Stop the spread: predictors of inadequate syphilis treatment in pregnancy.

BackgroundMany syphilis infected pregnant women do not receive treatment, representing a major missed opportunity to reduce the risk of syphilis-related adverse pregnancy outcomes. This study explored correlates of treatment among pregnant women with syphilis in Guangzhou, China.MethodsPregnant women with a diagnosis of syphilis in Guangzhou between January 2014 and December 2016 were included. Information of syphilis treatment and correlates were extracted from a comprehensive national case-reporting system. Multivariate logistic regression was used to identify the correlations between information on the demographic characteristics, previous history, clinical characteristics about current syphilis, information of diagnosing hospital, and receiving no treatment or inadequate treatment among syphilis-seropositive pregnant women. A causal mediation analysis was used to explore the potential mediating role of the timing of syphilis diagnosis in the correlates.ResultsAmong 1248 syphilis-seropositive pregnant women, 379 (30.4%) women received no treatment or inadequate treatment. Migrant pregnant women (adjusted OR = 1.83, 95% CI: 1.25–2.73), multiparous participants (adjusted OR = 3.68, 95% CI: 2.51–5.50), unmarried participants (adjusted OR = 3.21, 95% CI: 1.97–5.28) and unemployed participants (adjusted OR = 2.43, 95% CI: 1.41–4.39) were more likely to receive no treatment or inadequate treatment. Participants who with history of syphilis infection (adjusted OR = 0.59, 95% CI: 0.42–0.82) and with high school and higher education participants (adjusted OR = 0.69, 95% CI: 0.49–0.97) were less likely to receive untreated or inadequately treatment. And that the impact of all these factors (except for the migrants) on treatment status are fully mediated through the syphilis diagnosis time, with the direct effect of migrants that would have resulted in a higher rate of no or inadequate treatment (OR = 2.34, 95% CI: 1.08–5.32) was partially cancelled out by the syphilis diagnosis time.ConclusionsPregnant women who were migrant without local residence and women with syphilis diagnosed at a later gestational age were more likely to slip through the cracks of the existing antenatal care system. More programs should focus on eliminating these gaps of residence-related health inequalities. This research highlights actionable elements for health services interventions that could increase syphilis treatment rates among pregnant women.

Doxycycline is an alternative antibiotic drug for the treatment of syphilis, but data on its efficacy, especially data on its efficacy against late latent syphilis, are limited. A retrospective study was conducted to evaluate the effectiveness of doxycycline for the treatment of patients with different stages of syphilis. Patients who received doxycycline treatment between June 2011 and June 2014 were involved. The serological response to doxycycline was defined as either a negative toluidine red unheated serum test (TRUST) result or a ≥4-fold decrease in titer at 12 months following the treatment. Univariate and multivariate logistic regression analyses were performed to identify factors associated with the serological response. During the study period, a total of 163 syphilis patients were treated with doxycycline, and 118 patients completed doxycycline treatment and the 12-month follow-up. Among the 118 patients, the serological response rate at 12 months was 100.0% (7/7) in patients with primary syphilis, 96.9% (62/64) in patients with secondary syphilis, 91.3% (21/23) in patients with early latent syphilis, and 79.2% (19/24) in patients with late latent syphilis. The total serological response rates were 92.4% (109/118) for preprotocol (PP) patients and 66.9% (109/163) for all intention-to-treat (ITT) patients. In multivariate analysis, patients who serologically responded at 12 months following treatment were positively associated with a higher baseline TRUST titer and an earlier syphilis stage than nonresponders. Our study showed excellent treatment outcomes in patients with different stages of syphilis. Our data, along with those from other reports, support the usage of doxycycline as a good alternative therapeutic option in the treatment of syphilis.

To describe the association between syphilis treatment status and adverse pregnancy and neonatal outcomes among pregnancies complicated by syphilis. Six jurisdictions that participated in SET-NET (Surveillance for Emerging Threats to Mothers and Babies Network) reported data on women with syphilis during pregnancy and outcomes that occurred during 2018-2021. Frequencies of adverse outcomes were reported by syphilis treatment status during pregnancy as defined by the 2021 Sexually Transmitted Infections Treatment Guidelines (inadequate, adequate, and no treatment). Adjusted risk ratios (aRRs) were modeled for each outcome comparing adequate treatment with no treatment and with inadequate treatment, controlling for the pregnant woman's age at infection, education level, insurance status, reported substance use, number of prenatal visits, and stage of syphilis. As of June 7, 2024, 1,682 singleton pregnancies complicated by syphilis were reported, with more than half of pregnant women adequately treated for syphilis (57.6%). Pregnant women with no or inadequate treatment had higher relative frequencies of adverse outcomes (stillbirth, prematurity, low birth weight [LBW], and neonatal intensive care unit [NICU] admission) than those with adequate treatment. The aRRs for stillbirth (9.9% vs 1.4%, aRR 3.72, 95% CI, 1.73-8.03), LBW (30.1% vs 9.9%, aRR 1.51, 95% CI, 1.07-2.14), and NICU admission (66.7% vs 27.0%, aRR 1.60, 95% CI, 1.28-1.98) were higher in pregnant women with no treatment compared with those with adequate treatment. Inadequate treatment was associated with LBW and NICU admission (24.9% vs 9.9%, aRR 1.81, 95% CI, 1.29-2.52; and 57.2% vs 27.0%, aRR 1.61, 95% CI, 1.31-1.99, respectively) compared with adequate treatment. The high relative frequencies of adverse pregnancy and neonatal outcomes associated with inadequately treated or untreated syphilis during pregnancy reinforce the importance of adequate treatment in mitigating the effects of syphilitic infection. Increased attention and systematic strategies are needed to address gaps in screening and treatment before and during pregnancy to reduce adverse pregnancy and neonatal outcomes.

Although doxycycline is widely used as an alternative to benzathine penicillin for the treatment of early and late latent syphilis, data on serological response following treatment with doxycycline among HIV-infected patients are limited. In this study, we analysed serological response to syphilis treatment with doxycycline among HIV-infected patients treated during a benzathine penicillin shortage period and compared with treatment response among patients treated with benzathine penicillin. Cases with neurosyphilis and those treated with suboptimal doses or with concurrent medications in association with benzathine penicillin or doxycycline were excluded. Fifty patients treated with doxycycline from September 2014 to December 2016 were compared with 115 patients treated with benzathine penicillin for early, late latent or latent syphilis of unknown duration. Patients treated with doxycycline were slightly older [(median 49 years old, 95% confidence interval (95% CI) 43-56] than those in the penicillin group (median 44 years old, 95% CI 37-50; P = 0.007). Groups had no statistically significant differences regarding sex, HIV suppression under treatment and syphilis stages. Serological response to treatment, defined as a nonreagent Venereal Disease Research Laboratory (VDRL) or at least a four-fold reduction in VDRL titres measured 6-12 months after treatment, was seen in 72% (95% CI 58-84) of patients treated with doxycycline and 70% (95% CI 60-78) of patients treated with penicillin (P = 0.753). We found no statistically significant differences in serological response to treatment with doxycycline or benzathine penicillin among HIV-infected patients with early, late latent or latent syphilis of unknown duration. Our findings suggest that doxycycline is an acceptable treatment to HIV-infected patients with nontertiary stages of syphilis.

To describe syphilis treatment status and prenatal care among people with syphilis during pregnancy to identify missed opportunities for preventing congenital syphilis. Six jurisdictions that participated in SET-NET (Surveillance for Emerging Threats to Pregnant People and Infants Network) conducted enhanced surveillance among people with syphilis during pregnancy based on case investigations, medical records, and linkage of laboratory data with vital records. Unadjusted risk ratios (RRs) were used to compare demographic and clinical characteristics by syphilis stage (primary, secondary, or early latent vs late latent or unknown) and treatment status during pregnancy (adequate per the Centers for Disease Control and Prevention's "Sexually Transmitted Infections Treatment Guidelines, 2021" vs inadequate or not treated) and by prenatal care (timely: at least 30 days before pregnancy outcome; nontimely: less than 30 days before pregnancy outcome; and no prenatal care). As of September 15, 2023, of 1,476 people with syphilis during pregnancy, 855 (57.9%) were adequately treated and 621 (42.1%) were inadequately treated or not treated. Eighty-two percent of the cohort received timely prenatal care. Although those with nontimely or no prenatal care were more likely to receive inadequate or no treatment (RR 2.50, 95% CI, 2.17-2.88 and RR 2.73, 95% CI, 2.47-3.02, respectively), 32.1% of those with timely prenatal care were inadequately or not treated. Those with reported substance use or a history of homelessness were nearly twice as likely to receive inadequate or no treatment (RR 2.04, 95% CI, 1.82-2.28 and RR 1.83, 95% CI, 1.58-2.13, respectively). In this surveillance cohort, people without timely prenatal care had the highest risk for syphilis treatment inadequacy; however, almost a third of people who received timely prenatal care were not adequately treated. These findings underscore gaps in syphilis screening and treatment for pregnant people, especially those experiencing substance use and homelessness, and the need for systems-based interventions, such as treatment outside of traditional prenatal care settings.

ObjectivesSyphilis is a global health concern with an estimated 12 million infections occurring annually. Due to the increasing rates of new syphilis infections being reported in patients infected with HIV,...

To describe the effects of human immunodeficiency virus (HIV) infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users. Cohort study of intravenous drug users. Medical clinic in a hospital-based methadone maintenance treatment program in New York City. Fifty patients with syphilis, of whom 31 were HIV seropositive and 19 HIV seronegative. Serologic tests for syphilis and clinical manifestations. Stage of syphilis at presentation was not associated with HIV serologic status. No unusual or fulminant manifestations of early syphilis or neurosyphilis were noted among HIV-seropositive cases. Maximum nontreponemal titers were higher among HIV-seropositive (median, 1:128) than among HIV-seronegative (median, 1:32) patients with syphilis (P = 0.05); this difference was present only among patients with first-episode syphilis. All 26 evaluable, HIV-seropositive patients treated for syphilis responded appropriately, including 13 patients given standard or less-than-standard doses of penicillin. Seven of 43 patients (16%) showed reversion to negative treponemal antibody assay results after treatment for syphilis; this finding was not associated with HIV infection, CD4 count, or stage of syphilis. Low nontreponemal titer was weakly associated with treponemal test reversion. Infection with HIV did not alter the stage at presentation, clinical course, serologic manifestations, or response to treatment of syphilis in this cohort of intravenous drug users.

Characteristics of pregnant patients with COVID-19 and liver injury

BackgroundSyphilis screening can be successfully integrated into antenatal clinics, and potentially avert significant morbidity and mortality to unborn infants. A minority of male partners report for testing and treatment, increasing the likelihood of reinfection. We conducted a qualitative study to understand factors influencing male partners to seek treatment after syphilis notification by their pregnant partners.MethodsA purposeful sample of 54 adults who participated in the STOP (Syphilis Treatment of Partners) study was stratified by gender (24 women, 30 male partners) and enrolled for in-depth interviews which were audio recorded, transcribed, and analyzed using the thematic approach.ResultsThe participants’ median age (IQR) was 32 years (25–44), 87% were married, and 57.4% (31/74) had attained secondary education. Fourteen of 22 (63%) female participants reported that they sometimes experienced domestic violence. Male participant’s knowledge of syphilis and their perception of their valued role as responsible fathers of an unborn baby facilitated return. Female’s fear of partner‘s violence and poor communication between partners, were barriers against delivery of the notification forms to partners and subsequent treatment of partners. For men, fear of injection pain, perceptions of syphilis as a genetic disease and as a woman’s problem, busy work schedules, poor access to good STD services, shared facilities with women in clinics, as well as HIV-related stigma were important barrier factors.ConclusionsThe return to the clinic for treatment of male partners after partner notification by infected pregnant women, was low due to limited knowledge about syphilis, fear of painful injection, fears of domestic violence, lack of communication skills (individual characteristics) and syphilis disease characteristics such as signs and symptoms. This, combined with health services characteristics such as structural barriers that hinder male partner treatment, low access, low capacity, work/time challenges, inadequate laboratory services and low clinic personnel capacity; threatens efforts to eliminate mother-to-child infection of syphilis. Improved public messaging about syphilis, better services, legal and policy frameworks supporting STD notification and treatment in resource-constrained settings are needed for effective STD control.Trial registrationClinicaltrials.govNCT02262390., Date Registered October 8 2014.

Little is known about cytokine responses to syphilis infection in HIV-1-infected individuals. We retrospectively identified patients with HIV-1 and Treponema pallidum coinfection. Plasma samples from before, during, and after coinfection were analyzed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. Thirty-six patients were included. IL-10 levels increased significantly in patients with primary or secondary stage syphilis from a median of 12.8 pg/mL [interquartile range (IQR), 11.0-27.8] before infection to 46.7 pg/mL (IQR, 28.4-78.9) at the time of diagnosis (P = 0.027) and decreased to 13.0 pg/mL (IQR, 6.2-19.4) after treatment of syphilis (P <0.001). TNF-alpha levels showed no significant change from before to during syphilis in patients with primary or secondary stage syphilis (median 3.9 pg/mL (IQR, 3.3-9.6) and 9.0 pg/mL (IQR, 5.4-12.6), respectively (P = 0.31); however, treatment of syphilis was associated with a significant decrease in TNF-alpha to a median of 4.2 pg/mL (IQR, 2.7-6.8) (P <0.001). No significant changes in cytokine levels were observed in coinfected with latent stage syphilis.IL-10 and TNF-alpha levels correlated positively with plasma HIV RNA values at the time of diagnosis (r = 0.38, P = 0.023, and r = 0.64, P <0.001, respectively) and correlated inversely with CD4 T cell counts (-0.35, P = 0.036 and r = -0.34, P = 0.042, respectively). HIV-1 and early stage syphilis coinfection were associated with an increase in IL-10. IL-10 and TNF-alpha both decreased after treatment of syphilis. TNF-alpha and IL-10 correlated with low CD4 T cell counts and high plasma HIV RNA values.

IntroductionRates of congenital syphilis and substance use disorder (SUD) have concurrently risen in pregnant patients. Specific substances and their association with inadequately treated syphilis have not yet been identified. The objective of our study was to characterize SUD, including specific drugs of use, among pregnant people with syphilis to determine the association between SUD and adequacy of syphilis treatment.MethodsPatients diagnosed with syphilis during pregnancy between January 1, 2021 and December 31, 2022 were identified. SUD was identified via chart review and confirmed or supported by the use of universal screening for self‐reported SUD, ICD‐10 codes for mothers and neonates, and toxicology. Maternal demographics and delivery and neonatal outcomes were compared among those with and without SUD. Logistic regression models adjusted for maternal age, Black race, nulliparity, and hypertension were used to produce odds ratios relating SUD to delivery and neonatal outcomes. The timing of penicillin treatment initiation less than 30 days versus 30 or more days before delivery in individuals with and without SUD was compared.ResultsOf 225 patients with syphilis during pregnancy, 40 (17.8%) had SUD. Compared to those without SUD, those diagnosed with SUD were more likely to be Non‐Hispanic White with late and limited prenatal care. They were almost six times more likely to have preterm delivery (aOR 5.98 [95% CI 2.47–14.79]) and three times more likely to develop pre‐eclampsia with severe features (aOR 3.48 [95% CI 1.41–8.41]). The most common primary drugs of use included non‐prescription opioids (32%), methamphetamines (32%), and cannabis (20%). Frequency of syphilis treatment initiation less than 30 days before delivery was higher in individuals with SUD (52% vs. 21%, p = 0.001). Methamphetamine was the most common primary drug of use among patients with SUD who were inadequately treated for syphilis and its rate of use was significantly higher when compared to patients with SUD who were adequately treated (9/21 [43%] vs. 4/19 [21%], p = 0.041).ConclusionsPregnant people with SUD, and specifically use of methamphetamines, were more likely to have inadequate syphilis treatment than those without SUD. In addition, demographic and prenatal characteristics differed between individuals with and without SUD, with poorer delivery outcomes observed in patients with SUD and syphilis compared to a syphilis population alone. Future research is needed that addresses the impact of medication‐assisted therapies for the treatment of methamphetamine use on rates of adequate syphilis treatment.

BackgroundCongenital syphilis (CS) incidence has been increasing for the past decade. Previous studies have identified various barriers associated with the entry, retention and linkage into care along the CS Prevention Cascade. In order to develop a targeted intervention to engage community health workers (CHWs) on the CS Prevention Cascade, we conducted a qualitative study to gather their perspective on factors associated with the rise of CS.Figure 1:Qualitative Themes of Community Health Worker Perspectives on the Congenital Syphilis Prevention Cascade*Table 1:Perceived barriers to care leading to acquisition of syphilis and other sexually transmitted infection among women of childbearing age, from the perspective of community health workers.MethodsFrom Chicago, IL, USA, we recruited CHWs who work directly with women of childbearing age in health systems with high CS incidence, to participate in semi-structured interviews. Questions were related to prenatal and obstetric care, syphilis clinical care, sociostructural and psychosocial factors related to the diagnosis. Thematic qualitative analyses were performed to analyze perceived barriers to STI care and management, including maternal syphilis.Table 1:Perceived barriers to care leading to acquisition of syphilis and other sexually transmitted infection among women of childbearing age, from the perspective of community health workers.Results12 CHWs from 5 different organizations completed the study. Generally, the most frequently cited barriers to syphilis care for women of childbearing age are transportation and patient understanding/knowledge, followed by stigma, lost to clinical follow-up, mistrust in the medical system and poor communication. Additional factors identified included issues related to appointment burden, financial stressors, domestic partner violence, inadequate partner testing and treatment, disclosure to partner, substance and alcohol use, and mental health comorbidities. The CHWs all described interest in engaging patients to help overcome these factors including assisting in transportation, education initiatives, and improved communication cohesion with providers. (Figure 1, Table 1)ConclusionNumerous factors identified by CHWs were associated with inadequate testing and treatment of syphilis among women of childbearing age. This data is pivotal to creating novel and effective interventions that engage CHWs along the CS Prevention Cascade, and contribute to reducing the burden of this preventable disease.DisclosuresLilly Cheng-Immergluck, MD, MS, American Academy of Pediatrics: Board Member|Department of Energy: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support

Little is known about the epidemiology of syphilis among adolescents and young adults. This study examined, among more than 17000 young people aged 13-22 years old, trends in rates of syphilis testing and infection; characteristics of infected adolescents; and agreement about syphilis staging and treatment between provider and chart reviewer. Rates of syphilis testing increased but rates of syphilis infection did not increase significantly over a 5-year period. A majority of infected men reported only opposite-sex sexual contact. High agreement between providers and chart reviewers was found. These findings demonstrate the need for complete assessment of risk factors and use of local epidemiology in screening practices.

Background: Congenital syphilis (CS) is a significant public health challenge, requiring early diagnosis and treatment to improve infant outcomes. The aim of this study is to describe public health outcomes of infectious syphilis cases among pregnant patients and factors associated with a CS diagnosis for their infant. Methods: We conducted a retrospective review of demographic and clinical characteristics of infectious syphilis cases diagnosed during pregnancy and resulting infant outcomes in Alberta from 2017 to 2020 from the provincial communicable disease database. Adequate maternal treatment was defined as receiving at least one dose of Benzathine penicillin G-LA 2.4 million units IM at least 28 days before delivery. Univariate and multivariate analysis was performed to determine factors associated with CS diagnosis using SPSS version 25. Results: A total of 374 cases of infectious syphilis were diagnosed in pregnancy, with two patients being diagnosed twice in a single pregnancy. The majority (79.1%; n=296) of women had a live birth, followed by therapeutic abortion (9.4%; n=35), stillbirth (7.5%; n=28) and spontaneous abortion (4.0%; n=15). Infant records (n=265) were available for review (n=117 CS cases and 148 non-cases). Correlates associated with CS were screening time in third trimester (adjusted odds ratio [AOR] 8.4, 95% confidence interval [CI], 2.9–24.6) and fewer than 28 days before delivery (AOR 8.1, 1.4–47.8 [vs. first and second trimester] and inadequate treatment (AOR 86.1, CI, 15.9–466.5). Among the CS cases, 23.1% (n=27) were stillborn compared with one (0.7%) stillbirth in the non-CS infants (p&lt;0.001). Conclusion: The early identification and treatment of syphilis in pregnancy is crucial to preventing poor infant outcomes.

Efficacy of treatment for syphilis in pregnancy