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

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

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

Vaginal Practices of HIV-Negative Zimbabwean Women

Background. Vaginal practices (VPs) may increase HIV risk by injuring vaginal epithelium or by increasing risk of bacterial vaginosis, an established risk factor for HIV. Methods. HIV-negative Zimbabwean women (n = 2,185) participating in a prospective study on hormonal contraception and HIV risk completed an ancillary questionnaire capturing detailed VP data at quarterly followup visits for two years. Results. Most participants (84%) reported ever cleansing inside the vagina, and at 40% of visits women reported drying the vagina using cloth or paper. Vaginal tightening using cloth/cotton wool, lemon juice, traditional herbs/powders, or other products was reported at 4% of visits. Women with ≥15 unprotected sex acts monthly had higher odds of cleansing (adjusted odds ratio (aOR): 1.17, 95% CI: 1.04–1.32). Women with sexually transmitted infections had higher odds of tightening (aOR: 1.42, 95% CI: 1.08–1.86). Conclusion. Because certain vaginal practices were associated with other HIV risk factors, synergism between VPs and other risk factors should be explored

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

Time is of the essence: impact of delays on effectiveness of contact tracing for COVID-19, a modelling study

Summary Background With confirmed cases of COVID-19 declining in many countries, lockdown measures are gradually being lifted. However, even if most social distancing measures are continued, other public health measures will be needed to control the epidemic. Contact tracing via conventional methods or mobile app technology is central to control strategies during deescalation of social distancing. We aimed to identify key factors for a contact tracing strategy (CTS) to be successful. Methods We evaluated the impact of timeliness and completeness in various steps of a CTS using a stochastic mathematical model with explicit time delays between time of infection and symptom onset, and between symptom onset, diagnosis by testing, and isolation (testing delay). The model also includes tracing of close contacts (e.g. household members) and casual contacts, followed by testing regardless of symptoms and isolation if positive, with different delays (tracing delay) and coverages (tracing coverage). We computed effective reproduction numbers of a CTS (R cts ) for a population with social distancing measures and various scenarios for isolation of index cases and tracing and quarantine of its contacts. Findings For the best-case scenario (testing and tracing delays of 0 days and tracing coverage of 80%), and assuming that around 40% of transmission occur before symptom onset, the model predicts that the effective reproduction number of 1.2 (with social distancing only) will be reduced to 0.8 by adding contact tracing. A testing delay of 2 days requires tracing delay to be at most 1 day, or tracing coverage to be at least 80% to keep R cts below 1. With a testing/isolation delay of 3 days, even the most efficient CTS cannot reach R cts values below 1. The effect of minimizing tracing delay (e.g., with app-based technology) declines with decreasing coverage of app use, but app-based tracing alone remains more effective than conventional tracing alone even with 20% coverage. The proportion of transmissions per index case that can be prevented depends on testing and tracing delays, and ranges from up to 80% in the best-case scenario (testing and tracing delays of 0 days) to 42% with a 3-day testing delay and 18% with a 5-day testing delay. Interpretation In our model, minimizing testing delay had the largest impact on reducing onward transmissions. Optimizing testing and tracing coverage and minimizing tracing delays, for instance with app-based technology, further enhanced CTS effectiveness, with a potential to prevent up to 80% of all transmissions. Access to testing should therefore be optimized, and mobile app technology may reduce delays in the CTS process and optimize contact tracing coverage. Research in context Evidence before this study We searched PubMed, bioRxiv, and medRxiv for articles published in English from January 1, 2020, to June 20, 2020, with the following keywords: (“2019-nCoV” OR “novel coronavirus” OR “COVID-19” OR “SARS-CoV-2”) AND “contact tracing” AND “model*”. Population-level modelling studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suggested that isolation and tracing alone might not be sufficient to control outbreaks and additional measures might be required. However, few studies have focused on the effects of lifting individual measures once the first wave of the epidemic has been controlled. Lifting measures must be accompanied by effective contact tracing strategies (CTS) in order to keep the effective reproduction number below 1. A detailed analysis, with special emphasis on the effects of time delays in testing of index patients and tracing of contacts, has not been done. Added value of this study We performed a systematic analysis of the various steps required in the process of testing and diagnosing an index case as well as tracing and isolating possible secondary cases of the index case. We then used a stochastic transmission model which makes a distinction between close contacts (e.g. household members) and casual contacts to assess which steps and (possible) delays are crucial in determining the effectiveness of CTS. We evaluated how delays and the level of contact tracing coverage influence the effective reproduction number, and how fast CTS needs to be to keep the reproduction number below 1. We also analyzed what proportion of onward transmission can be prevented for short delays and high contact tracing coverage. Assuming that around 40% of transmission occurs before symptom onset, we found that keeping the time between symptom onset and testing and isolation of an index case short (Implications of all the available evidence Our analyses highlight that CTS will only contribute to containment of COVID-19 if it can be organised in a way that time delays in the process from symptom onset to isolation of the index case and his/her contacts are very short. The process of conventional contact tracing should be reviewed and streamlined, while mobile app technology may offer a tool for gaining speed in the process. Reducing delay in testing subjects for SARS-CoV-2 should be a key objective of CTS