Congenital Syphilis and Herpes Simplex Virus Infection: An Update for the Pediatrician

Educational Objectives

The goal of this program is to improve the management of congenital infections in infants. After hearing and assimilating this program, the clinician will be better able to:

1. Screen newborns for congenital syphilis, herpes simplex virus, and Zika virus infection.

2. Provide a management plan for infants with congenital syphilis or herpes simplex virus infection.

Summary

Syphilis: caused by Treponema pallidum, subspecies pallidum (thin, motile spirochete); yaws, endemic syphilis, and pinta caused by other subspecies; rates of congenital, primary, and secondary syphilis increasing in United States, most rapidly in women of childbearing age

Congenital syphilis: rates vary by state, from 0 to 93/100,000 live births; clinical manifestations — range from no symptoms to stillbirth; hydrops fetalis and preterm delivery possible; most common features hepatosplenomegaly (protuberant belly in newborn), snuffles (clear rhinorrhea shortly after birth), and periostitis (“flail limb” held in pseudoparalysis position); other features include lymphadenopathy, pneumonia (bilateral infiltrations on chest radiography), dark red “copper spot” rash on hands and feet, diffuse desquamating lesions, and thrombocytopenia; skin lesions and nasal discharge highly contagious; late manifestations — typically present in adulthood; interstitial keratitis; eighth cranial nerve deafness; Hutchinson teeth (peg-shaped incisors); frontal bossing; saddle nose; Clutton joints; early identification prevents progression to later findings; another late manifestation is saber shins

Testing for congenital syphilis: because organism does not grow in culture, serologic testing used; nontreponemal testing — assesses reaction to nonspecific antigen; results semiquantitative (titers); strength of reaction wanes over time; treponemal antigen testing — assesses specific reaction to T pallidum; reported as reactive or nonreactive; positive result typically persists for life; nontreponemal tests — rapid plasma reagin (RPR); Venereal Disease Research Laboratory (VDRL) test (used only in cerebrospinal fluid [CSF]); treponemal tests — fluorescent treponemal antibody adsorption (FTA-ABS); T pallidum particle agglutination assay (TP-PA); T pallidum enzyme immunoassay (TP-EIA); order of testing — some clinicians perform treponemal test to assess for lifetime exposure, then use nontreponemal test to assess current status; most screen using RPR with confirmatory treponemal test; false-positive results possible on RPR with, eg, recent immunization, febrile illness, or pregnancy; polymerase chain reaction (PCR) not widely available

Assessment and treatment of congenital syphilis: 4 categories described in American Academy of Pediatrics (AAP) Red Book

Proven or highly probable congenital syphilis: infant has either abnormal findings on physical examination consistent with congenital syphilis, serum nontreponemal titer >4 times maternal titer, or positive confirmatory testing using dark-field microscopy or PCR (usually performed on snuffles discharge); assess CSF for cell count, protein, and VDRL; check for thrombocytopenia; if indicated, check radiography of long bones (periostitis) and chest (pneumonia), liver transaminases, neuroimaging, ophthalmologic examination, and hearing screen; treatment requires intravenous penicillin for 10 days before discharge; intramuscular (IM) regimen available (but rarely used)

Possible congenital syphilis: infant has normal physical examination with nontreponemal titer ≤4 times greater than maternal titer, with either inadequate (or undocumented) treatment of maternal syphilis during pregnancy, treatment with nonpenicillin regimen, or adequate treatment given <4 wk before delivery; basic evaluation and treatment same as for patients in proven/highly probable category

Congenital syphilis “less likely”: infant has normal physical examination, nontreponemal titer ≤4 times greater than maternal titer, and appropriate treatment of maternal syphilis >4 wk before delivery with no evidence of maternal reinfection, exposure, or relapse; no assessment needed; provide single dose of IM penicillin

Congenital syphilis unlikely: infant has normal physical examination, nontreponemal titer ≤4 times greater than maternal titer, and appropriate maternal treatment before pregnancy with low maternal nontreponemal titer; no assessment or treatment needed; repeat RPR at 3 to 6 mo of age (should reach 0)

Herpes simplex virus (HSV): large, enveloped, double-stranded DNA virus; historically, serotype 1 (HSV-1) associated with gingivostomatitis (80% of adults carry HSV in mouth), and serotype 2 (HSV-2) associated with genital herpes; with changing sexual practices, genital or oral lesions now equally likely to be HSV-1 or HSV-2; both serotypes establish latency (lifelong infection) with periodic reactivation; triggers include stress and pregnancy; genital HSV more likely to recur than oral

Congenital HSV infection: occurs in ≈1/3000 live births; although mothers who acquire primary genital HSV late in pregnancy are at highest risk for transmission (25%-60% risk for genital herpes in infant), reactivation much more common (<2% risk); therefore, reactivation results in many more cases; most mothers asymptomatic; intrauterine infection rare; most cases acquired perinatally; some postnatal transmission occurs from oral herpes

Clinical manifestations: disseminated HSV — occurs in ≈25%; infants extremely ill with sepsis and liver injury; skin lesions occur in 70%; presents at 1 to 2 wk of life; mortality rate high, even with treatment; central nervous system (CNS) HSV — occurs in ≈30%; no sepsis or liver injury; skin lesions present in ≈70%; presents at slightly later age; skin eye mouth (SEM) disease — occurs in ≈45%; vesicles occur in ≈80%; possible to have mouth and eye lesions only; SEM disease presents early

Testing for congenital HSV: culture of swab specimen gold standard for diagnosis (particularly for SEM), but PCR used in most laboratories (good sensitivity and specificity); swab eye, mouth, nasopharynx, rectum, and any lesions; assess CSF or blood for HSV by PCR; assess for thrombocytopenia and liver dysfunction; multinucleated giant cells seen on Tzank test (rarely performed)

Assessment and treatment of congenital HSV: parenteral acyclovir used for 14 days in SEM and 21 days in disseminated and CNS infection; consult ophthalmologist (herpes keratitis treated topically); obtain magnetic resonance imaging of brain; HSV classically infects temporal lobes, but any part of brain may be affected in newborn; all children also require enteral suppressive therapy, ie, acyclovir for ≥6 mo (dose based on body surface area); check absolute neutrophil count and creatinine monthly (for rare leukopenia and renal issues); skin outbreak occurs in ≈20% when suppressive therapy stopped; treat with enteral acyclovir for 7 days; if second outbreak occurs, provide suppressive therapy for another 6 mo; recurrences typically limited to skin

Zika virus: in 2019, confirmed infections only reported in 5 states (<10 cases per state); all cases imported (ie, recent travel to endemic area); Puerto Rico only US location with ongoing local transmission

Congenital Zika virus infection: Rice et al found ≈14% of US mothers with confirmed infection had infants with Zika-associated birth defect or neurodevelopmental abnormality; microcephaly occurred in 6%; AAP Red Book chapter on Zika virus includes evaluation, type and timing of testing, consultation, and neurodevelopmental assessment

Readings

American Academy of Pediatrics. Herpes simplex. In: Kimberlin DW et al, eds. Red Book: 2018-2021 Report of the Committee on Infectious Diseases. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018:437-49; American Academy of Pediatrics. Syphilis. In: Kimberlin DW et al, eds. Red Book: 2018-2021 Report of the Committee on Infectious Diseases. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018:773-88; American Academy of Pediatrics. Zika virus. In: Kimberlin DW et al, eds. Red Book: 2018-2021 Report of the Committee on Infectious Diseases. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018:894-901; Arrieta AC et al: Congenital syphilis. N Engl J Med 2019 Nov 28;381(22):2157. doi: 10.1056/NEJMicm1904420; Fa F et al: Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: a literature review. Prenat Diagn 2019 Oct 30. doi: 10.1002/pd.5587; Harris JB et al: Neonatal herpes simplex viral infections and acyclovir: an update. J Pediatr Pharmacol Ther 2017 Mar-Apr;22(2):88-93; Rice ME et al: Vital signs: Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection — U.S. territories and freely associated states, 2018. MMWR Morb Mortal Wkly Rep 2018 Aug 10;67(31):858-67; The Lancet: Congenital syphilis in the USA. Lancet 2018 Oct 6;392(10154):1168. doi: 10.1016/S0140-6736(18)32360-2.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Bender was recorded at Aloha Update: Pediatrics 2019, presented by the American Academy of Pediatrics, California District IX, Chapter 2, in association with Children’s Hospital Los Angeles Medical Group, and held October 12-18, 2019, on Kauai, HI. For information about upcoming CME conferences from the Children’s Hospital Los Angeles Medical Group, please visit www.chla.org/cme-conferences. The Audio Digest Foundation thanks Dr. Bender; the American Academy of Pediatrics, California District IX, Chapter 2; and Children’s Hospital Los Angeles Medical Group for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD662302

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.