The topical microbicide PRO 2000 protects against genital herpes infection in a mouse model.
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Vaginal gel formulations containing the naphthalene sulfonate polymer PRO 2000 are being developed as topical microbicides to protect against infection with sexually transmitted disease (STD) pathogens. A mouse model was used to determine whether PRO 2000 could protect against genital herpes in vivo. Animals received a single intravaginal application of 15 microL of a 10% PRO 2000 aqueous solution or a 4.0% or 0.5% PRO 2000 vaginal gel formulation 20 s prior to intravaginal challenge with 4.0 log10 pfu of herpes simplex virus type 2. Treatment with the 4.0% gel provided complete protection against infection; treatment with the 0.5% gel or 10% solution provided 81% and 80% protection, respectively. Furthermore, the 4% gel provided significant protection even when viral challenge was delayed until 60 min after treatment. This is the first report to show that PRO 2000 can protect against infection with an STD pathogen in vivo. (+info)
A randomized, double-blind, placebo-controlled trial of 5-fluorouracil for the treatment of cervicovaginal human papillomavirus.
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OBJECTIVE: To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV). METHODS: A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap) test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression of HPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4-6-month and 12-month follow-up evaluations. Data were analyzed using the Chi square test with significance established at P < 0.05. RESULTS: A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P < 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months. CONCLUSION: Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo. (+info)
Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.
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OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen. (+info)
Effect of a cellulose acetate phthalate topical cream on vaginal transmission of simian immunodeficiency virus in rhesus monkeys.
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Human immunodeficiency virus type 1 (HIV-1) infection continues to spread in developing countries, mostly through heterosexual transmission. The development of a safe and cost-effective topical microbicide, effective against a range of STDs including HIV-1, would greatly impact the ongoing epidemic. When formulated in a vehicle, a micronized form of cellulose acetate phthalate (CAP), which is an inactive pharmaceutical excipient, has been shown to inactivate HIV-1, herpes simplex virus types 1 and 2, cytomegalovirus, Neisseria gonorrhoeae, Trichomonas vaginalis, Haemophilus ducreyi, and Chlamydia trachomatis in vitro. Formulated CAP was also shown to be effective against herpes simplex virus type 2 in vivo. Here we show that a formulation of CAP protected four of six rhesus monkeys from vaginal infection with simian immunodeficiency virus. Thus, CAP may be a candidate for use as a topical microbicide for preventing HIV-1 infection in humans. (+info)
Vaginal mucosa serves as an inductive site for tolerance.
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These data demonstrate that tolerance can be induced by vaginal Ag exposure. In these experiments, mice were given vaginal agarose gel suppositories containing either 5 mg OVA or saline for 6 h. Mice were given suppositories either during the estrous (estrogen dominant) or diestrous (progesterone dominant) stage of the estrous cycle. Mice were restrained during the inoculation period to prevent orovaginal transmission of the Ag. After 1 wk, mice were immunized s. c. with OVA in CFA. After 3 wk, mice were tested for delayed-type hypersensitivity responses by measuring footpad swelling and measuring in vitro proliferation of lymphocytes to Ag. Using ELISA, the magnitude of the serum Ab response was also measured. In some mice, FITC conjugated to OVA was used to track the dissemination of the protein into the systemic tissues. The magnitude of footpad swelling was significantly reduced in mice receiving OVA-containing suppositories during estrus compared with mice receiving saline suppositories. Concomitant decreases in the Ag-specific proliferative response were also observed in lymph node lymphocytes and splenocytes. Conversely, mice inoculated during diestrus did not show a decreased response to Ag by either footpad response or in vitro proliferation. Serum Ab titers in the estrus-inoculated mice did not decrease significantly. These data demonstrate that the reproductive tract can be an inductive site for mucosally induced tolerance. However, unlike other mucosal sites such as the lung and gastrointestinal tract, reproductive tract tolerance induction is hormonally regulated. (+info)
Terconazole cream for non-Candida albicans fungal vaginitis: results of a retrospective analysis.
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OBJECTIVE: Although it is FDA-approved for use in vulvovaginal candidiasis caused by non-Candida albicans species, terconazole cream has not been been studied in patients with these infections. We sought to assess the clinical and mycological efficacy of terconazole cream in women with non-C. albicans vaginitis. METHODS: The records of patients who had received a 7-day course of terconazole cream for culture-proved non-C. albicans vaginitis were reviewed. Data with regard to patient demographics, clinical and mycologic response to therapy within 1 month of treatment, and outcome with other antifungal therapies were analyzed. RESULTS: Twenty-eight patients received terconazole cream for non-C. albicans infections. Three patients did not return for follow-up. The median age was 45 years. Seven (28%) patients were nulliparous. The median duration of symptoms was 3 years. Nine patients (36%) had received terconazole within the 6 months prior to referral. Overall, there were 20 C. glabrata cases, 3 C. parapsilosis, and 2 C. lusitaniae. Fourteen (56%) patients achieved a mycologic cure; 11 (44%) noted a resolution of their symptoms. Prior terconazole use was not associated with treatment failure (P = 0.09). Ten failures received boric acid suppositories as subsequent treatment; a cure was effected in 4 (40%). Two of three patients (67%) were eventually cured with flucytosine cream. Five (20 %) patients remained uncured. CONCLUSIONS: Terconazole cream may be an appropriate first-line treatment for non C. albicans vaginitis, even in patients who have previously received the drug. (+info)
Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide.
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OBJECTIVE: We sought to determine the safety and acceptability of vaginal gel formulation PC-503 among low risk, abstinent women. The active ingredient was 2% pharmaceutical grade lambda carrageenan, a sulphated polymer that is generally recognised as safe by the US Food and Drug Administration. METHODS: 35 women in five sites applied 5 ml of the PC-503 gel vaginally once a day for 7 days while abstaining from sexual intercourse. Visual vaginal examinations were performed on days 1, 4, and 8. STI testing and vaginal pool Gram stain preparations were done on days 1 and 8. Participants were asked about product acceptability. RESULTS: 34 of the 35 women enrolled completed 7 days' use. Following product use, five reported mild symptoms including "bladder fullness," "genital warmth," or discomfort, and lower abdominal pain, and one had moderate pale yellow cervical discharge. Using the Nugent criteria, three women had bacterial vaginosis (BV) before and after use; three had BV before but not after, and two had BV after but not before. Most of the women found PC-503 to be pleasant or neutral in feel and smell and considered extra lubrication to be an advantage; however, one third found it to be messy. CONCLUSIONS: Vaginal use of PC-503 gel did not cause significant adverse effects in a small number of low risk, sexually abstinent women. Further testing in larger numbers of sexually active women is planned. A smaller volume of gel may be more acceptable to some women. (+info)
Efficacy of clindamycin vaginal ovule (3-day treatment) vs. clindamycin vaginal cream (7-day treatment) in bacterial vaginosis.
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OBJECTIVE: To compare the efficacy and safety of a 3-day regimen of clindamycin vaginal ovules with a 7-day regimen of clindamycin vaginal cream for the treatment of bacterial vaginosis (BV). METHODS: Women with a clinical diagnosis of BV were treated with a 3-day course of clindamycin ovules or a 7-day course of clindamycin cream administered intravaginally. Three hundred and eighty-four patients received study drug and were included in the evaluable patient population (ovule group, n = 204; cream group, n = 180). Assessments included pelvic examination and diagnostic testing. Primary efficacy endpoints were a resolution of two of three diagnostic criteria at the first follow-up visit and three of three diagnostic criteria at the second. RESULTS: Cure rates in the evaluable patient population were similar between treatment groups: 53.7% (109/204) for the ovule group and 47.8% (85/180) for the cream group (p = 0.2471, 95% CI -4.1-16.0%). The most commonly reported medical event, vulvovaginal pruritus, had similar incidence in both treatment groups. CONCLUSIONS: A 3-day course of clindamycin vaginal ovules is as effective and well-tolerated as a 7-day course of clindamycin vaginal cream in the treatment of BV. (+info)