Bacterial vaginosis-associated bacteria in cisgender men who have sex with women: prevalence, association with non-gonococcal urethritis and natural history.

OBJECTIVES: Bacterial vaginosis-associated bacterium 2 (BVAB2), Mageeibacillus indolicus and Sneathia spp are highly predictive of bacterial vaginosis (BV) in cisgender women. They have been associated with non-gonococcal urethritis (NGU) in cisgender men in some but not all populations. We evaluated this association in a cross-sectional study of cisgender men who have sex with women only (MSW). METHODS: MSW without gonorrhoea attending a sexual health clinic (SHC) from 2014 to 2018 completed a computer-assisted self-interview, clinical interview and examination. NGU was defined as ≥5 polymorphonuclear leucocytes/high-power field in urethral exudates plus either urethral symptoms or visible discharge. Urine was tested for Chlamydia trachomatis and Mycoplasma genitalium using Aptima (Hologic) and for BVAB2, M. indolicus, Sneathia spp, Trichomonas vaginalis, Ureaplasma urealyticum, Haemophilus influenzae, herpes simplex virus and adenovirus using quantitative PCR. RESULTS: Of 317 MSW age 17-71, 67 (21.1%) had Sneathia spp, 36 (11.4%) had BVAB2, and 17 (5.4%) had M. indolicus at enrolment. Having ≥3 partners in the past 2 months was the only characteristic that was more common among MSW with than those without these bacteria (BVAB2: 47% vs 23%, M. indolicus: 53% vs 24%, Sneathia spp: 42% vs 22%; p≤0.03 for all). One-hundred seventeen men (37%) were diagnosed with NGU at enrolment. There was no significant association of BVAB2, M. indolicus or Sneathia spp with NGU (adjusted OR=0.59, 95% CI 0.14 to 2.43; aOR=3.40, 95% CI 0.68 to 17.06; aOR=0.46, 95% CI 0.16 to 1.27). Of 109 MSW with monthly samples, 34 (31.2%) had one of the bacteria at one or more follow-up visits, 22 of which were co-colonised with >1. Median persistence over 6 months did not differ significantly (BVAB2=30.5 days, IQR=28-87; M. indolicus=87 days, IQR=60-126; Sneathia spp=70 days, IQR=30-135; p≥0.20 for each comparison). CONCLUSIONS: Neither BVAB2, M. indolicus nor Sneathia spp were associated with increased risk of prevalent NGU in MSW attending an SHC.

Epidemiologic Evidence on the Role of Lactobacillus iners in Sexually Transmitted Infections and Bacterial Vaginosis: A Series of Systematic Reviews and Meta-Analyses.

ABSTRACT: Although Lactobacillus crispatus -dominated vaginal microbiotas are thought to protect against bacterial vaginosis (BV) and sexually transmitted infections, the role of Lactobacillus iners -dominated microbiotas is less clear. To better understand the impact of L. iners on common cervicovaginal infections, we conducted systematic reviews of the associations between L. iners compared with L. crispatus and 8 outcomes: Chlamydia trachomatis (Ct), BV, human papillomavirus, cervical dysplasia, human immunodeficiency virus, genital herpes, Trichomonas vaginalis , and Neisseria gonorrhoeae . On April 30, 2021, we searched PubMed, Embase, Cochrane Library, and Web of Science for epidemiologic studies of reproductive-age, nonpregnant, cisgender women that used marker gene sequencing to characterize vaginal microbiota composition and presented an effect estimate for the association between L. iners , compared with L. crispatus , and outcomes of interest. For outcomes with ≥3 eligible results presenting the same form of effect estimate, we conducted random-effects meta-analysis. The review protocol was registered prospectively (PROSPERO CRD42020214775). Six Ct studies were included in meta-analysis, which showed L. iners -dominated microbiotas were associated with 3.4-fold higher odds of Ct compared with L. crispatus -dominated microbiotas (95% confidence interval, 2.1-5.4). Three BV studies were included in meta-analysis, which indicated L. iners -dominated microbiotas were associated with 2.1-fold higher prevalence of BV compared with L. crispatus -dominated microbiotas (95% confidence interval, 0.9-4.9). Evidence was too sparse to perform meta-analysis for the remaining outcomes. L. iners -dominated vaginal microbiotas may be suboptimal compared with L. crispatus -dominated microbiotas for BV and Ct. These reviews highlight evidence gaps regarding the remaining outcomes and opportunities to improve epidemiologic rigor in vaginal microbiome science.

Differences in influenza vaccination by gender identity and state-level gender equity policies: Behavioral Risk Factor Surveillance System, 2015-2019.

BACKGROUND: It is estimated that there are one million transgender and over 340,000 gender non-conforming people in the United States, many of whom face significant health disparities including access to healthcare. Although previous studies have reported greater vaccine uptake in women compared to men, national-level estimates of influenza vaccine uptake among transgender and non-binary people are unknown. This study aims to characterize differences in influenza vaccine uptake by gender identity and examine associations between vaccination status and state-level gender equity policies. METHODS: We used cross-sectional data from adults participating in the 2015-2019 United States Behavioral Risk Factors Surveillance System surveys. Weighted prevalence differences (PDs) and associated confidence intervals (CIs) of being unvaccinated against influenza by self-reported gender identity were estimated using generalized linear regression models. RESULTS: Compared to cisgender women (unvaccinated prevalence = 57.3%), the prevalence of being unvaccinated was significantly higher among cisgender men (64.4%; PD = 7.0 per 100, 95% CI: 6.7-7.4), transgender women (65.4%; PD = 8.1 per 100, 95% CI 4.0-12.2), transgender men (64.6%; PD = 7.3 per 100, 95% CI: 2.7-11.8), and gender non-conforming individuals (64.6%; PD = 7.2 per 100, 95% CI: 1.3-13.2). This pattern was similar among individuals living in states with protective versus restrictive gender equity policies. CONCLUSIONS: Our results identified a disparity in influenza vaccine uptake among individuals across the gender spectrum. To improve vaccine equity, future research should explore barriers to and facilitators of vaccine uptake by gender identity, which could inform policies and health promotion interventions to improve uptake co-designed and implemented with the transgender and non-binary communities.

Acceptability and Use of the Dapivirine Vaginal Ring and Daily Oral Pre-exposure Prophylaxis (PrEP) During Breastfeeding in South Africa, Malawi, Zimbabwe, and Uganda.

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants' understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products.

Intimate Partner Violence and Engagement in the HIV Care Continuum among Women in Sub-Saharan Africa: A Prospective Cohort Study.

Research suggests that women's experience of intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV (WLHIV) in Malawi, South Africa, Uganda, and Zimbabwe. At enrollment, 15% of the 351 participants self-reported physical IPV. IPV experience was not associated with time to first engagement in HIV care or the proportion virally suppressed after 6 months on ART. Women reporting physical IPV were less likely to initiate ART within 6 months of becoming eligible (adjusted RR 0.74, 95% CI 0.53-1.03). IPV screening is critical to identify survivors and link them to appropriate services. However, addressing IPV may not increase engagement in HIV care or viral load suppression among WLHIV in sub-Saharan Africa.

A Novel Curriculum Review Process for Initiating the Incorporation of Antiracist Principles Into Epidemiology Course Work.

There is growing acknowledgement of the legacy of White supremacy and racism in the discipline of epidemiology. Our department in the University of Washington School of Public Health undertook a systematic effort to begin addressing institutionalized racism and inclusive teaching in our courses. In July 2020, we introduced a new tool (the "Course Development Plan" (CDP)) to advance our curriculum. The CDP includes 2 components: 1) a guideline document that provides strategies on how to modify curricula and classroom teaching to incorporate antiracism and principles of equity, diversity, and inclusion (EDI); and 2) a structured worksheet for instructors to share EDI and antiracism practices they already incorporate and practices they plan to incorporate into their classes. Worksheets for each class are submitted prior to the beginning of the quarter and are reviewed by a peer faculty member and at least 1 epidemiology student; reviewers provide written feedback on the CDP worksheet. Further evaluation to assess the impact of the CDP process on classroom climate is ongoing. In this commentary, we discuss our department's efforts, the challenges we faced, and our hopes for next steps.

Feasibility of community at-home dried blood spot collection combined with pooled reverse transcription PCR as a viable and convenient method for malaria epidemiology studies.

BACKGROUND: Many Plasmodium infections in endemic regions exist at densities below the limit of detection of standard diagnostic tools. These infections threaten control efforts and may impact vaccine and therapeutic drug studies. Simple, cost-effective methods are needed to study the natural history of asymptomatic submicroscopic parasitaemia. Self-collected dried blood spots (DBS) analysed using pooled and individual quantitative reverse transcription polymerase chain reaction (qRT-PCR) provide such a solution. Here, the feasibility and acceptability of daily at-home DBS collections for qRT-PCR was studied to better understand low-density infections. METHODS: Rapid diagnostic test (RDT)-negative individuals in Katakwi District, northeastern Uganda, were recruited between April and May 2021. Venous blood samples and clinic-collected DBS were taken at enrollment and at four weekly clinic visits. Participants were trained in DBS collection and asked to collect six DBS weekly between clinic visits. Opinions about the collection process were solicited using daily Diary Cards and a Likert scale survey at the final study visit. Venous blood and DBS were analysed by Plasmodium 18S rRNA qRT-PCR. The number of participants completing the study, total DBS collected, and opinions of the process were analysed to determine compliance and acceptability. The human internal control mRNA and Plasmodium 18S rRNA were evaluated for at-home vs. clinic-collected DBS and venous blood to assess quality and accuracy of at-home collected samples. RESULTS: One-hundred two adults and 29 children were enrolled, and 95 and 26 completed the study, respectively. Three individuals withdrew due to pain or inconvenience of procedures. Overall, 96% of participants collected ≥ 16 of 24 at-home DBS, and 87% of DBS contained ≥ 40 µL of blood. The procedure was well tolerated and viewed favourably by participants. At-home collected DBS were acceptable for qRT-PCR and showed less than a one qRT-PCR cycle threshold shift in the human control mRNA compared to clinic-collected DBS. Correlation between Plasmodium falciparum 18S rRNA from paired whole blood and DBS was high (R = 0.93). CONCLUSIONS: At-home DBS collection is a feasible, acceptable, and robust method to obtain blood to evaluate the natural history of low-density Plasmodium infections by qRT-PCR.

Association Between Vaginal Bacterial Microbiota and Vaginal Yeast Colonization.

BACKGROUND: Vaginal yeast is frequently found with Lactobacillus-dominant microbiota. The relationship between vaginal yeast and other bacteria has not been well characterized. METHODS: These analyses utilized data from the Preventing Vaginal Infections trial. Relative abundance of vaginal bacteria from 16S ribosomal ribonucleic acid gene amplicon sequencing and quantities of 10 vaginal bacteria using taxon-directed polymerase chain reaction assays were compared at visits with and without detection of yeast on microscopy, culture, or both. RESULTS: Higher relative abundances of Megasphaera species type 1 (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.52-0.95), Megasphaera species type 2 (RR, 0.81; 95% CI, 0.67-0.98), and Mageeibacillus indolicus (RR, 0.46; 95% CI, 0.25-0.83) were associated with lower risk of detecting yeast. In contrast, higher relative abundances of Bifidobacterium bifidum, Aerococcus christensenii, Lactobacillus mucosae, Streptococcus equinus/infantarius/lutentiensis, Prevotella bivia, Dialister propionicifaciens, and Lactobacillus crispatus/helveticus were associated with yeast detection. Taxon-directed assays confirmed that increasing quantities of both Megasphaera species and M indolicus were associated with lower risk of detecting yeast, whereas increasing quantities of L crispatus were associated with higher risk of detecting yeast. CONCLUSIONS: Despite an analysis that examined associations between multiple vaginal bacteria and the presence of yeast, only a small number of vaginal bacteria were strongly and significantly associated with the presence or absence of yeast.

Genetic Variation in Toll-Like Receptor 5 and Colonization with Flagellated Bacterial Vaginosis-Associated Bacteria.

Bacterial vaginosis (BV) is a vaginal dysbiotic condition linked to negative gynecological and reproductive sequelae. Flagellated bacteria have been identified in women with BV, including Mobiluncus spp. and BV-associated bacterium-1 (BVAB1), an uncultivated, putatively flagellated species. The host response to flagellin mediated through Toll-like receptor 5 (TLR5) has not been explored in BV. Using independent discovery and validation cohorts, we examined the hypothesis that TLR5 deficiency-defined by a dominant negative stop codon polymorphism, rs5744168-is associated with an increased risk for BV and increased colonization with flagellated bacteria associated with BV (BVAB1, Mobiluncus curtisii, and Mobiluncus mulieris). TLR5 deficiency was not associated with BV status, and TLR5-deficient women had decreased colonization with BVAB1 in both cohorts. We stimulated HEK-hTLR5-overexpressing NF-κB reporter cells with whole, heat-killed M. mulieris or M. curtisii and with partially purified flagellin from these species; as BVAB1 is uncultivated, we used cervicovaginal lavage (CVL) fluid supernatant from women colonized with BVAB1 for stimulation. While heat-killed M. mulieris and CVL fluid from women colonized with BVAB1 stimulate a TLR5-mediated response, heat-killed M. curtisii did not. In contrast, partially purified flagellin from both Mobiluncus species stimulated a TLR5-mediated response in vitro We observed no correlation between vaginal interleukin 8 (IL-8) and flagellated BVAB concentrations among TLR5-sufficient women. Interspecies variation in accessibility of flagellin recognition domains may be responsible for these observations, as reflected in the potentially novel flagellin products encoded by Mobiluncus species versus those encoded by BVAB1.

Elevated Risk of Bacterial Vaginosis Among Users of the Copper Intrauterine Device: A Prospective Longitudinal Cohort Study.

BACKGROUND: Limited evidence suggests that the nonhormonal contraceptive copper intrauterine device (Cu-IUD) may increase bacterial vaginosis (BV) risk, possibly due to increased volume and duration of menses, a common side effect of Cu-IUD use. Although increases in bleeding typically resolve within 6-12 months following initiation, evaluations of the association between Cu-IUD and BV have not included more than 6 months of follow-up. METHODS: This secondary analysis of a human immunodeficiency virus type 1 prevention trial included 2585 African women ages 18-45 followed for up to 33 months. Women reported contraceptive use each month. BV was evaluated by Nugent score in 6-monthly intervals and, if clinically indicated, by Amsel criteria. Andersen-Gill proportional hazards models were used to (1) evaluate BV risk among Cu-IUD users relative to women using no/another nonhormonal contraceptive and (2) test changes in BV frequency before, while using, and following Cu-IUD discontinuation. RESULTS: BV frequency was highest among Cu-IUD users at 153.6 episodes per 100 person-years (95% confidence interval [CI]: 145.2, 162.4). In adjusted models, Cu-IUD users experienced 1.28-fold (95% CI: 1.12, 1.46) higher BV risk relative to women using no/another nonhormonal contraception. Compared to the 6 months prior to initiation, BV risk was 1.52-fold (95% CI: 1.16, 2.00) higher in the first 6 months of Cu-IUD use and remained elevated over 18 months of use (P < .05). Among women who discontinued Cu-IUD, BV frequency was similar to pre-initiation rates within 1 year. CONCLUSIONS: Cu-IUD users experienced elevated BV risk that persisted throughout use. Women and their providers may wish to consider BV risk when discussing contraceptive options.

Vaginal Bacteria and Risk of Incident and Persistent Infection With High-Risk Subtypes of Human Papillomavirus: A Cohort Study Among Kenyan Women.

BACKGROUND: Bacterial vaginosis (BV) is associated with an increased risk of high-risk human papillomavirus (hrHPV), whereas Lactobacillus-dominated vaginal microbiotas are associated with reduced burden of hrHPV. Few epidemiologic studies have prospectively investigated the relationships between vaginal bacteria and hrHPV, particularly among women from countries in Africa. METHODS: We conducted a prospective cohort study nested within the Preventing Vaginal Infections trial to evaluate associations between vaginal bacteria and hrHPV incidence and persistence. Sexually active, HIV-seronegative women aged 18 to 45 years who had a vaginal infection at screening were eligible to enroll. Analyses were restricted to participants enrolled in Kenya and randomized to placebo. At enrollment and months 2, 4, 6, 8, 10, and 12, hrHPV testing, quantitative polymerase chain reaction (measuring taxon quantity per swab), and 16S rRNA gene amplicon sequencing of the vaginal microbiota were performed. Generalized estimating equations multinomial logistic regression models were fit to evaluate associations between vaginal bacteria and incident and persistent hrHPV. RESULTS: Eighty-four participants were included in this analysis. Higher concentrations of Lactobacillus crispatus were inversely associated with persistent hrHPV detection. Specifically, 1 tertile higher L. crispatus concentration was associated with 50% reduced odds of persistent hrHPV detection (odds ratio, 0.50; 95% confidence interval, 0.29-0.85). CONCLUSIONS: This study is consistent with reports that vaginal L. crispatus is associated with reduced susceptibility to hrHPV persistence. Evidence from in vitro studies provides insight into potential mechanisms by which L. crispatus may mediate hrHPV risk. Future studies should further explore in vivo mechanisms that may drive this relationship and opportunities for intervention.

Clustering of subpatent infections in households with asymptomatic rapid diagnostic test-positive cases in Bioko Island, Equatorial Guinea independent of travel to regions of higher malaria endemicity: a cross-sectional study.

BACKGROUND: Prevalence of falciparum malaria on Bioko Island remains high despite sustained, intensive control. Progress may be hindered by high proportions of subpatent infections that are not detected by rapid diagnostic tests (RDT) but contribute to onward transmission, and by imported infections. Better understanding of the relationship between subpatent infections and RDT-detected infections, and whether this relationship is different from imported versus locally acquired infections, is imperative to better understand the sources of infection and mechanisms of transmission to tailor more effective interventions. METHODS: Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed on a sub-set of samples from the 2015 Malaria Indicator Survey to identify subpatent infections. Households with RDT(+) individuals were matched 1:4 with households with no RDT(+) individuals. The association between living in a household with an RDT(+) individual and having a subpatent infection was evaluated using multivariate hierarchical logistic regression models with inverse probability weights for selection. To evaluate possible modification of the association by potential importation of the RDT(+) case, the analysis was repeated among strata of matched sets based on the reported eight-week travel history of the RDT(+) individual(s). RESULTS: There were 142 subpatent infections detected in 1,400 individuals (10.0%). The prevalence of subpatent infections was higher in households with versus without an RDT(+) individual (15.0 vs 9.1%). The adjusted prevalence odds of subpatent infection were 2.59-fold greater (95% CI: 1.31, 5.09) for those in a household with an RDT(+) individual compared to individuals in a household without RDT(+) individuals. When stratifying by travel history of the RDT(+) individual, the association between subpatent infections and RDT(+) infections was stronger in the strata in which the RDT(+) individual(s) had not recently travelled (adjusted prevalence odds ratio (aPOR) 2.95; 95% CI:1.17, 7.41), and attenuated in the strata in which recent travel was reported (aPOR 1.76; 95% CI: 0.54, 5.67). CONCLUSIONS: There is clustering of subpatent infections around RDT(+) individual(s) when both imported and local infection are suspected. Future control strategies that aim to treat whole households in which an RDT(+) individual is found may target a substantial portion of infections that would otherwise not be detected.

Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring.

BACKGROUND: A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). METHODS: HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network-020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. RESULTS: Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). CONCLUSIONS: The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. CLINICAL TRIALS REGISTRATION: NCT016170096 and NCT00514098.

Association between vaginal washing and detection of Lactobacillus by culture and quantitative PCR in HIV-seronegative Kenyan women: a cross-sectional analysis.

OBJECTIVES: Vaginal washing has been associated with reductions in cultivable Lactobacillus and an increased risk of both bacterial vaginosis (BV) and HIV infection. The effect of vaginal washing on the quantity of individual Lactobacillus species is not well characterised. This analysis tested the hypothesis that vaginal washing would be associated with a lower likelihood of Lactobacillus spp. detected by both culture and quantitative PCR (qPCR). METHODS: We conducted a cross-sectional study of 272 HIV-seronegative women enrolled in an open-cohort study in Mombasa, Kenya. Vaginal washing and sexual risk behaviours were assessed using face-to-face interviews. Vaginal Lactobacillus spp. were detected using cultivation and PCR methods, with L. crispatus, L. jensenii and L. iners concentrations measured using qPCR assays targeting the 16S rRNA gene. Poisson regression with robust SEs was used to assess associations between vaginal washing and Lactobacillus detection by culture and qPCR. RESULTS: Eighty percent (n=217) of participants reported vaginal washing in the prior week. One-fifth (n=58) of participants had BV by Nugent score. In unadjusted analysis, vaginal washing was associated with a 45% decreased likelihood of Lactobacillus spp. detection by culture (prevalence ratio (PR): 0.55, 95% CI 0.37 to 0.82). Adjusting for age and condomless sex in the prior week did not change the magnitude of the association (adjusted PR (aPR): 0.56, 95% CI (0.37 to 0.85). Vaginal washing was associated with approximately a 40% reduction in L. crispatus detection (aPR: 0.57, 95% CI 0.36 to 0.92), but was not significantly associated with L. jensenii (aPR: 0.68, 95% CI 0.42 to 1.09) or L. iners detection (aPR: 1.03, 95% CI 0.92 to 1.15). CONCLUSIONS: Vaginal washing in the prior week was associated with a significantly reduced likelihood of detecting cultivable Lactobacillus and L. crispatus by qPCR. Given associations between Lactobacillus detection and improved reproductive health outcomes, these results provide motivation for additional study of vaginal washing cessation interventions to improve vaginal health.

High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Bacterial vaginosis (BV) is the most common vaginal infection among women of reproductive age and is associated with important adverse health outcomes. Estimates of the burden of BV and associated costs are needed to inform research priorities. METHODS: We conducted a systematic review and meta-analysis of global BV prevalence among reproductive-aged women in the general population. We searched PubMed and Embase and used random effects models to estimate BV prevalence by global regions. We estimated the direct medical costs of treating symptomatic BV. Assuming a causal relationship, we also estimated the potential costs of BV-associated preterm births and human immunodeficiency virus cases in the United States. RESULTS: General population prevalence of BV is high globally, ranging from 23% to 29% across regions (Europe and Central Asia, 23%; East Asia and Pacific, 24%; Latin America and Caribbean, 24%; Middle East and North Africa, 25%; sub-Saharan Africa, 25%; North America, 27%; South Asia, 29%). Within North America, black and Hispanic women have significantly higher (33% and 31%, respectively) prevalence compared with other racial groups (white, 23%; Asian, 11%; P < 0.01). The estimated annual global economic burden of treating symptomatic BV is US $4.8 (95% confidence interval, $3.7-$6.1) billion. The US economic burden of BV is nearly tripled when including costs of BV-associated preterm births and human immunodeficiency virus cases. CONCLUSIONS: The BV prevalence is high globally, with a concomitant high economic burden and marked racial disparities in prevalence. Research to determine the etiology of BV and corresponding prevention and sustainable treatment strategies are urgently needed to reduce the burden of BV among women. Additionally, the exceptionally high cost of BV-associated sequelae highlights the need for research to understand potential causal linkages between BV and adverse health outcomes.

Complex decisions: correlates of injectable contraceptive discontinuation following HIV-1 seroconversion in an HIV prevention trial.

Contraceptive adherence during acute and recent HIV-1 infection is important to maternal and child health given the elevated risk of vertical HIV-1 transmission and additional complications of pregnancy. Injectable contraception (IC) is the most common non-barrier modern contraception method used in sub-Saharan Africa (SSA). Adherence to IC after HIV-1 seroconversion is not well understood. We examined factors associated with IC discontinuation among women in SSA diagnosed with HIV-1 infection while participating in a clinical trial of biomedical HIV-1 prevention. After diagnosis with HIV-1 infection in the VOICE trial, 255 women from South Africa, Uganda, and Zimbabwe enrolled in a longitudinal observational study (MTN-015). Contraceptive method was assessed at MTN-015 baseline and at 3, 12, and 24 months post-seroconversion. Correlates of IC discontinuation were examined by Cox proportional hazard modeling. IC use was reported at baseline by 78% of women enrolled (198/255), of which 92% (182/198) completed at least one follow-up visit. Two-thirds of women (66%, 121/182) continued on IC during the follow-up period (median 24 months). Lower rates of IC discontinuation were observed in women who reported having had at least one child (HR 0.39, 95% CI 0.20-0.82) or earning a personal income (HR 0.51, 95% CI 0.30-0.87) at baseline. These findings suggest that many women with HIV-1 infection face complex decision-making regarding family planning in the years that follow seroconversion and highlight that some women may discontinue IC use despite on-site provision of family planning services. Understanding the broader context of family planning choices in recently seroconverted women may be key to more effective linkages between family planning services and HIV-1 testing and care.

Mycoplasma genitalium Infection in Kenyan and US Women.

BACKGROUND: Little is known about the natural history of Mycoplasma genitalium (MG) infection in women. We retrospectively tested archived vaginal fluid samples to assess MG prevalence, incidence, persistence, recurrence and antimicrobial resistance markers among women participating in the Preventing Vaginal Infections trial, a randomized trial of monthly presumptive treatment to reduce vaginal infections. METHODS: High-risk, nonpregnant, HIV-negative women aged 18 to 45 years from Kenya and the United States were randomized to receive metronidazole 750 mg + miconazole 200 mg intravaginal suppositories or placebo for 5 consecutive nights each month for 12 months. Clinician-collected swabs containing cervicovaginal fluid were tested for MG using Hologic nucleic acid amplification testing at enrollment and every other month thereafter. Specimens that were MG+ underwent additional testing for macrolide resistance-mediating mutations by DNA sequencing. RESULTS: Of 234 women enrolled, 221 had available specimens and 25 (11.3%) had MG at enrollment. Among 196 women without MG at enrollment, there were 52 incident MG infections (incidence, 33.4 per 100 person-years). Smoking was independently associated with incident MG infection (adjusted hazard ratio, 3.02; 95% confidence interval, 1.32-6.93), and age less than 25 years trended toward an association (adjusted hazard ratio, 1.70; 95% confidence interval, 0.95-3.06). Median time to clearance of incident MG infections was 1.5 months (interquartile range, 1.4-3.0 months). Of the 120 MG+ specimens, 16 specimens from 15 different women were macrolide resistance-mediating mutation positive (13.3%), with no difference by country. CONCLUSIONS: M. genitalium infection is common among sexually active women in Kenya and the Southern United States. Given associations between MG and adverse reproductive health outcomes, this high burden of MG in reproductive-aged women could contribute to substantial morbidity.

Impact of Periodic Presumptive Treatment for Bacterial Vaginosis on the Vaginal Microbiome among Women Participating in the Preventing Vaginal Infections Trial.

Background: Evidence suggests that specific vaginal bacteria associated with bacterial vaginosis (BV) may increase the risk of adverse health outcomes in women. Among women participating in a randomized, double-blinded trial, we assessed the effect of periodic presumptive treatment (PPT) on detection of select vaginal bacteria. Methods: High-risk women from the United States and Kenya with a recent vaginal infection received intravaginal metronidazole 750 mg plus miconazole 200 mg or placebo for 5 consecutive nights each month for 12 months. Vaginal fluid specimens were collected via polyester/polyethylene terephthalate swabs every other month and tested for bacteria, using quantitative polymerase chain reaction (PCR) assays targeting the 16S ribosomal RNA gene. The effect of PPT on bacterium detection was assessed among all participants and stratified by country. Results: Of 234 women enrolled, 221 had specimens available for analysis. The proportion of follow-up visits with detectable quantities was lower in the PPT arm versus the placebo arm for the following bacteria: BVAB1, BVAB2, Atopobium vaginae, Leptotrichia/Sneathia, and Megasphaera. The magnitude of reductions was greater among Kenyan participants as compared to US participants. Conclusions: Use of monthly PPT for 1 year reduced colonization with several bacteria strongly associated with BV. The role of PPT to improve vaginal health should be considered, and efforts to improve the impact of PPT regimens are warranted.

Association of Recent Bacterial Vaginosis With Acquisition of Mycoplasma genitalium.

We assessed the association between recent bacterial vaginosis (BV) and incident Mycoplasma genitalium, a sexually transmitted bacterium associated with adverse female reproductive health outcomes. Female sex workers in Mombasa, Kenya, completed a monthly sexual behavior interview and clinical examination. During February 2005-February 2006, vaginal fluid specimens collected from women every other month were tested for M. genitalium by nucleic acid amplification testing. Vaginal microbiota were assessed monthly and categorized by Nugent score (0-3 = normal microbiota, 4-6 = intermediate microbiota disruption, and 7-10 = BV). A discrete failure time analysis for multiple events using logistic regression was employed to estimate the odds of incident M. genitalium infection at follow-up visits among women with BV (vs. normal microbiota) at the preceding visit. Among the 280 women, 54.3% were positive for human immunodeficiency virus. At baseline, 16.1% had prevalent M. genitalium infection and 40.4% had prevalent BV. There were 59 incident M. genitalium infections among 50 women, for an incidence rate of 34.6 cases per 100 person-years. Following adjustment for age, human immunodeficiency virus status, and time, prior BV was associated with a 3.5-fold increase in odds of incident M. genitalium (adjusted odds ratio = 3.49, 95% confidence interval: 1.86, 6.56). This strong association suggests that BV may enhance susceptibility to M. genitalium infection.