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Ocular syphilis is a serious complication of Treponema pallidum infection that can occur at any stage of syphilis and affect any eye structure. It remains unknown if certain T. pallidum strains are associated with ocular infections; therefore, we performed genotyping and whole genome sequencing (WGS) to characterize strains from patients with ocular syphilis. Seventy-five ocular or non-ocular specimens from 55 ocular syphilis patients in 14 states within the United States were collected between February 2016 and November 2020. Sufficient T. pallidum DNA was available from nine patients for genotyping and three for WGS. Genotyping was done using the augmented Centers for Disease Control and Prevention typing scheme, and WGS was performed on Illumina platforms. Multilocus sequence typing allelic profiles were predicted from whole genome sequence data. T. pallidum DNA was detected in various specimens from 17 (30.9%) of the 55 patients, and typing was done on samples from 9 patients. Four complete strain types (14d10/g, 14b9/g, 14d9/g, and 14e9/f) and five partial types were identified. WGS was successful on samples from three patients and all three strains belonged to the SS14 clade of T. pallidum. Our data reveal that multiple strain types are associated with ocular manifestations of syphilis. While genotyping and WGS were challenging due to low amounts of T. pallidum DNA in specimens, we successfully performed WGS on cerebrospinal fluid, vitreous fluid, and whole blood.IMPORTANCESyphilis is caused by the spirochete Treponema pallidum. Total syphilis rates have increased significantly over the past two decades in the United States, and the disease remains a public health concern. In addition, ocular syphilis cases has also been on the rise, coinciding with the overall increase in syphilis rates. We conducted a molecular investigation utilizing traditional genotyping and whole genome sequencing over a 5-year period to ascertain if specific T. pallidum strains are associated with ocular syphilis. Genotyping and phylogenetic analysis show that multiple T. pallidum strain types are associated with ocular syphilis in the United States.
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There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.
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No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.
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Centers for Disease Control and Prevention, U.S. , Doxiciclina , Profilaxis Posexposición , Enfermedades Bacterianas de Transmisión Sexual , Humanos , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Minorías Sexuales y de Género , Enfermedades Bacterianas de Transmisión Sexual/prevención & control , Estados UnidosAsunto(s)
Antibacterianos , Azitromicina , Farmacorresistencia Bacteriana , Macrólidos , Sífilis , Treponema pallidum , Humanos , Antibacterianos/farmacología , Antibacterianos/provisión & distribución , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Macrólidos/farmacología , Macrólidos/uso terapéutico , América del Norte , Sífilis/tratamiento farmacológico , Sífilis/genética , Sífilis/microbiología , Treponema pallidum/efectos de los fármacos , Treponema pallidum/genética , Treponema pallidum/aislamiento & purificación , Azitromicina/farmacología , Azitromicina/uso terapéutico , Estados Unidos , Canadá , Penicilina G Benzatina/farmacología , Penicilina G Benzatina/provisión & distribución , Penicilina G Benzatina/uso terapéutico , Doxiciclina/farmacología , Doxiciclina/provisión & distribución , Doxiciclina/uso terapéuticoRESUMEN
BACKGROUND: Routine sexually transmitted infection and human immunodeficiency virus (STI/HIV) testing and HIV pre-exposure prophylaxis (PrEP) use are recommended for men who have sex with men (MSM) at increased risk of HIV. METHODS: Using Healthverity, a large administrative dataset in the United States, we assessed STI/HIV testing, chlamydia and gonorrhea positivity by specimen type, and HIV PrEP use among MSM and men who have sex with men and women (MSMW) at their first visits (index date) for those at increased risk of HIV and STIs from 2019 through 2022. RESULTS: Among 81,716 MSM and MSMW aged 15-64 years at their index date visit, STI testing rates were 57.9% for chlamydia, 58.1% for gonorrhea, and 52.2% for syphilis testing, respectively; 55.5%, 30.9%, and 18.1% had HIV testing, HIV PrEP use, and PrEP initiation, respectively, among the patients who did not have HIV. Of patients with chlamydia and gonorrhea testing, 48% were tested from the genital site only and 25% from three anatomic sites (rectal, pharyngeal, and urogenital). Chlamydia and gonorrhea positivity was 9.8% for chlamydia rectal infection, 7.3% for gonorrhea rectal infection, and 5.3% for gonorrhea pharyngeal infection. CONCLUSION: Our results present current medical services provided during initial clinic visits for MSM and MSMW in private outpatient settings. Our study suggests that the assessment of STI/HIV testing is periodically needed due to the high prevalence of infection, and efforts to promote HIV PrEP for MSM and MSMW in private settings are urgently needed.
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Neisseria gonorrhoeae is widespread globally. Primary prevention is unsuccessful and antimicrobial resistance threatens optimal management. There is no specific vaccine and natural infection studies show that N. gonorrhoeae can avoid and suppress immune responses. In addition to extensive variation in expression and specificity of many gonococcal surface antigens, it induces a robust inflammatory response through the Th17 pathway with a large influx of neutrophils and inflammatory cytokines but evades macrophages. The Th1- and Th2-mediated response is suppressed, resulting in low, short-lived antibody titers. Real-world evidence suggests that gonorrhea cases are reduced among recipients of N. meningitidis group B vaccines containing outer membrane vesicles (OMV). Although the first randomized trial of an OMV-containing MenB vaccine against N. gonorrhoeae infection did not show statistically significant vaccine efficacy, ongoing trials might shed further light. Several candidate vaccine antigens for a gonococcal-specific vaccine are being evaluated preclinically but only one has reached clinical trials.
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Proctitis is an inflammatory condition of the distal rectum that can be associated with common sexually transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis. For persons presenting with ulcerative findings on examination, in addition to syphilis, Mpox, lymphogranuloma venereum, and herpes simplex virus should be in the differential. Providers should also be aware that there are evolving data to support a role for Mycoplasma genitalium in proctitis. Performing a comprehensive history, clinical evaluation including anoscopy, and rectal nucleic amplification STI testing may be useful in identifying the cause of proctitis and targeting treatment.
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Linfogranuloma Venéreo , Proctitis , Enfermedades de Transmisión Sexual , Sífilis , Humanos , Sífilis/complicaciones , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/complicaciones , Enfermedades de Transmisión Sexual/terapia , Linfogranuloma Venéreo/complicaciones , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/tratamiento farmacológico , Proctitis/diagnóstico , Proctitis/tratamiento farmacológico , Proctitis/etiologíaRESUMEN
Importance: Despite a lack of effectiveness data in humans, tecovirimat was widely prescribed to people with HIV (PWH) with mpox during the 2022 mpox epidemic, particularly PWH with low CD4+ T-cell counts or severe mpox clinical manifestations. Objective: To evaluate if PWH with mpox who were treated with tecovirimat within 7 days of symptom onset were less likely to have mpox disease progression. Design, Setting, and Participants: This cohort study included PWH diagnosed with mpox at 4 hospitals in Atlanta, Georgia, between June 1 and October 7, 2022. Patients were grouped according to whether they were treated with tecovirimat within 7 days of mpox symptom onset (early tecovirimat cohort) or they did not receive tecovirimat or received the drug 7 or more days after symptom onset (late or no tecovirimat cohort). Multivariable logistic regression models were used to identify factors associated with progression of mpox disease. The 2 cohorts were then matched 1:1 using propensity scores based on the identified factors, and mpox disease progression was compared. Exposures: Treatment with tecovirimat within 7 days of mpox symptom onset. Main Outcome and Measures: Progression of mpox disease, defined as the development of at least 1 severe mpox criterion established by the US Centers for Disease Control and Prevention, after symptom day 7. Results: After propensity score matching, a total of 112 PWH were included in the analysis; 56 received tecovirimat within 7 days of mpox symptom onset (early tecovirimat group) and 56 were either treated later or did not receive tecovirimat (late or no tecovirimat group). In the early tecovirimat group, the median (IQR) age was 35 (30-42) years; 54 individuals (96.4%) were cisgender men, 46 (82.1%) were Black individuals, and 10 (17.9%) were individuals of other races (American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, or White) or unknown race. In the late or no tecovirimat group, the median (IQR) age was 36 (32-43) years; 54 (96.4%) were cisgender men, 49 (87.5%) were Black individuals, and 7 (12.5%) were individuals of other races or unknown race. Mpox disease progression occurred in 3 PWH (5.4%) in the early tecovirimat group and in 15 PWH (26.8%) in the late or no tecovirimat group (paired odds ratio, 13.00 [95% CI, 1.71-99.40]; P = .002). Conclusion and Relevance: Results of this cohort study support starting tecovirimat in all PWH as soon as an mpox diagnosis is suspected. Additional research is warranted to confirm these findings.
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Infecciones por VIH , Mpox , Masculino , Humanos , Adulto , Estudios de Cohortes , Benzamidas , Progresión de la Enfermedad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológicoRESUMEN
BACKGROUND: In the Southeastern United States, the 2022 mpox outbreak disproportionately impacted people who are black and people with HIV (PWH). METHODS: We analyzed a cohort of 395 individuals diagnosed with mpox across 3 health care systems in Atlanta, Georgia between 1 June 2022 and 7 October 2022. We present demographic and clinical characteristics and use multivariable logistic regression analyses to evaluate the association between HIV status and severe mpox (per the US Centers for Disease Control and Prevention definition) and, among PWH, the associations between CD4+ T-cell count and HIV load with severe mpox. RESULTS: Of 395 people diagnosed with mpox, 384 (97.2%) were cisgender men, 335 (84.8%) identified as black, and 324 (82.0%) were PWH. Of 257 PWH with a known HIV load, 90 (35.0%) had > 200â copies/mL. Severe mpox occurred in 77 (19.5%) individuals and there was 1 (0.3%) death. Tecovirimat was prescribed to 112 (28.4%) people, including 56 (72.7%) people with severe mpox. In the multivariable analysis of the total population, PWH had 2.52 times higher odds of severe mpox (95% confidence interval [CI], 1.01-6.27) compared with people without HIV. In the multivariable analysis of PWH, individuals with HIV load > 200â copies/mL had 2.10 (95% CI, 1.00-4.39) times higher odds of severe mpox than PWH who were virologically suppressed. Lower CD4+ T-cell count showed a significant univariate association with severe mpox but was not found to be significantly associated with severe mpox in multivariable analysis. CONCLUSIONS: PWH with nonsuppressed HIV loads had more mpox complications, hospitalizations, and protracted disease courses than people without HIV or PWH with suppressed viral loads. PWH with nonsuppressed HIV loads who are diagnosed with mpox warrant particularly aggressive monitoring and treatment.
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Infecciones por VIH , Mpox , Estados Unidos , Masculino , Humanos , Benzamidas , Recuento de Linfocito CD4 , Centers for Disease Control and Prevention, U.S.RESUMEN
OBJECTIVES: Mpox is a viral disease caused by monkeypox, a highly contagious orthopoxvirus that resulted in a global outbreak beginning in spring 2022. Diagnosis is confirmed via polymerase chain reaction (PCR) testing of swabs from mucocutaneous lesions. Rare reports have documented the histologic changes of mpox lesions, but the cytologic features have not been described. We present the cytology findings of samples taken from swabs of mucocutaneous mpox lesions in 3 different patients. METHODS: The patients were all male, aged 55, 43, and 37 years, all with mpox confirmed by PCR testing. Swabs from chest (cases 1 and 2) and tongue (case 3) lesions were directly sampled and submitted in Aptima (case 1) or PreservCyt solution (cases 2 and 3). Liquid-based preps were prepared and stained using the Papanicolaou method. Specimens were assessed for viral cytopathic changes. RESULTS: All cases showed nuclear cytopathic changes (enlarged nuclei with open chromatin and prominent red nucleoli), 2 cases demonstrated multinucleated keratinocytes, and 1 case showed potential Guarnieri bodies. The chromatin margination and nuclear molding typical of herpesviruses was not appreciated. CONCLUSIONS: The cytopathic changes of monkeypox are not specific, but their recognition could prompt appropriate PCR testing. Monkeypox shows distinct cytologic changes compared with herpesviruses.
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Monkeypox virus , Mpox , Humanos , Masculino , Monkeypox virus/genética , Mpox/diagnóstico , Mpox/epidemiología , Núcleo Celular , Cromatina , Brotes de EnfermedadesRESUMEN
BACKGROUND: Treponema pallidum prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by quantitative polymerase chain reaction (qPCR). Factors associated with oral shedding were also examined. METHODS: Pretreatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs were collected in the presence and absence of oral lesions. Following DNA extraction, qPCR and whole-genome sequencing (WGS) were performed to assess burden and strain variability. RESULTS: All 32 participants were male, mean age was 35 years, and 90.6% with human immunodeficiency virus (HIV). T. pallidum oral PCR positivity varied by stage: 16.7% primary, 44.4% secondary, and 62.5% in early latent syphilis. Median oral T. pallidum burden was highest in secondary syphilis at 63.2 copies/µL. Lesion PCR positivity was similar in primary (40.0%) and secondary syphilis (38.5%). Age 18-29 years was significantly associated with oral shedding (vs age 40+ years) in adjusted models. WGS identified 2 distinct strains. CONCLUSIONS: T. pallidum DNA was directly detected at oral and lesion sites in a significant proportion of men with early syphilis. Younger age was associated with oral shedding. Ease of oral specimen collection and increased PCR availability suggest opportunities to improve syphilis diagnostic testing. Clinical Trials Registration. NCT03637660.
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Sífilis , Treponema pallidum , Humanos , Masculino , Sífilis/diagnóstico , Sífilis/microbiología , Sífilis/epidemiología , Treponema pallidum/genética , Treponema pallidum/aislamiento & purificación , Adulto , Prevalencia , Adulto Joven , Adolescente , Boca/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Persona de Mediana Edad , ADN Bacteriano/genética , Estados Unidos/epidemiología , Secuenciación Completa del Genoma , Infecciones por VIH/epidemiología , FemeninoRESUMEN
BACKGROUND: Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks. METHODS: This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing. FINDINGS: Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per µL and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction. INTERPRETATION: In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks. FUNDING: Gilead Sciences.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Adulto , Humanos , Infecciones por VIH/tratamiento farmacológico , Cápside , Piridonas/efectos adversos , Fármacos Anti-VIH/efectos adversos , ARN/uso terapéutico , Carga ViralRESUMEN
BACKGROUND: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is well tolerated, cost-effective, and yields high sustained virologic response rates, yet it has remained financially inaccessible to many patients. METHODS: Participants of the Women's Interagency HIV Study (an observational US cohort) with human immunodeficiency virus (HIV) and HCV (RNA+) reporting no prior hepatitis C treatment were followed for DAA initiation (2015-2019). We estimated risk ratios (RRs) of the relationship between time-varying health insurance status and DAA initiation, adjusting for confounders with stabilized inverse probability weights. We also estimated weighted cumulative incidences of DAA initiation by health insurance status. RESULTS: A total of 139 women (74% Black) were included; at baseline, the median age was 55 years and 86% were insured. Most had annual household incomes ≤$18 000 (85%); advanced liver fibrosis (21%), alcohol use (45%), and recreational drug use (35%) were common. Across 439 subsequent semiannual visits, 88 women (63%) reported DAA initiation. Compared with no health insurance, health insurance increased the likelihood of reporting DAA initiation at a given visit (RR, 4.94; 95% confidence limit [CL], 1.92 to 12.8). At 2 years, the weighted cumulative incidence of DAA initiation was higher among the insured (51.2%; 95% CL, 43.3% to 60.6%) than the uninsured (3.5%; 95% CL, 0.8% to 14.6%). CONCLUSIONS: Accounting for clinical, behavioral, and sociodemographic factors over time, health insurance had a substantial positive effect on DAA initiation. Interventions to increase insurance coverage should be prioritized to increase HCV curative therapy uptake for persons with HIV.
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Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Femenino , Persona de Mediana Edad , Antivirales/efectos adversos , Hepacivirus , VIH , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Resultado del Tratamiento , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Seguro de SaludRESUMEN
BACKGROUND: Centers for Disease Control recommends that the decision to provide sexually transmitted infection (STI)/human immunodeficiency virus (HIV) testing and presumptive treatment to patients who report sexual assault and abuse (SAA) be made on an individual basis. METHODS: The 2019 Centers for Medicare & Medicaid Services national Medicaid data set was used. The SAA visits were identified by International Classification of Diseases 10th Revision Clinical Modification (O9A4 for pregnancy-related sexual abuse, T74.2 for confirmed sexual abuse, and Z04.4 for alleged rape). The initial SAA visit was defined as the patient's first SAA-related visit. Medical services were identified by International Classification of Diseases 10th Revision Clinical Modification codes, Current Procedural Terminology codes, and National Drug Code codes. RESULTS: Of 55,113 patients at their initial SAA visits, 86.2% were female; 63.4% aged ≥13 years; 59.2% visited emergency department (ED); all STI/HIV tests were provided in ≤20% of visits; presumptive gonorrhea and chlamydia treatment was provided in 9.7% and 3.4% of visits, respectively; pregnancy test was provided in 15.7% of visits and contraception services was provided in 9.4% of visits; and diagnosed anxiety was provided in 6.4% of visits. Patients who visited ED were less likely to have STI testing and anxiety than those visited non-ED facilities, but more likely to receive presumptive treatment for gonorrhea, testing for pregnancy, and contraceptive services. About 14.2% of patients had follow-up SAA visits within 60 days after the initial SAA visit. Of 7821 patients with the follow-up SAA visits within 60 days, most medical services provided were chlamydia testing (13.8%), gonorrhea testing (13.5%), syphilis testing (12.8%), HIV testing (14.0%); diagnosed anxiety (15.0%), and posttraumatic stress disorder (9.8%). CONCLUSIONS: Current medical services during SAA visits for Medicaid patients are described in this evaluation. More collaboration with staff who handle SAA will improve SAA-related medical services.
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Infecciones por Chlamydia , Gonorrea , Infecciones por VIH , Delitos Sexuales , Enfermedades de Transmisión Sexual , Embarazo , Humanos , Anciano , Femenino , Estados Unidos/epidemiología , Masculino , Gonorrea/diagnóstico , Gonorrea/epidemiología , VIH , Medicaid , Salud Mental , Medicare , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiologíaRESUMEN
Otosyphilis can be challenging to diagnose, but, if left unrecognized, it may cause irreversible damage. An immunologic interplay between syphilis and human immunodeficiency virus (HIV) makes coinfection likely and may predispose people with HIV to neurosyphilis. In this study, we present a case of a man in his 50s with hearing loss and vertigo diagnosed with otosyphilis as well as a new diagnosis of HIV. This case and corresponding discussion serve to inform the noninfectious disease-trained clinician of the symptoms, diagnostics, and treatment options for otosyphilis as well as to discuss the relationship between HIV and syphilis and demonstrate the importance of disease recognition.
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Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome and the capture and removal of 5'-C-phosphate-G-3' (CpG) methylated host DNA using the NEBNext Microbiome DNA enrichment kit followed by MDA with the REPLI-g single cell kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93 to 98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit-propagated isolates, containing >14 T. pallidum genomic copies/µL of sample for SWGA and >129 genomic copies/µL for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole-genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which has been challenging until now. IMPORTANCE Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogen Treponema pallidum subspecies pallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions and, if left untreated, can progress through multiple stages with various clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past 2 decades, WGS data are needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of an SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers of T. pallidum.
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Sífilis , Treponema pallidum , Animales , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Conejos , Sífilis/microbiología , Treponema pallidum/genética , Secuenciación Completa del GenomaRESUMEN
In preparation for the 2021 Centers for Disease Control and Prevention (CDC) sexually transmitted infections (STIs) treatment guidelines, the CDC convened an advisory group in 2019 to examine recent literature addressing updates in the epidemiology, diagnosis, and management of STIs. This article summarizes recent data in each of these key topic areas as they pertain to bacterial vaginosis (BV), the most common cause of vaginal discharge. The evidence reviewed primarily focused on updates in the global epidemiology of BV, risk factors for BV, data supportive of sexual transmission of BV-associated bacteria, BV molecular diagnostic tests, and novel treatment regimens. Additionally, recent literature on alcohol abstinence in the setting of 5-nitroimidazole use was reviewed.