Development and validation of an individualised nomogram to predict mother-to-child transmission in pregnant women with syphilis in China: a retrospective cohort study.

OBJECTIVES: The elimination of mother-to-child transmission (MTCT) of syphilis has been set as a public health priority. However, an instrument to predict the MTCT of syphilis is not available. We aimed to develop and validate an intuitive nomogram to predict the individualised risk of MTCT in pregnant women with syphilis in China. DESIGN: Retrospective cohort study. SETTING: Data was acquired from the National Information System of Prevention of MTCT of Syphilis in Guangdong province between 2011 and 2020. PARTICIPANTS: A total of 13 860 pregnant women with syphilis and their infants were included and randomised 7:3 into the derivation cohort (n=9702) and validation cohort (n=4158). PRIMARY OUTCOME MEASURES: Congenital syphilis. RESULTS: Among 13 860 pregnant women with syphilis and their infants included, 1370 infants were diagnosed with congenital syphilis. Least absolute shrinkage and selection operator regression and multivariable logistic regression showed that age, ethnicity, registered residence, marital status, number of pregnancies, transmission route, the timing of syphilis diagnosis, stage of syphilis, time from first antenatal care to syphilis diagnosis and toluidine red unheated serum test titre were predictors of MTCT of syphilis. A nomogram was developed based on the predictors, which demonstrated good calibration and discrimination with an area under the curve of the receiver operating characteristic of 0.741 (95% CI: 0.728 to 0.755) and 0.731 (95% CI: 0.710 to 0.752) for the derivation and validation cohorts, respectively. The net benefit of the predictive models was positive, demonstrating a significant potential for clinical decision-making. We have also developed a web calculator based on this prediction model. CONCLUSIONS: Our nomogram exhibited good performance in predicting individualised risk for MTCT of syphilis, which may help guide early and personalised prevention for MTCT of syphilis.

Treponema pallidum PCR with blood and cerebrospinal fluid of newborns exposed and not exposed to syphilis during pregnancy.

INTRODUCTION: Congenital syphilis (CS) has severe adverse outcomes, including abortion and death. Diagnosis of CS in asymptomatic newborns remains difficult. This study aims to evaluate an in-house polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) and blood samples (BS) to identify T. pallidum DNA in newborns. METHODOLOGY: We performed an exploratory cross-sectional study that included newborns exposed to syphilis during pregnancy (SEG) and non-exposed (SNEG) newborns, between 2019 and 2020. In-house conventional PCR for T. pallidum targeting the tpp47 gene was used to analyze CSFS and dried blood spots. RESULTS: BS was obtained from 54 newborns (33 SEG/21 SNEG) and CSF from 55 newborns (33 SEG/22 SNEG). Twenty-five (71.4%) SEG newborns had reactive BS rapid plasmatic reagins (RPR), and all of them had RPR titers less than or equal to the corresponding maternal titers. All RPR CSF tests were negative. PCR for T. pallidum DNA was positive in 19/33 (57.6%) BS, and in 22/33 CSF. The only SEG newborn with clinical signs of early CS had a positive CSF PCR and a negative BS PCR. Conversely, among SNEG newborns, PCR was positive in 2/21 BS and 5/22 (22.7%) CSF. CONCLUSIONS: T. pallidum DNA was identified using our PCR tests. The exposed group did not present abnormalities that would indicate CS. This prevented conclusions regarding sensitivity and specificity. Dried spot permitted bedside collection, easy transportation, and storage. Further research is needed to evaluate and improve the accuracy of CS low-cost PCR tests, especially for limited resource settings.

Sociodemographic and clinical characteristics associated with maternal and congenital syphilis - A prospective study in Peru.

OBJECTIVES: The objective of this study was to explore the factors and outcomes associated with gestational syphilis in Peru. METHODS: Women from the miscarriage, vaginal delivery, and C-section wards from a large maternity hospital in Lima with or without syphilis diagnosis were enrolled and their pregnancy outcomes compared. Maternal syphilis status using maternal blood and child serostatus using cord blood were determined by rapid plasma reagin (RPR) and rapid syphilis tests. The newborns' clinical records were used to determine congenital syphilis. RESULTS: A total of 340 women were enrolled, 197 were positive and 143 were negative for RPR/rapid syphilis tests. Antibody titers in sera from cord and maternal blood were comparable with RPR titers and were highly correlated (rho = 0.82, P <0.001). Young age (P = 0.009) and lower birth weight (P = 0.029) were associated with gestational syphilis. Of the women with gestational syphilis, 76% had received proper treatment. Mothers of all newborns with congenital syphilis also received appropriate treatment. Treatment of their sexual partners was not documented. CONCLUSIONS: Syphilis during pregnancy remains a major cause of the fetal loss and devastating effects of congenital syphilis in newborns.

Severe pulmonary hypertension and circulatory failure associated with Congenital syphilis. Case report.

BACKGROUND: Congenital syphilis is a vertical infection caused by Treponema pallidum. Despite the implementation of preventive strategies during pregnancy, its incidence is increasing, and it constitutes an important public health problem. Most patients with congenital syphilis are asymptomatic; however, a small group may develop severe disease at birth with the need of advanced resuscitation in the delivery room, acute hypoxemic respiratory failure, and hemodynamic instability. Therefore, awareness is needed. METHODS AND RESULTS: This series describes the clinical course of two late preterm infants with congenital syphilis who developed acute hypoxemic respiratory failure, pulmonary hypertension, and circulatory collapse early after birth. Integrated hemodynamic evaluation with neonatologist-performed echocardiography (NPE) and therapeutic management is provided. CONCLUSIONS: A comprehensive hemodynamic evaluation including early and serial functional echocardiography in these patients is needed to address the underlying complex pathophysiology and to help to establish accurate treatment.

Factors influencing the positivity of diagnostic tests for congenital syphilis.

OBJECTIVE: The objective of this study was to analyze the factors that influence the positivity of treponemal and non-treponemal tests in cases of congenital syphilis. METHODS: This cross-sectional and correlational study was carried out from the analysis of the database of Disease and Notification Information System (SINAN, in Portuguese) using the data obtained through the Epidemiological Surveillance Group 29, with 639 notifications of congenital syphilis between 2007 and 2018. The data were analyzed by a descriptive and inferential analysis from logistic regression with a significance level of 5% (p≤0.05). RESULTS: The positivity of the treponemal test was higher by 4.5 times in infants living in rural areas and 19.6 times among those whose mothers obtained the diagnosis of syphilis after birth. The treponemal test showed positivity 3.2 times higher for the variable "having been diagnosed between 2007 and 2015" and 5.5 times higher for the variable "having been diagnosed with maternal syphilis in the postpartum period." CONCLUSION: This study shows that testing during prenatal care is essential for early diagnosis and prevention of syphilis complications.

Scoping review of hearing loss attributed to congenital syphilis.

BACKGROUND: There are no narrative or systematic reviews of hearing loss in patients with congenital syphilis. OBJECTIVES: The aim of this study was to perform a scoping review to determine what is known about the incidence, characteristics, prognosis, and therapy of hearing loss in children or adults with presumed congenital syphilis. ELIGIBILITY CRITERIA: PROSPERO, OVID Medline, OVID EMBASE, Cochrane Library (CDSR and Central), Proquest Dissertations and Theses Global, and SCOPUS were searched from inception to March 31, 2023. Articles were included if patients with hearing loss were screened for CS, ii) patients with CS were screened for hearing loss, iii) they were case reports or case series that describe the characteristics of hearing loss, or iv) an intervention for hearing loss attributed to CS was studied. SOURCES OF EVIDENCE: Thirty-six articles met the inclusion criteria. RESULTS: Five studies reported an incidence of CS in 0.3% to 8% of children with hearing loss, but all had a high risk of bias. Seven reported that 0 to 19% of children with CS had hearing loss, but the only one with a control group showed comparable rates in cases and controls. There were 18 case reports/ case series (one of which also reported screening children with hearing loss for CS), reporting that the onset of hearing loss was usually first recognized during adolescence or adulthood. The 7 intervention studies were all uncontrolled and published in 1983 or earlier and reported variable results following treatment with penicillin, prednisone, and/or ACTH. CONCLUSIONS: The current literature is not informative with regard to the incidence, characteristics, prognosis, and therapy of hearing loss in children or adults with presumed congenital syphilis.

The resurgence of syphilis in Australia.

BACKGROUND: Syphilis infections have been increasing in Australia over the past decade. This phenomenon has been associated with a re-emergence of congenital syphilis. OBJECTIVE: The aim of this article is to describe recent epidemiological trends of syphilis infection in Australia, including demographics in which infection rates are rising, such as women of reproductive age. This article also provides an overview of the clinical course and the principles of management for syphilis. DISCUSSION: Considered by some as a disease of bygone eras, the resurgence of syphilis in Australia requires clinicians to be alert to this infection once again. Increased testing, prompt management and thorough contact tracing are all required to reverse this trend. Congenital syphilis is a potentially devastating yet preventable consequence of rising infections among women of reproductive age. Universal syphilis screening is recommended for all pregnant women at the initial antenatal visit and is now also recommended in the third trimester in several Australian jurisdictions.

Provider-Reported Barriers in Sexual Health Care Services for Women With Upstream Barriers: The Case of Syphilis and Congenital Syphilis in Southern Colorado, 2022.

BACKGROUND: Syphilis and congenital syphilis rates have increased sharply in Colorado in the past 5 years. Congenital syphilis is passed during pregnancy in utero and can cause lifelong physical, developmental, and neurologic problems for the child, or can lead to miscarriage, stillbirth, or early infant death. Congenital syphilis is easily prevented if the mother receives timely testing, treatment, and prenatal care. Providers can play a key role in preventing congenital syphilis for women with social vulnerabilities, who have a higher likelihood of syphilis and/or congenital syphilis infection. METHODS: We surveyed 23 and interviewed 4 health care providers in southern Colorado in 2022 to record their experiences in providing sexual health care services. We asked providers with direct care experience about perceived barriers in effectively treating syphilis. RESULTS: The most significant barriers reported in the survey were the cost of treatment (26%) and the loss to follow-up (22%). Interviews revealed further challenges, including discretionary testing procedures, delays in screening results, treatment referral issues, and stigma around substance use and sexual activity. CONCLUSIONS: Elevated syphilis and congenital syphilis rates pose significant public health challenges. Coordinated interventions are necessary to effectively reduce the transmission of syphilis and congenital syphilis among women with upstream barriers. Potential care solutions include expanding rapid, point-of care testing and treatment options, supporting bicillin delivery or web-based inventory systems, offering anti-stigma training for providers, offering mental and behavioral health resources at providers' clinics, and expanding partnerships with syringe access programs.

Update on syphilis in pregnancy: marrying basic science advances and clinical perseverance to solve an ancient public health problem.

PURPOSE OF REVIEW: While the clinical disease of syphilis, its consequences in pregnancy, and its sensitivity to penicillin treatment have remained relatively unchanged for a century or more, new technologies and basic discoveries in syphilis research have translated into tangible advances in clinical diagnosis, treatment, and prevention. The purpose of this review is to help the reader understand some of the recent relevant scientific publications on syphilis and its causative organism in a clinical obstetric context. RECENT FINDINGS: Rates of adult and congenital syphilis have risen dramatically in the last decade despite public health efforts. Penicillin shortages and lack of screening or adequate treatment have all contributed to global disease burden. Advances in genomic and microbiological characterization of this spirochete have led to new developments in serologic and molecular diagnosis as well as evaluation of potential vaccine candidates. Until a syphilis vaccine is available, substance use disorders and lack of screening in pregnancy are associated with increased congenital syphilis, and these challenges will require novel solutions to fully address this public health crisis. SUMMARY: Addressing the burden of congenital syphilis demands that obstetricians stay well informed of new tools and resources for diagnosis, treatment, and prevention of syphilis now and in the future.

Congenital syphilis: the re-emergence of a forgotten disease.

A preterm newborn presented at birth with generalised oedema, disseminated bullous and desquamative exanthema with palmoplantar involvement and hepatomegaly, admitted to the neonatal intensive care unit with severe multisystemic disease, haemodynamic instability and respiratory distress. The mother had a history of treated latent syphilis before pregnancy. Venereal Disease Research Laboratory screening was negative in the first trimester, titre 1:2 in second trimester and 1:32 in the third trimester, a result only available to the medical team at birth. The mother's rapid plasma reagin (RPR) titre was 1:64 at birth. The newbon's RPR titre was 1:256, confirming the diagnosis of early congenital syphilis. The newborn was treated with aqueous penicillin G, with clinical and laboratorial progressive recovery. Congenital syphilis is a preventable disease, but despite prenatal screening programmes, it remains a significant public health issue worldwide with high morbidity and mortality.

[Association of illicit drug use in pregnant women and congenital syphilis in a public hospital in Mexico]. / Asociación del consumo de drogas ilícitas en mujeres embarazadas y sífilis congénita en un Hospital Público de México.

We conducted a nested case-control study within a cohort with the aim of studying the association between illicit drug use and congenital syphilis (CS). Cases were diagnosed based on treponemal and non-treponemal tests conducted both in the mother and the newborn (NB). Multivariate analysis with logistic regression was performed. A total of 6171 births with a mean gestational age of 37.8 weeks were recorded and 62 CS events were diagnosed (incidence 10.5 events/1000 NB). Associated maternal factors were illicit drug use (OR 14.08, 95% CI 1.19-166.6), <5 prenatal visits (OR 2.9, 95% CI 1.12-7.53), more than two sexual partners (OR 3.76, 95% CI 1.62-8.71) and professional education level (OR 0.06, 95% CI 0.005-0.85). Among the mothers of the cases presented, the prevalence of illicit drug use was 22.6% and the most frequent drugs were methamphetamines and cannabis.

Congenital bullous syphilis in a newborn: A novel approach to diagnosis using immunohistochemical staining on a blister roof.

We describe a rare presentation of congenital bullous syphilis in a premature neonate born with extensive skin desquamation. The newborn was noted to have diffuse erythema with widespread, superficial skin desquamation in addition to plantar bullae and erosions, and an absence of mucosal involvement. Immunohistochemical syphilis diagnostic staining was performed on a blister roof, highlighting a novel diagnostic approach for congenital bullous syphilis.

Pemphigus syphiliticus with Jarisch-Herxheimer reaction in a newborn.

Congenital syphilis is a serious, disabling, and life-threatening infection that is transmitted transplacentally from mother to fetus. Early diagnosis is often difficult because affected infants are usually asymptomatic at birth and clinical findings are often subtle and nonspecific. Pemphigus syphiliticus is an early presentation of congenital syphilis which is characterized by fluid-filled vesicles and bullae which appear mostly on the extremities and tend to rapidly desquamate and erode. Awareness of the clinicians to this early cutaneous manifestation and possible treatment reaction will allow for prompt diagnosis and adequate treatment of syphilis-infected patients.

Clinical-Demographic and Laboratory Profile of the Mother-Child Binomial With Syphilis in a Tertiary-Level Hospital in Mexico.

BACKGROUND: Congenital syphilis (CS) remains a major public health problem, and its incidence is increasing worldwide. METHODS: Retrospective, observational, and descriptive study of cases with CS and their mothers at a tertiary-level hospital in Mexico from 2017 to 2022. Medical records of patients with CS and a structured collection of epidemiological, clinical, and laboratory data were analyzed and classified in the Centers for Disease Control scenarios as confirmed, probable, less probable, or unlikely. RESULTS: One hundred eighty cases were diagnosed with a compatible definition of congenital syphilis, and we identified 43 (21.21%) confirmed proven. Among those proven cases, 15.6% had hematological, 13.3% skin, 12.2% liver, 6.7% pulmonary, 6.6% neurological, 5.8% eye, 5.6% bone, and 0.6% hearing involvements. According to the clinical stages of maternal syphilis, 119 (66.1%) were in the late latent phase, 49 (27.2%) in the early latent phase, 7 (3.9%) in the secondary stage, and 5 (2.8%) in the primary stage. Mothers with tertiary syphilis were not detected. CONCLUSION: Regardless of negative antenatal screening, health care workers should consider the diagnosis of congenital syphilis. Infants are still undiagnosed at birth, and only a tiny percentage exhibits symptoms. The wide range of clinical manifestations of this preventable infection can be misdiagnosed for various other diseases, causing diagnostic delays that can have serious consequences.

Syphilis for dermatologists: Current concepts.

Dermatologists are familiar with the classic aspects of syphilis. Our objective in this update is to display novel features of sexually acquired syphilis, its pathophysiology, natural history, atypical clinical variants, skin of color, clinical pearls, and prospects. Textbook knowledge, congenital syphilis, epidemiology, and historical data are excluded.