Spiral Organisms

1. Spiral Organisms • Treponema • pallidum: syphilis • Bejel (subsp. endemicum - non-venereal variant – African, etc.) • carateum: pinta Pinta (non-venereal – erythematous skin lesions only) • pertenue: yaws (non-venereal – papilloma skin lesions) • vincentii: ANUG (trench mouth – mixed anaerobic infection) Acute necrotizing ulcerative gingivitis (ANUG) • denticola: periodontitis • Leptospira • interrogans: leptospirosis • Borrelia • recurrentis: epidemic relapsing fever • hermsii: endemic relapsing fever • burgdorferi: Lyme disease • Spirillum (rat bite fever) • minus

2. SPIROCHETES

3. Key Words • Spirochete • Axial filament • Darkfield microscopy • Treponema pallidum • Syphilis • Hard painless chancre • Primary lesion • Secondary Lesion • Tertiary Lesion • Anti-cardiolipin antibodies • VDRL, RPR, TPHA, FTA-ABS • Borrelia burgdorferi -Lyme disease • Relapsing fever (other borrelia) • Leptospira (leptospirosis)-Weil’s Disease

4. General Characteristics • Elongated, motile (endoflagella- axial filament), spiral bacteria • Structurally complex – central protoplasmic cylinder bounded by a cytoplasmic membrane & cell wall of similar structure to that of Gram –ve bacteria.

5. General Characteristics • Larger spirochetes are gram negative, others are too thin to be seen with light microscope. • Seen under Dark Ground Microscope by staining with silver

6. What are Spirochetes? • Small, motile, slender, helically coiled, flexible bacteria • Require special staining techniques; Gram-stain ineffective • Dark field • Fluorescent • Silver stain for tissue • Wright’s or Giemsa may detect Borrelia in blood smears

7. Classification of Spirochetes • Human pathogens belong to following 3 genera: • Treponema • Leptospira • Borrelia • Others (saprophytes) are found in water, sewage and in mouth & genital tracts of humans.

8. Comparative Morphology

9. Treponema • Main treponemes are: T. pallidum - Syphilis:Venereal (sexual) disease T. pertenue - Yaws Non venereal T. carateum - Pinta disease • All three species are morphologically identical

10. Treponema pallidum Characteristics : • Discovered by Schaudin & Hoffman in 1905. • Better seen under DGM - prolonged Giemsa stain, Silver impregnation method Fontana’s – smears Levaditi’s – tissue sections

11. Characteristics of T.pallidum • Morphology – thin, 10μ with tapering ends • Culture – • Do not grow on artificial media. • Virulent strains can be maintained in rabbit testis by serial passages e.g. Nichol’s strain – used for diagnosis & research • Reiter’s strain – nonpathogenic strain cultivated for diagnosis.

12. Characteristics of T.pallidum • Very delicate, easily killed by drying or heating at 42C for an hr. • Antigenicity – 3 types of Abs are produced. • Non specific - Reagin Ab • Group specific – found in T.pallidum & Reiter strains. • Species specific – polysaccharide Ag of T.pallidum

13. Pathogenicities • Causes Syphilis which can be: • Venereal • Congenital • Non venereal

14. Venereal Syphilis • Sexually transmitted disease. • Entry through minute abrasions on mucosa or skin. • Incubation period - about a month (10 to 90 days). • Infectivity is maximum during first 2 years of disease – primary, secondary & early latent stages

15. Stages of venereal syphilis • Primary syphilis – • hard chancre on genitals: painless, avascular, circumscribed, indurated & ulcerated lesion; covered with a thick glairy exudate rich in spirochetes • Heals spontaneously in 10-40 days

16. Primary Lesions

17. Stages of venereal syphilis • Secondary syphilis – • Most infectious stage • Sets in 2-6 months after 1 lesion heals. • Pt is asymptomatic but widespread dissemination occurs via blood • Maculopapular skin rashes on the body, mucous patches in the oropharyngeal area & condylomata at mucocutaneous junctions

18. Stages of venereal syphilis • Latent syphilis – quiescent stage which follows secondary stage • Tertiary syphilis – after 10 to 20years, cardiovascular lesions like aneurysm, aortitis • Late tertiary or quaternary syphilis –neurosyphilis : tabes dorsalis or general paralysis of insane

20. Congenital syphilis • Mother to fetus via placenta • After 4th month of gestation • Clinical features – keratitis, saddle shaped nose, Hutchinsons teeth, 8th nerve deafness. Non venereal syphilis • In doctors & nurses • Rarely by blood transfusion

21. Saddle shaped nose Hutchinsons teeth

22. Laboratory Diagnosis • Microscopy – • Dark ground(DGM) - used in 1 & 2 syphilis • Silver staining • Direct fluorescent Ab test (DFA – TP) • Serology – mainstay of diagnosis • Non specific test/ standard tests for syphilis • Group specific test • Specific tests

23. Non specific / Standard tests • Test for reagin Ab using cardiolipin Ag. • Wasserman complement fixation test • Kahn flocculation test • VDRL (Venereal Disease ResearchLaboratory) test • RPR (Rapid Plasma Reagin) test • Biological false positive reactions are seen in 1% of human sera

24. Group specific test • Using Reiter strain Ag – Reiter protein CFT Specific tests • Using Nichol’s strain • T. pallidum immobilisation (TPI) test • T. pallidum haemagglutination test (TPHA) • Fluorescent treponemal Ab absorption test (FTA-ABS) – very specific, standard reference test • T. pallidum enzyme immunoassay(TP-EIA)

25. Non-treponemal False Positives (1-2%; generally low titer) • Autoimmune disease • Injection drug use • TB • Vaccinations • Pregnancy • Infectious mononucleosis • HIV • Rickettsial infections • Spirochetal infections other than pallidum • Bacterial endocarditis

26. Non-treponemal reactivity diminishes over time (aside: also after successful treatment)

27. Evaluating Serologies • Non-treponemal antibodies develop 4-8 weeks after infection (within 2 weeks of chancre formation in 70% of patients) • 4-fold increase in titer may be seen in early syphilis; in secondary, titers are often high • Quantitative tests are used to assess treatment; 4-fold decreases demonstrate adequate therapy. Increases after treatment suggest reinfection or relapse. • Positive CNS reactivity indicates neurosyphilis • Confirm positives with treponemal-specific tests

28. Syphilis Serologic Testing

29. Treatment • Penicillin is the drug of choice • 2nd line- Erythromycin, Tetra/ Doxycycline • Neurosyphilis - Ceftriaxone

30. CDC-Recommended Treatments for Syphilis (2002) • Primary, secondary, or early latent syphilis * • Recommended: benzathine penicillin G, 2.4 million units in a single dose, intra muscularly Penicillin allergy: doxycycline, 100 mg by mouth twice daily for 14 days • Late latent syphilis, syphilis of unknown duration, tertiary syphilis • Recommended: benzathine penicillin G, 2.4 million units weekly for 3 weeks, in tramuscularly Penicillin allergy: doxycycline, 100 mg by mouth twice daily for 28 days • Neurosyphilis, syphilitic eye disease, syphilitic auditory disease • Recommended: Aqueous crystalline penicillin G, 18-24 million units per day ad ministered as 3-4 million units intravenously every 4 hours or continuous in fusion for 10-14 days Alternative: procaine penicillin 2.4 million units intramuscularly once daily plus probenecid 500 mg by mouth 4 times a day, both for 10-14 days *Latent syphilis is defined as seroreactivity without other evidence of disease. Early latent syphilis is diagnosed in patients infected within the preceding year as defined by 1 of the following: (1) a documented seroconversion; (2) unequivocal symptoms of primary or secondary syphilis; or (3) a sex partner documented to have primary, secondary, or early latent syphilis. Pregnant women should not be treated with doxycycline. Patients with non–life-threatening allergies to penicillin should ideally be desensitized. Patients with serious allergies to sulfonamides should not be treated with probenecid-containing regimens.

31. Prevention and Control • Screening • All pregnant woman at first prenatal visit • Individuals with other STDs • High risk behaviors (drug use, prostitution, etc.); again at 28 weeks gestation if pregnant • Exposure • Reporting of contacts and tracing of sexual partners • Education