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PubMed1994

Genital human papillomavirus infection.

Genital human papillomavirus (HPV) infection is a common sexually transmitted disease that at the present time is not effectively controlled or treated. Many infections are inapparent and transient. However, some HPV infections result in persistent lesions that in some cases undergo carcinogenic progression. A subset of genital HPVs, designated high-risk types, are preferentially associated with high-grade dysplasias and carcinomas. About 90% of cervical cancers contain high-risk HPV DNA, most often HPV16. Development of a subunit vaccine against high-risk genital HPVs is a desirable and, it appears, an increasingly feasible long-term goal. The viral E6 and E7 oncoproteins are selectively maintained and expressed in progressed HPV tumors and could potentially be targets for therapeutic vaccines. The L1 major virion structural proteins have recently been shown to self-assemble into virus-like particles when expressed in insect cells. These particles might serve as the basis for a prophylactic vaccine to prevent genital HPV infection.

Antibodies, Viral↗

PubMedDate not supplied

Repetitive male genital self-mutilation: a case report and discussion of possible risk factors.

Male genital self-mutilation is an infrequently reported occurrence in the medical literature. The reports describing such cases have focused mostly on surgical repair. The case reports written from a psychiatric point of view have outlined possible risk factors contributing to this behavior. Typically, reports depict cases of a single episode of self-mutilation. To date, we have found twelve cases that have addressed the specific issue of repeated episodes of genital self-mutilation. In this article, we report the case of a 49-year-old man who succeeded in castrating himself after sequential episodes of genital mutilation. We will review previous cases of repetitive male genital self-mutilation and draw comparisons between those and our patient's case to arrive at common risk factors that may alert the clinician to this type of behavior.

Genitalia, Male↗

PubMed2002

Neurophysiology and pharmacology of female genital sexual response.

Vaginal sexual arousal is a vasocongestive and neuromuscular event controlled by facilitatory parasympathetic and inhibitory sympathetic inputs. Autonomic preganglionic parasympathetic and inhibitory sympathetic fibers to the vagina and clitoris originate in the spinal cord in the sacral parasympathetic nucleus at the sacral level and in the dorsal gray commissure and the intermediolateral cell column at the thoracolumbar level, respectively. Parasympathetic fibers are conveyed by the pelvic nerve, and sympathetic fibers are conveyed by the hypogastric nerve and the paravertebral sympathetic chain. The activity of these spinal nuclei is controlled by descending projections from the brain and sensory afferens (conveyed in the pudendal, hypogastric, pelvic, and vagus nerves) from the genitalia. A key but unresolved issue concerns the neurotransmitters involved in the control of genital sexual arousal. At the peripheral level, acetylcholine plays a minor role in the regulation of vaginal blood flow, however, recent data suggests that it may be involved in the control of vaginal smooth muscle contractions. Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal, whereas noradrenaline is likely inhibitory. Within the central nervous system, serotoninergic projections from the brain to the spinal cord likely inhibit the induction of genital arousal by peripheral informations (spinal reflex). Although some neurotransmitters regulating the display of sexual behavior have been identified (for example, dopamine), their involvement in the control of genital sexual arousal has not been invested. Anatomical and electrophysiological data point to a contribution of the paraventricular nucleus of he hypothalamus and the median preoptic area, respectively, as key elements in the control of genital arousal. The recent development of models allowing the assessment of vaginal sexual arousal in anesthetized female rats should assist in deciphering the neurochemical pathways controlling vaginal sexual arousal and the development of suitable pharmacological treatment for female sexual dysfunctions.

Acetylcholine↗

PubMed1997

A prospective study of the correlation between genital pathogens and morbidity following diathermy loop excision of the transformation zone.

A prospective study of 48 women was carried out to estimate the incidence of common genital pathogens in women referred to colposcopy clinic requiring diathermy loop excision and to compare patient morbidity in the subgroups with and without genital pathogens. Of the 43 women included in the analysis, genital pathogens were present in 24 cases (56%) and absent in 19 (44%) of the 24 positive cases, 19 (79%) women had pathogen(s) on the cervical swab, 24 (100%) had pathogen(s) on the high vaginal swab and 15 (63%) had both a positive cervical and high vaginal swab (HVS). The most frequently isolated groups of organisms were mixed anaerobes, alone (four HVS and four cervical) or in combination with Gardnerella vaginalis (four HVS and three cervical) or coliforms (two HVS and two cervical). The mean duration of bleeding and vaginal discharge in the two study groups was not statistically significant (t value 1.97, P 0.05; and t value 0.48, P 0.5, respectively). However, the mean duration of bleeding graded by the patient as being moderate to severe was significantly different in the two groups (t value 3.18 P 0.01). Fifty-six per cent of the women in the study had confirmed genital pathogens, predominantly anaerobes, and the prolonged moderate-to-severe bleeding in this group suggests a potential role for prophylactic bacteriocides, although the study size was unable to implicate a single pathogen.

Journal Article↗

PubMed1999

Should women with genital condyloma acuminata have routine diagnostic colposcopy in addition to cervical smear screening?

We aimed to evaluate the difference in the pick up rate of high grade cervical abnormalities using both primary colposcopy and cervical smear compared with cervical cytology screen only on women with genital warts. We also wished to establish whether this group was at high risk of sexually transmittable infections (STIs) and whether there is a correlation between those with high grade CIN and other STIs. This was a retrospective analysis based in the Department of Genito-Urinary Medicine, Dundee Teaching Hospitals Trust, Dundee, UK. We studied all women (n =117) attending the Department with genital warts between January 1995 and March 1997 who were screened by both cervical cytology and colposcopy High grade cervical abnormalities (CIN II-CIN III) were diagnosed in 10 patients (8.5.%) using cervical screening only and in 41 patients (35%) (CIN II-III) when primary colposcopy and histopathology were undertaken. Of 117 women screened for sexual transmittable infection there were 53 with a positive diagnosis (48%). Of the 53 positive there were 17 women (30%) with high grade CIN. We conclude that women with genital warts are a high risk group, both in terms of having high grade cervical abnormalities and sexually transmittable infection. The result suggests that, when practicable primary colposcopy should be performed as a routine screening tool, on this group of patients over and above cervical cytology screening. All patients with genital warts should be referred to genitourinary medicine for STI screening.

Journal Article↗

PubMed2001

Medical complications of female genital mutilation.

More than 130 million women are subjected to genital mutilation. Despite increasing efforts to reduce the practice, there are many obstacles to eliminating this 2,000-year-old practice, which is based on strong cultural traditions. As college health clinicians provide care to more international students from countries where female genital mutilation is performed, increased awareness and knowledge of the procedure will enable clinicians to understand and manage its complications. We report a case of obstructive uropathy resulting in hydronephrosis secondary to female genital mutilation and review the medical literature regarding this and other complications of genital mutilation "surgery."

Adult↗

PubMed2003

Maternal group B streptococcal (GBS) genital tract colonization at term in women who have asymptomatic GBS bacteriuria.

OBJECTIVE: To determine the rate of positive group B streptococcus (GBS) cultures at 35-37 weeks gestation in women who have first trimester asymptomatic GBS bacteriuria. METHODS: Pregnant women with asymptomatic first trimester GBS bacteriuria had genital cultures for GBS performed at 35-37 weeks gestational age. Serotyping was performed by the standard Lancefield capillary precipitin method. RESULTS: Fifty-three women with positive urine cultures had genital cultures performed at 35-37 weeks. Sixteen of the 53 (30.2%; 95% confidence interval: 18.4-44.3%) third trimester vaginal cultures were positive for GBS. Five of eight (63%) of the women with typable urine serotypes had the same typable serotype in the third trimester genital culture. CONCLUSION: Genital tract cultures at 35-37 weeks for GBS correlate poorly with first trimester asymptomatic GBS bacteriuria. Recommendations for GBS prophylaxis in labor in women who have first trimester asymptomatic GBS bacteriuria should be investigated further and reconsidered.

Adolescent↗

PubMed2002

Validation of a high sensitive immunoenzymatic assay to establish the origin of immunoglobulins in female genital secretions.

Several studies were carried out to characterize the humoral immune response on mucosal genital surfaces. However, the results obtained so far were particularly conflicting due to the absence of validation methods. The aim of this study was to develop and validate a quantitative ELISA method, which is sensitive and reproducible, to measure immunoglobulin and secretory immunoglobulin concentrations in various biological fluids. This quantitative, sensitive (detection limit = 1 microg/L) and reproducible (coefficient of variation < 15%) method could be of interest to study the effects of viral infections on mucosal non-specific immune response in genital tract. To explore the humoral response, serum, saliva, vaginal secretions, and cervicovaginal secretions from 18 women, 20-45 years old, were evaluated for total-IgA, secretory IgA, IgM, and IgG. Albumin level was also evaluated by immuno-nephelometry. The secretion rates of immunoglobulins were measured by calculating their relative coefficients of excretion by reference to albumin. Despite large individual variations, median immunoglobulin levels were higher in the endocervical secretions than in the cervicovaginal secretions. When we compared the rates of immunoglobulins in genital fluids, IgG prevalence was higher (80%) in cervicovaginal and endocervical secretions than IgA prevalence (12%). In contrast, digestive mucosal secretions, such as saliva, contained mostly IgA (80%). In cervicovaginal and endocervical secretions, IgG and IgM originated mainly from serum, whereas a local synthesis provided total-IgA and secretory IgA. These results allowed us to raise a possible hypothesis for the origin of immunoglobulins in the genital tract. They illustrated the peculiar feature of the female reproductive tract and the difficulty for this tissue to contribute in the mucosal associated lymphoid tissue. The low secretory-IgA and total-IgA levels could explain the particular sensitivity of the vagina and the cervix to infections.

Adolescent↗

PubMed1999

Mucosal immune system of the human genital tract.

In contrast to the pronounced dominance of secretory IgA over other immunoglobulin isotypes in human saliva, tears, milk, and gastrointestinal fluids, secretions of both female and male genital tracts contain more IgG than secretory IgA. Both IgG and IgA are derived, to a variable degree, from the systemic immunoglobulin pool as well as from local synthesis. The origin of IgG- and IgA-plasma cell precursors destined for the genital tract is unknown, but indirect evidence suggests that mucosal inductive sites localized in the rectum, small intestine, and especially in the nasal cavity contribute such precursors to the female genital tract. Several studies indicated that intranasal immunization of various species, including humans, was efficient at inducing antigen-specific antibody responses in the female genital tract; however, whether this route is also effective in males has not been explored.

Female↗

PubMed2000

Correlation between human immunodeficiency virus type 1 RNA levels in the female genital tract and immune activation associated with ulceration of the cervix.

To address the hypothesis that local immune activation resulting from genital ulceration enhances human immunodeficiency virus type 1 (HIV-1) replication and shedding into the genital tract, paired plasma and cervicovaginal lavage (CVL) samples were obtained from 12 HIV-infected women before and after treatment of cervical intraepithelial lesions. Two weeks after treatment, inflammation and ulceration of the cervix were accompanied by major increases in mean concentrations of HIV-1 RNA (200-fold), tumor necrosis factor-alpha, interleukin 6, and soluble markers shed by activated lymphocytes and macrophages (sCD25 and sCD14, respectively) in CVL samples (P<.01 for each), but not plasma. Strong temporal and quantitative correlations were observed between concentrations of immunological markers and HIV-1 load in this compartment during a 10-week follow-up. Furthermore, in the presence of genital ulceration, HIV-1 in CVL samples was more readily captured by antibodies directed against virion-associated HLA-DR, a marker of host-cell activation, compared with virus in plasma. We suggest that local immune activation increases HIV-1 load in genital secretions, potentially increasing the risk of HIV-1 transmission.

Adult↗

PubMed2001

Penetration of the nucleoside analogue abacavir into the genital tract of men infected with human immunodeficiency virus type 1.

The male genital tract is considered an anatomical reservoir during therapy for human immunodeficiency virus infection, because the blood-testis barrier may prevent antiretroviral drugs (e.g., the protease inhibitors ritonavir, saquinavir and nelfinavir) from entering the male genital tract. To our knowledge, there are currently no available data on the penetration of the nucleoside analogue abacavir into the male genital tract. Our report shows that abacavir has good penetration into the male genital tract.

Anti-HIV Agents↗

PubMed2002

Patient and physician partnerships in managing genital herpes.

Genital herpes simplex virus infections are widespread throughout the world and are characterized by stigma, myth, and anxiety by patients and the public but are perceived as trivial by most physicians. Surveys in the United States, Europe, Australia, and South Africa have measured the unfavorable effect of genital herpes on infected patients, health care resources, and workplace productivity. These surveys identified limited satisfaction of patients with current care and support (41% satisfied), although satisfaction scores were greater for patients receiving suppressive antiviral therapy (56% satisfied). Bridging the gap between patients and physicians is vital for improving the management of genital herpes. Key to facilitating patient-physician partnerships is education and recognition by physicians that patients with genital herpes may have expert knowledge. In effective partnerships, physicians and patients can have informed constructive discussions such that patients share in the responsibility for managing their disease and in therapeutic decision making.

Antiviral Agents↗

PubMed2003

Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects.

To determine the efficacy and safety of valacyclovir (500 mg twice daily) for the suppression of recurrent genital herpes simplex virus infections in human immunodeficiency virus (HIV)-infected subjects, a randomized, double-blind, placebo-controlled, multicenter international trial was conducted. A total of 293 HIV-seropositive subjects receiving antiretroviral therapy were enrolled. The proportion of subjects who did not have a recurrence of genital herpes at 6 months was 65% among valacyclovir recipients versus 26% among placebo recipients (relative risk, 2.5; 95% confidence interval, 1.8-3.5). The time to first genital herpes recurrence was significantly shorter in the placebo group (median, 59 days) than in the valacyclovir group (median, >180 days). Valacyclovir was well tolerated; the incidence of adverse events for the 2 treatment groups was similar when the duration of treatment was considered. There were no episodes of thrombotic microangiopathy. Valacyclovir was safe and effective for the suppression of recurrent genital herpes infection in HIV-infected individuals.

Acyclovir↗

PubMed2004

Valacyclovir and acyclovir for suppression of shedding of herpes simplex virus in the genital tract.

BACKGROUND: Valacyclovir exhibits better oral absorption and higher, more prolonged serum concentrations than oral acyclovir. The efficacy of valacyclovir and acyclovir on genital herpes simplex virus (HSV) shedding was assessed in a double-blind, 3-period crossover trial. METHODS: Sixty-nine immunocompetent participants with genital HSV-2 received oral valacyclovir, acyclovir, and matching placebo in random order for 7-week periods. Participants provided daily genital mucosal swabs for HSV detection by viral culture and polymerase chain reaction (PCR). RESULTS: HSV was detected at least once in 62 (90%) participants by culture and in 68 (98%) by PCR. During placebo, the total HSV shedding rate was 15.4% of days by culture (PCR, 40.2%); the subclinical shedding rate was 6.6% by culture (PCR, 27.1%). Both antivirals were associated with lower HSV shedding by culture (relative risk [RR], 0.03 [95% confidence interval [CI], 0.01-0.07] for valacyclovir and RR, 0.05 [95% CI, 0.03-0.10] for acyclovir) and PCR (RR, 0.18 [95% CI, 0.12-0.26] for valacyclovir and RR, 0.20 [95% CI, 0.15-0.28] for acyclovir), compared with placebo. No significant differences in frequency and quantity of HSV were detected by PCR between the valacyclovir and acyclovir arms. CONCLUSIONS: Although the suppression of viral replication is not complete, valacyclovir and acyclovir are highly effective in suppressing the frequency and quantity of genital HSV shedding.

Acyclovir↗

PubMed2004

Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis.

BACKGROUND: Bacterial vaginosis (BV) is associated with human immunodeficiency virus (HIV) acquisition. We examined the association between BV and BV-associated bacteria and expression of HIV in the female genital tract. METHODS: HIV RNA, lactobacilli, Gardnerella vaginalis, and Mycoplasma hominis in cervicovaginal lavage (CVL) samples were quantified by polymerase chain reaction (PCR). Gynecologic evaluation included Nugent score assessment, Amsel criteria assessment, detection of other genital-tract infections, and dysplasia grading. CD4 cell count, plasma HIV RNA level, and antiretroviral history were obtained. RESULTS: A total of 203 CVL samples from women with Nugent scores of 7-10 (BV group) and 203 samples from women with Nugent scores of 0-3 (no-BV group) were matched by plasma HIV RNA level and analyzed. After controlling for plasma HIV RNA level and Nugent score in univariate analyses, we found that G. vaginalis and M. hominis bacterial counts, Candida vaginitis, and herpes simplex virus (HSV) were positively associated with CVL HIV RNA levels. In multivariate analysis, only lactobacilli bacterial counts (P=.006; inverse association), M. hominis bacterial counts (P=.0001; positive association), Candida vaginitis (P=.007), and HSV (P=.03) were significantly associated with CVL HIV RNA levels. CONCLUSION: Bacteria associated with BV increase genital-tract HIV RNA levels. Quantitative bacterial counts for lactobacilli and M. hominis are better correlates of CVL HIV RNA than are Nugent score or Amsel criteria. Since plasma virus and CD4 cell levels did not differ between the BV and no-BV groups, these data suggest that the bacterial flora associated with BV influence genital-tract HIV shedding.

Adult↗

PubMed2005

Genital tract shedding of herpes simplex virus type 2 in women: effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization.

BACKGROUND: Genital infections due to herpes simplex virus type 2 (HSV-2) are characterized by frequent reactivation and shedding of the virus and by the attendant risk of transmission to sexual partners. We investigated the effects of vaginal coinfections and hormonal contraceptive use on genital tract shedding of HSV-2 in women. METHODS: A total of 330 HSV-2-seropositive women were followed every 4 months for a year. At each visit, one vaginal swab specimen was obtained for detection of HSV-2 by polymerase chain reaction, a second vaginal swab specimen was obtained for detection of group B Streptococcus (GBS) organisms and yeast by culture, and a vaginal smear was obtained for the diagnosis of bacterial vaginosis by Gram staining. RESULTS: HSV-2 DNA was detected in 88 (9%) of 956 vaginal swab specimens. Independent predictors of genital tract shedding of HSV-2 were HSV-2 seroconversion during the previous 4 months (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.3-6.8), bacterial vaginosis (aOR, 2.3; 95% CI, 1.3-4.0), high-density vaginal GBS colonization (aOR, 2.2; 95% CI, 1.3-3.8), and use of hormonal contraceptives (aOR, 1.8; 95% CI, 1.1-2.8). CONCLUSIONS: The present study identifies hormonal contraceptive use, bacterial vaginosis, and high-density vaginal GBS colonization as risk factors for genital tract shedding of HSV-2 in women. Because hormonal contraceptives are used by millions of women worldwide and because bacterial vaginosis and vaginal GBS colonization are common vaginal conditions, even modest associations with HSV-2 shedding would result in substantial attributable risks for transmission of the virus.

Adolescent↗

PubMed2005

Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.

BACKGROUND: Famciclovir, the oral prodrug of penciclovir, is effective for the treatment of recurrent genital herpes. This randomized, clinic-initiated, double-blind trial compared the therapeutic efficacy and safety of treatment with famciclovir at dosages of 125 mg, 250 mg, and 500 mg twice daily for 5 days with placebo in immunocompetent adults with a recurrent episode of genital herpes. METHODS: Efficacy and tolerability were assessed in 308 patients with lesions present for no more than 6.5 h at the time of the first dose. Two assessments per day were performed to increase the precision of the determination of study end points. RESULTS: All doses of famciclovir were significantly more effective than placebo in reducing the time to cessation of viral shedding, complete lesion healing, and loss of all lesion-associated symptoms, particularly lesion tenderness, pain, and itching. Patients receiving treatment with famciclovir were significantly less likely to experience new lesions than were patients receiving placebo. All doses of famciclovir were tolerated as well as placebo was. There was no difference in efficacy or tolerability among the different doses of famciclovir; the lowest effective dose was 125 mg twice per day. CONCLUSIONS: In immunocompetent adults with recurrent genital herpes, a 5-day course of famciclovir at a dosage of 125 mg, 250 mg, or 500 mg twice per day was significantly more effective than was placebo in reducing the duration of viral shedding and symptoms and in accelerating lesion healing. These results support the use of treatment with famciclovir at a dosage of 125 mg for 5 days as an effective, well-tolerated treatment for episodes of recurrent genital herpes.

2-Aminopurine↗

PubMed2005

Impact of immunization with glycoprotein D2/AS04 on herpes simplex virus type 2 shedding into the genital tract in guinea pigs that become infected.

In recent clinical trials, a vaccine that contained herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) and the adjuvant AS04 afforded HSV-seronegative women significant protection against HSV-2 genital disease and limited protection against infection. Similarly, in guinea pigs, immunization with the vaccine provided significant protection against genital HSV-2 disease but did not prevent mucosal infection. We explored the impact of immunization on the magnitude of latent virus infection and on the frequency and magnitude of virus reactivation as measured by both recurrent disease and viral shedding into the genital tract. Guinea pigs immunized with gD2/AS04 were shown by quantitative polymerase chain reaction (qPCR) analysis to have significantly less latent viral DNA in the ganglia than did naive control guinea pigs and to have a reduced incidence and frequency of recurrent disease. By contrast, all immunized guinea pigs shed virus into the genital tract with a frequency comparable to that seen in control guinea pigs. However, the amount of virus shed was significantly reduced, as measured by qPCR. These data suggest that immunization could affect transmission by altering viral shedding patterns.

Adjuvants, Immunologic↗