What is Syphilis?
Syphilis is a sexually transmitted disease caused by bacteria called Treponema Pallidum. Mode of transmission is via direct contact with infections lesion during sexual intercourse and from mother to child in the womb. Hence pregnant women are routinely screened for syphilis.
The stages of Syphilis
Primary syphilis
Syphilis is a sexually transmitted disease caused by bacteria called Treponema Pallidum. Mode of transmission is via direct contact with infections lesion during sexual intercourse and from mother to child in the womb. Hence pregnant women are routinely screened for syphilis.
The stages of Syphilis
Primary syphilis
- Primary syphilis infection usually occur 2-6 weeks post infection.
- Typically there will be a single (less often multiple) painless sore called chancre at the genitalia area.
- The lymph nodes in the groin area will also be enlarged but seldom cause pain.
Secondary Syphilis
- This will occur 2-6 months after primary syphilis infection.
- There will be wide spread non-itchy rash but more typically involving the hands and feet.
- Sometimes there will also be mucous membranes lesions on the genitalia infected sites.
- They may also present as patchy alopecia (bald patches on scalp).
- There will also be generalized lymph nodes enlargement.
Latent Syphilis
Tertiary Syphilis
- This occurs 3 months post infection and does not have any symptoms or clinical signs.
- Early latent syphilis : < 1 year post infection
- Late latent syphilis > 1 year post infection
Tertiary Syphilis
- This happens 5-10 years after secondary syphilis
- Comprises of Benign Tertiary Syphilis, Cardiovascular Syphilis and Neurosyphilis.
- Neurosyphilis will present with neurologic abnormalities, cognitive disturbances, eye and auditory symptoms.
Diagnostic Tests
1. Dark Field Microscopy:
1. Dark Field Microscopy:
- Specimen is taken from the primary chancre ulcer/ moist lesions of secondary syphilis for microscopic examination of Treponema Pallidum.
2. Serology Non-Treponemal tests:
3. Serology Treponemal Tests:
4. Cerebrospinal fluid for microscopy and serology
- Venereal Disease Research Laboratory (VDRL) and Rapid Plasma Reagin (RPR) tests are used as screening tests and can be used to monitor response to treatment.
- If VDRL/RPR is positive confirmatory Treponemal test is carried out.
- If syphilis is treated early the VDRL/RPR result may be negative
- Serological Scar means persistent positive result occur in treatment of late infections.
3. Serology Treponemal Tests:
- These tests include Treponema Pallidum Particle Agglutination (TPPA) test, Treponema Pallidum Haemagllutination Assay (TPHA) test, Fluorescent Treponomal Antibody Absorption test (FTA-Abs) and Line Immunoassay (LIA).
- There are rapid diagnostic tests like Treponemal EIA test and Abbott Determine Syphilis TP tests that are specific and can be used as screening tests.
- Even after treatments, the test results will remain positive hence it is not useful in monitoring treatment response.
4. Cerebrospinal fluid for microscopy and serology
- The cerebrospinal fluid is sent to test for white blood cell count, protein and globulin levels, LIA IgG & IgM, VDRL and TPHA.
- This is a test used for suspected Neurosyphilis.
- In Neurosyphilis, the total protein is raised >0.4g/l, the mononuclear cell count is raised >5cells/mm3
- If there is positive VDRL in the absence of gross blood contamination of Neurosyphilis is made.
- LIA test is a more sensitive test.
Treatment of Syphilis
For all stages of syphilis, penicillin remains the drug of choice. For patients with penicillin allergy alternative antibiotics include doxycycline, tetracycline, erythromycin and azithromycin. However the treatment success is better with penicillin.
For all stages of syphilis, penicillin remains the drug of choice. For patients with penicillin allergy alternative antibiotics include doxycycline, tetracycline, erythromycin and azithromycin. However the treatment success is better with penicillin.
Treatment regime for Early Syphilis
Early syphilis includes primary syphilis, secondary syphilis and latent syphilis of less than 1 year duration.
Recommended regime is a single dose of intra-muscular Benzathine penicillin G 2.4million units or intra-muscular aq. Procaine penicillin G 600,000 units daily for 10 days. For HIV patients, Penicillin G injections once weekly for 3 weeks are recommended.
For patients who are allergic to penicillin, they can be treated with:
Early syphilis includes primary syphilis, secondary syphilis and latent syphilis of less than 1 year duration.
Recommended regime is a single dose of intra-muscular Benzathine penicillin G 2.4million units or intra-muscular aq. Procaine penicillin G 600,000 units daily for 10 days. For HIV patients, Penicillin G injections once weekly for 3 weeks are recommended.
For patients who are allergic to penicillin, they can be treated with:
- Oral Azithromycin 500 mg twice daily for 10 days
- Oral doxycycline 100 mg twice daily for 2 weeks
- Oral erythromycin 500 mg 4 times daily for 2 weeks
- Oral tetracycline 500 mg 4 times daily for 2 weeks
Treatment of late syphilis
Late syphilis includes latent syphilis of more than 1 year duration, cardiovascular syphilis and late benign syphilis. The duration of treatment is longer in these cases.
The recommended treatment regime is intra-muscular injection of Benzathine Penicillin G 2.4 million units weekly for 3 doses or intra-muscular injection of Aq. Procaine Penicillin G 600,000 units daily for 17-21 days.
For patients who are allergic to penicillin, they can be treated with:
Late syphilis includes latent syphilis of more than 1 year duration, cardiovascular syphilis and late benign syphilis. The duration of treatment is longer in these cases.
The recommended treatment regime is intra-muscular injection of Benzathine Penicillin G 2.4 million units weekly for 3 doses or intra-muscular injection of Aq. Procaine Penicillin G 600,000 units daily for 17-21 days.
For patients who are allergic to penicillin, they can be treated with:
- Oral erythromycin 500 mg 4 times daily for 4 weeks
- Oral doxycycline 100 mg twice daily for 4 weeks
- Oral tetracycline 500 mg 4 times daily for 4 weeks
Treatment of Neurosyphilis & syphilis involving ears & eyes
A high sustained blood level of penicillin is required for adequate drug penetration through the blood brain barrier to target treatment on the brain. Penicillin is still the drug of choice.
Recommended regimes include:
1. Intravenous Aq. Crystalline Benzyl Penicillin 3-4 million units every 4 hourly for 10 days followed by Intra-muscular Benzathine Penicillin G 2.4 million units weekly for 3 weeks
OR
2.Intra-muscular Aq. Procaine penicillin G 2.4 million units daily for 10 days together with oral probenecid 500 mg tabs 4 times daily for 10 days followed by intra-muscular Benzathine Penicillin G 2.4 million units weekly for 3 weeks.
For those who are allergic to penicillin they can be treated with alternative antibiotics like:
1.Oral doxycycline 100 mg twice daily for 4 weeks OR
2.Oral erythromycin 500 mg 4 times daily for 4 weeks OR
3.Tetracycline 500 mg 4 times daily for 4 weeks
A high sustained blood level of penicillin is required for adequate drug penetration through the blood brain barrier to target treatment on the brain. Penicillin is still the drug of choice.
Recommended regimes include:
1. Intravenous Aq. Crystalline Benzyl Penicillin 3-4 million units every 4 hourly for 10 days followed by Intra-muscular Benzathine Penicillin G 2.4 million units weekly for 3 weeks
OR
2.Intra-muscular Aq. Procaine penicillin G 2.4 million units daily for 10 days together with oral probenecid 500 mg tabs 4 times daily for 10 days followed by intra-muscular Benzathine Penicillin G 2.4 million units weekly for 3 weeks.
For those who are allergic to penicillin they can be treated with alternative antibiotics like:
1.Oral doxycycline 100 mg twice daily for 4 weeks OR
2.Oral erythromycin 500 mg 4 times daily for 4 weeks OR
3.Tetracycline 500 mg 4 times daily for 4 weeks
Oral Steroid cover
Oral prednisolone of 20 mg 3 times daily (total of 60mg) is given 24 hours before treatment and for another 2 days after starting therapy. This is to minimize the Jarisch-Herxheimer reaction that may occur 4-12 hours after 1st dose of antibiotics. Jarisch-Herxheimer reaction is a fever reaction that is accompanied by muscle ache, headache and other symptoms.
Treatment of syphilis in Pregnancy
All pregnant women should be tested for syphilis. They should be treated with penicillin just like those non-pregnant patients. If Jarisch-Herxheimer reaction may increase risk of premature labor or fetal distress.
For those who are allergic to penicillin, they can be treated with erythromycin just like non-pregnant patients. But erythromycin has poor penetration across placenta, the infant should be routinely treated with penicillin at birth. Tetracycline antibiotics are contraindicated in pregnancy.
Pregnant women who have been treated should have monthly RPR/VDRL for the rest of pregnancy.
Oral prednisolone of 20 mg 3 times daily (total of 60mg) is given 24 hours before treatment and for another 2 days after starting therapy. This is to minimize the Jarisch-Herxheimer reaction that may occur 4-12 hours after 1st dose of antibiotics. Jarisch-Herxheimer reaction is a fever reaction that is accompanied by muscle ache, headache and other symptoms.
Treatment of syphilis in Pregnancy
All pregnant women should be tested for syphilis. They should be treated with penicillin just like those non-pregnant patients. If Jarisch-Herxheimer reaction may increase risk of premature labor or fetal distress.
For those who are allergic to penicillin, they can be treated with erythromycin just like non-pregnant patients. But erythromycin has poor penetration across placenta, the infant should be routinely treated with penicillin at birth. Tetracycline antibiotics are contraindicated in pregnancy.
Pregnant women who have been treated should have monthly RPR/VDRL for the rest of pregnancy.
Follow up post treatment
Non-Treponemal quantitative VDRL/PRP tests should be retested at 3 months, 6 months, 12 months, 18 months and 24 months post treatment for a total period of 2 years.
After treatment in early syphilis, the VDRL/RPR levels should show a 4 times decrease in titers within 6 months. If it doesn’t show a decline, there may be treatment failure and it is an indication to retreat with 3 doses of intra-muscular Benzathine penicillin injections.
Reinfection/ relapse of syphilis should be suspected if the clinical signs persist/recur or if the VDRL/RPR titers rise to 4 times or more. In such cases, cerebrospinal fluid should be examined to rule out Neurosyphilis before treatment.
All patients with Neurosyphilis must be monitored for life every 6 monthly. Cerebrospinal examinations should be repeated every 6-12 months until the cell count normalizes.
Non-Treponemal quantitative VDRL/PRP tests should be retested at 3 months, 6 months, 12 months, 18 months and 24 months post treatment for a total period of 2 years.
After treatment in early syphilis, the VDRL/RPR levels should show a 4 times decrease in titers within 6 months. If it doesn’t show a decline, there may be treatment failure and it is an indication to retreat with 3 doses of intra-muscular Benzathine penicillin injections.
Reinfection/ relapse of syphilis should be suspected if the clinical signs persist/recur or if the VDRL/RPR titers rise to 4 times or more. In such cases, cerebrospinal fluid should be examined to rule out Neurosyphilis before treatment.
All patients with Neurosyphilis must be monitored for life every 6 monthly. Cerebrospinal examinations should be repeated every 6-12 months until the cell count normalizes.
Sexual contacts of patients with syphilis
Sexual contacts within last 3 months of patients with primary syphilis are at risk of syphilis. Sexual contacts within last 6 months of patients with secondary syphilis are at risk of syphilis. Sexual contacts within last 12 months of patients with early latent syphilis are at risk of syphilis.
Sexual contacts that were exposed 3 month prior to the diagnosis of primary, secondary or early latent syphilis should be given epidemiologic treatment if follow up is uncertain. They can be treated with a single shot of Intra-muscular Benzathine Penicillin G 2.4 million units or oral azithromycin 1 gram immediately or with oral doxycycline 100 mg twice daily for 2 weeks.
The sexual partners of those who have late syphilis should be screened for syphilis and treated if tested positive.
Sexual contacts within last 3 months of patients with primary syphilis are at risk of syphilis. Sexual contacts within last 6 months of patients with secondary syphilis are at risk of syphilis. Sexual contacts within last 12 months of patients with early latent syphilis are at risk of syphilis.
Sexual contacts that were exposed 3 month prior to the diagnosis of primary, secondary or early latent syphilis should be given epidemiologic treatment if follow up is uncertain. They can be treated with a single shot of Intra-muscular Benzathine Penicillin G 2.4 million units or oral azithromycin 1 gram immediately or with oral doxycycline 100 mg twice daily for 2 weeks.
The sexual partners of those who have late syphilis should be screened for syphilis and treated if tested positive.
Congenital Syphilis
Syphilis can infect the infant when mother has contracted syphilis during pregnancy.
Who should be evaluated?
Infants should be evaluated if they are born to seropositive mothers who:
Infants born should undergo thorough physical examination. Blood tests like RPR, VDRL, LIA IgM or EIA IgM levels should be tested. Microscopic examinations of suspicious lesions and body fluid should be examined. If suspected of Neurosyphilis then cerebrospinal fluid should be examined.
Syphilis can infect the infant when mother has contracted syphilis during pregnancy.
Who should be evaluated?
Infants should be evaluated if they are born to seropositive mothers who:
- Are treated for syphilis < 1 month before pregnancy
- Have untreated syphilis
- Treated with syphilis with non-penicillin antibiotics
- Did not have decrease RPR/VDRL titers post treatment.
- Treated but no follow up on serology titers
Infants born should undergo thorough physical examination. Blood tests like RPR, VDRL, LIA IgM or EIA IgM levels should be tested. Microscopic examinations of suspicious lesions and body fluid should be examined. If suspected of Neurosyphilis then cerebrospinal fluid should be examined.
When to treat the infant?
If the infant has clinical signs of active disease, a positive syphilis serology, an abnormal cerebrospinal fluid result, a positive LIA IgM, a VDRL titer 4 times greater than in mother, when treatment of mother was inadequate or when non-penicillin drugs are used to treat the mother, the infant should be treated.
Treatment Regimens for infants born with syphilis
They can be treated with:
If the infant has clinical signs of active disease, a positive syphilis serology, an abnormal cerebrospinal fluid result, a positive LIA IgM, a VDRL titer 4 times greater than in mother, when treatment of mother was inadequate or when non-penicillin drugs are used to treat the mother, the infant should be treated.
Treatment Regimens for infants born with syphilis
They can be treated with:
- Intra-muscular Aq. Procaine Penicillin G 50,000 units per kg one dose daily for 10 days OR
- Intravenous Aq. Crystalline Penicillin G 50,000 units per kg every 12 hourly daily for first 7 days of life and every 8 hours thereafter for a total of 10 days.
- Single dose Intramuscular injection of Benzathine Penicillin 50,000 units may be used if infant’s evaluation is normal if not a 10 day course is needed.
Follow up for infants treated for congenital syphilis
The infants should be followed up every 2-3 monthly until they are tested nonreactive or until their titer falls by 4 times. The RPR/VDRL is expected to fall by 3 months of age and become nonreactive by 6months of age.
The infants should be followed up every 2-3 monthly until they are tested nonreactive or until their titer falls by 4 times. The RPR/VDRL is expected to fall by 3 months of age and become nonreactive by 6months of age.