Expanded Histopathology and Tropism of Ebola Virus in the Rhesus Macaque Model: Potential for Sexual Transmission, Altered Adrenomedullary Hormone Production, and Early Viral Replication in Liver.

The pathogenesis of Ebola virus disease (EVD) is still incomplete, in spite of the availability of a nonhuman primate modelfor more than 4 decades. To further investigate EVD pathogenesis, a natural history study was conducted using 27 Chinese-origin rhesus macaques. Of these, 24 macaques were exposed intramuscularly to Kikwit Ebola virus and euthanized at predetermined time points or when end-stage clinical disease criteria were met, and 3 sham-exposed macaques were euthanized on study day 0. This study showed for the first time that Ebola virus causes uterine cervicitis, vaginitis, posthitis, and medullary adrenalitis. Not only was Ebola virus detected in the interstitial stromal cells of the genital tract, but it was also present in the epididymal and seminal vesicular tubular epithelial cells, ectocervical and vaginal squamous epithelial cells, and seminal fluid. Furthermore, as early as day 3 after exposure, Ebola virus replicative intermediate RNA was detected in Kupffer cells and hepatocytes. These findings in the nonhuman model provide additional insight into potential sexual transmission, possible disruption of sympathetic hormone production, and early virus replication sites in human EVD patients.

Morphological spectrum of neovaginitis in autologous sigmoid transplant patients.

AIMS: Autologous intestinal grafts are used to (re)create a vagina in selected patients. The risk of diversion colitis is mentioned as a disadvantage, although its prevalence remains unclear. This study aimed to assess the histopathological characteristics of the sigmoid-derived neovaginal epithelial lining after diverting surgery and correlate these with clinical findings. METHODS AND RESULTS: Biopsy specimens were obtained from the epithelial lining of the sigmoid-derived neovagina and remaining rectosigmoid as regular follow-up from 26 patients with a median age of 22 years (range 19-52) and median postoperative follow-up of 13 months (range 6-52). Medical history, neovaginal symptoms and sexual activity were documented. An experienced gastrointestinal histopathologist assessed the specimens using a descriptive item-score, comprising signs of chronic and active inflammation. Inflammatory changes were observed in 21 (80.7%) neovaginal and one (3.8%) rectosigmoid specimens. The neovaginal appearance was characterized by an increase of lymphoid aggregates and lymphoplasmacellular infiltrate. Other common features were the presence of polymorphonuclear neutrophils and Paneth cell metaplasia. Neovaginal discharge was correlated with the presence of inflammatory changes (P = 0.008, Spearman's rho = 0.506). DISCUSSION: Acute and chronic inflammation of the sigmoid-derived neovagina was commonly observed and consistent with a proposed diagnosis of diversion neovaginitis. Neovaginal discharge correlates with this histopathological entity.

Emphysematous vaginitis.

BACKGROUND: Emphysematous vaginitis is a rare condition, characterized by the presence of multiple gas-filled cysts in the vaginal and/or exocervical mucosa. Although its etiology is not completely understood, it is self-limited, with a benign clinical course. Vaginal discharge, sometimes bloody, and pruritus are the most common symptoms. Chronic and acute inflammation can be found, and diseases that impair the immune system and pregnancy have been associated with this condition. CASE REPORT: A 48-year-old postmenopausal woman, with a history of hysterectomy with several comorbidities, presented with a 4-month history of bloody discharge and vulvar pruritus. Examination showed multiple cystic lesions, 1 to 5 mm, occupying the posterior and right lateral vaginal walls. Speculum examination produced crepitus. Vaginal wet mount was normal, except for diminished lactobacilli; results of Trichomonas vaginalis DNA test and vaginal cultures were negative. Lugol's iodine applied to the vagina was taken up by the intact lesions. Biopsy result showed typical features of emphysematous vaginitis. CONCLUSIONS: This is an unusual entity, presenting with common gynecological complaints, and both physicians and pathologists should be aware to prevent misdiagnosis and overtreatment.

High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

Emphysematous vaginitis in a gravid woman.

A primigravida in her late 20s presented to the obstetrics and gynaecology department in labour. On per speculum examination, multiple cystic lesions, 1-5 mm in size were observed occupying the anterior, posterior and lateral vaginal walls. Vaginal wet mount was normal and vaginal cultures were negative. Biopsy findings were consistent with emphysematous vaginitis. Vaginitis emphysematosa is a rare, benign self-limiting condition that presents with multiple, air-filled cysts in the vaginal or ectocervical mucosa. This condition is seen in both gravid and non gravid women, usually associated with a Trichomonas or Gardnerella infection.

The clinical spectrum of Trichomonas vaginalis infection and challenges to management.

Trichomonas vaginalis is the most common curable sexually transmitted infection worldwide. T vaginalis infections in women can range from asymptomatic to acute inflammatory vaginitis. In men, this infection is typically asymptomatic but is increasingly being recognised as a cause of non-gonococcal urethritis. Diagnosis of T vaginalis has traditionally been made by direct microscopic examination of a wet mount of vaginal fluid or through the use of culture. The recent commercial availability of nucleic acid amplification tests for the detection of T vaginalis has seen these replace culture as the gold standard for diagnosis. Nitroimidazoles (ie, metronidazole and tinidazole) are the mainstay of therapy. In the case of treatment failure due to drug resistance or in the case of a severe nitroimidazole allergy, alternative intravaginal therapies exist, although their effectiveness has not been evaluated systematically. Novel systemic agents other than nitroimidazoles for the treatment of T vaginalis are needed, and efforts to promote and support antimicrobial drug development in this setting are necessary.

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

OBJECTIVE: The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. MATERIALS AND METHODS: Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. RESULTS: Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. CONCLUSIONS: Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Necrotizing Vaginitis in a 45-Year-Old Woman With Metastatic Breast Cancer.

Vaginitis emphysematosa (VE) is a rare, benign, and self-limited condition often diagnosed by the presence of intramuscular vaginal air observed on computed tomography (CT) scan. Although it is a nonpathologic, self-limited condition requiring no intervention, it is important to rule out a more serious infectious pathology. This report highlights a clinical dilemma and the potential consequences of over-reliance on CT in distinguishing benign VE from pathologic necrotizing vaginitis. A high clinical suspicion for infection should be maintained, especially when relevant clinical and laboratory markers suggest a more serious pathology. We describe the case of a 45-year-old woman who presented to the hospital with abdominal pain and vaginal bleeding. CT scan demonstrated intramuscular vaginal air, which was reported as VE. Classic imaging findings of VE falsely reassured clinicians. She died shortly thereafter of necrotizing vaginitis.

Prevalence of bacterial vaginosis and aerobic vaginitis and their associated risk factors among pregnant women from northern Ethiopia: A cross-sectional study.

This study aimed to determine the prevalence of bacterial vaginosis (BV) and aerobic vaginitis (AV) and their associated risk factors among pregnant women from Ethiopia. Also, this study investigated the bacterial pathogens and their antibiotic resistance in AV cases. A total of 422 pregnant women from northern Ethiopia were participated in this study. Socio-demographic and clinical data were recorded. Vaginal swabs were collected and used for wet mount and Gram stain methods to evaluate the AV and BV scores according to the Nugent's and Donder's criteria, respectively. In AV cases the bacterial pathogens and their antibiotic resistance were determined using standard methods. The possible risk factors for AV and BV in pregnant women were investigated. The prevalence rates of BV and AV were 20.1% (85/422) and 8.1% (34/422), respectively. BV was more common in symptomatic vs. asymptomatic people (P < 0.001), and in second trimester vs. first trimester samples (P = 0.042). However, AV was more common in secondary school vs. primary and those who were unable to read and write (P = 0.021) and in housewife women vs. employee (P = 0.013). A total of 44 bacterial strains were isolated from AV cases, of which the coagulase-negative staphylococci (CoNS) (38.6%) and Staphylococcus aureus (29.5%) were the most predominant bacteria, respectively. The highest resistance rate was observed against penicillin (100.0%) in staphylococci, while 86.7% of them were sensitive to ciprofloxacin. The resistance rate of Enterobacteriaceae ranged from 0.0% for ciprofloxacin and chloramphenicol to 100.0% against amoxicillin/clavulanate. The prevalence of BV was higher than AV in pregnant women. This higher prevalence of BV suggests that measures should be taken to reduce the undesired consequences related to BV in the pregnancy. The circulation of drug-resistant bacteria in vaginal infections requires a global surveillance to reduce the risks to pregnant mothers and infants.

The effect of vaginally administered genistein in comparison with hyaluronic acid on atrophic epithelium in postmenopause.

PURPOSE: The quality of life in postmenopause is seriously affected by the symptoms related to vaginal atrophy. To evaluate in a 3-month, prospective, randomized, double blind, study whether vaginal suppositories containing genistein might improve genital symptoms, colposcopical and cytologic findings or modify DNA cytometric features in postmenopausal women affected by vaginal atrophy, in comparison with vaginal suppositories containing hyaluronic acid (HA). METHODS: A total of 62 postmenopausal women were randomly assigned to receive intravaginally 97 µg of genistein (group A, n = 31) or 5 mg of HA (group B, n = 31) daily for 15 days continuously/month for 3 months. Vaginal and cervical smear, colposcopy, vaginal biopsy were performed before and at the end of the study. Maturation value (MV) was calculated. Flow cytometric analysis of DNA ploidy (DI) and S-phase fraction (SPF) were performed. RESULTS: After 90 days of study, a significant improvement was obtained in genital symptoms, colposcopy scores and MV (p < 0.001) in both groups; the improvement obtained by genistein was more effective especially regarding genital score (p value between groups 0.001). No significant change was found in SPF value and DI. CONCLUSION: Both treatments improved genital symptoms, colposcopical features and MV, although genistein was more effective on genital score. Both treatments did not significantly influence flow cytometry parameters, although genistein showed slight decrease in DI, with a normalization of the aneuploid content present in some cases that could represent an additional application of intravaginal phytoestrogen therapy, providing an alternative therapy of vaginal atrophy in postmenopausal patients. The results of this investigation should be considered preliminary and need to be verified in larger, prospective studies.

Hair in the vagina: a case series.

BACKGROUND: : Lack of estrogen after menopause can cause many changes in the lower genital tract of women, including involution of the introitus and collapse of the vestibule into the genital cleft. CASES: : Six cases of hypoestrogenic women are described, with the unusual finding of entrapment of terminal hairs between agglutinated genital folds or in the vagina. In symptomatic cases, there were severe inflammatory changes accompanying these findings. The initial case prompted a lengthy and costly diagnostic process to no avail. A MEDLINE search yielded several cases of pilonidal disease of the clitoris in younger women, but no reports of hair in the vagina of postmenopausal women. CONCLUSIONS: : This report is noteworthy because pilonidal disease in the lower genital tract of postmenopausal women is a less-known clinical entity. A hypothesis is offered based on its clinical similarity to pilonidal disease in the presacral area.

Papular colpitis: a distinct clinical entity? Symptoms, signs, histopathological diagnosis, and treatment in a series of patients seen at the Rotterdam vulvar clinic.

OBJECTIVE: To study demographic, clinical, and histopathological data as well as treatment outcome in women with papular colpitis. MATERIALS AND METHODS: Data of women (n = 18) visiting the Rotterdam vulvar clinic and meeting the diagnostic criteria for papular colpitis were retrospectively analyzed using patient records. RESULTS: Papular colpitis is usually seen in perimenopausal women and is frequently associated with copious, nonoffensive vaginal discharge and dyspareunia. Histopathological diagnosis consistently shows dense lymphocytic infiltrates. In approximately half of the women, the vulva shows Zoon-like abnormalities. Treatment with topically applied 10% hydrocortisone acetate seemed to be moderately effective. CONCLUSIONS: Papular colpitis seems to be a distinct, relatively rare and possibly autoimmune-related condition. Treatment with 10% hydrocortisone acetate may have a dramatic effect, but recurrences are common and long-term follow-up is warranted.

Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: case report.

Benign melanotic lesions of the vagina are uncommon and only a few cases have been reported in the literature. A 34-year-old woman was referred because of a Vaginal Intraepithelial Neoplasia 1 biopsy result. On the gynecological examination, two different hyperpigmented areas were noted in the vagina. The colposcopic visualization of the cervix and vagina found an aceto-white lesion at the right lateral wall of the upper third of the vagina. Biopsies from three areas were taken. Histological study reported a melanosis of the vagina and HPV infection. An immunohistochemical panel of epithelial markers was performed in vaginal samples, such as Cytokeratin AE1/AE3 and epithelial membrane antigen, mesenchymal marker: vimentin; melanocytic makers: protein S-100 and HMB45 (Human Melanoma Black); proliferating cell marker: proliferating cell nuclear antigen (PCNA), and P-53 oncoprotein. High Risk (16, 18, 31, 45) and Low Risk (6, 11) HPV types were studied by In Situ Hybridization using the same vaginal samples. CK, EMA and Vimentin were 2+. Melanocytic markers, HMB45 and S100, and PCNA were 1+ in basal cell layer. P-53 was negative. The melanotic tissue and acetowhite lesion were positives to HPV Types 6,11. In conclusion, melanosis of the vagina is a uncommon benign pathology. Usually, melanosis is present in women over 40 years old. We present a case of melanosis of the vagina in a young woman infected with low-risk HPV types and review the literature.

Desquamative inflammatory vaginitis: differential diagnosis and alternate diagnostic criteria.

OBJECTIVE: To describe alternate diagnostic protocols and describe the differential diagnosis for desquamative inflammatory vaginitis (DIV). MATERIALS AND METHODS: One hundred one cases of DIV were audited retrospectively. All patients were seen exclusively by the authors in their private practices using diagnostic criteria applicable to local practice limitations. Other potential etiologies (infection, contact irritant vaginitis, fixed drug eruptions, immunobullous diseases, estrogen hypersensitivity vulvovaginitis, and graft-vs-host disease) were excluded by history, examination, and focused trials of treatment. Historical triggers in the study cohort and a control group of 75 women with lichen planus also drawn from the authors' private practice were compared. Patients were treated with 4 to 6 weeks of topical vaginal antibiotics, 94% with clindamycin, and response to treatment was recorded at subsequent follow-up. RESULTS: All patients were white. Of 101 patients, 57 (56%) had historical triggers, most frequently diarrhea or antibiotic treatment. Of the 75 women in the control group with vaginal lichen planus, 11 had historical triggers (15%, p <.0001). Of 101 patients, examination revealed classic ecchymotic findings in 55 (54%), confluent erythema in 36 (36%), involvement of the upper vagina in 8 (8%), and heavy discharge in only 2 (2%). Of 101 patients, 54 (54%) had no significant abnormality on laboratory microbiological testing. Moreover, 20 (20%) had a pure growth of a commensal organism on culture, of which 13 were group B streptococci. Of 101 patients, 96 (95%) were symptomatically and objectively improved at initial review. On the other hand, 45 (45%) required maintenance treatment. Of this group, 10 patients who had triggers for their vaginitis, which were ongoing, were cured when their triggers were finally controlled or cured, leaving 35 patients who required long-term maintenance therapy. CONCLUSIONS: Desquamative inflammatory vaginitis seems to be a distinct entity of vaginitis that, in an office setting, can be distinguished from other diagnostic possibilities by careful clinical evaluation and focused trials of treatment. The majority of women responded promptly to intravaginal antibiotics, with approximately 35% of cases requiring maintenance therapy. More than half the cases have an historical trigger. We postulate that DIV occurs when a trigger causes shifts in vaginal homeostasis, resulting in an inflammatory response associated with increased epithelial cell turnover.

Vulvovaginal-gingival syndrome.

Vulvovaginal-gingival syndrome is a distinct variant of classic lichen planus frequently associated with mucocutaneous scarring and vaginal stricture formation, therefore early diagnosis and treatment through a multidisciplinary approach is essential. Management is challenging and is characterised by wide variation in treatments and lack of evidence-based therapeutic approaches. Literature review with particular regard to therapeutic approaches is performed with a view towards a cooperative treatment study.

The apparition macrophage and Döderlein bacillus is negatively correlated in class I Papanicolaou smear: A morphological examination.

BACKGROUND: Nonspecific vaginitis, also known as Bacterial vaginosis, unlike genital candidiasis and trichomoniasis, is caused by microbiome breakdown. Döderlein's bacillus are gram-positive bacillus that form a microbiome, reproduce in the female vagina after gaining sexual maturity, secrete lactic acid, and prevent the growth of other vaginitis-causing bacteria. Clue cell are squamous epithelial cells with Gardnerella sp. attached to their cell surface. The presence of clue cell is one of the diagnostic criteria for nonspecific vaginitis. Additionally, although macrophages are reported to protect against candidal vaginitis, there are no reports of studies examining the association between macrophages and clue cell. MATERIALS AND METHODS: After re-staining 300 class I specimens by cervical cancer screening with Papanicolaou staining, the appearance of Döderlein's bacillus, macrophages, and clue cell was observed. RESULT: Age group and appearance of Döderlein's bacillus were negatively correlated. The rate of appearance of macrophages was positively correlated with the age group. In people aged 50 years or more, the appearance rate of clue cells was significantly lower in the macrophage appearance group than that in the non-appearance group. CONCLUSION: This study suggested that macrophages, and not Döderlein's bacillus, may play an important role in defense against nonspecific vaginitis.

Qualification of a non-animal vaginal irritation method admitted as nonclinical assessment model (NAM) in the Incubator Phase of the United States Food and Drug Administration (US FDA) Medical Devices Development Tool (MDDT).

The U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) classifies personal lubricants as Class II medical devices. Because of this status and the nature of body contact common to personal lubricants, CDRH reviewers routinely recommend a standard biocompatibility testing battery that includes: an in vivo rabbit vaginal irritation (RVI) test; an in vivo skin sensitization test, such as the guinea pig maximization test (GPMT); and an in vivo acute systemic toxicity test using mice or rabbits. These tests are conducted using live animals, despite the availability of in vitro and other non-animal test methods that may be suitable replacements. The only test included in the biocompatibility battery currently conducted using in vitro assay(s) is cytotoxicity. FDA's recently launched Predictive Toxicology Roadmap calls for the optimization of non-animal methods for the safety evaluation of drugs, consumer products and medical devices. In line with these goals, a Consortium comprising the Institute for In Vitro Sciences, Inc. (IIVS), industry, the Consumer Healthcare Products Association (CHPA), and the PETA International Science Consortium (PETA-ISC) is qualifying the use of an in vitro testing method as replacement for the RVI test. Participating companies include manufacturers of personal lubricants and those interested in the advancement of non-animal approaches working collaboratively with the FDA CDRH to develop an in vitro testing approach that could be used in place of the RVI in pre-market submissions. Personal lubricants and vaginal moisturizers with diverse chemical and physical properties (e.g., formulation, viscosity, pH, and osmolality) in their final undiluted form will be the focus of the program. In vitro vaginal irritation data generated using commercially available human reconstructed vaginal tissue model(s) will be paired with existing in vivo RVI data and analyzed to develop a Prediction Model for the safety assessment of these products. This research plan has been accepted into the FDA CDRH Medical Device Development Tools (MDDT) program as a potential non-clinical assessment model (NAM). The proposed NAM aligns with the goals of the recently launched FDA Roadmap to integrate predictive toxicology methods into safety and risk assessment with the potential to replace or reduce the use of animal testing.

[Safety of promestriene capsule used in postmenopausal atrophic vaginitis].

OBJECTIVE: To investigate the safety and efficacy of promestriene capsule used in the treatment of postmenopausal atrophic vaginitis. METHODS: Fifty-three women at age of 45 - 75 years (more than one year history of menopause) diagnosed with postmenopausal atrophic vaginitis were enrolled in self-control study. They all had typicalsymptoms of postmenopausal vaginitis. Promestriene was given by continuous therapy for 20 days, then maintenance therapy for for 8 weeks (1 pill two times per week used). The level of follicle stimulation hormone (FSH) and estradiol (E(2)) in serum was and thickness of endometrium were detected before and after treatment. The routine biochemical test was used as index to monitoring the safety. The vaginal mature index (VMI), the atrophic vaginitis evaluating score and vaginal healthy evaluating score were evaluated for therapeutic effect. In the mean time, adverse effect was recorded. RESULTS: (1) SAFETY: during promestriene treatment, no case with adverse effect was observed. Before treatment, the mean level of FSH and E(2) was (71 +/- 3) U/L and (41 +/- 18) pmol/L, the mean thickness of endometrium was (2.4 +/- 0.9) mm. After treatment, the mean level of FSH and E(2) was (67 +/- 22) U/L and (43 +/- 37) pmol/L, the mean thickness of endometrium was (2.5 +/- 1.3) mm. No significant difference was observed (P > 0.05). (2) Therapeutic effect: VMI were 42 +/- 15 before and 54 +/- 8 after treatment. The atrophic vaginitis evaluating score were 3.4 +/- 1.7 before and 1.5 +/- 1.4 after treatment. Vaginal healthy evaluating score were 7.8 +/- 2.4 before and 12.0 +/- 2.4 after treatment. They all showed significant difference (P < 0.01). (3) Adverse effect: six cases with vaginal bleeding, 3 cases with breast nodules and 1 case with cervical polyp was observed, however, it was uncertain whether those events were associated with promestriene use. CONCLUSION: The premestriene capsule was safe and effective in the treatment of postmenopausal atrophic vaginitis.

Efficacy of low-dose estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of two vaginal doses of estradiol (E2) compared with placebo in the treatment of atrophic vaginitis. METHODS: In a multi-center, randomized, double-blind, parallel-group study, 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks. Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health. Additional analyses included maturation of vaginal and urethral mucosa. Safety assessments included endometrial biopsy, adverse events, changes in laboratory tests, and physical examinations. After 12 weeks of treatment, all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52. RESULTS: Vaginal tablets with 25 mcg and 10 mcg E2 showed significant (P<.001) improvement in composite score of vaginal health. Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2. Over 12 weeks, both active treatments resulted in greater decreases in vaginal pH than placebo. There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms. The efficacy was maintained to week 52 with 25 mcg E2. CONCLUSION: Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms, improved urogenital atrophy, decreased vaginal pH, and increased maturation of the vaginal and urethral epithelium. Those improvements were greater with 25 mcg than with 10 mcg E2. Both doses were effective in the treatment of atrophic vaginitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00465192 and NCT00464971 LEVEL OF EVIDENCE: I.