Effectiveness of a Culturally Tailored HIV and Sexually Transmitted Infection Prevention Intervention for Black Women in Community Supervision Programs: A Randomized Clinical Trial.

Importance: Concentrated epidemics of HIV and sexually transmitted infections (STIs) have persisted among Black women in community supervision programs (CSPs) in the United States. Accumulating research has highlighted the effectiveness of culturally tailored HIV/STI interventions for Black women; however, there is a dearth of such interventions for the large number of Black women in CSPs. Objective: To determine the effectiveness of a 5-session culturally tailored group-based intervention (Empowering African-American Women on the Road to Health [E-WORTH]) with individualized computerized modules and streamlined HIV testing in reducing STIs and condomless sex vs a 1-session streamlined HIV testing control condition. Design, Setting, and Participants: This randomized clinical trial was conducted from November 18, 2015, (first recruitment) to August 20, 2019 (last 12-month follow-up). Black women mandated to probation, parole, or alternative-to-incarceration programs in New York City who had a history of drug use were recruited and randomized to receive either E-WORTH or a streamlined HIV testing control condition. Both conditions were delivered by Black female staff at a large CSP. The analysis took an intention-to-treat approach. Intervention: E-WORTH included a 1-hour individual HIV testing and orientation session and 4 weekly 90-minute group sessions. The control condition included one 30-minute session of HIV testing and information. Main Outcomes and Measures: Primary outcomes were incidence of any STI (biologically assayed chlamydia, gonorrhea, and Trichomonas vaginalis) at the 12-month assessment and the number of condomless acts of vaginal or anal intercourse in the past 90 days during the 12-month period. Results: A total of 352 participants who identified as Black or African American were enrolled, including 79 (22.5%) who also identified as Latinx. The mean (SD) age was 32.4 (11.0) years. A total of 172 participants (48.9%) were assigned to the E-WORTH condition, and 180 (51.1%) were assigned to the control condition. Compared with control participants, participants assigned to the E-WORTH condition had 54% lower odds of testing positive for any STI at the 12-month follow-up (odds ratio, 0.46; 95% CI, 0.25-0.88; P = .01) and reported 38% fewer acts of condomless vaginal or anal intercourse during the 12-month period (incidence rate ratio, 0.62; 95% CI, 0.39-0.97; P = .04). Conclusions and Relevance: The magnitudes of effects found across biological and behavioral outcomes in this randomized clinical trial indicate the feasibility and effectiveness of implementing E-WORTH in real-world CSPs. The findings lend further evidence to the promise of culturally tailored HIV/STI interventions for Black women. Trial Registration: ClinicalTrials.gov Identifier: NCT02391233.

Sexually Transmitted Infections in Pregnancy: A Narrative Review of the Global Research Gaps, Challenges, and Opportunities.

BACKGROUND: Sexually transmitted infections (STI), such as chlamydial, gonorrheal, and trichomonal infections, are prevalent in pregnant women in many countries and are widely reported to be associated with increased risk of poor maternal and neonatal outcomes. Syndromic STI management is frequently used in pregnant women in low- and middle-income countries, yet its low specificity and sensitivity lead to both overtreatment and undertreatment. Etiologic screening for chlamydial, gonorrheal, and/or trichomonal infection in all pregnant women combined with targeted treatment might be an effective intervention. However, the evidence base is insufficient to support the development of global recommendations. We aimed to describe key considerations and knowledge gaps regarding chlamydial, gonorrheal, and trichomonal screening during pregnancy to inform future research needed for developing guidelines for low- and middle-income countries. METHODS: We conducted a narrative review based on PubMed and clinical trials registry searches through January 20, 2020, guidelines review, and expert opinion. We summarized our findings using the frameworks adopted by the World Health Organization for guideline development. RESULTS: Adverse maternal-child health outcomes of potential interest are wide-ranging and variably defined. No completed randomized controlled trials on etiologic screening and targeted treatment were identified. Evidence from observational studies was limited, and trials of presumptive STI treatment have shown mixed results. Subgroups that might benefit from specific recommendations were identified. Evidence on harms was limited. Cost-effectiveness was influenced by STI prevalence and availability of testing infrastructure and high-accuracy/low-cost tests. Preliminary data suggested high patient acceptability. DISCUSSION: Preliminary data on harms, acceptability, and feasibility and the availability of emerging test technologies suggest that etiologic STI screening deserves further evaluation as a potential tool to improve maternal and neonatal health outcomes worldwide.

Call to action for health systems integration of point-of-care testing to mitigate the transmission and burden of sexually transmitted infections.

OBJECTIVES: In 2016, WHO estimated 376 million new cases of the four main curable STIs: gonorrhoea, chlamydia, trichomoniasis and syphilis. Further, an estimated 290 million women are infected with human papillomavirus. STIs may lead to severe reproductive health sequelae. Low-income and middle-income countries carry the highest global burden of STIs. A large proportion of urogenital and the vast majority of extragenital non-viral STI cases are asymptomatic. Screening key populations and early and accurate diagnosis are important to provide correct treatment and to control the spread of STIs. This article paints a picture of the state of technology of STI point-of-care testing (POCT) and its implications for health system integration. METHODS: The material for the STI POCT landscape was gathered from publicly available information, published and unpublished reports and prospectuses, and interviews with developers and manufacturers. RESULTS: The development of STI POCT is moving rapidly, and there are much more tests in the pipeline than in 2014, when the first STI POCT landscape analysis was published on the website of WHO. Several of the available tests need to be evaluated independently both in the laboratory and, of particular importance, in different points of care. CONCLUSION: This article reiterates the importance of accurate, rapid and affordable POCT to reach universal health coverage. While highlighting the rapid technical advances in this area, we argue that insufficient attention is being paid to health systems capacity and conditions to ensure the swift and rapid integration of current and future STI POCT. Unless the complexity of health systems, including context, institutions, adoption systems and problem perception, are recognised and mapped, simplistic approaches to policy design and programme implementation will result in poor realisation of intended outcomes and impact.

STI update: Testing, treatment, and emerging threats.

Fast, sensitive molecular diagnostic tests that use urine or self-collected swabs may lead to more screening opportunities and be more acceptable to patients, resulting in faster and more accurate diagnosis and treatment of gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium infection.

Increased intracellular Cl- concentration mediates Trichomonas vaginalis-induced inflammation in the human vaginal epithelium.

Trichomonas vaginalis is a primary urogenital parasite that causes trichomoniasis, a common sexually transmitted disease. As the first line of host defense, vaginal epithelial cells play critical roles in orchestrating vaginal innate immunity and modulate intracellular Cl- homeostasis via the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel that plays positive roles in regulating nuclear factor-κB (NF-κB) signalling. However, the association between T. vaginalis infection and intracellular Cl- disequilibrium remains elusive. This study showed that after T. vaginalis infection, CFTR was markedly down-regulated by cysteine proteases in vaginal epithelial cells. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to NF-κB signalling activation via serum- and glucocorticoid-inducible kinase-1. Moreover, heightened [Cl-]i and activated NF-κB signalling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP through NF-κB-mediated up-regulation of phosphodiesterase 4. The results conclusively revealed that the intracellular Cl- of the human vaginal epithelium could be dynamically modulated by T. vaginalis, which contributed to mediation of epithelial inflammation in the human vagina.

Common Sexually Transmitted Infections in Women.

The spread of sexually transmitted infections (STIs) remains a significant public health issue in the United States. Social, economic, and behavioral implications affecting the spread of STIs have been identified. The most important social factor in the United States is the stigma associated with discussing sex and STI screening. In this article, specific recommendations for women are included regarding screening, diagnosing, and treating common vaginal and cervical infections. Screening women for infections of the vagina and cervix is essential because untreated infections may result in complications that have current and long-term health consequences and impact quality of life.

Advancing prevention of sexually transmitted infections through point-of-care testing: target product profiles and landscape analysis.

OBJECTIVES: Advancing the field of point-of-care testing (POCT) for STIs can rapidly and substantially improve STI control and prevention by providing targeted, essential STI services (case detection and screening). POCT enables definitive diagnosis and appropriate treatment in a single visit and home and community-based testing. METHODS: Since 2014, the WHO Department of Reproductive Health and Research, in collaboration with technical partners, has completed four landscape analyses of promising diagnostics for use at or near the point of patient care to detect syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and the human papillomavirus. The analyses comprised a literature review and interviews. Two International Technical Consultations on STI POCTs (2014 and 2015) resulted in the development of target product profiles (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management, public health and epidemiology participated in the consultations with representation from all WHO regions. RESULTS: The landscape analysis identified diagnostic tests that are either available on the market, to be released in the near future or in the pipeline. The TPPs specify 28 analytical and operational characteristics of POCTs for use in different populations for surveillance, screening and case management. None of the tests that were identified in the landscape analysis met all of the targets of the TPPs. CONCLUSION: More efforts of the global health community are needed to accelerate access to affordable quality-assured STI POCTs, particularly in low- and middle-income countries, by supporting the development of new diagnostic platforms as well as strengthening the validation and implementation of existing diagnostics according to internationally endorsed standards and the best available evidence.

A cross-sectional analysis of Trichomonas vaginalis infection among heterosexual HIV-1 serodiscordant African couples.

OBJECTIVES: Trichomonas vaginalis is the most prevalent curable STI worldwide and has been associated with adverse health outcomes and increased HIV-1 transmission risk. We conducted a cross-sectional analysis among couples to assess how characteristics of both individuals in sexual partnerships are associated with the prevalence of male and female T. vaginalis infection. METHODS: African HIV-1 serodiscordant heterosexual couples were concurrently tested for trichomoniasis at enrolment into two clinical trials. T. vaginalis testing was by nucleic acid amplification or culture methods. Using Poisson regression with robust standard errors, we identified characteristics associated with trichomoniasis. RESULTS: Among 7531 couples tested for trichomoniasis, 981 (13%) couples contained at least one infected partner. The prevalence was 11% (n=857) among women and 4% (n=319) among men, and most infected individuals did not experience signs or symptoms of T. vaginalis. Exploring concordance of T. vaginalis status within sexual partnerships, we observed that 61% (195/319) of T. vaginalis-positive men and 23% (195/857) of T. vaginalis-positive women had a concurrently infected partner. In multivariable analysis, having a T. vaginalis-positive partner was the strongest predictor of infection for women (relative risk (RR) 4.70, 95% CI 4.10 to 5.38) and men (RR 10.09, 95% CI 7.92 to 12.85). For women, having outside sex partners, gonorrhoea, and intermediate or high Nugent scores for bacterial vaginosis were associated with increased risk of trichomoniasis, whereas age 45 years and above, being married, having children and injectable contraceptive use were associated with reduced trichomoniasis risk. Additionally, women whose male partners were circumcised, had more education or earned income had lower risk of trichomoniasis. CONCLUSIONS: We found that within African HIV-1 serodiscordant heterosexual couples, the prevalence of trichomoniasis was high among partners of T. vaginalis-infected individuals, suggesting that partner services could play an important role identifying additional cases and preventing reinfection. Our results also suggest that male circumcision may reduce the risk of male-to-female T. vaginalis transmission.

Multilocus sequence typing of Trichomonas vaginalis clinical samples from Amsterdam, the Netherlands.

OBJECTIVES: In this cross-sectional epidemiological study we aimed to identify molecular profiles for Trichomonas vaginalis and to determine how these molecular profiles were related to patient demographic and clinical characteristics. SETTING: Molecular typing methods previously identified two genetically distinct subpopulations for T. vaginalis; however, few molecular epidemiological studies have been performed. We now increased the sensitivity of a previously described multilocus sequence typing (MLST) tool for T. vaginalis by using nested PCR. This enabled the typing of direct patient samples. PARTICIPANTS: From January to December 2014, we collected all T. vaginalis positive samples as detected by routine laboratory testing. Samples from patients either came from general practitioners offices or from the sexually transmitted infections (STI) clinic in Amsterdam. Epidemiological data for the STI clinic patients were retrieved from electronic patient files. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the success rate of genotyping direct T. vaginalis positive samples. The secondary outcome was the relation between T. vaginalis genotypes and risk factors for STI. RESULTS: All 7 MLST loci were successfully typed for 71/87 clinical samples. The 71 typed samples came from 69 patients, the majority of whom were women (n=62; 90%) and half (n=34; 49%) were STI clinic patients. Samples segregated into a two population structure for T. vaginalis representing genotypes I and II. Genotype I was most common (n=40; 59.7%). STI clinic patients infected with genotype II reported more sexual partners in the preceding 6 months than patients infected with genotype I (p=0.028). No other associations for gender, age, ethnicity, urogenital discharge or co-occurring STIs with T. vaginalis genotype were found. CONCLUSIONS: MLST with nested PCR is a sensitive typing method that allows typing of direct (uncultured) patient material. Genotype II is possibly more prevalent in high-risk sexual networks.

Trichomonas vaginalis infection among homeless and unstably housed adult women living in a resource-rich urban environment.

OBJECTIVE: The social context of poverty is consistently linked to Trichomonas vaginalis infection, yet few studies regarding T. vaginalis have been conducted exclusively among low-income individuals. We identified social determinants of health associated with prevalent T. vaginalis infection among homeless and unstably housed adult women. METHODS: Between April and October of 2010, we conducted cross-sectional T. vaginalis screening and behavioural interviews in an existing cohort of San Francisco homeless and unstably housed women. Data were analysed using multivariable logistical regression. RESULTS: Among 245 study participants, the median age was 47 years and 72% were of non-Caucasian race/ethnicity. T. vaginalis prevalence was 12%, compared to 3% in the general population, and 33% of infected individuals reported no gynaecological symptoms. In adjusted analysis, the odds of T. vaginalis infection were lower among persons older than 47 years, the population median (OR=0.14, 95% CI 0.04 to 0.38), and higher among those reporting recent short-term homeless shelter stays (OR=5.36, 95% CI 1.57 to 18.26). Race and income did not reach levels of significance. Sensitivity analyses indicated that testing all women who report recent unprotected sex would identify more infections than testing those who report gynaecological symptoms (20/30 vs 10/30; p=0.01). CONCLUSIONS: The prevalence of T. vaginalis is high among homeless and unstably housed adult women, over one-third of infected individuals have no gynaecological symptoms, and correlates of infection differ from those reported in the general population. Targeted screening and treatment among impoverished women reporting recent unprotected sex, particularly young impoverished women and all women experiencing short-term homelessness, may reduce complications related to this treatable infection.

The incidence of Trichomonas vaginalis infection in women attending nine sexually transmitted diseases clinics in the USA.

OBJECTIVES: Trichomoniasis (TV) is associated with an increased risk of acquisition of sexually transmitted diseases (STDs) and HIV. The purpose of this study is to evaluate factors associated with incidence TV among female STD clinic attendees in the USA. METHODS: Data were collected from women participating in a randomised controlled trial evaluating brief risk reduction counselling at the time of HIV testing to reduce sexually transmitted infections (STIs) incidence in STD clinics. Participants recruited from STD clinics underwent STI testing at baseline and 6-month follow-up. TV testing was performed using Nucleic Acid Amplification Test. RESULTS: 1704 participants completed study assessments. Prevalence of TV was 14.6%, chlamydia 8.6%, gonorrhoea 3.0%, herpes simplex virus 2 44.7% and HIV 0.4%. Cumulative 6-month incidence of TV was 7.5%. Almost 50% of the incident TV cases had TV at baseline and had received treatment. Factors associated with incidence of TV were having chlamydia, TV and HIV at baseline: TV relative risk (RR)=3.37 (95% CI 2.35 to 4.83, p<0.001); chlamydia RR=1.92 (95% CI 1.23 to 2.99, p=0.04); and HIV=1.59 (95% CI 1.01 to 2.50, p=0.047). CONCLUSIONS: Prevalent and incident TV is common among STD clinic attendees; and baseline TV is the main risk factor for incident TV, suggesting high rates of reinfection or treatment failures. This supports the importance of rescreening women after treatment for TV, evaluating current treatment regimens and programmes to ensure treatment of sexual partners. CLINICAL TRIAL NUMBER: NCT01154296.

[Vulvovaginal trichomoniasis: epidemiology, clinical and parasitological characteristics]. / Trichonomose vulvovaginale: Etude épidémiologique, Clinique et parasitilogique.

BACKGROUND: Trichomonas vaginalis infection is the most prevalent nonviral sexual transmitted infection. The World Health Organization estimates that its prevalence is 170 million cases worldwide each year. In women, he represents the third cause of vaginitis. AIM: to determine the prevalence, to evaluate predisposing factors and to study the clinical and parasitological characteristics of vulvovaginal trichomoniasis in a Tunisian population during a period of 18 months. METHODS: This is a transversal study concerning 924 women. We administered a questionnaire to obtain information about the possible risk factors of vulvovaginal trichomoniasis. Vaginal swabs were collected with the help of sterile transportable cotton swabs, followed by microscopic examination. Data were statistically analyzed. RESULTS: Trichomonas vaginalis infection was diagnosed in 3,5% of cases. The study various potential risk factors showed that trichomoniasis was significatively associated with multiple partners, long-term corticotherapy. However, the pregnancy was a protector factor. CONCLUSION: The research for factors allows not only to explain the appearance of this infection but also, and especially, to establish a disease prevention to avoid their second offense or, at best their arisen in women at risk.

Multipurpose prevention technologies: the future of HIV and STI protection.

Every day, more than 1 million people are newly infected with sexually transmitted infections (STIs) that can lead to morbidity, mortality, and an increased risk of human immunodeficiency virus (HIV) acquisition. Existing prevention and management strategies, including behavior change, condom promotion, and therapy have not reduced the global incidence and prevalence, pointing to the need for novel innovative strategies. This review summarizes important issues raised during a satellite session at the first HIV Research for Prevention (R4P) conference, held in Cape Town, on October 31, 2014. We explore key STIs that are challenging public health today, new biomedical prevention approaches including multipurpose prevention technologies (MPTs), and the scientific and regulatory hurdles that must be overcome to make combination prevention tools a reality.

Trichomonas vaginalis infection induces vaginal CD4+ T-cell infiltration in a mouse model: a vaccine strategy to reduce vaginal infection and HIV transmission.

BACKGROUND: Complications related to the diagnosis and treatment of Trichomonas vaginalis infection, as well as the association between T. vaginalis infection and increased transmission of and susceptibility to human immunodeficiency virus, highlight the need for alternative interventions. We tested a human-safe, aluminum hydroxide-adjuvanted whole-cell T. vaginalis vaccine for efficacy in a BALB/c mouse model of vaginal infection. METHODS: A whole-cell T. vaginalis vaccine was administered subcutaneously to BALB/c mice, using a prime-boost vaccination schedule. CD4(+) T-cell infiltration in the murine vaginal tissue and local and systemic levels of immunoglobulins were measured at time points up to 4 weeks following infection. RESULTS: Vaccination reduced the incidence and increased the clearance of T. vaginalis infection and induced both systemic and local humoral immune responses. CD4(+) T cells were detected in vaginal tissues following intravaginal infection with T. vaginalis but were not seen in uninfected mice. The presence of CD4(+) T cells following T. vaginalis infection can potentially increase susceptibility to and transmission of human immunodeficiency virus. CONCLUSIONS: The vaccine induces local and systemic immune responses and confers significantly greater protection against vaginal infection than seen in unvaccinated mice (P < .005). These data support the potential for a human vaccine against T. vaginalis infection that could also influence the incidence of human immunodeficiency virus infection.

Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women.

BACKGROUND: Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections. METHODS: Human immunodeficiency virus (HIV)-negative women 18-45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture). RESULTS: Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48-.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62-1.37). CONCLUSIONS: Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs.

Trichomonas vaginalis origins, molecular pathobiology and clinical considerations.

PURPOSE OF REVIEW: To integrate a selection of the most recent data on Trichomonas vaginalis origins, molecular cell biology and T. vaginalis interactions with the urogenital tract microbiota with trichomoniasis symptoms and clinical management. RECENT FINDINGS: Transcriptomics and proteomics datasets are accumulating, facilitating the identification and prioritization of key target genes to study T. vaginalis pathobiology. Proteins involved in host sensing and cytoskeletal plasticity during T. vaginalis amoeboid transformation were identified. T. vaginalis was shown to secrete exosomes and a macrophage migration inhibitory factor-like protein that both influence host-parasite interactions. T. vaginalis co-infections with Mycoplasma species and viruses were shown to modulate the inflammatory responses, whereas T. vaginalis interactions with various Lactobacillus species inhibit parasite interactions with human cells. T. vaginalis infections were also shown to be associated with bacterial vaginosis. A broader range of health sequelae is also becoming apparent. Diagnostics for both women and men based on the molecular approaches are being refined, in particular for men. SUMMARY: New developments in the molecular and cellular basis of T. vaginalis pathobiology combined with data on the urogenital tract microbiota and immunology have enriched our knowledge on human-microbe interactions that will contribute to increasing our capacity to prevent and treat T. vaginalis and other sexually transmitted infections.

HPTN 035 phase II/IIb randomised safety and effectiveness study of the vaginal microbicides BufferGel and 0.5% PRO 2000 for the prevention of sexually transmitted infections in women.

OBJECTIVES: To estimate the effectiveness of candidate microbicides BufferGel and 0.5% PRO 2000 Gel (P) (PRO 2000) for prevention of non-ulcerative sexually transmitted infections (STIs). METHODS: Between 2005 and 2007, 3099 women were enrolled in HIV Prevention Trials Network (HPTN) protocol 035, a phase II/IIb evaluation of the safety and effectiveness of BufferGel and PRO 2000 for prevention of STIs, including Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV). Incidences of STIs were determined by study arm, and HRs of BufferGel and PRO 2000 versus placebo gel or no gel control groups were computed using discrete time Andersen-Gill proportional hazards model. RESULTS: The overall incidence rates were 1.6/100 person-years at risk (PYAR) for NG, 3.9/100 PYAR for CT and 15.3/100 PYAR for TV. For BufferGel versus placebo gel, HRs were 0.99 (95% CI 0.49 to 2.00), 1.00 (95% CI 0.64 to 1.57) and 0.95 (95% CI 0.71 to 1.25) for prevention of NG, CT and TV, respectively. For PRO 2000, HRs were 1.66 (95% CI 0.90 to 3.06), 1.16 (95% CI 0.76 to 1.79) and 1.18 (95% CI 0.90 to 1.53) for prevention of NG, CT and TV, respectively. CONCLUSIONS: The incidence of STIs was high during HIV Prevention Trials Network 035 despite provision of free condoms and comprehensive risk-reduction counselling, highlighting the need for effective STI prevention programmes in this population. Unfortunately, candidate microbicides BufferGel and PRO2000 had no protective effect against gonorrhoea, chlamydia or trichomoniasis. TRIAL REGISTRATION NUMBER: NCT00074425.