Syphilis

Sample for Syphilis

• The serum of the patient is needed.

Indication

• For the diagnosis of syphilis.

Definition of syphilis

1. The disease syphilis was reported in the medical literature as early as 1495.
2. In the treatment of syphilis. Heavy metals, such as arsenic, were replaced by penicillin in 1940.
3. Treponema pallidum is a member of the order Spirochaetales and the family Treponemataceae.

Syphilis microbiology

Spirochetes:

1. It is a gram-negative organism and looks like a corkscrew.
2. These are fine, spiral 8 to 24 coils organisms. These are approximately 6 to 15 µ mm long.
3. These bacteria can move in a spinning fashion called axial filaments.
4. These bacteria replicate by transverse fission.

5. This organism can not grow in ordinary media.
6. These have a gram-negative cell membrane.
7. These are too small to see under the light microscope.
   1. So a special procedure is used to see these organisms like dark-field, immunofluorescence, and silver stain.
   2. Also, serological tests can help to diagnose syphilis.
8. Syphilis is a chronic venereal disease.
9. This was discovered in epidemic form in the 16th century in Europe.
10. The first diagnostic blood test for syphilis was introduced by Wassermann in 1906.
11. Afro-Americans are infected 30 times more than white Americans.

Mode of spread:

1. Syphilis is caused by Spirochaete Treponema Pallidum, and its natural host is humans.
2. The most common source of infection is a cutaneous or mucosal lesion in the primary or secondary stage of the disease.
   1. During sexual acts, the organism enters the body through minute abrasion of the skin or mucous membranes.
   2. Once it enters the body, the spirochetes are immediately disseminated.
3. In congenital syphilis, it spreads across the placenta to the fetus.
4. The incubation period is 2 to 4 weeks.
5. Syphilis can spread through:
   1. sexual contact
   2. Congenital
   3. Direct contact with the lesion.

Treponema-associated diseases in humans:

1. T. Pallidum = Syphilis
2. T. pallidum variant = Bejel
3. T. carateum = Pinta
4. T. pertenue = Yaws

Syphilis has four clinical stages :

1. Clinically syphilis is divided into four stages:
   1. Primary stage.
   2. Secondary stage.
   3. Latent stage.
   4. Tertiary or late stage.
2. Incubation period:
   1. This is 2 to 4 weeks (3 to 6 weeks average), and the range may be 1.5 to 13 weeks.
   2. . The primary stage starts after this incubation period.
3. The primary stage:
   1. This is characterized by the appearance of a chancre at the primary site of inoculation.
   2. In the male, the lesion is at the penis, and in the female are multiple lesions on the vagina or the cervix.
   3. It has a firm and usually painless ulcer called Chancre.
   4. These ulcers are shallow and are at the site of infection.

syphilis primary chancre

1. 4.  Enlarged lymph nodes may be seen and are painless.
      
   5. This heals spontaneously in 3 to 8 weeks. This stage last 4 to 6 weeks (the range is 2 to 8 weeks).
   6. The lesion is positive for the spirochetes.
   7. Serological tests for syphilis are often negative in the early phase of the disease, so advise darkfield microscopy or a direct fluorescent antibody test.
   8. In the primary stage, Chancre usually heels, followed by the secondary stage.
2. The secondary stage:
   1. 25% of untreated cases from the primary chancre go into the secondary stage.
   2. Secondary stage last for about 4 to 12 weeks.
   3. The Patient may develop this stage after roughly 2 months of the chancre (or 6 to 8 weeks).
   4. 6 to 8 weeks later, the infection becomes generalized; this is the bacteremia stage.
   5. This is characterized by the appearance of systemic lesions on:
      1. Mucous membrane lesions may be seen in the oral cavity (may be seen in 60% of the cases).
   6. There are widespread rashes of the skin.
      1. These rashes (about 80%) are small red flat lesions distributed over the body.
      2. These rashes typically involve palms and soles.
      3. Cutaneous surfaces, warts-like lesions called Condylomata, are seen. Usually seen in moist and warm sites like the perianal area, vulva, and scrotum.
      4. Any organ, including CNS, eyes, kidneys, and bones, may be involved.
   7. This is a highly infectious stage and contains many organisms (treponemes).
   8. Generalized lymphadenopathy is seen in 50% (75%) of cases.
   9. Asymptomatic involvement of the central nervous system is seen in roughly 30% of the cases.
   10. Other rare complications are arthritis, hepatitis, glomerulonephritis, periostitis, and sometime iridocyclitis and chorioretinitis.
   11. These mucocutaneous lesions are highly infectious.
   12. During the last part of the secondary stage, visible lesions disappear, and the patient enters the latent stage.
3. Latent syphilis: 
   1. The latent stage may last about 3 to 5 years.
   2. The disease has been dormant for many years. The symptoms of the second stage have resolved.
   3. But serological tests are positive.
   4. 25% or more will have a relapse and develop an infectious lesion of the skin, like secondary syphilis.
      1. After 4 years, there are generally no more relapses, and this disease may be noninfectious except the pregnant mothers.
   5. This ultimately develops into cardiovascular or neurosyphilis.
   6. Roughly 1/3 of cases progress into the tertiary stage.
4. Late syphilis:
   1. This occurs after 10 to 20 years of the primary lesion.
   2. There are two main types:
   3. Cardiovascular involvement in the form of Aortitis and aneurysm.
   4. Neurosyphilis may be:
      1. General paralysis with dementia, tremors, and spastic paralysis.
      2. Tabes dorsalis with ataxic gate, trophic changes in joints in the form of Charcot’s joints.
      3. There may be optic atrophy.
      4. Meningovascular syphilis causes a headache, cranial nerve palsies, and Argyll- Robertson pupil (pupillary loss of reaction to light).
5. Tertiary stage:
   1. This stage appears 3 to 10 years after the primary lesion (another source says 6 to 40 years takes to develop the tertiary stage).
   2. This is also called late syphilis and is a noninfectious stage.
   3. This is characterized by granulomatous skin lesions called gummas, which may occur on a mucous membrane, subcutaneous tissue, bone, and viscera.
   4. 25% of the patients may develop neurologic, ocular, and cardiovascular diseases.
6. Late or quaternary stage:
   1. 10 to 20 years after primary syphilis, there are two main clinical sequences:
   2. Neurosyphilis may present as follows:
      1. General paralysis of insane with dementia, tremor, and spastic paralysis.
      2. Tabes dorsalis with characteristic features of ataxic gait, atrophic changes in joints, Charcot’s joints, and there may be optic atrophy.
   3. Meningovascular syphilis with a headache, cranial nerve palsies, and papillary loss of reaction to light (Argyll-Robertson pupil).

The main presentation of syphilis is:

1. Gumma formation.
   1. The gummatous lesion appears after 3 to 10 years of the primary lesion in about 15% of the untreated cases.
   2. These are granulomatous lesions.
   3. These are noninfectious lesions mainly found in the skin and the bone.
2. Cardiovascular involvement.
   1. These are seen after at least 10 years of the primary infection in 10% of the untreated cases.
   2. An aneurysm exists in the aorta (ascending part) or aortic arch.
3. Neurosyphilis.
   1. This disease is seen in roughly 8% of untreated cases.
   2. Neurosyphilis presentation is as follows:
      1. Asymptomatic patients when patients look normal. But the CSF is serologically positive.
      2. Subacute meningitis, where the patients have a fever, stiff neck, and headache.
4. CSF examination shows:
   1. Increased proteins.
   2. Low glucose level.
   3. Increased number of lymphocytes.
   4. Positive tests for syphilis.
5. Meningovascular syphilis is when the brain’s blood vessels and meninges are damaged.
   1. There are cerebrovascular occlusion and infarction of the tissue in the brain, meninges, and spinal cord.
6. Tabes dorsalis affects the spinal cord.
   1. In this case, the posterior column and dorsal roots are involved.

Congenital syphilis:

1. Bacteria can enter into fetal circulation at any time from the placenta during pregnancy. So these bacteria can cross the placental barrier.
2. The chances are more when the mother is in the primary or secondary stage to infect the fetus.
3. Without treatment, roughly 40% of the fetus will die in utero around the 4th month of the pregnancy.
4. The manifestation of congenital syphilis are:
   1. Stillbirth.
   2. Infantile syphilis.
   3. Hepatosplenomegaly and bone abnormalities.
   4. There are pancreatic fibrosis and pneumonitis.
   5. The lungs may be firm and pale.
   6. Tissues are positive for the spirochetes.
5. Congenital syphilis was clinically seen as:
   1. Latent infection when there are no symptoms, but infants are serologically positive.
   2. The early stage appears after the end of the second year.
      1. Most infants are healthy at birth, and symptoms appear in the first few weeks.
      2. There are generalized skin rashes and nasal deformities. Hepatitis, meningitis, anemia, and bone lesions.
6. Late syphilis manifestations appear in the first few weeks of life.
   1. They may not be able to thrive.
   2. There is bone sclerosis.
   3. Joint effusion and arthritis.
   4. Interstitial keratitis.
   5. Juvenile general paralysis of the insane and tabes.
   6. Deafness.
   7. Notching of the incisor teeth.

Diagnosis of syphilis:

1. Specific tests for syphilis are:
   1. Treponema pallidum immobilization test (TPI).
   2. Fluorescent treponemal antibody absorption test (FTA-ABS).
   3. The micro hemagglutination assay for treponema pallidum (MHA-TP).
   4. Reiter protein complement fixation test (RPCF).
      1. Reiter protein is produced by the non-pathogenic treponema called the Reiter strain.
2. Darkfield examination.
   1. This is a direct examination of Treponema pallidum from the syphilitic lesion.
3. Immunological tests.
   1. Cardiolipin test. This is the first serologic test. This was dependent upon the complement activation.
   2. Cardiolipin is from the beef heart and is a phospholipid.
   3. VDRL (Venereal disease research laboratory test) is based on cardiolipin.
4. Examination of the CSF.

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