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Treponema pallidum can be transmitted from mother to child at any stage of pregnancy or during delivery. Among women with untreated primary, secondary, early latent, or late latent syphilis at delivery, approximately 30%, 60%, 40%, and 7% of infants, respectively, will be infected. Treatment of the mother for syphilis ≥30 days before delivery is required for effective in utero treatment.

Congenital syphilis has been reported despite adequate maternal treatment. Factors that contribute to treatment failure include maternal stage of syphilis (early stage, meaning, primary, secondary, or early latent syphilis), advancing gestational age at treatment, higher Venereal Disease Research Laboratory (VDRL) titers at treatment and delivery, and short interval from treatment to delivery (<30 days) (133Sheffield JS, Sanchez PJ, Morris G, et al. Congenital syphilis after maternal treatment for syphilis during pregnancy. Am J Obstet Gynecol 2002;186:569-73., 134Alexander JM, Sheffield JS, Sanchez PJ, et al. Efficacy of treatment for syphilis in pregnancy. Obstet Gynecol 1999;93:5-8.). In 2005, the rate of congenital syphilis declined to 8 per 100,000 live-born infants (135CDC. Sexually transmitted disease surveillance, 2005. Atlanta, GA: U.S. Department of Health and Human Services. November 2006. Available at http://www.cdc.gov/std/stats05/05pdf/2005-exordium.pdf.), down from 14.3 cases per 100,000 in 2000 and 27.9 cases per 100,000 in 1997. Overall, cases of congenital syphilis have decreased 74% since 1996. The continuing decline in the rate of congenital syphilis probably reflects the substantially reduced rate of primary and secondary syphilis among women during the last decade.

Drug use during pregnancy, particularly cocaine use, has been associated with increased risk for maternal syphilis and congenital infection (136Sison CG, Ostrea EM, Reyes MP, et al. The resurgence of congenital syphilis: a cocaine-related problem. J Pediatr 1997;130:289-92.). Similarly, HIV-infected women have a higher prevalence of untreated or inadequately treated syphilis during pregnancy, which places their newborns at higher risk for congenital syphilis (137Schulte JM, Burkham S, Hamaker D, et al. Syphilis among HIVinfected mothers and their infants in Texas from 1988 to 1994. Sex Transm Dis 2001;28:315-20.). Mother-to-child HIV transmission might be higher when syphilis coinfection is present during pregnancy (137Schulte JM, Burkham S, Hamaker D, et al. Syphilis among HIVinfected mothers and their infants in Texas from 1988 to 1994. Sex Transm Dis 2001;28:315-20., 138Lee MJ, Hallmark RJ, Frenkel LM, et al. Maternal syphilis and vertical perinatal transmission of human immunodeficiency virus type-1 infection. Int J Gynaecol Obstet 1998;63:247-52., 139Mwapasa V, Rogerson SJ, Kwiek JJ, et al. Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi. AIDS 2006;20:1869-77.); transmission does not appear to be higher if the mother's syphilis is effectively treated before pregnancy (137Schulte JM, Burkham S, Hamaker D, et al. Syphilis among HIVinfected mothers and their infants in Texas from 1988 to 1994. Sex Transm Dis 2001;28:315-20.).

Although approximately two thirds of sexually transmitted diseases (STDs) diagnosed annually in the United States occur among persons aged <24 years, such individuals account for less than 25% of early syphilis cases. Nevertheless, the prevalence and incidence of syphilis among HIV-infected youth and of HIV infection among youth with syphilis are appreciable; in a study of 320 HIV-infected and uninfected U.S. adolescents aged 12-19 years, the prevalence of syphilis was 9% among HIV-infected girls and 6% among HIV-infected boys (140Vermund SH, Wilson CM, Rogers AS, et al. Sexually transmitted infections among HIV infected and HIV uninfected high-risk youth in the REACH study. Reaching for Excellence in Adolescent Care and Health. J Adolesc Health 2001;29(3 Suppl):49-56.). In a meta-analysis of 30 studies, the median HIV seroprevalence among persons infected with syphilis in the United States was 15.7% (27.5% among men and 12.4% among women with syphilis) (141Blocker ME, Levine WC, St Louis ME. HIV prevalence in patients with syphilis, United States. Sex Transm Dis 2000;27:53-9.).

Untreated early syphilis during pregnancy can lead to spontaneous abortion, stillbirth, hydrops fetalis, preterm delivery, and perinatal death in up to 40% of pregnancies (142Singh R, McCloskey J. Syphilis in pregnancy. Venereology 2001:14:121-31.). Among children with congenital syphilis, two characteristic syndromes of clinical disease exist: early and late congenital syphilis. Early congenital syphilis refers to clinical manifestations appearing within the first 2 years of life. Late congenital syphilis refers to clinical manifestations appearing in children >2 years old.

At birth, infected infants may manifest such signs as hepatosplenomegaly, jaundice, mucocutaneous lesions (e.g., skin rash, nasal discharge, mucous patches, condyloma lata), lymphadenopathy, pseudoparalysis of an extremity, anemia, thrombocytopenia, pneumonia, and skeletal lesions (e.g., osteochondritis, periostitis, or osteitis). In a study of 148 infants born to mothers with untreated or inadequately treated syphilis, 47% had clinical, radiographic, or conventional laboratory findings consistent with congenital syphilis, and 44% had a positive rabbit infectivity test, PCR assay, or IgM immunoblot of serum, blood, or CSF (143Michelow IC, Wendel GD Jr, Norgard MV, et al. Central nervous system infection in congenital syphilis. N Engl J Med 2002;346:1792-8.). However, as many as 60% of infants with congenital syphilis do not have any clinical signs at birth (144Glaser JH. Centers for Disease Control and Prevention guidelines for congenital syphilis. J Pediatr 1996;129:488-90.). If untreated, these "asymptomatic" infants can develop clinically apparent disease in the ensuing 3 weeks to 6 months. In addition, fever, nephrotic syndrome, and hypopituitarism may occur.

The manifestations of acquired syphilis in older children and adolescents are similar to those of adults (see Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults,) (16CDC. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from the CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.). HIV-infected persons with acquired early syphilis might be at increased risk for neurologic complications and uveitis and have higher rates of treatment failure (145CDC. Symptomatic early neurosyphilis among HIV-positive men who have sex with men-four cities, United States, January 2002-June 2004. MMWR 2007;56:625-8.).

The standard serologic tests for syphilis in adults are based on the measurement of IgG antibody. Because IgG antibody in the infant reflects transplacental passively transferred antibody from the mother, interpretation of reactive serologic tests for syphilis among infants is difficult. Therefore, the diagnosis of neonatal congenital syphilis depends on a combination of results from physical, laboratory, radiographic, and direct microscopic examinations.

All infants born to women with reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal test (e.g., VDRL slide test, rapid plasma reagin [RPR], or the automated reagin test). Neonatal serum should be tested because of the potential for maternal blood contamination of the umbilical cord blood specimens. Specific treponemal tests, such as the fluorescent treponemal antibody absorption (FTA-ABS) test and T. pallidum particle agglutination (TP-PA) test, are not necessary to evaluate congenital syphilis in the neonate. No commercially available IgM test is recommended for diagnostic use. (Note: Some laboratories use treponemal tests, such as EIA, for initial screening, and nontreponemal tests for confirmation of positive specimens (146Pope V. Use of treponemal tests to screen for syphilis. Infect Med 2004;21:399-404.). However, such an approach with congenital syphilis has not been published.)

Congenital syphilis can be definitively diagnosed if T. pallidum is detected by using darkfield microscopic examination or direct fluorescent antibody staining of lesions or body fluids such as umbilical cord, placenta, nasal discharge, or skin lesion material from the infant. Failure to detect T. pallidum does not definitively rule out infection because false-negative results are common. Pathologic examination of placenta and umbilical cord with specific fluorescent antitreponemal antibody staining is recommended.

Evaluation of suspected cases of congenital syphilis should include a careful and complete physical examination. Further evaluation depends on maternal treatment history for syphilis, findings on physical examination, and planned infant treatment and may include a complete blood count and differential and platelet count, long bone radiographs, and CSF analysis for VDRL, cell count, and protein. HIV-infected infants might have increased cell counts and protein concentrations even in the absence of neurosyphilis. Other tests should be performed as clinically indicated (e.g., chest radiograph, liver-function tests, cranial ultrasound, ophthalmologic examination, and auditory brainstem response).

A proven case of congenital syphilis requires visualization of spirochetes by darkfield microscopy or fluorescent antibody testing of body fluid(s). Finding that an infant's serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer suggests infection but is not a criterion in the case definition. A presumptive case of syphilis is defined as maternal untreated or inadequately treated syphilis at delivery, regardless of findings in the infant, or a reactive treponemal test result and signs in an infant of congenital syphilis on physical examination, laboratory evaluation, long bone radiographs, positive CSF VDRL test, or an abnormal CSF finding without other cause.

For diagnosis of acquired syphilis, a reactive nontreponemal test must be confirmed by a specific treponemal test such as FTA-ABS or TP-PA. Treponemal tests usually will remain positive for life, even with successful treatment. The prozone phenomenon (a weakly reactive or falsely negative) reaction might occur more frequently in HIV-infected persons (147Juardo R, Campbell J, Martin PD. Prozone phenomenon in secondary syphilis. Has its time arrived? Arch Intern Med 1993;153:2496-8.). Treponemal antibody titers do not correlate with disease activity and should not be used to monitor treatment response. CSF should be evaluated among HIV-infected adolescents with acquired syphilis of unknown or < 1 year's duration or if they have neurologic or ocular symptoms or signs; many clinicians recommend a CSF examination for all HIV-infected patients with syphilis (16CDC. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from the CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.).

Not applicable.

All seroreactive infants (or infants whose mothers were seroreactive at delivery) should receive careful follow-up examinations and serologic testing (i.e., a nontreponemal test) every 2-3 months until the test becomes nonreactive or the titer has decreased fourfold (AIII). Nontreponemal antibody titers should decline by age 3 months and should be nonreactive by age 6 months if the infant was not infected (i.e., if the reactive test result was caused by passive transfer of maternal IgG antibody) or was infected but adequately treated. The serologic response after therapy might be slower for infants treated after the neonatal period. Whether children with congenital syphilis who also are HIV-infected take longer to become nonreactive and require retreatment is not known.

Treponemal tests should not be used to evaluate treatment response because the results for an infected child can remain positive despite effective therapy. Passively transferred maternal treponemal antibodies can be present in an infant until age 15 months. A reactive treponemal test after age 18 months is diagnostic of congenital syphilis. If the nontreponemal test is nonreactive at this time, no further evaluation or treatment is necessary. If the nontreponemal test is reactive at age 18 months, the infant should be fully (re)evaluated and treated for congenital syphilis (AIII).

Infants whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal (AII). A reactive CSF VDRL test or abnormal CSF indices that cannot be attributed to other ongoing illness requires retreatment for possible neurosyphilis.

HIV-infected children and adolescents with acquired early syphilis (i.e., primary, secondary, early latent) should have clinical and serologic response monitored at age 3, 6, 9, 12, and 24 months after therapy (AIII); nontreponemal test titers should decline by at least fourfold by 6-12 months after successful therapy, with examination of CSF and retreatment strongly considered in the absence of such decline. For syphilis of longer duration, follow-up is indicated at 6, 12, and 24 months; fourfold decline should be expected by 12-24 months. If initial CSF examination demonstrated a pleocytosis, repeat lumbar puncture should be conducted at 6 months after therapy, and then every 6 months until the cell count is normal (AIII). Follow-up CSF examinations also can be used to evaluate changes in the VDRL-CSF or CSF protein levels after therapy, but changes in these parameters occur more slowly than changes in CSF cell counts. Data from HIV-infected adults with neurosyphilis suggest that CSF abnormalities might persist for extended times, and close clinical follow-up is warranted (145CDC. Symptomatic early neurosyphilis among HIV-positive men who have sex with men-four cities, United States, January 2002-June 2004. MMWR 2007;56:625-8.).

Syphilis in an HIV-infected child (congenital or acquired) manifesting as IRIS has not been reported, and only very rare reports of syphilis-associated IRIS in adults (primarily syphilitic ocular inflammatory disease) have been reported (156Moloney G, Branley M, Kotsiou G, et al. Syphilis presenting as scleritis in an HIV-positive man undergoing immune reconstitution. Clin Experiment Ophthalmol 2004;32:526-8.).

After treatment of congenital syphilis, children with increasing or stable nontreponmenal titers at age 6-12 months or children who are seropostive with any titer at 18 months should be evaluated (e.g., including a CSF examination) and considered for retreatment with a 10-day course of parenteral penicillin (AIII).

The management of failures of treatment of acquired syphilis in older children and adolescents is identical to that in adults (16CDC. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from the CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.). Retreatment of patients with early-stage syphilis should be considered for those who 1) do not experience at least a fourfold decrease in serum nontreponemal test titers 6-12 months after therapy, 2) have a sustained fourfold increase in serum nontreponemal test titers after an initial reduction posttreatment, or 3) have persistent or recurring clinical signs or symptoms of disease (BIII). If CSF examination does not confirm the diagnosis of neurosyphilis, such patients should receive 2.4 million units IM benzathine penicillin G administered at 1-week intervals for 3 weeks (BIII). Certain specialists have also recommended a course of aqueous penicillin G IV or procaine penicillin IM plus probenicid (as described above for treatment of neurosyphilis) for all patients with treatment failure, although data to support this recommendation are lacking (CIII). If titers fail to respond appropriately after retreatment, the value of repeat CSF evaluation or retreatment has not been established.

Patients with late-latent syphilis should be retreated if they 1) have clinical signs or symptoms of syphilis, 2) have a fourfold increase in serum nontreponemal test titer, or 3) experience an inadequate serologic response (less than fourfold decline in nontreponemal test titer) within 12-24 months after therapy if initial titer was high (>1:32) (BIII). Such patients should have a repeat CSF examination. If the repeat CSF examination is consistent with CNS involvement, retreatment should follow the neurosyphilis recommendations (AIII); those without a CSF profile indicating CNS disease should receive a repeat course of benzathine penicillin, 2.4 million units IM weekly for 3 weeks (BIII), although certain specialists recommend following the neurosyphilis recommendations in this situation as well (CIII).

Retreatment of neurosyphilis should be considered if the CSF white blood cell count has not decreased 6 months after completion of treatment or if the CSF-VDRL remains reactive 2 years after treatment (BIII).

No recommendations have been developed for secondary prophylaxis or chronic maintenance therapy for syphilis in HIV-infected children.

Not applicable.