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.

Semen: A modulator of female genital tract inflammation and a vector for HIV-1 transmission.

In order to establish productive infection in women, HIV must transverse the vaginal epithelium and gain access to local target cells. Genital inflammation contributes to the availability of HIV susceptible cells at the female genital mucosa and is associated with higher HIV transmission rates in women. Factors that contribute to genital inflammation may subsequently increase the risk of HIV infection in women. Semen is a highly immunomodulatory fluid containing several bioactive molecules with the potential to influence inflammation and immune activation at the female genital tract. In addition to its role as a vector for HIV transmission, semen induces profound mucosal changes to prime the female reproductive tract for conception. Still, most studies of mucosal immunity are conducted in the absence of semen or without considering its immune impact on the female genital tract. This review discusses the various mechanisms by which semen exposure may influence female genital inflammation and highlights the importance of routine screening for semen biomarkers in vaginal specimens to account for its impact on genital inflammation.

Comparison of viromes in vaginal secretion from pregnant women with and without vaginitis.

BACKGROUND: Although some studies have investigated the bacterial community in vaginal tract of pregnant women, there are few reports about the viral community (virome) in this type of microenvironment. METHODS: To investigate the composition of virome in vaginal secretion samples, 40 vaginal secretion samples from pregnant women with vaginitis and 20 vaginal secretion samples from pregnant women without vaginitis, pooled into 4 and 2 sample pools, respectively, were subjected to viral metagenomic analysis. RESULTS: Results indicated virus sequences showing similarity to human papillomavirus (HPV), anellovirus, and norovirus were recovered from this cohort of pregnant women. Further analysis indicated that 15 different defined types and one unclassified type of HPV were detected from pregnant women with vaginitis while only 3 defined types of HPV were detected in pregnant women without vaginitis. Five different groups of viruses from the family Anelloviridae were present in pregnant women with but none of them were detected in pregnant women without vaginitis. Norovirus was detected in 3 out of the 4 sample pools from pregnant women with vaginitis but none in the pregnant women without vaginitis. Twelve complete genomes belonging to 10 different types of HPV, and 5 novel anllovirus genomes belonging 2 different genera in Anelloviridae were acquired from these libraries, based on which phylogenetical analysis and pairwise sequence comparison were performed. Phageome in these samples was also briefly characterized and compared between two groups. CONCLUSION: Our data suggested that virome might play an important role in the progression of vaginitis in pregnant women.

Association Between Common Vaginal Infections and Cervical Non-Human Papillomavirus (HPV) 16/18 Infection in HPV-Vaccinated Women.

BACKGROUND: How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. METHODS: We performed an analysis in 2039 AS04-HPV16/18-vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. RESULTS: Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09-1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62-1.69]). CONCLUSIONS: Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.

The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo.

The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44-56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.

Hormonal Contraception and Vaginal Infections Among Couples Who Are Human Immunodeficiency Virus Serodiscordant in Lusaka, Zambia.

OBJECTIVE: To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis. METHODS: Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest. RESULTS: There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97). CONCLUSION: We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.

Efficacy and safety of combined high-dose interferon and red light therapy for the treatment of human papillomavirus and associated vaginitis and cervicitis: A prospective and randomized clinical study.

BACKGROUND: We evaluated the efficacy and safety of combined high-dose interferon (IFN) and red light therapy for the treatment of subclinical and latent human papillomavirus (HPV) infections. METHODS: Ninety women diagnosed with subclinical or latent HPV infection were randomized to receive topical application of low-dose recombinant IFNα-2b (1 million IU), high-dose IFNα-2b (9 million IU), or a combination of high-dose IFNα-2b and red light therapy on the cervix and vagina. All patients received treatment once daily for 4 weeks. HPV titer was measured immediately and 4, 8, and 12 weeks after treatment to determine the rates of viral clearance and infection cure. Treatment of HPV-associated vaginitis and cervicitis was also evaluated. RESULTS: Results showed that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates and infection cure rates were higher in the high-dose IFN and combination groups compared to the low-dose IFN group. High-dose IFN and combination therapies were significantly effective against both low-risk and high-risk HPV infections. Although the cure rates for vaginitis and cervicitis were significantly higher in the high- compared to the low-dose IFN group, rates were even higher in the combination group compared to the high-dose IFN group. Mild adverse effects were reported by a very small subset of patients (3/30) in the combination group. CONCLUSIONS: This study suggests that combination of high-dose IFN and red light therapy is safe and effective against subclinical and latent HPV infections.

Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections.

[Low rate of oropharyngeal human papillomavirus infection among women with cervical lesion. Preliminary results from the South-Eastern Hungarian population]. / Oropharyngealis humán papillomavírus ritka elofordulása cervicalis laesióval rendelkezo nokben. Elozetes eredmények dél-magyarországi vizsgálat alapján.

INTRODUCTION: Although the natural history of cervical and oral human papillomavirus infection has been intensively investigated in the past years, the ability of this virus to infect oral and genital mucosae in the same individual and its potential to co-infect both cervical and oral mucosa are still unclear. AIM: The aim of the authors was to assess the presence of oropharyngeal human papillomavirus infection in women with cervical lesions in the South-Eastern Hungarian population. METHOD: The total of 103 women have been included in the study between March 1, 2013 and January 1, 2015. Brushing was used to collect cells from the oropharyngeal mucosa. Human papillomavirus DNA was detected using polymerase chain reaction, and Amplicor line blot test was used for genotyping. RESULTS: Oropharyngeal human papillomavirus infection was detected in 2 cases (3%). The detected genotypes were 31, 40/61 and 73 in the oropharyngeal region. CONCLUSIONS: The results indicate that in women with cervical lesions oropharyngeal human papillomavirus infection rarely occurs.

An association between Trichomonas vaginalis and high-risk human papillomavirus in rural Tanzanian women undergoing cervical cancer screening.

OBJECTIVE: The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania. METHODS: For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae. RESULTS: The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37]). CONCLUSIONS: Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16).

In vivo evaluation of safety and toxicity of a Lactobacillus jensenii producing modified cyanovirin-N in a rhesus macaque vaginal challenge model.

Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across the cervicovaginal mucosa in women is influenced by many factors including the microbiota and the presence of underlying inflammation. It is important that potential HIV preventative agents do not alter the mucosal environment in a way that enhances HIV acquisition. We examined the impact of a "live" microbicide on the vaginal mucosal environment in a rhesus macaque repeated vaginal simian-HIV (SHIVSF162P3) challenge model. The microbicide contained a human vaginal Lactobacillus jensenii expressing the HIV-1 entry inhibitor, modified Cyanovirin-N (mCV-N), and henceforth called LB-mCV-N. Macaques were colonized vaginally each week with LB-mCV-N and sampled six days after colonization for culturable bacteria, pH and cervical-vaginal cytokines during the duration of the six-week study. We show that macaques that retained the engineered LB-mCV-N strain in their vaginal microbiota, during SHIV challenge, had lower pH, when colonization levels were higher, and had no evidence of inflammatory cytokines. Indeed, Interleukin-13, a mediator of inflammation, was detected less often in LB-mCV-N colonized macaques than in controls and we found higher levels of Interleukin 1 receptor antagonist (IL-1RA) in LB-mCV-N colonized macaques during the SHIV challenge period. We noted an inverse correlation between levels of mucosal IL-1RA and peak plasma viral load, thus higher IL-1RA correlated with lower viral load in LB-mCV-N treated macaques. These data support the use of LB-mCV-N as a safe "live" microbicide and suggest that lactobacilli themselves may positively impact the mucosal environment.

Nanopharmaceuticals for improved topical vaginal therapy: can they deliver?

Nanopharmaceuticals have the potential to revolutionise medical treatment by permitting the design of more potent, less toxic "smart" therapeutics, ultimately leading to personalised medicine. This review summarises the challenges and potential uses of nanodelivery system for the topical drug therapy of vaginal diseases. The vaginal route of drug administration remains a challenge in the development of novel drug therapies, including nanomedicines. We attempted to provide an unbiased overview of currently investigated nanodelivery systems, some of which remain to be extensively studied under laboratory conditions, and some of which are already in clinical trials. Most nanodelivery systems are aimed at improving the treatment of vaginal infections, including HIV prevention. Promising new approaches in nanopharmaceutical design are discussed in this review, as well as the controversies related to mucoadhesiveness of nanopharmaceuticals.

Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women.

BACKGROUND: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity. METHODS: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated. Immune mediators and viral RNA were quantified in plasma and cervicovaginal lavage (CVL). The CVL antimicrobial activity was also determined. RESULTS: Compared to HIV-uninfected participants, HIV-HVL women had higher levels of mucosal but not systemic proinflammatory cytokines and chemokines, higher Nugent scores, and lower Escherichia coli bactericidal activity. In contrast, there were no significant differences between HIV-LVL and HIV-uninfected controls. After adjusting for PVL, HIV genital tract shedding was significantly associated with higher CVL concentrations of IL-6, IL-1ß, MIP-1α, and CCL5 (RANTES) and higher plasma concentrations of MIP-1α. High PVL was associated with higher CVL levels of IL-1ß and RANTES, as well as with higher Nugent scores, lower E. coli bactericidal activity, smoking, and lower CD4 counts; smoking and CD4 count retained statistical significance in a multivariate model. CONCLUSIONS: Further study is needed to determine if the relationship between mucosal inflammation and PVL is causal and to determine if reducing mucosal inflammation is beneficial.

Arginine inactivates human herpesvirus 2 and inhibits genital herpesvirus infection.

Arginine, among the amino acids, has demonstrated unique properties, including suppression of protein-protein interactions and virus inactivation. We investigated the effects of arginine on the infectivity of human herpesvirus 2 (HHV-2) and the potential application of arginine as a chemotherapeutic agent against genital herpes. Arginine directly inactivated HHV-2 and characterization of the inactivation demonstrated that 1 M arginine at pH 4.3 inactivated the virus more efficiently compared to 0.1 M citrate or 1 M sodium chloride, indicating that neither acidic pH nor ionic strength alone is sufficient for virus inactivation. The effect of arginine was rapid and concentration-dependent. Although virus inactivation was efficient at an acidic pH, arginine inactivated the virus even at a neutral pH, provided that a higher arginine concentration and prolonged incubation time were used. In addition, arginine suppressed the multiplication of HHV-2 under the conditions at which its effect on cell viability was insignificant. Pilot mouse model studies revealed a marked suppression of death by arginine when the mice were infected with HHV-2 through the vaginal route, followed by an intermittent application of acidic arginine by vaginal instillation.

Alpha and gamma herpesvirus detection in two herds of farmed red deer (Cervus elaphus) in New Zealand.

CASE HISTORY: In September 2004 two hinds on Farm 1 were observed with epiphora and keratoconjunctivitis, and corneal scarring. A low pregnancy rate in some hinds had been recorded that year. In the same year six yearling deer were observed on Farm 2 with keratitis, uveitis and corneal scarring. CLINICAL AND PATHOLOGICAL FINDINGS: On Farm 1, conjunctival swabs and blood samples were collected from the hinds with ocular lesions, and from 24 other hinds. The two affected hinds were immunosuppressed with dexamethasone for 7 days. Conjunctival, nasal and vaginal swabs were collected daily before euthanasia and necropsy on the eighth day. Subsequently, another five non-pregnant hinds were similarly immunosuppressed and necropsied, and the reproductive tracts of 20 non-pregnant hinds were collected following slaughter. Semen samples were collected from four stags implicated with reproductive failure. On Farm 2, conjunctival swabs were collected from six hinds with ocular lesions and from 14 unaffected deer. Viral culture, consensus primer PCR and sequencing for specific herpesviruses was carried out on conjunctival swabs, buffy coat from blood samples, semen and reproductive tracts. Necropsy samples were also examined using gross pathology and histopathology. On Farm 1, a type 2 rhadinovirus (CvRhV) was detected in the conjunctiva of one hind with keratoconjunctivitis using PCR. Following immunosuppression, gross vesicular and histological vaginal lesions typical of infection with alphaherpesvirus were observed in samples of vaginal tissue from the same hind. Buffy coat, vaginal and lumbar spinal nervous tissues were also positive for cervid herpesvirus 1 (CvHV-1) using PCR. Herpesviruses were not detected in reproductive tracts, ocular or semen samples of the other deer. CvRhV was detected in buffy coats from four other hinds and in a conjunctival swab from one hind, all without ocular lesions, using PCR. On Farm 2, conjunctival swabs from two deer with keratitis were culture positive for CvHV-1. Two culture-negative conjunctival samples from deer without ocular lesions were positive for CvHV-1 by PCR. In two other affected animals, presence of CvRhV was confirmed by PCR and sequencing. DIAGNOSIS: Infection with CvHV-1 associated with keratitis and vulvovaginitis, and CvRhV infection in deer with and without ocular lesions. CLINICAL RELEVANCE: CvHV-1 is a likely cause of keratoconjunctivitis and possibly reproductive tract pathology in deer. Investigation of ocular lesions and reproductive failure in farmed deer should include CvRhV and CvHV-1.

Genital tract inflammation during early HIV-1 infection predicts higher plasma viral load set point in women.

BACKGROUND: The biggest challenge in human immunodeficiency virus type 1 (HIV-1) prevention in Africa is the high HIV-1 burden in young women. In macaques, proinflammatory cytokine production in the genital tract is necessary for target cell recruitment and establishment of simian immunodeficiency virus (SIV) infection following vaginal inoculation. The purpose of this study was to assess if genital inflammation during early HIV-1 infection predisposes women to rapid disease progression. METHODS: Inflammatory cytokine concentrations were measured in cervicovaginal lavage (CVL) from 49 women 6, 17, 30, and 55 weeks after HIV-1 infection and from 22 of these women before infection. Associations between genital inflammation and viral load set point and blood CD4 cell counts 12 months after infection were investigated. RESULTS: Elevated genital cytokine concentrations 6 and 17 weeks after HIV-1 infection were associated with higher viral load set points and, to a lesser extent, with CD4 depletion. CVL cytokine concentrations during early infection did not differ relative to preinfection but were elevated in women who had vaginal discharge, detectable HIV-1 RNA in their genital tracts, and lower blood CD4 counts. CONCLUSION: Genital inflammation during early HIV-1 infection was associated with higher viral load set point and CD4 depletion, which are markers of rapid disease progression. Strategies aimed at reducing genital inflammation during early HIV-1 infection may slow disease progression.

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.

Melanosis of the vagina and human papillomavirus infection, an uncommon pathology: Case Report / Melanosis de la vagina e infección por virus del papiloma humano, una patología poco común: Reporte de un Caso

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.

Las lesiones melanóticas de la vagina son infrecuentes. y Solo pocos casos han sido reportados. Se presenta el caso de una mujer de 34 años quien es referida con diagnóstico de una Neoplasia Intraepitelial Vaginal 1. Al examen ginecológico, se encontraron dos áreas hiperpigmentadas en la vagina. La exploración colposcópica del cuello uterino y vagina reveló la presencia de una lesión aceto-blanca en la pared lateral derecha del tercio superior de la vagina. Muestras de biopsias fueron tomadas en dichas áreas. El estudio histológico reportó una melanosis de la vagina y una infección por el virus del Papiloma Humano (VPH). Se realizó un panel de estudio inmunohistoquímico de marcadores epiteliales en las muestras vaginales: tales como citoqueratina AE1/AE3 y antígeno epitelial de membrana; marcador mesenquimal: vimentin; marcadores melanóticos: proteina S-100 y HMB45 (Human Melanoma Black); marcadores de proliferación celular: antígeno de proliferación nuclear (PCNA), y la oncoproteína P-53. Se realizó Hibridización In Situ para establecer los tipos de alto (16, 18, 31, 45) y bajo (6, 11) riesgo de VPH en las muestras vaginales. Los marcadores CK, EMA y Vimentin fueron 2+. Los marcadores melanótico, el HMB45 y el S100, y el PCNA fueron 1+ en la capa basal. P-53 fue negativo. El tejido melanótico y la lesión acetoblanca fueron positivos al VPH 6,11. En conclusión, la melanosis vaginal es una patología poco frecuente. Usualmente, se ha reportado en mujeres mayores de 40 años. Presentamos un caso de una melanosis de la vagina infectada con un tipo de VPH de bajo riesgo en una mujer joven y una revisión de la literatura.

Anal sex, vaginal practices, and HIV incidence in female sex workers in urban Kenya: implications for the development of intravaginal HIV prevention methods.

Multiple intravaginal HIV prevention methods, including microbicide gels, barriers, and intravaginal rings, are in clinical development in Africa. Development of intravaginal HIV prevention products requires an understanding of sexual behavior, sexually transmitted infection (STI), and vaginitis prevalences, and sexual and vaginal practices in potential target populations. We assessed these factors in a cohort of Kenyan female sex workers (FSW). Women who reported exchanging sex for money/gifts at least three times in the past month and who were HIV uninfected were enrolled and followed for 6 months. STI prevalence and HIV incidence were analyzed by multivariate logistic regression analysis, controlling for demographic and behavioral factors. Thirty-seven percent (74/200) reported having had anal sex. Frequency of anal sex was higher with regular and casual partners than with primary partners. Women were less likely to use condoms for anal sex than for vaginal sex with regular or casual partners. Vaginal washing was universal (100%). HIV incidence was 5.6 per 100 person-years (95% CI 1.62, 11.67). HIV incidence was not associated with any demographic or risk behavior. The relatively high rate of anal sex and universal vaginal washing may complicate both safety and efficacy evaluation of intravaginal products and should be taken into account in trial design. This FSW population had significant HIV incidence and needs continued HIV prevention interventions.