Limitations Background:
Although not recommended by the American Academy of Pediatrics (AAP) for pregnant women, some laboratories are using “reverse screening
(RS)” for the serologic screening for syphilis. This method of testing starts with a treponemal specific enzyme immunoassay (EIA) or
chemiluminescence immunoassay (CIA) screening test followed by a nontreponemal test (i.e. RPR) if the EIA or CIA is positive. Discordant
treponemal and nontreponemal results may occur, prompting the need for a “tie-breaker” treponemal test such as a Treponema pallidum particle
agglutination assay (TPPA).
RS may identify mothers with no history of syphilis or syphilis treatment, but with a reactive treponemal test and a nonreactive nontreponemal test.
Such discordant results have resulted in uncertainty in management of the neonate, creating maternal serologic scenarios for which there are
currently no guidelines or algorithms to guide the evaluation and management of these neonates. The AAP provides no guidance for neonates
born to mothers with discordant results using reverse screening. The Centers for Disease Control (CDC) provides some guidance in the evaluation
of suspected congenital syphilis (CS), but they are not specific to RS.
Methods:
We reviewed the literature for RS in pregnant women and developed a draft algorithm for management of neonates. We posed clinical scenarios to
specialists with extensive pediatric syphilis experience. The proposed algorithm is a conservative approach to the management of these infants
and reflects a synthesis of approaches, but the final algorithm may not reflect the approach of each contributing author.
Results:
A proposed algorithm was developed for the evaluation and treatment of infants born to mothers with reactive tests for syphilis using reverse
screening.
Conclusion:
Current AAP and CDC guidelines for CS are not tailored to reverse screening. Evidence-based data for evaluating these neonates is limited. We
have developed a conservative proposed algorithm for the management of neonates born to mothers with discordant serology using RS.
Congenital Syphilis: Management Dilemmas using Reverse Screening
Michelle Sewnarine MD1,2, Sujatha Rajan MD1,2, Geoffrey A. Weinberg MD3,4, Kenneth Bromberg MD5,6, Sunil Sood MD1,2, Lorry Rubin MD1,2
1Cohen Children’s Medical Center of New York of the Northwell Health System, New Hyde Park, NY 2Hofstra Northwell School of Medicine at Hofstra University, Hempstead, NY
3Golisano Children’s Hospital, Rochester, NY 4University of Rochester School of Medicine and Dentistry, Rochester, NY
5Brooklyn Hospital Center, Brooklyn, NY 6Icahn School of Medicine at Mount Sinai, New York, NY
Background • Diagnosis of congenital syphilis (CS) can be difficult. Many neonates with suspected CS are asymptomatic or exhibit non-specific clinical
findings. In addition, it may be difficult to interpret reactive syphilis serology in neonates, given the passive transfer of maternal antibodies to the
neonate.
• The traditional screening test for syphilis is a nontreponemal serologic test (e.g. RPR, VDRL), followed by a specific treponemal test (e.g.
Treponema pallidum particle agglutination [TPPA] or fluorescent treponemal antibody-absorption test [FTA-ABS]) if the former is positive.
• Recently, several laboratories are performing reverse sequence screening for the diagnosis of syphilis. The initial test is a treponemal specific
enzyme immunoassay (EIA) or chemiluminescence immunoassay (CLIA) followed by a nontreponemal test if the EIA or CIA is positive.
- A discordant screening treponemal test and nontreponemal test result may occur, prompting the need for a “tie-breaker” confirmatory
treponemal test such as a TPPA or FTA-ABS test.
• The use of reverse screening (RS) poses a diagnostic dilemma and treatment challenge for pediatricians evaluating newborns born to mothers
with discordant results.
- A positive CIA/EIA screening test followed by a nonreactive nontreponemal test and a nonreactive confirmatory treponemal test may
represent early primary syphilis or a false-positive result in low-risk women with no history of treated syphilis.
- Another challenging situation is when a pregnant woman has a negative result using a traditional nontreponemal test in the prenatal period
and a reverse screening test is performed in the peripartum period that shows a positive result. The peripartum period may be the first time
the woman is tested with a treponemal test. If the nontreponemal test is negative, this result may be interpreted as early primary syphilis, the
prozone effect, late latent syphilis, latent syphilis of unknown duration, or treated syphilis. Other than past appropriately treated syphilis,
transmission to the neonate is possible in all of the above stages of syphilis infection.
- Maternal treatment for latent syphilis in the peripartum or postpartum period may influence the decision to evaluate and treat the neonate.
• Currently, there are no guidelines for the evaluation and management of newborns born to mothers with reactive serologic tests for syphilis using
RS.
Abstract
M. Sewnarine
269-01 76th Avenue
New Hyde Park, NY 11040
P (718) 470-3480
F (718) 470-0887
• We reviewed the literature for RS in pregnant women and found it lacking in providing guidance to clinicians evaluating newborns. The literature
provided an interpretation of the various combinations of serologies which may be encountered with RS. However, it did not provide information
about management of the neonate. We posed clinical scenarios to specialists with extensive pediatric syphilis experience. Therefore, based on
expert consensus, we developed a draft algorithm for management of neonates. The proposed algorithm is a conservative approach to the
management of these infants and reflects a synthesis of approaches, but the final algorithm may not reflect the approach of each contributing
author.
Definitions:
• High-risk mother: History of HIV and/or other STIs, inadequate prenatal care, unprotected sexual intercourse with several partners, new sexual
partners during pregnancy, mother is a sex worker, mother has signs and/or symptoms of syphilis, has a partner with clinical or serologic
evidence of syphilis, or follow-up is uncertain.
• Low-risk mother: Not fulfilling the criteria of a high-risk mother.
#707
• Current AAP and CDC guidelines for the evaluation of congenital syphilis are not tailored to reverse screening.
• Evidence-based data for evaluating these neonates is limited.
• We have developed a conservative proposed algorithm for the management of neonates born to mothers with discordant syphilis serology using
reverse sequence screening.
• There is a need for studies to validate the safety and efficacy of this approach.
Conclusions
References
1. CDC, Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(3):45-48.
2. Kimberlin DW (Ed.) Red Book®: 2015 Report of the Committee on Infectious Diseases. Syphilis. 30th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2015:755-768.
3. Mmeje O, Chow J, Davidson L, Shieh J, Schapiro J, Park I. Discordant Syphilis Immunoassays in Pregnancy: Perinatal Outcomes and
Implications for Clinical Management. Clinical Infectious Diseases 2015; 61(7):1049-53.
4. Patel SJ, Klinger R, O’Toole D, Schillinger J. Missed Opportunities for Preventing Congenital Syphilis Infection in New York City. Obstetrics &
Gynecology 2012; 120:882-8.
5. Park I, Chow J, Bolan G, Stanley M, Shieh J, Schapiro J. Screening for Syphilis with the Treponemal Immunoassay: Analysis of Discordant
Serology Results and Implications for Clinical Management. The Journal of Infectious Diseases 2011; 204:1297-304.
6. Peterman T, Newman D, Davis D, Su J. Do Women with Persistently Negative Nontreponemal Test Results Transmit Syphilis During
Pregnancy? Sexually Transmitted Diseases 2012; 40:311-315.
7. Wicher V, Wicher K. Pathogenesis of Maternal-Fetal Syphilis Revisited. Clinical Infectious Diseases 2001; 33:354-363.
• This algorithm represents expert consensus, but is not yet validated.
• The algorithm is a conservative approach and neonates may receive unnecessary evaluation and/or treatment due to lack of evidence-based
data.
Mother’s Serology Interpretation of Serology Results in a Mother with No History of Treatment
CIA/EIA+, RPR -, TPPA+ Early primary syphilis, the prozone effect, late latent syphilis, or latent syphilis of unknown duration
CIA/EIA+, RPR -, TPPA- Early primary syphilis or false-positive CIA/EIA
CIA/EIA+, RPR -, TPPA equivocal Early primary syphilis, the prozone effect, late latent syphilis, latent syphilis of unknown duration, or false-positive CIA/EIA and/or TPPA
Results
Methods
Maternal CIA/EIA
CIA/EIA + CIA/EIA -
RPR + RPR -
Evaluate and treat
per American
Academy of
Pediatrics (AAP)
recommendations
TPPA + TPPA - or TPPA equivocal
Documented
appropriately treated
syphilis before or
during pregnancy?
Low-risk mother2
No evaluation and
no treatment of
baby. Recheck
mother’s serology
within 4 weeks.
High-risk
mother1
Yes No
Follow AAP algorithm
recommendations *
AAP full evaluation3 of baby and
PCN pending results4
Baby’s RPR - and
negative evaluation
Baby’s RPR ≥ 1:1 or
positive evaluation (abnormal exam or
abnormal/incomplete results)
Treatment:
b-PCN x 1 dose or PCN x 10 days Treatment:
PCN x 10 days
No further
evaluation
Proposed algorithm for evaluation and treatment of
infants born to mothers with reactive serologic tests for
syphilis using “reverse screening”
1 Modified from CDC
criteria of high-risk mother:
History of HIV and/or other
STIs, inadequate prenatal
care, unprotected sexual
intercourse with several
partners, new sexual partners
during pregnancy, mother is a
sex worker, mother has signs
and/or symptoms of syphilis,
has a partner with clinical or
serologic evidence of syphilis,
or follow-up is uncertain.
2 Low-risk mother: Not
fulfilling the criteria of a high-
risk mother.
3 AAP full evaluation: RPR,
CBC, CSF analysis for cell
count, protein, and VDRL,
and testing for HIV infection.
Other tests as clinically
indicated: e.g. LFTs, chest
x-ray, long bone x-rays, eye
exam, neuroimaging, and
auditory brainstem response.
4 If baby’s RPR is nonreactive
and the provider determines
mother’s risk of untreated
syphilis is low, treatment with
b-PCN x 1 dose can be
considered without an
evaluation.
PCN = penicillin (aqueous
penicillin G or procaine
penicillin G)
b-PCN = benzathine penicillin
Mother CIA/EIA+, RPR-, TPPA+ and documented appropriately treated syphilis before or during pregnancy = past treated syphilis
If no evidence of clinical reinfection/relapse in mother + baby’s RPR < fourfold mother’s + baby’s exam normal No evaluation +/- b-PCN x 1
*