Syphilis-symptoms,diagnosis,treatment,complication in pregnancy and neonate

Syphilis is a systemic infection caused by the spirochete Treponema pallidum pallidum, which is of particular concern during pregnancy because of the risk of transplacental (major route) and intrapartum(minor) transmission.

Clinical manifestation of syphilis

The clinical manifestation of syphilis in pregnant woman is same as in non-pregnant woman.

Complications in pregnancy:

• Miscarriage
• Preterm birth
• Stillbirth
• Impaired fetal growth

Complications in neonate:

• Congenital infection (nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, and osseous lesions, pseudoparalysis of an extremity).
• Neonatal mortality

Screening

• All pregnant women: screen at the first prenatal encounter
• Women at high risk of infection(diagnosed with STD during pregnancy, commercial sex worker, having unprotected sex with more than one partner [or monogamous sex with a partner who is not monogamous], resident in an area of high syphilis prevalence, uninsured women, women living in poverty, illicit drug users): repeat screening at 28 to 32 weeks and at delivery
• Women who have not been screened in pregnancy or who deliver a stillborn after 20 weeks of gestation: screen at delivery

Neonates should not be discharged from the hospital unless the syphilis serologic status of the mother has been determined at least one time during pregnancy and preferably again at delivery if at risk.

HIV testing is strongly recommended for those known to have a sexually transmitted disease, such as syphilis, due to the high risk of coexistent disease. HIV testing should be repeated at the time of repeat syphilis screening.

Diagnosis

Nontreponemal tests : 

• Rapid Plasma Reagin (RPR)
• Venereal Disease Research Laboratory (VDRL)
• Toluidine Red Unheated Serum Test (TRUST). 

Titers are essential for monitoring treatment response.

Treponemal tests:

• Treponema pallidum hemagglutination assay (TPHA)
•  Fluorescent treponemal antibody absorption (FTA-ABS)
•  Microhemagglutination test for antibodies to Treponema pallidum (MHA-TP)
• T. pallidum particle agglutination assay (TPPA)
• T. pallidum enzyme immunoassay (TP-EIA) 
• Chemiluminescence immunoassay (CIA)

Dark field microscopy– seen as slender, actively motile with coils

In a patient without prior syphilis, a diagnosis of syphilis is made when both nontreponemal and treponemal tests are reactive. Confirmatory testing is necessary due to the potential for a false-positive screening test result. False positive test is more common in pregnancy.

Maternal Treatment

Parenteral (IM or IV) penicillin G (to be given after antigen sensitivity testing) is only therapy effective in pregnancy for treating maternal disease, preventing transmission to the fetus, and treating established fetal disease.

Penicillin allergy

• It is reported by 8%–10% percent of pregnant women
• Major symptoms of concern are immunoglobulin E (IgE)-mediated (immediate) responses, such as urticaria, angioedema or anaphylaxis with airway obstruction, bronchospasm or hypotension
• Penicillin desensitization is recommended for women with a positive skin test who require penicillin therapy
• Such patients should be desensitized and treated with penicillin.

Penicillin desensitization

• It involves exposing the patient to a small amount of penicillin and gradually increasing the dose until an effective level is reached, followed by the appropriate therapeutic penicillin regimen. 
• It can be achieved either orally or intravenously. Oral desensitization is simpler and safer. 

Procedure

1. Written consent should be taken

2. IV access and vital sgns (temperature, HR, BP, RR, oxygen saturation, peak flow) should be obtained

3. At bedside: Epinephrine 0.3 mg (for adults) for IM injection, oxygen, normal saline, peak flow meter, and BP cuff, albuterol, injectable preparation of diphenhydramine, and methylprednisolone.

4. A nurse must closely observe the patient throughout the protocol (one-to-one).

• Patients should be observed for signs of anaphylaxis at least overnight before discharge. The benzathine formulation provides sustained release of penicillin; therefore, in cases of latent syphilis, desensitization need not be repeated before subsequent outpatient doses of benzathine penicillin G to complete the three-dose regimen. 
• Once the course is completed, if penicillin is required in the future, the desensitization procedure should be repeated.

If penicillin desensitization is not possible, the World Health Organization (WHO) suggests using one of the following alternative regimens 

Early syphilis (primary, secondary, or latent in pregnancy 

• Erythromycin 500 mg orally four times daily for 14 days(73.2 % response)
• Ceftriaxone 1 g intramuscularly once daily for 10 to 14 days(77.6% response)
• Azithromycin 2 g once orally (when local susceptibility to azithromycin is likely, 85.5%)

Late syphilis

• Erythromycin 500 mg orally four times daily for 30 days 

Erythromycin and azithromycin do not cross the placental barrier completely so the fetus is not effectively treated hence the infants should receive a 10 to 15 day course of penicillin treatment.

• Missed doses are not acceptable for pregnant women receiving therapy for late latent syphilis. Pregnant women who miss any dose of therapy must repeat the full course of therapy.
• For women with a history of adequately treated syphilis who do not have ongoing risk, no further treatment is necessary

Monitoring

• A non-treponemal titer should be obtained just before initiating therapy
• Titers should be repeated at 28–32 weeks gestation and at delivery
• Serologic titers can be checked monthly in women at high risk for reinfection or in geographic areas in which the prevalence of syphilis is high.
• In early syphilis, serologic testing should be performed 6 and 12 months following treatment and at any time if clinical symptoms recur. In general, such patients should experience an adequate response by 12 months. 
• In late syphilis (including late latent syphilis) serologic testing should be done at 6, 12, and 24 months.
• Following treatment, a decline in maternal nontreponemal serologic titers does not guarantee that fetal treatment has been adequate. Thus, neonates should be evaluated for congenital syphilis after delivery

Potential complications of treatment

Jarish- Herxheimer Reaction:

• It is an acute febrile reaction accompanied by headache, myalgia, rash, and hypotension symptoms that can occur within the first 24 hours after the initiation of any therapy for syphilis.
• These symptoms occur most frequently among persons who have early syphilis, presumably because bacterial burdens are higher during these stages resulting in release of large amounts of treponemal lipopolysaccharide from dying spirochetes and an increase in circulating cytokine levels (tumor necrosis factor alpha [TNF-alpha], interleukin-6, interleukin-8).
• The Jarisch-Herxheimer reaction may also precipitate uterine contractions, preterm labor, and/or nonreassuring fetal heart rate tracings in pregnant women treated in the second half of pregnancy but this should not prevent or delay therapy .
• All patients should be counseled about the risks and clinical features of this febrile reaction, and told to contact their provider if symptoms occur. 
• Management is supportive care (eg, antipyretics, intravenous fluids).

Treatment failure — 

• a fourfold increase in the nontreponemal titer after treatment 
• A fourfold decline in the titer, equivalent to a change of two dilutions (eg, from 1:16 to 1:4 or from 1:32 to 1:8), is considered to be an acceptable response to syphilis therapy.
•  Retreatment is reasonable if a fourfold decline from pretreatment titer has not occurred by six months.

Inadequate maternal treatment- 

• likely if delivery occurs within 30 days of therapy, clinical signs of infection are present at delivery, or the maternal antibody titer at delivery is fourfold higher than the pretreatment titer

Prenatal diagnosis  

• Fetal infection should be suspected if there are characteristic findings on ultrasound examination after 20 weeks of gestation in a woman with untreated or inadequately treated syphilis. 
• Before 18 to 20 weeks, fetal abnormalities are not usually seen because of fetal immunologic immaturity. 
• Findings on ultrasound are nonspecific and include hepatomegaly and placentomegaly (early findings) anemia, ascites, and hydrops(late findings).

Diagnostic testing of amniotic fluid or fetal blood definitively establishes intrauterine infection, but invasive procedures to obtain these specimens can be associated with serious complications and thus are not indicated

Neonatal treatment

• maternal penicillin treatment is curative for fetal infection in most cases.
• infants with reactive nontreponemal tests should be followed serologically to ensure the nontreponemal test returns to negative 
• 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.

If the patient first presents for pregnancy care when she is in labor and her nontreponemal or treponemal test is positive, maternal evaluation and treatment for syphilis are performed as described above but intrapartum care and procedures are not impacted.