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1.
Microb Pathog ; 152: 104769, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33524569

RESUMO

OBJECTIVES: Syphilis is a sexually transmitted disease of global prevalence. Current diagnostic methods lack sensitivity and specificity, which limits the early diagnosis and prognosis of the disease. MiRNAs hold great promise as potential biomarkers for infectious diseases diagnosis. We previously profiled the expression of miRNAs in PBMCs from patients with different stages of syphilis. We aimed to further confirm the miR-101-3p, miR-195-5p, and miR-223-3p expression profiles and evaluate their diagnostic value in syphilis infection. METHODS: The expression levels of PBMC-derived miR-101-3p, miR-195-5p, and miR-223-3p were analyzed in 133 syphilis patients, 18 non-syphilis patients, and 23 healthy controls by RT-qPCR. ROC analysis was used to evaluate the differentiation power of these miRNAs in syphilis diagnosis, while the correlation between the expression of these miRNAs and TRUST titer was also statistically analyzed. RESULTS: These miRNAs were significantly upregulated in syphilis patients in a stage-specific manner. ROC analysis indicated that miR-223-3p was powerful in discriminating between controls and patients with early, primary, secondary, and latent syphilis, as well as serological cure; the miR-195-5p/miR-223-3p panel showed an improved capacity to differentiate between syphilis patients, primary, or serofast-stage syphilis and controls, while the three miRNAs combined showed an improved capacity to differentiate latent syphilis or serological cure from controls. Importantly, miR-101-3p and miR-223-3p singly or jointly could specifically distinguish syphilis from non-syphilis patients. Moreover, TRUST titer was significantly correlated with miR-101-3p expression. CONCLUSIONS: MiR-101-3p, miR-195-5p, and miR-223-3p might singly or jointly be potential diagnostic biomarkers at different stages of syphilis.

2.
BMC Genomics ; 22(1): 76, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482734

RESUMO

BACKGROUND: Though interest in human simple sequence repeats (SSRs) is increasing, little is known about the exact distributional features of numerous SSRs in human Y-DNA at chromosomal level. Herein, totally 540 maps were established, which could clearly display SSR landscape in every bin of 1 k base pairs (Kbp) along the sequenced part of human reference Y-DNA (NC_000024.10), by our developed differential method for improving the existing method to reveal SSR distributional characteristics in large genomic sequences. RESULTS: The maps show that SSRs accumulate significantly with forming density peaks in at least 2040 bins of 1 Kbp, which involve different coding, noncoding and intergenic regions of the Y-DNA, and 10 especially high density peaks were reported to associate with biological significances, suggesting that the other hundreds of especially high density peaks might also be biologically significant and worth further analyzing. In contrast, the maps also show that SSRs are extremely sparse in at least 207 bins of 1 Kbp, including many noncoding and intergenic regions of the Y-DNA, which is inconsistent with the widely accepted view that SSRs are mostly rich in these regions, and these sparse distributions are possibly due to powerfully regional selection. Additionally, many regions harbor SSR clusters with same or similar motif in the Y-DNA. CONCLUSIONS: These 540 maps may provide the important information of clearly position-related SSR distributional features along the human reference Y-DNA for better understanding the genome structures of the Y-DNA. This study may contribute to further exploring the biological significance and distribution law of the huge numbers of SSRs in human Y-DNA.

3.
BMC Biol ; 19(1): 5, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33441133

RESUMO

BACKGROUND: Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. RESULTS: We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28-34%, genus level). PHP also outperformed these two alignment-free methods much (24-38% vs 18-20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. CONCLUSIONS: The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

4.
BMC Microbiol ; 21(1): 3, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397284

RESUMO

BACKGROUND: Chlamydia trachomatis is the most common sexually transmitted infection and the bacterial agent of trachoma globally. C. trachomatis undergoes a biphasic developmental cycle involving an infectious elementary body and a replicative reticulate body. Little is currently known about the gene expression dynamics of host cell mRNAs, lncRNAs, and miRNAs at different stages of C. trachomatis development. RESULTS: Here, we performed RNA-seq and miR-seq on HeLa cells infected with C. trachomatis serovar E at 20 h post-infection (hpi) and 44 hpi with or without IFN-γ treatment. Our study identified and validated differentially expressed host cell mRNAs, lncRNAs, and miRNAs during infection. Host cells at 20 hpi showed the most differential upregulation of both coding and non-coding genes while at 44 hpi in the presence of IFN-γ resulted in a dramatic downregulation of a large proportion of host genes. Using RT-qPCR, we validated the top 5 upregulated mRNAs and miRNAs, which are specific for different stages of C. trachomatis development. One of the commonly expressed miRNAs at all three stages of C. trachomatis development, miR-193b-5p, showed significant expression in clinical serum samples of C. trachomatis-infected patients as compared to sera from healthy controls and HIV-1-infected patients. Furthermore, we observed significant upregulation of antigen processing and presentation, and T helper cell differentiation pathways at 20 hpi whereas T cell receptor, mTOR, and Rap1 pathways were modulated at 44 hpi. Treatment with IFN-γ at 44 hpi showed the upregulation of cytokine-cytokine receptor interaction, FoxO signaling, and Ras signaling pathways. CONCLUSIONS: Our study documented transcriptional manipulation of the host cell genomes and the upregulation of stage-specific signaling pathways necessary for the survival of the pathogen and could serve as potential biomarkers in the diagnosis and management of the disease.

5.
Methods Mol Biol ; 2199: 209-236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33125653

RESUMO

Efficient and comprehensive data management is an indispensable component of modern scientific research and requires effective tools for all but the most trivial experiments. The LabDB system developed and used in our laboratory was originally designed to track the progress of a structure determination pipeline in several large National Institutes of Health (NIH) projects. While initially designed for structural biology experiments, its modular nature makes it easily applied in laboratories of various sizes in many experimental fields. Over many years, LabDB has transformed into a sophisticated system integrating a range of biochemical, biophysical, and crystallographic experimental data, which harvests data both directly from laboratory instruments and through human input via a web interface. The core module of the system handles many types of universal laboratory management data, such as laboratory personnel, chemical inventories, storage locations, and custom stock solutions. LabDB also tracks various biochemical experiments, including spectrophotometric and fluorescent assays, thermal shift assays, isothermal titration calorimetry experiments, and more. LabDB has been used to manage data for experiments that resulted in over 1200 deposits to the Protein Data Bank (PDB); the system is currently used by the Center for Structural Genomics of Infectious Diseases (CSGID) and several large laboratories. This chapter also provides examples of data mining analyses and warnings about incomplete and inconsistent experimental data. These features, together with its capabilities for detailed tracking, analysis, and auditing of experimental data, make the described system uniquely suited to inspect potential sources of irreproducibility in life sciences research.

6.
BMJ Open ; 10(12): e041503, 2020 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-33376172

RESUMO

OBJECTIVES: Underscreening of HIV and syphilis in clinical settings is pervasive in resource-constrained settings. Heavy patient loads and competing health priorities in these settings inhibit provider's ability to meet screening coverage targets. The objective of this study was to examine determinants of provider-initiated HIV and syphilis testing uptake at sexually transmitted disease (STD) clinics in China. DESIGN: A cross-sectional study was performed between July 2016 and December 2016. SETTING: Seven STD clinics in Guangdong Province, China. PARTICIPANTS: Heterosexual STD clinic patients met the inclusion criteria, regardless of their interest in receiving HIV or syphilis testing. OUTCOME MEASURES: The syphilis and HIV testing uptake determined by patient receipt of results. RESULTS: A total of 1943 individuals were recruited in this study. Among those participants, 60.6% (1177/1943) and 74.3% (1443/1943) conducted HIV testing and syphilis testing during the study, respectively, of whom, 2.2% (26/1177) and 21.5% (310/1443) were found to be HIV-positive and syphilis-positive, respectively. The most common reason for rejecting HIV and syphilis testing was a low self-perceived risk of HIV and syphilis infection. After adjusting for covariates, condom use in the last sexual act, consistent condom use in the last 6 months, having paid sex in the last 6 months and having received any kind of HIV/STD-related knowledge during the last 12 years were positively associated with both HIV and syphilis testing uptake. CONCLUSIONS: The low-level of HIV and syphilis testing uptake, alongside with the high-level of engagement in risky sexual behaviours among heterosexual STD clinic patients, warranted a more targeted and intensive behavioural interventions to promote HIV and syphilis testing in this population.

7.
Sex Transm Dis ; Publish Ahead of Print2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33346591

RESUMO

BACKGROUND: Chlamydia trachomatis detection plays a crucial role in early diagnosis and treatment of C. trachomatis infection. In the current study the capability of sexually transmitted disease (STD) laboratories to detect C. trachomatis was investigated in Guangdong, China. METHODS: An external quality assessment panel including five positive samples with different C. trachomatis loads and two negative samples was distributed to 654 participating laboratories in October 2019, and the test results were analyzed by Guangdong Central STD Laboratory. The use of various C. trachomatis detection methods in Guangdong from 2015 to 2019 was also retrospectively investigated. RESULTS: Of the 654 participating STD laboratories, 559 (85.47%) used immune chromatographic-rapid diagnostic tests (IC-RDTs) to detect C. trachomatis in 2019, and 95 (14.53%) used nucleic acid amplification tests (NAATs). The rate of NAATs use increased approximately fourfold from 2015 to 2019. The sensitivity of IC-RDTs decreased markedly from 97.32% to 30.89% with decreasing C. trachomatis load, whereas that of NAATs was 97.62%-100% in all positive samples. With respect to negative samples the specificity of IC-RDTs was 97.13%-97.30% and that of NAATs was 98.95%-100%. Laboratories using IC-RDTs were less likely to detect C. trachomatis than those using NAATs in samples with C. trachomatis loads ≤ 20000 copies/mL (p < 0.0001). Further analysis indicated no significant difference (p > 0.05) in detection rate among the four IC-RDT assays commonly used by the participating laboratories. CONCLUSIONS: IC-RDTs are commonly used for C. trachomatis detection by many laboratories in Guangdong, but their low sensitivity may lead to missed diagnoses. NAATs exhibit high sensitivity and specificity, and should be recommended for C. trachomatis detection in STD laboratories.

8.
BMC Infect Dis ; 20(1): 950, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308173

RESUMO

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/uso terapêutico , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/genética , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , China/epidemiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/isolamento & purificação , Prevalência , RNA Ribossômico 23S/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia
9.
Infect Dis Poverty ; 9(1): 147, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33092641

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) self-testing may help improve test uptake among female sex workers. China has implemented many HIV self-testing programs among men who have sex with men, creating an opportunity for promotion among female sex workers. However, there is a limited literature on examining HIV self-testing among female sex workers. This study aimed to examine HIV self-testing experiences and its determinants among female sex workers in China. METHODS: A venue-based, cross-sectional study was conducted among Chinese female sex workers in 2019. Participants completed a survey including social-demographic characteristics, sexual behaviors, and HIV self-testing history, the distribution of which were analyzed using descriptive analysis. Multivariable logistic regression was conducted to identify associations with HIV self-testing. RESULTS: Among 1287 Chinese female sex workers, 1072 (83.3%, 95% confidence interval [CI] 81.2-85.3%) had ever tested for HIV, and 103 (8.0%, 95% CI 6.6-9.6%) had ever used HIV self-testing. More than half reported that the self-test was their first HIV test (59.2%, 61/103), around one-fifth reported HIV self-testing results influenced the price of sex (21.4%, 22/103). A minority of individuals reported ever experiencing pressure to undertake HIV self-testing (6.8%, 7/103). After adjusting for covariates, HIV self-testing was positively associated with receiving anal sex in the past month (adjusted odds ratio [aOR] = 2.2, 95% CI 1.4-3.5), using drugs before or during sex (aOR = 2.8, 95% CI 1.8-4.5), injecting drugs in the past 6 months (aOR = 2.6, 95% CI 1.2-6.0), being diagnosed with other sexually transmitted infections (aOR = 1.6, 95% CI 1.0-2.5), tested for other sexually transmitted infections in the past six months (aOR = 3.4, 95% CI 2.1-5.5), ever tested in the hospital (aOR = 3.4, 95% CI 2.0-5.6), and ever tested in the community (aOR = 1.5, 95% CI 1.2-1.9). CONCLUSIONS: Our findings suggest that HIV self-testing could expand overall HIV testing uptake, increase HIV testing frequency, reach sub-groups of high-risk female sex workers and has limited potential harms among female sex workers. HIV self-testing should be incorporated among Chinese female sex workers as a complement to facility-based HIV testing services.

10.
Sex Transm Dis ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33093287

RESUMO

OBJECTIVES: We conducted an observational study to determine whether syphilis patients who do not demonstrate serological cure or lack of seroreversion in nontreponemal (NT) antibody titers after initial therapy benefit from re-treatment and cerebrospinal fluid (CSF) analysis. METHODS: We enrolled syphilis patients from STD clinics in Guangzhou, China who had persistent NT titers after therapy. Serological non-response was defined as < 4-fold decline in baseline NT titers after therapy. Lack of seroreversion was defined as demonstrating a > 4-fold NT titer decline but without seroreversion to negative, or having persistent low-level titers (i.e. 1:1-1:2) after therapy. Following consent, we abstracted medical record data regarding syphilis diagnoses, initial and re-treatment regimens, and serological outcomes. NT titers were obtained from participants at enrollment and follow-up. We evaluated CSF findings among a subgroup of participants relative to re-treatment. RESULTS: From March 2012 - February 2016, we enrolled 135 HIV-negative syphilis patients with persistent NT titers after initial therapy. Among 116 participants with > 12 months of follow-up, 60 (52%) received re-treatment for syphilis. Overall, there were no significant differences in serological response between those who were retreated versus not among serological non-responders (29% vs 27%; p=1.0) or among participants without seroconversion (41% vs 37%; p=0.8). Of 60 participants who underwent CSF analyses, eight (13%) had CSF abnormalities, but only two (3%) met neurosyphilis criteria after re-treatment. CONCLUSIONS: Most HIV-negative syphilis patients who have serological non-response or lack of seroreversion following therapy do not benefit from re-treatment in the short-term, and neurosyphilis is uncommon.

11.
J Invest Dermatol ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32918951

RESUMO

Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide. Azithromycin is effective in treating Chlamydia infection; however, resistance to this antibiotic is increasing, and it is important that new therapeutic strategies are developed. Here, we demonstrated that inhibitors targeting each kinase in the ERK/RSK cascade significantly decreased the size and number of inclusions, as well as the number of infectious progeny. The suppressive effects of the inhibitors were observed across the Chlamydia serotypes D, E, F, and L1 and across Hela, McCoy, and Vero host cells. When combined with azithromycin, all the inhibitors exerted a synergistic suppressive effect on Chlamydia infection. Knockdown experiments using siRNA demonstrated that ERK1/2 and RSK1 were crucial for Chlamydia infection. Moreover, BVD-523, a first-in-class ERK1/2 inhibitor currently undergoing a phase II clinical trial, suppressed Chlamydia infection both in cell culture and in a mouse model. These observations demonstrated not only that the ERK/RSK pathway plays a critical role in Chlamydia infection, but also that these kinases have potential as targets for host-directed therapy against Chlamydia trachomatis.

12.
Sex Transm Infect ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769203

RESUMO

OBJECTIVE: To estimate the potential effects of an intense sex work crackdown on syphilis transmission in Guangdong Province, China. METHODS: We developed a deterministic compartmental model of syphilis transmission among female sex workers (FSW) and their male clients in Guangdong Province, China. We based model assumptions on census data and scientific literature, and we fitted the model to sentinel surveillance estimates of syphilis prevalence (positive results in both treponemal and non-treponemal tests) among FSW between 2009 and 2013. We estimated the impact of an intense sex work crackdown in 2014 by comparing the number of new syphilis infections between 2014 and 2020 in crackdown versus basecase (no crackdown) scenarios. In modelling scenarios, we examined main crackdown mechanisms of impact, including changed number of FSW engaging in sex work, reduction of weekly transactions, condom usage rate and syphilis diagnosis rate. RESULTS: In the basecase, predicted syphilis prevalence in FSW decreased from 2% in 2014 to 0.4% in 2020. In crackdown scenarios, syphilis incidence was predicted to transiently decrease and then to rebound relative to basecase levels a few years later. Shorter crackdowns led to higher, faster rebounds. CONCLUSIONS: Short-term intense crackdowns may exacerbate syphilis transmission among FSW and further marginalise an already vulnerable group. This study provides a quantitative, infection-related basis for changing sex work policies to reduce harms.

13.
Infect Drug Resist ; 13: 1775-1780, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606827

RESUMO

Introduction: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae (N. gonorrhoeae) becomes a grave public health problem in the world. A strengthened Antimicrobial Resistance Surveillance Program is needed to track the trend of AMR development. However, the lack of a proper antimicrobial susceptibility test (AST) method is a barrier to expand the AMR surveillance in China. Traditional agar dilution (AD) method is laborious and E-test strips have no approval license for clinical use. Herein, a Chinese group modified the microdilution (MD) method for clinical ASTs. The objective of this study is to compare the MD method with the AD method for N. gonorrhoeae AST. Materials and Methods: A total of 166 clinical isolates were tested for antimicrobial susceptibility of ceftriaxone, spectinomycin, azithromycin, ciprofloxacin, tetracycline, and penicillin using MD and AD method simultaneously. Results of MD method were read manually or automatically. Rates of essential agreement (EA), category agreement (CA), minor error, and very major error were compared. Results: The total EAs (compared with results read manually) of penicillin, tetracycline, ciprofloxacin, spectinomycin, ceftriaxone, and azithromycin were 90.4%, 97.0%, 85.5%, 100.0%, 94%, and 72.3%; and CAs were 82.5%, 94.0%, 100%, 100%, 95.2%, and 94%, respectively. Conclusion: We conclude that the MD method might be an alternative for clinical AST of N. gonorrhoeae in China. In particular, MD method has the potency of accurate differentiation of isolates resistant to ceftriaxone or azithromycin, which were empirically recommended for gonococcal treatment, but its quality remained suboptimal, and further improvement is needed for clinical use.

14.
BMC Infect Dis ; 20(1): 455, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600260

RESUMO

BACKGROUND: Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. METHODS: Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. DISCUSSION: Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. TRIAL REGISTRATION: ChiCTR1900022409 (10 April, 2019).


Assuntos
Testes Diagnósticos de Rotina/métodos , Promoção da Saúde/métodos , Homossexualidade Masculina , Imunoensaio/métodos , Programas de Rastreamento/métodos , Minorias Sexuais e de Gênero , Sorodiagnóstico da Sífilis/métodos , Sífilis/diagnóstico , Treponema pallidum/imunologia , Sorodiagnóstico da AIDS/métodos , China , Crowdsourcing/métodos , Testes Diagnósticos de Rotina/efeitos adversos , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/imunologia , HIV-2/imunologia , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Motivação , Mídias Sociais , Sífilis/microbiologia , Sorodiagnóstico da Sífilis/efeitos adversos
15.
J Infect Dis ; 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32710788

RESUMO

Whole-genome sequencing (WGS) of Treponema pallidum subsp. pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples. We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China. By combining parallel, pooled whole-genome amplification (ppWGA) with hybrid selection, we generated high quality genomes from four of eight chancre-swab samples and two of two rabbit-passaged isolates, all subjected to challenging storage conditions. This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China.

16.
World J Surg ; 44(7): 2237-2242, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32123981

RESUMO

BACKGROUND: The ankle and heel are challenging regions to reconstruct functionally. Here, we explored the feasibility and clinical outcomes of a modified anterior tibial artery perforator-pedicled propeller flap for the repair of soft-tissue defects of the ankle and heel. PATIENTS AND METHODS: Between January 2013 and December 2015, 12 patients with soft-tissue defects of the ankle and/or heel underwent reconstructive surgery that included our flap technique. The flaps measured 20 × 8 cm to 7 × 4 cm. A hand-held Doppler was used to identify a proper constant perforator in the distal ankle. In each case, the base of the flap was well preserved. The flap was transposed (180° rotation) to reach and cover the defect. RESULTS: The average follow-up time was 13 months (10-28 months). We observed good texture matches and contour in all of the flaps. All patients could walk and wear normal footwear. All but one flap survived completely without complications. Partial loss was observed in one patient, and the necrotic region was healed with secondary intention. CONCLUSION: Our modified anterior tibial artery free-style perforator-pedicled propeller flap provides a novel option for functional ankle and heel reconstruction. LEVEL OF EVIDENCE: Level IV.

17.
Sex Transm Dis ; 47(4): 232-237, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32011419

RESUMO

BACKGROUND: Partner notification (PN) is an essential component of syphilis control and is recommended by Chinese Sexually Transmitted Disease guidelines. However, in China, studies examining local practice are limited. This study evaluated PN outcomes among persons with early syphilis infection in an urban district in China. METHODS: From 2011 to 2017, persons diagnosed with early syphilis were asked to participate in an evaluation of supportive patient referral partner services for all recent sex partners, and the contact and case finding indices were determined in Nanshan District, Shenzhen, China. RESULTS: During the study period, 642 index patients with early syphilis reported 1749 sex partners. Of those partners, 678 were potentially contactable and 525 (30%) were contacted. The overall contact index was 0.82. Among the 1749 partners reported, 1108 (63%) were described as casual partners, and only 37 (3%) were contacted (contact index 0.13) compared with 641 partners who were either spouses and regular partners (contact index, 1.37). Among those 525 partners contacted, 418 (80%) were tested, and 205 (39%) were diagnosed with and treated for syphilis. Among those, 9 (4%) were primary, 26 (13%) were secondary, 16 (8%) were early latent, and 154 (49%) were other syphilis infections. The overall case finding index was 0.29. CONCLUSIONS: There is a need to improve PN practices in China, which include developing operational guidelines of PN and to develop and evaluate novel PN ways like using Internet-based strategy.

18.
BMC Infect Dis ; 20(1): 165, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087699

RESUMO

BACKGROUND: Treponema pallidum (T. pallidum) infection evokes significant immune responses, resulting in tissue damage. The immune mechanism underlying T. pallidum infection is still unclear, although microRNAs (miRNAs) have been shown to influence immune cell function and, consequently, the generation of antibody responses during other microbe infections. However, these mechanisms are unknown for T. pallidum. METHODS: In this study, we performed a comprehensive analysis of differentially expressed miRNAs in healthy individuals, untreated patients with syphilis, patients in the serofast state, and serologically cured patients. miRNAs were profiled from the peripheral blood of patients obtained at the time of serological diagnosis. Then, both the target sequence analysis of these different miRNAs and pathway analysis were performed to identify important immune and cell signaling pathways. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for microRNA analysis. RESULTS: A total of 74 differentially regulated miRNAs were identified. Following RT-qPCR confirmation, three miRNAs (hsa-miR-195-5p, hsa-miR-223-3p, hsa-miR-589-3p) showed significant differences in the serofast and serologically cured states (P < 0.05). One miRNA (hsa-miR-195-5p) showed significant differences between untreated patients and healthy individuals. CONCLUSIONS: This is the first study of miRNA expression differences in peripheral blood mononuclear cells (PBMCs) in different stages of T. pallium infection. Our study suggests that the combination of three miRNAs has great potential to serve as a non-invasive biomarker of T. pallium infections, which will facilitate better diagnosis and treatment of T. pallium infections.


Assuntos
Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , Sífilis/sangue , Transcriptoma/genética , Treponema pallidum/imunologia , Biomarcadores , Perfilação da Expressão Gênica , Humanos , MicroRNAs/imunologia , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Testes Sorológicos , Sífilis/diagnóstico , Sífilis/microbiologia , Treponema pallidum/isolamento & purificação
19.
Vaccine ; 38(13): 2849-2858, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32088017

RESUMO

INTRODUCTION: Men who have sex with men (MSM), especially those infected with human immunodeficiency virus (HIV), are at disproportionate risk for human papillomavirus (HPV) infection. Data about anal HPV prevalence among MSM in southern China are limited. METHODS: MSM were recruited between January 1 and August 31, 2017 in three metropolitan cities: Guangzhou, Shenzhen and Wuxi. A self-completed tablet-based questionnaire was used to collect information about socio-demographic/sexual behavioral characteristics, history of sexually transmitted infections (STIs) and recreational drug use. An anal brush was used to collect exfoliated cells for HPV DNA testing and genotyping, and a blood sample was taken for HIV testing. Penile/anal warts were checked by a clinician. RESULTS: A total of 536 MSM were enrolled, including 39 HIV-positive and 497 HIV-negative individuals. Compared with HIV-negative MSM, prevalence of any HPV genotype (79.5% vs 46.7%), any high-risk genotype (64.1% vs 36.6%) and any nonavalent vaccine-preventable genotype (53.9% vs 31.6%) was significantly higher in HIV-positive MSM, with all P < 0.01. HIV infection (adjusted odds ratio [AOR], 4.28; 95% confidence interval [CI], 1.87-9.80), using recreational drugs (AOR, 1.87; 95% CI, 1.22-2.87), having ≥ 3 years of sexual experience (AOR, 1.52; 95% CI, 1.01-2.28), having ≥ 6 lifetime male partners (AOR, 1.92; 95% CI, 1.29-2.86), and engaging receptive anal intercourse (AOR, 2.30; 95% CI, 1.48-3.57) were associated with higher anal HPV prevalence. Any HPV prevalence increased with age, from 24.5% at < 20 years to 55.8% at ≥ 40 years. CONCLUSIONS: Anal HPV prevalence was high among MSM in southern China, significantly associated with HIV status and sexual experience. HPV prevalence increased with age among MSM. A targeted HPV vaccination program for teenage MSM might be necessary. Our findings will inform targeted HPV modelling among MSM in China.

20.
J Invest Dermatol ; 140(8): 1566-1575.e1, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31930972

RESUMO

Treponema pallidum (Tp) infection-induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs in host immunity. We assessed whether microRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that microRNA-101-3p (miR-101-3p) levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, whereas toll-like receptor (TLR) 2 levels were higher in patients with syphilis than in healthy controls. In vitro, stimulation of THP-1 cells with Tp increased miR-101-3p expression. Moreover, miR-101-3p reduced expression levels of TLR2 mRNA and protein in THP-1 cells via binding to the 3' untranslated region of TLR2. Likewise, miR-101-3p inhibited production of inflammatory cytokines, including IL-1ß, IL-6, tumor necrosis factor-α, and IL-12, in Tp-stimulated macrophages. IL-1ß and IL-6 mRNA expression levels were reduced by transfection of macrophages with a TLR2-specific small interfering RNA. Conversely, overexpression of TLR2 upregulated cytokine expression. Patients with secondary syphilis exhibited the highest levels of plasma IL-6, which were negatively correlated with miR-101-3p. In conclusion, Tp infection upregulates miR-101-3p expression, which in turn inhibits the TLR2 signaling pathway, leading to reduced cytokine production.

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