Tamizaje de sífilis congénita en el binomio madre-hijo: validez de la sangre de cordón / Screening for congenital syphilis in mother-child binomial: validity of cord blood / Triagem da sífilis congênita no binomio mãe-filho: validade do sangue do cordão

La sangre de cordón es una alternativa no invasiva que ha sido empleada para el tamizaje de sífilis congénita. Los objetivos del trabajo fueron evaluar la validez del uso de sangre de cordón como muestra para tamizaje de casos presuntivos de sífilis congénita, determinar la prevalencia de sífilis materna, estudiar la tasa de casos presuntivos de sífilis congénita y establecer el porcentaje de madres no estudiadas para sífilis en el periparto. Se realizó un análisis retrospectivo y observacional entre junio de 2017 y mayo de 2018. Se relevaron datos de serología de sangre de cordón y sangre de la madre. Se utilizó Unheated Serum Reagin como prueba de tamizaje y FTA-Abs y/o quimioluminiscencia como confirmatorias. Se excluyeron los binomios madre-hijo sin estudio de sangre de cordón. Binomios madre-hijo estudiados: 2.487. Sensibilidad y especificidad: 82,29% IC 95% (73,17- 89,33) y 99,96% IC 95% (99,76-100,00), respectivamente. Prevalencia de sífilis materna: 4,04%. Tasa de caso presuntivo de sífilis congénita: 26/1.000 RNV. Madres sin registros de serología para sífilis en el periparto: 70 (2,86%). La sangre de cordón no sería una muestra válida para el tamizaje debido a la baja sensibilidad encontrada, aunque en muchos casos es la única oportunidad de evaluar el binomio madre-hijo.

Cord blood is a non-invasive alternative which has been used for screening of congenital syphilis. The aims of the present study were to evaluate the validity of the use of cord blood as a sample for the screening of a probable congenital syphilis case, to study the prevalence of maternal syphilis, to analyse the rate of probable congenital syphilis case and to determine the percentage of non-studied mothers for syphilis in the peripartum. A retrospective and observational analysis was conducted between June 2017 and May 2018. Cord blood and maternal blood serology results were taken from the Laboratory Information System. Unheated Serum Reagin was used as a screening test and FTA-Abs and/or quimioluminiscense as confirmatory studies. Infant-mother binomies without cord blood studies were excluded. Infant-mother binomies studied: 2487. Sensibility and specificity 82.29% [95% CI: 73.17 to 89.33] and 99.96% [95% CI: 99.76 to 100.00], respectively. MSP prevalence: 4.04%. Probable congenital syphilis case rate: 26/1000 NB. Non-studied mothers for syphilis in the peripartum: 70 (2.86%). Cord blood would not be a valid sample for screening due to the low sensibility found, although in many cases it is the only opportunity to evaluate the infant-mother binomies.

O sangue do cordão é uma alternativa não invasiva que tem sido usada para triagem da sífilis congênita. Os objetivos do trabalho foram avaliar a validade do uso do sangue do cordão como amostra para o rastreio de um caso presumível de sífilis congénita, determinar a prevalência da sífilis materna, estudar a taxa de caso presumível de sífilis congénita e estabelecer a percentagem de mães em que não se analisa a sífilis no periparto. Foi realizada entre junho de 2017 e maio de 2018 uma análise retrospectiva e observacional, onde foram colectados os dados do Sistema de Computação Laboratorial de sorologia sangue do cordão e sangue da mãe. Foi utilizado um Unheated Serum Reagin como teste de triagem e FTA-Abs e/ou quimiluminescência como confirmatórias. Os binomios mãe-filho foram excluídos sem o estudo do sangue do cordão. Binomios mãe-filho estudado: 2.487. Sensibilidade e especificidade: 82,29% IC 95% (73,17-89,33) y 99,96% IC 95% (99,76-100,00), respectivamente. Prevalência de SFM: 4,04%. Taxa CPSC: 26/1.000 RNV. Mães sem registros sorológicos para sífilis no periparto: 70 (2,86%). O sangue do cordão não seria uma amostra válida para triagem devido à baixa sensibilidade encontrada, no entanto em muitos casos é a única oportunidade do avaliar o binomios mãe-filho.

TPPA titer as a new adaptation for early diagnosis of congenital syphilis: a retrospective analysis of observation over three years in Yunnan, China.

BACKGROUND: Early diagnosis of congenital syphilis (CS) is difficult. This study aimed to determine the serological response discipline of syphilis passive antibody (SPA) in infants born to mothers with syphilis and provide the basis for the early diagnosis of CS. METHODS: Thirty-three infants born to mothers with syphilis and six infants with CS were recruited. The toluidine red unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA) titers were followed up after birth. RESULTS: The results showed that serological response in the serum of infants with the TPPA titer decreased threefold at 3rd month, or the titer dropped to a minimum of 1:40 at 9th month was SPA. The TPPA titer of 6 CS cases remained positive after 3-year follow-up, and the titer did not decline after treatment and maintained longer. The infants with TRUST titer ≥ 1:4 at birth were prone to become syphilis serofast, while TRUST titer < 1:4 turned to negative quickly. CONCLUSION: In infants with SPA, the TRUST converted negative earlier than the TPPA. The lower the TPPA initial titer was, the shorter the seroreversion time required. The TPPA titer can be used to predict CS in infants born to mothers with syphilis.

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.

Congenital syphilis presenting with liver lesions.

Congenital syphilis is a prevalent infection in much of the world but rare in contexts where antenatal screening and treatment are available. In the UK in 2016, three cases of congenital syphilis were reported in babies born to women who were seronegative at the time of booking and hence a high degree of clinical vigilance is required in the unwell infant. We present the case of a seven-week-old baby girl with congenital syphilis with the unusual finding of discrete liver lesions. This baby was successfully treated with intravenous ceftriaxone.

Congenital syphilis in neonates with nonreactive nontreponemal test results.

OBJECTIVE: Infants whose mothers had syphilis during pregnancy were studied to determine how often exposed newborns with normal physical examinations and nonreactive nontreponemal serologic tests had abnormal laboratory or radiographic studies. STUDY DESIGN: Retrospective analysis of prospectively collected data from infants born to mothers with syphilis and had a normal examination and a nonreactive nontreponemal test. Some infants had IgM immunoblotting, PCR testing or rabbit infectivity testing (RIT) performed. RESULTS: From 1984 to 2002, 115 infants had a nonreactive serum Venereal Disease Research Laboratory (VDRL)/rapid plasma reagin (RPR) test and a normal physical examination at birth. Among 87 infants born to mothers who had untreated syphilis, 4 had a positive serum IgM immunoblot or PCR test, but none had spirochetes recovered by RIT. Two infants had anemia, one had an elevated serum alanine aminotransferase concentration and one with Down's syndrome had direct hyperbilirubinemia. Among 14 infants born to mothers treated <4 weeks before delivery, none had abnormal laboratory or radiographic tests, although 1 of 11 had a reactive serum IgM immunoblot. Among 14 infants born to mothers treated ⩾4 weeks before delivery, none had abnormal laboratory or radiographic tests. CONCLUSION: Newborns with normal physical examination and nonreactive nontreponemal test results are unlikely to have abnormalities detected on conventional laboratory and radiographic testing.

Improving the antenatal and post-partum management of women presenting to Sexual Health Services with positive syphilis serology through audit.

The incidence of congenital syphilis remains low in the UK, but the morbidity and mortality to babies born to women who are untreated for the condition make testing for the disease antenatally one of the most cost-effective screening programmes. Women attending North Middlesex Hospital, UK with a positive syphilis test at their antenatal booking visit are referred to St Ann's Sexual Health Clinic, London, for management and contact tracing. We were concerned that our initial audit revealed that a large proportion of women referred to our service never attended and recorded partner notification was poor. Following the implementation of recommendations, specifically the introduction of an electronic referral system, re-audit showed an improvement in attendance, contact tracing, documentation and communication.

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.

Recurrent Fever, Anemia, Arthralgia, and Genu Varum as Late Manifestations of Congenital Syphilis.

We report an unusual case of recurrent fever, inflammatory knee pain, genu varum, persistent anemia, and high erythrocyte sedimentation rate in a 28-month-old boy as late manifestations of congenital syphilis (CS). Despite standard penicillin treatment at the end of the first month of life, it recurred later in life, more than once. In the first relapse, manifested by a likely gumma lesion, the prior penicillin treatment plus a negative venereal disease research laboratory result unduly led to exclusion of CS. A second treatment with penicillin led to complete clinical resolution. Although rare, bow legs, recurrent fever, anemia, and inflammatory arthralgias may be manifestations of late CS. Congenital syphilis should be considered throughout early childhood, especially if history of syphilis infection is present. A negative venereal disease research laboratory result does not exclude late syphilis, present in nearly 30% of these patients. The possibility of atypical symptoms of this "great masquerader" should always be borne in mind.

[Congenit syphilis in a baby]. / Kongenit syfilis hos en baby.

A pregnant Caucasian woman with newly diagnosed syphilis in the secondary stage was hospitalized for observation while being treated with penicillin. After one dose of penicillin the foetus was delivered by a caesarean section at gestational age 28 weeks + five days due to a reduced blood flow in arteria cerebri media. He was small for gestational age with birth weight 1,320 g. He received intensive care for eight weeks and intravenously administered benzyl penicillin 80.000 IE × 2 in 15 days. At corrected age one year he was developmentally normal. The incidence of syphilis is increasing and this case illustrates that screening and awareness of syphilis in the Western world is important.

Maternal/child seroprevalence of antibodies against Treponema pallidum at four general hospitals in the state of Morelos, Mexico.

BACKGROUND AND AIMS: Treponema pallidum can cause syphilis in pregnant women and congenital syphilis in the newborn. In Latin America, 330,000 pregnant women are diagnosed with syphilis every year. Adequate prenatal care to detect syphilis reduces maternal morbidity and fetal and neonatal mortality and morbidity. We undertook this study to determine T. pallidum seroprevalence among pregnant and puerperal women from Morelos, Mexico, as well as to evaluate the sexual behavior, demographic and clinical variables associated with the infection. METHODS: A cross-sectional study was carried out among pregnant and puerperal women from four general hospitals from Morelos, Mexico during 2005-2009. Women answered a questionnaire and provided a blood sample to detect antibodies against T. pallidum. RESULTS: A total of 2331 women were analyzed with 0.26% of T. pallidum seroprevalence. There were four cases with active syphilis and two cases with latent syphilis, as well as two cases of congenital syphilis. Illiterate women had 6.7 times higher risk of being infected. Women who did not undergo a urine test had a 5.3 times higher risk for infection and women who do not have piped water inside their household had a 5.0-fold higher risk of having anti-T. pallidum antibodies. All seropositive cases were from the same hospital (Cuautla General Hospital) with demographic, sexual behavior and medical care characteristics different from the other three hospitals. CONCLUSIONS: Syphilis during pregnancy and congenital syphilis are still present in Mexico. It may be that the more urban a population the higher the chance of the prevalence of maternal syphilis. It would be beneficial to reinforce the observance of the Official Mexican Norm and to implement rapid diagnostics tests to contend with this public health problem.

[Western blot as a confirming test in the laboratory diagnosis of syphilis].

Two hundred and ninety-five patients who had been found to have Treponema pallidum antibodies detected by enzyme immunoassay were additionally studied by a Western blot test to confirm their presence. Every four cases were ascertained to be false-positive, false seropositivity being more frequent in the presence of IgM antibody against T. palladium. Spinal fluid analysis provided evidence for the course of neurosyphilis in 5 cases. The diagnosis of congenital syphilis was verified in 2 children who had p15, p17, p45, and 47. The findings demonstrate it necessary to extensively use a Western blot in the health care system.

[Iridoschisis associated to congenital syphilis: serological confirmation at the 80's]. / Iridosquisis asociada a sífilis congénita: confirmación serológica a los 80.

CLINICAL CASE: Female in her eighties is admitted suffering from unilateral ocular pain. On examination we observed, as well as corneal abrasion, a bilateral iridoschisis with a frayed iris, unfolded between its stromal layers. DISCUSSION: This rare case is related either to senile degenerative change or to angle-closure glaucoma. However, it is also associated with congenital syphilis with or without the presence of interstitial keratitis. Infant conjunctivitis and a "salt and pepper" appearance of the fundus oculi complete the diagnosis. It is confirmed that the patient had suffered from congenital late syphilis, cured by the age of 80: this confirmation is reached by treponemal (RPR-) and non-treponemal (TPHA+) serological tests.

[Serological diagnosis of syphilis--current problems and controversies]. / Diagnostyka serologiczna kily--aktualne problemy i kontrowersje.

Serology remains the mainstay of diagnosis of syphilis. It's most important issues are: the knowledge of typical and atypical symptoms of the disease, the need of the testing in particular clinical and epidemiological situations, the interpretation of tests' results. The most frequent dilemmas and the relevance of serological tests in congenital syphilis and neurosyphilis, as well as the quality (standardization and reproducibility) of laboratory testing are discussed.

[Diagnosis of congenital syphilis at delivery: maternal serum or cord blood?]. / Pesquisa de sífilis congénita al momento del parto: Suero materno o sangre de cordón?

UNLABELLED: Congenital syphilis (CS) is an important health problem in Chile, with a rate of 0.25/1,000 live newborn (NB) during year 2004. In 2000, the Chilean Ministry of Public Health recommended to perform a screening in cord blood at the moment of delivery. Instead, the Centers for Disease Control and Prevention guidelines recommend the screening in maternal serum since cord blood has up to 5% of false (-) versus 0.5% of maternal serum, both with respect to the NB serum. OBJECTIVE: Maternal serum and NB cord blood were studied during one year to determine the best screening method at delivery. METHODS: RPR was performed and positive results were confirmed by treponemic test (immunochromatographyDetermine, ELISA Captia, Ig and IgM, and MHA-Tp). Serologically confirmed patients were evaluated by the specialist to define CS cases. RESULTS: Between June 1999 and August 2000 2,741 binomies were studied; of these, 37 (1.3%) were RPR reactive and 2.704 were non-reactive. In 11 of the 37 reactive cases, mother and NB were RPR reactive (Group I), in 9 cases the NB was RPR reactive and the mother was non-reactive (Group II), and the other 17 were NB non-reactive and mother reactive (Group III). In group I, 7/11 (64%) were true (+)s and 4/11(36%)) false (+)s of RPR. In group II, 9/9 (100%) corresponded to false (+)s of RPR in cord blood, and in group III, 11/17 (65%) corresponded to false (+)s of RPR in maternal blood but 6/17 (35%) were found to be cases of syphilis during pregnancy. Three of them were not treated opportunely and were designed as CS. In total 9 NB corresponded to CS (6 in group I and 3 in group III). If the screening had been performed only in cord blood, three NB with CS would have not been diagnosed. CONCLUSION: Even when maternal serum has a high rate of false (+)s, it has better sensitivity than cord blood for the diagnosis of CS, thus it is suggested to perform the screening at delivery with maternal serum instead of cord blood samples.

Pesquisa de sífilis congénita al momento del parto: ¿Suero materno o sangre de cordón? / Diagnosis of congenital syphilis at delivery: Maternal serum or cord blood?

La sífilis congénita (SC) es un problema importante en Chile, con una tasa de 0,25/1.000 recién nacidos (RNs) vivos en el año 2004. En el año 2000, el Ministerio de Salud recomendaba como tamizaje al momento del parto una muestra de sangre de cordón. El Centro de Control y Prevención de Enfermedades, (CDC), Atlanta, E.U.A. recomendó, desde 1998, el tamizaje al parto con suero materno ya que respecto del suero del RN, la sangre de cordón y el suero materno tienen respectivamente hasta 5 y 0,5 por ciento> de falsos negativos. Objetivo: Determinar el mejor tamizaje al momento del parto. Métodos: Se estudiaron muestras de suero materno y sangre de cordón de los RNs durante un año. Se realizó RPR y de ser positiva, pruebas treponémicas confirmatorias (imunocromatográfico Determine®, ELISA Captia® IgG e IgM y microhemaglutinación). Todos los pacientes confirmados fueron vistos por el especialista para definir los casos de SC. Resultados: Entre junio de 1999 y agosto del 2000 se estudiaron 2.741 binomios madre-RN; de éstos 37/2.704 (1,3 por ciento) fueron RPR reactivos. Once eran RPR reactivo en la madre y en el RN (Grupo I), 9 eran RPR reactivo en el RN y no reactivo en la madre (Grupo II) y 17 eran RN con RPR no reactivo y reactivo en la madre (Grupo III). En el Grupo I hubo 64 por ciento> (7/11) de verdaderos (+)s y 36 por ciento (4/11) de falsos (+)s del RPR. En el Grupo II, 9/ 9 (100 por cientoo), correspondieron a falsos (+)s del RPR en sangre de cordón y en el Grupo III, 11/17 (67 por ciento>) correspondieron a falsos (+)s del RPR en sangre materna pero hubo 6/17 (35 por ciento>) que correspondían a sífilis durante el embarazo y en tres de ellas no hubo tratamiento intra-embarazo, por lo que fueron catalogadas como SC y los RNs debieron ser tratados. En total hubo 9 RNs que correspondieron a SC (6 del grupo I y 3 del grupo III). Si sólo se hubiese realizado tamizaje en sangre de cordón, 3 RNs con SC no se hubiesen....

Congenital syphilis (CS) is an important health problem in Chile, with a rate of 0.25/1,000 live newborn (NB) during year 2004. In 2000, the Chilean Ministry of Public Health recommended to perform a screening in cord blood at the moment of delivery. Instead, the Centers for Disease Control and Prevention guidelines recommend the screening in maternal serum since cord blood has up to 5 percent of false (-) versus 0.5 percent of maternal serum, both with respect to the NB serum. Objective: Maternal serum and NB cord blood were studied during one year to determine the best screening method at delivery. Methods: RPR was performed and positive results were confirmed by treponemic test (immunochromatographyDetermine®, ELISA Captia®, Ig and IgM, and MHA-Tp). Serologically confirmed patients were evaluated by the specialist to define CS cases. Results: Between June 1999 and August 2000 2,741 binomies were studied; of these, 37 (1.3 percent) were RPR reactive and 2.704 were non-reactive. In 11 of the 37 reactive cases, mother and NB were RPR reactive (Group I), in 9 cases the NB was RPR reactive and the mother was non-reactive (Group II), and the other 17 were NB non-reactive and mother reactive (Group III). In group I, 7/11 (64 percent) were true (+)s and 4/11(36 percent)) false (+)s of RPR. In group II, 9/9 (100 percent) corresponded to false (+)s of RPR in cord blood, and in group III, 11/17 (65 percent) corresponded to false (+)s of RPR in maternal blood but 6/17 (35 percent) were found to be cases of syphilis during pregnancy. Three of them were not treated opportunely and were designed as CS. In total 9 NB corresponded to CS (6 in group I and 3 in group III). If the screening had been performed only in cord blood, three NB with CS would have not been diagnosed. Conclusion: Even when maternal serum has a high rate of false (+)s, it has better sensitivity than cord blood for the diagnosis of CS, thus it is suggested to perform the screening ...

The need and plan for global elimination of congenital syphilis.

In every society, congenital syphilis (CS) has significant medical, economic, societal and emotional burdens; these are poorly characterized but high. Inexplicably, the elimination of CS has failed to attract international attention. Yet, the cornerstones of programs to do this universally are in place, the recent development of new diagnostic tools offers the now-practical possibility of testing every pregnant woman, testing is cost-effective, and programs for the elimination of CS can be joined with other programs to enhance efficiency. The magnitude of the CS burden, globally, rivals that of HIV infection in neonates yet receives little attention. The newly proposed World Health Organization Strategy for the Global Elimination of Congenital Syphilis aims to mobilize resources and provide a plan to address this under-recognized health problem.

Occurrence of congenital syphilis after maternal treatment with azithromycin during pregnancy.

OBJECTIVE: To evaluate the efficacy of azithromycin in preventing congenital syphilis. METHOD: Five pregnant women with syphilis who were allergic to penicillin were given azithromycin, 1 g daily orally or intravenously, in different hospitals. The duration of the therapy ranged from 1 day to 10 days. A second course of therapy was provided at 28 weeks gestation. The babies were given a physical examination and blood test for serum rapid plasma reagin test (RPR), treponema pallidum hemagglutination test (TPHA), and fluorescent treponemal antibody adsorption test (FTA-ABS-19-sIgM) within three months after birth. RESULTS: Five infants born to these mothers developed skin rashes. Four of the infants had hepatomegaly and one showed osteochondritis. The tests RPR, TPHA, and FTA-ABS-19-sIgM were positive. The RPR titers varied from 1:64 to 1:256 and the babies were diagnosed with congenital syphilis. They were successfully treated with penicillin. CONCLUSIONS: Successful therapy for syphilis during pregnancy demands maternal care as well as prevention or cure of congenital infection. The failure of azithromycin in preventing congenital syphilis in our report suggests that azithromycin should not be recommended as an alternative in treating syphilitic pregnant women or fetal syphilis.

Congenital syphilis: a continuing but neglected problem.

Congenital syphilis was rare in most affluent countries but there has been a slight resurgence recently in several European countries. In large parts of the world and particularly sub-Saharan Africa congenital syphilis is a significant public health problem. The cornerstone of congenital syphilis control is antenatal screening and treatment of mothers with penicillin, which is a cost-effective intervention. In affluent countries it should be strengthened among those at high risk. Clinicians should be more vigilant for the possibility of babies being born with congenital syphilis, which is often asymptomatic. In developing countries not only does antenatal care screening need to be strengthened by implementing point-of-care decentralised screening and treatment but alternative innovative approaches to controlling congenital syphilis should be explored. There is an urgent need for international health agencies to support focused approaches to tackling the tragedy of continuing congenital syphilis. This could be a part of a pro-poor strategy to meet the Millennium Development Goals.