| 1. |
- Gullsby, Karolina
(författare)
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Molecular detection and epidemiological studies of atypical bacteria causing respiratory tract infections
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Respiratory infections are common causes of morbidity and mortality. Chlamydia pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis cause respiratory infection, often with similar symptoms. Molecular diagnostic methods are preferred since these bacteria are difficult to culture. The aim of this thesis was to evaluate and improve the diagnostics and knowledge of the epidemiology of these bacteria.A real-time polymerase chain reaction (PCR) method targeting the IS481 element present in the genome of B. pertussis was compared to culture and serology results, and a duplex real-time PCR method was constructed for detecting C. pneumoniae and M. pneumoniae, which was compared to two endpoint PCR methods. Both real-time PCR methods showed high sensitivity and specificity.Typing of 624 M. pneumoniae samples, collected from 1996 to 2017 from four counties, was performed by P1 typing and multiple-locus variable number tandem repeat analysis (MLVA). A polyclonal distribution of strains was seen over all epidemic periods, but strains of P1 type 2/variant 2 and MLVA types 3-5-6-2 and 4-5-7-2 predominated in 2010−2013. A shift from type 2 strains to different variant 2 strains was seen and a new variant, 2e, was detected in 2016−2017. An A2063G mutation associated with macrolide resistance was detected by a fluorescence resonance energy transfer (FRET) PCR method in one (0.16%) of 608 M. pneumoniae strains.Molecular characterisation using whole-genome sequencing of 93 B. pertussis isolates, collected between 1986 and 2016 from three counties showed that there were polyclonal strains in the county of Dalarna, Gävleborg and Uppsala in the years 2014−2016. Changes in virulence-related genes were detected: a shift from isolates harbouring the ptxP3 allele in favour of ptxP1 was seen, and almost all isolates had a disrupted prn gene. No detection of macrolide resistance in B. pertussis was detected.In conclusion, the validated real-time PCR methods for detection of B. pertussis, C. pneumoniae and M. pneumoniae have led to improved diagnostic methods for use in clinical laboratories. The molecular characterisation of M. pneumoniae and B. pertussis strains has contributed to the wider understanding of the genetic changes that has occurred over the epidemic periods, but further studies is needed.
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| 2. |
- Hadfield, James, et al.
(författare)
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Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion
- 2017
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory Press. - 1088-9051 .- 1549-5469. ; 27:7, s. 1220-1229
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.
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| 3. |
- Hokynar, Kati, et al.
(författare)
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The Finnish New Variant of Chlamydia trachomatis with a Single Nucleotide Polymorphism in the 23S rRNA Target Escapes Detection by the Aptima Combo 2 Test
- 2019
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- In 2019, more than 200 cases of Chlamydia trachomatis negative/equivocal by the Aptima Combo 2 assay (AC2, target: 23S rRNA) with slightly elevated relative light units (RLUs), but positive by the Aptima Chlamydia trachomatis assay (ACT, target: 16S rRNA) have been detected in Finland To identify the cause of the AC2 CT false-negative specimens, we sequenced parts of the CT 23S rRNA gene in 40 specimens that were AC2 negative/equivocal but ACT positive. A single nucleotide polymorphism (SNP; C1515T in the C. trachomatis 23S rRNA gene) was revealed in 39 AC2/ACT discordant specimens. No decrease in the number of mandatorily notified C. trachomatis cases was observed nationally in Finland in 2010-2019. When RLUs obtained for AC2 negative specimens were retrospectively evaluated in 2011-2019, a continuous increase in the proportion of samples with RLUs 10-19 was observed since 2014, and a slight increase in the proportion of samples with RLUs 20-84 in 2017-2019, indicating that the Finnish new variant of C. trachomatis might have been spreading nationally for several years. This emphasizes that careful surveillance of epidemiology, positivity rate and test performance are mandatory to detect any changes affecting detection of infections.
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| 4. |
- Pesonen, Erkki, et al.
(författare)
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Dual role of infections as risk factors for coronary heart disease.
- 2007
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 192:2, s. 370-375
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of the study was to explore whether exposure to microbial agents determines the prevalence of acute coronary events. Methods and results: Patients with unstable angina pectoris and myocardial infarction (N = 335) and their paired controls were investigated. The subjects answered a questionnaire about their childhood contagious diseases: varicella, scarlet fever, measles, rubella, mononucleosis and mumps. Blood samples were taken for bacterial and viral serology. The odds ratio for CHD was highest in the upper quartile of the enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae HSP60 IgG antibody titers (1.86, p = 0.001, 1.57, p < 0.048 and 1.70, p = 0.016, respectively). The antibody titers increased cumulatively the risk for CHD (odds ratios 1.89, 2.24, 3.92 and p-values < 0.001, 0.001 and 0.047). Childhood contagious diseases (n = 6) had a protecting effect against CHD (odds ratio 0.86, p = 0.013). The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p = 0.007). Conclusions: Infections have a dual role in the genesis of CHD. EV, HSV and C. pneumoniae heat shock protein 60 IgG antibodies are associated with increased risk for CHID. Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.
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| 5. |
- Pesonen, Erkki, et al.
(författare)
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Elevated infection parameters and infection symptoms predict an acute coronary event.
- 2008
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Ingår i: Therapeutic Advances in Cardiovascular Disease. - : SAGE Publications. - 1753-9447 .- 1753-9455. ; 2:6, s. 419-424
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The etiology and significance of flu-like symptoms often appearing before myocardial infarction should be clarified. METHODS: In a case-control study of 323 matched controls and a random sample of 110 out of 351 cases the presence of infection symptoms during the preceding four weeks before admission were asked and blood samples taken. RESULTS: Enterovirus (EV), herpes simplex virus (HSV), and Chlamydia pneumoniae IgA titers were significantly higher in cases than in controls (p<0.001, 0.008 and 0.046, respectively). Flu-like symptoms appeared significantly more often in patients than in controls the most common one being fatigue (p<0.001). In controls with fatigue, EV and HSV titers showed a trend to be higher (1.50 vs 1.45 and 4.29 vs 3.73) than in controls without fatigue but only HSV titers were statistically significantly higher (3.47 vs 3.96, p = 0.02). Even CRP and amyloid A concentrations (3.49 vs 2.08, p<0.0001 and 5.70 vs 3.77 mg/l, p = 0.003, respectively) as well as C4 (0.40 vs 0.44, p = 0.02) were higher in controls with fatigue. CONCLUSIONS: Odds ratios for a coronary event in a logistic regression model were 4.79 for fatigue and 2.72 for EV antibody levels in their fourth quartile. A linear-by-linear association test showed increasing number of single symptoms with higher EV titer quartiles (p = 0.004).
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| 6. |
- Pesonen, Erkki, et al.
(författare)
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Infections as a stimulus for coronary occlusion, obstruction, or acute coronary syndromes.
- 2009
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Ingår i: Therapeutic Advances in Cardiovascular Disease. - : SAGE Publications. - 1753-9447 .- 1753-9455.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : Atherosclerosis is considered to be an inflammatory disease. Infections are a significant cause of inflammation. Acute infections might precipitate acute coronary syndromes (ACS) whereas chronic infections might be stimuli for the development of atherosclerosis. METHODS: : Coronary angiograms were done on 211 of 335 patients with ACS and the percentage of coronary obstruction was determined. Serum antibody levels to Chlamydia pneumoniae, C. pneumoniae heat shock protein 60 (CpnHSP60), human heat shock protein 60 (hHSP60), enterovirus (EV), herpes simplex virus (HSV), cytomegalovirus (CMV), and two major periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were measured in healthy controls (n = 355) and all patients. RESULTS: : Serum antibody levels to periodontal pathogens did not correlate with ACS. However, IgA-class antibody levels to Aggregatibacter actinomycetemcomitans (p = 0.021), CpnHSP60 (p = 0.048) an hHSP60 (p = 0.038) were higher in patients with coronary occlusion or obstruction compared to those without any obstruction. Odds ratios for coronary changes in the highest quartile as compared to the lower quartiles were for A. actinomycetemcomitans IgA 7.84 (95% CI 1.02-60.39, p = 0.048), for CpnHSP60 IgA 8.61 (1.12-65.89, p = 0.038), and for human HSP60 IgA 3.51 (0.79-15.69, p = 0.100). CONCLUSIONS: : We have previously reported that EV and HSV titres correlated significantly to acute coronary events. They do not correlate to the degree of coronary obstruction as shown here. However, infection by A. actinomycetemcomitans or C. pneumoniae or host response against them associated with coronary obstruction. Clinical coronary events may arise by the effect of acute infections and obstructing lesions by a chronic inflammatory stimulus.
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| 7. |
- Pesonen, Erkki, et al.
(författare)
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Mannose-binding lectin as a risk factor for acute coronary syndromes.
- 2009
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Ingår i: Annals of Medicine. - : Informa UK Limited. - 1365-2060 .- 0785-3890. ; 41, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Background. Mannose-binding lectin (MBL) is a multifunctional protein involved in innate immunity. We tested whether MBL and elevated viral and bacterial antibodies were risk factors for acute coronary events. Design. Controlled cohort study. Methods. A total of 354 patients with unstable angina pectoris (UA) or acute myocardial infarction (AMI) were compared with 334 paired controls. Results. Enterovirus titres were associated with increased risk of UA (odds ratio 10.04, P<0.001) and AMI (odds ratio 3.18, P=0.003), but titres did not correlate with either MBL concentration or genotype. Chlamydia pneumoniae heat shock protein 60 IgG concentrations were also associated with increased risk of UA (odds ratio 1.63, P=0.049). Compared to asymptomatic controls, patients had lower complement C3 serum concentrations (P<0.001), higher MBL serum concentration, and more frequently had MBL genotypes that determined high MBL levels (P<0.001). High MBL genotypes had odds ratios of 1.16 (P=0.010) for UA and 1.12 (P=0.007) for AMI. The elevation of MBL concentrations in the acute phase correlated with MBL concentrations after recovery (r=0.85, P<0.001). Conclusions. Elevated microbial titres, indicating an on-going inflammation, were associated with cardiovascular events. MBL might have a dual role both decreasing susceptibility to infections and increasing the risk of acute coronary syndromes.
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| 8. |
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| 9. |
- Pussinen, Pirkko J., et al.
(författare)
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The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. Methods: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. Results: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p < 0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p < 0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p < 0.001) and 4.69 (1.10-20.01, p = 0.037), respectively. Conclusions: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 10. |
- Unemo, Magnus, 1970-, et al.
(författare)
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Finnish new variant of Chlamydia trachomatis escaping detection in the Aptima Combo 2 assay also present in Örebro County, Sweden, May 2019
- 2019
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Ingår i: Eurosurveillance. - : European Centre for Disease Prevention and Control. - 1560-7917 .- 1025-496X. ; 24:26
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Tidskriftsartikel (refereegranskat)abstract
- We identified the first two cases of the Finnish new variant of Chlamydia trachomatis (F-nvCT) beyond Finland in two clinical urogenital specimens in Örebro County, Sweden. These Aptima Combo 2 assay-negative specimens were Aptima Chlamydia trachomatis (CT) assay positive and had the characteristic C1515T mutation in the 23S rRNA gene. From 22 March to 31 May 2019, 1.3% (2/158) of the CT-positive cases in Örebro County were missed because of the F-nvCT. International awareness, investigations and actions are essential.
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