Point of care diagnostics for sexually transmitted infections: perspectives and advances

Accurate and inexpensive point-of-care (POC) tests are urgently needed to control sexually transmitted infection epidemics, so that patients can receive immediate diagnoses and treatment. Current POC assays for Chlamydia trachomatis and Neisseria gonorrhoeae perform inadequately and require better assays. Diagnostics for Trichomonas vaginalis rely on wet preparation, with some notable advances. Serological POC assays for syphilis can impact resource-poor settings, with many assays available, but only one available in the U.S. HIV POC diagnostics demonstrate the best performance, with excellent assays available. There is a rapid assay for HSV lesion detection; but no POC serological assays are available. Despite the inadequacy of POC assays for treatable bacterial infections, application of technological advances offers the promise of advancing POC diagnostics for all sexually transmitted infections.     

Administration of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection: A case series

The incidence of syphilis infection among pregnant women is persistently high in Japan and in several developed countries. Here, we report the utility of intravenous benzylpenicillin in 13 infants born to mothers with syphilis infection. Because the recommended treatment (intramuscular benzathine benzylpenicillin) is not available in Japan, we intravenously administered benzylpenicillin for 10 days, which is used for treatment in high-risk cases. The administration of benzylpenicillin in low-risk infants resulted in an extended duration of parent-to-infant separation and increased the infants’ exposure to invasive procedures. Thus, establishing evidence of the adequacy of no-treatment follow-up in low-risk groups and introducing intramuscular injections of benzathine benzylpenicillin may improve the management of infants suspected with congenital syphilis in Japan.     

产前超声筛查不同年龄段孕妇胎儿畸形的差异性分析

目的分析不同年龄段孕妇产前超声筛查出的胎儿畸形的差异性。方法选取在我院行产前超声筛查的孕妇6119例,按年龄分成≤19岁、20~24岁、25~29岁、30~34岁、35~39岁及≥40岁6组,将产前超声筛查结果与产前诊断中心检查、引产后尸体检查或产后新生儿检查结果进行比较,计算超声筛查胎儿畸形的准确率;分析各组胎儿六大类严重畸形的检出率、畸形数目及畸形类型情况。结果 6119例孕妇共有胎儿畸形204例,超声准确诊断186例(91.18%)。其中,≤19岁组六大类严重畸形检出率最高(53.33%),与其余各组比较差异均有统计学意义(均P0.05);≥40岁组多发畸形发生率最高(60.00%),但仅与25~29岁组(25.45%)比较差异有统计学意义(P0.05)。204例胎儿畸形类型以先天性心脏畸形检出数最高,神经系统畸形和颜面部畸形次之。结论孕妇年龄过小容易发生胎儿严重畸形;年龄过大容易发生胎儿多发畸形,且神经系统和先天性心脏畸形的发生几率增高。     

梅毒螺旋体TP0772蛋白的原核表达和免疫反应性鉴定

目的 利用原核基因工程技术克隆表达梅毒螺旋体TP0772基因,探讨其在梅毒血清学诊断中的应用.方法 PCR扩增获得TP0772基因,构建pET-28b-TP0772重组质粒,转化到大肠杆菌BL21中,以IPTG诱导蛋白质表达,经镍柱纯化后通过质谱技术鉴定.采用免疫印迹法测定其与梅毒患者血清的免疫反应性.建立基于重组TP0772抗原的ELISA间接法并对30份TPPA阳性血清和25份TPP阴性血清进行方法学评价.结果 PCR扩增获得约850 bp的基因片段,成功构建原核表达载体pET-28b-TP0772.目的蛋白分子量约为32kDa,以包涵体的表达形式存在,约占菌体总蛋白的30%.经质谱技术和免疫印迹分析证实重组蛋白为TP0772蛋白,并能够与梅毒患者血清发生特异性结合反应.ELISA测定TPPA阳性血清和阴性血清的符合率分别为93%（28/30）和96%（24/25）.结论 通过DNA重组技术成功获得了重组TP0772蛋白,其与梅毒阳性血清具有良好的免疫反应性,为优化梅毒的血清学诊断方法奠定基础.     

Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta

IntroductionNon-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators.Materials and methodsStudies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem^®). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier.ResultsPost-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were significantly (p < 0.001) better visualized on post-contrast liposomal-Gd images. DCE-MRI with the conventional Gd agent demonstrated retrograde opacification of the placenta from fetal edge to the myometrium, consistent with the anatomy of the rat placenta. However, no consistent and reproducible visualization of the retroplacental space was demonstrated on the conventional Gd-enhanced images. The retroplacental space was only visualized on post-contrast T1w images acquired using the liposomal agent (SNR = 15.5 ± 3.4) as a sharply defined, hypo-enhanced interface. The retroplacental space was also visible as a similar hypo-enhancing interface on CE-CT images acquired using a liposomal CT contrast agent. Tissue analysis demonstrated undetectably low transplacental permeation of liposomal-Gd, and was confirmed by lack of permeation through a perfused human placental model.ConclusionsContrast-enhanced T1w-MRI performed using liposomal-Gd enabled clear visualization of placental margins and delineation of the retroplacental space from the rest of the placenta; the space is undetectable on non-contrast imaging and on post-contrast T1w images acquired using a conventional, clinically approved Gd chelate contrast agent.     

Estimating influenza disease burden among pregnant women: Application of self-control method

To evaluate influenza disease burden among pregnant women, an epidemiological study using the self-control method was conducted. Study subjects were 12,838 pregnant women who visited collaborating maternity hospitals and clinics in Osaka Prefecture, Japan, before the 2013/14 influenza season. As a study outcome, hospitalization due to respiratory illnesses between the 2010/11 and 2013/14 seasons was collected from each study subject through a baseline survey at the time of recruitment and a second survey after the 2013/14 season. The hospitalization rates during pregnancy and non-pregnancy periods was calculated separately. To compare the hospitalization rate during pregnancy with that during non-pregnancy within the same single study subject, Mantel-Haenzel rate ratios (RR_MH) were calculated.During the four seasons examined in this study, nine and 17 subjects were hospitalized due to respiratory illnesses during pregnancy and non-pregnancy periods, respectively. The hospitalization rate was 2.54 per 10,000 woman-months during pregnancy and 1.08 per 10,000 woman-months during non-pregnancy. The RR_MH for the hospitalization rate during pregnancy compared with that during non-pregnancy was 4.30 (95% confidence interval, 1.96–9.41).Our results suggest that during the influenza season, pregnant women have a higher risk than non-pregnant women for hospitalization due to respiratory illnesses. The self-control method appears to be an appropriate epidemiological method for evaluating the disease burden of influenza among pregnant women.