| 1. |
- Shaw, L. M., et al.
(author)
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Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease
- 2018
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 14:11, s. 1505-1521
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The Alzheimer's Association convened a multidisciplinary workgroup to develop appropriate use criteria to guide the safe and optimal use of the lumbar puncture procedure and cerebrospinal fluid (CSF) testing for Alzheimer's disease pathology detection in the diagnostic process. METHODS: The workgroup, experienced in the ethical use of lumbar puncture and CSF analysis, developed key research questions to guide the systematic review of the evidence and developed clinical indications commonly encountered in clinical practice based on key patient groups in whom the use of lumbar puncture and CSF may be considered as part of the diagnostic process. Based on their expertise and interpretation of the evidence from systematic review, members rated each indication as appropriate or inappropriate. RESULTS: The workgroup finalized 14 indications, rating 6 appropriate and 8 inappropriate. DISCUSSION: In anticipation of the emergence of more reliable CSF analysis platforms, the manuscript offers important guidance to health-care practitioners and suggestions for implementation and future research. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 2. |
- Beale, M. A., et al.
(author)
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Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis
- 2021
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:12
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Journal article (peer-reviewed)abstract
- Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides. Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked to a rapid expansion occurring since the end of the twentieth century.
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| 3. |
- Beale, M., et al.
(author)
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CONTEMPORARY SYPHILIS IS CHARACTERISED BY RAPID GLOBAL SPREAD OF PANDEMIC TREPONEMA PALLIDUM LINEAGES
- 2021
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In: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 97:Suppl. 1, s. A17-A17
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Journal article (other academic/artistic)abstract
- Background: Syphilis is an important sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The last two decades have seen syphilis incidence rise in many high-income countries, yet the evolutionary and epidemiological relationships that underpin this are poorly understood, as is the global T. pallidum population structure.Methods: We assembled a geographically and temporally diverse collection of clinical and laboratory samples, performing direct sequencing on the majority, and combining these with 133 publicly available sequences to compile a dataset comprising 726 T. pallidum genomes. We analysed the resulting genomes using detailed phylogenetic analysis and clustering.Results: We show that syphilis globally can be described by only two deeply branching lineages, Nichols and SS14. We show that both of these lineages can be found circulatingcon currently in 12 of the 23 countries sampled. To provide further phylodynamic resolution we subdivided Treponema pallidum subspecies pallidum into 17 distinct sublineages. Importantly, like SS14, we provide evidence that two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analysis showed that recent isolates circulating in 14 different countries were genetically identical in their core genome to those from other countries, suggesting frequent exchange through international transmission pathways. This contrasts with the majority of samples collected prior to 1983, which are phylogenetically distinct from these more recently isolated sublineages. Bayesian temporal analysis provided evidence of a population bottleneck and decline occurring during the late 1990s, followed by a rapid population expansion a decade later. This was driven by the dominant T. pallidum sublineages circulating today, many of which are resistant to macrolides.Conclusion: Combined we show that the population of contemporary syphilis in high-income countries has undergone a recent and rapid global expansion. This dataset will provide a framework for future characterisation and epidemiological investigation of syphilis populations.
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| 4. |
- Cole, Michelle Jayne, et al.
(author)
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No widespread dissemination of Chlamydia trachomatis diagnostic : escape variants and the impact of Neisseria gonorrhoeae positivity on the Aptima Combo 2 assay
- 2022
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In: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 98:5, s. 366-370
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Journal article (peer-reviewed)abstract
- OBJECTIVES: (NG) with the Hologic Aptima CT (ACT) assay was recommended to identify any CT variants.METHODS: From June to October 2019, specimens with discrepant AC2/ACT CT results were submitted to Public Health England and screened for detectable CT DNA using an inhouse real-time (RT)-PCR. When enough DNA was present, partial CT 23S rRNA gene sequencing was performed. Analysis of available relative light units and interpretative data was performed.RESULTS: A total of 317 discordant AC2/ACT specimens were collected from 315 patients. Three hundred were tested on the RT-PCR; 53.3% (n=160) were negative and 46.7% (n=140) were positive. Due to low DNA load in most specimens, sequencing was successful for only 36 specimens. The CT 23S rRNA wild-type sequence was present in 32 specimens, and two variants with C1514T or G1523A mutation were detected in four specimens from three patients. Of the discordant specimens with NG interpretation, 36.6% of NG-negative/CT-negative AC2 specimens had detectable CT DNA on the inhouse RT-PCR vs 53.3% of NG-positive/CT-negative specimens.CONCLUSIONS: No widespread dissemination of AC2 diagnostic-escape CT variants has occurred in England. We however identified the impact of NG positivity on the discordant AC2/ACT specimens; a proportion appeared due to NG positivity and the associated NG signal, rather than any diagnostic-escape variants or low DNA load. Several patients with gonorrhoea may therefore receive false-negative AC2 CT results. Single diagnostic targets and multiplex diagnostic assays have their limitations such as providing selection pressure for escape mutants and potentially reduced sensitivity, respectively. These limitations must be considered when establishing diagnostic pathways.
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