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Congenital Syphilis/prevention/treatment

It is a severe, disabling, and often life-threatening infection seen in infants. A pregnant mother who has syphilis can spread the disease through the placenta to the unborn infant in utero.

causes

Traponema pallidum bacerium

 

Prevention measures

Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women by;

  1. Routine serologic screening of pregnant women during the first prenatal visit
  2. Additional testing at 28 weeks’ gestation and
  3. Again at delivery is warranted for women who are at increased risk or live in communities with increased prevalence of syphilis infection .
  4. Moreover, as part of the management, provision of information concerning ongoing risk behaviors and treatment of sex partners should be obtained to assess the risk for reinfection.
  5. Routine screening of newborn serum or umbilical cord blood is not recommended, as diagnosis at this time does not prevent symptomatic congenital syphilis in some newborns.
  6. No mother or newborn infant should leave the hospital without maternal serologic status having been documented at least once during pregnancy, and preferably again at delivery if at risk.

 Evaluation and Treatment of Neonates (Infants Aged <30 Days)

The diagnosis of congenital syphilis can be difficult, as maternal nontreponemal and treponemal IgG antibodies can be transferred through the placenta to the fetus.This complicates the interpretation of reactive serologic tests for syphilis in neonates.

Therefore, treatment decisions frequently must be made on the basis of ;

1) Identification of syphilis in the mother;

2) Adequacy of maternal treatment;

3) Presence of clinical, laboratory, or radiographic evidence of syphilis in the neonate; and

4) comparison of maternal (at delivery) and neonatal nontreponemal serologic titers using the same test, which should be conducted by the same lab.

Reactive nontreponemal and treponemal test

All neonates born to mothers who have reactive nontreponemal and treponemal test results should be should be tested with a quantitative nontreponemal serologic test (RPR or VDRL) performed on the neonate’s serum.The reason why umbilical blood cannot be used is because it can be come contaminated with maternal blood and give a false-positive results.

Reactive serologic tests

  1. All neonates born to women who have reactive serologic tests for syphilis should be examined thoroughly for evidence of congenital syphilis such as;
  • Nonimmune hydrops
  • Jaundice
  •  Hepatosplenomegaly
  • Rhinitis
  • Skin rash, and
  • Pseudoparalysis of an extremity
  1. Pathologic examination of the placenta or umbilical cord using specific staining (e.g., silver) or a T. pallidum PCR test using a CLIA-validated test should be considered.
  2. Darkfield microscopic examination or PCR testing of suspicious lesions or body fluids (e.g., bullous rash and nasal discharge) also should be performed.
  3. In addition to these tests, for stillborn infants, skeletal survey demonstrating typical osseous lesions might aid in the diagnosis of congenital syphilis.

Scenarios to consider

The following scenarios describe the congenital syphilis evaluation and treatment of neonates born to women who have reactive serologic tests for syphilis during pregnancy.

Scenario 1: Proven or highly probable congenital syphilis

Any neonate with:

  1. an abnormal physical examination that is consistent with congenital syphilis;
    or
  2. a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother’s titer;
    or
  3. a positive darkfield test or PCR of lesions or body fluid(s).

The absence of a fourfold or greater titer for a neonate does not exclude congenital syphilis.

Recommended Evaluation/investigations
  • CSF analysis for VDRL, cell count, and protein
  • Complete blood count (CBC) and differential and platelet count
  • Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver-function tests, neuroimaging, ophthalmologic examination, and auditory brain stem response).

**CSF test results obtained during the neonatal period can be difficult to interpret; normal values differ by gestational age and are higher in preterm infants. Values as high as 25 white blood cells (WBCs) /mm3 and/or protein of 150 mg/dL might occur among normal neonates; lower values (i.e., 5 WBCs/mm3 and protein of 40 mg/dL).This  might be considered the upper limits of normal.

Recommended Regimens
  • Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days
    or
  • Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days

If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy.

Scenario 2: Possible Congenital Syphilis

Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal to or less than fourfold the maternal titer and one of the following:

  1. mother was not treated, inadequately treated, or has no documentation of having received treatment;
    or
  2. mother was treated with erythromycin or a regimen other than those recommended in these guidelines (i.e., a nonpenicillin G regimen);††
    or
  3. mother received recommended treatment <4 weeks before delivery.

A women treated with a regimen other than recommended in these guidelines should be considered untreated.

Recommended evaluation/ investigations
  • CSF analysis for VDRL, cell count, and protein**
  • CBC, differential, and platelet count
  • Long-bone radiographs
Recommended Regimens
  • Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days
    or
  • Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
    or
  • Benzathine penicillin G 50,000 units/kg/dose IM in a single dose

Before using the single-dose benzathine penicillin G regimen, the complete evaluation (i.e., CSF examination, long-bone radiographs, and CBC with platelets) must be normal, and follow-up must be certain.

Neonates born to mothers with untreated early syphilis at the time of delivery are at increased risk for congenital syphilis, and the 10-day course of penicillin G may be considered even if the complete evaluation is normal and follow-up is certain.

Scenario 3: Congenital Syphilis less likely

Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal to or less than fourfold the maternal titer and both of the following are true:

  1. mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and
  2. mother has no evidence of reinfection or relapse.
Recommended Evaluation/investigations

No evaluation is recommended.

Recommended Regimen
  • Benzathine penicillin G 50,000 units/kg/dose IM in a single dose*

*Another approach involves not treating the infant, but rather providing close serologic follow-up every 2-3 months for 6 months for infants whose mother’s nontreponemal titers decreased at least fourfold after appropriate therapy for early syphilis or remained stable for low-titer, latent syphilis (e.g., VDRL <1:2; RPR <1:4).

Scenario 4: Congenital Syphilis unlikely

Any neonate who has a normal physical examination and a serum quantitative nontreponemal serologic titer equal to or less than fourfold the maternal titer and both of the following are true:

  1. mother’s treatment was adequate before pregnancy and
  2. mother’s nontreponemal serologic titer remained low and stable (i.e., serofast) before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
Recommended Evaluation

No evaluation is recommended.

Recommended Regimen

No treatment is required, but infants with reactive nontreponemal tests should be followed serologically to ensure the nontreponemal test returns to negative (see Follow-Up). Benzathine penicillin G 50,000 units/kg as a single IM injection might be considered, particularly if follow-up is uncertain and the neonate has a reactive nontreponemal test.

Follow-Up

  1. All neonates with reactive nontreponemal tests should receive careful follow-up examinations and serologic testing (i.e., a nontreponemal test) every 2–3 months until the test becomes nonreactive.
  2. In the neonate who was not treated because congenital syphilis was considered less likely or unlikely, nontreponemal antibody titers should decline by age 3 months and be nonreactive by age 6 months, indicating that the reactive test result was caused by passive transfer of maternal IgG antibody.
  3. At 6 months, if the nontreponemal test is nonreactive, no further evaluation or treatment is needed; if the nontreponemal test is still reactive, the infant is likely to be infected and should be treated.
  4. Treated neonates that exhibit persistent nontreponemal test titers by 6–12 months should be re-evaluated through CSF examination and managed in consultation with an expert.
  5. Retreatment with a 10-day course of a penicillin G regimen may be indicated. Neonates with a negative nontreponemal test at birth and whose mothers were seroreactive at delivery should be retested at 3 months to rule out serologically negative incubating congenital syphilis at the time of birth.
  6. Treponemal tests should not be used to evaluate treatment response because the results are qualitative and passive transfer of maternal IgG treponemal antibody might persist for at least 15 months.
  7. Neonates whose initial CSF evaluations are abnormal should undergo a repeat lumbar puncture approximately every 6 months until the results are normal. A reactive CSF Venereal Disease Research Laboratory (VDRL) test or abnormal CSF indices that persist and cannot be attributed to other ongoing illness requires retreatment for possible neurosyphilis and should be managed in consultation with an expert.

Special Considerations

Penicillin Allergy

Infants and children who require treatment for congenital syphilis but who have a history of penicillin allergy or develop an allergic reaction presumed secondary to penicillin should be desensitized and then treated with penicillin.

Penicillin Shortage

During periods when the availability of aqueous crystalline penicillin G is compromised, the following is recommended.

  1. For neonates with clinical evidence of congenital syphilis (Scenario 1), check local sources for aqueous crystalline penicillin G (potassium or sodium). If IV penicillin G is limited, substitute some or all daily doses with procaine penicillin G (50,000 U/kg/dose IM a day in a single daily dose for 10 days).

If aqueous or procaine penicillin G is not available, ceftriaxone (in doses appropriate for birthweight) can be considered with careful clinical and serologic follow-up and in consultation with an expert, as evidence is insufficient to support the use of ceftriaxone for the treatment of congenital syphilis. Management might include a repeat CSF examination at age 6 months if the initial examination was abnormal. Ceftriaxone must be used with caution in infants with jaundice.

  1. For neonates without any clinical evidence of congenital syphilis (Scenario 2 and Scenario 3), use

a. procaine penicillin G, 50,000 U/kg/dose IM a day in a single dose for 10 days

or

b. Benzathine penicillin G, 50,000 U/kg IM as a single dose.

If any part of the evaluation for congenital syphilis is abnormal or was not performed, CSF examination is not interpretable, or follow-up is uncertain, procaine penicillin G is recommended. A single dose of ceftriaxone is inadequate therapy.

  1. For premature infants who have no clinical evidence of congenital syphilis (Scenario 2 and Scenario 3) and might not tolerate IM injections because of decreased muscle mass, IV ceftriaxone can be considered with careful clinical and serologic follow-up and in consultation with an expert. Ceftriaxone dosing must be adjusted according to birthweight.
HIV Infection

Evidence is insufficient to determine whether neonates who have congenital syphilis and HIV or whose mothers have HIV infection require different therapy or clinical management than is recommended for all neonates. All neonates with congenital syphilis and HIV infection should be managed similarly as neonates with congenital syphilis who do not have HIV infection.

Evaluation and Treatment of Infants and Children with Congenital Syphilis

Infants and children aged ≥1 month who are identified as having reactive serologic tests for syphilis should be examined thoroughly and have maternal serology and records reviewed to assess whether they have congenital or acquired syphilis. Any infant or child at risk for congenital syphilis should receive a full evaluation and testing for HIV infection.

Recommended Evaluation

  • CSF analysis for VDRL, cell count, and protein
  • CBC, differential, and platelet count
  • Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver function tests, abdominal ultrasound, ophthalmologic examination, neuroimaging, and auditory brain-stem response)
Recommended Regimen
  • Aqueous crystalline penicillin G 200,000–300,000 units/kg/day IV, administered as 50,000 units/kg every 4–6 hours for 10 days

If the infant or child has no clinical manifestations of congenital syphilis and the evaluation (including the CSF examination) is normal, treatment with up to 3 weekly doses of benzathine penicillin G, 50,000 U/kg IM can be considered. A single dose of benzathine penicillin G 50,000 units/kg IM up to the adult dose of 2.4 million units in a single dose can be considered after the 10-day course of IV aqueous penicillin to provide more comparable duration of treatment in those who have no clinical manifestations and normal CSF. All of the above treatment regimens also would be adequate for children who might have other treponemal infections.

Follow-Up

Careful follow-up examinations and serologic testing (i.e., a nontreponemal test) of infants and children should be performed every 3 months. This should be done until the test becomes nonreactive or the titer has decreased fourfold.  Treponemal tests should not be used to evaluate treatment response, because the results are qualitative and persist after treatment. Also passive transfer of maternal IgG treponemal antibody might persist for at least 15 months after delivery.

Repeat lumbar puncture 6 month until normal values for infant and children whose csf evaluation is abnormal. A reactive CSF VDRL test or abnormal CSF indices that persists after 2 years of follow up requires retreatment. This could be possible neurosyphilis and should be managed in consultation with an expert.

Special Considerations

Penicillin Allergy

Infants and children who require treatment for congenital syphilis but who have a history of penicillin allergy should be desensitized and treated with penicillin.

In case of Penicillin Shortage ceftriaxone can be used.
  1. Ceftriaxone (in doses appropriate for age and weight) can be considered with careful clinical and serologic follow-up.
  2. Infants and children receiving ceftriaxone should be managed in consultation with an expert.This is becouse evidence is insufficient to support the use of ceftriaxone for the treatment of congenital syphilis in infants or children.
  3. For infants aged ≥30 days, use 75 mg/kg IV/IM of ceftriaxone  once daily for 10–14 days
  4. Children, the dose should be 100 mg/kg of ceftriaxone a day in a single daily dose.
  5. Infants and children without any clinical evidence of infection (see Scenario 2 and Scenario 3 above).
HIV Infection

All infants and children with congenital syphilis and HIV infection should be managed like infants and children without HIV infection.

CONGENITAL SYPHILIS COMPLICATIONS

The following complications may develop in patients suffering from Congenital syphilis:

  • Hypoglycemia
  • Severe anemia
  • Thrombocytopenia
  • Blindness
  • Deafness
  • Nonimmune hydrops
  • Acidosis
  • Pancreatitis
  • Liver failure
  • Failure to thrive
  • Respiratory failure
  • Leukemoid reaction
  • Nephrotic syndrome
  • Meningoencephalitis
  • Neurological problems
  • Pulmonary hemorrhage
  • Necrotizing enterocolitis
  • Deformity of facial features
  • Disseminated intravascular coagulation

 

 

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