Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Syphilis

Last Updated: November 6, 2013; Last Reviewed: November 6, 2013

Panel's Recommendations for Syphilis
Panel's Recommendations

Congenital Syphilis

  • Infants should be evaluated and treated per guidelines for congenital syphilis, given the following maternal factors: 
    • Untreated or inadequately treated syphilis (including treatment with erythromycin or any other non-penicillin regimen) 
    • Lack of documentation of having received treatment, 
    • Receipt of treatment <30 days before delivery, 
    • Treatment with penicillin but maternal nontreponemal antibody titer at delivery is fourfold higher than the pretreatment titer, or 
    • Fourfold or greater increase in nontreponemal antibody titer suggesting relapse or reinfection (AII)
  • Note: For comprehensive discussion and recommendations, see Centers for Disease Control and Prevention Sexually Transmitted Disease Treatment Guidelines, 2010.
  • Treatment for proven or highly probable congenital syphilis is aqueous crystalline penicillin G for 10 days (AII).
  • If congenital syphilis is diagnosed after age 1 month, the dosage of aqueous crystalline penicillin G should be increased per treatment guidelines (AII).
  • An alternative to aqueous crystalline penicillin G is procaine penicillin G for 10 days (BII).
  • All seroreactive infants (or infants whose mothers were seroreactive at delivery) should receive careful follow-up examinations and serologic testing (a nontreponemal test) every 2 to 3 months until the test becomes nonreactive or the titer has decreased fourfold (AIII). Infants whose initial cerebrospinal fluid (CSF) evaluations are abnormal should undergo repeat lumbar puncture approximately every 6 months until the results are normal (AII).
  • After treatment of congenital syphilis, children with increasing or stable nontreponemal titers at ages 6 to 12 months should be evaluated (i.e., including a CSF examination) and treated with a 10-day course of parenteral penicillin (AIII).
  • Infants in whom the nontreponemal test is reactive at age 18 months should be fully evaluated or re-evaluated (physical, serological, CSF, radiographic exams) and treated or re-treated for congenital syphilis (AIII).

Sexually-Acquired Syphilis

Early Syphilis

  • Acquired syphilis in children and adolescents is treated with a single dose of benzathine penicillin G for early-stage disease (i.e., primary, secondary, and early latent disease) (AII).
  • HIV-infected children and adolescents with early syphilis (i.e., primary, secondary, early latent) should receive a single dose of benzathine penicillin G. Those with primary and secondary syphilis should have clinical and serologic response monitored at 3, 6, 9, 12, and 24 months after therapy, and those with early latent syphilis should have clinical and serologic response monitored at 6, 12, 18, and 24 months after therapy (AIII). (For comprehensive discussion and recommendations, see the Centers for Disease Control and Prevention STD Treatment Guidelines, 2010).
  • Re-treatment of patients with early-stage syphilis (i.e., primary, secondary, early latent) and evaluation for HIV infection is recommended for those who: 
    • Do not experience at least a fourfold decrease in serum nontreponemal test titers 6 to 12 months after therapy,
    • Have a sustained fourfold increase in serum nontreponemal test titers after an initial reduction post-treatment, or 
    • Have persistent or recurring clinical signs or symptoms of disease. 
  • Individuals whose titers do not decline should at a minimum receive additional clinical and serologic follow-up. If such additional follow-up cannot be ensured, re-treatment is recommended. Because occult central nervous system infection may be signaled by persistently elevated serum nontreponemal test titers, evaluation of CSF can be considered in the event of such persistently elevated titers (BIII)
  • If initial CSF examination demonstrates pleocytosis, repeat lumbar puncture should be conducted, and then every 6 months until the cell count is normal (AIII).

Late Latent Syphilis

  • For late latent disease, 3 doses of benzathine penicillin G should be administered over 3 weeks (AIII).
  • Patients with late-latent syphilis should have CSF examination if they have clinical signs or symptoms attributable to syphilis, a fourfold increase in serum nontreponemal test titer, or experience an inadequate serologic response (i.e., less than fourfold decline in nontreponemal test titer) within 12 to 24 months after therapy if initial titer was high (>1:32) (BIII). CSF examination should also be performed. Treatment for neurosyphilis should be initiated if CSF examination is positive for neurosyphilis.
  • Benzathine penicillin G should be administered at 1-week intervals for 3 weeks to patients in whom CSF examination does not confirm the diagnosis of neurosyphilis (AIII)

Neurosyphilis

  • Neurosyphilis should be treated with aqueous penicillin G for 10 to 14 days (AII).
  • If a patient has signs or symptoms consistent with neurosyphilis, and repeat CSF examination is consistent with CNS involvement and cannot be attributable to other ongoing illness, re-treatment for neurosyphilis is recommended (AIII);
  • Re-treatment 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 white blood cell count or protein is not normal 2 years after treatment (BIII).

For All Syphilis

Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children with clinical outcomes and/or validated endpoints; I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion

Studies that include children or children/adolescents, but not studies limited to post-pubertal adolescents

Dosing Recommendations for Prevention and Treatment of Syphilis
Preventive Regimen 
Indication First Choice Alternative Comments/Special Issues
Primary Prophylaxis
N/A
N/A
Primary Prophylaxis Indicated for:
  • N/A
Criteria for Discontinuing Primary Prophylaxis:
  • N/A
Criteria for Restarting Primary Prophylaxis:
  • N/A
Secondary Prophylaxis
N/A N/A Secondary Prophylaxis Indicated:
  • N/A
Criteria For Discontinuing Secondary Prophylaxis
  • N/A
Criteria For Restarting Secondary Prophylaxis
  • N/A
Treatment Congenital
Proven or Highly Probable Disease:
  • Aqueous crystalline penicillin G 100,000–150,000 units/kg body weight per day, administered as 50,000 units/kg body weight per dose IV every 12 hours for the first 7 days of life, and then every 8 hours for 10 days 
  • If diagnosed after 1 month of age, aqueous penicillin G 200,000–300,000 unit/kg body weight per day, administered as 50,000 units/kg body weight per dose IV every 4–6 hours (maximum 18–24 million units per day) for 10 days
Possible Disease:
  • Treatment options are influenced by several factors, including maternal treatment, titer, and response to therapy; and infant physical exam, titer, and test results. Scenarios that include variations of these factors are described and treatment recommendations are provided in detail on pages 36–37 of the Centers for Disease Control STD Treatment Guidelines, 2010

Acquired:
Early Stage (Primary, Secondary, Early Latent):

  • Benzathine penicillin 50,000 units/kg body weight (maximum 2.4 million units) IM for 1 dose
Late Latent:
  • Benzathine penicillin 50,000 units/kg body weight (maximum 2.4 million units) IM once weekly for 3 doses 
Neurosyphilis (Including Ocular):
  • Aqueous penicillin G 200,000–300,000 units/kg body weight per day administered as 50,000 units/kg body weight per dose IV every 4–6 hours (maximum 18–24 million units per day) for 10–14 days
Congenital
Proven or Highly Probable Disease (Less Desirable if CNS Involvement):
  • Procaine penicillin G 50,000 units/kg body weight IM once daily for 10 days 
Possible Disease:
  • Treatment options are influenced by several factors, including maternal treatment, titer, and response to therapy; and infant physical exam, titer, and test results. Scenarios that include variations of these factors are described and treatment recommendations are provided in detail on pages 36–37 of the Centers for Disease Control STD Treatment Guidelines, 2010
For treatment of congenital syphilis, repeat the entire course of treatment if >1 day of treatment is missed. 

Examinations and serologic testing for children with congenital syphilis should occur every 2–3 months until the test becomes non-reactive or there is a fourfold decrease in titer. Children with increasing titers or persistently positive titers (even if low levels) at ages 6–12 months should be evaluated and considered for re-treatment.

In the setting of maternal and possible infant HIV infection, the more conservative choices among scenario-specific treatment options may be preferable.

Children and adolescents with acquired syphilis should have clinical and serologic response monitored at 3, 6, 9, 12, and 24 months after therapy.
Key to Acronyms: CDC = Centers for Disease Control and Prevention; IM = intramuscular; IV = intravenous; STD = sexually transmitted disease

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