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.

Neonates at risk for congenital syphilis: radiographic and cerebrospinal fluid evaluations.

OBJECTIVE: To review the infants at risk for congenital syphilis (CS) and determine the optimal use of evaluations such as cerebrospinal fluid (CSF), the venereal disease research laboratory (VDRL) test, and long bone radiography studies. METHODS: A retrospective chart review of all of the infants at risk for CS from January 1997 to December 2002 at the Regional Medical Center at Memphis was conducted. Subjects were identified from a database of prenatal maternal records. Infant charts showing a diagnosis of presumptive CS were reviewed and data were collected. RESULTS: Of the 24,245 deliveries, maternal serology (rapid plasma reagin and microhemagglutination for treponemal antibody) was reactive in 250 women during pregnancy. Of 92 infants with a presumptive diagnosis of syphilis, only 2 (2.1%) were symptomatic. CSF examination for VDRL was feasible in 74 (80%) of the 92 infants. Only 1 (1.35%) of the 74 infants had a positive CSF-VDRL. Three infants had radiographic changes that were consistent with CS. CONCLUSIONS: The burden of syphilis in pregnancy remains high. Proper evaluation of neonates is important in preventing long-term consequences. The frequency of positive CSF and long bone radiography studies remains low. These evaluations should be made based on the symptoms and plan of treatment for individual neonates.

Congenital syphilis: beta2-microglobulin in cerebrospinal fluid and diagnosis of neurosyphilis in an affected newborn.

Meningoencephalitis in neonatal congenital syphilis (CS) is a difficult diagnosis because of the limitation of standard cerebrospinal fluid (CSF) tests. This limitation means that new markers in CSF tests are needed to establish whether meningitis is present in presumptive cases of CS. beta2-Microglobulin (beta2-m) is raised in CSF recovered from neonates with central nervous system (CNS) infections, but it does not correlate with cellular count or proteins in the CSF. We present a preterm newborn with symptomatic CS. First-day CSF showed 50 cells/mm3, protein of 220 mg/dL and a beta2-m concentration of 16.9 mg/dL (normal <2.25 mg/dL). Serial determinations of beta2-m showed a marked reduction (76%) after 10 days of appropriate treatment. At 30 days of life, beta2-m was already within the normal range (1.8 mg/dL). Cerebral ultrasonography showed ventricular dilatation, moderate periventricular echogenicity, subependimal hemorrhages, and linear hyperechoic areas in the thalamus and basal ganglia. We suggest that beta2-microglobulin is very useful in the diagnosis of CNS involvement and in monitoring the response to treatment. In addition, infants with CS may exhibit CNS imaging findings similar to those observed in other intrauterine CNS infections.

Central nervous system infection in congenital syphilis.

BACKGROUND: Identification of infants with Treponema pallidum infection of the central nervous system remains challenging. METHODS: We used rabbit-infectivity testing of the cerebrospinal fluid to detect T. pallidum infection of the central nervous system in infants born to mothers with syphilis. The results were compared with those of clinical, radiographic, and conventional laboratory evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase-chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and rabbit-infectivity testing of serum or blood. RESULTS: Spirochetes were detected in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing. Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for rabbit-infectivity testing was associated with a negative test result (P=0.001). Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22 percent) who had no prior antibiotic exposure. These 17 infants included 41 percent (16 of 39) of those with some abnormality on clinical, laboratory, or radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on physical examination that were consistent with congenital syphilis; and 41 percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit-infectivity testing of serum or blood. Only one infant who had normal findings on clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test. Overall, central nervous system infection was best predicted by IgM immunoblotting of serum or PCR assay of serum or blood. CONCLUSIONS: Most infants with T. pallidum infection of the central nervous system can be identified by physical examination, conventional laboratory tests, and radiographic studies. However, the identification of all such infants requires the use of additional tests, including IgM immunoblotting and PCR assay.

Congenital syphilis and fluorescent treponemal antibody test reactivity after the age of 1 year.

BACKGROUND: Many believe that a persistently reactive fluorescent treponemal antibody absorption (FTA-ABS) is manifested with congenital syphilis after the age of 1 year, that it is useful in the retrospective diagnosis of children with congenital syphilis, and that it can be used to confirm other treponemal tests. GOAL: To determine whether a reactive FTA-ABS after the age of 12 months is indicative of congenital syphilis. STUDY DESIGN: Prospective outpatient follow-up evaluation until at least the age of 12 months was conducted for 194 babies born to mothers with reactive syphilis serology at delivery, and for two additional children with congenital syphilis diagnosed when they were younger than 1 year (total, 196 children). RESULTS: In the study group, 54 children had reactive FTA-ABS (reactors) until the age of at least 12 months or more, and 142 children had nonreactive FTA-ABS (nonreactors) at the age of 12 months or more. Of the 54 reactors, 17 (31%) had evidence of congenital syphilis at birth, whereas evidence of congenital syphilis was seen in 14 of the 142 (10%) nonreactors (P = 0.0002). At 15 months, nonreactive FTA-ABS developed in six reactors, and eventually in 15 of 44 reactors (34%) tested. CONCLUSIONS: A reactive FTA-ABS may be seen at 12 months in children with and without evidence of congenital syphilis at birth. Not all children with congenital syphilis will manifest reactive FTA-ABS at 12 months, and FTA-ABS reactivity wanes with time.

Lumbar puncture in the evaluation of possible asymptomatic congenital syphilis in neonates.

OBJECTIVE: To evaluate the usefulness of lumbar puncture (LP) in the initial evaluation of symptom-free infants for congenital syphilis. STUDY DESIGN: We retrospectively studied infants who had successful LPs and were born to untreated or inadequately treated seropositive women between 1990 and 1993 in two hospitals in Washington, D.C. We identified 329 such symptom-free infants (syphilis group). The cerebrospinal fluid (CSF) VDRL was reactive in two (0.6%) infants. The CSF leukocyte and protein concentrations of these infants were compared with those in 84 symptom-free control infants who were born to seronegative women and who had LPs performed in 1993 to rule out sepsis because of associated risk factors. Control infants had negative results for bacterial cultures (CSF and blood) and bacterial antigen tests (CSF and urine). RESULTS: Thirty control subjects and 67 infants in the syphilis group had traumatic taps (CSF erythrocytes > 500 x 10(6)/L), and hence were excluded from the analysis of cell count and proteins. Birth weights and gestational ages were similar in both groups. The CSF leukocyte and protein values were similar in the syphilis group and in control infants: mean CSF leukocytes 7.7 x 10(6)/L (mean 7.7/mm3, range 0 to 57/mm3, SD 8.8) versus 6.9 x 10(6)/L (mean 6.9/mm3, range 0 to 31/mm3, SD 7), p = 0.5, and mean protein concentration 981 mg/L (range 270 to 2280 mg/L, SD 376) versus 936 mg/L (range 360 to 1750 mg/L, SD 368), p = 0.96, respectively. The combination of CSF leukocyte values > 5 x 10(6)/L (> 5/mm3) or protein values > 400 mg/L (> 40 mg/dl) was found in 97.8% of the infants in the syphilis group, compared with 95.3% of the control group. CONCLUSION: Because of the low yield of reactive CSF VDRL and the similar CSF leukocyte and protein values in the syphilis group and the control infants, the role of routine LP in the initial evaluation of symptom-free infants for congenital syphilis should be reconsidered.

Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of infants treated for congenital syphilis.

Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various hours and days of treatment in 163 infants undergoing therapy for congenital syphilis. The CSF levels were compared for three treatment regimens. Aqueous penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN), 50,000 U/kg per day, was used in 100 children. Mean CSF penicillin levels were 0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment groups. The mean CSF penicillin concentration among the 63 infants treated with either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p < 0.001). Among those who received A-PEN, the difference in dosage was not associated with a significant difference in mean CSF penicillin concentration (p = 0.68). All the specimens obtained from patients who received A-PEN, but only 82% of those from patients who received P-PEN, had treponemicidal concentrations (> or = 0.018 microgram/ml). However, 33.3% (9/27) of specimens from infants who received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin concentrations < 0.018 microgram/ml. These data suggest that administration of A-PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired, especially for infants with severe disease or congenital neurosyphilis.

IgM antibody to Treponema pallidum in cerebrospinal fluid of infants with congenital syphilis.

OBJECTIVES: To characterize the neonatal IgG and IgM response to specific Treponema pallidum antigens in the cerebrospinal fluid (CSF) of infants with congenital syphilis. DESIGN: Cross-sectional survey. SETTING: Newborn nursery and neonatal intensive care unit of a county hospital in Dallas, Tex. PARTICIPANTS: Twenty-one infants born to mothers with reactive serologic tests for syphilis were enrolled. Group 1 consisted of six infants with clinical and laboratory evidence of congenital syphilis; group 2, six asymptomatic infants born to mothers with untreated syphilis; and group 3, nine asymptomatic infants whose mothers were treated for syphilis before delivery. SELECTION PROCEDURES: Random sample. MEASUREMENTS AND RESULTS: Immunoblotting was used to examine the IgM and IgG reactivities of neonatal serum and CSF against T pallidum antigens. Among serum samples of all group 1 infants, a specific IgM response to T pallidum antigens with apparent molecular masses of 47, 45, and 17 kd was observed. Cerebrospinal fluid IgM reactivity to a 47-kd antigen of T pallidum was seen in four group 1 infants. Serum samples from two group 2 and three group 3 infants demonstrated IgM reactivity against the 47-kd antigen and, in some cases, against the 45-kd antigen of T pallidum. None of 15 group 2 and 3 infants had a positive CSF IgM immunoblot result. The IgG reactivity in CSF was similar in the three groups and was directed against T pallidum antigens with apparent molecular masses of 72, 59, 47, 45, 42, 37, 34, 17, and 15 kd. CONCLUSIONS: A specific IgM response to T pallidum antigens, particularly the 47-kd antigen, was detected in the CSF of some infants with clinical and laboratory evidence of congenital syphilis. The potential usefulness of this test for the diagnosis of congenital neurosyphilis merits further study.

Late-onset congenital syphilis. A retrospective look at University of Iowa Hospital admissions.

A retrospective review of 766,742 hospital admissions was performed between 1966 and 1986 at the University of Iowa Hospital for the diagnosis of congenital syphilis. Although 88 individuals were identified with this diagnosis, adequate treatment was documented in only 33 (38%). Thirty-nine of the 88 individuals identified were initially seen for visual complaints by the ophthalmology department. We recommend that all physicians increase their index of suspicion for this disease, and institute appropriate therapy and follow-up if late congenital syphilis is diagnosed.

[Meningeal attacks during the course of congenital syphilis and therapeutic consequences]. / Atteinte méningée au cours de la syphilis congénitale et conséquences thérapeutiques.

In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies. Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests. Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF without correlation with severity of clinical features, CSF protein levels or CSF cytologic findings. The TPHA test was positive in only four children and the VDRL test was always negative. Passage of antibodies into the CSF is possible (1 case in this study after treatment of the mother), but TPHA is helpful in developing countries of research of neurosyphilis.

[Specific serologic reactions in the cerebrospinal fluid in congenital syphilis and therapeutic implications]. / Réactions sérologiques spécifiques dans le liquide céphalorachidien au cours de la syphilis congénitale et conséquences thérapeutiques.

In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies. Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests. Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF; positivity of this test was not correlated with severity of clinical features, CSF protein levels or CSF cytologic findings. The TPHA test was positive in only four children and the VDRL test was consistently negative. These findings are similar to those reported in another group of patients with meningeal involvement proven by the demonstration of IgM in the CSF using recent techniques. Passage of antibodies into the CSF is possible (1 case in this study) but for safety patients with specific IgG in the CSF should be given penicillin in a dosage that provides treponema-killing levels in situ (100,000 U/kg/d). Use of this dosage is recommended whenever sensitive techniques for CSF analysis are not available.

Congenital syphilis in The Netherlands: diagnosis and clinical features.

From 1982 to 1985 the 19S IgM-Fluorescent Treponemal Antibody Absorption (19S-IgM-FTA-ABS) test gave a positive result in 19 children. These 19 children plus one dizygotic twin sister were evaluated. Seventeen children were diagnosed as having congenital syphilis and treated. Clinical evidence was seen in 10 children, CSF abnormalities in seven, radiological abnormalities in eight. Of the 17 children treated, only one did not meet the Center for Disease Control (CDC) criteria of a compatible case of congenital syphilis. Of the children not diagnosed as having congenital syphilis, one child was considered to be a compatible case of congenital syphilis according to the CDC-criteria. The CDC-criteria may be a valuable aid in diagnosing congenital syphilis. Guidelines for adequate therapy are given.

Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis.

Congenital syphilis: a diagnostic and therapeutic dilemma.

Seventy-eight newborn infants born to mothers with serologic evidence of syphilis (positive serum rapid plasma reagin and fluorescent treponemal antibody-absorption tests) were prospectively evaluated to derive diagnostic and therapeutic criteria for congenital syphilis. Sixty-one infants were asymptomatic with normal serum IgM and normal roentgenograms (Group I). Eight infants had clinical and/or laboratory evidence of infection at birth (Group II). Nine infants presented with late onset infection (Group III). Elevated serum IgM and abnormal roentgenologic findings were consistently present in symptomatic infants in Groups II and III. Cerebrospinal fluid (CSF) examination was normal in all asymptomatic infants and in all infants with late onset disease. One of the eight infants in Group II examined at birth had positive CSF Venereal Disease Research Laboratory determinations, but all other CSF findings were within normal limits, and a second infant with a slight increase in CSF protein had no clinical evidence of central nervous system (CNS) involvement. Of those asymptomatic infants who returned for follow-up 75% and 100% were seronegative by 3 and 6 months, respectively. The symptomatic infants remained seropositive up to 18 months of age. Infants who had no clinical evidence of CNS involvement at birth remained normal at follow-up and had normal CSF findings. The two infants with CNS symptoms at birth continued to have developmental delay despite normal CSF findings. The incidence of CNS involvement in congenital syphilis appears to be extremely low. The value of routine spinal fluid examination is discussed.

Cerebrospinal fluid concentrations of aqueous procaine penicillin G in the neonate.

Simultaneous serum and CSF samples were obtained following the intramuscular administration of 50,000 units/kg of aqueous procaine penicillin G in 25 neonates. Penicillin activity was detected in the sera and CSF of all patients. Peak serum levels were noted at four hours (mean +/- SEM, 17.1 +/- 6.3 micrograms/ml). Peak CSF levels were noted at 12 hours (0.70 +/- 0.35 microgram/ml). The serum level at 24 hours was 2.1 +/- 0.98 microgram/ml (range, 0.2 to 5.8 micrograms/ml); the CSF level at 24 hours was 0.12 +/- 0.05 micrograms/ml (range, 0.03 to 0.27 microgram/ml). These results demonstrate that spirocheticidal levels (greater than or equal to 0.03 microgram/ml) are achieved for at least 24 hours in the CSF following the intramuscular administration of aqueous procaine penicillin G in neonates.