Clinical characteristics and outcomes for paediatric patients admitted with congenital or acquired syphilis: a population-based cohort study.

OBJECTIVES: Paediatric congenital and acquired syphilis cases have been increasing since 2012 in the USA. Potential differences in associated hospitalisation trends and healthcare utilisation between the two syphilis entities have not yet been assessed. We sought to compare these entities and describe their clinical characteristics, distribution and impact in the USA. METHODS: We conducted a population-based cohort study using the 2016 Kids' Inpatient Database (KID) to identify and characterise syphilis-associated hospitalisations among paediatric patients (age 0-21 years) in the USA during the year of 2016. Length of stay and hospitalisation costs for patients with congenital and acquired syphilis were compared in multivariable models. RESULTS: A total of 1226 hospitalisations with the diagnosis of syphilis were identified. Of these patients, 958 had congenital syphilis and 268 were acquired cases. The mean cost of care for congenital syphilis was $23 644 (SD=1727), while the treatment of a patient with acquired syphilis on average cost $10 749 (SD=1966). Mean length of stay was 8 days greater and mean total costs were $12 895 (US dollars) higher in the congenital syphilis cohort compared with the acquired syphilis cohort. In congenital syphilis, there were greater frequency of cases in the Southern and Western regions of the USA (p<0.001). CONCLUSION: Congenital syphilis was associated with greater healthcare-related expenditure than acquired syphilis in paediatric patients. In addition to improving patient outcomes, congenital syphilis prevention efforts may significantly reduce healthcare utilisation burden and cost.

Congenital syphilis: A contemporary update on an ancient disease.

Congenital syphilis (CS) rates reached a 20-year high in the United States in 2018. Unlike previous years, most babies diagnosed with CS were born to mothers who received prenatal care, indicative of the need for better provider education and guideline adherence. Current rates suggest that screening for syphilis should be performed at the first prenatal care visit and twice during the third trimester. There are two diagnostic algorithms available for use in the United States (traditional and reverse) and providers must understand how to perform each algorithm. Treatment should be administered according to stage of syphilis per Centers for Disease Control recommendations with best neonatal outcomes seen when treatment is initiated >30 days before delivery. Benzathine Penicillin G remains the only recommended treatment of syphilis during pregnancy. In viable pregnancies, a pretreatment ultrasound is recommended to identify sonographic evidence of fetal infection and treatment should be initiated with continuous fetal monitoring to evaluate for the Jarisch-Herxheimer reaction which can cause preterm labor and fetal distress. After adequate syphilotherapy, a fourfold decline in maternal nontreponemal titers may not be observed by delivery and does not correlate with rates of CS.

Notification and management of congenital syphilis in the Northern Territory 2009 to 2014.

OBJECTIVE: To determine whether cases of congenital syphilis in the Northern Territory between 2009 and 2014 were correctly notified based on probable or confirmed case criteria stipulated by the Communicable Diseases Network Australia (CDNA). METHODS: Pregnant women with positive syphilis serology defined as reactive treponemal test and rapid plasma reagin titre ≥1:8 were identified from the Northern Territory Syphilis Register Information System. Risk classification was performed based on local guidelines, and CDNA criteria for probable/confirmed cases of congenital syphilis were applied to determine whether cases were appropriately notified. RESULTS: Thirty-four cases of positive maternal syphilis serology in pregnancy were identified from 31 women; all were Indigenous. Twenty-one cases fulfilled criteria for probable congenital syphilis; 1 case was formally notified to the Centre for Disease Control. Twenty cases (95%) fulfilling CDNA criteria for probable congenital syphilis were not notified over the study period. CONCLUSIONS: Application of standard case definitions significantly increases the rate of congenital syphilis cases in the Northern Territory. Improved education regarding CDNA criteria for notification of congenital syphilis is necessary for clinicians and public health staff. Emerging evidence has supported the recent simplification of CDNA criteria for notification of congenital syphilis, effective 1 July 2015.

31-Week Premature Male with Congenital Syphilis.

The incidence of syphilis is on the rise in many parts of the U.S., including South Dakota. We present a case of congenital syphilis and review the evaluation, clinical course, and treatment of this devastating disease process.

[Early congenital syphilis: a case report]. / Sífilis congénita precoz: a propósito de 2 casos clínicos.

INTRODUCTION: Congenital syphilis (CS) is a multisystemic infection of the newborn (NB) which can produce severe symptoms, and in some cases, even be fatal. In recent years, the incidence of syphilis has increased worldwide and similarly, the cases of CS in neonates have increased. OBJECTIVE: To report two cases of early and severe presentation of CS, focusing on the importance of prevention of vertical transmission and monitoring of treated mothers. The diagnostic difficulties are discussed. CLINICAL CASES: Two premature newborns that were diagnosed with probable CS present in the newborn period are presented. In the first case, due to a high index of suspicion, but without confirmatory testing, treatment was started with good clinical response. In the second case, CS was confirmed through positive serology and the specific treatment was given. CONCLUSION: CS has significant diagnostic challenges as there is no test for early confirmation, therefore, a high index of suspicion might be key in the treatment and consequent prognosis. Due to the current epidemiology of the condition, it is also important to focus on preventive measures.

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

BACKGROUND: The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. METHODS AND FINDINGS: Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. CONCLUSIONS: Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment. In this analysis, most adverse outcomes occurred among women who attended ANC but were not tested or treated for syphilis, highlighting the need to improve the quality of ANC as well as ANC coverage. In addition, improved ANC data on syphilis testing coverage, positivity, and treatment are needed. Please see later in the article for the Editors' Summary.

Congenital syphilis in the 21st century.

While the prevalence of congenital syphilis continues to be low throughout most of the developed world, there has been a slight resurgence of the disease in several European countries, including Spain. In this context, we need to become more familiar with the signs and symptoms of this disease and consider its diagnosis in patients with only mild clinical manifestations. A definitive diagnosis may be difficult or even impossible in patients whose diagnostic tests reveal low positive titers or inconsistent results. The cornerstone of congenital syphilis control is prenatal screening and the treatment of infected mothers with penicillin, an effective and economical intervention. Based on a review of the literature supplemented by data from our own clinical experience, this article provides a detailed description of the clinical manifestations of congenital syphilis as well as the various diagnostic methods and treatments available.

Congenital syphilis in a preterm newborn with gastrointestinal disorders and postnatal growth restriction.

BACKGROUND: Congenital syphilis (CS) depends on the placental transmission of Treponema pallidum (TP) spirochetes from an infected mother to fetus during pregnancy. It shows a wide clinical variability with cutaneous and visceral manifestations, including stillbirths, neonatal death, and asymptomatic cases. Preterm infants with CS may have more severe features of disease than the term ones, due to the combined pathogenic effect of both CS and prematurity. CASE PRESENTATION: We report on a female preterm (32+6 weeks of gestation) newborn showing most of the typical CS manifestations, in addition to gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth restriction. The mother resulted positive at the syphilis screening test of the first trimester of pregnancy, but she did not undergo any treatment. At birth, our newborn was VDRL positive (antibody titer four times higher compared to the mother), and she was treated with intravenous benzathine benzylpenicillin G for 10 days (50,000 IU/Kg three times per day). Poor tolerance to enteral nutrition (abdominal distension, increased biliary type gastric secretions) was observed. A barium enema X-Ray identified a colon stenosis within the descending tract. However, the poor general conditions due to a concurrent fungal sepsis did not allow to perform any surgical procedure, and a conservative approach with total parenteral nutrition was started. The following evolution was marked by difficulties in enteral feeding including refusal of food and vomiting, to which also contributed the neurological abnormalities related to a perinatal asphyxia, and the affective deprivation for the physical absence of the mother during hospitalization. At 5 months of age, after the introduction of an amino acid-based formula (Neocate LCP Nutricia ®), an improvement of enteral feeding was observed, with no further and significantly decreased episodes of abdominal distension and vomiting respectively, and regular stool emission. A psychological support offered to the family allowed a more stable bond between the mother and her baby, thus providing a significant additional benefit to food tolerance and growth. She was discharged at 5 months of age, and included in a multidisciplinary follow-up. She at present shows global growth delay, and normal development apart from mildly increased tone of lower limbs. CONCLUSIONS: Our report highlights less common clinical CS manifestations like gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth delay. Moreover, it underlines how prematurity may worsen the clinical evolution of such congenital infection, due to the additional pathogenic effect of possible associated diseases and/or conditions like sepsis, hypoxic/ischemic injury, or use of drugs. CS may be observed also in high-income countries, with high rates of antenatal screening and availability of prenatal treatment. A multidisciplinary network must be guaranteed to the affected subjects, to ensure adequate care and improve the quality of life for patients and their families.

Disseminated intravascular coagulation with intracranial haematoma in neonatal congenital syphilis.

Disseminated intravascular coagulation (DIC) although a well known complication in neonatal sepsis is extremely rare in congenital syphilis and there are scanty reports of this entity in the literature. Intracranial bleeding following DIC in neonatal congenital syphilis is even rarer, and has been reported only once earlier. We are reporting the second case of neonatal DIC with intracranial haematoma due to congenital syphilis in a newborn. Our patient also had clinical and biochemical evidence of hepatitis which predisposes to DIC. Extensive investigations and emergent use of imaging modalities including ultrasound and CT scan led to early diagnosis and treatment in our patient, who could therefore be salvaged from an otherwise life threatening disease.

Resurgence of congenital syphilis: diagnosis and treatment.

Despite comprehensive antenatal screening recommendations and inexpensive treatment, congenital syphilis has long been and continues to be a public health concern, causing substantial morbidity and adverse outcomes. The following article reviews syphilis etiology and presentation, clinical disease, laboratory diagnosis, and treatment of congenital syphilis. A case will be presented describing a 31-week male infant exposed to infectious syphilis in utero. The neonate presented with classic signs of infection at birth. After initial serology testing of the infant, appropriate treatment was commenced. The infant received crystalline penicillin G for a period of ten days in consultation with pediatric infectious disease specialists. As expected, the infant's rapid plasma reagin (RPR) titers declined by three and six months of age. An interdisciplinary approach provided safe and optimal care for this infant. He was discharged, stable, and thriving at 38 weeks corrected age. Long-term multidisciplinary management and follow-up were arranged.

Congenital syphilis in a 4-month-old infant with limb weakness.

We describe a rare case of a 4-month-old girl presenting with a several month history of reduced movement to the left arm accompanied by a maculopapular rash to the limbs. X-ray findings included inflammatory periosteal changes to the radius and ulna. Treponema pallidum IgM was detected in both baby and mother, and a diagnosis of congenital syphilis was made. This case is an interesting clinical picture with a variety of important differential diagnoses, including non-accidental injury, malignancy, autoimmune disease and other congenital infections. With an increasing rate of congenital syphilis infection in the developed world, it is vital that clinicians are able to recognise symptoms to ensure prompt diagnosis and treatment. In this respect, we can attempt to avoid the chronic and potentially life-threatening complications of untreated infection.

A risk model for congenital syphilis in infants born to mothers with syphilis treated in gestation: a prospective cohort study.

OBJECTIVE: To explore the risk factors underlying congenital syphilis (CS) and to build a hazards model to assess the risk of CS in offspring born to mothers with syphilis treated in gestation. METHODS: This prospective study observed 554 pregnant women with syphilis and their offspring recruited from August 2002 to May 2007 in Shenzhen Centre for Chronic Disease Control and Prevention. After treatment, all the women were followed up until the diagnosis of CS in their offspring was confirmed or denied. Comparisons were made between women bearing infants with CS and women bearing infants without CS to reveal the risk factors for CS. ORs and their 95% CI were calculated for each risk factor by using logistical regression analysis. RESULTS: Twenty-nine (5.2%) infants were diagnosed with CS. Univariable analyses showed that the reciprocal logarithm of the titre of non-treponemal antibodies in mothers (log (1/T); OR=11.18, p<0.001), gestational week (GW) at treatment (OR=1.10, p<0.001) and the interaction between these two variates (OR=1.09, p<0.001) was associated with CS. Multivariable analysis showed that only the interaction was significantly associated with CS (OR=1.09, p=0.047). CONCLUSIONS: The risk of CS could be predicted by the interaction between GW x log (1/T). Early treatment given to women with syphilis during antenatal care may be the only effective method to decrease the risk of CS.

Congenital syphilis: refining newborn evaluation and management in Shenzhen, southern China.

INTRODUCTION: Consistent definitions of congenital syphilis are critical for determining true incidences and setting up targets of elimination. This study aimed to assess the evaluation and management of infants at high risk of congenital syphilis with an antenatal syphilis-screening programme in the Shenzhen SEZ and to develop feasible definitions for the detection of congenital syphilis in China. METHODS: A retrospective study was conducted of all standardised records of pregnant women with positive syphilis between 2003 and 2007. Infants at high risk of congenital syphilis were evaluated by laboratory tests at birth and longitudinal follow-up. A screening test-positive congenital syphilis case was defined based on a positive 19S-IgM-FTA-ABS result at birth. Assuming that 19S-IgM-FTA-ABS was the gold standard, the sensitivity and specificity of the ascertainment methods were calculated. RESULTS: During the study period, 1010 live infants were born to women with active syphilis during pregnancy. 19S-IgM-FTA-ABS detected 42 screening-positive congenital syphilis cases and another nine cases were identified by longitudinal follow-up only. Using 19S-IgM-FTA-ABS as the gold standard, 'fourfold rapid plasma reagin (RPR) titres' had the highest sensitivity and specificity compared with the other two follow-up methods. DISCUSSION: 19S-IgM-FTA-ABS makes congenital syphilis case classification simpler and faster for newborns. In areas where 19S-IgM-FTA-ABS is not available, comparing newborn RPR titres with maternal titres can be an alternative method. Meanwhile, positive follow-up results act as treatment indicators for older infants. As congenital syphilis definitions vary over the country, the Shenzhen programme suggested a practical model for surveillance and treatment in areas with or without available 19S-IgM-FTA-ABS testing.

Congenital syphilis, the great imitator-case report and review.

Syphilis is caused by a spirochaete bacterium called Treponema pallidum. Vertical transmission of spirochaetes can lead to congenital infection of the fetus in pregnant women who are inadequately treated or not treated at all, causing various clinical manifestations including stillbirth and neonatal death, cutaneous and visceral manifestations, or asymptomatic infection. We present a severe case of syphilis in a 3-month-old boy with skin lesions, portal hypertension, and anaemia. Because the mother was tested negative for syphilis antibodies at 16 weeks of gestation, a diagnosis of congenital syphilis was initially not considered. This case shows that transmission of T pallidum can still occur in high-income countries with a high rate of antenatal screening. Early recognition might be hampered if physicians do not consider congenital syphilis as a possible diagnosis. Congenital syphilis should be considered in any severe and diagnostically challenging infectious disease case, even in the context of negative antenatal screening.

Congenital syphilis unusually presenting with prematurity-related severe neonatal morbidities including meconium obstruction: A case report and review of the literature.

RATIONALE: Congenital syphilis (CS) can manifest as a variety of clinical presentations according to the severity in symptomatic infants during neonatal period. Preterm neonates with CS may have more clinical evidences of infection and be more severely affected by CS compared with term ones. With increasing survival of markedly premature infants for recent decades, CS may be a challenging problem in those with severe manifestations associated with combined pathophysiologies of CS and prematurity. PATIENT CONCERNS: A very low birth weight infant at 32 weeks gestation presented with an unusual CS presentation consisting of prematurity-associated severe neonatal morbidities including meconium obstruction, prolonged cholestatic jaundice with elevated liver enzymes, and disseminated intravascular coagulation with a bleeding diathesis, in addition to common or typical manifestations of CS. DIAGNOSES: Congenital syphilis. INTERVENTIONS: Therapy consisting of a complete course of parenteral penicillin, blood component therapy, proximal ileotomy with inspissated meconium evacuation and distal loop ileostomy, and other conservative treatments. OUTCOMES: Resolution with normal gastrointestinal function and improved liver function was observed. LESSONS: This case suggests that in premature infants CS may manifest as unusual severe neonatal morbidities that may result from combination of syphilitic pathologies and contributors or conditions associated with prematurity including multisystem immaturity.

Diagnostic and Therapeutic Knowledge and Practices in the Management of Congenital Syphilis by Pediatricians in Public Maternity Hospitals in Brazil.

The study aimed to assess conformity with Brazil's standard protocol for diagnostic and therapeutic practices in the management of congenital syphilis by pediatricians in public maternity hospitals. A cross-sectional study was conducted in 2015 with 41 pediatricians working in all the public maternity hospitals in Teresina, the capital of Piauí State, Northeast Brazil, through self-completed questionnaires. The study assessed the conformity of knowledge and practices according to the Brazilian Ministry of Health protocols. The study has made evident low access to training courses (54%) and insufficient knowledge of the case definition of congenital syphilis (42%) and rapid tests for syphilis (39%). Flaws were observed in the diagnostic workup and treatment of newborns. Requesting VDRL (88%) and correct treatment of neurosyphilis (88%) were the practices that showed the highest conformity with standard protocols. Low conformity with protocols leads to missed opportunities for identifying and adequately treating congenital syphilis. Based on the barriers identified in the study, better access to diagnostic and treatment protocols, improved recording on prenatal cards and hospital patient charts, availability of tests and medicines, and educational work with pregnant women should be urgently implemented, aiming to reverse the currently inadequate management of congenital syphilis and to curb its spread.

The QualiRede intervention: improving the performance of care continuum in HIV, congenital syphilis, and hepatitis C in health regions.

INTRODUCTION: Care continuum models have supported recent strategies against sexually transmitted diseases, such as HIV and Hepatitis C (HCV). METHODS: HIV, HCV, and congenital syphilis care continuum models were developed, including all stages of care, from promotion/prevention to clinical control/cure. The models supported the intervention QualiRede, developed by a University-Brazilian National Health System (SUS) partnership focused on managers and other professionals from six priority health regions in São Paulo and Santa Catarina. Indicators were selected for each stage of the care continuum from the SUS information systems and from the Qualiaids and QualiAB facility's process evaluation questionnaires. The indicators acted as the technical basis of two workshops with professionals and managers in each region: the first one to identify problems and to create a Regional Technical Group; and the second one to design action plans for improving regional performance. RESULTS: The indicators are available at www.qualirede.org. The workshops took place in the regions of Alto Tietê, Baixada Santista, Grande ABC, and Registro (São Paulo) and of Foz do Rio Itajaí (Santa Catarina), which resulted in regional action plans in São Paulo, but not in Santa Catarina. A lack of awareness was observed regarding the new HIV and HCV protocols, as well as an incipient use of indicators in routine practices. CONCLUSION: Improving the performance of the care continuum requires appropriation of performance indicators and coordination of care flows at local, regional, and state levels of management.

Factors associated with inadequate follow-up of children with congenital syphilis.

OBJECTIVE: To analyze factors associated with outpatient follow-up of children with congenital syphilis. METHODS: A non-concurrent cohort study performed in primary care units and three reference maternity hospitals in Fortaleza (Ceará State). Data were collected from September 2013 to September 2016 in the notification forms and in the medical records of hospitalization and outpatient follow-up, and they were presented considering an adequate and inadequate follow-up. Children who attended the primary care unit or referral outpatient clinic during the period recommended by the Ministry of Health were considered adequately followed up and performed the recommended examinations. Pearson's chi-square and Fisher's exact tests were used in the comparative analysis. The estimated risk of adequate non-follow-up was verified by simple and multiple logistic regression. RESULTS: The total of 460 children with congenital syphilis were notified, of which 332 (72.2%) returned for at least one appointment and were part of the study. Exactly 287 (86.4%) children attended the primary health unit; however, there was no reference to congenital syphilis in 236 (71.1%) medical records and no information on the venereal disease research laboratory (VDRL) test was found in 264 (79.5%) children. There was nonadherence to subsequent appointments by 272 (81.9%) individuals. The following variables had a statistically significant association with the non-adequate follow-up of the children: marital status of the mothers, number of prenatal appointments, number of pregnancies, blood count, and radiography of long bones. CONCLUSIONS: Most children with congenital syphilis attended primary care for follow-up, but the services do not meet the recommendations of the Brazilian Ministry of Health for adequate follow-up.

Syphilis and borreliosis during pregnancy.

Syphilis and lyme borreliosis have similar etiologic, clinical, and epidemiologic characteristics. Both are multisystem infectious disorders spread worldwide. Their clinical course can be divided into three stages and as to spirochetal origin, antibiotic therapy is similar too. Taxonomical relationship of Treponema and Borrelia could explain also congenital manifestations well-known in syphilis, and suggested in borreliosis. Therapy of pregnant women with syphilis and lyme borreliosis should follow the same strategy.