CHAPTER 45

The Spirochetes

14th ed. Bailey & Scotts

Copyright © 2014, by Mosby, an imprint of Elsevier Inc.

 Objectives
• Describe the bacterial agents discussed in this chapter in terms of their morphologic
characteristics, taxonomy, and growth conditions.
• Identify the four stages of syphilis—primary, secondary, latent, and tertiary—according to
their clinical symptoms, antibody production, transmission, and infectivity.
• Explain congenital syphilis, including transmission and clinical manifestations.
• Define reagin, cardiolipin, and biological false-positive results.
• Differentiate reagin and treponemal antibodies, including their specificity and association
with disease.
• Identify the various serologic methods that use specific or nonspecific nontreponemal
antigens.
• Describe the basic principles for the rapid plasma reagin (RPR), Venereal Disease
Research Laboratory (VDRL), fluorescent treponemal antibody absorption (FTA-ABS), and
microhemagglutination test for antibody to Treponema pallidum (MHA-TP) assays.

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 Objectives (cont’d)
• Compare Borrelia spp. to the other spirochetes discussed in this chapter, including its
morphologic characteristics and growth conditions.
• Describe the pathogenesis for relapsing fever and Lyme disease, including the routes of
transmission, vectors, and disease presentation.
• Explain the methodology and clinical significance for using a two-step diagnostic
procedure for Borrelia spp. infections.
• Describe the pathogenesis associated with leptospirosis, including the two major stages of
the disease and the recommended clinical specimens.
• Describe Brachyspira spp., including potential pathogenesis, appropriate specimen,
transmission, and clinical significance.
• Correlate patient signs and symptoms with laboratory data to identify the most likely
etiologic agent.

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General Characteristics
• Demonstrates helical (spiral shaped),
gram-negative bacilli.
• Genera are differentiated by:
• Number of axial fibrils
• Number of insertion disks
• Biochemical tests
• Metabolic features

Note
endoflagella

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Spirochetes
• Microscopy:
– Thin, tightly coiled, flattened helically shaped Gram negative bacteria,
0.1 – 0.5µm; axial filaments; corkscrew motility
– Phase contrast or Dark-field microscopy
• Moves in a corkscrew fashion through its environment
– Thought to enable pathogenic spirochetes to burrow through hosts’
tissues
• Three genera cause human disease:
– Treponema – Venereal disease and Non Venereal disease
– Borrelia – Lyme disease (B. burgdorferi) and Relapsing fever (B.
recurrentis)
– Leptospira interrogans – Leptospirosis
• Treponema – Pathogens – HUMANS ONLY!
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Treponema pallidum

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Treponema spp.
• Are best observed using dark-field microscopy.
• Pathogenic treponemes are microaerophilic.
• Epidemiologic factors and pathogenesis
• Enter host by penetrating mucous membranes.
• Entering breaks the skin.

• Disease:
• T. pallidum causes syphilis:
• Primary—Appearance of chancre
• Secondary—Fever, weight loss, and widespread rash
• Early latent—Subclinical but not dormant (<1 year)
• Latent—Asymptomatic and noninfectious (>1 year)
• Tertiary—Tissue-destructive phase (10 to 25 years)
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Spirochetes – Treponema
• T. pallidum pallidum is most widespread
– Causative agent – syphilis (STD / VD)
– Reservoir – Humans only
– Culture – Easily destroyed (Sensitive)
– Animal cell culture (Fastidious)
– Transmission – almost solely via sexual contact
– Can also be spread from an infected mother to her fetus
– Can result in fetal death or mental retardation and malformation
– Virulence – motility
– Diseases – 4 phases (10, 20, Latent, 30) and Congenital Syphilis
– Immune response – Produce various Non-specific Ab’s (Reagin) and
Specific Treponemal Ab’s

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RPR test
• RPR principle –
– Detect non-specific Ab called reagin which react with cardiolipin
antigen reagent
– Screening test for syphilis

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 Syphilis – different phases:
• Primary (10) Syphilis – Chancre (small, painless lesion on genitals, mouth, fingers, lips)
– Extremely infectious → lasts 3-6 days → no scarring→ spontaneously
dissappear
• Secondary (20) Syphilis – Spread → blood
– Widespread rash → last months, Extremely infectious
• Latent Syphilis – Clinical inactive (No signs & symptoms)
– Latent → 30 yrs
– Relatively uncommon → due to effective antibiotic therapy
• Tertiary Syphilis – Gummas (‘rubbery’ lesions in bones, CNS, skin)
– May affect any body tissue → neurosyphilis or cardiovascular
– Complications → inflammation & hyper-immune response
• Congenital Syphilis – Fetal death (10 or 20 syphilis); mental retardation, fetal
malformation, widespread rash (Mother has latent syphilis)
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Spirochetes of Treponema pallidum pallidum

Copyright © 2011 Pearson Education Inc. Figure 21.10

Serodiagnosis
• Treponemal antibody testing
• Antibodies toward the organism

• Nontreponemal antibody testing

• Reagin antibodies produced toward mammalian cells
• Two common flocculation tests
• VDRL is a quantitative test.
• RPR is used for presumptive serologic screening.

• The RPR test is a nontreponemal testing procedure for the

serologic detection of syphilis.
• The RPR card antigen suspension is a carbon- particle cardiolipin
antigen that detects reagin, an antibody like substance present in
the sera from syphilitic persons and occasionally in sera of persons
with other acute orCopyright
chronic conditions.
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Clinical presentations of Syphilis

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 Lab diagnosis – Syphilis:
• 10, 20, Congenital Syphilis – detect Ab’s against bacteria causing syphilis
• Tertiary Syphilis – difficult to diagnose
• Specimens: Blood, body fluids (CSF, discharge), tissue
• IgM (↓ with therapy) appear first then IgG (Persist longer)
Tests: (Non-treponemal tests) and(Treponemal tests)
SCREENING Tests: CONFIRMATORY Tests:
– VDRL FTA-abs
(Venereal Disease Research Laboratory) (Fluorescent Treponemal Ab. Absorption)
– RPR TPHA
(Rapid Plasma Reagin) (Treponema Pallidum Haemagglutination Assay)
– EIA (Treponemal tests) DARKFIELD MICROSCOPY → Discharge
(Enzyme Immunoassay – IgG & IgM)

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Treponema testing

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Timing of serologic responses in syphilis infection
 Spirochetes

• Treponema
– Prozone phenomenon – screening undiluted specimens with non-
treponemal test alone.
– Lead to false negatives due to high titers of Ab.
– Detected – Test diluted (higher) & undiluted serum samples
– Commonly seen in early infection and co-infection with HIV
– Diluting the serum, the blocking antibody is also diluted decreasing
its concentration – proper precipitation reaction to occur.
– Biological false positives in late stage during chronic infections due
to lack of sensitivity (non-treponemal test).

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Prozone phenomenon

No crosslinking of
Abs – beads do not
agglutinate
Prozone phenomenon
Spirochetes
• Treatment
– Penicillin is the drug of choice
– Ineffective against tertiary syphilis
• Prevention – Abstinence and safe sex

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Spirochetes
• Treponema
• Nonvenereal treponemal diseases
– Three non-sexually transmitted diseases:
– Primarily seen in impoverished children in unsanitary conditions
– Bejel (Endemic nonvenereal syphilis) – T. pallidum endemicum
– Yaws – T. pallidum pertenue is the causative agent
– Pinta – T. carateum is the causative agent

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Borrelia spp.
• Causes borreliosis or relapsing fever and Lyme disease..
• Epidemiologic factors and pathogenesis
• Relapsing fever
• Fever, headache, and myalgia within 2 to 15 days after infection.
• Louseborne: B. recurrentis
• Tickborne: B. hermsii, B. turicatae, B. parkeri, and B. mazzotti
• Lyme disease
• Is caused by B. burgdorferi.
• Is transmitted by the hard tick (genus Ixodes).
• Three stages:
• Erythema migrans—Ring-shaped skin lesion and non-specific symptoms
• Arthritis and neurologic disorders—Weeks to months after infection
• Chronic arthritis or acrodermatitis chronica atrophicans (ACA)
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Spirochetes
• Borrelia
– Lightly staining, Gram-negative spirochetes, larger in comparison
– Two species cause disease in humans:
B. burgdorferi B. recurrentis Borrelia sp.
Hard ticks Body louse Soft ticks
↓ ↓ ↓
LYME DISEASE EPIDEMIC or ENDEMIC
RELAPSING FEVER

– Tick life cycle important in understanding spread of Lyme disease

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Life cycle of the deer tick Ixodes

Copyright © 2011 Pearson Education Inc. Figure 21.15

Borrelia burgdorferi

Copyright © 2011 Pearson Education Inc. Figure 21.14

 Spirochetes
• Borrelia
– Lyme disease
– Shows a broad range of signs and symptoms
– Three phases of disease in untreated patients:
– Expanding red “bull’s-eye” rash occurs at infection site in 75%
cases
– Neurological symptoms and cardiac dysfunction (10% cases)
– Severe arthritis that can last for years
– Result of the body’s immune response

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Lyme Disease Pathology

• Borrelia
– Lyme disease
– Increase of cases in the United States
– Humans coming in closer association with Borrelia-infected
deer ticks
– Antimicrobial drugs effectively treat first stage of Lyme disease
– Treatment of later stages difficult because symptoms primarily
result from the immune response
– Prevention is best achieved by avoiding ticks

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Spirochetes
• Borrelia
– Relapsing fever (epidemic and endemic)
– Characterized by recurring episodes of septicemia and fever,
seperated by asymptomatic periods due to:
– Body’s repeated efforts to remove the spirochetes
– Cyclic variation of Borrelia surface antigens

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 Diagnosis
• Direct detection
• Observation of the organism using dark- or bright-field microscopy is
useful in cases of relapsing fever.
• B. burgdorferi is best visualized using Warthin-Starry silver stain.

• Cultivation using Kelly medium

• Serodiagnosis
• Is the standard method for diagnosing Lyme disease.
• Immunoblotting confirms positive tests.
• Molecular methods are used for diagnosis.

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Leptospira
• Two major groups
• Leptospira interrogans sensu stricto (human leptospirosis)
• L. biflexa (environmental strain)
• Epidemiologic factors and pathogenesis
• Causes leptospirosis, a zoonosis.
• L. interrogans can infect most animals worldwide.
• Humans become infected through direct or indirect contact with urine or
blood from an animal.
• Organisms enter through breaks in the skin or conjunctiva

• Disease ranges from mild fever (anicteric) to severe organ dysfunction

(icteric).
• Cultured to semisolid media enriched with Fletcher or Stuart rabbit serum.
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 Spirochetes
• Leptospira (L. interrogans)
– Highly motile, obligate aerobic, axial filaments
– Characteristic hooked spirochete (resemble - ?)
– Reservoir – found in numerous wild and domestic animals → Zoonosis
– Transmission – enters cuts/abrasions in skin and mucous membranes
via direct (urine of infected animal) or indirect (lakes, streams etc.)
– Disease – Leptospirosis
– Travels via the bloodstream → CNS, liver & kidney, damage blood vessel
linings
– Bacteremia eventually resolves → only in kidney → URINE!
– Eradication – Impractical due to the various animal reservoirs
– Prevention – Vaccine available for livestock and pets

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Leptospira interrogans

Copyright © 2011 Pearson Education Inc. Figure 21.18