CamScanner Usage Quiz

General Characteristics of Spirochetes

• Spirochete - a type of bacteria resembling "coiled hair"
• Thin, helical, tightly coiled (corkscrew) spirals
• Regular intervals and tapered or pointed ends
• Gram-negative
• Divide by transverse fission
• Motile – rotational and forward movement

Treponema Species

• Treponema pallidum:
  • Subspecies pallidum (Syphilis)
  • Subspecies endemicum (Bejel)
  • Subspecies pertenue (Yaws)
• Treponema carateum (Pinta)

Classification of Human Treponema

• Pathogenic Treponema:
  • T. pallidum (syphilis)
  • T. pallidum subspecies endemicum (bejel)
  • T. pallidum subspecies pertenue (yaws)
  • T. carateum (pinta)
• Non-pathogenic Treponema:
  • Oral commensals
  • T. denticola
  • T. macrodenticum
  • T. orale
  • T. microdentium

Treponema pallidum

• Slender, corkscrew-shaped
• Regularly spaced 1 µm apart
• Seen only with immuno-fluorescent stain or dark-field microscope
• Pointed tapering ends
• Stains with difficulty except with Giemsa or silver stain

Treponema pallidum Structure

• Outer sheath: Glycosaminoglycan coating (mucoid layer)
• Outer membrane: Encloses axial fibrils, contains peptidoglycan
• Endoflagella/axial filaments/periplasmic fibrils: Rotational and flexion movements, encased by outer membrane
• Inner cytoplasmic membrane: Within endoflagella, providing osmotic stability
• Cytoplasmic tubules/body fibrils: Near inner membrane

Physiologic Properties

• Microaerophilic (1%-4% oxygen), aerobic or anaerobic (depending on species)
• Do not grow on cell-free media
• Inoculate in testes of rabbits or anterior eye chamber
• Slow growing
• No TCA cycle – depend on host cells for purines, pyrimidines and most amino acids
• Remain motile in presence of reducing substances for 3-6 days at 25°C
• Remain viable in whole blood or plasma stored at 4°C for at least 24 hours
• Part of normal flora of humans or animals.
• Sensitive to penicillin

Treponema pallidum Characteristics

• Cannot be cultured in vitro
• Absence of tricarboxylic acid cycle
• Dependence on host cells for nutrients
• Sensitivity to oxygen
• Lack of catalase and superoxide dismutase genes
• Too thin for light microscopy
• Visualizable by darkfield illumination or fluorescent antibody staining

Treponema Culture

• Non-pathogenic or saprophytic strains (Reiter strain)
• Anaerobic culture in vitro → 30 hours doubling time
• Defined medium containing amino acids, vitamins, minerals, salts and serum albumin

Other Characteristics

• Rapidly killed or immobilized by drying, high temperature (42°C) and trivalent arsenical, mercury & bismuth
• Slow rate of killing using penicillin due to metabolic inactivity and slow multiplication rate of organism

Virulence Factors

• Outer membrane proteins covalently bound to lipids: keep proteins inaccessible to antibodies
• Hyaluronidase: Facilitates perivascular infiltration, enhancing invasiveness
• Coating of fibronectin: Protects against phagocytosis, evasion of immune system
• Species-specific Ag on cell surface: Protect against phagocytosis and evasion of immune system
• Hemolysin: Hemolysis of RBC

T. pallidum Infection

• Endothelium → Endarteritis → Brain & Cardiovascular Lesions
• Resistance to phagocytosis
• Adherence to host tissues
• Hyaluronidase production → Enhanced invasiveness → Tissue destruction & Lesions
• Immune response

Syphilis Transmission and Progression

• Transmission Methods: Intimate contact, mucous membrane penetration, break in epidermis, vertical transmission, blood transfusion
• Primary Phase Symptoms: Chancre at site of penetration (primary site of initial replication)

Epidemiology

• Syphilis is NOT highly contagious
• 30% chance of acquiring after single exposure to infected partner
• Transmission rate depends on stage of disease.

Immunity

• Initial response: production of anti-phospholipid antibodies
• Temporary depression of CMI
• IgG anti-treponemal antibodies – immobilize and kill organisms
• Factors contributing to persistent infection
  • Delayed synthesis of protective IgG antibodies
  • CMI not protective
  • Organisms covered by fibronectin

Pathogenesis

• Adherence to skin or mucosal membranes → produce hyaluronidase (promote tissue invasion)
• Organism becomes coated with host fibronectin
• Soon after infection → hematogenous spread → other skin sites & to other organs
• Skin lesions of primary syphilis → represent the primary site of initial replication

Pathology

• Main lesion: endarteritis (blood vessels and perivascular areas)
• Extensive tissue necrosis and scarring
• Spirochetes appear in lesions and blood during first 2 stages → highly communicable

Infectious Dose

• Estimated average inoculum: 500-1,000 in humans
• 60 treponemes – infect 50%
• Inoculation occurs at any body site; external genitalia – most common
• Mouth, anus, cervix, other sites.

Primary, Secondary, and Late Syphilis Stages

• Primary: Chancre at entry site; endarteritis & periarteritis; PMNs & macrophages
• Secondary: (+) clinical signs of disseminated disease; skin lesions
• Late: Systemic spread → virtually all tissues involved

Syphilis Stages: Primary, Secondary, Latent, and Tertiary Stages

• Primary: Chancre at site of inoculation
• Secondary: Rash, lymphadenopathy
• Latent: Period without symptoms; treponemes may remain dormant
• Tertiary: Gummas, cardiovascular, and neurological complications.

Clinical Features of Syphilis

• Granulomatous lesions (gummas) in skin, bones, and liver (hepar lobatum)
• Degenerative CNS changes (late neurosyphilis) – meningovascular, general paresis, tabes dorsalis
• CV lesions – aortitis, aortic aneurysm, aortic valve insufficiency/regurgitation

Late Neurosyphilis

• Develops in 1/6 of cases, usually > 5 years after infection
• CNS and spinal cord involvement
• Cerebral atrophy most prominent in frontal lobes
• Dementia, seizures, wasting, etc.

Tabes Dorsalis Morphology

• Dorsal column degeneration
• Orthopedic pain (Charcot joints)
• Reflexes decreased (deep tendon)
• Shooting pain
• Argyll-Robertson pupils
• Locomotor ataxia
• Impaired proprioception

Argyll Robertson Pupil (Light-Near Dissociation)

• Bilateral small pupils
• (+) constriction on accommodation
• (-) constriction when exposed to bright light

Hepar Lobatum (Liver Lesions)

• Markedly nodular and irregular liver with scarring
• Appearance due to healing of multiple gummatous lesions

Condylomata lata

• Moist, pale papules in anogenital region, axilla, and mouth. (Secondary syphilis lesions)

Other manifestations:

• Syphilitic meningitis
• Chorioretinitis
• Hepatitis
• Nephritis (immune complex type)
• Periostitis

Acquired Syphilis: Latent Stage

• Eclipse/window period, usually 2 years
• Clinically inactive; (+) serologic tests
• 30% of untreated infection
• Early latent (infection < 12 mos.) and Late latent (infection > 12 mos. ago)

Acquired Syphilis: Tertiary Stage

• 1/3 of untreated patients
• Activation of dormant treponemes 3–30 years later in untreated cases
• Diffuse, chronic inflammation; all tissues involved
• Degenerative, irreversible necrotic lesions; no spirochetes on lesions

Laboratory Tests

• Specimen: tissue fluid from early surface lesions; blood serum for serology
• Dark-field Examination: Typical motile spirochetes; exudates from skin lesion; primary, secondary and congenital syphilis
• Immunofluorescence: Fluorescent spirochetes; more useful

Diagnostic Tests

• Microscopy: Darkfield, Direct fluorescent antibody staining (DFTA)
• Culture: Not available
• Serology:
  • Nontreponemal: Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin Test (RPR), Unheated Serum Reagin (USR) Test, Toluidine Red Unheated Serum Test (TRUST), Wasserman Test
  • Treponemal: Fluorescent Treponemal Antibody Absorption (FTA-ABS), Treponema pallidum Particle Agglutination (TP-PA), Enzyme Immunoassay

Serologic Tests: Nontreponemal Tests

• Antigens: measured amounts of cardiolipin (from beef heart), cholesterol & purified lecithin
• Antibodies: syphilitic IgG and IgM reaginic antibodies vs. lipoprotein-like material released from damaged host cells & cardiolipin released from the treponemes
• VDRL & RPR – flocculation tests; detect IgG & IgM early in infection

Serologic Tests: Treponemal Tests

• Measure antibodies vs. T. pallidum antigens
• Confirmatory
• Serial dilution of serum not done
• Report as reactive or non-reactive

Serologic Tests : Treponemal Tests

• T. pallidum Particle Agglutination (TP-PA): Most widely used in U.S.
• T. pallidum Hemagglutination (TPHA) & micro-hemagglutination (MHA-TP)
• Fluorescent Treponemal Antibody Absorption (FTA-ABS): Most common used

Serologic Tests: Treponemal Tests

• If (+) IgM FTA in blood of newborn → (+) in utero infection
• Not helpful in diagnosis of neurosyphilis but if (-), exclude neurosyphilis

Conditions with false (+) Treponemal Tests

• Pyoderma
• Rheumatoid arthritis
• SLE
• Psoriasis
• Crural ulceration
• Skin neoplasm
• Drug addiction
• Mycoses
• Lyme disease
• Acne vulgaris

Diagnosis of neurosyphilis and congenital syphilis

• Based on clinical symptoms & laboratory findings
• VDRL test on CSF highly specific but not sensitive
• (+) FTA-ABS CSF test consistent with neurosyphilis but not diagnostic

Serologic test results in infants

• (+) serologic test results in infants may represent passive transfer of Ab's from mothers
• Measure antibody titers in sera for 6 months
  • If non-infected: Ab titers decrease to undetectable levels within 3 months of birth
  • If remains elevated, (+) congenital syphilis

Nucleic Acid-Based Tests (PCR)

• For detecting T. pallidum in genital lesions, infant blood, and CSF

Screening Algorithms (Traditional and Reverse)

• Traditional: Screens with non-treponemal test (RPR/VDRL); Positive → Treponemal Test (FTA-ABS/TP-PA), Confirm
• Reverse: Screens with treponemal test (FTA/TP-PA); Positive → Non-treponemal Test (RPR/VDRL), Confirm

Interpretation of Serologic Test Results

• Table correlating non-specific and specific test results with possible diagnoses.

Treatment, Prevention & Control

• If < 1 year of disease: Benzathine penicillin IM single dose

• 1 year of disease: Benzathine penicillin IM once a week x 3 weeks

• Late stages: admitted, Penicillin IV x 10 days
• WHO recommended treatments for early and late syphilis in adults and adolescents, as well as pregnant women and infants.

Treponema pallidum subspecies endemicum: Bejel

• Endemic syphilis; Primarily in Africa, Middle East, SE Asia, and elsewhere; Usually children
• Person-to-person infection (contaminated eating utensils)

Endemic Syphilis (Bejel) Lesions

• Primary: Nondescript oral lesions
• Secondary: Oral papules & mucosal patches
• Late: Gummas of skin, bones, and nasopharynx

Yaws (T. pertenue)

• Endemic among children (<15 y/o) in humid, hot tropical countries
• Mode of transmission (MOT): Direct contact with infected skin lesions
• Primary lesion: Ulcerating papule/papillomatous lesions, usually on arms or legs; with abundant, contagious spirochetes
• Late: Destructive lesions of the skin, lymph nodes (LN), and bones → scar formation common
• Cross-immunity with syphilis; Same diagnosis & treatment as syphilis; Dramatic improvement with penicillin

Pinta (T. carateum)

• Endemic in all age groups in Mexico, Central & South America, the Philippines, and some areas of the Pacific
• MOT: Direct contact OR through flies or gnats
• Incubation: 1–3 weeks
• Primary lesion: Scaly, painless pruritic papule on exposed areas → erythematous rash
• Secondary: Enlarged plaques (persist months to years)
• Late: Disseminated, recurrent hypo-pigmentation or depigmentation of skin lesion, scarring and disfigurement

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