CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024.

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.

Urgent Need to Understand and Prevent Gonococcal Infection: From the Laboratory to Real-World Context.

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 Neisseria meningitidis group B vaccines containing outer membrane vesicles (OMVs). 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.

Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis.

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.

Associations Between HIV and Severe Mpox in an Atlanta Cohort.

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 > 200 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 > 200 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.

STI/HIV testing, STIs, and HIV PrEP use among men who have sex with men (MSM) and men who have sex with men and women (MSMW) in United States, 2019-2022.

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.

FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.

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.

Health Insurance and Initiation of Direct-Acting Antivirals for Hepatitis C in US Women With Human Immunodeficiency Virus.

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.

Sexually Transmitted Infection/Human Immunodeficiency Virus, Pregnancy, and Mental Health-Related Services Provided During Visits With Sexual Assault and Abuse Diagnosis for US Medicaid Beneficiaries, 2019.

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.

Enteric Infections in Men Who Have Sex With Men.

BACKGROUND: Enteric pathogens are often associated with exposure to food, water, animals, and feces from infected individuals. However, in sexual networks of men who have sex with men (MSM), transmission of enteric pathogens may occur during direct or indirect oral-anal contact. METHODS: We performed a scoping review of the literature for studies prior to July 2019 with key terms for gastrointestinal syndromes ("proctitis," "enteritis," "proctocolitis"), enteric pathogens or sexually transmitted infections (STIs), and outbreaks using multiple electronic databases. RESULTS: We identified 5861 records through database searches, bibliography reviews, and keyword searches, of which 117 references were included in the pathogen-specific reviews. CONCLUSIONS: The strength of observational data describing enteric pathogens in MSM and possible sexual transmission of enteric pathogens varies by pathogen; however, a robust body of literature describes the sexual transmission of Campylobacter, Giardia lamblia, and Shigella (particularly antimicrobial-resistant strains) in sexual networks of MSM. Providers are encouraged to consider enteritis or proctocolitis in MSM as possibly having been sexually transmitted and encourage targeted STI testing. Risk/harm reduction and prevention messages should also be incorporated, though there is an acknowledged paucity of evidence with regards to effective strategies. Further research is needed to understand the transmission and prevention of enteric pathogens in MSM.

Diagnosis and Management of Bacterial Vaginosis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

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.

Surveillance for Disseminated Gonococcal Infections, Active Bacterial Core Surveillance (ABCs)-United States, 2015-2019.

BACKGROUND: Disseminated gonococcal infections (DGIs) are thought to be uncommon; surveillance is limited, and case reports are analyzed retrospectively or in case clusters. We describe the population-level burden of culture-confirmed DGIs through the Active Bacterial Core surveillance (ABCs) system. METHODS: During 2015-2016, retrospective surveillance was conducted among residents in 2 ABCs areas and prospectively in 3 ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae from a normally sterile site. A case report form was completed for each case and antimicrobial susceptibility testing (AST) was performed on available isolates. RESULTS: During 2015-2019, 77 DGI cases were identified (a rate of 0.13 cases per 100 000 population) and accounted for 0.06% of all reported gonorrhea cases in the 3 surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16 to 67 years of age; blood (55%) and joint (40%) were the most common sterile sites. Among 29 isolates with AST results during 2017-2019, all were susceptible to ceftriaxone. CONCLUSIONS: DGI is an infrequent complication of N gonorrhoeae; because it can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations.

Diagnosis and Management of Trichomonas vaginalis: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.

Trichomonas vaginalis is likely the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of trichomoniasis, as African Americans are >4 times more likely to be infected than persons of other races. Since publication of the 2015 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines, additional data have bolstered the importance of T. vaginalis infection sequelae in women, including increased risk of human immunodeficiency virus (HIV) acquisition, cervical cancer, preterm birth, and other adverse pregnancy outcomes. Less is known about the clinical significance of infection in men. Newly available diagnostic methods, including point-of-care assays and multiple nucleic acid amplification tests, can be performed on a variety of genital specimens in women and men, including urine, allowing more accurate and convenient testing and screening of those at risk for infection. Repeat and persistent infections are common in women; thus, rescreening at 3 months after treatment is recommended. In vitro antibiotic resistance to 5-nitroimidazole in T. vaginalis remains low (4.3%) but should be monitored. High rates of T. vaginalis among sexual partners of infected persons suggest a role for expedited partner treatment. A randomized controlled trial in HIV-uninfected women demonstrated that multidose metronidazole 500 mg twice daily for 7 days reduced the proportion of women with Trichomonas infection at 1 month test of cure compared with women receiving single-dose therapy (2 g). The 2-g single-dose oral metronidazole regimen remains the preferred treatment in men.

Sexually Transmitted Infections Treatment Guidelines, 2021.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

Coinfection With Chlamydial and Gonorrheal Infection Among US Adults With Early Syphilis.

ABSTRACT: Among 865 adults with early syphilis considered for a multicenter treatment trial, 234 (27%) were excluded before enrollment because of bacterial sexually transmitted infection coinfection. Coinfection with Neisseria gonorrhoeae (29%), Chlamydia trachomatis (22%), or both (23%) was common. Study findings highlight the need for comprehensive bacterial sexually transmitted infection screening in patients with syphilis.

Recommendations for Providing Quality Sexually Transmitted Diseases Clinical Services, 2020.

This report (hereafter referred to as STD QCS) provides CDC recommendations to U.S. health care providers regarding quality clinical services for sexually transmitted diseases (STDs) for primary care and STD specialty care settings. These recommendations complement CDC's Sexually Transmitted Diseases Treatment Guidelines, 2015 (hereafter referred to as the STD Guidelines), a comprehensive, evidence-based reference for prevention, diagnosis, and treatment of STDs. STD QCS differs from the STD Guidelines by specifying operational determinants of quality services in different types of clinical settings, describing on-site treatment and partner services, and indicating when STD-related conditions should be managed through consultation with or referral to a specialist. These recommendations might also help in the development of clinic-level policies (e.g., standing orders, express visits, specimen panels, and reflex testing) that can facilitate implementation of the STD Guidelines. CDC organized the recommendations for STD QCS into eight sections: 1) sexual history and physical examination, 2) prevention, 3) screening, 4) partner services, 5) evaluation of STD-related conditions, 6) laboratory, 7) treatment, and 8) referral to a specialist for complex STD or STD-related conditions.CDC developed the recommendations by synthesizing relevant, evidence-based guidelines and recommendations issued by other experts; reviewing current practice in the United States; soliciting Delphi ratings by subject matter experts on STD care in primary care and STD specialty care settings; discussing the scientific evidence supporting the proposed recommendations at a consultation meeting of experts and institutional stakeholders held November 20, 2015, in Atlanta, Georgia; conducting peer reviews of draft recommendations and supporting evidence; and discussing draft recommendations and supporting evidence during meetings of the CDC/Health Resources and Services Administration Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment STD Work Group. These recommendations are intended to help health care providers in primary care or STD specialty care settings offer STD services at their clinical settings and to help the persons seeking care live safer, healthier lives by preventing and treating STDs and related complications.

Estimating Recommended Gonorrhea and Chlamydia Treatment Rate Using Linked Medical Claims, Prescription, and Laboratory Data in US Private Settings.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends specific regimens for chlamydia and dual therapy for gonorrhea to mitigate antimicrobial-resistant gonorrhea in the CDC 2015 sexually transmitted disease treatment guidelines. Only limited studies examining adherence to these recommendations have been conducted at private practices in the United States. METHODS: We used the OptumLabs Data Warehouse, a comprehensive, longitudinal data asset with deidentified persons with linked commercial insurance claims and clinical information, to identify persons aged 15 to 60 years who had valid nucleic acid amplification testing results demonstrating urogenital or extragenital gonorrhea or chlamydia in 2016 to 2018. We defined valid laboratory results as positive or negative. We then assessed the time of their first positive test result and the type of treatment within 30 days to determine if there was evidence in the claims record that the CDC-recommended treatment was provided. We defined presumed treatment if the date of treatment was before the date of the positive test result within 30 days. RESULTS: Among 6476 patients with positive gonorrhea test results and 26,847 patients with positive chlamydia test results only, 34.8% and 64.2% had evidence of receiving the CDC-recommended therapy, respectively. Approximately 11.6% of patients with positive gonorrhea test results with recommended dual treatment and 7.1% of patients with positive chlamydia test results only with recommended chlamydia treatment were presumptively treated. CONCLUSION: Analysis of treatment claims and medical records from private settings indicated low rates of recommended gonorrhea and chlamydia treatment. Validation of treatment claims is needed to support further quality of care interventions based on these data.

Evidence Review for Centers for Disease Control and Prevention Guidance Development on Laboratory Testing to Detect Treponema pallidum Infection (Syphilis).

The articles in this supplement address key questions on syphilis diagnostics, provide reference tables of test performances, and discuss optimal specimens and knowledge gaps. Laboratory-developed genetic direct detection tests could be most useful at the point of care and add to the currently available serologic methods of nontreponemal and treponemal tests.