Ainsliaea fragrans champ. Extract prevents cervicitis in BALB/c mice and regulates MyD88-NF-κB signaling pathway in MALP-2-stimulated RAW264.7 cells.

Ethnopharmacological relevance Ainsliaea fragrans Champ. (A. fragrans) is used to treat infection of the lower genital tract in gynecology, such as cervicitis and pelvic inflammatory disease. This study analyzed the therapeutic efficiency of A. fragrans on cervicitis and the inhibition mechanism of AF-p2 in MALP-2-stimulated RAW264.7 cells. Materials and methods The anti- Ureaplasma urealyticum (Uu) activity of A. fragrans and AF-p2 were determined by antimicrobial susceptibility testing. The activity of A. fragrans extracts (AFext) was evaluated in female BALB/c mice with cervicitis induced by Uu. Furthermore, the therapeutic mechanism of AFext and AF-p2 on myeloid differentiation factor 88 (MyD88) pathway were studied in macrophage activating lipopeptide-2 (MALP-2) irritated RAW264.7 cells. Results AFext could suppress the proliferation of Uu in vitro, including the azithromycin resistant strains. Meanwhile, AFext prevented cervicitis caused by Uu infection in BALB/c mice. Moreover, both AFext and AF-p2 could significantly suppress the nitric oxide (NO) production as well as other proinflammatory cytokines (IL-1ß,IL-6,TNF-α) in MALP-2 stimulated RAW264.7 cells. Moreover, AF-p2 also down-regulated iNOS, p65, Iκ-Bα, MyD88 and cyclooxygenase-2 (COX-2) levels in RAW264.7 cells. Conclusion This study indicated that AFext had a therapeutic effect in cervicitis induced by Uu infection. Furthermore, the lead compound AF-p2 showed an anti-infectious effect in MALP-2 irritated RAW264.7 cells through downregulating MyD88-NF-κB signaling pathway.

[THE ROLE OF NO AND MEXIDOL IN CONTRACTILITY OF OVARIAN AND CERVICAL PARTS OF UTERUS UNDER THE CONDITION OF IMMUNE-MEDIATED INJURY IN MICE].

Contractility of ovarian (OP) and cervical parts (CP) of uterus under the condition of immune-mediated injury which was induced by immunization with bovine serum albumin (BSA) was investigated. It was shown that under the activation of energy-synthesizing function of mitochondria with Mexidol the frequency of reductions in both uterine parts decreased, the amplitude and contractility index in the OP and CP as well as the duration of the active state in CP increased. Mexidol under the condition of immunization with BSA leads to the decrease in amplitude in 2,6 time and contractility index in 2,2 time in OP and to the increase of them in CP. It was shown that contractility features of ovarian and cervical parts of uterine under the condition of BSA- induced immunization were caused by changes of mitochondria functional state and were associated with nitric oxide.

Prevention and control of sexually transmissible infections among hotel-based female sex workers in Dhaka, Bangladesh.

BACKGROUND: Hotel-based sex workers in Bangladesh have high rates of sexually transmissible infections (STIs), high client turnover and low condom use. Two monthly clinic-based strategies were compared: periodic presumptive treatment (PPT) and enhanced syndromic management (ESM) - one round of presumptive treatment followed by treatment based on assessment and laboratory tests. METHODS: A randomised controlled trial compared PPT and ESM by prevalence and incidence, behaviour, retention, cost and STI incidence and prevalence. Demographic, behavioural and clinical data were collected from women at two clinics in Dhaka. All women received presumptive treatment and were randomised to receive PPT or ESM at nine monthly visits. RESULTS: In total, 549 women (median age: <20 years) were enrolled. At baseline, the prevalence of chlamydia (Chlamydia trachomatis) and gonorrhoea (Neisseria gonorrhoeae) was 41% (ESM: 41%; PPT: 42%). After 9 months, chlamydia and gonorrhoea decreased to 7% overall, (ESM: 7.4%; PPT: 6.8%). At each visit, 98% of women receiving ESM met the therapy criteria and were treated. Retention was low (50%). Total costs were 50% lower per visit for each woman for PPT (ESM: $11.62 v. PPT: $5.80). The number of sex work sessions was reduced from 3.3 to 2.5 (P<0.001), but income did not change. Coercion was reduced but condom use at last sex did not change significantly. CONCLUSIONS: Monthly PPT and ESM were effective approaches for STI control. PPT offered a feasible, low-cost alternative to ESM. Educational aspects led to a reduction in coercion and fewer sessions. Implementation studies are needed to improve condom use and retention.

Urethritis/cervicitis pathogen prevalence and associated risk factors among asymptomatic HIV-infected patients in South Africa.

BACKGROUND: To determine sexually transmitted infection (STI) prevalence, and patient characteristics associated with detection of urethritis/cervicitis pathogens, among HIV-infected individuals offered voluntary STI screening at a South African HIV treatment center. METHODS: Individuals, asymptomatic for genital discharge, were screened for Neisseria gonorrhoeae (NG), Chlamydia trachomatis, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) infections (real-time polymerase chain reaction assay), for syphilis and herpes simplex type 2 (serologically), and for bacterial vaginosis and Candida (microscopy, women only). Patients' most recent CD4 and viral load results were recorded. Demographic, clinical, and behavioral data were collected by nurse-administered questionnaire. RESULTS: Compared with men (n = 551), women (n = 558) were younger (mean age, 35.0 vs. 37.9 years; P < 0.001), reported more STIs in the past year (65.5% vs. 56.5%; P = 0.002), had more urethritis/cervicitis pathogens detected (21.3% vs.16.4%, P = 0.035), and were less aware of their partner's HIV status (53.1% vs. 62.3%; P = 0.007). The overall prevalence of individual urethritis/cervicitis pathogens was TV (7.6%), MG (6.1%), NG (5.4%), and C. trachomatis (2.1%). Multivariate analysis highlighted 4 significant factors associated with the detection of specific urethritis/cervicitis pathogens, namely female gender (TV, adjusted odds ratio [aOR] 2.53, 95% confidence interval [CI]: 1.47-4.37), having a regular sexual partner in the past 3 months (NG, aOR 2.26, 95% CI: 1.01-5.08), suboptimal condom use with regular partners (TV, aOR 2.07, 95% CI: 1.25-3.42), and a history of genital warts in the past year (NG, 2.25, 95% CI: 1.26-4.03). CONCLUSIONS: Asymptomatic urethritis/cervicitis pathogens were highly prevalent in this population. Few urethritis/cervicitis pathogen-associated patient characteristics were identified, emphasizing the need for affordable STI diagnostics to screen HIV-infected patients.

The known unknowns of HPV natural history.

The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.

Multiple human papilloma virus types in cervical infections: competition or synergy?

Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR-based commercial microarray assay for mucosal types. Of the HPV-positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV-16 infection had 0.4 times the odds of having HPV-51 compared with women not infected with HPV-16. HPV-16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type-specific protection, depending on whether the types vaccinated against compete with other HPV types or not.

Combined hormonal contraception may be protective against Neisseria gonorrhoeae infection.

BACKGROUND: The role of hormonal contraception on acquisition of gonorrhea has not been well-characterized, as the transmission dynamics of Neisseria gonorrhoeae are poorly understood. The purpose of this study is to determine the influence of hormonal contraception on gonococcal infection in women exposed to males with gonococcal urethritis. METHODS: Females aged 15 to 35 years reporting sexual contact to a male partner diagnosed with N. gonorrhoeae were enrolled. Demographic and sexual histories, physical findings, and laboratory tests were collected. Women testing positive and negative for cervical N. gonorrhoeae were compared using chi and Fisher exact tests, with multivariable logistic regression performed on those factors independently associated with gonococcal infection on univariate analysis. RESULTS: N. gonorrhoeae infection occurred in 68 of 107 (64%) women. Women using combined hormonal contraception were significantly less likely than nonusers to test positive for N. gonorrhoeae (32% vs. 76%; prevalence ratio: 0.42; 95% confidence interval: 0.22, 0.78; P = 0.006). Gonorrhea was also less common in depomedroxyprogesterone acetate users. A new sexual partner was also associated with testing positive for gonorrhea (35% vs. 13%; prevalence ratio: 1.47; 95% confidence interval: 1.13, 1.90; P = 0.004). CONCLUSIONS: Women using combined hormonal contraceptives or depomedroxyprogesterone acetate were less likely to test positive for N. gonorrhoeae after sexual exposure compared with nonusers. Our data suggest that, in addition to contraceptive benefits, modern hormonal contraception may have a protective effect on the acquisition of N. gonorrhoeae.

Epidemiology of Chlamydia trachomatis infection in women and the cost-effectiveness of screening.

BACKGROUND: The majority of Chlamydia trachomatis infections in women are asymptomatic, but may give rise to pelvic inflammatory disease (PID) and tubal infertility. Screening programmes aim at reducing morbidity in individuals by early detection and treatment, and at decreasing the overall prevalence of infection in the population. A number of modelling studies have tried to calculate the threshold prevalence of chlamydia lower genital tract infection above which screening becomes cost-effective. There is considerable debate over the exact complication rates after chlamydia infections, and more precise estimates of PID and tubal infertility are needed, for instance to be inserted in economic models. METHODS: With reference to key studies and systematic reviews, an overview is provided focusing on the epidemiology of chlamydia infection and the risk-estimates of its late complications. RESULTS: In the literature, the generally assumed risk of developing PID after lower genital tract chlamydia infection varies considerably, and is up to 30%. For developing tubal infertility after PID the risks are 10-20%. This implies that the risk of test-positive women of developing tubal infertility would range between 0.1 and 6%. We included chlamydia IgG antibody testing in a model and estimated a risk of tubal infertility up to 4.6%. CONCLUSION: The risk of developing late complications after chlamydia lower genital tract infection appears low. High quality RCTs dealing with the transition from cervicitis to infertility are needed to broaden the evidence. In screening programmes, chlamydia antibody testing, as an intermediate marker for potential adverse sequelae, might enable more precise estimates.

Persistent antibodies to HPV virus-like particles following natural infection are protective against subsequent cervicovaginal infection with related and unrelated HPV.

Whether persistent human papillomavirus (HPV) IgG antibodies following natural infection are protective against subsequent infection is unknown. In a cohort of 508 college women followed for 3 y, persistent seropositivity was defined as the presence of type-specific HPV virus-like particle (VLP) antibodies at > or = 2 consecutive visits 1 y apart. Protection from incident infection with any HPV was conferred by persistent antibodies to HPV16 (p = 0.02), HPV31 (p < 0.001), HPV33 (p = 0.03), HPV35 (p = 0.002), HPV52 (p = 0.007), HPV45 (p = 0.003), and HPV53 (p = 0.01). The risk of incident infection with species-specific HPV types was also decreased in women with persistent antibodies to any HPV type in that group, suggesting that exposure to HPV with persistent development of antibody response can be protective, and may explain the decreased efficacy of HPV vaccine in women with prior exposure.

Worldwide impact of the human papillomavirus vaccine.

OPINION STATEMENT: Nearly 500,000 new cases of cervical cancer and 274,000 cervical cancer deaths are occurring worldwide each year. Approximately 80% of the 500,000 new cases occur in developing countries and this percentage is expected to increase to 90% by 2020. In developing countries, cervical cancer tends to affect relatively young poor women and is the single largest cause of years of life lost to cancer, since screening and treatment programs, and health care, in general, are relatively inaccessible to these women. Each 5-year delay in vaccinating women against HPV may lead to the deaths of 1.5 to 2 million women from cervical cancer in developing countries. The high efficacy of the two available cervical cancer vaccines and their proven ability to reduce the incidence of cervical cancer precursor lesions offer hope that the vaccine will have enormous worldwide impact and may dramatically reduce the cervical cancer burden. The current vaccines protecting against HPV-16 and HPV-18 may prevent up to 70% of new cervical cancers. Vaccine cross-reactivity for HPV-31, -33, -45, and -52 suggest that an even higher percentage of cervical cancers might be prevented with its use. Currently, the prohibitive cost of the vaccine precludes its widespread implementation. Cooperation between governments, international health organizations, and the vaccine industry is needed to overcome this significant barrier so that women are no longer denied a potentially life-saving advance. Worldwide HPV vaccination and cervical cancer screening should be made an international priority.

Preventing recurrent sexually transmitted diseases in minority adolescents: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of a randomized controlled trial of the Sexual Awareness For Everyone (SAFE) behavioral intervention on teenagers (aged 14 to 18 years) compared with adult rates of reinfection with Neiserria gonorrhea or Chlamydia trachomatis cervicitis, and to identify behaviors associated with recurrent infection. METHODS: Mexican-American and African-American females with a nonviral sexually transmitted disease (STD) were enrolled in SAFE or assigned to the control group. All participants were interviewed and examined at baseline, 6, and 12 months. The primary outcome variable was reinfection with N. gonorrhea or C. trachomatis. Secondary outcomes were changes in risky sexual behavior. RESULTS: Teens randomized to participation in SAFE had a statistically lower incidence of recurrent N. gonorrhea and C. trachomatis at 0 to 6 months (52%, P=.04) and cumulatively (39%, P=.04) compared with teens in the control group. Cumulatively, teens as a group had higher rates of reinfection (33.1%) than adults (14.4%) (P<.001). Adolescent reinfection was explained by unprotected sex with untreated partners (adjusted odds ratio [OR] 5.58), nonmonogamy (adjusted OR 5.14), and rapid partner turnover (adjusted OR 2.02). In adults, reinfection was predicted by unprotected sex with untreated partners (adjusted OR 4.90), unsafe sex (adjusted OR 2.18), rapid partner turnover (adjusted OR 3.13), and douching after sex (adjusted OR 2.14). CONCLUSION: Sexual Awareness for Everyone significantly reduced recurrent STDs in teenagers. Adults and teens randomized to the SAFE intervention had significant decreases in high-risk sexual behaviors as compared with those in the control group. Although not specifically designed for teens, the SAFE intervention worked very well in this high-risk population. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, ClinicalTrials.gov, HSC2004415H. LEVEL OF EVIDENCE: I.

Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa.

OBJECTIVES: To demonstrate the value of routine, basic sexually transmitted infection (STI) screening at enrolment into an HIV-1 vaccine feasibility cohort study and to highlight the importance of soliciting a history of receptive anal intercourse (RAI) in adults identified as "high risk". METHODS: Routine STI screening was offered to adults at high risk of HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviours and STI prevalence were summarised and the value of microscopy assessed. Associations between prevalent HIV-1 infection and RAI or prevalent STI were evaluated with multiple logistic regression. RESULTS: Participants had a high burden of untreated STI. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. RAI was reported by 36% of male and 18% of female participants. RAI was strongly associated with HIV-1 in men (adjusted odds ratio (aOR) 3.8; 95% CI 2.0 to 6.9) and independently associated with syphilis in women (aOR 12.9; 95% CI 3.4 to 48.7). CONCLUSIONS: High-risk adults recruited for HIV-1 prevention trials carry a high STI burden. Symptom-directed treatment may miss many cases and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. STI screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk of HIV-1 acquisition.

[Potentialities of cytology in preventive examinations of samples from the uterine cervix]. / Vozmozhnosti tsitologicheskogo metoda issledovaniia pri prifilakticheskon osmotre materiala shei ki matki.

The primary detection rate of inflammatory diseases of the neck of uterus, like inflammations of different etiopathogenesis, bacterial vaginosis and candidosis, went up, 2000-2002, by 3.2%; the above rate increase in women with gynecology history by 8.1%. The detection rate of bacterial vaginosis grew by 22%. Total cytological examinations of sample from the ectocervix and endocervix do not only insure the detection of morphologically changed cells, they also characterize their bacterial composition.

[Preliminary study on the relationship between loads of human papillomavirus in cervical carcinoma and cervical intraepithelial neoplasia].

OBJECTIVE: To explore the relationship between loads of human papillomavirus in cervical carcinoma and cervical intraepithelial neoplasia. METHODS: From December 2001 to May 2002, 9075 married women aged from 35 to 50 years who lived in the areas with a high incidence of cervical carcinoma of Shanxi Province were screened high risk types of human papillomavirus (HPV) infection using hybrid capture II (HC-II). Of them, 2087 women with positive human papillomavirus further underwent colposcopy and multi-focal directed punch biopsies plus endocervical currettage. RESULTS: Two thousand and eighty-seven women were found with positive human papillomavirus infection, comprising 1402 (67.2%) women who were diagnosed as cervicitis, 663 (31.8%) women diagnosed as cervical intraepithelial neoplasia [including cervical intraepithelial neoplasia (CIN) I to III], and 22 (1.1%) women diagnosed as cervical squamous cell carcinoma (SCC). HPV-DNA loads of women with chronic and acute cervicitis were 150 +/- 11 and 108 +/- 13, respectively, with no significant difference between two groups statistically (P = 0.225). HPV-DNA loads for women with CIN I, CIN II and CIN III were 332 +/- 29, 358 +/- 35, and 370 +/- 31, respectively, all significantly higher than that of women with cervicitis (P = 0.000), but there were no significant differences among three groups (P > 0.05). HPV-DNA loads of women with cervical squamous cell carcinoma was 593 +/- 86, much higher than those of women with varied grades of cervical intraepithelial neoplasia and cervicitis (P < 0.05 and P < 0.01). CONCLUSIONS: The new technology using HC-II is an effective method to detect HPV infection in cervix. Viral loads of HPV-DNA increase with severity of cervical neoplasia. So it could be used for screening primary cervical carcinoma.

Suppression of endogenous IL-10 gene expression in dendritic cells enhances antigen presentation for specific Th1 induction: potential for cellular vaccine development.

A new paradigm for designing vaccines against certain microbial pathogens, including Chlamydia trachomatis, is based on the induction of local mucosal Th1 response. IL-10 is an anti-inflammatory cytokine that exerts negative immunoregulatory influence on Th1 response. This study investigated whether biochemical modulation of endogenous IL-10 expression at the level of APCs is a practical strategy for enhancing the specific Th1 response against pathogens controlled by Th1 immunity. The results revealed that the high resistance of genetically engineered IL-10-/- (IL-10KO) mice to genital chlamydial infection is a function of the predilection of their APCs to rapidly and preferentially activate a high Th1 response. Thus, in microbiological analysis, IL-10KO mice suffered a shorter duration of infection, less microbial burden, and limited ascending infection than immunocompetent wild-type mice. Also, IL-10KO were resistant to reinfection after 8 wk of the primary infection. Cellular and molecular immunologic evaluation indicated that IL-10KO mice induced greater frequency of chlamydial-specific Th1 response following C. trachomatis infection. Moreover, IL-10KO APCs or antisense IL-10 oligonucleotide-treated wild-type APCs were potent activators of Th1 response from naive or immune T cells. Furthermore, both Ag-pulsed dendritic cells from IL-10KO mice and IL-10 antisense-treated dendritic cells from wild-type mice were efficient cellular vaccines in adoptive immunotherapeutic vaccination against genital chlamydial infection. These findings may furnish a novel immunotherapeutic strategy for boosting the Th1 response against T cell-controlled pathogens and tumors, using IL-10-deficient APCs as vaccine delivery agents.

1998 guidelines for treatment of sexually transmitted diseases. Centers for Disease Control and Prevention.

These guidelines for the treatment of patients who have sexually transmitted diseases (STDs) were developed by CDC staff members after consultation with a group of invited experts who met in Atlanta on February 10-12, 1997. The information in this report updates the "1993 Sexually Transmitted Diseases Treatment Guidelines" (MMWR 1993;42[no. RR-14]). Included are new recommendations for treatment of primary and recurrent genital herpes and management of pelvic inflammatory disease; a new patient-applied medication for treatment of genital warts; and a revised approach to the management of victims of sexual assault. Revised sections describe the evaluation of urethritis and the diagnostic evaluation of congenital syphilis. These guidelines also include expanded sections concerning STDs among infants, children, and pregnant women and the management of patients who have asymptomatic human immunodeficiency virus infection, genital warts, and genital herpes. Guidelines are provided for vaccine-preventable STDs, including recommendations for the use of hepatitis A and hepatitis B vaccines.

Vaginal and cervical pH in bacterial vaginosis and cervicitis during pregnancy.

The purpose of our study is to see whether vaginal and cervical pH are helpful to screen for bacterial vaginosis and cervicitis during pregnancy. One hundred and seven pregnant women underwent prospectively both vaginal pH and cervical pH measurement and screening for microbial infections of the lower genital tracts at 10, 20 and 30 gestational week between February 1993 and August 1993. The value of vaginal pH significantly elevated in bacterial vaginosis (P < 0.05). Vaginal pH values also significantly elevated in patients who had had sexual intercourse 2 days before the dates of examinations (P < 0.01). Cervical pH value exhibited no significant change in bacterial vaginosis and cervicitis. Vaginal pH is a valid indicator for screening of bacterial vaginosis during pregnancy. However, vaginal pH might be influenced by the presence of semen. Cervical pH is not a useful parameter for screening of cervicitis during pregnancy.