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Genital ulceration as a presenting manifestation of infectious mononucleosis.

This article describes a case of infectious mononucleosis (IM) in a 16-year-old female adolescent who presented with fever, sore throat, cervical lymphadenopathy and genital ulcerations. Initially, this patient was thought to have herpes simplex viral infection secondary to the characteristic multiple genital ulcers. Seven cases (including this case) have reported an association between Epstein-Barr virus (EBV) infection and genital ulcerations. IM as a cause of genital ulcerations should be included in the differential diagnosis.

Adolescent↗

Detection of HSV-2 in genital ulcers from STD patients in Dar es Salaam, Tanzania.

BACKGROUND: Genital ulcer disease (GUD) is common in many developing countries. Several reports indicate that there is an association with HIV infection. Analysis by polymerase chain reaction (PCR) has demonstrated that the ulcers are frequently caused by herpes simplex type 2 (HSV-2), although HSV-1 is becoming increasingly important in many parts of the world. Comparable studies have not been performed in Tanzania. OBJECTIVES: To determine the prevalence of HSV-2 and HSV-1 in genital ulcers in Dar es Salaam, Tanzania and determine their possible association with HIV infection. STUDY DESIGN: Samples were collected from 70 consecutive patients with GUD attending a clinic for sexually transmitted diseases. Specimens from ulcers were analysed by PCR for the presence of HSV-2 and HSV-1, and sera were examined for antibodies against HSV-2 and HIV. RESULTS AND DISCUSSION: HSV-2 DNA was detected in 64% of the specimens from ulcers while HSV-1 DNA was not found in any of them. Antibodies to HSV-2 and HIV were detected in 79.7 and 42% of the patients' sera, respectively. Although there was a significant positive association between HIV and HSV-2 seropositivity, HSV-2 DNA in genital ulcers was not more prevalent among HIV seropositive than among HIV seronegative individuals. CONCLUSION: The prevalence of HSV-2 antibodies among Tanzanian patients with genital ulcers is very high, and HSV-2 is detected in most of the ulcers. There is an association between infections with HIV and HSV-2, but the relationship is not clear.

Adult↗

Ritual female genital surgery among Ethiopian Jews.

Ritual female genital surgery is usually associated with Muslim countries although it is normative also among Ethiopian Coptic Christians. Ethiopian Jewish women immigrants to Israel report that ritual female genital surgery was normative in their culture in Ethiopia, but expressed no desire to continue the custom in Israel. This contrasts with Israeli Bedouin Muslims, who were reported to regard ritual female genital surgery as an important part of their identity. Physical examination of 113 Ethiopian Jewish immigrant women in Israel found a variety of lesions in about a third of women, with 27% showing total or partial clitoral amputation. The heterogeneity of the physical findings contrasts with uniform verbal reports in interviews of having undergone a ritual of female genital surgery.

Adolescent↗

Prevalence of urinary and fecal incontinence and symptoms of genital prolapse in women.

BACKGROUND: Urinary incontinence is common in women. How often incontinence occurs has been only briefly investigated. Studies on the prevalence of fecal incontinence are few. The epidemiology of genital prolapse symptoms is unknown. This epidemiological study describes a general population of women aged 40 and 60 years with regard to the prevalence and frequency of urinary and fecal incontinence and the prevalence of genital prolapse symptoms. METHODS: A questionnaire on medical background, urinary and fecal incontinence, and genital prolapse symptoms was sent to 1000 40-year-old and 1000 60-year-old randomly selected women. RESULTS: Sixty-seven per cent answered: 53% were continent for urine; 9% of the 40-year-olds and 19% of the 60-year-olds had urinary incontinence weekly or more often. Detrusor instability score was significantly higher in the 60-year-olds. Incontinence of flatus, weekly or more often, was reported by 9% and 19%, loose feces by 5% and 8%, and solid feces by 0.3% and 1.7% according to the 40- and 60-year-olds, respectively. Fifty-three per cent reported no flatus incontinence. Of the prolapse symptoms investigated, 15% of the females reported pelvic heaviness, 4% genital bulge, and 12% use of fingers in the vagina or perineum by defecation. CONCLUSIONS: Incontinence of urine is common in this population. Flatus incontinence is as common, but the concept must be operationalized if used as an endpoint in research. The International Continence Society's (ICS) definition of urinary incontinence is unpractical for use in epidemiological research. We suggest leakage weekly or more often as a criterion for significant incontinence in epidemiological research.

Adult↗

Antibody response to the herpes simplex virus type 2 AG-4 antigen in guinea pigs with genital herpes infections.

Female guinea pigs, inoculated intravaginally with a herpes simplex virus-type 2 (HSV-2) strain M1, developed typical symptoms of a primary and recurrent genital herpes infection. Sera from HSV-2 infected guinea pigs taken during the primary or recurrent stages of the genital infection contained complement (C)-fixing antibody which reacted with an apparent type specificity to an early 4 h HSV-2 infected cell extract (AG-4) when compared to a 4 h HSV-1 infected cell extract. This C-fixing anti-AG-4 activity was shown to be associated with the IgG2 subclass and directed primarily against HSV-2 infected cell polypeptide (ICP)6 and ICP8. Furthermore, C-fixing anti-AG-4 levels remained constant after the primary infection and during recurrences for over 6 months. Thus, while the anti-AG-4 response in guinea pigs was of the IgG type, it varied from that found previously in human genital HSV-2 sufferers which was of the IgM type. Also, while an IgG anti-AG-4 response in human genital HSV-2 sufferers is associated with a reduction in the number of recurrences, this reduction is not apparent in the guinea pig model.

Animals↗

Genital tract tumors in Proteus syndrome: report of a case of bilateral paraovarian endometrioid cystic tumors of borderline malignancy and review of the literature.

Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. Characteristic manifestations include: overgrowth and hypertrophy of limbs and digits, connective tissue nevus, epidermal nevus and hyperostoses. Various benign and malignant tumors and hamartomas may complicate the clinical course of patients with the syndrome. Commonly encountered tumors include hemangiomas, lymphangiomas and lipomas. Tumors of the genital tract occur less often. Bilateral ovarian cystadenomas are regarded as having diagnostic value in Proteus syndrome when occurring within the first two decades of life. We describe a 3-year-old girl with Proteus syndrome who developed bilateral paraovarian villoglandular endometrioid cystadenomatous tumors of borderline malignancy (low malignant potential) of the broad ligament. Desmoplastic tumor implants, presumably noninvasive, were present in biopsies from the pelvic floor, cul-de-sac and omentum. This is the first recognized example of a cystic borderline epithelial tumor of the female genital tract and the first paraovarian tumor reported in a patient with Proteus syndrome. Previously reported tumors and cystic lesions involving the female genital tract and the male genital tract in patients with Proteus syndrome are reviewed. We suspect that specific testicular and paratesticular tumors may prove to have the same diagnostic value in Proteus syndrome as do bilateral cystic ovarian and paraovarian tumors.

Carcinoma, Endometrioid↗

Evidence for centrally initiated genital vasocongestive engorgement in the female rat: findings from a new model of female sexual arousal response.

PURPOSE: In spite of rapidly growing interest, few research tools have been developed to study female sexual dysfunction. Using the D(1)/D(2) agonist, apomorphine (APO), our objective was to develop a new model of the sexual arousal response in female rats based on one previously established for the male condition. METHODS: APO (80 micro g/kg, s.c.) was given during proestrus (P), estrus (E), metestrus (M), early diestrus (DI) and late diestrus (DII), and in ovariectomized (OVX) female Wistar rats. APO-induced behavioral and genital responses were characterized (30 min) using video monitoring. RESULTS: APO-induced reproducible, periodic morphological changes in the external genitalia. The onset, timing and duration of these female APO responses were consistent with genital vasocongestive arousal (GVA) responses in males (ie erections). APO-induced GVAs occurred throughout the estrous cycle, peaking in E (1.4+/-1.21 overall; 0.9+/-0.64 in DII; 1.8+/-1.66 in E) and were markedly diminished by ovariectomy (OVX, 0.4+/-0.51). CONCLUSION: APO induced a reproducible sexual arousal response in female rats involving obvious genital vasocongestive engorgement. Further, the findings demonstrate that the APO-induced genital arousal responses are hormonally regulated.

Animals↗

Changes to the cytokine microenvironment in the genital tract mucosa of HIV+ women.

As previous studies have indicated that genital tract mucosal T cell function may be impaired in HIV infection, we investigated the T cell cytokine mRNA in the genital tract mucosa of HIV-infected women to determine if there are alterations in the cytokine profile which may explain the T cell impairment. The in situ hybridization technique was used to investigate the T helper-1 (Th1: IL-2, interferon-gamma (IFN-gamma)) and Th2 cytokine (IL-4, IL-5, IL-10) mRNA profile in cervical biopsies from 10 HIV+ and 10 HIV- subjects. Cervical intraepithelial neoplasia (CIN) and genital infection had previously been excluded and the distribution of immunocompetent cells within the cervical mucosa was known for each subject. Non-parametric tests were used to compare the optical density (OD) of cytokine mRNA in the HIV+ and HIV- groups. Comparisons were also made between peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA OD for the Th2 cytokines IL-4, IL-5 and IL-10 than HIV women. There was also significantly lower IL-2 mRNA OD in the former group. HIV+ women had lower IFN-gamma mRNA than HIV- women, but the difference was not statistically significant. There was no correlation between cytokine mRNA OD and peripheral CD4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno-inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the susceptibility of HIV-infected women to recurrent genital tract infections and cervical neoplasia.

Adult↗

Dysregulated expression of IFN-gamma and IL-10 and impaired IFN-gamma-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection.

Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-gamma production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-gamma and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-gamma production by HSV-2-stimulated PBMCs. Enhanced production of IFN-gamma may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-gamma failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-gamma resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-gamma at different disease stages and the impaired ability of monocytic cells to respond to IFN-gamma may play a role in the pathogenesis of recurrent genital herpes disease.

Case-Control Studies↗

Effects of psycho-educational interventions on sexual health risks and psycho-social adaptation in young adults with genital herpes.

The purpose of this study was to test the outcomes of group psycho-educational intervention (PEI) led by nurses on sexual health risks (knowledge, behaviour, disease burden) and psycho-social adaptation (depression, mood states, self-efficacy) in young adults with the chronic disease, genital herpes. Two hundred and fifty-two young adults with symptomatic genital herpes participated in a randomized controlled trial (RCT). The intervention was participation in a three-session group PEI facilitated by a nurse in the community. Participants completed questionnaires measuring sexual health risks (herpes knowledge, sexual risk behaviour, disease burden of patterns of recurrences of outbreaks of the disease), and psycho-social adaptation (depression using the Beck Depression Inventory [BDI], mood states using the Profile of Mood States [POMS], and feelings of self-efficacy for protection from sexually transmitted diseases [PSTD]) at induction into the study, and at 3 and 6 months. Participants were mainly employed, Caucasian, single women in their twenties (X = 27.1 years, SD = 4.3), with some college education; 23% of the sample were men. After controlling for baseline knowledge about genital herpes, the experimental group had significantly more knowledge than the control group at 3 and 6 months' post-intervention. They also reported using condoms and spermicides to prevent the spread of genital herpes more often than did the control group. The implications for nurses in the community include the following: (a) PEI is an intervention that can be used by nurses in the community with a high-risk population; (b) group intervention is a viable treatment for people with a highly stigmatized, chronic sexually transmitted disease (STD); and (c) further testing of the use of PEI by nurses in the community with other high-risk populations is needed.

Adaptation, Psychological↗

432 Somali women's birth experiences in Canada after earlier female genital mutilation.

BACKGROUND: Women with previous female genital mutilation (sometimes referred to as circumcision) are migrating, with increasing frequency, to countries where this practice is uncommon. Many health care professionals in these countries lack experience in assisting women with female genital mutilation during pregnancy and birth, and they are usually untrained in this aspect of care. Somali women who customarily practice the most extensive form of female mutilation, who were resident in Ontario and had recently given birth to a baby in Canada, were surveyed to explore their perceptions of perinatal care and their earlier genital mutilation experiences. METHOD: Interviews of 432 Somali women with previous female genital mutilation, who had given birth to a baby in Canada in the past five years, were conducted at their homes by a Somali woman interviewer. RESULTS: Findings suggested that women's needs are not always adequately met during their pregnancy and birth care. Women reported unhappiness with both clinical practice and quality of care. CONCLUSIONS: Changes in clinical obstetric practice are necessary to incorporate women's perceptions and needs, to use fewer interventions, and to demonstrate greater sensitivity for cross-cultural practices and more respectful treatment than is currently available in the present system of care.

Canada↗

Cost-effectiveness of acyclovir suppression to prevent recurrent genital herpes in term pregnancy.

The objective of this paper is to determine whether acyclovir suppression provides a greater cost savings over no medical therapy in the management of recurrent genital herpes (HSV) in pregnancy. Estimates of the risk of HSV recurrence and cesarean delivery rates in acyclovir-treated and -untreated patients and frequency of neonatal acyclovir treatment were derived from literature reviews, prospective surveillance, and practices at our institution. Estimates of costs were derived from average hospital and outpatient clinic charges at our institution. Calculations were run separately for four different groups of patients: women whose first diagnosis of genital herpes occurred during the pregnancy, women whose diagnosis antedated pregnancy and who had infrequent recurrences, women whose diagnosis antedated pregnancy and had frequent recurrences, and all women with a history of genital herpes regardless of timing of diagnosis or frequency of recurrences. Suppressive acyclovir treatment of all term pregnant women with a history of genital herpes resulted in an estimated savings of $183.00 per patient or $36,600,000 per year. Women with their first episode of herpes diagnosed during pregnancy or with frequent recurrences benefitted even more, achieving a savings of $455.00 and $391.00 per patient, respectively. Assuming that prenatal acyclovir treatment is safe for the fetus, utilizing this management for all patients with recurrent HSV in pregnancy could immediately save $183 per patient. On a national level, this translates to $36,600,000 per year just in reduced obstetrical costs. If indirect costs associated with cesarean deliveries had been included in these calculations, the estimated savings would be even more substantial.

Acyclovir↗

[The development of the early genital anlage and its significance for the development of the large intestine--studies of rat embryos].

The morphology of infraumbilical malformations suggests that the development of the genital anlage is of great importance for the embryology of the cloaca. In rat embryos the development of the genital anlage is documented using scanning electron microscopy. This documentation suggests that the genital anlage develops in three phases. Of these, the development of the unpaired glandular hillock seems to be especially important. The genital anlage affects the development of the cloaca in two ways: firstly its ventral growth causes a ventral shifting of the greater part of the cloaca into the region of the genitalia and secondly the cloaca gains its definite position through the development and growth of the glandular hillock.

Animals↗

[Timing and technic of the surgical correction of childhood intersex genitals including the procedure for partial vaginal aplasia].

The author holds the opinion that surgical correction of intersexual outer genital should be performed before the second birthday. In case of an adrenogenital syndrome with deep (peripheral) junction of the vagina into the urogenital sinus, vaginoplasty of the introitus and displacement of the clitoris should be performed in a single session. The author describes his own operational technique. If the vagina enters the urogenital sinus near the bladder, the author recommends to employ the operation technique described by Hendrin for removal and reimplantation of the vagina into the perineum, combined with the author's own technique of displacing the clitoris. Partial absence or atrophy of the vagina was seen in 8 cases. The author describes his own abdominoperineal operation method for correcting this defect. In cases where the intersexual genital is to be corrected in the direction of a male genital, the author recommends shaft erection in the first session and urethroplasty in the second session according to the technique described by Denis Browne. In all, 132 patients were surgically treated for correction of an intersexual genital.

Child↗

Glycoprotein-D-adjuvant vaccine to prevent genital herpes.

BACKGROUND: An effective prophylactic vaccine would help control the spread of genital herpes. METHODS: We conducted two double-blind, randomized trials of a herpes simplex virus type 2 (HSV-2) glycoprotein-D-subunit vaccine with alum and 3-O-deacylated-monophosphoryl lipid A in subjects whose regular sexual partners had a history of genital herpes. In Study 1, subjects were seronegative for herpes simplex virus type 1 (HSV-1) and HSV-2; in Study 2, subjects were of any HSV serologic status. At months 0, 1, and 6, subjects received either vaccine or a control injection and were evaluated for 19 months. The primary end point was the occurrence of genital herpes disease in all subjects in Study 1 and in HSV-2-seronegative female subjects in Study 2. RESULTS: A total of 847 subjects who were seronegative for both HSV-1 and HSV-2 (268 of them women, in Study 1) and 1867 subjects who were seronegative for HSV-2 (710 of them women, in Study 2) underwent randomization and received injections. Vaccination was well tolerated and elicited humoral and cellular responses. Overall, the efficacy of the vaccine was 38 percent in Study 1 (95 percent confidence interval, -18 to 68 percent; 15 cases occurred in the vaccine group and 24 in the control group), and efficacy in female subjects was 42 percent in Study 2 (95 percent confidence interval, -31 to 74 percent; 9 cases occurred in the vaccine group and 16 in the control group). In both studies, further analysis showed that the vaccine was efficacious in women who were seronegative for both HSV-1 and HSV-2: efficacy in Study 1 was 73 percent (95 percent confidence interval, 19 to 91 percent; P=0.01), and efficacy in Study 2 was 74 percent (95 percent confidence interval, 9 to 93 percent; P=0.02). It was not efficacious in women who were seropositive for HSV-1 and seronegative for HSV-2 at base line or in men. CONCLUSIONS: These studies suggest that the glycoprotein D vaccine has efficacy against genital herpes in women who are seronegative for both HSV-1 and HSV-2 at base line but not in those who are seropositive for HSV-1 and seronegative for HSV-2. It had no efficacy in men, regardless of their HSV serologic status.

Adjuvants, Immunologic↗

Clinical findings among young women with genital human papillomavirus infection.

OBJECTIVE: The purpose of this study was to identify clinical signs and symptoms associated with detection of human papillomavirus (HPV) DNA in the female genital tract. STUDY DESIGN: A total of 516 university students (18 to 24 years old) enrolled in a cohort study that included the collection of genital specimens for HPV DNA testing every 4 months for up to 4 years. Reported symptoms and objective clinical findings of women with and without HPV DNA were compared by multivariate analysis. RESULTS: Acute and persisting HPV infections were not associated with discharge, itching, burning, soreness, or fissures. Clinical evidence of genital warts was statistically associated only with HPV types 6 and 11. Detection of any HPV DNA was associated with bacterial vaginosis (BV). Furthermore, a time lag analysis suggests that HPV infection usually precedes detection of BV. CONCLUSION: Most women who acquire genital HPV infection are asymptomatic; some, however, are at increased risk for BV.

Adult↗

Expectant management of preterm premature rupture of membranes complicated by active recurrent genital herpes.

OBJECTIVE: The study objective was to examine the neonatal outcome in pregnancies with early preterm premature rupture of the membranes (PPROM) who were managed expectantly despite the development of recurrent active genital herpes. STUDY DESIGN: Pregnancies complicated by PPROM at < or =14;31 weeks' gestation that developed an active recurrent genital herpes lesion were collected. The latency time from herpes lesion development to delivery and the neonatal outcome were analyzed. A control group of patients with PPROM at < or =14;31 weeks' gestation with no herpes infection was also obtained. RESULTS: A total of 29 patients were identified during the study period. The mean gestational age at herpes lesion development after PPROM was 28.7 weeks (range 24.6-31.0 weeks). The mean latency period from herpes development to delivery was 13.2 days (range 1-35 days). No cases of neonatal herpes developed in the delivered newborn infants and all neonatal cultures were negative (0 of 29 cases, 95% CI 0%-10.4%). Twelve newborn infants (41%) had major morbidity caused by prematurity and 3 of these (10.3%) died. There were no differences seen between the study cases and the control group. In the study, 15 of the 29 pregnancies were delivered beyond 30 weeks' gestation. If delivery had occurred on the day the herpes lesion developed, only 5 pregnancies would have been delivered beyond 30 weeks' gestation. CONCLUSION: On the basis of the 95% CI of these data, the maximum risk for development of a neonatal herpes infection in the face of PPROM and active recurrent genital herpes was 10.4%. This was equal to the mortality rate and was 75% lower than the major morbidity rate caused by prematurity. If delivery had occurred on the day the herpes lesions developed, on average, the neonates would have been nearly 2 weeks more premature, thereby potentially increasing the morbidity and mortality related to prematurity. These data concur with the American College of Obstetricians and Gynecologists consensus and expert opinion and would suggest that expectant management of PPROM at </=14;31 weeks' gestation with active recurrent genital herpes is warranted.

Adult↗

HIV-1 in genital tract and plasma of women: compartmentalization of viral sequences, coreceptor usage, and glycosylation.

Worldwide, 90% of HIV-1 infections are transmitted heterosexually. Because the genital mucosa are the sites of initial contact with HIV-1 for most exposed individuals, study of the virus from the genital tract is critical for the development of vaccines and therapeutics. Previous analyses of HIV-1 in various tissues have documented compartmentalization of viral genomes. Whether compartmentalization was associated with viral phenotypic differences or immune status, however, was not well understood. We compared HIV-1 gp120 env sequences from the genital tract and plasma of 12 women. Eight women displayed compartmentalized HIV-1 RNA genomes, with viral sequences from each site that were clearly discrete, yet phylogenetically related. The remaining four exhibited env sequences that were intermingled between the two sites. Women with compartmentalized HIV-1 genomes had higher CD4+ cell counts than those displaying intermingled strains (P = 0.02). Intrapatient HIV-1 recombinants comprising sequences that were characteristic of both sites were identified. We next compared viral phenotypes in each compartment. HIV-1 coreceptor usage was often compartmentalized (P 0.01). The number of N-linked glycosylation sites, associated with neutralization resistance, also differed between compartments (P < 0.01). Furthermore, disparities between the density of gp120 glycosylations in each compartment correlated with higher CD4+ counts (P = 0.03). These data demonstrate that the genital tract and plasma can harbor populations of replicating HIV-1 with different phenotypes. The association of higher CD4+ cell counts with compartmentalization of viral genomes and density of gp120 glycosylations suggests that the immune response influences the development of viral genotypes in each compartment. These findings are relevant to the prevention and control of HIV-1 infection.

Adult↗