Sgrùdadh air Spirochetes agus Treponema

### Ginearal Characteristics of Spirochetes

• Spirochete - means "coiled hair" in Greek
• Thin, helical, tightly coiled (corkscrew) spirals with regular intervals and tapered or pointed ends.
• Gram-negative bacteria
• Divide by transverse fission
• Motile, with rotational and forward movement.

### Treponema Species

• Treponema pallidum:
  • T. pallidum subspecies pallidum (Syphilis)
  • T. pallidum subspecies endemicum (Bejel)
  • T. pallidum subspecies pertenue (Yaws)
• Treponema carateum (Pinta)

### Classification of Human Treponemes

• Pathogenic Treponemes:
  • T. pallidum pallidum (Syphilis)
  • T. pallidum endemicum (Bejel)
  • T. pallidum pertenue (Yaws)
  • T. carateum (Pinta)
• Non-pathogenic Treponemes: Oral commensals (e.g., T. denticola, T. macropadentium, T. orae)

### Treponema pallidum

• Trepos - turn
• Nema - thread
• Pallid - pale
• Slender, corkscrew-shaped, regularly spaced 1 µm (micrometer) apart.
• Seen with immuno-fluorescence or dark-field microscopy.
• Pointed tapering ends.
• Difficult to stain except with Giemsa's or silver stain.

### Structure of Spirochetes

• Outer sheath: Coating (mucoid layer) of glycosaminoglycans. Encloses axial fibrils
• Outer membrane: Contains peptidoglycan; crucial for structural integrity
• Endoflagella/axial filaments/periplasmic fibrils: Within the periplasmic space, encased by the outer membrane, responsible for rotation and flexion movements.
• Inner cytoplasmic membrane: Encloses the protoplasmic cylinder, critical for maintaining osmotic stability.
• Cytoplasmic tubules/body fibrils: Located near the inner membrane.

### Physiological Properties of Treponema pallidum

• Microaerophilic: thrives with 1%–4% oxygen, can be aerobic or anaerobic depending on the species.
• Doesn't grow on cell-free media; cultured in rabbit testes or anterior eye chamber.
• Slow-growing bacteria
• Lacks a TCA (tricarboxylic acid) cycle and depends on host cells for purines, pyrimidines, and most amino acids.
• Remains motile in the presence of reducing substances at 25 °C for 3-6 days.
• Remains viable in whole blood or plasma at 4 °C for at least 24 hours.
• Some species are free-living parts of the normal human/animal flora.

### Characteristics of T. pallidum

• Cannot be cultured in vitro.
• Lacks a tricarboxylic acid (TCA) cycle.
• Dependent on host cells for nutrients.
• Sensitive to oxygen.
• Lacks superoxide dismutase and catalase genes.
• Very thin, difficult to observe with light microscopy.
• Visualized by darkfield or fluorescent antibody staining.

### Culture of Treponema pallidum

• Non-pathogenic or saprophytic strains (e.g. Reiter strain) grown anaerobically in vitro, doubling time of 30 hours.
• Defined medium containing amino acids, vitamins, minerals, salts, and serum albumin essential for culturing.

### Other Characteristics of Spirochetes

• Easily killed or immobilized by drying, high temperature (42°C), and trivalent arsenicals, mercury, and bismuth.
• Slow multiplication rate of organism results in a slow rate of killing utilizing penicillin.

### Virulence Factors of Treponema

• Outer membrane proteins covalently bound to lipids: Protect the proteins from antibodies. Facilitate attachment to host cells.
• Hyaluronidase: Promotes tissue invasion.
• Fibronectin Coating: Protects against phagocytosis. Enables evasion of the immune system.
• Species-specific antigens on cell surfaces: Promotes adherence to host cells, facilitates perivascular infiltration, and enhances invasiveness
• Hemolysis: Lysing of red blood cells (RBCs)

### Pathogenesis of Syphilis

• Adherence to skin or mucous membranes. Production of hyaluronidase promotes tissue invasion.
• Organism becomes coated with host fibronectin.
• Dissemination to other skin sites and organs soon after infection.
• Lesions of primary syphilis are the initial site of replication.

### Pathology of Syphilis

• Main lesion: endarteritis (inflammation of blood vessels) and perivascular (around the vessels) areas.
• Extensive tissue necrosis and scarring.
• Spirochetes are present in lesions and blood during the first 2 stages of infection, making the person highly infectious.

### Infectious Dose

• Estimated average inoculum for infection in humans: 500-1,000 spirochetes.
• 60 treponemes can infect 50% individuals.
• Entry into the body commonly occurs in the external genitalia, but also through the mouth, anus, cervix and other anatomical sites.

### Phases of Syphilis

• Primary: Chancre (ulcerating lesion) at the site of entry, endarteritis and periarteritis, PMNs and macrophages.
• Secondary: (+) clinical signs of disseminated disease, skin lesions.
• Late: Systemic spread to all tissues

### Stages of Syphilis

• Primary: Chancre at site of entry, endarteritis/periarteritis, PMNs/macrophages.
• Secondary: Disseminated disease, skin rash, lymph node involvement.
• Latent: No symptoms, organism present in body.
• Tertiary: Systemic involvement, gummas (granulomatous lesions) in skin, bones, and viscera (e.g., liver); CV (cardiovascular) lesions, neurosyphilis (CNS involvement).

### Immunity to Syphilis

• Initial response: production of anti-phospholipid antibodies.
• Temporary depression of cell-mediated immunity (CMI).
• IgG anti-treponemal antibodies: Immobilisation and kill organisms.
• Factors contributing to persistent infection: Delayed synthesis of protective IgG antibodies; CMI not protective; organisms covered by fibronectin.

### Epidemiology of Syphilis

• Not highly contagious.
• 30% chance of infection after a single exposure to an infected partner.
• Transmission rate dependent on the stage of the disease.

### Laboratory Tests for Syphilis

• Dark-field examination: Useful to detect motile spirochetes in exudates from skin lesions during primary, secondary, and congenital syphilis.
• Immunofluorescence: Detection of fluorescently stained spirochetes, generally more useful than dark-field microscopy.
• Nontreponemal tests: Measure antibodies against cardiolipin (e.g., VDRL, RPR). Screening tests; may give false-positive results.
• Treponemal tests: Measure antibodies against Treponema pallidum antigens (e.g., FTA-ABS, TP-PA). Confirmatory tests.
• Nucleic acid-based tests (PCR): For detection of T. pallidum in genital lesions, infant blood, and cerebrospinal fluid (CSF).
• VDRL test on CSF: Highly specific but not sensitive in testing for neurosyphilis.
• FTA-ABS CSF test: Consistent with neurosyphilis but not diagnostic.

### Conditions with False (+) Reactions

• Viral infections
• Rheumatoid arthritis
• SLE
• Acute or chronic illness
• Pregnancy
• Recent immunizations
• Drug addiction
• Leprosy
• Malaria

### Treatment of Syphilis 

• < 1 year of disease: Benzathine penicillin single dose.

• 1 year of disease: Benzathine penicillin IM once/week for 3 weeks.

• Late stages: Hospitalized, IV penicillin for 10 days.

### Complications of Treatment

• Jarisch-Herxheimer reaction: Due to lysis of treponemes and release of endotoxin-like substances, mediated by TNF (Tumor Necrosis Factor). Flu-like symptoms occur several hours after treatment administration.

### Endemic Syphilis (e.g., Bejel)

• Distribution: Primarily in Africa, Middle East, SE Asia
• Mostly affects children.
• Transmission: Person-to-person contact (contaminated eating utensils)
• Lesions: Oral lesions (primary); oral papules and mucosal patches (secondary); gummas in skin, bones, and nasopharynx (late)

### Yaws (T. pallidum subspecies pertenue)

• Endemic in humid, hot tropical countries among children (< 15 y/o).
• Transmission: Direct contact with infected skin lesions.
• Primary lesion: Ulcerating papule/papillomatous lesions (common in arms and legs).
• Late lesions: Destructive lesions in skin, lymph nodes, and bones, leading to scar formation.
• Cross-immunity with syphilis, so diagnosis and treatment are similar to syphilis. Significant improvement with penicillin treatment.

### Pinta (T. carateum)

• Endemic in Mexico, Central and South America, Philippines, some Pacific areas.
• Restricted to dark-skinned races.
• Transmission: Direct contact or by flies/gnats.
• Incubation: 1-3 weeks.
• Primary lesion: Scaly, painless pruritic papule on exposed areas.
• Secondary: Erythematous skin rash, enlarged plaques.
• Late: Disseminated hypo/hyperpigmentation, scarring, disfigurement