| 1. |
- Demczuk, Walter H.B., et al.
(författare)
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Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance : a Novel Antimicrobial Resistance Multilocus Typing Scheme for Tracking Global Dissemination of N. gonorrhoeae Strains
- 2017
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 55:5, s. 1454-1468
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Tidskriftsartikel (refereegranskat)abstract
- A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in Neisseria gonorrhoeae was developed and is publicly accessible (https://ngstar.canada.ca). The N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (penA, mtrR, porB, ponA, gyrA, parC, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire penA sequence, combining the historical nomenclature for penA types I to XXXVIII with novel nucleotide sequence designations; the full mtrR sequence and a portion of its promoter region; portions of ponA, porB, gyrA, and parC; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (n = 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (n = 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval [CI] = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (n = 100; 13.0%), ST-42 and ST-91 (n = 45; 5.9%), ST-64 (n = 44; 5.72%), and ST-139 (n = 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (n = 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (n = 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (n = 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (n = 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant N. gonorrhoeae strains.
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| 2. |
- Heymans, Raymond, et al.
(författare)
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Clonally Related Neisseria gonorrhoeae Isolates with Decreased Susceptibility to the Extended-Spectrum Cephalosporin Cefotaxime in Amsterdam, the Netherlands
- 2012
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 56:3, s. 1516-1522
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Tidskriftsartikel (refereegranskat)abstract
- From 2006 to 2008, Neisseria gonorrhoeae isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam sexually transmitted infections (STI) clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and N. gonorrhoeae multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four N. gonorrhoeae isolates with a cefotaxime MIC of >0.125 mu g/ml (group A), 54 with a cefotaxime MIC of 0.125 mu g/ml (group B), and a control group of 74 with a cefotaxime MIC of <0.125 mu g/ml (group C) were included. Fifty-three clonally related penA mosaic-positive isolates (penicillin-binding protein 2 type XXXIV) were identified in group A (n = 47 isolates; 64%) and B (n = 6 isolates; 11%). The 53 penA mosaic-positive isolates were predominantly NG-MAST ST1407 (87%) and contained an mtrR promoter A deletion (98%) and porB1b alterations G101K/A102N. All were assigned to the same NG-MLVA cluster that comprised in total 56 isolates. A correlation was found between decreased cefotaxime susceptibility and ST1407 that was highly prevalent among visitors of the Amsterdam STI clinic. The rapid spread of this strain, which also has been identified in many other countries, might be facilitated by high-risk sexual behavior and should be monitored closely to identify potential treatment failure. Quality-assured surveillance of ESC susceptibility on the national and international levels and exploration of new drugs and/or strategies for treatment of gonorrhea are crucial.
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| 3. |
- Junghans, Victoria, et al.
(författare)
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Effects of a local auxiliary protein on the two-dimensional affinity of a TCR-peptide MHC interaction
- 2020
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Ingår i: Journal of Cell Science. - : The Company of Biologists Ltd.. - 0021-9533 .- 1477-9137. ; 133:15
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Tidskriftsartikel (refereegranskat)abstract
- The affinity of T-cell receptors (TCRs) for major histocompatibility complex molecules (MHCs) presenting cognate antigens likely determines whether T cells initiate immune responses, or not. There exist few measurements of two-dimensional (2D) TCR-MHC interactions, and the effect of auxiliary proteins on binding is unexplored. Here, Jurkat T-cells expressing the MHC molecule HLA-DQ8-glia-α1 and the ligand of an adhesion protein (rat CD2) were allowed to bind supported lipid bilayers (SLBs) presenting fluorescently-labelled L3-12 TCR and rat CD2, allowing measurements of binding unconfounded by cell signaling effects or co-receptor binding. The 2D Kd for L3-12 TCR binding to HLA-DQ8-glia-α1, 14±5 molecules/μm2, was only marginally influenced by including CD2 up to ∼200 bound molecules/μm2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell-SLB contact size increased steadily with ligand density without affecting binding for contacts up to ∼20% of total cell area but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein-protein interaction can influence binding behavior at cell-cell contacts.
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| 4. |
- Karlsson, Marie, et al.
(författare)
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Levels of brominated flame retardants in Northern Fulmar (Fulmarus glacialis) eggs from the Faroe Islands
- 2006
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 367:2-3, s. 840-846
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Tidskriftsartikel (refereegranskat)abstract
- Eggs from Northern Fulmars (Fulmarus glacialis) were sampled in the Faroe Islands. The content of the brominated flame retardants tri- to decabromodiphenyl ethers (BDEs) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) were determined in nine samples in concentrations ranging from non-detectable to 7 ng g− 1(l.w.). The BDE levels were similar as in an earlier study of BDE levels in the fulmar eggs from the Faroe Islands but 10–1000 times lower compared to studies of eggs from seabirds and birds of prey from Europe. The two hexaBDEs #153 and #154 were the most abundant congeners, which represented around 50% of the total mean BDE concentration. The levels of BDE #209 were below the limit of detection (1.24 ng g− 1 l.w.) except for one sample, which showed a concentration of 7.18 ng g− 1 l.w. BTBPE was detected in eight samples and the mean level was 0.11 ng g− 1 l.w. This concentration was 150 times lower than the average total BDE concentration (including BDEs #28, #47, #100, #99, #154, #153, #183, #209). BTBPE has only been detected once before in biota. Also other bromo-containing compounds were detected in the fulmar eggs. One group identified was the polybrominated biphenyls (PBBs), but because of the absence of reference standards in the lab, these could not be quantified.
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| 5. |
- Wind, Carolien M., et al.
(författare)
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Successful Combination of Nucleic Acid Amplification Test Diagnostics and Targeted Deferred Neisseria gonorrhoeae Culture
- 2015
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:6, s. 1884-1890
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Tidskriftsartikel (refereegranskat)abstract
- Nucleic acid amplification tests (NAATs) are recommended for the diagnosis of N. gonorrhoeae infections because of their superior sensitivity. Increasing NAAT use causes a decline in crucial antimicrobial resistance (AMR) surveillance data, which rely on culture. We analyzed the suitability of the ESwab system for NAAT diagnostics and deferred targeted N. gonorrhoeae culture to allow selective and efficient culture based on NAAT results. We included patients visiting the STI Clinic Amsterdam, The Netherlands, in 2013. Patient characteristics and urogenital and rectal samples for direct N. gonorrhoeae culture, standard NAAT, and ESwab were collected. Standard NAAT and NAAT on ESwab samples were performed using the Aptima Combo 2 assay for N. gonorrhoeae and C. trachomatis. Two deferred N. gonorrhoeae cultures were performed on NAAT-positive ESwab samples after storage at 4 degrees C for 1 to 3 days. We included 2,452 samples from 1,893 patients. In the standard NAAT, 107 samples were N. gonorrhoeae positive and 284 were C. trachomatis positive. The sensitivities of NAAT on ESwab samples were 83% (95% confidence interval [CI], 75 to 90%) and 87% (95% CI, 82 to 90%), respectively. ESwab samples were available for 98 of the gonorrhea-positive samples. Of these, 82% were positive in direct culture and 69% and 56% were positive in the 1st and 2nd deferred cultures, respectively (median storage times, 27 and 48 h, respectively). Deferred culture was more often successful in urogenital samples or when the patient had symptoms at the sampling site. Deferred N. gonorrhoeae culture of stored ESwab samples is feasible and enables AMR surveillance. To limit the loss in NAAT sensitivity, we recommend obtaining separate samples for NAAT and deferred culture.
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| 6. |
- Wind, Carolien M., et al.
(författare)
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Test of cure for anogenital gonorrhoea using modern RNA-based and DNA-based nucleic acid amplification tests : a prospective cohort study
- 2016
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Ingår i: Clinical Infectious Diseases. - Cary, United Kingdom : Oxford University Press. - 1058-4838 .- 1537-6591. ; 62:11, s. 1348-1355
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of nucleic acid amplification tests (NAATs) to diagnose Neisseria gonorrhoeae infections complicates the performance of a test of cure (TOC) to monitor treatment failure, if this is indicated. As evidence for the timing of TOC using modern NAATs is limited, we performed a prospective cohort study to assess time to clearance when using modern RNA- and DNA-based NAATs.Methods: We included patients with anogenital gonorrhoea visiting the STI Clinic Amsterdam from March through October 2014. After treatment with ceftriaxone mono- or dual therapy (with azithromycin or doxycycline) anal, vaginal or urine samples were self-collected during 28 consecutive days, and analysed using an RNA-based NAAT (Aptima Combo 2) and a DNA-based NAAT (Cobas 4800). Clearance was defined as three consecutive negative results, and blips as isolated positive results following clearance.Results: We included 77 patients; five self-cleared gonorrhoea before treatment and ten were lost to follow-up. Clearance rate of the remaining 62 patients was 100%. Median time to clearance was two days, with a range of 1-7 days for RNA-based NAAT, and 1-15 days for DNA-based NAAT. The risk of finding a blip after clearance was 0.8% and 1.4%, respectively. One patient had a reinfection.Conclusions: If indicated, we recommend to perform a TOC for anogenital gonorrhoea at least 7 or 14 days after administering therapy, when using modern RNA- or DNA-based NAATs, respectively. When interpreting TOC results for possible treatment failure, both the occurrence of blips and a possible reinfection need to be taken into account.
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| 7. |
- Wind, Carolien M., et al.
(författare)
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Time to clearance of Chlamydia trachomatis RNA and DNA after treatment in patients coinfected with Neisseria gonorrhoeae : a prospective cohort study
- 2016
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Ingår i: BMC Infectious Diseases. - London, United Kingdom : BioMed Central. - 1471-2334. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Performing a test of cure (TOC) could demonstrate success or failure of antimicrobial treatment of Chlamydia trachomatis infection, but recommendations for the timing of a TOC using nucleic acid amplification tests (NAATs) are inconsistent. We assessed time to clearance of C. trachomatis after treatment, using modern RNA- and DNA-based NAATs.Methods We analysed data from patients with a C. trachomatis and Neisseria gonorrhoeae coinfection who visited the STI Clinic Amsterdam, The Netherlands, from March through October 2014. After treatment with ceftriaxone plus either azithromycin or doxycycline, patients self-collected anal, vaginal or urine samples during 28 consecutive days. Samples were analysed using an RNA-based NAAT (Aptima Combo 2) and a DNA-based NAAT (Cobas 4800 CT/NG). We defined clearance as three consecutive negative results, and defined "blips" as isolated positive results following clearance.Results: We included 23 patients with C. trachomatis and N. gonorrhoeae coinfection. All patients cleared C. trachomatis during follow-up, and we observed no reinfections. The median time to clearance (range) was 7 days (1-13) for RNA, and 6 days (1-15) for DNA. Ninety-five per cent of patients cleared RNA at day 13, and DNA at day 14. The risk of a blip after clearance was 4.4 % (RNA) and 1.7 % (DNA).Conclusions: If a TOC for anogenital chlamydia is indicated, we recommend performing it at least 14 days after initiation of treatment, when using modern RNA- and DNA-based assays. A positive result shortly after 14 days probably indicates a blip, rather than a treatment failure or a reinfection.
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