Draft Genome Sequence of Chlamydia trachomatis Strain 54, Isolated from the Urogenital Tract of a Male in Japan.
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SUBMITTER: Yamazaki T
PROVIDER: S-EPMC4616190 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
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Draft Genome Sequence of Chlamydia trachomatis Strain 54, Isolated from the Urogenital Tract of a Male in Japan.
Yamazaki Tomohiro T Matsuo Junji J Kikuchi Momoka M Miyamoto Kentaro K Oka Kentaro K Takahashi Motomichi M Takahashi Satoshi S Okubo Torahiko T Yamaguchi Hiroyuki H
Genome announcements 20151022 5
We report the draft genome sequence of Chlamydia trachomatis strain 54, isolated from the urogenital tract of a male in Japan, with unique polymorphic membrane proteins. Detailed genomic analysis will aid our understanding of the selective pressures that lead to sexual differentiation in chlamydial adaptive evolution. ...[more]
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Project description:BACKGROUND:Urogenital Chlamydia trachomatis infection remains prevalent and causes substantial reproductive morbidity. Recent studies have raised concern about the efficacy of azithromycin for the treatment of chlamydia infection. METHODS:We conducted a randomized trial comparing oral azithromycin with doxycycline for the treatment of urogenital chlamydia infection among adolescents in youth correctional facilities, to evaluate the noninferiority of azithromycin (1 g in one dose) to doxycycline (100 mg twice daily for 7 days). The treatment was directly observed. The primary end point was treatment failure at 28 days after treatment initiation, with treatment failure determined on the basis of nucleic acid amplification testing, sexual history, and outer membrane protein A (OmpA) genotyping of C. trachomatis strains. RESULTS:Among the 567 participants enrolled, 284 were randomly assigned to receive azithromycin, and 283 were randomly assigned to receive doxycycline. A total of 155 participants in each treatment group (65% male) made up the per-protocol population. There were no treatment failures in the doxycycline group. In the azithromycin group, treatment failure occurred in 5 participants (3.2%; 95% confidence interval, 0.4 to 7.4%). The observed difference in failure rates between the treatment groups was 3.2 percentage points, with an upper boundary of the 90% confidence interval of 5.9 percentage points, which exceeded the prespecified absolute 5-percentage-point cutoff for establishing the noninferiority of azithromycin. CONCLUSIONS:In the context of a closed population receiving directly observed treatment for urogenital chlamydia infection, the efficacy of azithromycin was 97%, and the efficacy of doxycycline was 100%. The noninferiority of azithromycin was not established in this setting. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00980148.).
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Project description:Chlamydia trachomatis is a major cause of ocular and sexually transmitted diseases worldwide. While much of our knowledge about its genetic diversity comes from serotyping or ompA genotyping, no quantitative assessment of genetic diversity within serotypes has been performed. To accomplish this, 507 urogenital samples from a multicenter U.S. study were analyzed by phylogenetic and statistical modeling. No B, Da, or I serotypes were represented. Based on our analyses, all but one previous urogenital B serotype was identified as Ba. This, coupled with the lack of B serotypes in our population, suggests that B has specific tropism for ocular mucosa. We identified a Ba/D recombinant (putative crossover nucleotide 477; P < 0.0001) similar to a B/D mosaic we described previously from an African trachoma patient. Computational analyses of the Ba/D recombinant indicated that upstream changes were less important for tissue tropism than downstream incorporation of the D sequence. Since most serotypes had nonsynonymous/synonymous ratios of <1.0, the major outer membrane protein, encoded by ompA, has many functional constraints and is under purifying selection. Surprisingly, all serotype groups except for J had a unimodal population structure indicating rapid clonal expansion. Of the groups with a unimodal structure, E and Ia and, to a lesser extent, G and K were prevalent, had infrequent incorporation of mutations, and, compared to other groups, had a relatively greater degree of diversifying selection, consistent with a selective sweep of mutations within these groups. Collectively, these data suggest a diverse evolutionary strategy for different serogroups of the organism.
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Project description:ObjectivesTo review the literature for non-standard treatment options for uncomplicated Chlamydia trachomatis (CT) infections in adolescents and adults.DesignSystematic review.Data sourcesOvid MEDLINE/PubMed, Ovid EMBASE, Cochrane Trials & Systematic Review Databases, CINAHL Plus with Full Text, Web of Science Core Collection, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and Health Canada Trials Database were searched for studies in English or French from 1 January 2006 to 6 August 2017. Keywords included CT, anti-infective or anti-bacterial agents, therapy/pharmacotherapy/management.Review methodsIncluded were primary research studies. Outcome measures included clinical or microbiological cure, treatment failure and adverse events. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed for risk of bias using the Revised Cochrane Risk of Bias V.2.0 tool for randomised and the Newcastle-Ottawa Quality Assessment Scale for non-randomised studies.Funding sourcePublic Health Agency of Canada.ResultsOf the 6899 records identified through the database search, 11 studies were included. One randomised controlled trial reported that delayed release doxycycline was non-inferior to azithromycin. Two studies examined higher doses of azithromycin but reported no additional benefit. One study looked at a 5-day azithromycin treatment regimen and reported a high cure rate. Two studies reported efficacy of sitafloxacin, and a single study supports the use of levofloxacin. Two phase 2 studies reported efficacy of single-dose rifalazil in both men and women. Only one retrospective study was identified that examined treatment in pregnant women and reported that efficacy with single-dose azithromycin exceeded that of amoxicillin and erythromycin. A single study examining the efficacy of a beta-lactam antibiotic was stopped early due to high treatment failures.ConclusionsThe paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections.Prospero registration numberCRD42017073096.
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