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Spirochetes and RickettsiaeSeptember, 2008Ken B. Waites, M.D., F(AAM)

Objectives To review and discuss

microbiological characteristics epidemiology virulence factors associated diseases laboratory detection

Of: Treponema pallidum Borrelia spp. Leptospira spp. Rickettsiae Ehrlichia spp.

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Treponema pallidum• Motile spirals 5-15 µm• Has not been

successfully cultured orsubcultured on artificialmedia but may multiply inrabbit epithelial cellcultures

• Very susceptible toenvironmental conditions

• Does not stain withaniline dyes

Stages of Syphilis• Primary chancre at site of inoculation:

painless hard chancre (1-3 weeks)• Secondary manifestations due to

spirochetes– rash – may be recurrent– mucous patches– condylomata lata– spirochetemia

• Lesions of other organs; hepatitis,meningitis

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Stages of Syphilis• Latent – no signs or symptoms

–early (less than 2 years)–late (later than 2 years)

• Tertiary syphilis:–cardiovascular – aortitis, valve lesions–benign tertiary (gumma formation)–central nervous system involvement–paresis (general paresis of the insane–tabes dorsalis (spinal cord)–meningovascular

Oral & Genital Chancres

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Skin Lesions of SecondarySyphilis

Condyloma lata

Disseminated rash

Tertiary Syphilis “Gumma”

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Congenital Syphilis• Transplacental• “Snuffles”• pneumonia and

hepatitis• tooth malformation

• Hutchinson’s incisors• Mulberry molars

• 8th nerve deafness• saber shins due to

persistent inflammation

“Notched” incisors

Diagnosis of Syphilis: Darkfield• Useful only if

lesion is present• Not useful for oral

lesions• Positive sooner

than serologytests

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Non Treponemal Tests (RPR, VDRL)• Screening test – inexpensive, easy and quick• Cardiolipin, lecithin, cholesterol antigens• Can be titered

– rising titer indicates active disease– falling titer indicates adequate therapy

• Reflect overall activity of disease• Limitations

– may become reactive in late primary disease– some patients who have been treated late in

course of disease may become “serofast” for life– false positives in some autoimmune, viral or

acute febrile states

RPR Nontreponemal Test

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Treponemal Tests

Treponema pallidum Particle Agglutination(TPPA)

–Gelatin particles sensitized with TP antigen–No absorption needed

Fluorescent Treponemal Antigen(FTA) Test

• FTA-ABS becomes reactive earlier than RPR• a few false positives in autoimmune disease• serofast for life

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Borrelia Characteristics• Large spirochetes

20-30 µm in length• Motile• Stainable with aniline

dyes (Giemsa)• May be observed

with conventionalmicroscopy

• Cultivable in artificialmedia

Relapsing Fever:B. recurrentis & others

– Endemic in Western U.S.– Transmission

» Ornithodoros - ticks on rats» Pediculus – human body lice» Infected rats by contact with blood

– Clinical» Febrile bacteremia with chills and headache» 3-10 recurrences common

– Diagnosis» Culture – rarely successful» Antibody detection» Antigenic shifts confound diagnosis and serology

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Lyme DiseaseBorrelia burgdorferi

• Agent identified in 1984• Reported from over 40 states• Not endemic in Alabama• Transmitted mainly by Ixodes ticks• Reservoir in mice• Clinical

• bloodstream invasion seeds tissues – nerves, heart, joints• three distinct stages

1. erythema chronicum migrans rash at site of tick bite2. neural and heart problems – months3. joints – arthritis – years

• Diagnosis – antibody production –problematic

Erythema Chronicum Migrans Rash

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Ixodes Tick Vectorfor Lyme Disease

Leptospira• Spirals – thin, tightly

coiled 10-20 µm• Obligate anaerobes• Grow in artificial

media supplementedby rabbit serum(Fletcher’s)

• May require 4 weeks• Leptospira interrogans

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Leptospirosis• Epidemiology

• parasitize animals, i.e., dogs, cats, pigs, other livestock,who carry them in kidney.

• Occasionally infect humans who come in contact with soilor water contaminated with urine.

• Pathogenesis – entry through mucous membranes or breaksin skin, gain access to bloodstream, kidney, liver, CNS

• Clinical – FUO, aseptic meningitis, jaundice, nephritis –Weil’s disease (L. interrogans serovar icterohaemorrhagiae)

• Diagnosis– culture: blood, CSF, urine– serology– darkfield examination

Rickettsiae• Obligate intracellular organisms• Most (except Coxiella) transmitted to humans by

arthropods• Contain both RNA and DNA• Cell walls similar to Gram negative bacteria• Stain with Giemsa• Reproduce by binary fission• Not routinely grown in diagnostic microbiology labs• Quickly destroyed by heat, drying and bactericidal

chemicals• Use serology for diagnosis

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Rickettsiae in Cytoplasm of Host Cell

Rickettsia: Pathology

• Organisms multiply in endothelium ofsmall vessels → vasculitis

• Cells swell, become necrotic →thrombose vessel

• Disseminated IntravascularCoagulation

• Organism may replicate withinphagocytic cells

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Selected Rickettsial Diseases of USA

Granulocyticehrlichiosis

MiceTickAnaplasmaphagocytophilum

Monocyticehrlichiosis

Deer, dogsTickEhrlichiachafeensis

Q feverLivestock, fish,birds, marsupials,arthropods

NoneCoxiella burnettii

Rocky Mt.Spotted Fever

Dogs, rabbits,rodents

TickR. rickettsii

Murine TyphusRodentsFleaR. typhi

Louse-borneTyphus

Flying squirrelLouse,Flea

Rickettsiaprowazekii

DiseaseReservoirVectorsAgent

Macular Rash of RMSF

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Ehrlichia chafeensis in amonocyte