Status of vaccine research and development of vaccines for herpes simplex virus

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.     

Male genital vitiligo

Vitiligo is a polygenetic multifactorial disease leading to melanocytic loss in skin and sometimes in hair. Genital areas may be involved and represent a specific therapeutic challenge. Surprisingly, data on male genital vitiligo remain scarce. This review aims to collate current knowledge on male genital vitiligo and to discuss the risks and benefits of the various therapeutic approaches. Male genital vitiligo is relatively frequent and often induces marked impairment of quality of life, with a specific impact on sex life. Prompt recognition of activity remains mandatory to halt disease progression, as repigmentation remains difficult to achieve in most cases. Thanks to progress in understanding of the pathophysiology of vitiligo, new therapeutic approaches are under development. Topical ruxolitinib, a JAK pathway inhibitor, is currently the product in the most advanced stage of development, with a very encouraging repigmentation rate on the face, although specific efficacy in genital area remains to be assessed. The next generation of treatments, such as topical WNT agonists, could be of great interest in genital vitiligo as they will not require combination with UV therapy and they may be able to enhance the differentiation and proliferation of melanocyte stem cells in this difficult-to-treat area.     

Effect of a Condom Cover on Vaginal Photoplethysmographic Responses

IntroductionThe vaginal photoplethysmograph (VPP) is a reusable intravaginal device often employed in sexual psychophysiology studies to assess changes in vaginal blood flow, an indicator of sexual arousal.AimTo test whether placing a disposable cover on the VPP probe impacts the acquired data. A condom cover would reduce risk of disease transmission and likely increase participant comfort but may negatively impact the VPP signal.MethodThe genital responses of 25 cisgender women (mean age = 21.3 years, standard deviation = 2.6) were assessed with VPP in a within-subjects design with 2 conditions—with and without a polyisoprene condom cover. Sexual responses were elicited by audiovisual film clips that varied in erotic intensity: nonsexual (nonsexual male-female interaction), low-intensity sexual (nude exercise), and high-intensity sexual (male-female intercourse). Women continuously rated their sexual arousal during stimulus presentations.Main Outcome MeasureChange in vaginal pulse amplitude and also self-reported sexual arousal.ResultsThe magnitude of sexual response to each stimulus category and the overall pattern of results were found to be highly similar in the cover-off and cover-on conditions. The high-intensity sexual stimulus category elicited a greater sexual response than all other categories. The low-intensity sexual category elicited a (small) genital response in only the cover-on condition, although we suspect this is a spurious finding. There was no difference in the average number of edited movement artifacts across conditions.Clinical ImplicationsPotential benefits of encasing the VPP probe with a protective cover include enhanced participant safety and comfort, especially if assessing genital responses of high-risk or immunocompromised samples. The use of a cover complies with current guidelines for reprocessing semi-critical medical devices (eg, vaginal ultrasound probes) in many regions.Strengths & LimitationsAlthough the idea of a VPP probe cover had been discussed among sexual psychophysiology researchers, this is the first study to empirically test whether a cover could jeopardize VPP data. Potential limitations include the use of a 10-Hz VPP sampling rate and a cover that was not tailored to the size of the VPP probe.ConclusionPlacing a protective cover on the VPP probe did not appear to meaningfully impact sexual arousal or the VPP data. Based on these results and the potential advantages of a protective cover, researchers may wish to integrate the use a condom cover in their experiment protocols and clinical applications.Sawatsky ML, Lalumière ML. Effect of a Condom Cover on Vaginal Photoplethysmographic Responses. J Sex Med 2020; 17:702–715.     

Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples

Differences of sex development (DSDs) are a group of congenital conditions characterized by a discrepancy between chromosomal, gonadal, and genital sex development of an individual, with significant impact on medical, psychological and reproductive life. The genetic heterogeneity of DSDs complicates the diagnosis and almost half of the patients remains undiagnosed. In this context, chromosomal imbalances in syndromic DSD patients may help to identify new genes implicated in DSDs. In this study, we aimed at describing the burden of chromosomal imbalances including submicroscopic ones (copy number variants or CNVs) in a cohort of prenatal syndromic DSD patients, and review their role in DSDs. Our patients carried at least one pathogenic or likely pathogenic chromosomal imbalance/CNV or low-level mosaicism for aneuploidy. Almost half of the cases resulted from an unbalanced chromosomal rearrangement. Chromosome 9p/q, 4p/q, 3q and 11q anomalies were more frequently observed. Review of the literature confirmed the causative role of CNVs in DSDs, either in disruption of known DSD-causing genes (SOX9, NR0B1, NR5A1, AR, ATRX, …) or as a tool to suspect new genes in DSDs (HOXD cluster, ADCY2, EMX2, CAMK1D, …). Recurrent CNVs of regulatory elements without coding sequence content (i.e. duplications/deletions upstream of SOX3 or SOX9) confirm detection of CNVs as a mean to explore our non-coding genome. Thus, CNV detection remains a powerful tool to explore undiagnosed DSDs, either through routine techniques or through emerging technologies such as long-read whole genome sequencing or optical genome mapping.     

Human leukocyte interferon-α in cream,for the treatment of genital warts in asian women a placebo-controlled,double-blind study

The purpose of this double-blind, placebo-controlled study was to determine and compare the clinical efficacy and tolerance of human leukocyte -interferon (incorporated 2 × 10⁶ IU/g) in hydrophilic cream to cure genital warts. Preselected Asian female patients (n=150) aged 18–40 years (mean 22.5), with the clinical and biopsy-confirmed diagnosis of genital warts (mean 2.64), predominantly flat vaginal condylomas, were randomly allocated to 3 parallel groups. Each patient was given a coded tube containing 80 g placebo/active preparation with a graduated applicator. Patients were instructed to inject 6 g of the either alloted placebo/active cream deep into the vagina thrice a day for 3 consecutive days (group A) or 4 consecutive days (group B) per week, and if not cured the same treatment was extended to 3 more weeks (maximum 4 weeks active treatment). To assess the clinical efficacy patients were examined on a week-to-week basis. A total clearance of warts (biopsy-confirmed) was evaluated as a complete cure. Patients cured during the treatment were spared further treatment and were requested to visit us after 16 weeks for relapse control. As for the remaining patients, empty tubes were collected, and similarly coded replacement tubes were given for further treatment (in total 588 tubes were used). By the end of the treatment 57.2% lesions (227/397) were eliminated in all the groups: 48% patients in group A, 90% patients in group B, and 10% patients in placebo groups taken as completely cured. Of the 150 patients 128 (85.3%) did not complain of any drug-related adverse symptoms. Transitory increase in body temperature (mean 38.4°C), accompanied by headache (14.6%) and generalized itching (6.6%) were the most frequently reported side effects; however, treatment was well tolerated by all the patients, and there were no dropouts. Our findings indicate that clinical efficacy is dose dependent, that is, the results of group B were significantly superior to that of group A (P < 0.05). Of the 49.3% cured patients (74/150) followed up for 6 months (monthly basis) seven had a relapse, and none had reinfection. It is concluded that clinical efficacy of leukocyte interferon-a to cure genital warts is dose dependent. These results further support the view that leukocyte interferon-a incorporated in hydrophilic cream can be considered a reliable, safe, and home-based treatment to cure vulvar and vaginal warts.Abbreviation HPV human papillomavirus     

Dynamic assessment of pelvic floor function in women using the intravaginal device test

The aim of the study was to assess pelvic floor function and dysfunction using intravaginal devices (IVD test). One hundred and eighty-five patients were evaluated, 65 (35.1%) in the control group without genital prolapse and 120 (64.9%) in the study group, with prolapse. Anatomic changes were evaluated on a scale described by Halban, and functional classification based on palpation of the muscles of the pelvic floor during contraction. Additionally, weighted vaginal devices were used to assess pelvic floor function. Statistic analysis was performed with the Spearman-Pearson correlation coefficient, the ² test and the response/ operator characteristic curve. There was an acceptable correlation between the IVD test and the functional classification of 0.75. Using this classification, the IVD test showed 86.58% sensitivity, 75.72% specificity, and had a positive predictive value 73.95% and a negative predictive value of 87.64%. Significant differences between pelvic floor muscle activity in those patients with and without genital prolapse were observed (X²=58.28, P=<0.005). It was concluded that pelvic floor assessment can be done through the evaluation of active muscle strength or pelvic floor integrity using the functional classification and the IVD test.EDITORIAL COMMENT: In 1988, Peattie and Plevnick introduced the use of weighted vaginal cones to exercise the pelvic floor muscles and treat stress urinary incontinence [1]. Contreras-Ortiz and Nuñez build on this earlier work, using a similar technique to assess pelvic floor muscle function and integrity. Specifically, pelvic floor function is assessed by a combination of digital palpation of the pubococcygeus muscle at rest and during contraction; pelvic floor integrity is assessed by the patient's ability to retain a weighted cone vaginally for 1 minute. Scoring of these two parameters can then be objectively followed for therapeutic response to treatment for urinary incontinence or pelvic relaxation. Many of us forget to palpate the pubococcygeus muscle at rest and during an elicited contraction during baseline or follow-up examination. As this study indicates, simple assessment of pelvic floor function and integrity is possible, and should be used both clinically and in research.     

Ureaplasma urealyticum infection in newborns: Three case reports

We report three newborns with different manifestations ofUreaplasma urealyticum infection; a term newborn with acute neonatal pneumonia and two very low birth weight infants with bronchopulmonary dysplasia and osteomyelitis of the femur, respectively. The association ofU. urealyticum with acute and chronic respiratory disease in term and preterm newborns has recently been reported. Our two cases are similar to other case reports from the literature, but we were unable to find any previous reports of osteomyelitis due toU. urealyticum in the premature babies. Isolation ofU. urealyticum in pure culture from the blood was considered to be related to local infection in all three patients. All patients were cured by erythromycin.     

Retropublic colpourethropexy with transabdominal anterior and/or posterior repair for the treatment of genuine stress urinary incontinence and genital prolapse

A new operative technique combining retropublic colpourethropexy with transabdominal internal anterior and/or internal posterior repair for the treatment of genuine stress incontinence (GSI) and genital prolapse is described in 75 cases. The overall success rate in correcting GSI was 92.0%, with a 94.8% success rate in the primary surgical group (n=58) and an 82.4% in the secondary group (n=17). Average follow-up has been 1.31 years (range 6 weeks–6 years). There was a 3.4% incidence of residual prolapse. Nine patients also underwent concomitant colpourethropexy. Overall surgical complications include febrile morbidity 4/75 (5.3%), wound infection 1/75 (1.3%), deep vein thrombosis 1/75 (1.3%) and partial ureteric obstruction 1/75 (1.3%). There were no statistically significant changes in multichannel urodynamic studies preoperatively and at 1 year following surgery. Onethird (2/6) of the GSI failures had low MUCP (<20 cm H₂O) prior to surgery and continued so at 1 year follow-up.EDITORIAL COMMENT: Genital prolapse is often present in patients who have GSI. If an operation is performed to correct the GSI, and those areas of weakness in the pelvic support system that are contributing to the genital prolapse are not treated, the genital prolapse will become more severe. In the operation which has been described, the colpopexy sutures will correct any cystourethrocele, and the removal of the wedge of tissue from the anterior superior vaginal wall will correct the cystocele. The removal of the wedge of tissue from the posterior superior vaginal wall will reduce the redundancy of the posterior vaginal fornix, but a culdeplasty of the Moschcowitz or Halban type is recommended to treat or prevent an enterocele and to place the vaginal apex in the hollow of the sacrum. Any coexistent rectocele must always be treated vaginally. If it is not treated, it will appear to be more advanced following elevation of the anterior vaginal wall by retropubic urethropexy and the anterior repair which has been recommended.Genital prolapse is best treated by a vaginal approach. When one must une an abdominal approach, ancillary procedures such as the authors have described should be considered. A bulbous upper vagina is ideal for childbearing but if the apical support system and vaginal wall is weakened it is predisposed to prolapse. If the surgeon, in operating for genital prolapse, which involves the upper vagina, will taper the vaginal apex and support it by obliteration of the cul-desac and shortening and reattachment of the uterosacralcardinal complex, postoperative prolapse will be less likely to recur.     

406例女性生殖道感染者支原体检出情况及耐药分析

目的分析女性生殖道感染者解脲支原体(UU)和人型支原体(MH)检出情况及体外耐药性,以指导临床合理用药。方法对406例女性生殖道感染者宫颈分泌物标本行支原体培养、鉴定和耐药性检测。结果①支原体阳性236例,感染率为58.13%,其中UU、MH、UU+MH阳性率分别占83.05%、5.93%、11.02%;②UU、MH、UU+MH对12种抗生素的平均耐药率分别为16.11%、33.93%、55.13%。UU阳性者中有23.98%耐4种以上抗生素,而MH及UU+MH感染者中分别有71.43%、96.15%的病例耐4种以上抗生素。结论①女性生殖道支原体感染以UU为主,UU+MH次之,单纯MH感染较少;②单纯UU感染耐药率相对较低,而MH、UU+MH感染耐药率较高,且多重耐药率高。③多西环素、米诺环素、交沙霉素可作为治疗支原体感染的首选用药,而环丙沙星、司帕沙星、左氧氟沙星、红霉素、罗红霉素宜尽量避免使用。     

妇科恶性肿瘤患者的生存期预测

目的建立一个预测临终期妇科肿瘤患者生存时间的评分办法。方法回顾性分析不再适于接受任何抗肿瘤治疗,并于院内死亡的91例临终期妇科恶性肿瘤患者的临床资料。91例患者年龄中位数56岁(13~83岁),从入院起生存中位数27d(1~240d)。分析19项临床和生化指标与生存时间的关系。对单因素分析方法显示的9项显著影响生存时间的指标进行多元逻辑回归分析,以逐步后退方法建立一个包括5项指标的回归模型。将各项指标的回归系数转换为简单分数,相加后得到每一例患者的预后评分。依据本评分方法将患者分为两组,A组≤9·5分,B组≥10分。结果单因素分析显示,对生存时间有显著影响的9项指标为:呼吸困难、Karnofsky功能指数(KPS)、年龄、发热、肿瘤发展速度、有无并发症、血尿素氮、肌酐、血小板。多元逻辑回归结果建立了包括呼吸困难、KPS、年龄、发热和血尿素氮5项指标在内的回归方程。方程的正确分辨能力83·5%。A组37例,平均生存时间为(65±7)d。B组54例,平均生存时间为(19±2)d。A组存活≥30d者占83·8%(31/37)、B组存活≤29d者占85·2%(46/54)。两组生存曲线的差异有统计学意义(P<0·001)。结论依据本组资料建立的评分办法简单实用,是预测临终患者生存时间的有效方法。