3. Syphilis
• Chronic venereal infection caused by the spirochete
Treponema pallidum.
• Source of infection : active cutaneous or mucosal
lesion in a sexual partner in early stages of syphilis.
4. Classification
Stage Acquired Congenital
Early Primary
Secondary
Latent
Late Latent
Benign Tertiary
Cardiovascular
Neurosyphilis
• Penicillin is the drug of choice for all stages of infection.
5. Acquired syphilis :
Primary syphilis :
• IP – between 14 & 28 days.
• A dull red macule → papular → indurated ulcer – Hard
Chancre.
• Inguinal lymph nodes enlarged, mobile, discrete & rubbery.
• Chancre and lymph nodes : painless.
• Without treatment, resolves within 2-6 weeks to leave thin
atrophic scar.
6. • Extra genital chancres – fingers, tongue, tonsil, nipple, anus.
• Diagnosed by Dark field microscopy or direct Fluorescent Ab
tests of exudates.
8. Secondary syphilis :
• 6-8 weeks after development of chancre when treponemes
disseminate.
• Mucocutaneous lesions & generalised lymphadenopathy.
• Fever, malaise, headache common.
• Rashes on trunk and characteristically on palms & soles.
• Condyloma lata in warm moist areas – vulva, perianal areas.
9. • Mucosal patches – genitalia, mouth, pharynx, larynx.
• Less common : hepatitis, renal ds, eye ds & GI abnormalities.
• Diagnosed by serological tests.
12. Latent syphilis :
• Asymptomatic but presence of positive syphilis serology.
1. Early Latency : within 1 year of infection, may be
transmitted sexually.
2. Late Latency : patient no longer sexually infectious.
17. Neurosyphilis :
• Asymptomatic infection with CSF abnormalities.
• Symptomatic forms :
Meningovascular disease, Tabes dorsalis, General paresis.
18. Congenital syphilis
• Greater chance during early stages of disease.
• Stigmata do not develop until 4th month of pregnancy.
Manifestations:
1. Still birth
Hepatomegaly, bone abnormalities, pancreatic fibrosis &
pneumonitis.
19. 2. Infantile syphilis
c/c rhinitis (snuffles) , mucocutaneous lesions.
visceral & skeletal changes, ascites, hydrops.
3. Late / Tardive syphilis
I. Hutchinson triad - notched central incisors, interstitial keratitis
with blindness & deafness from 8th nerve injury.
II. Saber shin deformity
III. Mulberry molars
IV. Saddle nose deformity
V. Clutton joints
22. Serological tests
1. Non treponemal ( non specific ) tests :
I. Venereal Disease Research Laboratory ( VDRL ) test
II. Rapid Plasma Reagin ( RPR ) test
2. Treponemal ( specific ) tests :
I. Treponemal antigen based Enzyme Immunoassay (EIA) for IgG
& IgM.
II. T.pallidum Hemagglutination Assay ( TPHA )
III. T.pallidum Particle Agglutination Assay ( TPPA )
IV. Fluorescent Treponemal Antibody-Absorbed ( FTA-ABS ) test
CSF examination
23. Management
Prophylaxis :
• Benzathine Penicillin 2.4 MU single dose before or
12 hrs within contact affords protection.
• Procaine Penicillin 2.4 MU i.m , into each buttock (
total 4.8 MU) , preceded by 1g of Probenecid helps
to prevent both Syphilis and Gonorrhea.
24. Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin
25. Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.
26. • Azithromycin 2g single dose is an another alternative.
• Successful treatment → resolution of clinical signs, declining
titers of non treponemal tests ( four fold decline).
27. Syphilis in Pregnancy
• T.pallidum enters fetal circulation after 20th week, fetal
infection unlikely before that.
• Perinatal effects max with primary & secondary syphilis.
• Penicillin – drug of choice.
• For 1° & 2° or latent syphilis of less than 1 yr duration,
Benzathine PenicillinG 2.4 MU i.m, as a single dose
(or)
Crystalline Benzyl Penicillin for 10 days
28. • When duration is > 1 yr,
Benzathine Penicillin 2.4 MU i.m, weekly for 3 doses is
given.
• Breast feeding is not contraindicated.
• Every neonate with congenital syphilis should be treated:
Benzyl Penicillin for 10 days
For Interstitial keratitis, local / systemic Glucocorticoids.
Alternative - Erythromycin stearate
500mg, once in 6 hrs x 2 weeks
29. Penicillins
• β lactum antibiotic, narrow spectrum.
• 1 MU = 0.6 g
MOA : interfere with synthesis of cell wall by inhibiting
transpeptidases ( required for maintaining cross linking).
i.e, is bactericidal.
31. Pharmacokinetics :
• PnG is acid labile, destroyed by gastric acids.
• Less than 1/3 of oral dose is absorbed in active form.
• Reaches most body fluids, 60% plasma protein bound.
• T ½ = 30 min
• Rapid renal excretion –
10% by glomerular filtration. 90% by tubular secretion.
• Tubular secretion blocked by Probenecid.
32. Repository Penicillin G injections
• Insoluble salts of PnG which must be given i.m, not i.v
• They release PnG slowly at site of injection
1. Procaine Penicillin G
Plasma levels attained are low , but sustained for
12-24 hrs.
2. Benzathine Penicillin G
Plasma conc very low , but effective for upto 4 weeks.
34. Doxycycline
• Tetracycline, broad spectrum antibiotic.
MOA :
▫ Primarily bacteriostatic.
▫ Inhibits protein synthesis by binding to 30S ribosomes .
• Intestinal absorption complete, no interference with food.
• ADR – irritative effects, phototoxicity.
• C/I in pregnancy – a/c hepatic necrosis, teeth & bone affected.
35. Ceftriaxone
• 3rd generation cephalosporin.
• Given parenteral.
• Bactericidal, MOA similar to penicillin.
• Longer duration of action, T ½ = 8hr
• Elimination equally in bile and urine.
• ADR – hypoprothombinemia & bleeding.
36. Erythromycin
MOA -
▫ Acts by inhibiting bacterial protein synthesis.
▫ It combines with 50S ribosome unit, interfere with translocation
• Is acid labile. Food delays absorption by delaying gastric emptying.
• Widely distributed in body. Crosses placenta, not BBB.
• 70-80% plasma protein bound.
• Primarily excreted in bile. Renal excretion minor.
• ADR- GI ds, hypersensitivity, reversible hearing impairment.
37. Treatment reactions
1. Allergy
2. Jarisch – Herxheimer Reaction :
▫ An acute febrile reaction that follows the treatment (1st
dose)
▫ Headache, malaise, myalgia, tachycardia, shivering,
exacerbations of lesions, even vascular collapse.
▫ Common in early syphilis. Rare and severe in late syphilis.
▫ May cause worsening of neurological disease, ophthalmic
disease, myocardial ischemia, laryngeal stenosis.
38. ▫ Is due to rapid destruction of large no. of spirochetes with
release of endotoxin.
▫ Lasts for 12-72 hrs, does not need interruption of therapy.
▫ Aspirin and sedation afford relief of symptoms.
▫ Cannot be prevented by giving graduated doses of penicillin.
▫ Prevent it in cardiovascular & neurosyphilis by –
Prednisolone in single daily dose of 30mg in morning, 2 days
before starting penicillin.
39. 3. Procaine Reaction
▫ After accidental intravenous injection of Procaine Penicillin.
▫ CNS stimulation, hallucination, fits, convulsions, fear of
impending death.
▫ Symptoms short lived.
▫ Verbal assurance & physical restraint necessary.
▫ Reaction prevented by aspiration before i.m injection to
ensure needle is not in blood vessel.
40. Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin
41. Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.