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ObjectivesWe evaluated how storing vaginal samples at room temperature in stabilising solutions versus immediate freezing affects 16S rRNA gene amplicon sequencing-based microbiota studies, aiming to simplify home and field collection. METHODS: Twenty participants self-collected six mid-vaginal swabs that were stored in two nucleic acid preservatives (three in modified Solution C2 (Qiagen) and three in Amies/RNALater (Sigma)) in January-February 2016. From each set, two were immediately frozen (-80°C) and one was shipped to the University of Idaho (Moscow, Idaho) with return shipping to the Institute for Genome Sciences (Baltimore, Maryland). Amplicon sequencing of the 16S rRNA gene was used to characterise the vaginal microbiota, VALENCIA was used to assign community state types (CSTs), and quantitative PCR (qPCR) of 16S rRNA genes was used to estimate bacterial abundance. Cohen's Kappa statistic was used to assess within-participant agreement. Bayesian difference of means models assessed within-participant comparisons between shipped and immediately frozen samples. RESULTS: There were 115 samples available for analysis. Average duration of transit for shipped samples was 8 days (SD: 1.60, range: 6-11). Within-participant comparisons of CSTs between shipped and immediately frozen samples revealed complete concordance (kappa: 1.0) for both preservative solutions. No significant differences comparing shipped and immediately frozen samples were found with taxon-level comparisons or bacterial abundances based on pan-bacterial qPCR. CONCLUSIONS: Short-term room temperature shipping of vaginal swabs placed in stabilising solutions did not affect vaginal microbiota composition. Home collection with mail-in of vaginal samples may be a reasonable approach for research and clinical purposes to assess the vaginal microbiota.
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Microbiota , ARN Ribosómico 16S , Manejo de Especímenes , Vagina , Humanos , Femenino , Vagina/microbiología , Manejo de Especímenes/métodos , ARN Ribosómico 16S/genética , Microbiota/genética , Adulto , Bacterias/aislamiento & purificación , Bacterias/genética , Bacterias/clasificación , Adulto Joven , Congelación , ADN BacterianoRESUMEN
ABSTRACT: Chlamydia trachomatis (CT) is the most commonly reported sexually transmitted infection in the United States. Untreated urogenital infection in women can result in adverse sequelae such as pelvic inflammatory disease and infertility. Despite national screening and treatment guidelines, rates continue to rise; because most infections are asymptomatic, the actual prevalence of CT infection is likely significantly higher than reported. Spontaneous clearance of CT in women (in the absence of antibiotic treatment) has been described in multiple epidemiologic studies. Given the serious consequences and high prevalence of CT infection, there is growing interest in understanding this phenomenon and factors that may promote CT clearance in women. Spontaneous CT clearance is likely the result of complex interactions between CT, the host immune system, and the vaginal microbiota (i.e., the communities of bacteria inhabiting the vagina), which has been implicated in CT acquisition. Herein, we briefly review current literature regarding the role of each of these factors in spontaneous CT clearance, identify knowledge gaps, and discuss future directions and possible implications for the development of novel interventions that may protect against CT infection, facilitate clearance, and prevent reproductive sequelae.
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Infecciones por Chlamydia , Microbiota , Enfermedades de Transmisión Sexual , Humanos , Femenino , Chlamydia trachomatis , Enfermedades de Transmisión Sexual/microbiología , Infecciones por Chlamydia/epidemiología , Vagina/microbiologíaRESUMEN
BACKGROUND: Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study. METHODS: Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0-3, no BV; 4-10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression. RESULTS: Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30-2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI, .99-1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39-16.35). BV symptoms did not affect any results. CONCLUSIONS: BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance.
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Infecciones por Chlamydia , Vaginosis Bacteriana , Humanos , Femenino , Vaginosis Bacteriana/complicaciones , Chlamydia trachomatis , Estudios Longitudinales , Vagina/microbiología , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/complicacionesRESUMEN
We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin.
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ABSTRACT: This secondary analysis (N = 43) compared computer-assisted self-interview (CASI) to clinician interview for self-report of 8 vulvovaginal symptoms. Concordance was moderate between interview modes (range, 70-86%) with itching and odor having highest agreement. Although prior reports suggest more responses on CASI, we found CASI did not significantly increase self-report of symptoms over clinician interview.
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Computadores , Humanos , AutoinformeRESUMEN
BACKGROUND: Shifts in public health infrastructure to respond to one emerging health threat may have unanticipated consequences for preexisting diseases. Previous research evaluating the impact of COVID-19 on sexually transmitted infections (STIs) has been conducted nationally, with little exploration of the impact on a granular geospatial level. This ecological study seeks to quantify the association between COVID-19 cases or deaths and chlamydia, gonorrhea, and syphilis cases for all US counties in 2020. METHODS: Separate, adjusted multivariable quasi-Poisson models with robust standard errors modeled the county-level association between 2020 COVID-19 cases and deaths per 100,000 and 2020 chlamydia, gonorrhea, or syphilis cases per 100,000. Models were adjusted for sociodemographic characteristics. RESULTS: Every 1000 additional COVID-19 cases per 100,000 was associated with a 1.80% increase in the average number of chlamydia cases ( P < 0.001) and a 5.00% increase in the average number of gonorrhea cases ( P < 0.001). Every 1000 additional COVID-19 deaths per 100,000 was associated with a 57.9% increase in the average number gonorrhea cases ( P < 0.001) and a 74.2% decrease in the average number of syphilis cases ( P = 0.004). CONCLUSIONS: Higher rates of COVID-19 cases and deaths were associated with increased rates of some STIs at the US county level. The underlying reasons for these associations could not be established by this study. The emergency response to an emerging threat may have unanticipated influence on preexisting diseases that varies by level of governance.
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COVID-19 , Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Enfermedades de Transmisión Sexual , Sífilis , Estados Unidos/epidemiología , Humanos , Gonorrea/epidemiología , Sífilis/epidemiología , Infecciones por Chlamydia/epidemiología , COVID-19/epidemiología , Enfermedades de Transmisión Sexual/epidemiologíaRESUMEN
A panel of experts generated 5 "key questions" in the management of adult syphilis. A systematic literature review was conducted and tables of evidence were constructed to answer these questions. Available data suggest no clinical benefit to >1 dose of benzathine penicillin G for early syphilis in human immunodeficiency virus (HIV)-infected patients. While penicillin remains the drug of choice to treat syphilis, doxycycline to treat early and late latent syphilis is an acceptable alternate option if penicillin cannot be used. There are very limited data regarding the impact of additional antibiotic doses on serologic responses in serofast patients and no data on the impact of additional antibiotic courses on long-term clinical outcomes. In patients with isolated ocular or otic signs and symptoms, reactive syphilis serologic results, and confirmed ocular/otic abnormalities at examination, a diagnostic cerebrospinal fluid (CSF) examination is not necessary, because up to 40% and 90% of patients, respectively, would have no CSF abnormalities. Based on the results of 2 studies, repeated CSF examinations are not necessary for HIV-uninfected patients or HIV-infected patients on antiretroviral therapy who exhibit appropriate serologic and clinical responses after treatment for neurosyphilis. Finally, several important gaps were identified and should be a priority for future research.
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Infecciones por VIH , Neurosífilis , Sífilis , Adulto , Antibacterianos/uso terapéutico , Centers for Disease Control and Prevention, U.S. , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Neurosífilis/diagnóstico , Penicilina G Benzatina/uso terapéutico , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Sífilis/prevención & control , Estados UnidosRESUMEN
ABSTRACT: The American Sexually Transmitted Diseases Association has, for several years, been conducting a cross-sector workshop to bring together a variety of stakeholders to develop ideas for collaboratively improving the sexually transmitted infection control efforts in the United States. In this summary, we share the content of discussions and ideas of the fourth annual workshop for future research and potential changes to practice with a focus on diagnostic capacity.
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Enfermedades de Transmisión Sexual , Humanos , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Among older adults, postoperative urinary tract infection is associated with significant harms including increased risk of hospital readmission and perioperative mortality. While risk of urinary tract infection is known to increase with age, the independent association between frailty and postoperative urinary tract infection is unknown. In this study we used 2014-2018 data from the U.S. National Surgical Quality Improvement Program (NSQIP) to investigate whether frailty is an independent risk factor for postoperative urinary tract infection, controlling for age and other relevant confounders. METHODS: Frailty was assessed using the modified Frailty Index. Postoperative urinary tract infection was defined as any symptomatic urinary tract infection (of the kidneys, ureters, bladder, or urethra) developing within 30 days of the operative procedure. To examine associations between frailty and other specific factors and postoperative urinary tract infection, chi squared tests, students t-tests, and logistic regression modelling were used. RESULTS: Urinary tract infection was identified after 22,356 of 1,724,042 procedures (1.3%). In a multivariable model controlling for age and other patient and surgical characteristics, the relative odds for urinary tract infection increased significantly with increasing frailty score. For example, compared to a frailty score of 0, the relative odds for urinary tract infection for a frailty score of 3 was 1.50 (95% confidence interval 1.41, 1.60). The relative odds associated with the maximum frailty score (5) was 2.50 (95% confidence interval 1.73, 3.61). CONCLUSIONS: Frailty is associated with postoperative urinary tract infection, independent of age. Further research should focus on the underlying mechanisms and strategies to mitigate this risk among frail adults.
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Fragilidad , Infecciones Urinarias , Humanos , Anciano , Fragilidad/diagnóstico , Fragilidad/epidemiología , Fragilidad/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Readmisión del Paciente , Factores de Riesgo , Infecciones Urinarias/epidemiología , Infecciones Urinarias/etiología , Estudios RetrospectivosRESUMEN
Importance: Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes. Observations: From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception. Conclusions and Relevance: Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.
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Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Infecciones Asintomáticas/epidemiología , Infecciones Asintomáticas/terapia , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/etnología , Trazado de Contacto , Farmacorresistencia Microbiana , Minorías Étnicas y Raciales/estadística & datos numéricos , Femenino , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Gonorrea/etnología , Infecciones por VIH/complicaciones , Infecciones por VIH/transmisión , Herpes Genital/diagnóstico , Herpes Genital/tratamiento farmacológico , Herpes Genital/epidemiología , Herpes Genital/etnología , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Herpes Simple/epidemiología , Herpes Simple/etnología , Humanos , Masculino , Tamizaje Masivo , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/tratamiento farmacológico , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/etnología , Mycoplasma genitalium , Técnicas de Amplificación de Ácido Nucleico , Distribución por Sexo , Minorías Sexuales y de Género/estadística & datos numéricos , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/etnología , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Sífilis/epidemiología , Sífilis/etnología , Serodiagnóstico de la Sífilis/métodos , Vaginitis por Trichomonas/diagnóstico , Vaginitis por Trichomonas/tratamiento farmacológico , Vaginitis por Trichomonas/epidemiología , Vaginitis por Trichomonas/etnología , Estados Unidos/epidemiologíaRESUMEN
Unique compositional and functional features of the cervicovaginal microbiota have been associated with protection against and risk for sexually transmitted infections (STI). In men, our knowledge of the interaction between the penile microbiota and STI is less developed. The current state of our understanding of these microbiota and their role in select STIs is briefly reviewed, along with strategies that leverage existing findings to manipulate genital microbiota and optimize protection against STIs. Finally, we focus on major research gaps and present a framework for future studies.
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Genitales Femeninos/microbiología , Genitales Masculinos/microbiología , Microbiota , Enfermedades de Transmisión Sexual/microbiología , Femenino , Humanos , Masculino , Microbiota/inmunología , Enfermedades de Transmisión Sexual/inmunologíaRESUMEN
BACKGROUND: Pelvic inflammatory disease (PID) leads to long-term reproductive consequences for cisgender women. Bacterial vaginosis (BV) and behavioral factors may play a role in PID pathogenesis. We assessed associations between BV, behavioral factors, and incident PID. METHODS: We analyzed participants (N = 2956) enrolled in the National Institutes of Health Longitudinal Study of Vaginal Flora, a cohort of nonpregnant cisgender women followed quarterly for 12 months. PID was defined by at least 1 of the following: cervical motion tenderness, uterine tenderness, or adnexal tenderness (160 cases). We tested associations between BV (measured using Nugent and Amsel criteria) and PID at the subsequent visit. Sociodemographic factors, sexual behaviors, and Chlamydia trachomatis (CT), untreated at baseline and concurrent with BV, were covariates in Cox proportional hazards models. Adjusting for the few Neisseria gonorrhoeae and Trichomonas vaginalis cases did not alter results. RESULTS: In multivariable modeling, Nugent-BV (adjusted hazard ratio [aHR], 1.53 [95% confidence interval {CI}, 1.05-2.21]), symptomatic Amsel-BV (aHR, 2.15 [95% CI, 1.23-3.75]), and vaginal douching (aHR, 1.47 [95% CI, 1.03-2.09]) were associated with incident PID. CONCLUSIONS: BV was associated with incident PID in a large prospective cohort, controlling for behavioral factors and sexually transmitted infections (STIs). Larger studies on how BV, STIs, behaviors, and host responses interactively affect PID risk are needed.
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Enfermedad Inflamatoria Pélvica/epidemiología , Conducta Sexual , Vagina/microbiología , Vaginosis Bacteriana/epidemiología , Adolescente , Adulto , Alabama/epidemiología , Femenino , Humanos , Estudios Longitudinales , Enfermedad Inflamatoria Pélvica/microbiología , Estudios Prospectivos , Parejas Sexuales , Factores Sociodemográficos , Vaginosis Bacteriana/complicaciones , Adulto JovenRESUMEN
INTRODUCTION: Many US women report same sex behaviour, yet data on risk factors and STIs in women who have sex with women (WSW), women who have sex with both men and women (WSB) and how these compare to women who have sex with men only (WSM) remain limited. Here we compared self-identified WSW, WSB and WSM attending two STI clinics in Baltimore, Maryland. METHODS: This was a retrospective analysis using a database of first clinic visits 2005-2016. WSW and WSB were compared with an age-matched random sample of WSM. Proportions were compared using the χ2 test. Acute STI (aSTI) was defined as gonorrhoea (Neisseria gonorrhoeae, GC), chlamydia (Chlamydia trachomatis, CT), trichomonas (Trichomonas vaginalis, TV) or early syphilis. Logistic regression was used to assess aSTI predictors. CT testing was not uniformly done, so a sensitivity analysis removing CT from the aSTI definition was conducted. RESULTS: Visits from 1095 WSW, 1678 WSB and 2773 WSM were analysed. WSB had equal or higher test positivity for all STIs except urogenital chlamydia, had more sexual partners, were more likely to engage in transactional sex and were more likely to report drug use and binge drinking than WSM (p≤0.01). WSW had lower test positivity for urogenital GC and CT than WSM or WSB, but comparable test positivity for TV, higher reported binge drinking and comparable reported substance use as WSM. Younger age and cocaine use predicted STI diagnosis only in WSM. CONCLUSIONS: WSB in these clinics bear an equal or higher burden of most STIs, have more partners and report more substance use than WSM. WSW carry a lower, but still substantial burden of STIs, and many report substance use. Factors predicting STI diagnosis differ between WSW, WSB and WSM suggesting that tailored STI prevention and testing approaches are needed in these groups.
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Bisexualidad/estadística & datos numéricos , Heterosexualidad/estadística & datos numéricos , Homosexualidad Femenina/estadística & datos numéricos , Conducta Sexual/estadística & datos numéricos , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Adolescente , Adulto , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Baltimore/epidemiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Parejas Sexuales , Enfermedades de Transmisión Sexual/microbiología , Enfermedades de Transmisión Sexual/parasitología , Adulto JovenRESUMEN
ABSTRACT: Intravaginal boric acid (IBA) represents one of the only options available to treat azole-resistant vulvovaginal candidiasis (VVC) and is included as part of multiple national guidelines (including the United Kingdom and the United States) for the treatment of VVC or recurrent bacterial vaginosis. Novel products using IBA are under development for treatment and suppression of VVC and bacterial vaginosis. Use of over-the-counter or clinician-prescribed IBA in reproductive-aged women is already widespread and may increase further if drug resistance in VVC rises. However, IBA is not a Food and Drug Administration-approved drug, and safety data are sparse. Given these factors, it is important to understand the currently available data on the safety of IBA use. Herein, we set out to synthesize human and animal data (converting, where appropriate, dose and serum values to standard units to facilitate comparison) to answer 2 key questions: (1) What are the data on the safety of IBA use for women? and (2) What are the data on the safety of IBA use in pregnancy? We find that, despite gaps, available data suggest IBA use is safe, at least when used in doses commonly described in the literature as being prescribed by clinicians. Information on harms in pregnancy is limited, and data remain insufficient to change current guidelines, which recommend IBA avoidance in pregnancy.
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Candidiasis Vulvovaginal , Vaginosis Bacteriana , Administración Intravaginal , Adulto , Ácidos Bóricos/uso terapéutico , Candidiasis Vulvovaginal/tratamiento farmacológico , Femenino , Humanos , Embarazo , Vaginosis Bacteriana/tratamiento farmacológicoRESUMEN
BACKGROUND: Bacterial vaginosis (BV) is the most cited cause of vaginal complaints among women of reproductive age. Its etiology and associated risk factors are not entirely understood. Here we examined the association between BV and at-risk alcohol consumption in women attending 2 sexually transmitted infection (STI) clinics in Baltimore, MD. METHODS: This was a retrospective cross-sectional analysis using data from first clinic visits from 2011-2016. At-risk alcohol use was defined as heavy episodic ("binge") drinking within the last 30 days or a self-report of having had vaginal or anal sex in the context of alcohol consumption. Pearson χ2 test and Student t test were used to assess baseline associations. Log binomial models were used to estimate prevalence ratios (PRs) before and after adjustments for potential confounding factors. RESULTS: Of the 10,991 women included in the analysis, 2173 (19.7%) met the clinical diagnostic criteria for BV. Having had vaginal or anal sex in the context of alcohol consumption was associated with an increased risk of BV (PR, 1.25; 95% confidence interval, 1.13-1.37), as was binge drinking (PR, 1.15; 95% confidence interval, 1.04-1.27) after adjustment for confounders. CONCLUSIONS: In this population, at-risk alcohol consumption was associated with an increased risk of BV. The mechanisms remain uncertain. Future prospective studies are needed to verify and evaluate causality in these associations.
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Vaginosis Bacteriana , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Baltimore/epidemiología , Estudios Transversales , Femenino , Humanos , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Vaginosis Bacteriana/epidemiologíaRESUMEN
Meta-analysis is a practical and powerful analytic tool that enables a unified statistical inference across the results from multiple studies. Notably, researchers often report the results on multiple related markers in each study (eg, various α-diversity indices in microbiome studies). However, univariate meta-analyses are limited to combining the results on a single common marker at a time, whereas existing multivariate meta-analyses are limited to the situations where marker-by-marker correlations are given in each study. Thus, here we introduce two meta-analysis methods, multi-marker meta-analysis (mMeta) and adaptive multi-marker meta-analysis (aMeta), to combine multiple studies throughout multiple related markers with no priori results on marker-by-marker correlations. mMeta is a statistical estimator for a pooled estimate and its SE across all the studies and markers, whereas aMeta is a statistical test based on the test statistic of the minimum P-value among marker-specific meta-analyses. mMeta conducts both effect estimation and hypothesis testing based on a weighted average of marker-specific pooled estimates while estimating marker-by-marker correlations non-parametrically via permutations, yet its power is only moderate. In contrast, aMeta closely approaches the highest power among marker-specific meta-analyses, yet it is limited to hypothesis testing. While their applications can be broader, we illustrate the use of mMeta and aMeta to combine microbiome studies throughout multiple α-diversity indices. We evaluate mMeta and aMeta in silico and apply them to real microbiome studies on the disparity in α-diversity by the status of human immunodeficiency virus (HIV) infection. The R package for mMeta and aMeta is freely available at https://github.com/hk1785/mMeta.
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Microbiota , Biomarcadores , Simulación por Computador , Humanos , Metaanálisis como Asunto , Análisis Multivariante , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Limited data suggest that personal lubricants may damage the vaginal mucosal epithelium, alter the vaginal microbiota, and increase inflammation. We compared vaginal cytokine profiles and microbiota before and after vaginal lubricant use and condomless vaginal sex. METHODS: Reproductive-age women were recruited to a 10-week observational cohort study and were asked to self-collect vaginal samples and behavioral diaries daily. This nested case-control analysis utilized samples collected before and after self-reported condomless sexual activity with lubricants (22 case participants) and without lubricants (22 control participants). Controls were matched to cases on race/ethnicity. Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3-V4 regions. Cytokine concentrations were quantified using a magnetic bead 41-plex panel assay and read using a Bio-Plex 200 array reader. Wilcoxon signed-rank tests were used to assess baseline differences in vaginal cytokines between cases and controls as well as differences pre- and post-exposure. Linear mixed effects models were used to examine differences in relative post-to-pre change in each individual cytokine between matched cases and controls. Similar analyses were conducted for the microbiota data. RESULTS: Mean age was 29.8 years (SD 6.8), and 63.6% were African American. There were few statistically significant changes in cytokines or microbiota before and after exposure in cases or controls. In mixed-effects modeling, the mean relative post-to-pre change of cytokines was higher in cases vs. controls for macrophage derived chemokine (MDC) (p = 0.03). The microbiota data revealed no significant changes when measured by similarity scores, diversity indexes and descriptive community state types (CST) transition analyses. However, post sexual activity, the mean relative abundance of L. crispatus decreased for those who used lubricants (particularly those who were L. iners-dominated prior to exposure). CONCLUSIONS: Although there were overall few differences in the vaginal microbiota and cytokine profiles of lubricant users and controls before and after condomless vaginal sex, there was a trend toward decreases in relative abundance of L. crispatus following use of lubricant. Future larger studies that take into account osmolarity and composition of lubricants may provide additional insights.
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Lubricantes , Microbiota , Adulto , Citocinas , Femenino , Humanos , ARN Ribosómico 16S/genética , VaginaRESUMEN
We reviewed the relevant syphilis diagnostic literature to address the following question: what are the performance characteristics, stratified by the stage of syphilis, for nontreponemal serologic tests? The database search included key terms related to syphilis and nontreponemal tests from 1960-2017, and for data related to the venereal disease research laboratory test from 1940-1960. Based on this review, we report the sensitivity and specificity for each stage of syphilis (primary, secondary, early latent, late latent, or unknown duration; tertiary as well as neurosyphilis, ocular syphilis, and otic syphilis). We also report on reactive nontreponemal tests in conditions other than syphilis, false negatives, and automated nontreponemal tests. Overall, many studies were limited by their sample size, lack of clearly documented clinical staging, and lack of well-defined gold standards. There is a need to better define the performance characteristics of nontreponemal tests, particularly in the late stages of syphilis, with clinically well-characterized samples. Published data are needed on automated nontreponemal tests. Evidence-based guidelines are needed for optimal prozone titrations. Finally, improved criteria and diagnostics for neurosyphilis (as well as ocular and otic syphilis) are needed.
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Neurosífilis , Sífilis , Humanos , Laboratorios , Sífilis/diagnóstico , Serodiagnóstico de la Sífilis , Treponema pallidumRESUMEN
BACKGROUND: Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV-) and HIV-infected (HIV+) individuals. METHODS: We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata. RESULTS: Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV-, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW. CONCLUSIONS: Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.
Asunto(s)
Microbioma Gastrointestinal , Infecciones por VIH , Minorías Sexuales y de Género , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Homosexualidad Masculina , Humanos , Masculino , ARN Ribosómico 16S/genéticaRESUMEN
Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIV-related intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies.