Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota.

BACKGROUND: Over-the-counter intra-vaginal lactic-acid containing douches are marketed as vaginal hygiene products that support optimal vaginal pH balance. We report the effect of a commercially available douche (Etos®) on the vaginal microbiota (VM) in a prospective study. RESULTS: Twenty-five healthy women were recruited through advertisements in 2015-2017 (ethical approval: METC-2014_413) and followed over three menstrual cycles. The participants had a median age of 24 years [IQR: 22-29], were mostly Dutch-Caucasian (88%), and 60% used combined oral contraceptives. All participants douched three times a week during the second cycle, starting on the first day of that cycle. Participants completed a questionnaire at baseline, kept a daily diary to report douching, menses, and sexual activity, self-collected vaginal swabs every other day during the first and third cycle and daily during the second cycle, and measured vaginal pH mid-cycle. A median of 44 vaginal swabs [inter-quartile range (IQR): 41-50] were assessed per participant by 16S rRNA gene (V3-V4 region) sequencing and a Candida albicans PCR was done at four time-points. At baseline, 21 participants (84%) had Lactobacillus-dominated VM (Lactobacillus crispatus (n = 14), L. iners (n = 6), or diverse Lactobacillus species (n = 1) and 4 participants (16%) had VM consisting of diverse anaerobes. In multinomial logistic regression models, a trend towards increased odds were observed for having diverse anaerobic VM in the second and third cycle, compared to the first cycle, after adjusting for menses [odds ratio (OR) = 1.4 (95% CI: 0.9-2.1) and OR = 1.7 (95% CI: 0.9-3.1), respectively] (p = 0.376). Douching did not affect vaginal pH. Menses increased the odds for having VM consisting of diverse anaerobes almost two-fold (OR = 1.7; 95% CI: 1.0-2.8), while douching during menses increased the odds 2.6 fold (OR = 2.6; 95% CI: 1.0-6.5), compared to not menstruating (p = 0.099). Participants were more likely to test positive for C. albicans after cycle 2, compared to cycle 1 [OR = 3.0 (95% CI: 1.2-7.2); p = 0.017]. CONCLUSION: The Etos® douche did not significantly affect the vaginal pH or VM composition, although increased odds for having diverse anaerobic VM was observed, especially when douching during menses. Furthermore, douching may promote C. albicans infections.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study.

OBJECTIVE: In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. METHODS: For this cross-sectional study we selected women aged 18-34 years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. RESULTS: The study population consisted of 592 women with a median age of 27 (IQR: 23-31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. CONCLUSIONS: We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier.

Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV. Cervicovaginal inflammation and other changes to the mucosal barrier are thought to have important roles but human data are scarce. We compared the human cervicovaginal proteome by mass spectrometry of 50 Rwandan female sex workers who had previously been clustered into four VMB groups using a 16S phylogenetic microarray; in order of increasing bacterial diversity: Lactobacillus crispatus-dominated VMB (group 1), Lactobacillus iners-dominated VMB (group 2), moderate dysbiosis (group 3), and severe dysbiosis (group 4). We compared relative protein abundances among these VMB groups using targeted (abundance of pre-defined mucosal barrier proteins) and untargeted (differentially abundant proteins among all human proteins identified) approaches. With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organizing proteins; decreasing keratins and cornified envelope proteins), increasing lactate dehydrogenase A/B as markers of cell death, increasing proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing pro-inflammatory cytokines, and decreasing immunoglobulins immunoglobulin G1/2. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier.

Prevalence of sexually transmitted infections, genital symptoms and health-care seeking behaviour among HIV-negative female sex workers in Kigali, Rwanda.

Timely diagnosis and treatment of sexually transmitted infections (STIs) is often hampered by the lack of symptoms, inadequate diagnostics and/or poor availability, accessibility and quality of treatment in resource-limited settings. Female sex workers (FSW) are highly vulnerable for HIV and key transmitters of STIs. Among FSW (n = 400) participating in a prospective HIV incidence study in Kigali, Rwanda, only 15% (17/116) of women with laboratory-diagnosed non-ulcerative STIs at baseline reported symptoms. Only 27% (20/74) of women self-reporting genital symptoms sought care at enrolment, and 39% (46/117) of women with self-reported genital symptoms during follow-up. During focus group discussions, FSW considered treatment-seeking and partner notification important. Shame and feeling disrespected by doctors or other health-care workers were identified as barriers to seeking health care. A comprehensive STI control programme targeting both symptomatic and asymptomatic FSW should be considered in this setting.

'Mama and papa nothing': living with infertility among an urban population in Kigali, Rwanda.

BACKGROUND: Not being able to procreate has severe social and economic repercussions in resource-poor countries. The purpose of this research was to explore the consequences of female and/or male factor infertility for men and women in Rwanda. METHODS: Both quantitative and qualitative methods were used. Couples presenting with female and/or male factor infertility problems at the infertility clinic of the Kigali University Teaching Hospital (n = 312), and fertile controls who recently delivered (n = 312), were surveyed about domestic violence, current and past relationships and sexual functioning. In addition, five focus group discussions were held with a subsample of survey participants, who were either patients diagnosed with female- or male-factor fertility or their partners. RESULTS: Domestic violence, union dissolutions and sexual dysfunction were reported more frequently in the survey by infertile than fertile couples. The psycho-social consequences suffered by infertile couples in Rwanda are severe and similar to those reported in other resource-poor countries. Although women carry the largest burden of suffering, the negative repercussions of infertility for men, especially at the level of the community, are considerable. Whether the infertility was caused by a female factor or male factor was an important determinant for the type of psycho-social consequences suffered. CONCLUSIONS: In Rwanda, as in other resource-poor countries, infertility causes severe suffering. There is an urgent need to recognize infertility as a serious reproductive health problem and to put infertility care on the public health agenda.

Sexual violence, HSV-2 and HIV are important predictors for infertility in Rwanda.

BACKGROUND: In order to formulate cost-effective health interventions aimed at preventing infertility it is necessary to identify modifiable risk factors for infertility in sub-Saharan Africa. This case-control study examined potential predictors and their population attributable fraction (PAF%) for various infertility types including lifestyle factors, sexual behaviour and reproductive tract infections (RTIs). METHODS: Sexually active women aged 21-45 year presenting with infertility problems at the infertility clinic of the Kigali University Teaching Hospital (n = 312), and fertile controls who recently delivered (n = 283) were surveyed together with their male partners. Participants were interviewed about socio-demographic characteristics, sexual behaviours and lifestyle factors, and were tested for HIV and RTIs. RESULTS: Variables significantly associated with tubal infertility were history of sexual violence [adjusted odds ratio (AOR) 2.41; 95% CI 1.36-4.25]; positive HIV (AOR 2.41; 95% CI 1.36-4.25), herpes simplex virus type 2 (HSV-2; AOR 1.67; 95% CI 1.03-2.71) and Chlamydia trachomatis serology (AOR 1.78; 95% CI 0.99-3.21), and current bacterial vaginosis by Amsel criteria (AOR 1.97; 95% CI 1.12-3.47). Among men, male factor infertility was associated with positive HIV (AOR 2.43; 95% CI 1.31-5.23) and HSV-2 serology (AOR 1.71; 95% CI 1.02-2.87) and current urologic abnormalities (AOR 2.38; 95% CI 1.01-5.31). Positive HSV-2 serostatus carried the greatest PAF% (26%) for tubal infertility, followed by positive HIV serostatus (20%) and history of sexual violence (17%). CONCLUSIONS: Although temporal relationships are difficult to ascertain, history of sexual violence, HSV-2 infection and HIV infection are important predictors of infertility in Rwanda.

Gender differences and factors associated with treatment-seeking behaviour for infertility in Rwanda.

BACKGROUND: This study examines perceptions of infertility causes, treatment-seeking behaviour and factors associated with seeking medical care in an urban infertile population in Rwanda, as well as the response of health providers. METHODS: Between November 2007 and May 2009 a hospital based survey was conducted among 312 women and 254 male partners in an infertile relationship. RESULTS: Infertility causes based on a medical diagnosis were mentioned by 24% of women and 17% of men. Male infertility awareness was low in both sexes with 28% of men and 10% of women reporting male-related causes. Seventy-four per cent of women and 22% of men had sought care for their infertility in the past. Seeking treatment in the formal medical sector was associated with higher income, being married and infertility duration of more than 5 years in both sexes. In women, higher education and being nulliparous and in men blaming oneself for the infertility was also associated with seeking formal medical care. Participants reported a wide array of treatments they received in the past, often including ineffective or even harmful interventions. CONCLUSION: Health authorities should invest in improving information, education and counselling on issues pertaining to causes and treatments of infertility, and in drawing up guidelines for the management of infertility at all levels of health care.

Prevalence, distribution and correlates of endocervical human papillomavirus types in Brazilian women.

We determined the prevalence, distribution and correlates of human papillomavirus (HPV) types in 386 mixed-income, sexually active women in São Paulo, Brazil. Endocervical samples were tested for HPV DNA with L1 primers MY09 and MY11; negative and indeterminate samples were retested using GP 5+/6+ consensus primers. HPV was detected in 35% of all women; high-risk/probable high-risk types in 20%; low-risk types in 7%; and an indeterminate type in 10%. Twenty-five HPV types were found overall: 17 (probable) high-risk types and eight low-risk types. Approximately one-third (29%) of women with HPV infection were positive for type 16 or 18 and 36% were positive for types 6, 11, 16 or 18. The presence of (probable) high-risk HPV was associated with younger age, more lifetime sex partners and abnormal vaginal flora. Additional studies mapping the distribution of HPV types worldwide are necessary to prepare for vaccination programmes and direct future vaccine development.

Home-based versus clinic-based self-sampling and testing for sexually transmitted infections in Gugulethu, South Africa: randomised controlled trial.

OBJECTIVES: To test whether more women are screened for sexually transmitted infections when offered home-based versus clinic-based testing and to evaluate the feasibility and acceptability of self-sampling and self-testing in home and clinic settings in a resource-poor community. METHODS: Women aged 14-25 were randomised to receive a home kit with a pre-paid addressed envelope for mailing specimens or a clinic appointment, in Gugulethu, South Africa. Self-collected vaginal swabs were tested for gonorrhoea, chlamydia and trichomoniasis using PCR and self-tested for trichomoniasis using a rapid dipstick test. All women were interviewed at enrollment on sociodemographic and sexual history, and at the 6-week follow-up on feasibility and acceptability. RESULTS: 626 women were enrolled in the study, with 313 in each group; 569 (91%) completed their 6-week follow-up visit. Forty-seven per cent of the women in the home group successfully mailed their packages, and 13% reported performing the rapid test and/or mailing the kit (partial responders), versus 42% of women in the clinic group who kept their appointment. Excluding partial responders, women in the home group were 1.3 (95% CI 1.1 to 1.5) times as likely to respond to the initiative as women in the clinic group. Among the 44% who were tested, 22% tested positive for chlamydia, 10% for trichomoniasis, and 8% for gonorrhoea. CONCLUSIONS: Self-sampling and self-testing are feasible and acceptable options in low-income communities such as Gugulethu. As rapid diagnostic tests become available and laboratory infrastructure improves, these methodologies should be integrated into services, especially services aimed at young women.

A comparison of two methods of partner notification for sexually transmitted infections in South Africa: patient-delivered partner medication and patient-based partner referral.

The objective of this study was to determine acceptability and feasibility of patient-based partner referral (PBPR) and patient-delivered partner medication (PDPM) among female sexually transmitted infection (STI) patients in a community-based STI screening study. Women were randomized to STI screening at home or at a clinic. STI patients could choose between PBPR and PDPM. Six-week follow-up interviews, and in-depth interviews, were conducted. STI prevalence was high. Most of the 106 women with an STI chose PDPM, mainly because partners would not have time or would not want to attend a clinic, and to ensure that partners received treatment. Nearly all partners reportedly took medication (94; 89% took it in front of the woman) or went to a clinic for treatment (92%). No adverse events were reported. Good communication emerged as the key to successful partner notification. In conclusion, PDPM could be used as a strategy to improve STI treatment coverage.

Preparing for microbicide trials in Rwanda: focus group discussions with Rwandan women and men.

The acceptability and feasibility of microbicide studies and future microbicide use are influenced by existing norms and values regarding sexual and contraceptive behaviour. In preparation for microbicide research in Rwanda, focus group discussions were conducted to assess sexual and contraceptive behaviour, preferences for vaginal lubrication, and hypothetical acceptability of microbicides among Rwandan women and men. Seven focus group discussions were conducted among sexually active married women, unmarried women, sex workers, female students, older women and men living in Kigali, Rwanda, and an additional group of women living in a rural area. The results indicate that condom use is low among Rwandan men and women and that condoms are mainly used by men during commercial sex. Women have limited power to negotiate condom or family planning use. Vaginal hygiene practices are very common and consist primarily of washing with water. Lubrication during sex is highly preferred by both men and women. Hypothetical microbicide acceptability after an explanation of what microbicides are and a demonstration with lubricant jelly was high.

Microbicide trials for preventing HIV/AIDS in South Africa: phase II trial partricipants' experiences and psychological needs.

The Microbicide Division of the Department of Medical Microbiology at MEDUNSA, South Africa, recently completed a phase II expanded safety trial of the candidate microbicide Carraguard. A microbicide is a vaginal product that women might use, if proven safe and effective, to protect themselves from HIV and possibly other sexually transmitted infections (STIs). The study participants were from Ga-Rankuwa and its neighbouring areas, an historically disadvantaged residential township near Pretoria. We conducted six focus group discussions with phase II trial participants to evaluate their experiences with trial participation and their psychological needs. Participants spontaneously talked about their experiences with the study gel and speculum examinations. They felt that they had received high quality medical care. They indicated that their personal hygiene and knowledge of the female reproductive system, HIV and other STIs had improved, which helped their familie and empowered them as women. Participants valued being able to discuss their anxiety about HIV/AIDS wit study staff. They felt that the study provided them with a supportive environment in which their personal problems (not necessarily restricted to HIV/AIDS) could be addressed. Some recommended that the study staf improve their professionalism and punctuality. They suggested the formation of participant support groups, an expressed a preference to remain involved in the trial. Some participants appeared to have become dependent o services provided during the trial. We have taken the results of these focus group discussions into account during planning for a phase III efficacy trial of Carraguard to be conducted in the same and other similar communities.

Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites.

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

Constraints faced by sex workers in use of female and male condoms for safer sex in urban zimbabwe.

We investigated whether female condoms are acceptable to sex workers in Harare and whether improved access to male and female condoms increases the proportion of protected sex episodes with clients and boyfriends. Sex workers were randomly placed in groups to receive either male and female condoms (group A, n = 99) or male condoms only (group B, n = 50) and were followed prospectively for about 3 months each. We found a considerable burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs) in our cohort at enrollment (86% tested HIV positive and 34% had at least one STI). Consistent male condom use with clients increased from 0% to 52% in group A and from 0% to 82% in group B between enrollment and first follow-up 2 weeks later and remained high throughout the study. Few women in group A reported using female condoms with clients consistently (3%-9%), and use of either condom was less common with boyfriends than with clients throughout the study (8%-39% for different study groups, visits, and types of condom). Unprotected sex still took place, as evidenced by an STI incidence of 16 episodes per 100 woman-months of follow-up. Our questionnaire data indicated high self-reported acceptability of female condoms, but focus group discussions revealed that a main obstacle to female condom use was client distrust of unfamiliar methods. This study shows that a simple intervention of improving access to condoms can lead to more protected sex episodes between sex workers and clients. However, more work is needed to help sex workers achieve safer sex in noncommercial relationships.

Is audio computer-assisted self-interviewing a feasible method of surveying in Zimbabwe?

BACKGROUND: Research into reproductive health is dependent on participants accurately reporting sensitive behaviours. We examined whether audio computer-assisted self-interviewing (ACASI), which increased sensitive behaviour reporting in the US, is a feasible method of surveying in developing countries. METHODS: Zimbabwean women in three educational groups were surveyed about demographics and family planning using interviewer and ACASI modes. An exit survey was administered to elicit information about the participants' opinions and experiences using ACASI. RESULTS: The majority of women (86%) preferred ACASI to interviewer mode. The reasons mentioned were always related to increased confidentiality and privacy. Ability to use ACASI and user preferences varied with educational level. More women with primary school or less education (53%) reported problems with computer use than women in the higher educational groups (10-12%). The percentage of women having perfect response concordance between ACASI and interviewer modes increased significantly with education (64%, 81%, and 84% respectively; P(trend) < 0.001). CONCLUSIONS: Use of ACASI may be more feasible in Zimbabwe and other developing countries than was originally thought, but ACASI programs should continue to be improved and tested in various countries and population groups.

Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women.

OBJECTIVES: Lesions on the vaginal and cervical mucosa may facilitate transmission of HIV and other sexually transmitted diseases (STDs). We evaluated the relationship between intravaginal practices and the presence of colposcopic lesions in Zimbabwean women. METHODS: Users and nonusers of intravaginal practices were seen at enrollment, and at 1 and 6 months. Interviewing, counseling, and pelvic and colposcopic examinations were performed at each study visit. Specimens were collected at enrollment and 6 months. RESULTS: Colposcopic lesions were found at least once in 83% of the participants (n = 162), and in 66% of all exams (n = 430). Most lesions were classified as related to infection with human Papillomavirus (HPV) (58%) or another pathogen (20%), but 11% of lesions could have been caused by intravaginal practices (signal lesions). Intravaginal practices were not associated with an increased incidence in signal lesions (95 and 124 lesions per 100 person-years of follow-up for users and nonusers respectively; p = .290), nor with the presence of signal lesions in multivariate baseline (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.37-4.72; p = .666) and six month transition models (OR, 1.67; 95% CI, 0.59-4.70; p = .333). CONCLUSIONS: No associations between intravaginal practices and colposcopic lesions were found in this study. However, the potential effect of intravaginal practices on the cervical and vaginal mucosa, and on subsequent HIV and STD transmission, warrants further study. The usefulness of colposcopy as a research tool in areas with high prevalences of HIV and HPV is questioned.

Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women.

One hundred sixty-nine Zimbabwean women were studied to determine whether the use of intravaginal practices (cleaning with the fingers, wiping the vagina, and inserting traditional substances) are associated with disturbances of vaginal flora and acquisition of sexually transmitted diseases (STDs). Subjects were interviewed and received counseling and a pelvic examination at enrollment, 1 month, and 6 months, and vaginal specimens were collected at enrollment and at 6 months. Users were more likely than nonusers to have vaginal flora disturbances but were not more likely to acquire an STD (relative risk [RR], 2.15; P=.188). Certain vaginal flora disturbances were associated with increased STD incidence and HIV prevalence. The absence of lactobacilli from the vaginal flora was associated with being positive for human immunodeficiency virus in baseline (odds ratio [OR], 0.24; P=.001) and 6-month transition multivariate models (OR, 0.39; P=.025). The presence of clue cells at baseline was associated with a higher incidence of STDs (RR, 1. 94; P=.025).

Risk factors for HIV infection at enrollment in an urban male factory cohort in Harare, Zimbabwe.

Between March 1993 and March 1995, volunteers at 40 Harare factories were interviewed regarding sociodemographic characteristics and behavior; HIV serostatus was also determined. Among 2,691 men enrolled, HIV prevalence was 19.4%. Prevalence rose 2-fold with each year of age in young men (< 23 years). In a multivariate logistic model that included sociodemographic and behavioral variables, compared with those between 25 and 44 years, both younger men (OR = 0.51) and older men (OR = 0.49) were less likely to be HIV positive. In addition, marriage (OR = 2.01), history of sexually transmitted disease (STD) (genital ulcer, OR = 4.93, urethral discharge OR = 1.75), multiple partners (OR = 1.58), cash payment for sex (OR = 2.55) and condom use (OR = 1.35) were all independent risk factors for HIV infection. Home ownership conferred lower risk. Self-reported condom use was seen as a marker of correct personal risk assessment men who used condoms reported more risk behavior and had a higher prevalence of HIV, either because condom use was not consistent or because infection occurred prior to adoption of condoms. This study confirms established risk factors in a general population sample not selected for high risk of HIV infection. It suggests rapid acquisition of infection among young men and the importance of marriage (and separation of spouses) as correlates of HIV infection.