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PubMed1999

The effect of doxycycline treatment on the development of protective immunity in a murine model of chlamydial genital infection.

Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) worldwide. Antibiotics are effective in treating infection; however, reinfection is common. This observation has led to the conclusion that infection fails to elicit a protective antichlamydial immune response. It was postulated that high reinfection rates might be due to early eradication of organisms from genital tissue after antibiotic intervention, which could negatively influence the development of naturally acquired protective immunity. This hypothesis was tested by use of a murine model of female genital infection. The findings show that doxycycline intervention of infection, although very effective in eradicating chlamydiae from genital tissue and preventing upper genital tract disease, significantly inhibits the development of protective immunity. If antibiotic intervention of human chlamydial genital infection has a similar effect on protective immunity, it could have important implications in the understanding of immunity to infection and future public health efforts to control chlamydial STD.

Animals↗
PubMed2000

Herpes simplex virus type 1 as a cause of genital herpes: impact on surveillance and prevention.

This study compared characteristics of patients who had herpes simplex virus (HSV) type 1 with characteristics of patients who had HSV-2, by use of data from a cross-sectional analysis. Data were collected in an urban sexually transmitted diseases clinic from patients who had positive genital HSV cultures. Overall, 17.1% (95% confidence interval [CI], 14.9%-19.3%) of 1145 genital HSV isolates obtained during 1993-1997 were HSV-1. The proportion of HSV-1 among initial genital herpes infections was higher among men who had sex with men (46.9%) than among women (21.4%) and was lowest among heterosexual men (14.6%). White race (odds ratio [OR], 3.7; 95% CI, 2.3-5.9) and receptive oral sex in the preceding 2 months (OR, 2.8; 95% CI, 1.9-4.3) significantly increased the odds that initial infections were HSV-1 rather than HSV-2. Genital HSV-1 may often be acquired through contact with a partner's mouth. These data suggest that seroprevalence studies based solely on HSV-2 type-specific assays underestimate overall prevalence of genital HSV infection.

Adult↗
PubMed2001

Variation of human immunodeficiency virus type 1 viral RNA levels in the female genital tract: implications for applying measurements to individual women.

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.

Cervix Uteri↗
PubMed2003

The health and economic burden of genital warts in a set of private health plans in the United States.

We estimated the prevalence of and costs associated with genital warts among privately insured individuals from the perspective of a private health plan in the United States. Health care claims data were derived from a sample of 3,664,686 privately insured individuals. The database was limited to cases of disease for which an insurance claim was generated, with costs reflecting inpatient, outpatient, and pharmacy payments from all sources. We identified 5095 cases of genital warts (1.7 cases per 1000 person-years) billed through the health plans during 2000. The prevalences of and health plan costs associated with genital warts were highest among women aged 20-24 years (6.2 cases and $1692 in costs per 1000 person-years) and men aged 25-29 years (5.0 cases and $1717 in costs per 1000 person-years). On average, individual episodes of care for genital warts involved 3.1 physician visits and incurred costs of $436. These are the first age- and sex-specific estimates of the prevalence and cost of genital warts for a US health plan.

Condylomata Acuminata↗
PubMed2005

Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Orally administered antiviral therapy for genital herpes improves the time to lesion healing and resolves symptoms during an outbreak. Although traditional therapy for a recurrent episode for healthy adults has consisted of twice-daily dosing for 5 days, recent studies have indicated that shorter courses of antiviral therapy are effective. This study was conducted to assess the efficacy and safety of a patient-initiated, single-day regimen of famciclovir therapy, compared with placebo, in immunocompetent adult patients with recurrent genital herpes. METHODS: This multicenter, multinational, randomized, double-blind, parallel-group, placebo-controlled study compared single-day, patient-initiated oral famciclovir (1000 mg given twice daily) with placebo for the treatment of recurrent genital herpes. Patients were instructed to initiate therapy within 6 h after onset of prodromal symptoms or genital herpes lesions. RESULTS: Famciclovir reduced (P < .001) the time to healing of nonaborted lesions (i.e., those that progressed [corrected] beyond the papule stage) (median time, 4.3 vs. 6.1 days) and all nonaborted and aborted lesions (median time, 3.5 vs. 5.0 days), compared with placebo. The proportion of patients with aborted lesions was larger in the famciclovir group than in the placebo group (23.3% vs. 12.7%; P = .003). Adverse events in the famciclovir group were infrequent overall; most were of mild-to-moderate severity and were similar to adverse events in the placebo group. CONCLUSIONS: A single-day regimen of patient-initiated famciclovir treatment was well tolerated and safe, and the healing of recurrent genital herpes lesions occurred approximately 2 days faster than with placebo. Moreover, single-day famciclovir treatment stopped the development or progression of lesions beyond the papule stage. This convenient single-day regimen has the potential for improving patient compliance and satisfaction with therapy.

2-Aminopurine↗
PubMed2006

Protective immunity to genital herpes simplex virus type 1 and type 2 provided by self-adjuvanting lipopeptides that drive dendritic cell maturation and elicit a polarized Th1 immune response.

Genital herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) infections are a significant health problem worldwide. While it is believed that CD4+ Th1 cells are among the effectors to herpes immunity, developing an epitope-based clinical vaccine capable of inducing an effective anti-herpes CD4+ Th1-mediated protection is still under investigation. Few molecules achieve this target without the aid of external immuno-adjuvant. The present study was undertaken to examine the immunogenicity in mice of five CD4+ T cell epitope peptides (gD1-29, gD49-82, gD146-179, gD228-257, and gD332-358), recently identified from the HSV-1 glycoprotein D (gD), covalently linked to a palmitic acid moiety (lipopeptides) using the high-yielding chemoselective ligation method and delivered subcutaneously in free-adjuvant saline. Their protective efficacy was evaluated in a progestin-induced susceptibility mouse model of genital herpes following intravaginal challenge with either HSV-1 or HSV-2. Four out of five gD lipopeptides effectively induced virus-specific CD4+ Th1 responses associated with a reduction of virus replication in the genital tract and protection from overt signs of genital disease. A cocktail of three highly immunogenic lipopeptides provoked maturation of dendritic cells, induced interferon gamma (IFN-gamma)-producing CD4+ T cells, and protected against both HSV- 1 and HSV-2 infections. Depletion of specific T cell subsets from lipopeptideimmunized mice before intravaginal HSV challenges demonstrated that CD4+ T cells were primarily responsible for this protection. The strength of induced T cell immunity, together with the ease of construction and safety of these totally synthetic self-adjuvanting lipopeptides, provide a molecularly defined formulation that could combat genital herpes and other human viral infections for which induction of Th1 immunity is crucial.

Adjuvants, Immunologic↗
PubMed2005

Douching, pelvic inflammatory disease, and incident gonococcal and chlamydial genital infection in a cohort of high-risk women.

Douching has been linked to gonococcal or chlamydial cervicitis and pelvic inflammatory disease (PID) in retrospective studies. The authors conducted a 1999-2004 prospective observational study of 1,199 US women who were at high risk of acquiring chlamydia and were followed for up to 4 years. Cervical Neisseria gonorrhoeae and Chlamydia trachomatis were detected from vaginal swabs by nucleic acid amplification. PID was characterized by histologic endometritis or pelvic pain and tenderness plus one of the following: oral temperature >38.3 degrees C, leukorrhea or mucopus, erythrocyte sedimentation rate >15 mm/hour, white blood cell count >10,000, or gonococcal/chlamydial lower genital tract infection. Associations between douching and PID or gonococcal/chlamydial genital infections were assessed by proportional hazards models. The 4-year incidence rate of PID was 10.9% and of gonococcal and/or chlamydial cervicitis was 21.9%. After adjustment for confounding factors, douching two or more times per month at baseline was associated with neither PID (adjusted hazard ratio = 0.76, 95% confidence interval: 0.42, 1.38) nor gonococcal/chlamydial genital infection (adjusted hazard ratio = 1.16, 95% confidence interval: 0.76, 1.78). Frequency of douching immediately preceding PID or gonococcal/chlamydial genital infection was not different between women who developed versus did not develop outcomes. These data do not support an association between douching and development of PID or gonococcal/chlamydial genital infection among predominantly young, African-American women.

Adolescent↗
PubMed1995

Human papillomavirus infection and genital warts: update on epidemiology and treatment.

The treatment of genital warts remains frustrating since it is often painful, expensive, and unsuccessful. Moreover, little is known about the infectivity and natural history of exophytic genital warts or subclinical genital infection with human papillomavirus. The traditional goals of therapy for sexually transmitted diseases--eradication of infection, elimination of symptoms, prevention of long-term sequelae, and interruption of transmission--are currently not attainable for or applicable to genital warts. The medical literature from January 1988 to August 1993 was reviewed for recent studies on the treatment of exophytic warts. The following treatments were included in the reviewed studies: podofilox (which was recently approved by the Food and Drug Administration), podophyllin, cryotherapy, topical 5-fluorouracil, intralesional interferon, systemic interferon, and laser surgery. No single treatment modality was superior to another, and recurrence rates associated with all modalities were high. Treatment of genital warts should be guided by preferences of the patient, and a specific therapeutic regimen should be chosen with consideration of expense, efficacy, convenience, and potential for adverse effects.

Condylomata Acuminata↗
PubMed1997

Genital herpes infection: a review.

Genital herpes infection is life-long and may result in painful and recurrent genital lesions, systemic complications, serious psychosocial morbidity, and rare but serious outcomes in neonates born to infected women, including permanent neurological handicap and death. Herpes simplex virus (HSV)-2 is the principal cause, with an increasing proportion of first-episode disease caused by HSV-1. Genital HSV transmission is usually due to asymptomatic viral shedding by people who are unaware that they are infected and clinical screening fails to detect most infections. Type-specific serological assays can distinguish the two viral subtypes, but these are expensive and currently restricted to a few research settings. Most infections are asymptomatic, or cause a mild illness which does not lead to health service attendance; but the limited evidence suggests a rise in disease incidence, perhaps related to a fall in HSV-1 age-specific prevalences. The prevalences of HSV genital infections increase with age and numbers of sexual partners, with higher rates in specific ethnic and low socioeconomic groups. However, infection is not restricted to high-risk populations. Antiviral agents, such as acyclovir, can reduce disease severity, prevent recurrences and shorten periods of viral shedding, but currently there are no effective population control measures. This may change with the advent of HSV vaccines, if their safety and long-term efficacy are confirmed. Possible applications for vaccines may include the suppression of disease and recurrences in patients with genital infections (immunotherapy), the prevention of viral transmission to their seronegative partners, and immunoprevention through vaccinating the latter. Economic evaluations of existing and potential control strategies, age-specific population HSV-1 and 2 seroprevalence studies for targeting future interventions, and cohort studies to elucidate the natural history of HSV-2 infections are needed.

Antiviral Agents↗
PubMed1982

Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease.

Guinea pigs inoculated intravaginally with herpes simplex virus type 2 (HSV-2) developed a self-limiting infection characterized by vesiculo-ulcerative lesions on the external genital skin, urinary retention, and hindlimb paralysis. Infection rarely resulted in death. Virologic, histologic, and immunoperoxidase data suggested the following scheme for viral pathogenesis: initial replication in the introitus, vagina, and bladder; spread via sensory nerves to the lumbosacral dorsal root ganglia and spinal cord, and transmission via peripheral nerves to the external genital skin to produce the characteristic lesions. After recovery from primary infection, animals developed recurrent vesicular lesions, shed virus from genital sites in the absence of lesions, and harbored latent HSV-2 in dorsal root ganglia. Genital infection in the guinea pig shares many features with genital herpes in humans and provides a model to explore mechanisms of latency and reactivation and to evaluate several methods for control of recurrent disease.

Animals↗
PubMed1989

T lymphocytes in genital lymph nodes protect mice from intravaginal infection with herpes simplex virus type 2.

Herpes simplex virus type 2 (HSV-2) is a human venereal pathogen that causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. Intravaginal vaccination of mice with an attenuated strain of HSV-2 rapidly induces immunity to a lethal intravaginal challenge with wild-type HSV-2. This resistance is transferrable to syngeneic mice with genital lymph node (GLN) cells but not with cells from other lymphoid sources. Here we demonstrate that minimal numbers of HSV-2-stimulated GLN T lymphocytes are required for resistance to genital infection by HSV-2 and that such cells migrate preferentially into HSV-2-infected genital tissue. Furthermore, the results suggest that HSV-2-specific cytotoxic T lymphocytes from the GLN may be one effector cell population participating locally in genital immunity to the virus. These findings indicate that mucosal immunity to genital HSV-2 infection requires the antigen stimulation of migratory T cells in the GLN.

Animals↗
PubMed2005

Topical microbicides for the prevention of genital herpes infection.

Genital herpes is one of the most prevalent sexually transmitted infections worldwide and is the most common cause of genital ulcers. Despite increased public awareness and the initiation of efforts to prevent transmission, the prevalence of herpes simplex virus (HSV) type 2 continues to increase. What makes HSV so difficult to control is that most sexual and perinatal transmission occurs during unrecognized or asymptomatic shedding. The impact of genital herpes as a public health threat is amplified because of its epidemiological synergy with HIV/AIDS. Thus, there is an urgent need for novel prophylactic methods, such as topical microbicides designed for genital application, to prevent both HSV and HIV transmission. Several candidate microbicides are being advanced to clinical trials based on in vitro activity and animal studies. These include compounds that inactivate virus directly, those that enhance innate immunity, and drugs that block viral binding and entry. A more vigorous evaluation of the safety of these and other candidate topical microbicides in development should include assessment of the impact of repeated application on innate host defences in the genital tract.

Administration, Intravaginal↗
PubMed1994

Heavy lifting at work and risk of genital prolapse and herniated lumbar disc in assistant nurses.

Lifting of heavy burdens increases the intra-abdominal pressure, and may induce an increased risk of prolapse of the female internal genitals. While taking care of patients, the nursing staff in hospitals and nursing homes are exposed to heavy lifting. Scientifically uncontrolled causal observations among assistant nurses gave rise to the assumption of an increased risk. To test this hypothesis, a register study was carried out to investigate the risk of genital prolapse among assistant nurses compared with the female Danish population in general. For validation, the incidence of operation due to herniated lumbar disc was investigated. Two registers were used for the analyses, a pension fund register and the Danish National Registry of Hospitalized Patients. Some 28,619 assistant nurses, aged 20-69 years, and 1,652,533 controls of similar age were included. Operations due to genital prolapse and herniated lumbar disc were recorded during one year. The odds ratio (OR) with 95 per cent confidence intervals for the risk of operation due to genital prolapse was significantly increased among assistant nurses, OR = 1.6 (1.3-1.9), P < 0.0001. Correspondingly, the risk of operation for herniated lumbar disc was significantly increased for assistant nurses, OR = 1.6 (1.2-2.2), P < 0.01. We conclude that operations due to genital prolapse are more common among assistant nurses than among the overall female population. Based on this finding, we hypothesize that heavy lifting at work may be the underlying cause. This study confirmed the suggestion of previous epidemiological studies that herniated lumbar disc is associated with heavy lifting at work.

Adult↗
PubMed2003

Immunology of the human genital tract.

PURPOSE OF REVIEW: Despite much interest in the mechanisms of immune protection against sexually transmitted diseases (STDs), little is known about the role of the immune system in the genital tract. A better knowledge is needed to understand not only host protection against STDs, but also how tolerance is established in pregnancy to avoid rejection of the foetus. RECENT FINDINGS: The immune system of the genital tract displays characteristic features that are unique, and therefore distinct from those of other mucosal and systemic immune sites. It is functionally separate from the mucosal immune systems of the lung or intestine, and contrary to these systems, antibodies in the genital tract are dominated by IgG and not IgA. Most of the IgA is polymeric and consists of equal proportions IgA1 and IgA2. Polymeric IgA is actively transported via the polymeric immunoglobulin receptor on the basolateral surface of the epithelial cell, whereas it is not known how IgG antibodies are secreted. Antibody levels and isotypes exhibit strong hormonal dependence. Less is known about cell-mediated immune responses in the genital tract. Interest has focused on adhesion molecules, the existence of regulatory T and natural killer cells, and whether innate and early adaptive immune responses may be stimulated by local vaginal, intranasal or intestinal vaccinations. These topics are reviewed here and the most recent developments in these areas are reported. SUMMARY: A greater knowledge of immune activation and the homing of leukocytes to the genital tract is important for future attempts to design vaccines against STDs, as well as in understanding foetal tolerance.

Antibody Formation↗
PubMed2004

Female genital mutilation.

PURPOSE OF REVIEW: The purpose of this review is to provide an up to date account of recent papers and attitude on female genital mutilation in the past year. It is aimed at all professionals caring and supporting women/girls with female genital mutilation, and to identify gaps. RECENT FINDINGS: Given the multidisciplinary complexity of the practice of female genital mutilation, it is surprising how little empirical research (both quantitative and qualitative) exists. There is a paucity of rigorous research into its prevalence, its health consequences for those girls/women experiencing the practice, the understanding of professionals who have to address the issue, the implementation of existing legislation and the impact of programme interventions intended to change people's attitudes to, and the practice of, female genital mutilation. The overwhelming majority of literature focuses on the same topics, often drawing upon the same less-than-rigorous research data. SUMMARY: Worldwide, there are approximately 13 million refugees and asylum seekers, and human rights violations are seen as contributing factors to people fleeing their homeland. In the United States, those seeking asylum or refugee status are asked about their life experiences. African women are asked about ritual genital surgery, as it may be an indicator of their gynaecological, obstetric and sexual health. Health and social care professionals in host countries, in Europe, Australia, Canada, the USA and the UK, for example, are increasingly encountering this vulnerable client group in their practice and are finding that they are ill-prepared to deal with presenting complex health needs and challenges.

Adolescent↗
PubMed2000

Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. WHS 001 Study Team.

OBJECTIVE: To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus. DESIGN: A prospective analysis of 55 HIV-1-infected women. METHODS: Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load. RESULTS: Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03). CONCLUSION: HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

Adult↗
PubMed2004

The impact of syndromic treatment of sexually transmitted diseases on genital shedding of HIV-1.

OBJECTIVES: To examine the impact of sexually transmitted diseases (STD) syndromic treatment on genital shedding of HIV and the impact among women in whom STD treatment was not successful. DESIGN: Seventy-one HIV-infected women were included; 60 had symptomatic STD [72% with genital discharge syndrome (GDS) and 28% with genital ulcer syndrome (GUS)] and 11 controls did not have symptomatic STD. Cervical HIV load in 94% women was measured at baseline and after STD treatment. RESULTS: Cervical HIV load at entry was significantly higher in women with symptomatic STD than in controls [median, 3.15; interquartile range (IQR), 1.90-3.34 versus median, 1.90; IQR, 1.90-2.19 log10 RNA copies/swab, respectively; P = 0.024]. Women with STD were also more likely to have detectable cervical HIV RNA (68% versus 27%; P = 0.016). Cervical HIV load was significantly higher in women with GUS than in those with GDS (median 3.46; IQR, 2.84-4.18 versus median, 2.83; IQR, 1.90-3.31 log10 copies/swab; P = 0.019). There was no significant reduction in genital HIV shedding after syndromic treatment of GDS or GUS. However, significant decreases were limited to only those with clinical improvement (median, 2.91; IQR, 1.90-3.45 versus median, 2.25; IQR, 1.90-3.08 log10 RNA copies/swab, respectively; P = 0.006). GUS was significantly associated with treatment failure, independent of plasma HIV RNA load and CD4 T-cell count (odds ratio, 4.79; 95% confidence interval, 1.32-17.46). CONCLUSIONS: The fact that STD syndromic treatment impacts very little in reducing genital HIV shedding underscores the need for appropriate validation of STD syndromic diagnosis and management to control heterosexual transmission of HIV.

Adolescent↗
PubMedDate not supplied

Genital infections with herpes simplex virus in a university student population.

The frequency of clinically evident genital infections with herpes simplex virus among students attending a large urban public university was studied. One-hundred ninety-eight students experienced 222 episodes of this disease over a one-year period. The mean age of the students, both undergraduate and graduate, with the diagnosis of genital herpes ranged from 23.6 years for those with a single initial episode to 24.9 years for those with recurrent episodes. The male-to-female ratio and socioeconomic class of students with genital herpes were not significantly different from those of the general university population. The incidences of both initial and recurrent episodes of genital herpes were statistically significantly higher during the months of July through October (with the exception of September). Genital herpes was a frequently diagnosed sexually transmitted disease among this student population.

Adult↗