ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Congenital syphilis: Clinical features and diagnosis

Congenital syphilis: Clinical features and diagnosis
Author:
Simon R Dobson, MD, FRCP(C)
Section Editors:
Sheldon L Kaplan, MD
Leonard E Weisman, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Jun 2022. | This topic last updated: Mar 26, 2021.

INTRODUCTION — Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a pregnant woman to her fetus. Infection can result in stillbirth, prematurity, or a wide spectrum of clinical manifestations; only severe cases are clinically apparent at birth [1].

The clinical features and diagnosis of congenital syphilis will be discussed here. The evaluation, management, and prevention of congenital syphilis are discussed separately. (See "Congenital syphilis: Evaluation, management, and prevention".)

Syphilis in pregnancy and acquired syphilis also are discussed separately:

(See "Syphilis in pregnancy".)

(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)

(See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Clinical manifestations'.)

(See "Syphilis: Treatment and monitoring".)

(See "Neurosyphilis".)

(See "Syphilis: Screening and diagnostic testing".)

CASE DEFINITION — The Centers for Disease Control and Prevention (CDC) case definition for congenital syphilis is provided in the table (table 1) [1]. Other case definitions may differ slightly from the CDC definition [2]. In general, case definitions for congenital syphilis require only one of two criteria:

The child has physical, laboratory, or radiographic signs of congenital syphilis (confirmed/highly probable congenital syphilis), or

The child was born to a mother with untreated, inadequately, or suboptimally treated syphilis (presumed congenital syphilis) (table 2)

Some experts would also presume infants to have congenital syphilis if their mothers had contact with a person with primary or secondary syphilis within 90 days before delivery and were not treated or were inadequately treated [3,4].

EPIDEMIOLOGY — Congenital syphilis is a significant public health problem, complicating an estimated one million pregnancies per year throughout the world [5]. The incidence of congenital syphilis reflects the rate of syphilis in women of childbearing age [6]. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Epidemiology'.)

Most cases develop because the mother received no prenatal care or insufficient treatment for syphilis before or during pregnancy (table 2) [7-10]. Among women with untreated early syphilis, 40 percent of pregnancies result in spontaneous abortion [11]. (See "Syphilis in pregnancy", section on 'Prevalence'.)

In the United States, the rate of congenital syphilis among infants <1 year of age peaked at approximately 100 cases per 100,000 live births in 1991 (in part because of a change in the case definition to include infants born to women with untreated or inadequately treated syphilis in 1988), then declined steadily in the 1990s and early 2000s [8]. Since 2012, there has been a steady year-on-year increase in reported cases [12,13]. In 2018, there were a total of 1306 reported cases of congenital syphilis in the United States, including 78 syphilitic stillbirths and 16 infant deaths [13,14]. This represents the highest reported rate since 1991. The 2018 case rate (33 cases per 100,000 live births) represents a 40 percent increase relative to 2017 and a nearly 400 percent increase relative to 2012. As is expected, the increase in rates of congenital syphilis parallels increases in primary and secondary syphilis among all women and reproductive-aged women during this period (figure 1) [12-15].

Poor access to prenatal care is an important risk factor for congenital syphilis. Among the 458 cases of congenital syphilis reported to the Centers for Disease Control and Prevention in 2014, nearly one-quarter were born to mothers who did not receive prenatal care [12]. Among the 314 cases in which the mother received prenatal care, 135 (43 percent) received no treatment for syphilis during the pregnancy and 94 (30 percent) received inadequate treatment. Similarly, in a report by the New York City Department of Health and Mental Hygiene of 578 syphilis infections reported in pregnant women during 2010 to 2016, >85 percent did not result in congenital infection, presumably because of early screening and treatment [16]. Of the 68 cases of congenital syphilis that occurred, 31 percent were born to women who received no prenatal care or did not have a syphilis test ≥45 days before delivery. In addition, of the women who had appropriate testing during pregnancy, 15 percent received no or inadequate treatment. Obstacles to accessing health care identified in this report included substance use, mental health disorders, recent arrival in the United States, unstable housing, and lack of health care coverage.

The rate of congenital syphilis is increased among infants born to mothers with HIV infection. However, the contribution of maternal coinfection with syphilis and HIV to vertical transmission of either syphilis or HIV is not completely understood. (See "Syphilis in patients with HIV", section on 'Effect of syphilis on HIV'.)

The rate of congenital syphilis is generally low among children adopted internationally; however it is relatively increased among those adopted from Africa (table 3). Given the difficulty in confirming adequate treatment/treatment response of the birth mother and the risk of long-term sequelae in untreated children, we recommend screening international adoptees for congenital syphilis (regardless of the country of origin). (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)

TRANSMISSION — Humans are the only natural host of T. pallidum [17]. Congenital syphilis generally is acquired through transplacental transmission of spirochetes in the maternal bloodstream or, occasionally, through direct contact with an infectious lesion during birth [18-20]. (See "Syphilis in pregnancy", section on 'Vertical transmission'.)

Transplacental transmission of T. pallidum can occur at any time during gestation but occurs with increasing frequency as gestation advances. Women with untreated primary or secondary syphilis are more likely to transmit syphilis to their fetuses than women with latent disease (60 to 90 versus 40 percent in early latent and <10 percent in late latent syphilis) [21,22]. The risk of transmission decreases with increasing time since primary or secondary infection and is only 2 percent after four years.

T. pallidum is not transferred in breast milk, but transmission may occur if the mother has an infectious lesion (eg, chancre) on her breast [23].

PATHOGENESIS — At the onset of congenital syphilis, T. pallidum is liberated directly into the circulation of the fetus, resulting in spirochetemia with widespread dissemination to almost all organs. The clinical manifestations result from the inflammatory response. The bones, liver, pancreas, intestine, kidney, and spleen are the most frequently and severely involved. The severity of the manifestations is variable and can range from isolated laboratory or radiographic abnormalities to fulminant involvement of multiple organ systems. Overt infection can manifest in the fetus, the newborn, or later in childhood (if the infant is not treated) [24].

The pathophysiology of and immune response to acquired syphilis infection are discussed separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV".)

EARLY CONGENITAL SYPHILIS

Clinical findings — Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two years of age [4]. Clinical manifestations in untreated infants usually appear by three months of age, most often by five weeks [4,25].

Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic at birth [12,26]. The presence of signs at birth depends upon the timing of intrauterine infection and treatment [17]. Among symptomatic infants, the most common findings include [12,27]:

Hepatomegaly

Jaundice

Nasal discharge ("snuffles")

Rash

Generalized lymphadenopathy

Skeletal abnormalities

Manifestations of early clinical syphilis are varied and unpredictable (table 4) [1,4,17,23,28,29]. Common clinical findings are reviewed here:

Placenta and umbilical cord – The placenta of neonates with congenital syphilis is often large, thick, and pale. The umbilical cord is edematous and may resemble a "barber's pole" with spiral stripes of red and light blue discoloration alternating with streaks of chalky white. It may be significantly inflamed with an abscess-like foci of necrosis within Wharton jelly, centered around the umbilical vessels (necrotizing funisitis) [30,31]. (See "Care of the umbilicus and management of umbilical disorders", section on 'Funisitis'.)

Hepatomegaly – Hepatomegaly occurs in almost all infants with congenital syphilis [10,23]. Hepatomegaly may or may not be associated with splenomegaly, but isolated splenomegaly does not occur. When noted on fetal ultrasonography, hepatomegaly may indicate failure of maternal treatment to prevent fetal infection [32]. Hepatomegaly is associated with jaundice and cholestasis. Laboratory findings may include elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and direct bilirubin; delayed prothrombin time; and visible spirochetes on liver biopsy (if one is performed) (see 'Laboratory abnormalities' below). Abnormalities of liver function may be exacerbated by penicillin therapy before improving [33]. Liver dysfunction generally resolves slowly, even after adequate therapy.

Rhinitis – Syphilitic rhinitis ("snuffles") (picture 1) may herald the onset of congenital syphilis. It usually develops during the first week of life and seldom after the third month. The nasal discharge is white and may be bloody (secondary to mucosal erosion) or purulent if there is secondary bacterial infection. It is more severe and persistent than the nasal discharge of the common cold (see "The common cold in children: Clinical features and diagnosis", section on 'Clinical features'). The nasal discharge contains spirochetes, is contagious, and can transmit infection by direct contact. It should be examined by darkfield microscopy to confirm the diagnosis. (See 'Younger than one month' below.)

Rash – The rash of congenital syphilis usually appears one to two weeks after the rhinitis. It is maculopapular and consists of small, initially red or pink spots. The lesions may occur anywhere, but are more prominent on the back, buttocks, posterior thighs, and soles (picture 2). The rash generally progresses over one to three weeks, followed by desquamation and crusting. As it fades, the lesions become dusky red or copper-colored, and the pigmentation may persist. If present at birth, the rash may be widely disseminated and bullous (pemphigus syphiliticus). Ulcerative lesions and bullous fluid contain spirochetes, are contagious, and can transmit infection by direct contact; samples of such lesions should be examined by darkfield microscopy to confirm the diagnosis. (See 'Younger than one month' below.)

Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include fissures, mucous patches, and condylomata lata. The fissures occur around the lips, nares, and anus. They bleed easily and heal with scarring. The mucous patches may occur on any mucous membrane, particularly those in the mouth and genitalia. Condylomata lata are flat, wart-like, moist lesions around the mouth, nares, anus, and other areas of the skin where there is moisture or friction. They contain spirochetes and can transmit infection.

Generalized lymphadenopathy – Generalized, nontender lymphadenopathy is a common manifestation. Palpable epitrochlear lymphadenopathy in an infant is highly suggestive of congenital syphilis [23].

Other manifestations – Other manifestations of congenital syphilis may include [1,4,10,17,23,28,29]:

Nonimmune fetal hydrops

Fever (may be more prominent in infants born to mothers who are affected late in pregnancy and whose serology is negative at delivery)

Myocarditis

Pneumonia

Failure to move an extremity secondary to pain ("pseudoparalysis of Parrot")

Sepsis due to other bacteria (eg, Escherichia coli, group B streptococci, Yersinia species)

Ophthalmologic manifestations – Loss of eyebrows, chorioretinitis, uveitis, cataract, glaucoma, and chancre of the eyelid

Gastrointestinal manifestations – Rectal bleeding (from ileitis), necrotizing enterocolitis, malabsorption

Nephrotic syndrome (immune complex mediated; responsive to penicillin) [34-37] (see "Congenital and infantile nephrotic syndrome", section on 'Infectious causes')

Central nervous system syphilis — Central nervous system (CNS) syphilis in children with congenital infection may be asymptomatic or symptomatic. Asymptomatic CNS syphilis is indicated by abnormalities in the cerebrospinal fluid (see 'Cerebrospinal fluid abnormalities' below). Asymptomatic CNS syphilis occurs in approximately 40 percent of infants who have clinical, laboratory, or radiographic abnormalities of congenital syphilis, but is infrequent in infants without such manifestations [17,38-42].

Symptomatic CNS involvement is rare among infants with congenital syphilis in the era of penicillin therapy but may develop from ongoing dissemination in infants who are not treated in the neonatal period [17]. Symptomatic CNS syphilis in infants has two overlapping presentations: acute syphilitic leptomeningitis and chronic meningovascular syphilis.

Acute syphilitic leptomeningitis typically manifests during the first year of life, usually between three and six months. The clinical findings are suggestive of bacterial meningitis (eg, vomiting, bulging fontanelle, increased head circumference, splitting of the cranial sutures), but the CSF findings are more suggestive of aseptic meningitis (predominance of mononuclear cells, modest increase in protein, normal glucose) [17,23]. Acute syphilitic leptomeningitis generally responds to penicillin therapy.

Chronic meningovascular syphilis typically manifests toward the end of the first year [17]. The clinical findings include signs of progressive hydrocephalus, cranial nerve palsies, papilledema, optic atrophy, neurodevelopmental regression, and seizures. Syphilitic endarteritis may cause cerebral infarction in the second year of life.

In addition, pituitary gland involvement may manifest with persistent hypoglycemia or diabetes insipidus [43,44].

Radiographic abnormalities

Long-bone radiographs — Abnormal long-bone radiographs are a common manifestation of early congenital syphilis (occurring in 60 to 80 percent) and may be the sole manifestation in infants born to mothers with untreated syphilis [45,46]. The changes usually are present at birth but may appear in the first few weeks of life. Long-bone abnormalities may be associated with pathologic fractures or pain, which may limit movement of the involved extremity, giving the appearance of paralysis ("pseudoparalysis of Parrot") [47].

The radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic; the femur, humerus, and tibia are most frequently involved. Findings may include [47-49]:

Metaphyseal lucent bands (this finding may occur in response to other systemic illnesses) (image 1).

Symmetric localized demineralization and osseous destruction of the medial portion of the proximal tibial metaphysis (Wimberger sign), which also may occur in neonatal hyperparathyroidism and osteomyelitis.

Metaphyseal serration ("sawtooth metaphysis").

Diaphyseal periostitis with new bone formation (may occur in other conditions) (image 2).

Irregular areas of increased density and rarefaction ("moth-eaten" appearance) (image 3 and image 4).

Long-bone abnormalities may be helpful in the diagnosis of congenital syphilis and may be warranted in [50-52]:

Neonates who have Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titers less than fourfold the maternal titer, normal physical examination, and whose mothers were not treated or were inadequately treated (table 2); were treated ≤4 weeks before delivery; or have evidence of relapse or reinfection (fourfold or greater increase in titers). (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Possible congenital syphilis'.)

Infants and children with reactive VDRL or RPR and with abnormal skeletal findings on physical examination (eg, extremity pain, lack of movement of one or more extremities). (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Proven or highly probable disease' and "Congenital syphilis: Evaluation, management, and prevention", section on 'Evaluation and management of children >1 month of age'.)

Chest radiographs — Complete opacification of both lung fields ("pneumonia alba") is the classic radiographic appearance of pneumonia in infants with congenital syphilis. However, a fluffy, diffuse infiltrate involving all lung areas is more common in the era of penicillin therapy.

Laboratory abnormalities

Hematologic studies — Hematologic abnormalities of early congenital syphilis may include [10,53,54]:

Anemia – Direct Coomb test (also known as direct antiglobulin test) negative hemolytic anemia in the neonatal period; nonhemolytic anemia after the neonatal period

Thrombocytopenia

Leukopenia or leukocytosis

Hemolysis is often accompanied by cryoglobulinemia, immune complex formation, and macroglobulinemia. It does not respond to therapy and may last for weeks.

Cerebrospinal fluid abnormalities — Laboratory evidence of CNS involvement may include [10,51,52]:

Reactive CSF VDRL.

CSF pleocytosis (defined by consensus as >25 white blood cells [WBC]/microL for infants <1 month, although some experts use a threshold of >5 WBC/microL).

Elevated CSF protein (defined by consensus as >150 mg/dL in term infants <1 month of age and >170 mg/dL in preterm infants <1 month of age, although some experts use a threshold of >40 mg).

However, none of these findings is highly sensitive or specific [40,42]. In an observational study that used the rabbit infectivity test as the reference standard for identification of spirochetes in the CSF, the sensitivity and specificity of reactive CSF VDRL, elevated CSF WBC, and elevated CSF protein were as follows [40]:

Reactive CSF VDRL – Sensitivity 54 percent, specificity 90 percent

Elevated CSF WBC count – Sensitivity 38 percent, specificity 88 percent

Elevated CSF protein – Sensitivity 56 percent, specificity 78 percent

The significance of a reactive CSF VDRL in a neonate is not clear, since there may be false positives (related to maternal nontreponemal immunoglobulin G [IgG] antibodies that cross the placenta and diffuse into the fetal CSF or contamination of the CSF with blood from a traumatic lumbar puncture) and false negatives (neonates with initial nonreactive CSF VDRL may subsequently develop signs of neurosyphilis). (See 'Congenital neurosyphilis' below.)

Examination of the CSF for T. pallidum DNA by polymerase chain reaction (PCR) may prove more useful for definitive diagnosis of congenital neurosyphilis [18,40,41], but this test is not widely available. (See 'Diagnostic tests' below.)

LATE CONGENITAL SYPHILIS — Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two years of age [4]. Manifestations of late congenital syphilis are related to scarring or persistent inflammation from early infection and are characterized by gumma formation in various tissues [55]. Late congenital syphilis develops in approximately 40 percent of infants born to women with untreated syphilis during pregnancy. Some manifestations of late congenital syphilis can be prevented by treatment of the mother during pregnancy or treatment of the infant within the first three months of life [56,57]. However, other manifestations (eg, keratitis, saber shins) may occur or progress despite appropriate therapy [58].

Manifestations of late congenital syphilis include (table 5) [1,23,57,59,60]:

Facial features – Frontal bossing (picture 3), saddle nose, short maxilla, protuberant mandible.

Eyes – Interstitial keratitis (picture 4) (bilateral, usually occurs around puberty but can occur anytime between 4 and 30 years), secondary glaucoma, corneal scarring, optic atrophy.

Ears – Sensorineural hearing loss associated with late congenital syphilis typically develops suddenly at 8 to 10 years of age and often accompanies interstitial keratitis. The higher frequencies are affected first; normal conversational tones are affected later. Syphilis-associated hearing loss may respond to long-term glucocorticoid therapy [61].

Oropharynx – Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth [upper central incisors most commonly affected] (picture 5); before eruption, Hutchinson teeth are visible on dental radiographs), mulberry molars (maldevelopment of the cusps of the first molars) (picture 6), and perforation of the hard palate (picture 7) (virtually pathognomonic for congenital syphilis).

Cutaneous – Rhagades (perioral fissures or a cluster of scars radiating around the mouth) (picture 8), gummas (granulomatous inflammatory response to spirochetes) in the skin or mucous membranes.

Neurologic – Intellectual disability, arrested hydrocephalus, cranial nerve palsies

Skeletal – Anterior bowing of the shins ("saber shins") (picture 9), enlargement of the sternoclavicular portion of the clavicle (Higoumenakis sign), painless arthritis of the knees ("Clutton joints") (picture 10), and, rarely, other joints.

Hematologic – Paroxysmal cold hemoglobinuria. (See "Paroxysmal cold hemoglobinuria".)

Among these manifestations, Hutchinson triad (Hutchinson teeth, interstitial keratitis, and sensorineural hearing loss), mulberry molars, and Clutton joints are relatively specific for congenital syphilis [23,59].

DIFFERENTIAL DIAGNOSIS — The manifestations of congenital syphilis in neonates may be similar to those of other neonatal infections or newborn conditions, including:

Toxoplasmosis infection (see "Toxoplasmosis and pregnancy", section on 'Fetal infection' and "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Clinical features')

Rubella virus infection (see "Congenital rubella", section on 'Evaluation')

Cytomegalovirus infection (see "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Clinical manifestations')

Herpes simplex virus infection (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Evaluation and diagnosis')

Neonatal sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Evaluation and initial management')

Neonatal hepatitis (see "Causes of cholestasis in neonates and young infants")

Hydrops fetalis (see "Nonimmune hydrops fetalis", section on 'Etiology and prenatal management of disorders associated with hydrops' and "Postnatal diagnosis and management of hemolytic disease of the fetus and newborn", section on 'Diagnosis')

Long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an extremity (see "Differential diagnosis of the orthopedic manifestations of child abuse" and "Brachial plexus syndromes", section on 'Neonatal brachial plexus palsy')

Vesicular lesions (see "Vesicular, pustular, and bullous lesions in the newborn and infant")

Historical features, additional findings, and/or laboratory testing usually differentiate these conditions from congenital syphilis.

DIAGNOSTIC TESTS — The diagnosis of syphilis is complicated by the absence of a method to culture T. pallidum on laboratory media. In clinical settings, the diagnosis of syphilis may be established by:

Direct visualization of T. pallidum by darkfield microscopy (picture 11) or fluorescent antibody staining of infected body fluids or lesions, placenta, or umbilical cord

Demonstration of the T. pallidum by special stains (picture 12) or histopathologic examination [62,63]

Demonstration of serologic reactions typical of syphilis

Tests that may be used to establish the diagnosis of congenital syphilis in research settings include:

Animal inoculation (ie, rabbit infectivity test)

Detection of T. pallidum DNA in a clinical specimen (eg, polymerase chain reaction [PCR]) [18,40,41,64]

These testing methods are discussed in detail separately. (See "Syphilis: Screening and diagnostic testing", section on 'Diagnostic tests'.)

Darkfield microscopy can be performed on body fluids (eg, nasal discharge) or moist skin lesions [65]. Darkfield microscopy enables demonstration of thin, delicate, corkscrew-shaped organisms with rigid, tightly wound spirals (picture 11). A positive darkfield slide illustrates the characteristic motility associated with T. pallidum: a forward and backward motion with rotation about the longitudinal axis [65]. Soft side-to-side bending and twisting may also be seen. Failure to identify spirochetes with darkfield microscopy does not exclude the diagnosis of syphilis. Darkfield microscopy depends upon the direct visualization of live, active spirochetes, characteristics that are rapidly destroyed by the previous use of antibiotics.

Serologic testing can establish a diagnosis of proven/highly probable, at-risk, or unlikely congenital syphilis infection (see 'Interpretation' below). Serologic tests include nontreponemal tests (eg, Venereal Disease Research Laboratory or rapid plasma reagin [RPR]) and treponemal tests (eg, fluorescent treponemal antibody absorption [FTA-ABS], T. pallidum particle agglutination, enzyme immunoassay, chemiluminescence immunoassay, microhemagglutination test for T. pallidum [MHA-TP]) [1].

Nontreponemal tests are inexpensive and rapidly performed. They are sensitive, but not specific. Nontreponemal tests generally are used in the evaluation of neonates with possible congenital syphilis because they provide quantitative results, which can be compared with simultaneously obtained maternal results to categorize neonatal infection [52]. The neonate's nontreponemal titer usually is one to two dilutions less than that of the mother [66]. When the mother's titer is low, the neonate may have nonreactive serology but remains at risk for congenital syphilis. (See 'Congenital syphilis less likely' below.)

Serologic tests for immunoglobulin G [IgG] antibodies are problematic because it is not possible to differentiate between passively acquired maternal antibody and endogenous antibody produced by the fetus/neonate. The ability to detect immunoglobulin M [IgM] antibodies, which do not cross the placenta, would confirm fetal infection. Unfortunately, a sufficiently sensitive and specific IgM assay is not available for routine use in the assessment of congenital syphilis [51]. The fluorescent anti-treponemal IgM antibody test IgM FTA-ABS was used in the past, but because of lack of sensitivity [67,68], the Centers for Disease Control and Prevention suspended its use for diagnostic testing of infants.

The rabbit infectivity test (RIT), which involves the inoculation of cerebrospinal fluid [CSF] or other body fluids into rabbits to determine the presence of viable T. pallidum, is the reference standard test for congenital syphilis [23,25,55]. However, routine use of RIT is not practical because it involves animal testing and is not widely available.

PCR has been used on neonatal blood and CSF for diagnosis of congenital syphilis, but these tests are not widely available [18,40,41,69]. Compared with isolation of the spirochetes by rabbit infectivity testing, the sensitivity and specificity of PCR on cerebrospinal fluid was 65 to 71 percent and 97 to 100 percent, respectively [40,41]. Among 17 infants who had spirochetes detected in CSF by rabbit inoculation, blood PCR was the best predictor of central nervous system infection with T. pallidum [40].

APPROACH TO DIAGNOSIS — The vagaries of the maternal history and signs or lack of signs in the newborn in combination with the potential consequences of delayed or missed diagnosis of congenital syphilis demand a "safety first" approach to both diagnosis and treatment [4]. The Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) Committee on Infectious Diseases provide guidelines for the evaluation and management of congenital syphilis (algorithm 1 and table 6) [51,52]. Maternal nontreponemal test results are required for entry into the algorithm.

The CDC and AAP guidelines recommend that maternal samples be screened according to the traditional algorithm (ie, a nontreponemal test followed by a treponemal test if the nontreponemal test is positive). However, some laboratories screen samples in reverse (ie, a treponemal test before the nontreponemal test) [70]. Interpretation of results with reverse sequence screening is discussed separately. (See "Syphilis: Screening and diagnostic testing", section on 'Serologic testing algorithms'.)

Point-of-care testing (usually linked with HIV testing) using immunochromatographic strips provides an alternative to laboratory testing that is particularly useful in resource-limited settings. These tests can be done during antenatal visits, do not require the laboratory infrastructure necessary for conventional tests, and can be performed on finger-stick blood samples. They are easy to perform, it is easy to interpret their results, and they have a quick turnaround time of 20 minutes or so. They have good sensitivity and specificity, comparable to those of conventional treponemal and nontreponemal tests [70,71].

Clinical suspicion — The diagnosis of congenital syphilis should be suspected in all infants born to women who have reactive nontreponemal and treponemal tests for syphilis; the treponemal test is necessary to exclude a false-positive nontreponemal test (see "Syphilis in pregnancy"). The diagnosis of congenital syphilis also should be suspected in infants born to women who are identified clinically or through contact tracing as having early syphilis during the three months after delivery [4].

In addition, the possibility of congenital syphilis should be considered in infants and children with the following nonspecific clinical findings, particularly in infants born to women with a history of syphilis or risk factors for syphilis (see "Syphilis in pregnancy", section on 'Prevalence'):

Unexplained prematurity (<37 weeks gestation)

Unexplained hydrops fetalis

Enlarged placenta

Failure to move an extremity ("pseudoparalysis")

Persistent rhinitis (picture 1)

Persistent maculopapular or papulosquamous rash (picture 2), particularly in the diaper area

Jaundice, hepatomegaly

Neonatal pneumonia

Generalized lymphadenopathy

Anemia (Coomb [direct antiglobulin] test negative)

Thrombocytopenia

Sensorineural hearing loss

Interstitial keratitis

Finally, the possibility of congenital syphilis should be suspected in children who are adopted internationally. (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)

Initial evaluation

Younger than one month — The initial evaluation of infants younger than one month of age who were born to women with reactive nontreponemal and treponemal test results should include (algorithm 1 and table 6) [51,52]:

A quantitative nontreponemal test (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) on infant serum; testing umbilical cord blood could yield a false positive result if the cord blood is contaminated with maternal blood. The nontreponemal test that is performed on the infant should be the same that was done on the mother so that the infant's titers can be compared with those of the mother.

Physical examination for evidence of congenital syphilis and darkfield microscopic examination or direct fluorescent antibody staining of suspicious lesions or body fluids (eg, nasal discharge). (See 'Early congenital syphilis' above and 'Diagnostic tests' above.)

Pathologic examination of the placenta or umbilical cord with specific fluorescent antitreponemal antibody staining (if possible) [20,31,72]. Characteristic histopathologic features are described separately. (See "Care of the umbilicus and management of umbilical disorders", section on 'Funisitis'.)

Additional evaluation depends upon the findings from the initial evaluation and is discussed separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Subsequent evaluation and management'.)

Older than one month — The initial evaluation of infants and children older than one month of age with clinical, radiographic, or laboratory manifestations compatible with congenital syphilis should include a quantitative VDRL or RPR, physical examination, and darkfield microscopic examination (if it is available) or direct fluorescent antibody staining of suspicious body fluids [51,52].

Infants and children who are found to have reactive serologic tests for syphilis when they are older than one month of age should have maternal serology and records reviewed to assess whether the child has congenital or acquired syphilis, although this distinction may be difficult [1,24]. Additional evaluation of such children may include [51,52]:

Cerebrospinal fluid (CSF) analysis for VDRL, cell count, and protein

Complete blood count with differential and platelet count

Evaluation and testing for HIV infection

Other tests as clinically indicated (eg, chest radiograph, long-bone radiographs, liver function tests, abdominal ultrasonography, ophthalmologic examination, and auditory brainstem response, and neuroimaging studies)

CSF and complete blood count abnormalities may occur in both congenital and acquired syphilis, but radiographic abnormalities are more suggestive of congenital than acquired syphilis. (See 'Radiographic abnormalities' above.)

Interpretation — To maximize treatment of children potentially infected with T. pallidum, the CDC provides categories of congenital syphilis infection that encompass infants with proven or highly probable disease, as well as those who are at risk of congenital syphilis without any clinical evidence of infection. The inclusion of infants at risk for congenital syphilis helps to ensure that possible cases are treated, although not all treated infants will be infected [51].

Proven or highly probable congenital syphilis — Congenital syphilis is proven or highly probable if the neonate (<1 month of age) has any of the following [51]:

An abnormal physical examination that is consistent with congenital syphilis

A serum quantitative nontreponemal serologic titer that is ≥4-fold the corresponding maternal titer (which is equivalent to two dilutions [eg, neonate's titer 1:32 and maternal titer 1:8])

A positive darkfield (picture 11) or fluorescent antibody test of lesions, body fluid(s), placenta, or umbilical cord (these procedures may not be available in all centers)

Neonates with proven or highly probable congenital syphilis should undergo further evaluation and treatment. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Subsequent evaluation and management'.)

Possible congenital syphilis — Neonates with normal physical examination and serum VDRL or RPR titers less than fourfold the maternal titer, but whose mothers were not treated or received inadequate/suboptimal therapy (table 2) are considered to have possible congenital syphilis [51,52].

Some experts would also consider infants to have possible congenital syphilis if their mothers had contact with a person with primary or secondary syphilis within 90 days before delivery and were not treated or were inadequately treated, even if the mother had nonreactive serology [3,4].

Additional evaluation and management of infants with possible congenital syphilis are discussed separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Possible congenital syphilis'.)

Congenital syphilis less likely — Infection is less likely if a neonate has a normal physical examination, serum VDRL or RPR titers are <fourfold the maternal titer, mother received appropriate treatment >4 weeks before delivery, and mother has no evidence of reinfection or relapse. However, these neonates are at risk and should receive treatment with a single dose of intramuscular penicillin G benzathine [51,52,73]. No additional evaluation is needed [51].

Management of infants in whom congenital syphilis is less likely is discussed separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Congenital syphilis less likely'.)

Congenital syphilis unlikely — A diagnosis of congenital syphilis is unlikely if the neonate has a normal physical examination, serum VDRL or RPR titers are <fourfold the maternal titer, mother was adequately treated before pregnancy, and mother's titers remained low (VDRL <1:2; RPR <1:4) and stable before and during pregnancy and at delivery [51]. These infants generally do not require any additional evaluation or treatment. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Congenital syphilis unlikely'.)

Congenital neurosyphilis — A lumbar puncture to evaluate central nervous system (CNS) syphilis should be performed in infants <1 month with proven or highly probable congenital syphilis; infants <1 month of age whose mothers were not adequately treated (possible congenital syphilis); and in infants and children who were identified as having reactive serologic tests for syphilis at older than one month of age (algorithm 1 and table 6) [51,52]. (See "Congenital syphilis: Evaluation, management, and prevention", section on 'Subsequent evaluation and management'.)

The diagnosis of congenital neurosyphilis can be difficult to establish. Given the lack of a widely available laboratory test with high sensitivity and specificity for CNS syphilis and the potential consequences of untreated CNS syphilis, the diagnosis of CNS syphilis usually is presumed in children with clinical, radiographic, and laboratory abnormalities compatible with congenital syphilis. Children with presumed congenital neurosyphilis should be treated with 10 days of parenteral penicillin [40]. (See 'Central nervous system syphilis' above and "Congenital syphilis: Evaluation, management, and prevention", section on 'Penicillin therapy'.)

Congenital versus acquired syphilis — In children who are found to have reactive serologic tests for syphilis when they are older than one month of age, the distinction between congenital and acquired syphilis can be difficult [1]. The ultimate diagnosis may rest upon maternal history and clinical judgment [1]. Radiographic abnormalities of the long bones are more suggestive of congenital than acquired syphilis. (See 'Radiographic abnormalities' above.)

The possibility of sexual abuse must be considered in children who are determined to have acquired syphilis. (See "Evaluation of sexual abuse in children and adolescents", section on 'Sexually transmitted infections'.)

REPORTING REQUIREMENTS — In the United States, congenital syphilis is a national notifiable disease [74]. However, reporting requirements vary by state. Reporting to the Centers for Disease Control and Prevention by the states is voluntary. For reporting purposes, congenital syphilis includes stillbirths due to syphilis, cases of congenital syphilis detected in newborns, and cases of congenitally acquired syphilis in infants and children [1].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Congenital syphilis (The Basics)")

SUMMARY AND RECOMMENDATIONS

Congenital syphilis is acquired through transplacental transmission of spirochetes. Women with untreated primary or secondary syphilis are more likely to transmit syphilis to their fetuses than women with latent disease. Treponema pallidum is not transferred in breast milk. In the United States, the reported cases of congenital syphilis have increased dramatically since 2012 (figure 1). (See 'Transmission' above and 'Epidemiology' above.)

Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two years of age. Manifestations of early clinical syphilis are varied and unpredictable (table 4). (See 'Early congenital syphilis' above.)

Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two years of age. Manifestations of late congenital syphilis are related to scarring or persistent inflammation from early infection (table 5). (See 'Late congenital syphilis' above.)

The differential diagnosis of congenital syphilis in neonates includes other congenital infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, neonatal sepsis) and other causes of neonatal hepatitis, hydrops fetalis, long-bone abnormalities, and cutaneous lesions. Historical features, additional clinical findings, and/or laboratory testing usually differentiate these conditions from congenital syphilis. (See 'Differential diagnosis' above.)

The Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) Committee on Infectious Diseases provide guidelines for the evaluation and management of congenital syphilis (algorithm 1 and table 6). (See 'Approach to diagnosis' above.)

The diagnosis of congenital syphilis should be suspected in all infants born to women who have reactive nontreponemal and treponemal tests for syphilis and infants/children with clinical findings compatible with congenital syphilis (table 4 and table 5). (See 'Clinical suspicion' above.)

The initial evaluation for congenital syphilis in infants and children should include a quantitative Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titer (for infants <1 month of age, the test should be the same as that which was performed on the mother); physical examination for evidence of congenital syphilis; darkfield microscopic examination or direct fluorescent antibody staining of suspicious lesions or body fluids (eg, nasal discharge); and, for newborns, pathologic examination of the placenta and umbilical cord with specific fluorescent antitreponemal antibody staining (if possible). (See 'Initial evaluation' above.)

The diagnosis of syphilis may be established by direct visualization of T. pallidum in clinical specimens (picture 11 and picture 12) or serologic reactions typical of syphilis. To prevent long-term morbidity, it is also important to identify (and treat) infants at risk for clinical syphilis. (See 'Interpretation' above.)

  1. Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 Case Definition. https://ndc.services.cdc.gov/case-definitions/syphilis-2018/ (Accessed on June 17, 2021).
  2. Risser WL, Hwang LY. Problems in the current case definitions of congenital syphilis. J Pediatr 1996; 129:499.
  3. Zenker PN, Berman SM. Congenital syphilis: trends and recommendations for evaluation and management. Pediatr Infect Dis J 1991; 10:516.
  4. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2019. p.1268.
  5. Walker DG, Walker GJ. Prevention of congenital syphilis--time for action. Bull World Health Organ 2004; 82:401.
  6. Sexually transmitted disease surveillance, 2015. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/std/stats15/std-surveillance-2015-print.pdf (Accessed on October 25, 2016).
  7. Reyes MP, Hunt N, Ostrea EM Jr, George D. Maternal/congenital syphilis in a large tertiary-care urban hospital. Clin Infect Dis 1993; 17:1041.
  8. Centers for Disease Control and Prevention (CDC). Congenital syphilis - United States, 2003-2008. MMWR Morb Mortal Wkly Rep 2010; 59:413.
  9. Caddy SC, Lee BE, Sutherland K, et al. Pregnancy and neonatal outcomes of women with reactive syphilis serology in Alberta, 2002 to 2006. J Obstet Gynaecol Can 2011; 33:453.
  10. Lago EG, Vaccari A, Fiori RM. Clinical features and follow-up of congenital syphilis. Sex Transm Dis 2013; 40:85.
  11. Centers for Disease Control and Prevention (CDC). Congenital syphilis--United States, 1998. MMWR Morb Mortal Wkly Rep 1999; 48:757.
  12. Bowen V, Su J, Torrone E, et al. Increase in incidence of congenital syphilis - United States, 2012-2014. MMWR Morb Mortal Wkly Rep 2015; 64:1241.
  13. Kimball A, Torrone E, Miele K, et al. Missed Opportunities for Prevention of Congenital Syphilis - United States, 2018. MMWR Morb Mortal Wkly Rep 2020; 69:661.
  14. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2018: Syphilis. Available at: https://www.cdc.gov/std/stats18/syphilis.htm (Accessed on March 25, 2021).
  15. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017: National profile-Overview: Syphilis. Available at: https://www.cdc.gov/std/stats17/syphilis.htm (Accessed on January 28, 2019).
  16. Slutsker JS, Hennessy RR, Schillinger JA. Factors Contributing to Congenital Syphilis Cases — New York City, 2010–2016. MMWR Morb Mortal Wkly Rep 2018; :1088.
  17. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005; 16:245.
  18. Grimprel E, Sanchez PJ, Wendel GD, et al. Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid. J Clin Microbiol 1991; 29:1711.
  19. Nathan L, Twickler DM, Peters MT, et al. Fetal syphilis: correlation of sonographic findings and rabbit infectivity testing of amniotic fluid. J Ultrasound Med 1993; 12:97.
  20. Qureshi F, Jacques SM, Reyes MP. Placental histopathology in syphilis. Hum Pathol 1993; 24:779.
  21. FIUMARA NJ, FLEMING WL, DOWNING JG, GOOD FL. The incidence of prenatal syphilis at the Boston City Hospital. N Engl J Med 1952; 247:48.
  22. INGRAHAM NR Jr. The value of penicillin alone in the prevention and treatment of congenital syphilis. Acta Derm Venereol Suppl (Stockh) 1950; 31:60.
  23. Kollmann TR, Dobson S. Syphilis. In: Infectious Diseases of the Fetus and Newborn Infant, 7th, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.524.
  24. Christian CW, Lavelle J, Bell LM. Preschoolers with syphilis. Pediatrics 1999; 103:E4.
  25. Herremans T, Kortbeek L, Notermans DW. A review of diagnostic tests for congenital syphilis in newborns. Eur J Clin Microbiol Infect Dis 2010; 29:495.
  26. Ortiz-Lopez N, Diez M, Diaz O, et al. Epidemiological surveillance of congenital syphilis in Spain, 2000-2010. Pediatr Infect Dis J 2012; 31:988.
  27. Rawstron SA, Hawkes SJ. Treponema pallidum (Syphilis). In: Principles and Practice of Pediatric Infectious Diseases, 4th, Long SS, Pickering LK, Prober CG (Eds), Elsevier Saunders, Edinburgh 2012. p.941.
  28. Rathbun KC. Congenital syphilis. Sex Transm Dis 1983; 10:93.
  29. Ricci JM, Fojaco RM, O'Sullivan MJ. Congenital syphilis: the University of Miami/Jackson Memorial Medical Center experience, 1986-1988. Obstet Gynecol 1989; 74:687.
  30. Fojaco RM, Hensley GT, Moskowitz L. Congenital syphilis and necrotizing funisitis. JAMA 1989; 261:1788.
  31. Sheffield JS, Sánchez PJ, Wendel GD Jr, et al. Placental histopathology of congenital syphilis. Obstet Gynecol 2002; 100:126.
  32. Hollier LM, Harstad TW, Sanchez PJ, et al. Fetal syphilis: clinical and laboratory characteristics. Obstet Gynecol 2001; 97:947.
  33. Shah MC, Barton LL. Congenital syphilitic hepatitis. Pediatr Infect Dis J 1989; 8:891.
  34. Braunstein GD, Lewis EJ, Galvanek EG, et al. The nephrotic syndrome associated with secondary syphilis. An immune deposit disease. Am J Med 1970; 48:643.
  35. Gamble CN, Reardan JB. Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits. N Engl J Med 1975; 292:449.
  36. Kaplan BS, Wiglesworth FW, Marks MI, Drummond KN. The glomerulopathy of congenital syphilis--an immune deposit disease. J Pediatr 1972; 81:1154.
  37. Dobson SR, Taber LH, Baughn RE. Characterization of the components in circulating immune complexes from infants with congenital syphilis. J Infect Dis 1988; 158:940.
  38. Radcliffe M, Meyer M, Roditi D, Malan A. Single-dose benzathine penicillin in infants at risk of congenital syphilis--results of a randomised study. S Afr Med J 1997; 87:62.
  39. Paryani SG, Vaughn AJ, Crosby M, Lawrence S. Treatment of asymptomatic congenital syphilis: benzathine versus procaine penicillin G therapy. J Pediatr 1994; 125:471.
  40. Michelow IC, Wendel GD Jr, Norgard MV, et al. Central nervous system infection in congenital syphilis. N Engl J Med 2002; 346:1792.
  41. Sánchez PJ, Wendel GD Jr, Grimprel E, et al. Evaluation of molecular methodologies and rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central nervous system invasion by Treponema pallidum. J Infect Dis 1993; 167:148.
  42. Beeram MR, Chopde N, Dawood Y, et al. Lumbar puncture in the evaluation of possible asymptomatic congenital syphilis in neonates. J Pediatr 1996; 128:125.
  43. Daaboul JJ, Kartchner W, Jones KL. Neonatal hypoglycemia caused by hypopituitarism in infants with congenital syphilis. J Pediatr 1993; 123:983.
  44. Nolt D, Saad R, Kouatli A, et al. Survival with hypopituitarism from congenital syphilis. Pediatrics 2002; 109:e63.
  45. Moyer VA, Schneider V, Yetman R, et al. Contribution of long-bone radiographs to the management of congenital syphilis in the newborn infant. Arch Pediatr Adolesc Med 1998; 152:353.
  46. Brion LP, Manuli M, Rai B, et al. Long-bone radiographic abnormalities as a sign of active congenital syphilis in asymptomatic newborns. Pediatrics 1991; 88:1037.
  47. Kocher MS, Caniza M. Parrot pseudoparalysis of the upper extremities. A case report. J Bone Joint Surg Am 1996; 78:284.
  48. Case of the week. Newborn infant with hepatomegaly. VCU Health System. http://www.pedsradiology.com/Historyanswer.aspx?qid=144&fid=1 (Accessed on August 12, 2011).
  49. Rasool MN, Govender S. The skeletal manifestations of congenital syphilis. A review of 197 cases. J Bone Joint Surg Br 1989; 71:752.
  50. Cremin BJ, Fisher RM. The lesions of congenital syphilis. Br J Radiol 1970; 43:333.
  51. Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
  52. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021. p.729.
  53. Lascari AD, Diamond J, Nolan BE. Anemia as the only presenting manifestation of congenital syphilis. Clin Pediatr (Phila) 1976; 15:90.
  54. Bulova SI, Schwartz E, Harrer WV. Hydrops fetalis and congenital syphilis. Pediatrics 1972; 49:285.
  55. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93:105.
  56. PUTKONEN T. Does early treatment prevent dental changes in congenital syphilis? Acta Derm Venereol 1963; 43:240.
  57. Stamos JK, Rowley AH. Timely diagnosis of congenital infections. Pediatr Clin North Am 1994; 41:1017.
  58. OKSALA A. Interstitial keratitis after adequate penicillin therapy; a case report. Br J Vener Dis 1957; 33:113.
  59. Fiumara NJ, Lessell S. Manifestations of late congenital syphilis. An analysis of 271 patients. Arch Dermatol 1970; 102:78.
  60. Dorfman DH, Glaser JH. Congenital syphilis presenting in infants after the newborn period. N Engl J Med 1990; 323:1299.
  61. Adams DA, Kerr AG, Smyth GD, Cinnamond MJ. Congenital syphilitic deafness--a further review. J Laryngol Otol 1983; 97:399.
  62. Hardy JB, Hardy PH, Oppenheimer EH, et al. Failure of penicillin in a newborn with congenital syphilis. JAMA 1970; 212:1345.
  63. Rawstron SA, Vetrano J, Tannis G, Bromberg K. Congenital syphilis: detection of Treponema pallidum in stillborns. Clin Infect Dis 1997; 24:24.
  64. Burstain JM, Grimprel E, Lukehart SA, et al. Sensitive detection of Treponema pallidum by using the polymerase chain reaction. J Clin Microbiol 1991; 29:62.
  65. Larsen SA. Syphilis. Clin Lab Med 1989; 9:545.
  66. Rawstron SA, Bromberg K. Comparison of maternal and newborn serologic tests for syphilis. Am J Dis Child 1991; 145:1383.
  67. Stoll BJ, Lee FK, Larsen S, et al. Clinical and serologic evaluation of neonates for congenital syphilis: a continuing diagnostic dilemma. J Infect Dis 1993; 167:1093.
  68. Lefevre JC, Bertrand MA, Bauriaud R. Evaluation of the Captia enzyme immunoassays for detection of immunoglobulins G and M to Treponema pallidum in syphilis. J Clin Microbiol 1990; 28:1704.
  69. Woznicová V, Smajs D, Wechsler D, et al. Detection of Treponema pallidum subsp. pallidum from skin lesions, serum, and cerebrospinal fluid in an infant with congenital syphilis after clindamycin treatment of the mother during pregnancy. J Clin Microbiol 2007; 45:659.
  70. Lago EG. Current Perspectives on Prevention of Mother-to-Child Transmission of Syphilis. Cureus 2016; 8:e525.
  71. Bonawitz RE, Duncan J, Hammond E, et al. Assessment of the impact of rapid syphilis tests on syphilis screening and treatment of pregnant women in Zambia. Int J Gynaecol Obstet 2015; 130 Suppl 1:S58.
  72. Genest DR, Choi-Hong SR, Tate JE, et al. Diagnosis of congenital syphilis from placental examination: comparison of histopathology, Steiner stain, and polymerase chain reaction for Treponema pallidum DNA. Hum Pathol 1996; 27:366.
  73. Sheffield JS, Sánchez PJ, Morris G, et al. Congenital syphilis after maternal treatment for syphilis during pregnancy. Am J Obstet Gynecol 2002; 186:569.
  74. Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance System. http://www.cdc.gov/osels/ph_surveillance/nndss/phs/infdis.htm (Accessed on August 12, 2011).
Topic 14428 Version 34.0

References