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A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases.

BACKGROUND: Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV). METHODS: We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases. RESULTS: The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts. CONCLUSIONS: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.

Adult↗

[Prevention of Chlamydia trachomatis infections in women].

Over the past several years, the incidence of chronic salpingitis has increased relentlessly, with its accompanying pelvic pain, ectopic pregnancies, and tubal sterility. Chlamydia are a frequent etiologic agent. Preventing these infections is difficult, nevertheless proper care will be given by recalling four key words: avoidance, diagnosis, education, and treatment. It is important to discourage early sexual activity and multiple sexual partners, to encourage the use of condoms, and avoid the use of an intrauterine device in adolescents. Atypical presentations of salpingitis must be recognized and treated effectively, thus preventing the spread of infection. Education on venereal diseases should be presented in secondary schools, during military service, and other similar groups, but especially during physician visits for contraception.

Adolescent↗

The role of the laboratory in a Chlamydia control programme in a developing country.

The laboratory components of a Chlamydia trachomatis disease control programme for a developing country are reviewed. Early diagnosis of chlamydial infections is the most cost effective means of preventing the long term sequelae of trachoma, pelvic inflammatory disease, ectopic pregnancy and infertility, which are now a major public health burden to the health care system in developing countries. Public health strategies are required to establish both a co-ordinated limited system of laboratory services, and to promote the diagnosis and treatment of disease syndromes in the absence of laboratory support. Laboratory tests for the specific diagnoses of chlamydial infections requiring different levels of expertise and equipment can be instituted within settings appropriate to the resources and technical expertise available. Emphasis is given to appropriate cost effective utilization of laboratory testing.

Chlamydia Infections↗

Issues in the management of sexually transmitted diseases in Papua New Guinea.

This paper outlines three important issues in the clinical management of sexually transmitted diseases (STDs) in Papua New Guinea which have, until now, gone unrecognized or been neglected. Suggestions for possible solutions are made. The high prevalence of both chlamydial and trichomonal infections in women cannot be ignored. Both of these infections have been shown to increase the transmission of HIV. The current algorithm for the treatment of vaginal discharges does not include treatment for trichomonal infection in the first instance, yet trichomoniasis has been shown to be the most common STD in community studies both here and elsewhere. Trichomoniasis is usually asymptomatic in men, but still increases the risk of HIV transmission; furthermore, it causes illness in their female partners and thus needs to be treated. The current recommended regimens for the treatment of gonococcal and chlamydial infection are complex due to the number of drugs recommended for gonorrhoea to combat the problem of drug resistance, and the length of therapy for chlamydia. Compliance with such a regimen is likely to be poor, particularly in asymptomatic partners. We need to consider the relative advantages provided by a drug which could be given as a single oral dose for chlamydia, and perhaps for both infections. Azithromycin is one possibility, as it has been shown to be effective for chlamydial infection in numerous studies, and has been found satisfactory for gonorrhoea where local isolates were susceptible. Testing of a small number of isolates from Papua New Guinea has shown that azithromycin may be suitable for use here, but further susceptibility testing needs to be performed. Utilization of services for STDs, particularly by women, is extremely low. This is due to a combination of factors involving limited knowledge of symptomatology and its significance, the asymptomatic nature of many infections, the structure of the services, health worker behaviour, and social attitudes. To address these issues we must make modifications to STD service provision, as well as provide widespread information about the potentially serious consequences of contracting STDs, including both infertility and AIDS. Possible modifications to the services are discussed, and include making routine screening available for women through currently existing services such as family planning and antenatal clinics and considering the possibility of establishing Women's Health Clinics which would provide all primary reproductive health services in an integrated manner.

Anti-Bacterial Agents↗

Inhibition of Chlamydia trachomatis growth in endometrial cells by copper: possible relevance for the use of the copper IUD.

There is agreement that the relative risk of developing pelvic inflammatory disease (PID) increases among women who use the intrauterine contraceptive device (IUD). The role of Chlamydia in causing PID among IUD users is not clear. The present study demonstrates that Chlamydia trachomatis growth can be inhibited in cultured human endometrial cells by copper ions at concentrations known to be released by the copper IUDs. More than 98% inhibition was produced with 10(-5) and 10(-6) M of copper. Both C. trachomatis serovar E and a lymphogranuloma venereum Chlamydia serovar L2 (LGV) were inhibited by the copper ions. Although the mechanism of the inhibition is not known, the continuous presence of the copper ions during and after adherence appeared to be necessary for maximal effect. If such inhibition occurs in vivo, it is possible that copper ions released from the copper-containing IUD may partially protect against chlamydial infection.

Cells, Cultured↗

Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections.

The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30 years, but the use of a vaginal spermicide and condoms for the prevention of sexually transmitted infections has not been examined in randomised studies. We report a single-blind randomised field trial to assess the effect of N-9 film on the rate of gonococcal and chlamydial cervical infection in women at high risk of these diseases. 343 women were randomly assigned to use either condoms and N-9 (186 women) or condoms and a placebo (157). Compliance with condom use was much the same in the two groups. Overall, N-9 reduced the rate of cervical infection by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who used N-9 for more than 75% of their coital acts the infection rate was reduced by 40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was not higher in N-9 users than in placebo users, but the rate of symptomatic irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use was more protective against cervical infection than N-9 use. The rate of infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom compliance. The use of a vaginal N-9 spermicide with condoms whenever possible seems to be a better strategy than the use of condoms only for prevention of gonococcal and chlamydial cervical infection.

Administration, Intravaginal↗

Behavioral intervention to increase condom use among high-risk female adolescents.

OBJECTIVE: To determine whether condom use among high-risk female adolescents could be increased by a behavioral intervention, with the use of infection with Chlamydia trachomatis as a biomarker of condom practices. DESIGN: Prospective, randomized, controlled intervention. SETTING: Urban family planning and sexually transmitted disease clinics. PARTICIPANTS: Two hundred nine female adolescents, aged 15 through 19 years, who were treated for C. trachomatis genitourinary infection, were randomly assigned to standard (control) or experimental (behavioral intervention) groups. One hundred twelve subjects returned for follow-up 5 to 7 months after enrollment and comprise the study subjects. MEASUREMENTS: Subjects completed a multiinstrument questionnaire measuring sexual behavior, condom practices, attitudes and beliefs, cognitive complexity, sociodemographics, and motivation at enrollment and follow-up. Endourethral and endocervical sites were sampled for C. trachomatis. RESULTS: Among the 112 subjects who returned for repeated examination, those who had received the experimental intervention reported increased use of condoms by their sexual partners for protection against sexually transmitted diseases (odds ratio = 2.4; p = 0.02) and for vaginal intercourse (odds ratio = 3.1; p = 0.005) at the 6-month follow-up. Multivariable logistic regression analysis controlling for condom use at enrollment demonstrated that the experimental intervention (odds ratio = 2.8; p = 0.03) and the higher cognitive complexity (odds ratio = 4.6; p = 0.02) independently contributed to greater condom use at follow-up. Despite greater use of condoms among the group who had received the intervention, use remained inconsistent and rates of reinfection with C. trachomatis were not significantly different (26% vs 17%; p = 0.3). CONCLUSION: Although a brief behavioral intervention among high-risk female adolescents can increase condom use by their sexual partners, incident infection does not appear to be reduced, because condom use remained inconsistent.

Adolescent↗

Contraception and the prevention of sexually transmitted diseases.

Sexually transmitted diseases (STDs) are a major cause of ill health in women and their sexual partners and children. Contraceptive methods alter in various ways the risk of acquiring STD but assessment of the odds ratio is difficult due to the many confounding factors. Spermicides have been reported to kill a wide range of bacteria and viruses including HIV in vitro and to protect in vivo from infection by gonorrhoea, chlamydia and pelvic inflammatory disease (organisms unspecified). Spermicides will not cure pre-existing infections. Condoms and diaphragms will give some protection from bacterial and viral infections in all parts of the genital tract. Hormonal contraception and tubal ligation give protection to the upper genital tract but not the cervix. Carcinoma of the cervix follows the same pattern as STDs. The risk of pelvic infection in intrauterine device users is discussed in the chapter by Bromham (pp 100-123, this issue).

Adult↗

The spermicide nonoxynol-9 does not inhibit Chlamydia trachomatis in vitro.

The antimicrobial effects of the active ingredient, nonoxynol-9, and the base component of a commercially available spermicide were tested in vitro against Chlamydia trachomatis. The infectivity of cell-free elementary bodies was not affected by nonoxynol-9 or the base after incubation for 30, 60, or 180 min in direct contact with serial twofold dilutions of each agent. The spermicide's effect on the in-vitro growth of C. trachomatis was evaluated after exposure of C. trachomatis-infected McCoy cells to serial dilutions of each agent for 2 hr and for 72 hr. A significant cytopathic effect of nonoxynol-9 on the host cell membrane was observed at concentrations of spermicide between 100% and 0.0014%. However, neither agent was effective in inhibiting the intracellular growth of C. trachomatis at concentrations (0.0014-0.0004%) of nonoxynol-9 that produced no evident cytopathic effect on McCoy cells. Thus, nonoxynol-9 was found to be ineffective in inhibiting infectivity or subsequent growth of C. trachomatis.

Cell Membrane↗

The contraceptive sponge's protection against Chlamydia trachomatis and Neisseria gonorrhoeae.

To investigate the effect of the contraceptive sponge on the incidence of sexually transmitted diseases, we conducted a clinical trial among a high-risk population of women in Bangkok, Thailand. Two hundred fifty-five women were randomly assigned either to use the sponge or not and were evaluated weekly for gonorrhea and chlamydial infection. After adjustment by logistic regression for potentially confounding factors, women using the sponge were less likely to have contracted chlamydial infection (odds ratio [OR], 0.6; 90% confidence interval [CI], 0.4-1.0) and gonorrhea (OR, 0.9; CI, 0.6-1.3) as compared with women not using the sponge. These estimates probably underestimate the degree of protection because some exposure was misclassified in this pilot phase of the study. These results are consistent with other studies indicating that spermicides protect against gonorrhea and also demonstrating protection against an organism of even greater public health concern, Chlamydia trachomatis.

Adult↗

In vitro evaluations of condoms with and without nonoxynol 9 as physical and chemical barriers against Chlamydia trachomatis, herpes simplex virus type 2, and human immunodeficiency virus.

Simulated in vitro intercourse conditions demonstrated that unlubricated latex condoms provide an effective physical barrier to high concentrations of Chlamydia trachomatis, herpes simplex virus type 2, and human immunodeficiency virus. However, since condoms can be damaged after manufacturing inspection and prior to use, latex condoms alone should not be perceived as absolute protection against STDs. Nonoxynol 9 used in conjunction with condoms provided additional, yet still not foolproof, protection against the three viruses.

Chlamydia trachomatis↗

Do spermicides containing nonoxynol-9 prevent sexually transmitted infections? A meta-analysis.

BACKGROUND AND OBJECTIVES: There are conflicting opinions on whether to recommend spermicides containing nonoxynol-9 for prevention of sexually transmitted diseases, including human immunodeficiency virus (HIV). GOAL: To systematically review and summarize the medical literature on the effect of spermicides containing nonoxynol-9 on prevention of gonorrhea, chlamydial infection, and HIV. STUDY DESIGN: Meta-analysis. Potential articles were identified through computerized literature searches. Articles were included if the design was clinical trial, cohort, case-control, or cross-sectional; original outcome data were presented for gonorrhea, chlamydial infection, or HIV; and spermicides containing nonoxynol-9 were used separately from other barrier methods. Study characteristics including design, population, spermicide dose, and delivery method were abstracted. Relative risks (RR) and 95% confidence intervals (CI) were determined from information published in the study or from study authors. Summary risk estimates were computed for clinical trials. RESULTS: Twelve eligible articles were identified, including six clinical trials and six observational studies. Eleven articles evaluated gonorrhea; each found a reduced risk of infection with spermicide use. Among six clinical trials, the summary RR was 0.62 (95% CI, 0.49-0.78). The five articles evaluating chlamydial infection also found significant reduction among spermicide users, with the four clinical trials having a summary RR of 0.75 (95% CI, 0.62-0.91). The degree of spermicidal protection against gonorrhea and chlamydial infection did not differ materially among studies with different study designs or spermicidal preparations (i.e., sponge, gel, suppository, or film). Three studies evaluated degree of protection according to consistency of use and found stronger protection with more consistent use. The two studies on spermicidal prevention of HIV had contrasting results: An observational study found a significant protective effect (RR = 0.1), whereas a clinical trial found a nonsignificantly increased risk (RR = 1.7). CONCLUSIONS: Nonoxynol-9-containing spermicides have an appreciable protective effect against both gonorrhea and chlamydial infection, and wider use of spermicides might substantially reduce the incidence of these diseases. However, insufficient data exist to judge their effect on HIV transmission, and more research on the effect of nonoxynol-9 on HIV transmission is urgently needed to make evidence-based clinical decisions and public health recommendations in the future.

Chlamydia Infections↗

High prevalence of chlamydia and Pap-smear abnormalities in pregnant adolescents warrants routine screening.

A prospective cohort of pregnant adolescent patients who planned to deliver at 1 of 3 Perth metropolitan hospitals was studied; 1 subgroup of this cohort was offered universal screening for cervical chlamydial infection and Pap-smear abnormalities (screened), and the remainder of the cohort were offered screening at the discretion of the attending medical staff (control). High prevalences of both chlamydial infection (27%) and Pap-smear abnormalities (38%) were detected in the screened cohort. The majority of Pap-smear abnormalities were inflammatory atypia, but high-grade Bethesda lesions were also diagnosed. In the control group, the prevalence of positive swabs and abnormal Pap-smear reports in those tested was also high (22% and 35% respectively), but significantly fewer patients were tested (18% and 33% respectively in the control group, compared to 92% and 94% in the screened group; both p<0.001). Screening and treatment of chlamydia was associated with a significant decrease in the incidence of newborn febrile morbidity (10% versus 25%; p=0.02). In view of the high prevalence of positive results, it is cost-effective to offer universal screening in this setting. Failure to introduce a specific screening policy can result in a significant number of patients being denied the advantages of diagnosis and treatment.

Adolescent↗

The need for a chlamydial culture service.

In a prospective study of unselected, female patients attending a sexually transmitted disease clinic one in eight patients would have been errouneously declared free of infection in the absence of a chlamydial culture service. Chlamydia trachomatis is now accepted as a causative organism of non-specific urethritis and post-gonococcal urethritis in men and non-specific genital infection in women. Thus, facilities for isolation of C. trachomatis should be an essential aid in the management of women attending STD clinics. Male patients would also benefit if such facilities were readily available.

Bacteriology↗

Sentinel surveillance of Chlamydia trachomatis infection in women terminating pregnancy.

AIMS: To evaluate demographic characteristics of women terminating their pregnancy for sentinel surveillance of Chlamydia trachomatis infection and to report changing prevalences of C trachomatis over time within this study population. DESIGN: Screening for C trachomatis in women seeking induced abortion was introduced in 1984 at the Department of Gynecology, Regional Hospital, Trondheim, Norway. Over the study years our department has used a precoded medical record covering sociodemographic, medically relevant data, also recording outcome of the C trachomatis test. Throughout the study the Department of Microbiology applied cell culture, enzyme immunoassay, and, during the most recent years a nucleic acid test to identify C trachomatis. STATISTICAL METHODS: Chi square test for linear trend and unconditional logistic regression. RESULTS: Over the study period, women having induced abortion were characterised by being most often single and more often at younger age. The overall age-adjusted prevalence of C trachomatis declined from 9.2% in 1985 to 3.6% in 1995, the major decline occurring from 1987 to 1991, and affected all age-groups simultaneously. There was a 60% decrease in odds ratio of having a C trachomatis infection from 1985 to 1991, and the crude and the adjusted odds ratios did not differ for any year examined. CONCLUSION: Women deciding on pregnancy termination have demographic characteristics that identify high-risk groups for C trachomatis infection. Despite these characteristics, which were relatively constant over the study period, the study population changed from being a high- to a low-prevalence population of C trachomatis.

Abortion, Induced↗

Genital Chlamydia trachomatis (serotypes D-K) infection in Jamaican commercial street sex workers.

OBJECTIVES: To determine the prevalence of genital Chlamydia trachomatis infections in commercial street sex workers (CSSW) in Jamaica. METHODS: The prevalence of C trachomatis infection was determined in 129 Jamaican CSSW using the direct fluorescent antibody (DFA) method and the isolation techniques which utilise fluorescent and iodine staining of endocervical cytobrush specimens cultured in McCoy cells. The seroprevalence of C trachomatis in the CSSW was also compared with that in blood donors (n = 435), using the microimmunofluorescence (MIF) test. RESULTS: The DFA detected C trachomatis in 16% (21/129) of the specimens. The prevalence as determined by the iodine and fluorescein stained cultures was 24% (31/129) and 25% (33/129) respectively. The overall prevalence of current chlamydial infection detected by the isolation techniques used was 25% (33/129). As determined by the MIF test, a statistically significantly higher seroprevalence rate of C trachomatis (95%, 61/64) was found in CSSW compared with blood donors (53%, 229/435; OR 22.6; chi 2 = 49.8; p < 0.001). The prevalence of current infection in CSSW as indicated by the isolation of C trachomatis was not influenced by history of previous pelvic inflammatory disease (PID), sexually transmitted disease, or condom use. N gonorrhoeae (9%) and Candida albicans (7%) were found in comparatively low frequencies, while Trichomonas vaginalis (0%) was not found in specimens from the CSSW. CONCLUSIONS: A high seroprevalence rate and a high rate of current infection with C trachomatis occur in Jamaican CSSW. In order to control the spread and prevent the severe clinical complications and sequelae of C trachomatis infection, the diagnosis and treatment in such high risk groups such as CSSW should be optimised.

Adolescent↗

Azithromycin in the treatment of chlamydial cervicitis and eradication of Ureaplasma urealyticum in female lower genital tract.

From May 1995 to May 1996, thirty-six females with chlamydial cervicitis were enrolled at Bangrak Hospital's Venereal Disease Clinic in an open study to assess the efficacy and safety of a single, 1-gram oral dose of azithromycin. Thirty-five had positive C. trachomatis and one had a positive Gen-probe test. Twenty-two returned for their first and second follow-ups and 18 came back for their final follow-up (visit 4). Eradication rate was 100 per cent on all visits. Fourteen patients were excluded from the final analysis- three had dropped out from the beginning, ten had sexual intercourse without a condom and one had a positive Gen-probe test but negative C. trachomatis culture. U. urealyticum was isolated from the vaginal wall of 15 of the 36 cases and eradication rate was 0 per cent at visit 2 and visit 4. In conclusion, this study shows that a single, 1-gram oral dose of azithromycin is an effective and well-tolerated alternative therapy for chlamydial cervicitis.

Adolescent↗