Congenital syphilis in East Baton Rouge parish, Louisiana: providers' and women's perspectives.

BACKGROUND: Congenital syphilis is completely preventable through screening and treatment, but rates have been rising in the United States. Certain areas are at particularly high risk. We aimed to assess attitudes, knowledge, and barriers around effective prevention of congenital syphilis among health care providers and community women potentially at risk. METHODS: Two parallel studies were conducted: in-depth interviews with health care providers and focus groups with community women in the area of Baton Rouge, Louisiana. Each group was questioned about their experience in providing or seeking prenatal care, knowledge and attitudes about congenital syphilis, sources of information on testing and treatment, perceptions of risk, standards of and barriers to treatment. Results were transcribed into QSR NVivo V10, codes developed, and common themes identified and organized. RESULTS: Providers identified delays in testing and care, lack of follow-through with partner testing, and need for community connection for prevention, as major contributors to higher rates of congenital syphilis. Women identified difficulties in accessing Medicaid contributing to delayed start of prenatal care, lack of transportation for prenatal care, and lack of knowledge about testing and prevention for congenital syphilis. CONCLUSIONS: Providers and community members were in broad agreement about factors contributing to higher rates of congenital syphilis, although some aspects were emphasized more by one group or another. Evidence-based interventions, likely at multiple levels, need to be tested and implemented to eliminate congenital syphilis.

Massive Perivillous Fibrin Deposition Associated With Placental Syphilis: A Case Report.

Massive perivillous fibrin deposition (MPFD) and the related entity of maternal floor infarction (MFI) are uncommon placental disorders of unknown etiology, associated with adverse obstetric outcome and a significant risk of recurrence. We describe a 19-year-old mother with untreated syphilis who delivered a male neonate with low birth weight, skin desquamation, and pneumonia. Placenta examination showed the expected changes for syphilis but unexpectedly, also showed MPFD. To our knowledge, this is the first report of MPFD associated with placental syphilis, thus expanding the list of etiologies that may be related to MPFD/MFI. It is postulated that the syphilis infection in our case led to a hypercoaguable state, eventually resulting in MPFD. In the right clinical setting, syphilis might be considered in the differential diagnosis when MPFD/MFI is observed on placental examination. The recurrence risk of MFPD/MFI associated with infections is believed to be lower than idiopathic cases and, by extrapolation, this lower risk should apply to syphilis as well.

Congenital Syphilis as a Measure of Maternal and Child Healthcare, Brazil.

Syphilis is a sexually transmitted infection that has direct adverse effects on maternal and infant health through vertical Treponema pallidum transmission during early pregnancy. We evaluated congenital syphilis as a predictor of the quality of basic maternal and child healthcare in Brazil during 2010-2015. We investigated case rates and correlations with epidemiologic and socioeconomic indicators. We observed rising congenital syphilis incidence rates and increasing syphilis-associated perinatal and infant mortality rates in all regions. Case rates were highest in the Northeast, Southeast, and South, and congenital syphilis infant mortality rates were highest in the Northeast and Southeast. We observed correlations between congenital syphilis rates and infant death, spontaneous abortion (miscarriage), and stillbirth rates. We also noted correlations between rates of stillbirth caused by syphilis and inadequate prenatal care. Our study suggests gaps in basic healthcare for pregnant women and indicates the urgent need for measures to increase early diagnosis and appropriate treatment.

Evaluating congenital syphilis in a reverse sequence testing environment.

OBJECTIVES: To examine the effect of maternal reverse-sequence (RS) syphilis screening on management of infants at risk for congenital syphilis (CS) using a standardized approach. STUDY DESIGN: A retrospective study from 2011 to 2014 at an academic medical center using RS testing, involving chemiluminescent immunoassay (CIA), rapid plasma  reagin (RPR), and fluorescent treponemal antibody-absorption (FTA-ABS) assays for syphilis. Clinical management and outcomes of infants born to mothers with discordant (CIA+/RPR-/FTA+) serology were compared with national or internal guidelines. RESULTS: Sixty-three infants were classified as discordant (n = 21), presumed false positive (CIA+/RPR-/FTA-; n = 16), or true positive (CIA+/RPR+; n = 26) based on maternal serology. Only 24% of cases in the discordant group underwent recommended full evaluation. None of the evaluated infants in the discordant group (n = 8) were diagnosed with CS. CONCLUSIONS: Management of infants with discordant maternal RS serology remained reliant on clinical judgment. In our high-risk population, RS testing did not identify additional cases of CS.

Molecular detection of Treponema pallidum subspecies pallidum in 150-year-old foetal remains, southeastern France.

PURPOSE: Syphilis, caused by Treponema pallidum subspecies pallidum , is considered as an old disease affecting humans; traces of such infections, including congenital syphilis, are potentially identifiable in archaeological samples. The aim of this research was to perform macroscopic and molecular investigations of T. pallidum on six infant remains, buried between 1837 and 1867, from the cemetery of 'Les Crottes' in Marseille city (southeastern France). METHODOLOGY: Pathological analysis of bones from individuals, aged from the twenty-ninth week of amenorrhea to 4-9 months, was performed. Samples served also as a source of ancient DNA (aDNA) for PCR-based molecular investigations targeting T. pallidum DNA; all samples were also tested for Mycobacterium tuberculosis and Plasmodium falciparum DNA. Sequences characterized were cloned and sequenced, and compared to those available in databases.Results/Key findings. All samples tested displayed widespread osteoporotic lesions across the skeleton possibly related to some metabolic or infectious disorders. Subsequent molecular analysis revealed that one individual, SP332 (unborn, 29 amenorrhea weeks, inhumation date 1864-1866), exhibited positive signals for the five T. pallidum amplification systems tested; sequence analysis provided strong evidence for the effective detection of T. pallidum subspecies pallidum DNA. CONCLUSIONS: Individual SP332 is the first PCR-confirmed palaeopathological case of syphilis identified in France, and the youngest specimen ever to be diagnosed with certainty for congenital syphilis. Future research aimed at better characterizing this 150-year-old treponeme genome and exploring new archaelogical cases of syphilis in the very young should contribute to a better comprehension of the disease's history.

Sensitivity of nPCR for four types of membrane protein DNA and of two pairs of primers for Tpp47 DNA of Treponema pallidum in whole blood of congenital syphilis newborns.

BACKGROUND: Problems exist in congenital syphilis (CS) diagnosis and no single test can be used to diagnose CS. OBJECTIVE: To know whether there exist differences of nested polymerase chain reaction (nPCR) sensitivity among four membrane protein DNA and of nPCR between two pairs of primers for Tpp47. METHODS: We collected 30 CS patients as a study group, and 20 cases admitted to hospital for other reasons as a control group. The blood samples from newborns were left of blood for other examination, not special for the study. Following confirmed diagnosis, DNA was extracted from blood. nPCR examined for membrane protein DNA in both groups. RESULTS: Sensitivity of nPCR for Tpp15, Tpp17, Tpp45, and Tpp47 (total) was 6/30, 3/30, 1/30, and 20/30, respectively. The sensitivity of nPCR for Tpp47 was highest among that of four types of membrane protein DNA. The nPCR sensitivity of two pairs of primers (a and b) for Tpp47 was 11/30 and 13/30, respectively. There was no significant difference between two pairs of primers for Tpp47, and total sensitivity of nPCR for Tpp47 combining Tpp47a with Tpp47b was up to 20/30. CONCLUSION: Sensitivity of nPCR for Tpp47 was highest among that of four types of membrane protein DNA. Two pairs of primers for Tpp47 different bands could elevate nPCR sensitivity.

Detección de Treponema pallidum subespecie pallidum para el diagnóstico de sífilis congénita mediante reacción en cadena de la polimerasa anidada.

Introducción. La sífilis es una enfermedad producida por Treponema pallidum subespecie pallidum cuya incidencia mundial es de 12 millones de casos por año, aproximadamente; de estos, más de dos millones se presentan en mujeres gestantes, siendo la sífilis congénita la complicación más grave de esta infección en el embarazo.Objetivo. Detectar la presencia de T. pallidum subespecie pallidum en muestras clínicas para el diagnóstico de sífilis congénita mediante reacción en cadena de la polimerasa (PCR) anidada y determinar su concordancia con las pruebas serológicas.Materiales y métodos. Mediante PCR convencional y anidada, se amplificaron tres genes diana (polA, 16S ADNr y TpN47) y se confirmaron los productos de amplificación de los genes TpN47 y polA por secuenciación. Las pruebas serológicas empleadas fueron la VDRL (Venereal Disease Research Laboratory), la de reagina plasmática rápida (Rapid Plasma Reagin, RPR) y la de aglutinación de partículas para Treponema pallidum (Treponema pallidum Particle Agglutination Assay, TPPA).Resultados. La sensibilidad para la PCR convencional fue de 52 pg y, para la PCR anidada, de 0,52 pg. La especificidad con los iniciadores TpN47 y polA fue de 100 %; los resultados de la secuenciación mostraron una identidad de 97 % con T. pallidum. En 70 % de las muestras, los resultados de las pruebas serológicas y la PCR anidada concordaron.Conclusión. El gen TpN47 resultó ser el mejor blanco molecular para la identificación de T. pallidum. La PCR anidada se presenta como una alternativa de diagnóstico molecular promisoria para el diagnóstico de sífilis congénita.

Detección de Treponema pallidum subespecie pallidum para el diagnóstico de sífilis congénita mediante reacción en cadena de la polimerasa anidada / Detection of Treponema pallidum subspecies pallidum for the diagnosis of congenital syphilis by nested polymerase chain reaction

Resumen Introducción. La sífilis es una enfermedad producida por Treponema pallidum subespecie pallidum cuya incidencia mundial es de 12 millones de casos por año, aproximadamente; de estos, más de dos millones se presentan en mujeres gestantes, siendo la sífilis congénita la complicación más grave de esta infección en el embarazo. Objetivo. Detectar la presencia de T. pallidum subespecie pallidum en muestras clínicas para el diagnóstico de sífilis congénita mediante reacción en cadena de la polimerasa (PCR) anidada y determinar su concordancia con las pruebas serológicas. Materiales y métodos. Mediante PCR convencional y anidada, se amplificaron tres genes diana (polA, 16S ADNr y TpN47) y se confirmaron los productos de amplificación de los genes TpN47 y polA por secuenciación. Las pruebas serológicas empleadas fueron la VDRL (Venereal Disease Research Laboratory), la de reagina plasmática rápida (Rapid Plasma Reagin, RPR) y la de aglutinación de partículas para Treponema pallidum (Treponema pallidum Particle Agglutination Assay, TPPA). Resultados. La sensibilidad para la PCR convencional fue de 52 pg y, para la PCR anidada, de 0,52 pg. La especificidad con los iniciadores TpN47 y polA fue de 100 %; los resultados de la secuenciación mostraron una identidad de 97 % con T. pallidum. En 70 % de las muestras, los resultados de las pruebas serológicas y la PCR anidada concordaron. Conclusión. El gen TpN47 resultó ser el mejor blanco molecular para la identificación de T. pallidum. La PCR anidada se presenta como una alternativa de diagnóstico molecular promisoria para el diagnóstico de sífilis congénita.

Abstract Introduction. Syphilis is a disease produced by Treponema pallidum subspecies pallidum, which affects approximately 12 million people worldwide every year. Of these, more than 2 million are pregnant women whose babies end up having congenital syphilis, the worst form of this infection. Objective. To detect the presence of T. pallidum subspecies pallidum in clinical samples in order to diagnose congenital syphilis by means of nested PCR, and to determine its concordance with serological testing. Materials and methods. Three target genes (polA, 16S ADNr y TpN47) were amplified by conventional and nested PCR. The results from the amplification of the TpN47 and polA genes were confirmed by sequencing. The serological tests used were VDRL (Venereal Disease Research Laboratory), RPR (Rapid Plasma Reagin) y TPPA (Treponema pallidum Particle Agglutination Assay). Results. The sensitivity for the conventional PCR was 52 pg and 0.52 pg for the nested PCR. The specificity of primers TpN47 and polA was 100 %; the results of the sequencing showed a 97 % identity with T. pallidum. There was concordance between the serology and the nested PCR in 70% of the samples. Conclusion. The TpN47 gene was the best molecular target for the identification of T. pallidum. The nested PCR is a promising molecular tool for the diagnosis of congenital syphilis.

Estimating Benzathine Penicillin Need for the Treatment of Pregnant Women Diagnosed with Syphilis during Antenatal Care in High-Morbidity Countries.

BACKGROUND: Congenital syphilis continues to be a preventable cause of global stillbirth and neonatal morbidity and mortality. Shortages of injectable penicillin, the only recommended treatment for pregnant women and infants with syphilis, have been reported by high-morbidity countries. We sought to estimate current and projected annual needs for benzathine penicillin in antenatal care settings for 30 high morbidity countries that account for approximately 33% of the global burden of congenital syphilis. METHODS: Proportions of antenatal care attendance, syphilis screening coverage in pregnancy, syphilis prevalence among pregnant women, and adverse pregnancy outcomes due to untreated maternal syphilis reported to WHO were applied to 2012 birth estimates for 30 high syphilis burden countries to estimate current and projected benzathine penicillin need for prevention of congenital syphilis. RESULTS: Using current antenatal care syphilis screening coverage and seroprevalence, we estimated the total number of women requiring treatment with at least one injection of 2.4 MU of benzathine penicillin in these 30 countries to be 351,016. Syphilis screening coverage at or above 95% for all 30 countries would increase the number of women requiring treatment with benzathine penicillin to 712,030. Based on WHO management guidelines, 351,016 doses of weight-based benzathine penicillin would also be needed for the live-born infants of mothers who test positive and are treated for syphilis in pregnancy. Assuming availability of penicillin and provision of treatment for all mothers diagnosed with syphilis, an estimated 95,938 adverse birth outcomes overall would be prevented including 37,822 stillbirths, 15,814 neonatal deaths, and 34,088 other congenital syphilis cases. CONCLUSION: Penicillin need for maternal and infant syphilis treatment is high among this group of syphilis burdened countries. Initiatives to ensure a stable and adequate supply of benzathine penicillin for treatment of maternal syphilis are important for congenital syphilis prevention, and will be increasingly critical in the future as more countries move toward elimination targets.

Contribution of a Comparative Western Blot Method to Early Postnatal Diagnosis of Congenital Syphilis.

Serology has a pivotal role in the diagnosis of congenital syphilis (CS), but problems arise because of the passive transfer of IgG antibodies across the placenta. The aim of this study was to assess the diagnostic value of a comparative Western blot (WB) method finalized to match the IgG immunological profiles of mothers and their own babies at birth in order to differentiate between passively transmitted maternal antibodies and antibodies synthesized by the infants against Treponema pallidum Thirty infants born to mothers with unknown or inadequate treatment for syphilis were entered in a retrospective study, conducted at St. Orsola-Malpighi Hospital, Bologna, Italy. All of the infants underwent clinical, instrumental, and laboratory examinations, including IgM WB testing. For the retrospective study, an IgG WB assay was performed by blotting T. pallidum antigens onto nitrocellulose sheets and incubating the strips with serum specimens from mother-child pairs. CS was diagnosed in 11 out of the 30 enrolled infants; 9/11 cases received the definitive diagnosis within the first week of life, whereas the remaining two were diagnosed later because of increasing serological test titers. The use of the comparative IgG WB testing performed with serum samples from mother-child pairs allowed a correct CS diagnosis in 10/11 cases. The CS diagnosis was improved by a strategy combining comparative IgG WB results with IgM WB results, leading to a sensitivity of 100%. The comparative IgG WB test is thus a welcome addition to the conventional laboratory methods used for CS diagnosis, allowing identification and adequate treatment of infected infants and avoiding unnecessary therapy of uninfected newborns.

Finding a needle in the haystack: the costs and cost-effectiveness of syphilis diagnosis and treatment during pregnancy to prevent congenital syphilis in Kalomo District of Zambia.

BACKGROUND: In March 2012, The Elizabeth Glaser Pediatric AIDS Foundation trained maternal and child health workers in Southern Province of Zambia to use a new rapid syphilis test (RST) during routine antenatal care. A recent study by Bonawitz et al. (2014) evaluated the impact of this roll out in Kalomo District. This paper estimates the costs and cost-effectiveness from the provider's perspective under the actual conditions observed during the first year of the RST roll out. METHODS: Information on materials used and costs were extracted from program records. A decision-analytic model was used to evaluate the costs (2012 USD) and cost-effectiveness. Basic parameters needed for the model were based on the results from the evaluation study. RESULTS: During the evaluation study, 62% of patients received a RST, and 2.8% of patients tested were positive (and 10.4% of these were treated). Even with very high RST sensitivity and specificity (98%), true prevalence of active syphilis would be substantially less (estimated at <0.7%). For 1,000 new ANC patients, costs of screening and treatment were estimated at $2,136, and the cost per avoided disability-adjusted-life year lost (DALY) was estimated at $628. Costs change little if all positives are treated (because prevalence is low and treatment costs are small), but the cost-per-DALY avoided falls to just $66. With full adherence to guidelines, costs increase to $3,174 per 1,000 patients and the cost-per-DALY avoided falls to $60. CONCLUSIONS: Screening for syphilis is only useful for reducing adverse birth outcomes if patients testing positive are actually treated. Even with very low prevalence of syphilis (a needle in the haystack), cost effectiveness improves dramatically if those found positive are treated; additional treatment costs little but DALYs avoided are substantial. Without treatment, the needle is essentially found and thrown back into the haystack.

Challenges in the diagnosis and treatment of congenital syphilis.

Despite the advent of effective antibiotic treatment of Treponema pallidum, syphilis continues to be present in our population and recently has been increasing in frequency. The consequences can be especially dire in the setting of an untreated infection in pregnancy. This case report describes a case of congenital syphilis in a dichorionic-diamniotic twin pregnancy that resulted in a stillbirth of one twin and the characteristic findings of congenital syphilis in the surviving twin. This report demonstrates a number of challenges to the clinician in the effective and timely diagnosis and treatment of syphilis in pregnancy.

A case series of 130 neonates with congenital syphilis: preterm neonates had more clinical evidences of infection than term neonates.

BACKGROUND: The early clinical manifestations of congenital syphilis (CS) vary from asymptomatic to florid lesions, involving multisystem damage. But little is known about the differences of early clinical features between preterm and term neonates with CS. OBJECTIVES: To compare the clinical characteristics between preterm and term neonates with CS and analyze the possible underlying reasons for the differences. METHODS: Consecutive medical charts of infants at risk for CS from January 1999 to December 2009 were retrospectively reviewed. Neonates with positive 19S-IgM in serum were included in the study. RESULTS: Among the 1,670 cases at risk for CS, 130 neonatal cases with positive 19S-IgM in serum were included in the analysis, including 58 preterm ones and 72 full-term ones. Compared with term neonates with CS, preterm ones were more likely to have characteristic skin rash (36.2 vs. 9.7%, p < 0.001), hepatomegaly (51.7 vs. 25%, p = 0.02), splenomegaly (32.8 vs. 15.4%, p = 0.02), PRP titer ≥1:8 (96.6 vs. 70.8%, p < 0.001), thrombocytopenia (43.1 vs. 23.6%, p = 0.018), elevated CRP (65.5 vs. 36.5%, p = 0.002), and abnormal long bone X-ray results (94.6 vs. 68.1%, p < 0.001). Fewer mothers of preterm neonates with CS received treatment for syphilis (15.5 vs. 40.3%, p = 0.003). The rate of withdrawal of care was higher in preterm neonates with CS (31 vs.12.5%, p = 0.036). CONCLUSIONS: Preterm neonates with CS had more clinical evidences and suffered more than term ones.

Cost-effectiveness of a dual non-treponemal/treponemal syphilis point-of-care test to prevent adverse pregnancy outcomes in sub-Saharan Africa.

BACKGROUND: A dual nontreponemal/treponemal point-of-care test (Dual-POC) that simultaneously detects both nontreponemal and treponemal antibodies has been developed and evaluated. In this study, we compare the health and economic outcomes of the new test with existing syphilis tests/testing algorithms in a high prevalence setting. METHODS: We used a cohort decision analysis model to examine 4 testing/screening algorithms; the Dual-POC test, the laboratory-based rapid plasma reagin and Treponema pallidum haemagglutination assay (RPR+TPHA) algorithm, an onsite RPR testing, and point-of-care treponemal immunochromatographic strip (ICS) testing. Outcomes included miscarriage, stillbirth, congenital syphilis, low birth weight, and neonatal death. Disability-adjusted life-years were estimated for all health outcomes. The analytic horizon was the life expectancy for the mother and child. RESULTS: For a cohort of 1000 pregnant women in a historically high syphilis prevalence population (10% infected and 15% previously infected), the model predicted a total of 39 adverse pregnancy outcomes if no serologic screening were performed; 13 for the laboratory-based RPR+TPHA; 11 for the on-site RPR strategy; 5 for the Dual-POC strategy; and 2 for the ICS strategy. On the basis of assumption that the cost of ICS and the Dual-POC tests were the same, the ICS strategy was the most cost saving (saved $30,000) followed by the Dual-POC strategy (saved $27,000). CONCLUSIONS: The dual-POC test may help save cost in resource-poor settings where disease prevalence (and loss to follow-up) is high, while substantially reducing overtreatment.

[Congenital syphilis]. / Connatalis syphilis.

Syphilis has been a re-emerging disease in the past few decades. As a consequence, the prevalence of congenital syphilis is expected to be on the rise. Maternal syphilis may be related to several pathologies, such as miscarriage, stillbirth, or congenital syphilis in the child. Infants that acquire syphilis in utero are frequently asymptomatic, and the organ damage caused by the infection may be apparent only years later. Syphilis is a curable disease, and most of its complications in the infant can be prevented by screening and treating the mother. Every newborn potentially infected should be treated with penicillin immediately starting on the day of birth.

A systematic review of pediatric sensorineural hearing loss in congenital syphilis.

INTRODUCTION: Congenital syphilis is a known cause of progressive sensorineural hearing loss. The prevalence of syphilitic sensorineural hearing loss (SNHL) in childhood is not clearly defined. OBJECTIVE: To determine the frequency and characteristics of pediatric SNHL following intrauterine infection with or exposure to Treponema pallidum in order to develop evidence-based guidelines for audiologic monitoring. DATA SOURCES: Medline (1950-March 2008), EMBASE (1980-March 2008), CINAHL (1982-March 2008), BIOSIS Previews (1969-March 2008), and Cochrane databases. Manual search of references of identified articles and book chapters. STUDY SELECTION: Articles with an inception cohort of children infected with T. pallidum during pregnancy, positive serological identification of syphilis infection in the antenatal period or pathognomonic clinical signs of congenital syphilis infection, and longitudinal serial audiologic evaluations to identify the prevalence and progression of SNHL. DATA EXTRACTION: Patient information, maternal and infant serologic status, and audiometric data extracted in an independent fashion. Discrepancies resolved through mutual consensus. DATA SYNTHESIS: Descriptive statistics. RESULTS: One prospective cohort study met the inclusion criteria. No cases of SNHL in infants with early congenital syphilis treated with antibiotics in the neonatal period were identified. CONCLUSIONS: There have been no reports of children with confirmed congenital SNHL secondary to in utero syphilis infection. Newborns with positive syphilis serology should have hearing screening performed at birth and receive treatment with an appropriate course of penicillin therapy. Longitudinal hearing screening is recommended for all pediatric patients with congenital syphilis, as further studies documenting longitudinal audiometric data for patients previously treated either fully or partly for congenital syphilis are required.