptibility to penicillin G. The two isolates with the highest penicillin G MICs were the only isolates showing reduced susceptibility to ampicillin and cefuroxime. One of these isolates was also resistant to penicillin V. One percent of isolates displayed reduced susceptibility to rifampin, while 52% of the isolates were resistant to tetracycline, 74% were resistant to erythromycin, and 94% were resistant to sulfadiazine. The MICs of rifampin and tetracycline seemed to be associated with the serogroup of the isolates. In total, 18 sequence types (STs), 10 genosubtypes, and 8 different penA alleles were identified; the most common were ST-7, P1.20,9,35-1, and penA4, respectively. A high level of correlation was found between ST, genosubtype, and penA allele. In conclusion, N. meningitidis isolates from the African meningitis belt remain highly susceptible to the antibiotics used. Regarding beta-lactam antibiotics, rare isolates showed a reduced susceptibility to penicillins, but the expanded-spectrum cephalosporins are not affected at present.
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| 32. |
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| 33. |
- Hedberg, Sara Thulin, et al.
(author)
-
Combined real-time PCR and pyrosequencing strategy for objective, sensitive, specific, and high throughput identification of reduced susceptibility to penicillins in Neisseria meningitidis
- 2008
-
In: Antimicrobial Agents and Chemotherapy. - Washington, DC : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 52:2, s. 753-756
-
Journal article (peer-reviewed)abstract
- A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Pen(i)-specific sites and reduced susceptibility to penicillins was identified.
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| 34. |
- Hedberg, Sara Thulin, 1980-, et al.
(author)
-
Genetic characterisation of the emerging invasive Neisseria meningitidis serogroup Y in Sweden, 2000 to 2010
- 2011
-
In: Eurosurveillance. - Saint-Maurice, France : European Centre for Disease Prevention and Control. - 1025-496X .- 1560-7917. ; 16:23
-
Journal article (peer-reviewed)abstract
- Neisseria meningitidis serogroups B and C have beenresponsible for the majority of invasive meningococcaldisease in Europe. Recently, an increase of N. meningitidisdisease due to serogroup Y has been notedin Sweden (in 2010, the proportion was 39%, with anincidence of 0.23 per 100,000 population), as well as inother northern European countries. We aimed to investigatethe clonal pattern of the emerging serogroup Yin Sweden during 2000 to 2010. The serogroup Y isolatesidentified during this time (n=85) were characterisedby multilocus sequence typing and sequencing ofthe fetA, fHbp, penA, porA and porB genes. The mostfrequent clone (comprising 28 isolates) with identicalallele combinations of the investigated genes, waspartly responsible for the observed increased numberof N. meningitidis serogroup Y isolates. It was sulfadiazineresistant, with genosubtype P1.5-2,10-1,36-2,sequence type 23, clonal complex 23, porB allele 3-36,fetA allele F4-1, fHbp allele 25 and penA allele 22. Thefirst case with disease due to this clone was identifiedin 2002: there was a further case in 2004, six during2006 to 2007, eight during 2008 to 2009, with a peakof 12 cases in 2010. An unusual increase of invasivedisease in young adults (aged 20–29 years) caused bythis clone was shown, but no increase in mortality ratewas observed.
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| 35. |
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| 36. |
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| 37. |
- Heikkinen, Terho, et al.
(author)
-
Schould healthy children be vaccinated against influenza?
- 2006
-
In: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 165:4, s. 223-228
-
Journal article (peer-reviewed)abstract
- Influenza is often regarded as an illness of the elderly portion of the population because most of the excess mortality associated with influenza epidemics occurs in that age group. However, evidence derived from a large number of clinical studies carried out in different countries and various settings has clearly demonstrated that the burden of influenza is also substantial in children. The attack rates of influenza during annual epidemics are consistently highest in children, and young children are hospitalized for influenza-related illnesses at rates comparable to those for adults with high-risk conditions. Especially among children younger than 3 years of age, influenza frequently predisposes the patient to bacterial complications such as acute otitis media. Children also serve as the main transmitters of influenza in the community. A safe and effective vaccine against influenza has been available for decades, but the vaccine is rarely used even for children with high-risk conditions. Despite several existing problems related to influenza vaccination of children, the current evidence indicates that the advantages of vaccinating young children would clearly outweigh the disadvantages. Considering the total burden of influenza in children, children younger than 3 years of age should be regarded as a high-risk group for influenza, analogously with the age-based definition of high risk among persons 65 years of age or older. Annual influenza vaccination should be recommended to all children from 6 months to 3 years of age.
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| 38. |
- Hugosson, Svante, et al.
(author)
-
Invasive Haemophilus influenzae Disease : Epidemiology and Clinical Spectrum Before Large-scale H. influenzae Type b Vaccination
- 1995
-
In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 27:1, s. 63-67
-
Journal article (peer-reviewed)abstract
- In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (cases/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.
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| 39. |
- Issa, Mohamed, et al.
(author)
-
Neisseria meningitidis serogroup W-135 isolated from healthy carriers and patients in Sudan after the Hajj in 2000
- 2003
-
In: Scandinavian Journal of Infectious Diseases. - 0036-5548 .- 1651-1980. ; 35:4, s. 230-233
-
Journal article (peer-reviewed)abstract
- The first epidemic in the world of meningococcal disease due to serogroup W-135 was reported during the Hajj in 2000, with subsequent spread. The aims of the present study were to investigate whether the Hajj 2000 Neisseria meningitidis serogroup W-135 had also been carried to Sudan in the eastern part of the African meningitis belt, by examining healthy Sudanese pilgrims (Hajj 2000) and members of their families, and whether the strain was causing meningitis. The phenotypic character of W-135 meningococci from Sudanese carriers (n = 5) and patients (n = 2) 1 y later was similar to W-135 strains associated with Hajj 2000. The present study, using the combination of the 2 molecular techniques; sequencing of the porA gene for variable regions (VR1, VR2 and VR3) and pulsed-field gel electrophoresis of the entire genome (using SpeI and NheI), shows that the Hajj 2000 serogroup W-135 clone (P1.5,2,36-2 of the ET-37 complex) most probably was introduced into Sudan, by pilgrims returning from the Hajj 2000. This strain has not been diagnosed before in Sudan. Close epidemiological surveillance is required to identify a possible new emerging meningitis epidemic.
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| 40. |
- Issa, Mohamed, et al.
(author)
-
PCR of Cerebrospinal Fluid for Diagnosis of Bacterial Meningitis During Meningococcal Epidemics : an Example from Sudan
- 2003
-
In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 35:10, s. 719-723
-
Journal article (peer-reviewed)abstract
- Meningococcal disease is feared due to its rapid progression and high case fatality rate, especially in the African meningitis belt, where epidemics of meningococcal meningitis appear cyclically. Culture, direct microscopy and antigen detection are the basic methods for diagnosis and species identification of bacterial meningitis. These methods are known to have limitations, especially in developing countries. The aim of the present study was to document the application of PCR technology for the diagnosis of bacterial meningitis in cerebrospinal fluid (CSF) samples (n = 52) collected during epidemics in Sudan. In the application of PCR for detection of the causative agent of bacterial meningitis (based on the 16S rRNA gene), bacterial DNA was identified in 49 samples. Common bacterial species causing bacterial meningitis could be detected in 31 of the CSF samples (27 meningococci), while 18 contained DNA, mainly from normally contaminating bacteria. A specific PCR for group A meningococci (based on the sacC gene) was positive in 27 of the CSF samples. The results show that PCR technology is a sharpedged tool for confirmation of a diagnosis of meningococcal meningitis and for obtaining a direct genogrouping of group A meningococci in CSF. It is important to stress the use of direct and specific PCRs to avoid interference by contaminating bacteria, a great problem in samples from areas in the meningitis belt.
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| 41. |
- Jacobsson, Susanne, 1974-
(author)
-
Characterisation of Neisseria meningitidis from a virulence and immunogenic perspective that includes variations in novel vaccine antigens
- 2009
-
Doctoral thesis (other academic/artistic)abstract
- Neisseria meningitidis, also referred to as meningococcus, is a Gram-negative diplococcal bacterium best known as an important cause of meningitis and septicaemia worldwide. Meningococcal disease is a rare but life-threatening illness that may progress to death despite optimal medical care including appropriate antibiotic therapy. Case fatality remains high and survivors may suffer from significant sequelae because of impaired circulation and/or damages to the central nervous system. Prevention through vaccination remains a most effective approach to control disease. The main problem, however, is the absence of an effective vaccine against disease caused by a broad spectrum of group B isolates. Understanding how the meningococcus can be both a common commensal and a devastating human pathogen is a major task for researchers in the area of meningococcal disease. In paper I, we investigated and described the characteristics of fatal meningococcal isolates and compared these with non-fatal invasive meningococcal isolates. The diversity was high within the isolates from both patient groups. Group Y, serotypes 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2 were more common in fatal cases as were being elderly and female. The second major task in the area of meningococcal disease is to develop a group B vaccine. Six genes encoding antigens identified as promising vaccine candidates were examined in papers II & III. Based on our results, the prevalence of these genes and their sequence variation have the potential to constitute a meningococcal vaccine of broad range that also cover group B isolates in Sweden and other countries with a similar distribution of disease causing meningococci. In paper IV, we investigated the levels of IgG antibodies in serum directed against fHbp and NadA, two of the antigens included in papers II & III. Overall, the immune response to fHbp seems to be higher than the immune response to NadA, with a clear rise of anti-fHbp in the young adult groups (20-29 years).
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| 42. |
- Jacobsson, Susanne, et al.
(author)
-
Characteristics of Neisseria meningitidis isolates causing fatal disease
- 2008
-
In: Scandinavian Journal of Infectious Diseases. - London : Taylor & Francis. - 0036-5548 .- 1651-1980. ; 40:9, s. 734-744
-
Journal article (peer-reviewed)abstract
- The objectives of the present study were to describe a selection of characteristics of all available fatal meningococcal isolates (n=62) and to compare these with all the other invasive isolates (non-fatal, n=474) collected in Sweden from 1995 to 2004 (fatality rate of 12%). The coverage of the fatal isolates by presently discussed outer membrane vesicle (OMV) vaccines was also estimated. The isolates were characterized by serogroup, serotype, genosubtype, multilocus sequence type and antibiogram. Basic epidemiological data were gathered. The results of the fatal isolates showed 55% serogroup B, 27% C, 15% Y and 3% W-135, with a fatality rate of 11% for B, 12% for C, 17% for Y and 8% for W-135. Characteristics associated with higher mortality were age, gender, serogroup Y, serotype 14 and 15 and genosubtypes P1.7,16-29,35 and P1.5-1,10-4,36-2. In contrast, non-14/non-15 serotypes, the genosubtypes P1.5-1,10-8,36-2; P1.7-2,4,37 and P1.7,16,35, as well as reduced sensitivity for penicillin G were associated with decreased mortality. The presently discussed OMV vaccines could, based solely on the complete genosubtype, theoretically cover up to 44% of the fatal serogroup B cases and up to 100% if every variable region by itself is capable to induce protective immunity.
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| 43. |
- Jacobsson, Susanne, et al.
(author)
-
Molecular characterisation of group A Neisseria meningitidis isolated in Sudan 1985–2001
- 2003
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 111:11, s. 1060-1066
-
Journal article (peer-reviewed)abstract
- A total of 33 group A Neisseria meningitidis (Mc) isolates, collected in Sudan between 1985 and 2001, were studied in order to describe the changes over time in a country within the meningitis belt of Africa. The isolates were characterised by traditional phenotypic methods (serogrouping, serotyping, serosubtyping and antibiogram) and molecular techniques (genosubtyping, pulsed-field gel electrophoresis [PFGE] with restriction endonucleases SpeI and NheI, and multilocus sequence typing [MLST]). Three clones of group A Mc were identified: one before 1988 (sulphadiazine sensitive, serotype 4, genosubtype P1.7,13-1,35-1, sequence type 4 [ST-4]); another during and after the 1988 epidemic (sulphadiazine resistant, serotype 4, genosubtype P1.20,9,35-1, ST-5); and a third causing the 1999 epidemic (sulphadiazine resistant, serotype 4, genosubtype P1.20,9,35-1, ST-7). The first clone showed major differences compared to the other two. The second and third clones had many similarities with differences in only a single gene (pgm) in the MLST (47 of the 450 bp) but significant other differences according to the PFGE patterns. Within the clones, genosubtyping and MLST gave identical information (except one base substitution in the aroE gene in one isolate). However, the PFGE patterns showed changes over time within the clones, where SpeI revealed somewhat more diversity than NheI.
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| 44. |
- Jacobsson, Susanne, 1974-, et al.
(author)
-
Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease
- 2009
-
In: Vaccine. - Amsterdam : Elsevier. - 0264-410X .- 1873-2518. ; 27:10, s. 1579-1584
-
Journal article (peer-reviewed)abstract
- During the recent years, projects are in progress for designing broad-range non-capsular-based meningococcal vaccines, covering also serogroup B isolates. We have examined three genes encoding antigens (NadA, GNA1030 and GNA2091) included in a novel vaccine, i.e. the 5 Component Vaccine against Meningococcus B (5CVMB), in terms of gene prevalence and sequence variations. These data were combined with the results from a similar study, examining the two additional antigens included in the 5CVMB (fHbp and GNA2132).nadA and fHbp v. 1 were present in 38% (n=36), respectively 71% (n=67) of the isolates, whereas gna2132, gna1030 and gna2091 were present in all the Neisseria meningitidis isolates tested (n=95). The level of amino acid conservation was relatively high in GNA1030 (93%), GNA2091 (92%), and within the main variants of NadA and fHbp. GNA2132 (54% of the amino acids conserved) appeared to be the most diversified antigen. Consequently, the theoretical coverage of the 5CVMB antigens and the feasibility to use these in a broad-range meningococcal vaccine is appealing.
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| 45. |
- Jacobsson, Susanne, 1974-, et al.
(author)
-
Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens
- 2006
-
In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 24:12, s. 2161-2168
-
Journal article (peer-reviewed)abstract
- By the strategy “reverse vaccinology” a number of new antigens have been identified in Neisseria meningitidis, which are potential candidates for a highly needed broad-spectrum meningococcal vaccine. In the present study we examined the prevalence, sequence constancies and variations of the genes encoding three of these new antigens designated, genome-derived neisserial antigen (GNA) 1870, GNA1946 and GNA2132. All three genes were present in all N. meningitidis isolates tested. Concerning gna1870, three major variants of the gene sequences and deduced amino acid sequences were identified and 56% of the deduced amino acids were conserved in all isolates. In gna1946, 98% of the deduced amino acids were conserved and in gna2132, 54% of the deduced amino acids were conserved. Based on gene prevalence and conservation, all three antigens are promising candidates for an effective meningococcal vaccine against all N. meningitidis irrespective of serogroup.
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| 46. |
- Jacobsson, Susanne, 1974-, et al.
(author)
-
Seroprevalence of antibodies against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis
-
Other publication (other academic/artistic)abstract
- The IgG antibody levels directed against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis, were examined in order to investigate the extent of natural immunisation against these antigens in different age groups. As a comparison, the IgG antibody levels against Haemophilus influenzae type b were examined.In the two youngest age groups, below 10 years of age, relatively low levels of both anti-fHbp and anti-NadA were measured. A 9-fold higher concentration of anti-fHbp was noted in the age groups up to 29 years of age to its peak at 30-39 years, followed by decreased levels with age. Anti-NadA showed a certain increase up to 9 years followed by an even increase up to 49 years.
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| 47. |
- Jacobsson, Susanne, et al.
(author)
-
Seroprevalence of antibodies against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis
- 2009
-
In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 27:42, s. 5755-5759
-
Journal article (peer-reviewed)abstract
- The IgG antibody levels directed against fHbp and NadA, two potential vaccine antigens for Neisseria meningitidis, were examined in order to investigate the extent of natural immunisation against these antigens in different age groups. As a comparison, the IgG antibody levels against Haemophilus influenzae type b were examined. In the two youngest age groups, below 10 years of age, relatively low levels of both anti-fHbp and anti-NadA were measured. A 15-fold higher geometric mean concentration of anti-fHbp was noted in the age group 20-29 years as compared to the age group 15-19 years. The peak concentration was found at 30-39 years, followed by decreased levels with age. Anti-NadA showed a certain increase up to 9 years followed by an even increase up to 40-49 years.
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| 48. |
- Jurstrand, Margaretha, et al.
(author)
-
Characterization of Chlamydia trachomatis omp1 genotypes among sexually transmitted disease patients in Sweden
- 2001
-
In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 39:11, s. 3915-3919
-
Journal article (peer-reviewed)abstract
- A method for detection and genotyping of genital Chlamydia trachomatis infections based on omp1 gene amplification and sequencing was developed. DNA was extracted from urogenital or urine samples using a Chelex-based method, and an approximately 1,100-bp-long fragment from the omp1 gene was directly amplified and sequenced. Genotyping was performed by BLAST similarity search, and phylogenetic tree analysis was used to illustrate the evolutionary relationships between clinical isolates and reference strains. The method was used to determine the genotypes of C. trachomatis in 237 positive urogenital and/or urine specimens collected at a Swedish sexually transmitted disease clinic during 1 year. The most common genotypes corresponded to serotypes E (47%) and F (17%). The omp1 gene was highly conserved for genotype E (106 of 112 samples without any mutation) and F (41 of 42 samples without any mutation) strains but appear slightly less conserved for genotypes G (n = 6) and H (n = 6), where the sequences displayed one to four nucleotide substitutions relative to the reference sequence. Genotyping of samples collected at the follow-up visit indicated that two patients had become reinfected, while three other patients suffered treatment failure or reinfection. One woman appeared to have a mixed infection with two different C. trachomatis strains. This omp1 genotyping method had a high reproducibility and could be used for epidemiological characterization of sexually transmitted Chlamydia infections.
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| 49. |
- Kelly, Anne, 1978-, et al.
(author)
-
Gene variability and degree of expression of vaccine candidate factor H binding protein in clinical isolates of Neisseria meningitidis
- 2013
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 121:1, s. 56-63
-
Journal article (peer-reviewed)abstract
- The factor H binding protein (fHbp) is currently being evaluated in clinical trials as a vaccine candidate for a meningococcal group B vaccine. We have previously described the prevalence and sequence variation of fHbp (Jacobsson et al., 2009) and here we investigate the expression of the antigen. The present study includes isolates from carriers (n = 62) and patients with invasive Neisseria meningitidis infections (n = 146), of which 62 had a fatal outcome. Among the invasive isolates from patients with fatal and non-fatal infections fHbp allele 1 was most common (42% and 29% respectively), but it was only identified in 3% of the carrier isolates, where allele 16 was most frequent (13%). The Fluorescence-activated cell sorting analysis identified fHbp expression in all except seven isolates and further analysis by Western blot showed that five of these seven samples were indeed negative using a polyclonal anti-fHbp serum. The negative isolates belonged to serogroup B fHbp allele 24, Y allele 104, and W-135 allele 16 (all invasive). Two were non-serogroupable carrier isolates (allele 21 and 101). An interesting finding is that isolates from invasive infections with fatal outcome had lower expression of fHbp or lower affinity for the fHbp antibody compared to isolates from non-fatal invasive infections and carriers.
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| 50. |
- Ma, Yuqian, et al.
(author)
-
Genome-Wide Sequencing of Cellular microRNAs Identifies a Combinatorial Expression Signature Diagnostic of Sepsis
- 2013
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
-
Journal article (peer-reviewed)abstract
- Rationale: Sepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity. Objectives: We hypothesized changes in expression of microRNAs during sepsis may be of diagnostic value in the intensive care unit (ICU). Methods: Massively parallel sequencing of microRNAs was utilised for screening microRNA candidates. Putative microRNAs were validated using quantitative real-time PCR (qRT-PCR). This study includes data from both a training cohort (UK) and an independent validation cohort (Sweden). A linear discriminant statistical model was employed to construct a diagnostic microRNA signature. Results: A panel of known and novel microRNAs were detectable in the blood of patients with sepsis. After qRT-PCR validation, microRNA miR-150 and miR-4772-5p-iso were able to discriminate between patients who have systemic inflammatory response syndrome and patients with sepsis. This finding was also validated in independent cohort with an average diagnostic accuracy of 86%. Fractionating the cellular components of blood reveals miR-4772-5p-iso is expressed differentially in monocytes. Functional experiments using primary human monocytes demonstrate that it expressed in response to TLR ligation. Conclusions: Taken together, these data provide a novel microRNA signature of sepsis that should allow rapid point-of-care diagnostic assessment of patients on ICU and also provide greater insight into the pathobiology of this severe disease.
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