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Chapter 23

The Spirochetes

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Spirochetes
 Helical-shaped, motile, unicellular bacteria
 0.1- to 3.0-µm wide by 5- to 20-µm long
 Exhibit various types of motion in liquid media
 Free-living or survive in association with animal or human hosts
 Treponema pallidum subsp. pallidum
 Syphilis
 T. pallidum other subspecies
 Borrelia
 Relapsing fever
 Lyme disease
 Leptospira
 Leptospirosis
 Spirillum minor
 Rat-bite fever
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Leptospires
 Leptospira
 Obligate aerobic helical rods 0.1-µm by 5- to 15-µm long that
are tightly coiled, thin, and flexible.
 Leptospirosis: L. interrogans
 20 serovars
 Most common
• Icterohaemorrhagiae, Australis, and Canicola
 Virulence factors
 Unknown but may include
• Reduced phagocytosis
• Soluble hemolysin
• Endotoxins

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Electron Micrograph (EM)
Photograph of L. interrogans

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Infections Caused By Leptospires
 Organisms in mud or water enter through
breaks in the skin or intact mucosa.
 Symptoms
 Initial phase
• Fever, headache, malaise, and severe myalgia
• Conjunctival suffusion seen in less than half
• Can involve hepatic, renal, and central nervous systems
 Renal lesions are interstitial nephritis with glomerular
swelling and hyperplasia.
 Illness lasts from less than 1 week to 3 weeks.

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Leptospires (Cont.)
 Late manifestations caused by host
immunologic response to infection.
 Weil’s disease: severe systemic disease
 Jaundice, acute renal failure, hepatic failure,
intravascular disease
• Can be fatal

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Epidemiology
 Zoonotic disease
 Animal workers or in rat-infested surroundings
• Dog, rats, and other rodents are principal hosts
 Excreted in urine
 Freshwater recreational exposure
• Water contaminated by urine
 Can survive for months in water

 Infection
 Enters by contact with infected urine

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Laboratory Diagnosis
 Specimen collection
 Collect blood or cerebrospinal fluid (CSF) during first week of
illness
 Collect urine: yield higher after first week
• Direct microscopic detection is not recommended.
 Isolation and identification
 Culture: Fletcher’s, Stuart’s, or Ellinghausen-McCullough-
Johnson-Harris (EMJH) medium
• Use 1 to 2 drops of patient sample
 Serology: microscopic agglutination test (MAT) for
serotyping
 Immunoglobulin M (IgM) enzyme-linked immunosorbent
assay (ELISA) test

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Antimicrobial Susceptibility
 Susceptible to
 Streptomycin
 Tetracycline
 Doxycycline
 Penicillin
• Some limited effectiveness if used early (before fourth
day of illness)

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Borreliae
 Borrelia spp.
 Helical bacteria 0.2 to 0.5 µm by 3 to 20 µm in length
 Spirals vary between 3 to 10 per organism
• Less tightly coiled than leptospires
 Relapsing fever
 B. recurrentis and B. duttonii
• Pediculus humanus louse-borne infection
 Epidemic relapsing fever
• Transmission by crushing or scratching lice into skin
 B. hermsii
• Tick-borne infection: Ornithodoros ticks
 Endemic relapsing fever
– Transmitted by saliva during bite
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Virulence Factors
 Relapsing fever
 Evade complement by acquiring and displaying
suppressive complement regulators
• C4b-BP
• Factor H
 Relapses are caused by antigenic variation.
• Specific antibodies are rendered ineffective.

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Relapsing Fever
 Symptoms
 Incubation period is 2 to 15 days.
 High fever (104°F) with shaking chills
• Periods of 3 to 7 days
 Delirium
 Severe muscle aches and pain in bones and joints
• Followed by remission and subsequent repeat of symptoms
• Sometimes hepatosplenomegaly and jaundice
 Neurologic symptoms
• Lymphocytic meningitis and facial palsy
 Rarely fatal

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Photograph of B. recurrentis

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Relapsing Fever (Cont.)
 Laboratory diagnosis
 Direct examination of spirochetes in blood
• Thick and thin films of Giemsa or Wright-stained smears
 Culture
• Kelly medium
• Animal inoculation (rarely)
• Serology is difficult and impractical.
 Antimicrobial susceptibility
 Tetracyclines are the drugs of choice.
• Death of spirochetes can cause sudden endotoxin release
(Jarisch-Herxheimer reaction).
 Fever, chills, headache, myalgia

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B. burgdorferi Virulence Factors
 Bacterial spread
 Binds plasminogen and urokinase-type
plasminogen activator to its surface
• Could act as a protease to promote tissue invasion
 Complement evasion
 Binds factor H

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B. burgdorferi Clinical Manifestations
 Stage 1
• Erythematous papule that rapidly expands
 Erythema chronicum migrans: classic “bulls-eye rash” in 60% of patients
– Peripheral edema with central clearing
 Stage 2: acute
• Symptoms
 Disseminated infection
 Secondary skin lesions
 Joint and bone pain
 Neurologic and cardiac pathology
 Splenomegaly
 Malaise and fatigue
 Stage 3: chronic
• Chronic cardiac symptoms
• Chronic neurologic symptoms
• Chronic arthritis (most common symptom)
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B. burgdorferi
 Epidemiology
 B. burgdorferi
• Lyme disease
 First described in Lyme, Connecticut
 North America and Europe
 B. garinii and B. afzelii
• Asia and Europe
 Transmission
 Tick bites
 Protective clothing and repellent prevent infection.

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B. burgdorferi Infections
 Treatment
 Antibiotics: early stages doxycycline
 Late stages show no usefulness of antibiotics.
 Detection
 Generally only screen those with symptoms and
high-risk factors
• Generally test by serology

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Serologic Tests
 ELISAs to demonstrate reactive antibody
 Western blot to verify specificity
 Detection of 2 of 3 IgM bands
• 24 (OspC), 39, and 41 (flagellin) kDa
 Detection of 5 of 10 immunoglobulin G (IgG)
bands
• 18, 21, 28, 30, 39, 41, 45, 58, 66, 93 kDa

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Treponemes
 Treponema pallidum subsp. pallidum
 Syphilis
 Treponema pallidum subsp. pertenue
 Yaws
 Treponema pallidum subsp. endemicum
 Endemic syphilis
 Treponema pallidum subsp. carateum
 Pinta

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Virulence Factors
 Penetrate intact mucous membranes
 Crosses placenta
 Dissemination throughout the body and organ
systems
 Antigenic variation
 May help evade immune system

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Syphilitic Infection
 Transmission
 Infection caused by sexual contact (mucous
membranes)
• Can enter via cuts, abrasions, or directly through intact
mucous membranes
 Can enter other sites such as the lip or
transplacentally
 Incubation period
 Disseminate throughout the body
 10 to 90 days (usually about 3 weeks)

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Syphilitic Infection (Cont.)
 Primary syphilis
 Chancre at infection site (usually one but
sometimes several in human immunodeficiency
virus (HIV)–positive patients)
• Clean, smooth base, edge slightly raised and firm
• Painless but may be tender
• Heals in 3 to 6 weeks
 Base contains spirochetes that can be identified
by dark field microscopy or immunofluorescence
or serology.

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Syphilitic Infection (Cont.)
 Secondary syphilis
 Begins 2 to 12 weeks after chancre appearance
 Widespread macular rash (syphilitic roseola),
particularly palms and soles of feet
 Secondary lesions
• Condylomata lata
 Moist, gray-white plaques teeming with spirochetes
 Systemic symptoms
• Lymphadenopathy, headache, lesions of the mucous
membranes and the skin, and rash

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Syphilitic Infection (Cont.)
 Latent syphilis
 Early latent phase: initial 4 years relapses occur;
patient is infectious
 Late latent phase: indefinite duration; sometimes
no complications ever appear
 Detected only through serology

 Late syphilis (tertiary)


 Late complications of syphilis involving many
organs

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Tertiary (Late) Syphilis
 Complications
 Central nervous system (CNS) disease,
cardiovascular abnormalities, aortitis and valve
insufficiency, and granulomatous lesions
(gummas) in any organ
 Asymptomatic CNS disease
 CSF abnormalities without symptoms
• Pleocytosis, elevated protein levels, depressed glucose

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Tertiary (Late) Syphilis (Cont.)
 Congenital syphilis
 Intrauterine infection
 Nonimmune hydrops: disease of placenta that
causes fetal death
 Hepatosplenomegaly, meningitis,
thrombocytopenia, anemia, and bone lesions
 Visible deformities
• Deformed tibias or teeth

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Syphilis Epidemiology and
Specimen Collection
 Transmission
 Sexual contact, direct injection, direct contact with
lesions, transplacental transmission
 Specimen collection
 Primary or secondary lesion is cleaned with saline
and gently abraded with dry, sterile gauze.
• Transfer serous fluid to slide with saline
 Coverslip and examine using darkfield microscopy
 Usually use serology or direct exam
 Do not use oral lesions because of nonpathogenic
oral flora

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Detection
 Nontreponemal tests (primary or secondary
stage only, later stages less than 1%)
 Venereal disease research laboratory (VDRL)
• Cardiolipin antigen is mixed with patient serum or CSF.
 If positive, flocculation occurs and can be read
microscopically.
 Rapid plasma reagin (RPR)
• Black carbon particles are bound to cardiolipin and mixed
with patient sera.
 Particles agglutinate, thus indicating a positive test.

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Detection (Cont.)
 Treponemal tests (all stages, although more
effective for secondary and late stages)
 Confirm nontreponemal tests
 Titers remain high despite treatment.

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Detection (Cont.)
 Fluorescent treponemal antibody absorption test
(FTA-ABS)
 Patient sera is absorbed against nonpallidum spirochetes.
 Absorbed serum is then placed with T. pallidum
organisms, and secondary antihuman antibody
conjugated to a fluorescein is added.
 T. pallidum–particulate agglutination test (TP-PA)
 Antigens to T. pallidum are absorbed to gelatin particles.
 Patient sera added, and gelatin agglutinates
 Enzyme immunoassay (EIA) test kits are not
comparable.

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Treatment
 Penicillin
 Long-acting is preferred
• Benzathine penicillin
 Doxycycline and tetracycline
 If penicillin allergies
 Can develop Jarisch-Herxheimer reactions

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Other Treponemal Diseases
 T. pallidum subsp. pertenue
 Yaws: chronic nonvenereal disease
• Central Africa, South America, India, Indonesia, and Pacific
Islands
• Primary, secondary, and tertiary stages
 Lesions are elevated, granulomatous nodules.

 T. pallidum subsp. endemicum


 Endemic syphilis (bejel)
• Spread by direct contact or eating utensils
 Resembles yaws
• Middle East and desert regions
 Papules that usually go unnoticed
– Gummas of skin, bones, and nasopharynx
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Other Treponemal Diseases
(Cont.)
 T. pallidum subsp. carateum
 Pinta: ulcerative or papulosquamous skin lesions
that depigment
 South and Central America

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