WHO global research priorities for sexually transmitted infections.

Sexually transmitted infections (STIs) are widespread worldwide and negatively affect sexual and reproductive health. Gaps in evidence and in available tools have long hindered STI programmes and policies, particularly in resource-limited settings. In 2022, WHO initiated a research prioritisation process to identify the most important STI research areas to address the global public health need. Using an adapted Child Health and Nutrition Research Initiative methodology including two global stakeholder surveys, the process identified 40 priority STI research needs. The top priorities centred on developing and implementing affordable, feasible, rapid point-of-care STI diagnostic tests and new treatments, especially for gonorrhoea, chlamydia, and syphilis; designing new multipurpose prevention technologies and vaccines for STIs; and collecting improved STI epidemiologic data on both infection and disease outcomes. The priorities also included innovative programmatic approaches, such as new STI communication and partner management strategies. An additional six research areas related to mpox (formerly known as monkeypox) reflect the need for STI-related research during disease outbreaks where sexual transmission can have a key role. These STI research priorities provide a call to action for focus, investment, and innovation to address existing roadblocks in STI prevention, control, and management to advance sexual and reproductive health and wellbeing for all.

Vaccine value profile for herpes simplex virus.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are chronic, highly prevalent viral infections that cause significant morbidity around the world. HSV-2 is sexually transmitted and is the leading cause of genital ulcer disease (GUD). It also increases the risk of HIV acquisition, fueling the HIV epidemic. HSV-1 is typically acquired in childhood through nonsexual contact and contributes to oral and ocular disease, but it can also be sexually transmitted to cause GUD. Both HSV-1 and HSV-2 cause neonatal herpes and neurologic disease. Given the ubiquitous nature of HSV-1 and HSV-2 infections and the limited existing prevention and control measures, vaccination would be the most efficient strategy to reduce the global burden of morbidity related to HSV infection. Vaccine strategies include prophylactic vaccination, which would prevent infection among susceptible persons and would likely be given to adolescents, and therapeutic vaccinations, which would be given to people with symptomatic genital HSV-2 infection. This document discusses the vaccine value profile of both types of vaccines. This 'Vaccine Value Profile' (VVP) for HSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the HSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

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.

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.

Summary of the Centers for Disease Control and Prevention/National Institute of Allergy and Infectious Diseases Joint Workshop on Genital Herpes: 3-4 November 2022.

Genital herpes is caused by infection with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and currently has no cure. The disease is the second-most common sexually transmitted infection in the United States, with an estimated 18.6 million prevalent genital infections caused by HSV-2 alone. Genital herpes diagnostics and treatments are not optimal, and no vaccine is currently available. The Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "CDC/NIAID Joint Workshop on Genital Herpes." This report summarizes 8 sessions on the epidemiology of genital herpes, neonatal HSV, HSV diagnostics, vaccines, treatments, cures, prevention, and patient advocacy perspective intended to identify opportunities in herpes research and foster the development of strategies to diagnose, treat, cure, and prevent genital herpes.

Should We Be Testing for Mycoplasma genitalium on Initial Presentation? Trends in Persistent/Recurrent Urethritis Among Men Presenting for Care in STD Clinics, 2015-2019, STD Surveillance Network.

BACKGROUND: Mycoplasma genitalium is a major contributor to persistent/recurrent urethritis cases. However, there are limited published studies on recent trends of persistent/recurrent urethritis. METHODS: A retrospective analysis was conducted of men presenting with symptomatic urethritis in 16 sexually transmitted disease (STD) clinics from 2015 to 2019. Poisson regression was used to assess trends in the annual proportions of urethritis episodes with follow-up (FU) characterized with persistent/recurrent urethritis symptoms. Results were also stratified by results of chlamydia (CT) and gonorrhea (NG) testing and treatment prescribed. RESULTS: There were 99,897 urethritis episodes, from 67,546 unique men. The proportion of episodes with persistent/recurrent symptomatic FU visits increased 50.8% over a 4-year period (annual percentage change [APC], 11.3%; 95% confidence interval [CI], 6.5-16.3). Similar trends were observed in nonchlamydial nongonococcal urethritis episodes (APC, 12.7%; 95% CI, 6.8-18.9) but increases among those positive for NG (APC, 12.1%; 95% CI, -2.3 to -28.5) or for CT (APC, 7.3%; 95% CI, -6.7 to 23.5) were not statistically significant. Among episodes who received azithromycin as first-line treatment, increases in the proportion of persistent/recurrent FU visits were observed (APC, 12.6%; 95% CI, 8.6-16.7). For episodes where first-line treatment was doxycycline, no significant increases were detected (APC, 4.3%; 95% CI, -0.3 to 9.2). CONCLUSIONS: We found an increase in the proportion of urethritis episodes with persistent or recurrent symptoms over time. Given these observed trends in episodes negative for NG or CT, an etiology not detectable by routine diagnostics was a likely factor in increased persistence, suggesting patients with urethritis may benefit from diagnostic testing for M. genitalium during an initial symptomatic presentation.

Vital Signs: Missed Opportunities for Preventing Congenital Syphilis - United States, 2022.

Introduction: Congenital syphilis cases in the United States increased 755% during 2012-2021. Syphilis during pregnancy can lead to stillbirth, miscarriage, infant death, and maternal and infant morbidity; these outcomes can be prevented through appropriate screening and treatment. Methods: A cascading framework was used to identify and classify missed opportunities to prevent congenital syphilis among cases reported to CDC in 2022 through the National Notifiable Diseases Surveillance System. Data on testing and treatment during pregnancy and clinical manifestations present in the newborn were used to identify missed opportunities to prevent congenital syphilis. Results: In 2022, a total of 3,761 cases of congenital syphilis in the United States were reported to CDC, including 231 (6%) stillbirths and 51 (1%) infant deaths. Lack of timely testing and adequate treatment during pregnancy contributed to 88% of cases of congenital syphilis. Testing and treatment gaps were present in the majority of cases across all races, ethnicities, and U.S. Census Bureau regions. Conclusions and implications for public health practice: Addressing missed opportunities for prevention, primarily timely testing and appropriate treatment of syphilis during pregnancy, is important for reversing congenital syphilis trends in the United States. Implementing tailored strategies addressing missed opportunities at the local and national levels could substantially reduce congenital syphilis.

Safety of Longer-Term Doxycycline Use: A Systematic Review and Meta-Analysis With Implications for Bacterial Sexually Transmitted Infection Chemoprophylaxis.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis, gonorrhea, and chlamydia have significantly increased over the past decade in the United States. Doxycycline as chemoprophylaxis (i.e., postexposure prophylaxis) offers promise for addressing bacterial STIs. The goal of the current study was to evaluate the safety of longer-term doxycycline use (defined as 8 or more weeks) in the context of potential use as STI chemoprophylaxis through a systematic literature review and meta-analysis. METHODS: This review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to search MEDLINE/PubMed for clinical studies published from August 2003 to January 2023 that reported on adverse events with doxycycline use with a focus on side effects and metabolic effects of long-term use. RESULTS: A total of 67 studies were included in the systematic review. Overall, studies on longer-term doxycycline use reported 0% to greater than 50% adverse events ranging from mild to severe. Most common adverse events included gastrointestinal symptoms (i.e., nausea, vomiting, and abdominal pain), dermatologic (i.e., rash), and neurological (i.e., headache and dizziness) symptoms. Discontinuation of doxycycline due to adverse events was relatively uncommon in most studies. A meta-analysis of placebo controlled clinical trials (N = 18) revealed that gastrointestinal and dermatological adverse events were more likely to occur in the doxycycline group. CONCLUSIONS: Longer-term (8+ weeks) doxycycline use is generally safe and may be associated with minor side effects. Further research is needed on the potential metabolic impact of longer-term doxycycline use.

Pandemic Demand for SARS-CoV-2 Testing Led to Critical Supply and Workforce Shortages in U.S. Clinical and Public Health Laboratories.

COVID-19 has brought unprecedented challenges to clinical and public health laboratories. While U.S. laboratories have continued striving to provide quality test results during the pandemic, the uncertainty and lack of supplies became a significant hurdle, hindering day-to-day laboratory operations and the ability to increase testing capacity for both SARS-CoV-2 and non-COVID-19 testing. In addition, long-standing laboratory workforce shortages became apparent, hindering the ability of clinical and public health laboratories to rapidly increase testing. The American Society for Microbiology, the College of American Pathologists, the National Coalition of STD Directors, and the Emerging Infections Network independently conducted surveys in 2020 and early 2021 to assess the capacity of the nation's clinical laboratories to respond to the increase in demand for testing during the COVID-19 pandemic. The results of these surveys highlighted the shortages of crucial supplies for SARS-CoV-2 testing and supplies for other routine laboratory diagnostics, as well as a shortage of trained personnel to perform testing. The conclusions are based on communications, observations, and the survey results of the clinical laboratory, public health, and professional organizations represented here. While the results of each survey considered separately may not be representative of the entire community, when considered together they provide remarkably similar results, further validating the findings and highlighting the importance of laboratory supply chains and the personnel capable of performing these tests for any response to a large-scale public health emergency.

Congenital Syphilis in the Medicaid Program: Assessing Challenges and Opportunities Through the Experiences of Seven Southern States.

INTRODUCTION: Rates of congenital syphilis cases are increasing, particularly among lower socioeconomic populations within the southern United States. Medicaid covers a significant portion of these births, which provides an opportunity to improve birth outcomes. This project sought to collect information from key stakeholders to assess facilitators of and barriers to Medicaid funding of prenatal syphilis screening and to provide insight into improving screening and lowering incidence through the Medicaid program. METHODS: Seven southern states (Alabama, Georgia, Kentucky, Louisiana, North Carolina, South Carolina, and Tennessee) were identified for this assessment. Researchers conducted a legal and policy analysis for each state to gather information on factors affecting congenital syphilis prevention, identify knowledge gaps, and inform the development of interview guides. Seventeen structured interviews with 29 participants were conducted to gather information on facilitators and barriers to receiving timely prenatal syphilis screening through the Medicaid program. Interview transcripts were analyzed and compared to identify key themes. RESULTS: Barriers to timely prenatal syphilis screening include varied laws among the states on the timing of screening, Medicaid reimbursement policies that may not adequately incentivize testing, Medicaid enrollment issues that affect both enrollment and continuity of care, and lack of clear understanding among providers on recommended testing. CONCLUSION: This work provides insight into systemic issues that may be affecting rates of prenatal syphilis screening and incidence among Medicaid enrollees and others in the U.S. South. To address rising congenital syphilis cases, policymakers should consider requiring third trimester syphilis screening, adopting policies to enhance access to prenatal care, adapting Medicaid payment and incentive models, and promoting collaboration between Medicaid and public health agencies.

Mpox virus and transmission through sexual contact: Defining the research agenda.

In a Policy Forum piece, Dr. Nicola Low and colleagues define the research agenda for Mpox virus and transmission through sexual contact.

Field Services-Facilitated Treatment and Prevention: Challenges and Opportunities.

ABSTRACT: Assisted partner services (APS) is a longstanding public health strategy to reduce transmission of sexually transmitted infection (STI) and human immunodeficiency virus in the United States. However, with rapidly increasing rates of STI, innovations to APS are needed to allow health departments to conserve limited public health resources while improving the effectiveness of APS. Disease Intervention Specialists (DIS), public health staff who conduct APS, have a wealth of experience in identifying, locating, and interviewing index patients and their sexual partners, but are currently limited in the services that they are able to provide in the field. Although several state and local health departments are working to expand the role of DIS to incorporate less traditional APS activities, such programs are uncommon. We discuss several services that DIS could conceivably provide in the field, such as STI testing, treatment, and vaccination, and identify critical issues to be addressed to implement these changes in DIS activities on a larger scale. Broadening the scope of DIS activities may result in multiple benefits to health departments, including more effectively delivering STI testing and treatment to hard-to-reach populations, imparting more responsibility to DIS, thereby potentially increasing job satisfaction, and building a workforce that is better prepared for public health crises. Effective approaches to address variable state level regulations governing DIS scope of practice are needed.

HIV and Sexually Transmitted Infections Among Persons with Monkeypox - Eight U.S. Jurisdictions, May 17-July 22, 2022.

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.

Monkeypox Outbreak - Nine States, May 2022.

On May 17, 2022, the Massachusetts Department of Public Health (MDPH) Laboratory Response Network (LRN) laboratory confirmed the presence of orthopoxvirus DNA via real-time polymerase chain reaction (PCR) from lesion swabs obtained from a Massachusetts resident. Orthopoxviruses include Monkeypox virus, the causative agent of monkeypox. Subsequent real-time PCR testing at CDC on May 18 confirmed that the patient was infected with the West African clade of Monkeypox virus. Since then, confirmed cases* have been reported by nine states. In addition, 28 countries and territories,† none of which has endemic monkeypox, have reported laboratory-confirmed cases. On May 17, CDC, in coordination with state and local jurisdictions, initiated an emergency response to identify, monitor, and investigate additional monkeypox cases in the United States. This response has included releasing a Health Alert Network (HAN) Health Advisory, developing interim public health and clinical recommendations, releasing guidance for LRN testing, hosting clinician and public health partner outreach calls, disseminating health communication messages to the public, developing protocols for use and release of medical countermeasures, and facilitating delivery of vaccine postexposure prophylaxis (PEP) and antivirals that have been stockpiled by the U.S. government for preparedness and response purposes. On May 19, a call center was established to provide guidance to states for the evaluation of possible cases of monkeypox, including recommendations for clinical diagnosis and orthopoxvirus testing. The call center also gathers information about possible cases to identify interjurisdictional linkages. As of May 31, this investigation has identified 17§ cases in the United States; most cases (16) were diagnosed in persons who identify as gay, bisexual, or men who have sex with men (MSM). Ongoing investigation suggests person-to-person community transmission, and CDC urges health departments, clinicians, and the public to remain vigilant, institute appropriate infection prevention and control measures, and notify public health authorities of suspected cases to reduce disease spread. Public health authorities are identifying cases and conducting investigations to determine possible sources and prevent further spread. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.¶.

International Classification of Diseases (ICD) Codes Fail to Accurately Identify Injection Drug Use Associated Endocarditis Cases.

OBJECTIVES: Infective endocarditis (IE) secondary to injection drug use (IDU-IE) is a disease with high morbidity, cost, and rapid demographic evolution. Studies frequently utilize combinations of International Statistical Classification of Diseases (ICD) codes to identify IDU-IE cases in electronic medical records. This is a validation of this identification strategy in a US cohort. METHODS: Records from January 1, 2004 to September 31, 2015 for those aged ≥18yo with any ICD-coded IE encounter (inpatient or outpatient) were retrieved from the electronic medical record and then manually reviewed and classified as IDU-IE by strict and inclusive criteria. This registry was then used to assess the diagnostic accuracy of 10 identification algorithms that combined substance use, hepatitis C, and IE ICD codes. RESULTS: IE was present in 629 of the 2055 manually reviewed records; 109 reported IDU within 3 months of IE diagnosis and an additional 32 during their lifetime (141 cases). In contrast, no algorithm identified more than 46 (33%) of these cases. Algorithms assessing encounters with both an IE and substance use code had specificities >99% but sensitivities ≤11% with negative predictive values of 83% to 84% and positive predictive values ranging from 75% to 91%. Use of a hepatitis C OR substance use code with an IE-coded encounter resulted in higher sensitivities of 22% to 32% but more false positives and overall positive predictive value of <70%. This algorithm limited to age ≤45yo had the best, but still low, discrimination ability with an area under the receiver operating characteristic curve of 0.62. CONCLUSION: Substance use and hepatitis C codes have poor ability to accurately classify an IE-coded encounter as IDU-IE or routine IE.

Congenital Syphilis Diagnosed Beyond the Neonatal Period in the United States: 2014-2018.

BACKGROUND AND OBJECTIVES: During 2014-2018, reported congenital syphilis (CS) cases in the United States increased 183%, from 462 to 1306 cases. We reviewed infants diagnosed with CS beyond the neonatal period (>28 days) during this time. METHODS: We reviewed surveillance case report data for infants with CS delivered during 2014-2018 and identified those diagnosed beyond the neonatal period with reported signs or symptoms. We describe these infants and identify possible missed opportunities for earlier diagnoses. RESULTS: Of the 3834 reported cases of CS delivered during 2014-2018, we identified 67 symptomatic infants diagnosed beyond the neonatal period. Among those with reported findings, 67% had physical examination findings of CS, 69% had abnormal long-bone radiographs consistent with CS, and 36% had reactive syphilis testing in the cerebrospinal fluid. The median serum nontreponemal titer was 1:256 (range: 1:1-1:2048). The median age at diagnosis was 67 days (range: 29-249 days). Among the 66 mothers included, 83% had prenatal care, 26% had a syphilis diagnosis during pregnancy or at delivery, and 42% were not diagnosed with syphilis until after delivery. Additionally, 24% had an initial negative test result and seroconverted during pregnancy. CONCLUSIONS: Infants with CS continue to be undiagnosed at birth and present with symptoms after age 1 month. Pediatric providers can diagnose and treat infants with CS early by following guidelines, reviewing maternal records and confirming maternal syphilis status, advocating for maternal testing at delivery, and considering the diagnosis of CS, regardless of maternal history.