Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group.
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OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Cote d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated. (+info)
Decreased vaginal disease in J-chain-deficient mice following herpes simplex type 2 genital infection.
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J-chain-deficient (Jch(-/-)) mice were used to study the role of polymeric IgA (pIgA) in primary disease and protective immunity following genital herpes simplex type 2 (HSV-2) infection. Vaginal IgA in the Jch(-/-) mice was composed primarily of monomeric IgA and was not associated with secretory component (SC). In contrast, vaginal IgA in wild-type (WT) mice was predominantly polymeric and bound to SC. Following HSV-2 genital infection, the Jch(-/-) mice consistently exhibited fewer vaginal symptoms (P = 0.010) and mortality (P = 0.075) than did the WT mice. The variation in disease expression could not be explained by differences in local viral replication, since titers in vaginal wash fluid were comparable. To assess the effect of J chain deficiency on protective immunity, WT and Jch(-/-) mice were immunized intravaginally with attenuated HSV-2, challenged intravaginally with wild-type virus 5 weeks later, and evaluated for vaginal infection and neurological disease. Although the Jch(-/-) mice had reduced vaginal HSV-specific IgA and IgG levels following immunization, both WT and Jch(-/-) mice were protected from symptoms following wild-type virus challenge. We conclude that pIgA is not required for protective immunity against genital HSV-2 disease and that J chain deficiency offers some protection against symptoms following primary HSV-2 genital infection. (+info)
A new visual indicator of chlamydial cervicitis?
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OBJECTIVES: To determine the usefulness of endocervical discharge opacity as a risk indicator for chlamydial infection in relation to two acknowledged visual indicators--yellow endocervical discharge and easily induced mucosal bleeding of the cervix. METHODS: Women from two family planning clinics, a therapeutic abortion clinic, and a university student health clinic (n = 1418 total) consented to a pelvic examination and chlamydia testing, and completed a questionnaire on socio-demographics, sexual behaviour, medical history, and symptoms. A case of chlamydia was defined as positive by culture or blocked enzyme immunoassay in an endocervical swab. RESULTS: The prevalence of chlamydial infection in the clinics was 6.3%. All three of the visual indicators--yellow endocervical discharge, easily induced bleeding, and opaque cervical discharge--were statistically significantly and independently associated with chlamydial infection (odds ratios 2.8, 2.3, and 2.9 respectively), independent of clinic type. Adjustment for the other visual indicators made little difference to the odds ratios. CONCLUSION: Opacity of endocervical discharge was at least as important as the other two commonly acknowledged indicators of chlamydial cervicitis--yellow endocervical discharge and easily induced mucosal bleeding of the cervix. (+info)
A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women.
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BACKGROUND: Although the male condom provides a reliable means of preventing HIV transmission, a broader choice of methods is required particularly in circumstances where the negotiation of condom use is difficult. Development of new products that may be effective as topical vaginal microbicides is the focus of a great deal of research activity currently. The novel agent PRO 2000, a naphthalene sulphonate derivative with in vitro activity against HIV and other sexually transmissible pathogens, is one such compound. We have studied the local and systemic safety and tolerance of a vaginal gel formulation of this agent at two concentrations (0.5% and 4%) over a 2 week period of daily exposure in two cohorts of healthy sexually abstinent women (one in London, UK, and the other in Antwerp, Belgium). METHODS: This was a randomised, placebo controlled, double blind, three arm clinical trial conducted on two sites. Macroscopic evidence of genital epithelial changes was sought using colposcopy and evidence of microscopic inflammation was acquired using high vaginal biopsy from predetermined sites (UK cohort only). Blood levels of PRO 2000 were measured and laboratory safety tests, including coagulation screens, were performed. The impact on vaginal ecology was also assessed. RESULTS: 73 women were enrolled across both sites (36 UK, 37 Belgium); 24, 24, 25 in the 4%, 0.5%, and placebo groups respectively. Of these, 70 completed 2 weeks' exposure to the study gel. Three (all in the 4% group) withdrew owing to adverse events which were possibly or probably gel related. Cervicovaginal abrasion was seen colposcopically in three subjects after 14 days of gel use (two in the 4% group and one in the placebo group). Genital ulceration was not seen during gel use in any of the subjects who completed the study. Histological evaluation of vaginal biopsy samples (36 women only) showed evidence of increased inflammatory signs in one participant of the 4.0% group. One volunteer in the placebo group had moderate inflammation at screening and at follow up. Severe inflammation was not seen among any of the subjects tested. Plasma levels of PRO 2000 and laboratory safety tests showed no evidence of systemic absorption. No impact was seen on normal vaginal ecology in the UK cohort where samples were taken 12 hours after the last gel application. CONCLUSION: In this phase I study PRO 2000 gel was found to be generally well tolerated with promising local and systemic safety profiles. The 0.5% gel was better tolerated than the 4% gel as fewer genital epithelial adverse events were seen in the former. Phase II studies are about to begin in sexually active women. (+info)
Passive sentinel surveillance system for sexually transmitted diseases in primary healthcare sites in Ethiopia, 1991-3.
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BACKGROUND: In 1989 the ministry of health of Ethiopia launched an STD control programme to strengthen the STD case management capabilities at public health centres and hospitals. The programme included the introduction of a syndrome based system for notification of STD cases. We here report the data originated by the syndromic case reporting system under programme conditions. METHODS: 35 (17%) of the total 225 hospitals and public health centres of Ethiopia were included in the programme. Information relevant to the years 1991 to 1993 was analysed at mid 1994. RESULTS: 32 clinical sites (91% of the total) provided at least one monthly report. The proportion of monthly reports received was 65% of those due, ranging from 51% in 1991 to 73% in 1992 and 42% in 1993. A total of 77,294 consultations for STD related symptoms were recorded, including 70,200 new cases, 6588 repeated consultations, and 506 partners of STD patients. Among first attendant patients 38,459 (52.7%) were males with a male to female ratio of 1:1. Urethral discharge and vaginal discharge were the leading cause of consultation among males (58%) and females (64%) respectively. The frequency of genital ulcer diseases was 26% among males and 15% among females. Inguinal adenopathy in the absence of genital ulcers was also frequent, accounting for 10% of consulting males and 5% of females. Based on Gram stain, gonorrhoea was identified in 64% of the cases of urethral discharge, while trichomoniasis and candidiasis were identified by wet mount in 28% and 16% of the cases of vaginal discharge respectively. CONCLUSIONS: STDs are a common cause of consultation at public health centre sites in Ethiopia. A syndromic case reporting system proved to be efficient and produced valuable information to initiate assessment of the problem and to set up bases for monitoring trends of STD morbidity. (+info)
Expression of mucosal homing receptor alpha4beta7 is associated with enhanced migration to the Chlamydia-infected murine genital mucosa in vivo.
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The CD4 T helper cell type 1 (Th1) response is essential for the resolution of chlamydial genital infection in mice. However, not all Th1 clones are equally protective in eradicating the infection. Since oral immunization regimens produce protective immunity, we evaluated the role of the mucosa-associated homing receptor, alpha4beta7, in trafficking to the genital mucosa. Using a panel of CD4, Th1 cell lines and clones, we compared the lymphocyte homing patterns of a Chlamydia-specific, protective clone (P-MoPn), a nonprotective clone (N-MoPn), and a keyhole limpet hemocyanin (KLH)-specific cell line (KLH-1). T cells were labeled with the fluorescent dye PKH-26, adoptively transferred into Chlamydia-infected mice, and monitored at different time points throughout the course of a genital infection. We found that clones P-MoPn and N-MoPn migrated to similar extents to the genital tract and in significantly greater numbers than the KLH-specific T-cell line. Both clones and the KLH-1 line expressed similar levels of the adhesion molecules alpha4, beta1, CD44, and CD11a. However, clones P-MoPn and N-MoPn expressed higher levels of the mucosal homing receptor, alpha4beta7. Also, clones P-MoPn and N-MoPn but not the KLH-1 line migrated to the mesenteric lymph node, suggesting a mucosal recirculation pattern. Moreover, blocking alpha4beta7 adhesion interaction in vivo significantly reduced the recruitment of P-MoPn but not KLH-1 to the genital tract. These findings show that the mucosal homing receptor alpha4beta7 is utilized by a subset of CD4 cells during migration to the Chlamydia-infected genital tract. (+info)
Microbial flora of the lower genital tract during pregnancy: relationship to morbidity.
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Nineteen genera and groups of micro-organisms were isolated from the lower genital tract of 280 women at their first antenatal visit. Chlamydia, viruses, and T-strain mycoplasmas were not sought, and only routine methods of anaerobic culture were used. Growth was recorded as scanty, moderate or heavy. The population studied was grouped according to age, parity, gestational stage at booking, presence and degree of severity of lower genital tract morbidity, past history of vulvovaginitis, and suspicion of lower genital tract morbidity as evidenced by a request for a report on the microbiological findings. The frequency of isolation of the various microbes in health and in disease is given. The grading of Gram-stained smears bore no relation to the isolation rates of lactobacilli, but there was a significant increase (p less than 0-001) in the isolation rates of each of the following: Mycoplasma hominis, Bacteroides spp., Trichomonas vaginalis, Gram-variable cocco-bacilli, and anaerobic streptococci in those patients with smears in which lactobacilli were adjudged to be absent. The isolation of faecal streptococci was increased (p less than 0-001) in women aged more than 34 years. Escherichia coli (p less than 0-05) and anaerobic and microaerophilic streptococci (p less than 0-02) were isolated more frequently from those booking after the 25th week of pregnancy. The incidence of M. hominis (p less than 0-02) and of anaerobic streptococci (p less than 0-05) increased between the first and third trimesters. No significance positive correlations were established between the isolation rates of the various microbes and objective assessment of lower genital tract morbidity or the demonstration of pus cells, but lactobacilli were isolated less frequently (p less than 0-01) from those with morbidity. The isolation of Candida albicans (p less than 0-02), T. vaginalis (p less than 0-05), and M. hominis (p less than 0.05) was increased in patients in whom vulvovaginitis was suspected, and that of T. vaginalis (p less than 0-05) was increased in those with a past history of vulvovaginitis. The study indicates that, other than the pathogens T. vaginalis and C. albicans, only M. Hominis could be suspected, on statistical grounds, of being associated with disease of the lower genital tract during early pregnancy. (+info)
Immunity to vaginal herpes simplex virus-2 infection in B-cell knockout mice.
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We investigated the involvement of antibody in protection against vaginal herpes simplex virus type-2 (HSV-2) infection by comparing intact and B-cell knockout (KO) mice. Vaginal immunization of intact mice with attenuated HSV-2 markedly reduced an HSV-2 challenge infection in the vagina. In contrast, immunization of B-cell KO mice produced less immunity against the challenge infection and that immunity occurred in a different pattern. At 20 hr after challenge, immunostaining of virus proteins in the vaginal epithelium and shed virus protein titres in the vaginal secretions were not significantly different between immunized and non-immunized B-cell KO mice and were much greater than in immunized intact mice. At 48 hr after challenge, the vaginal infection in immunized B-cell KO mice was markedly less than at 20 hr but remained approximately sevenfold higher than in intact mice. This pattern of challenge infection in the vagina indicates that B cells, and probably the antibody derived from them, provided significant protection against reinfection in intact mice, especially during the first 20 hr after challenge, while other effector mechanisms became important between 20 and 48 hr after challenge. To determine whether T-cell immunity in immunized B-cell KO mice was equal to that in intact mice, we assessed interferon-gamma (IFN-gamma) secretion by memory T cells in vivo in the vagina at 20 hr after challenge. We found no significant differences in the up-regulation of major histocompatibility complex (MHC) class II antigens in the epithelium, up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in vascular endothelium, or recruitment of T cells to the mucosa, indicating that the memory T-cell response to virus challenge was the same in intact and B-cell KO mice. (+info)