Exploring changes in maternal and congenital syphilis epidemiology to identify factors contributing to increases in congenital syphilis in Florida: a two time-period observational study (2013-2014 vs 2018-2019).

OBJECTIVES: As, cases of congenital syphilis (CS) and infectious syphilis among women more than doubled in Florida and across the nation during 2013-2019, we sought to understand what may be contributing to these increases in Florida. DESIGN: A two time-period observational study. SETTING: Pregnant women with reported syphilis infections and their pregnancy outcomes (2013-2014 and 2018-2019) in Florida. PARTICIPANTS: 1213 pregnant women with reported syphilis infections living in Florida and 341 infants meeting the CS case definition. OUTCOME MEASURES: We assessed what proportion of the increase in CS was from increases in maternal syphilis infections. We examined maternal demographics, infection characteristics and timing of diagnoses that could explain the increase in CS. Finally, we reviewed if changes in presentation or severity of CS cases occurred. RESULTS: During 2013-2014, 83 (21%) of 404 pregnant women with syphilis delivered babies with CS. During 2018-2019, 258 (32%) of 809 pregnant women with syphilis delivered babies with CS. Comparing CS prevention rates, it was determined that 65% of the increase in CS was due to the increases in maternal syphilis infections. The proportion of maternal cases staged as primary or secondary increased over time (7%-13%) (p<0.01) and reports of drug use became slightly more common (6%-10%) (p=0.02). During 2018-2019, women delivering CS infants were more likely to be reinfected during the same pregnancy (27 (10%) vs 5 (6%) p=0.23) and more had negative third trimester screening tests (43 (17%) vs 7 (8% p=0.07)). The percentage of infants with CS who had ≥1 sign or symptom increased from 35% to 40%, and the combined total of stillbirths and infant deaths increased from 5 to 26. CONCLUSIONS: Recently, more pregnant women are being infected with syphilis and a higher per cent are not being treated to prevent CS. The reasons for this finding are unclear.

Predicting Emergence of Primary and Secondary Syphilis Among Women of Reproductive Age in US Counties.

BACKGROUND: Syphilis, a sexually transmitted infection that can cause severe congenital disease when not treated during pregnancy, is on the rise in the United States. Our objective was to identify US counties with elevated risk for emergence of primary and secondary (P&S) syphilis among women of reproductive age. METHODS: Using syphilis case reports, we identified counties with no cases of P&S syphilis among women of reproductive age in 2017 and 1 case or more in 2018. Using county-level syphilis and sociodemographic data, we developed a model to predict counties with emergence of P&S syphilis among women and a risk score to identify counties at elevated risk. RESULTS: Of 2451 counties with no cases of P&S syphilis among women of reproductive age in 2017, 345 counties (14.1%) had documented emergence of syphilis in 2018. Emergence was predicted by the county's P&S syphilis rate among men; violent crime rate; proportions of Black, White, Asian, and Hawaiian/Pacific Islander persons; urbanicity; presence of a metropolitan area; population size; and having a neighboring county with P&S syphilis among women. A risk score of 20 or more identified 75% of counties with emergence. CONCLUSIONS: Jurisdictions can identify counties at elevated risk for emergence of syphilis in women and tailor prevention efforts. Prevention of syphilis requires multidisciplinary collaboration to address underlying social factors.

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.

A New Call to Action to Combat an Old Nemesis: Addressing Rising Congenital Syphilis Rates in the United States.

Congenital syphilis (CS) is on the rise in the United States and is a growing public health concern. CS is an infection with Treponema pallidum in an infant or fetus, acquired via transplacental transmission when a pregnant woman has untreated or inadequately treated syphilis. Pregnant women with untreated syphilis are more likely to experience pregnancies complicated by stillbirth, prematurity, low birth weight, and early infant death, while their children can develop clinical manifestations of CS such as hepatosplenomegaly, bone abnormalities, developmental delays, and hearing loss. One of the ways CS can be prevented is by identifying and treating infected women during pregnancy with a benzathine penicillin G regimen that is both appropriate for the maternal stage of syphilis and initiated at least 30 days prior to delivery. In this article we discuss many of the challenges faced by both public health and healthcare systems with regards to this preventable infection, summarize missed opportunities for CS prevention, and provide practical solutions for future CS prevention strategies.

A Preparedness Model for Mother-Baby Linked Longitudinal Surveillance for Emerging Threats.

INTRODUCTION: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). OBJECTIVES: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants. METHODS: Mother-baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting). RESULTS: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing). DISCUSSION: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

Opening of Large Institutions of Higher Education and County-Level COVID-19 Incidence - United States, July 6-September 17, 2020.

During early August 2020, county-level incidence of coronavirus disease 2019 (COVID-19) generally decreased across the United States, compared with incidence earlier in the summer (1); however, among young adults aged 18-22 years, incidence increased (2). Increases in incidence among adults aged ≥60 years, who might be more susceptible to severe COVID-19-related illness, have followed increases in younger adults (aged 20-39 years) by an average of 8.7 days (3). Institutions of higher education (colleges and universities) have been identified as settings where incidence among young adults increased during August (4,5). Understanding the extent to which these settings have affected county-level COVID-19 incidence can inform ongoing college and university operations and future planning. To evaluate the effect of large colleges or universities and school instructional format* (remote or in-person) on COVID-19 incidence, start dates and instructional formats for the fall 2020 semester were identified for all not-for-profit large U.S. colleges and universities (≥20,000 total enrolled students). Among counties with large colleges and universities (university counties) included in the analysis, remote-instruction university counties (22) experienced a 17.9% decline in mean COVID-19 incidence during the 21 days before through 21 days after the start of classes (from 17.9 to 14.7 cases per 100,000), and in-person instruction university counties (79) experienced a 56.2% increase in COVID-19 incidence, from 15.3 to 23.9 cases per 100,000. Counties without large colleges and universities (nonuniversity counties) (3,009) experienced a 5.9% decline in COVID-19 incidence, from 15.3 to 14.4 cases per 100,000. Similar findings were observed for percentage of positive test results and hotspot status (i.e., increasing among in-person-instruction university counties). In-person instruction at colleges and universities was associated with increased county-level COVID-19 incidence and percentage test positivity. Implementation of increased mitigation efforts at colleges and universities could minimize on-campus COVID-19 transmission.

Syphilitic Reinfections During the Same Pregnancy-Florida, 2018.

ABSTRACT: We reviewed all cases of syphilis reported among pregnant women in Florida in 2018 for syphilitic reinfection. Nineteen (7.3%) of 261 pregnant women with syphilis were reported as reinfected during the same pregnancy. Timely rescreening and treatment prevented 6 (31.6%) of 19 reinfected women from delivering infants with congenital syphilis.

Association Between Social Vulnerability and a County's Risk for Becoming a COVID-19 Hotspot - United States, June 1-July 25, 2020.

Poverty, crowded housing, and other community attributes associated with social vulnerability increase a community's risk for adverse health outcomes during and following a public health event (1). CDC uses standard criteria to identify U.S. counties with rapidly increasing coronavirus disease 2019 (COVID-19) incidence (hotspot counties) to support health departments in coordinating public health responses (2). County-level data on COVID-19 cases during June 1-July 25, 2020 and from the 2018 CDC social vulnerability index (SVI) were analyzed to examine associations between social vulnerability and hotspot detection and to describe incidence after hotspot detection. Areas with greater social vulnerabilities, particularly those related to higher representation of racial and ethnic minority residents (risk ratio [RR] = 5.3; 95% confidence interval [CI] = 4.4-6.4), density of housing units per structure (RR = 3.1; 95% CI = 2.7-3.6), and crowded housing units (i.e., more persons than rooms) (RR = 2.0; 95% CI = 1.8-2.3), were more likely to become hotspots, especially in less urban areas. Among hotspot counties, those with greater social vulnerability had higher COVID-19 incidence during the 14 days after detection (212-234 cases per 100,000 persons for highest SVI quartile versus 35-131 cases per 100,000 persons for other quartiles). Focused public health action at the federal, state, and local levels is needed not only to prevent communities with greater social vulnerability from becoming hotspots but also to decrease persistently high incidence among hotspot counties that are socially vulnerable.

Identification of US Counties at Elevated Risk for Congenital Syphilis Using Predictive Modeling and a Risk Scoring System.

BACKGROUND: Although preventable through timely screening and treatment, congenital syphilis (CS) rates are increasing in the United States, occurring in 5% of counties in 2015. Although individual-level factors are important predictors of CS, given the geographic focus of CS, it is also imperative to understand what county-level factors are associated with CS. METHODS: This is a secondary analysis of reported county CS cases to the National Notifiable Diseases Surveillance System during the periods 2014-2015 and 2016-2017. We developed a predictive model to identify county-level factors associated with CS and use these to predict counties at elevated risk for future CS. RESULTS: Our final model identified 973 (31.0% of all US counties) counties at elevated risk for CS (sensitivity, 88.1%; specificity, 74.0%). County factors that were predictive of CS included metropolitan area, income inequality, primary and secondary syphilis rates among women and men who have sex with men, and population proportions of those who are non-Hispanic black, Hispanic, living in urban areas, and uninsured. The predictive model using 2014-2015 CS outcome data was predictive of 2016-2017 CS cases (area under the curve value, 89.2%) CONCLUSIONS: Given the dire consequences of CS, increasing prevention efforts remains important. The ability to predict counties at most elevated risk for CS based on county factors may help target CS resources where they are needed most.

Multistate Syphilis Outbreak Among American Indians, 2013 to 2015.

This article summarizes a multistate outbreak of heterosexual syphilis, including 134 cases of syphilis in adults and adolescents and at least 2 cases of congenital syphilis, which occurred on an American Indian reservation in the United States during 2013-2015. In addition to providing salient details about the outbreak, the article seeks to document the case-finding and treatment activities undertaken, their relative success or failure, and the lessons learned from a coordinated, multiagency response. Of 134 adult cases of syphilis, 40% were identified by enhanced, interagency contact tracing and partner services, 26% through symptomatic testing, and 16% through screening of asymptomatic individuals as the result of an electronic medical record screening prompt. A smaller proportion of cases were identified by community screening events in high-morbidity communities; high-risk venue-based screening events; other screening, including screening upon request; and prenatal screening at first trimester, third trimester, and day of delivery. Future heterosexual syphilis outbreak responders should act quickly to coordinate a package of high-yield case-finding and treatment activities-potentially including activities that seek to do the following: (1) increase prenatal screening, (2) improve community awareness and symptomatic test seeking, (3) educate providers and improve general screening for syphilis, (4) implement electronic medical record reminders for providers, (5) screen high-morbidity communities and at high-risk venues, and (6) form novel partnerships to accomplish partner services work when the context does not allow for traditional, disease intervention specialist-only partner services.

Use of National Syphilis Surveillance Data to Develop a Congenital Syphilis Prevention Cascade and Estimate the Number of Potential Congenital Syphilis Cases Averted.

BACKGROUND: Recent increases in reported congenital syphilis have led to an urgent need to identify interventions that will have the greatest impact on congenital syphilis prevention. We sought to create a congenital syphilis prevention cascade using national syphilis surveillance data to (1) estimate the proportion of potential congenital syphilis cases averted with current prevention efforts and (2) develop a classification framework to better describe why reported cases were not averted. METHODS: We reviewed national syphilis and congenital syphilis case report data from 2016, including pregnancy status of all reported female syphilis cases and data on prenatal care, testing, and treatment status of mothers of reported congenital syphilis cases to derive estimates of the proportion of pregnant women with syphilis who received prenatal care, syphilis testing, and adequate syphilis treatment at least 30 days before delivery, as well as the proportion of potential congenital syphilis cases averted. RESULTS: Among the 2508 pregnant women who were reported to have syphilis, an estimated 88.0% received prenatal care at least 30 days before delivery, 89.4% were tested for syphilis at least 30 days before delivery, and 76.9% received an adequate treatment regimen that began at least 30 days before delivery. Overall, an estimated 1928 (75.0%) potential congenital syphilis cases in the United States were successfully averted. Among states that reported at least 10 syphilis cases among pregnant women, the estimated proportion of potential congenital syphilis cases averted ranged from 55.0% to 92.3%. CONCLUSIONS: Although the majority of potential congenital syphilis cases in the United States were averted in 2016, there was substantial geographic variation, and significant gaps in delivering timely prenatal care, syphilis testing, and adequate treatment to pregnant women with syphilis were identified. The congenital syphilis prevention cascade is a useful tool to quantify programmatic successes and identify where improvements are needed.

Assessing stakeholder perceptions of the acceptability and feasibility of national scale-up for a dual HIV/syphilis rapid diagnostic test in Malawi.

OBJECTIVES: The WHO recommends pregnant women receive both HIV and syphilis testing at their first antenatal care visit, as untreated maternal infections can lead to severe, adverse pregnancy outcomes. One strategy for increasing testing for both HIV and syphilis is the use of point-of-care (rapid) diagnostic tests that are simple, proven effective and inexpensive. In Malawi, pregnant women routinely receive HIV testing, but only 10% are tested for syphilis at their first antenatal care visit. This evaluation explores stakeholder perceptions of a novel, dual HIV/syphilis rapid diagnostic test and potential barriers to national scale-up of the dual test in Malawi. METHODS: During June and July 2015, we conducted 15 semistructured interviews with 25 healthcare workers, laboratorians, Ministry of Health leaders and partner agency representatives working in prevention of mother-to-child transmission in Malawi. We asked stakeholders about the importance of a dual rapid diagnostic test, concerns using and procuring the dual test and recommendations for national expansion. RESULTS: Stakeholders viewed the test favourably, citing the importance of a dual rapid test in preventing missed opportunities for syphilis diagnosis and treatment, improving infant outcomes and increasing syphilis testing coverage. Primary technical concerns were about the additional procedural steps needed to perform the test, the possibility that testers may not adhere to required waiting times before interpreting results and difficulty reading and interpreting test results. Stakeholders thought national scale-up would require demonstration of cost-savings, uniform coordination, revisions to testing guidelines and algorithms, training of testers and a reliable supply chain. CONCLUSIONS: Stakeholders largely support implementation of a dual HIV/syphilis rapid diagnostic test as a feasible alternative to current antenatal testing. Scale-up will require addressing perceived barriers; negotiating changes to existing algorithms and guidelines; and Ministry of Health approval and funding to support training of staff and procurement of supplies.

Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control?

How do we spot the next sexually transmitted infection? Kyle Bernstein and colleagues look for lessons from past discovery.

Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015.

BACKGROUND: Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described. METHODS: All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing. RESULTS: Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11. CONCLUSIONS: MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.

Verifying Treatment of Reported Cases of Gonorrhea.

BACKGROUND: Verifying correct treatment of reported cases of gonorrhea may slow antibiotic resistance, but verification remains challenging for many sexually transmitted disease (STD) programs due to increased laboratory case reporting and decreased provider reporting. The objectives of this study were to document current reported levels of correct treatment of gonorrhea and to identify approaches and barriers to verifying treatment. METHODS: We reviewed funding opportunity reports for the Centers for Disease Control and Prevention's directly funded STD programs and conducted key-informant interviews to elicit further treatment verification details. RESULTS: Among STD programs containing at least one high-morbidity area, a median of 63.0% of gonorrhea cases were reported as treated correctly with a Centers for Disease Control and Prevention-recommended regimen, although the range reported was wide (11.2%-95.2%). Among cases with some type of documented treatment information, the proportion treated correctly was higher (median, 82.2%) but the use of correct treatment was quite variable among STD programs (range, 56.4%-98.5%). Approaches to verifying gonorrhea treatment included modifying outdated surveillance systems and educating providers about case reporting to enhance the passive capture of treatment information as well as active approaches that supported routine and immediate communication with providers regarding cases missing treatment information. Barriers to treatment verification included low levels of provider reporting, outdated surveillance systems, and human and financial resource constraints. CONCLUSIONS: Baseline assessments revealed that levels of correct gonorrhea treatment vary widely, even after accounting for those cases missing treatment information. Baseline data can help determine whether the active verification of treatment of all cases is warranted.