The vaginal microbiome and sexually transmitted infections are interlinked: Consequences for treatment and prevention

In a Perspective for our Collection on STI research, Janneke van de Wijgert discusses the latest on how the vaginal microbiota predisposes women to acquisition of STIs and discusses future potential for clinical intervention

Cultural norms and behavior regarding vaginal lubrication during sex: Implications for the acceptability of vaginal microbicides for the prevention of HIV/STIs

This paper presents the results of an extensive review of the literature pertaining to the relationship between vaginal lubrication and the acceptability of microbicides, spermicides, and male and female condoms. The review highlights the need for research that better elucidates norms, preferences, and practices regarding lubrication during sex within and across countries. The second part of the report presents the results of the first phase of a qualitative study on lubrication during sex showing that diverse personal and cultural factors shape preferences and practices and may ultimately affect the acceptability of microbicides. The immediate challenge is to provide women with an opportunity for empowerment and self-protection by introducing effective microbicides that are both acceptable to and feasible for use by women and men who are vulnerable to HIV/STIs. However, it is difficult to account for a variety of sexual preferences, practices, and personal and social circumstances in the development of a microbicide; ultimately, several different vaginal microbicides in different formulations will likely be needed to provide a full range of options for women and men from diverse settings

Rwanda VMB study

A clinical trial in Kigali, Rwanda, evaluating the effects of oral metronidazole or two different lactobacilli-containing vaginally applied probiotics (Ecologic Femi+ and Gynophilus LP) on the vaginal microbiota by microscopy and sequencing

Evaluation of Lysis Methods for the Extraction of Bacterial DNA for Analysis of the Vaginal Microbiota

BACKGROUND:Recent studies on the vaginal microbiota have employed molecular techniques such as 16S rRNA gene sequencing to describe the bacterial community as a whole. These techniques require the lysis of bacterial cells to release DNA before purification and PCR amplification of the 16S rRNA gene. Currently, methods for the lysis of bacterial cells are not standardised and there is potential for introducing bias into the results if some bacterial species are lysed less efficiently than others. This study aimed to compare the results of vaginal microbiota profiling using four different pretreatment methods for the lysis of bacterial samples (30 min of lysis with lysozyme, 16 hours of lysis with lysozyme, 60 min of lysis with a mixture of lysozyme, mutanolysin and lysostaphin and 30 min of lysis with lysozyme followed by bead beating) prior to chemical and enzyme-based DNA extraction with a commercial kit. RESULTS:After extraction, DNA yield did not significantly differ between methods with the exception of lysis with lysozyme combined with bead beating which produced significantly lower yields when compared to lysis with the enzyme cocktail or 30 min lysis with lysozyme only. However, this did not result in a statistically significant difference in the observed alpha diversity of samples. The beta diversity (Bray-Curtis dissimilarity) between different lysis methods was statistically significantly different, but this difference was small compared to differences between samples, and did not affect the grouping of samples with similar vaginal bacterial community structure by hierarchical clustering. CONCLUSIONS:An understanding of how laboratory methods affect the results of microbiota studies is vital in order to accurately interpret the results and make valid comparisons between studies. Our results indicate that the choice of lysis method does not prevent the detection of effects relating to the type of vaginal bacterial community one of the main outcome measures of epidemiological studies. However, we recommend that the same method is used on all samples within a particular study

HIV/AIDS Prevention Guidance for Reproductive Health Professionals in Developing-Country Settings

While the integration of information, technologies, and services to respond to HIV/AIDS may seem closely related, there are a variety of issues that continue to create obstacles to integration. Among these are the stigmatizing nature of HIV infection and AIDS and discrimination faced by those who are infected or perceived to be infected; sexual practices and identities that remain socially unacceptable; gender roles and relations that make it difficult for women and men to access information, services, and technologies on HIV prevention; reluctance to recognize the special needs of young people; and barriers to service delivery created by broader economic, social, cultural, and political factors. Of concern to reproductive health service providers are the burdens associated with providing additional services and resources needed for facilities, technologies, treatment options, and comprehensive training. This document provides an overview of the issues, challenges, and opportunities around integrating a broad range of HIV/AIDS interventions into existing reproductive and sexual health programs and services, and includes examples of successful interventions

Hormonal contraceptives and the acquisition of sexually transmitted infections: an updated systematic review.

BACKGROUND:Evidence suggests that some forms of hormonal contraception (HC) increase women's risk of non-HIV sexually transmitted infections (STIs), yet evidence has not been reviewed since 2008. We conducted an updated systematic review to incorporate studies published between January 2009 and June 2017 to examine the relationship between HCs and incident and/or recurrent STIs. METHODS:We searched PubMed and EMBASE to identify prospective studies comparing risk of Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Trichomonas vaginalis, between women using HC vs. non-hormonal methods or no methods. We summarize results by type of STI and HC and study quality using an adapted Newcastle-Ottawa Quality Assessment Scale. RESULTS:Thirty articles met the inclusion criteria. Depo-medroxyprogesterone acetate (DMPA) reduces the risk of trichomoniasis (consistent evidence) and may increase the risk of HSV-2 (strong effect, few studies); inconclusive evidence exists for HPV, chlamydia, gonorrhea and syphilis. Data on oral contraceptive pills (OCPs; generally not differentiated whether combined or progestin-only pills) suggest use is associated with a reduced risk of trichomoniasis with inconclusive findings for HSV-2, HPV, chlamydia, gonorrhea, and syphilis. Very few studies included norethisterone enanthate (Net-En) injectable, implants or the levonorgestrel IUD. CONCLUSIONS:DMPA and OCPs reduce the risk of trichomoniasis and DMPA may increase the risk of HSV-2. However, the potential for confounding cannot be ruled out. Future studies should specify the type of injectable or OCP used to increase understanding of biological pathways; more research is needed on implants and hormonal IUDs

The vaginal microbiota: what have we learned after a decade of molecular characterization?

We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A) to determine if consistent molecular vaginal microbiota (VMB) composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization) was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV) is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV), and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB

The significance of Lactobacillus crispatus and L. vaginalis for vaginal health and the negative effect of recent sex: a cross-sectional descriptive study across groups of African women

Background: Women in sub-Saharan Africa are vulnerable to acquiring HIV infection and reproductive tract infections. Bacterial vaginosis (BV), a disruption of the vaginal microbiota, has been shown to be strongly associated with HIV infection. Risk factors related to potentially protective or harmful microbiota species are not known. Methods: We present cross-sectional quantitative polymerase chain reaction data of the Lactobacillus genus, five Lactobacillus species, and three BV-related bacteria (Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia) together with Escherichia coli and Candida albicans in 426 African women across different groups at risk for HIV. We selected a reference group of adult HIV-negative women at average risk for HIV acquisition and compared species variations in subgroups of adolescents, HIV-negative pregnant women, women engaging in traditional vaginal practices, sex workers and a group of HIV-positive women on combination antiretroviral therapy. We explored the associations between presence and quantity of the bacteria with BV by Nugent score, in relation to several factors of known or theoretical importance. Results: The presence of species across Kenyan, South African and Rwandan women was remarkably similar and few differences were seen between the two groups of reference women in Kenya and South Africa. The Rwandan sex workers and HIV-positive women had the highest Gardnerella vaginalis presence (p = 0.006). Pregnant women had a higher Lactobacillus genus mean log (7.01 genome equivalents (geq)/ml) compared to the reference women (6.08 geq/ml). L. vaginalis (43%) was second to L. iners (81.9%) highly present in women with a normal Nugent score. Recent sexual exposure negatively affected the presence of Lactobacillus crispatus (<0.001), L. vaginalis (p = 0.001), and Lactobacillus genus (p < 0.001). Having more than one sexual partner in the last three months was associated with an increased prevalence of Gardnerella vaginalis (p = 0.044) and L. iners (p = 0.001). Conclusions: Although the composition of species across the studied African countries was similar, the presence of protective species i.e. Lactobacillus crispatus and L. vaginalis in women with a normal Nugent score appeared lower compared to non-African studies. Furthermore, Lactobacillus species were negatively affected by sexual behavioural. Strategies to support protective Lactobacillus species are urgently needed

Acceptability and Satisfaction of Contraceptive Vaginal Rings in Clinical Studies: A Systematic Review and Narrative Synthesis.

Introduction: Acceptability of and satisfaction with contraceptive methods are paramount for uptake and continuation. In the current context of multipurpose prevention of pregnancy and sexually transmitted diseases/HIV development, it is critical to have a better understanding of acceptability of and satisfaction with the contraceptive vaginal ring (CVR) including sexual satisfaction. The objective of this study was to review the evidence about acceptability of CVRs and general and sexual satisfaction of users. Methods: We searched PubMed, CINAHL, and Web of Science (until December 31, 2020) and selected original studies documenting actual use of hormonal CVR and explicitly addressing any of the 3 outcomes. Results: Of a total of 1,129 records screened, 46 studies were included. Most studies (n = 43, 93%) were prospective, conducted in high-income settings (n = 35), and reported on NuvaRing® use (n = 31). Overall, 27 (59%) studies included a comparison group, 38 (82%) studies used exclusively quantitative questionnaires, with qualitative only (n = 4, 9%), or mixed methods (n = 4, 9%) studies being less common. Ease of CVR insertion/removal/reinsertion was high in all the settings and improved with time of use, with qualitative studies supporting these findings. When mentioned, ring-related events were associated with discontinuation, and results on continuation of use were mixed. Among NuvaRing® studies, general satisfaction (being satisfied or very satisfied) was between 80 and 90% and tended to mirror continuation. Sexual satisfaction was less commonly reported and results were mixed. Overall, limited information was provided on actual CVR experiences of women (and men) and cultural norms that may affect sexuality and CVR use. Conclusion: Positive aspects of acceptability of and satisfaction with CVRs were reported, but ring-related events and factors, which may affect long-term CVR use, deserve further study. More information is needed on actual experiences of women using CVRs, relationship aspects, male partner opinions, and contextual norms to better understand the acceptability of and satisfaction with CVRs

Can a Topical Microbicide Prevent Rectal HIV Transmission?

Florian Hladik and Charlene Dezzutti discuss a macaque study of whether rectal simian immunodeficiency virus transmission can be prevented by topical pre-exposure application of tenofovir gel