Syphilis – Part 1- Diagnosis, VDRL, FTA-ABS, TPHA, RPR (Treponema Pallidum)
Sample
- The serum of the patient is needed.
Indication
- For the diagnose of syphilis.
Pathophysiology
- The disease syphilis was reported in the medical literature as early as 1495.
- In the treatment of syphilis. heavy metals, such as arsenic, were replaced by penicillin 1940.
- Treponema pallidum is a member of the order Spirochaetales and family Treponemataceae.
- Spirochetes are a gram-negative organism and look like corkscrews.
- These are fine, spiral 8 to 24 coils organism. These are approximately 6 to 15 µ mm long.
- These bacteria can move in a spinning fashion called axial filaments.
- These bacteria replicate by transverse fission.
- This organism can not grow in ordinary media.
- These have a gram-negative cell membrane.
- These are too small to see under the light microscope.
- So a special procedure is used to see these organisms like dark-field, immunofluorescence, and silver stain.
- Also, serological tests can help to diagnose syphilis.
- Syphilis is a chronic venereal disease.
- This was discovered in epidemic form in the 16th century in Europe.
- The first diagnostic blood test for syphilis was introduced by Wassermann in 1906.
- Afroamericans are infected 30 times more than white Americans.
- Mode of spread:
- Syphilis is caused by Spirochaete Treponema Pallidum and its natural host is humans.
- The most common source of infection is a cutaneous or mucosal lesion in the primary or secondary stage of the disease.
- During sexual acts, the organism enters the body through minute abrasion of the skin or mucous membranes.
- Once it enters the body, the spirochetes immediately being disseminated throughout the body.
- In congenital syphilis, it spreads across the placenta to the fetus.
- The incubation period is 2 to 4 weeks.
- Syphilis can spread through:
- sexual contact
- Congenital
- Direct contact with the lesion.
Treponema associated diseases in human:
- T. Pallidum = Syphilis
- T. pallidum variant = Bejel
- T. carateum = Pinta
- T. pertenue = Yaws
Syphilis has four clinical stages :
- Incubation period: This is 2 to 4 weeks.
- The primary stage:
- This is characterized by the presence of the chance at the primary site of inoculation.
- In the male is at the penis and in the female are multiple presents on the vagina or the cervix.
- It has a firm and usually painless ulcer called Chancre.
- Enlarged lymph nodes may be seen and are painless.
- This heals spontaneously in 3 to 8 weeks.
- The lesion is positive for the spirochetes.
- Serological tests for syphilis are often negative in the early phase of the disease so advise darkfield microscopy or a direct fluorescent antibody test.
- The secondary stage:
- 25% of untreated cases from the primary chancre goes into the secondary stage.
- The Patient may develop this stage after roughly 2 months of the chancre (or 6 to 8 weeks).
- 6 to 8 weeks later infection becomes generalized, this is the bacteremia stage.
- This is characterized by the appearance of the systemic lesions on:
- Mucous membranes, large mucous membrane lesions may be seen in the oral cavity.
- There are widespread rashes of the skin.
- These rashes are small red flat lesions distributed over the body.
- Cutaneous surfaces, warts like lesion called Condylomata are seen. Usually seen in the moist and warm sites like the perianal area, vulva, and the scrotum.
- Any organ may be involved including CNS, eyes, kidneys, and bones.
- This is a highly infectious stage and contains many organisms (treponemes).
- There is generalized lymphadenopathy in 50% of the cases.
- Other rare complications are arthritis, hepatitis, glomerulonephritis, periostitis, and sometime iridocyclitis and chorioretinitis.
- These mucocutaneous lesions are highly infectious.
- Latent syphilis: The disease is dormant for many years. The symptoms of the second stage have resolved.
- But serological tests are positive.
- 25% or more will have a relapse and develop the infectious lesion of the skin like secondary syphilis.
- After 4 years, there are generally no more relapses, and this disease may be noninfectious except the pregnant mothers.
- This ultimately develops into cardiovascular or neurosyphilis.
- Roughly 1/3 cases progress into the tertiary stage.
- late syphilis: This occurs after 10 o 20 years of the primary lesion.
- There are two main types:
- Cardiovascular involvement in the form of Aortitis and aneurysm.
- Neurosyphilis which may be:
- General paralysis with dementia, tremors, and spastic paralysis.
- Tabes dorsalis with ataxic gate, trophic changes in joints in the form of Charcot’s joints.
- There may be optic atrophy.
- Meningovascular syphilis gives a headache, cranial nerves palsies, and Argyll- Robertson pupil (pupillary loss of reaction to light).
- There are two main types:
- Tertiary stage:
- This stage appears 3 to 10 years after the primary lesion (another source says 6 to 40 years takes to develop the tertiary stage).
- This is also called late syphilis and is a noninfectious stage.
- This is characterized by granulomatous skin lesion called gummas, may occur on mucous membrane, subcutaneous tissue bone, and viscera.
- The main presentation is:
- Gumma formation.
- The gummatous lesion appears after 3 to 10 years of the primary lesion in about 15% of the untreated cases.
- These are a granulomatous lesion.
- These are noninfectious lesions mainly found in the skin and the bone.
- Cardiovascular involvement.
- These are seen after at least 10 years of the primary infection in 10% of the untreated cases.
- There is an aneurysm in the aorta (ascending part), or aortic arch.
- Neurosyphilis.
- This disease is seen in roughly 8% of the untreated cases.
- Neurosyphilis presentation is as follows:
- Asymptomatic when the patients are normally looking but the CSF is serologically positive.
- Subacute meningitis where the patients have a fever, stiff neck, and headache.
- CSF examination shows:
- Increased proteins.
- Low glucose level.
- Increased number of lymphocytes.
- Positive tests for syphilis.
- CSF examination shows:
- Meningovascular syphilis where there is damage to the blood vessels of the brain and meninges.
- There are cerebrovascular occlusion and infarction of the tissue in the brain, meninges, and spinal cord.
- Tabes dorsalis affects the spinal cord.
- In this case, there is the involvement of the posterior column and dorsal roots.
- Gumma formation.
- Late or quaternary stage: 10 to 20 years after primary syphilis, there are two main clinical sequences:
- Neurosyphilis may present as follows:
- General paralysis of insane with dementia, tremor, and spastic paralysis.
- Tabes dorsalis with characteristic features of ataxic gait, atrophic changes in joints, Charcot’s joints, and there may be optic atrophy.
- Meningovascular syphilis with a headache, cranial nerve palsies, and papillary loss of reaction to light (Argyll-Robertson pupil).
- Neurosyphilis may present as follows:
Clinical stage | Clinical presentation |
Primary stage | Chancre, painless |
Secondary stage |
1. Skin involvement with the presence of rashes 2. Involvement of CNS, bones, eyes, kidneys, arthritis 3. Condylomata latum |
Latent stage | 25% may relapse and again goes into the secondary stage |
Tertiary stage |
1. Neurosyphilis 2. Involvement of the cardiovascular system 3. Gumma of the skin and bone |
- Congenital syphilis:
- Bacteria can enter into fetal circulation at any time from the placenta during pregnancy. So these bacteria can cross the placental barrier.
- The chances are more when the mother is in the primary or secondary stage to infect the fetus.
- In the absence of the treatment, roughly 40% of the fetus will die in utero around the 4th month of the pregnancy.
- The manifestation of the congenital syphilis are:
- Stillbirth.
- Infantile syphilis.
- Hepatosplenomegaly, and bone abnormalities.
- There are pancreatic fibrosis and pneumonitis.
- The lungs may be firm and pale.
- Tissues are positive for the spirochetes.
- Congenital syphilis was clinically seen as:
- Latent infection when there are no symptoms but infants are serologically positive.
- The early-stage appears after the end of the second year.
- Most infants are healthy at birth and symptoms appear in the first few weeks.
- There are generalized skin rashes, nasal deformity. hepatitis, meningitis, anemia, and bone lesions.
- Late syphilis manifestations appear in the first few weeks of life.
- They may not be able to thrive.
- There is bone sclerosis.
- Joint effusion and arthritis.
- Interstitial keratitis.
- Juvenile general paralysis of the insane and tabes.
- Deafness.
- Notching of the incisor teeth.
The principle of the Various test
- Tests depended upon T.pallidum demonstration by:
- Darkfield direct microscopy: The Patient lesion is abraded and fluid is taken which is seen immediately directly under the dark field microscope. It has a sensitivity of 80 %.
- Fluorescent microscopy: Where again the sample is taken directly from the lesion and treated with fluorescently labeled antibody and seen under the fluorescent microscope.
- Non-treponemal tests measure antibodies against the cardiolipin.
- These serologic tests are:
- Venereal disease research laboratory (VDRL).
- Rapid plasma reagin (RPR).
- These tests become start positive after 1 to 2 weeks of infection and are positive by 4 to 6 weeks.
- Titer starts falling after the successful treatment.
- These nontreponemal tests are negative in the early stage of the disease, then the darkfield examination will be positive.
- These serologic tests are:
- ELIZA
- Treponemal serologic test detect antibody to the antigen and these are:
- Fluorescent treponemal antibody absorption (FTA-ABS).
- Microhemagglutination treponema Pallidum (MHA-TP).
- Treponemal serologic test detect antibody to the antigen and these are:
- TPHA (Treponema pallidum hemagglutination assay) is a treponemal antigen serologic test for syphilis.
- Tanned sheep red blood cells coated with antigen from Nichol’s strain of Treponema pallidum are treated with the serum of the patient.
- Sensitivity and specificity are just like the FTA-ABS test.
- This test is not useful for individuals who have had syphilis in the past.
- PCR is recommended for neurosyphilis.
Disease | dark field | RPR | VDRL | FTA-Abs | TP-PA | AIA | TPHA |
Primary syphilis 10 to 90 days |
Positive | positive | positive | negative | |||
Late primary | positive | positive | positive | positive | |||
Latent syphilis | positive/negative | positive | positive | positive | positive | ||
Secondary syphilis 6 weeks to 6 months |
positive | positive | positive | positive | positive | ||
Tertiary syphilis 10 to 30 years |
positive/negative | positive/ negative | positive | positive | positive | ||
Treated syphilis | negative | positive | positive | ||||
Congenital syphilis | positive | positive | positive |
- TP-PA = Treponema pallidum particle agglutination assay.
- FTA- Abs = Fluorescent treponemal antibody absorption.
- TPHA = Treponema pallidum haemagglutination test.
- RPR = Rapid plasma reagin.
- AIA = Automated immunoassay for syphilis antibody.
- VDRL = Venereal disease research laboratory test.
For the diagnosis of neurosyphilis advice:
- VDRL.
- Wasserman test.
- FTA.
- When these tests are positive on CSF in the latent syphilis are diagnostic for the diagnosis of neurosyphilis.
- FTA is more specific for the diagnosis.
Treatment
- The drug of choice is penicillin.