spirochetes Flashcards
Treponema pallidum microscopy
dark field only
Leptospira interrogans microscopy
Leptospira interrogans
Borrelia recurrentis microscopy
light microscopy
Borrelia burgdorferi microscopy
light microscopy
Treponema pallidum vector & reservoir
none
Leptospira interrogans vector & reservoir
Rats, mice, wild rodents, dogs, swine, cattle
Borrelia recurrentis vector and resevoir
“V. louse,tick
R. Rodents”
Borrelia burgdorferi vector and resevoir
V. tick (Ixodes ticks)
R. mouse, deer
Treponema pallidum transmission
Intimate sexual contact infective primary or secondary lesion
Passes through placenta resulting in congenital infection
No sexual spread >4 years after acquiring infection
Treponema pallidum disease
Syphilis
Leptospira interrogans transmission
Contact or ingest infected animal urine- contaminated water
Leptospira interrogans disease
Leptospirosis
Borrelia recurrentis transmission
Ticks or lice
Borrelia recurrentis disease
Relapsing fever
Borrelia burgdorferi transmission
Ticks
Borrelia burgdorferi disease
Lyme borreliosis
Treponema pallidum: Cultural Characteristics
long generation time - 30 hours
very sensitive to drying and heat (cannot be spread on surfaces)
microaerophilic (survives 3-5% oxygen)
differentiated by clinical associations only
structure - has 3 axial fibrils
obliterative endarteritis
characteristic of a lesion from syphilis
severe proliferating endarteritis (inflammation of the intima or inner lining of an artery) that results in an occlusion of the lumen of the artery
Pathogenesis of Syphilis
Passes through intact mucosa or abraded skin
Multiplies locally and disseminates to lymph nodes and other organs
Symptoms or signs when number of organisms reaches critical mass
Primary Syphilis
• consists of an ulcerative lesion at site of inoculation with regional adenopathy (inguinal for a genital lesion)
- Painless papule at site of inoculation which ulcerates – chancre
- Ulcer has smooth margins and crusted base
- Darkfield positive (organism can be collected from the chancre)
- Firm local adenopathy
- No systemic manifestations
- Heals spontaneously (self-limiting)
Secondary syphilis
systemic flu-like illness which may develop 2-10 weeks after primary lesion heals
- Papulosquamous rash – entire body including palms and soles (sandpaper- like)
- Moist areas→papules coalesce – condylomata lata (warts on genital areas)
- Other sites: hepatitis, aseptic meningitis, periostitis, nephritis (immune-complex type)
- Fever and generalized lymphadenopathy
- Heals spontaneously but may recur over four years
Untreated Syphilis
• 1/3 resolve the infection, i.e., cured
• Remaining 2/3 - 1/3 latent - 1/3 tertiary (late) syphilis Neurosyphilis Cardiovascular syphilis (prox. aorta) Late benign gummatous syphilis
Neurosyphilis
Asymptomatic – CSF infected without symptoms or signs
Meningovascular – Chronic meningitis → affects arteries and cranial nerves (base of brain – could lead to a stroke)
Paresis – Cortical degeneration with mental changes (cerebral cortex involvement)
Tabes dorsalis – Demyelination of posterior columns and dorsal roots
Loss of pain and temperature
Ataxia
Congenital Syphilis
Infection occurs in utero Normal at birth→multisystem disease later Rhinitis (purulent nasal discharge) Rash Bone and cartilage involvement (teeth) Liver, spleen, lymph nodes, CNS Prevent with treatment during pregnancy Routine screening recommended
Microscopic Diagnosis of Syphilis
Darkfield
Primary and secondary lesions
Direct Fluorescent Antibody Test
Immunofluorescence – monoclonal antibodies
Material from lesion or biopsy
PCR
(No cultures)
Syphilis Serology – Nontreponemal Tests
Reaginic antibodies
IgM and IgG against cardiolipin (membrane protein)
NOT directed against T. pallidum
VDRL – Venereal Disease Research Laboratories
Done on CSF
RPR – Rapid Plasma Reagin
Serum
Quantitated and used to follow treatment
Revert to negative after treatment of early disease (higher positives in early disease)
False positive tests common
Specific Treponemal Serology
- FTA-Abs – Fluorescent Treponemal Antibody-Absorption Test
- TPPA – PA = particle agglutination
- EIA and CIA (Chemiluminescence immunoassay)
Decrease false positives when confirming RPR
Remain positive for life
Fewer than 25% revert to negative (AIDS)
(higher positives in late disease)
FTA-Abs
Fluorescent Treponemal Antibody-Absorption Test
- Absorbed with non-T. pallidum treponeme
- Antigen is killed Reiter strain T. pallidum
TPPA – PA = particle agglutination
Treponemal antigens adsorbed onto gelatin particle or RBC
MHA-TP–Microhemagglutination Treponema pallidum
EIA and CIA
( Enzyme immunoassay (ELISA) ad Chemiluminescence immunoassay)
Cheap, automated, now in wide use for screening
* High false positive rate when used to screen low prevalence population
screening test
treatment of T. pallidum
Long acting formulation used (long generation time)
- Benzathine Penicillin G
- Treatment differs according to stage (primary and secondary get a one time injection, late gets IV infusion)
Jarisch-Herxheimer Reaction
Fever, chills, headache, hypotension
Release of toxic products from killed spirochetes
Alternative - Tetracyclines (not possible with some forms, must desensitize pcn allergies)
Borrelia
Borrelia are larger spirochetes that are visible in stained preparations. They have a mammalian reservoir with spread to humans by tick or louse vectors resulting in Relapsing Fever or Lyme Borreliosis
which spirochete can be seen on a blood smear?
B. recurrentis - on a Wright’s stained blood smear
Borrelia cultures
B. recurrentis – blood, serum or tissue-containing media
B. burgdorferi – Barbour, Stoenner, Kelly broth
not commonly done - usually rely on serologic tests
Relapsing Fever
B. recurrentis and related organisms escape immune recognition by altering their antigenic structure during infection
Gene switch from silent to expression locus (like N. gonorrhoeae) on plasmid
Relapses caused by emergence and multiplication of antigenic variants
Epidemiology – Relapsing Fever
Epidemic – Louse-borne relapsing fever in times of catastrophe such as war or famine - caused by B. recurrentis
Endemic – Tick-borne relapsing fever in
mountain regions of Western US. caused by other borrelia. associated with living in places with lots of rodents
Relapsing Fever: Clinical Manifestations
Fever Chills Muscle pain Headache Relapses – antigenic variation Resolves 3-5 days, remits after 7-9 days Each relapse is less severe
Diagnosis Relapsing Fever
Laboratory Diagnosis Blood smear Culture – rarely performed Serology Cross reactions with other spirochetes
Treatment of relapsing fever
Tetracycline, Erythromycin
Jarisch-Herxheimer reactions common
Epidemiology of Lyme Boreliosis
Zoonosis in which deer and white-footed mouse are primary reservoirs
- Spread by tick – Ixodes ricinus complex
Two year tick life cycle
All stages feed on humans
Nymphs in spring and summer major source
Pathogenesis: Lyme Borreliosis
Tick bite → multiply locally
Enter lymph or blood → disseminate to many sites
Antibody is associated with near disappearance of spirochetes
Suggests immune pathogenesis in late stage disease
Erythema migrans
Expanding erythematous lesion at site of tick bite - bulls-eye pattern
- Organisms cultured from biopsy
- Accompanied by flu-like illness
Early Disseminated Lyme Disease
Days to weeks after primary infection
Fatigue, headache, fever, malaise
Multiple skin lesions
Neurologic: Meningitis, radiculitis, facial nerve paralysis(most common) , other neuropathies
Cardiac: Heart block (more common), myocarditis
Arthritis: develops in 60% untreated – weeks to years later
Late Stage Lyme Disease
Arthritis
Recurrent episodes of pain and swelling of large joints especially knees
Encephalopathy
Fatigue, memory loss, cognitive defects
Controversial
Skin: acrodermatitis chronica atrophicans
Laboratory Diagnosis of Lyme Borreliosis
Culture is usually not available Serology ELISA or IFA Both IgM and IgG responses measured Confirm with western blot
DNA detection by PCR
Skin biopsy – 65%-75%
Synovial fluid – 50%-85%
CSF – 25%
Therapy and Prevention of Lyme Borreliosis
Antimicrobial therapy
Early – Doxycycline, amoxicillin, cefuroxime orally
Late – Oral as above or
Penicillin G or ceftriaxone parenterally
Prevention with repellants
Tick checks
Vaccine
Recombinant OspA Vaccine removed from market
Leptospira interrogans - Structural and Cultural Characteristics
Thin spirochete – 6-20 μm x 0.1μm
218 serovars
Specific syndromes associated with serotypes are not distinctive
Leptospires can be cultivated in liquid media
Epidemiology – Leptospirosis
Zoonosis with many animal hosts
Rats, mice, wild rodents, dogs, swine, cattle
Transmission
Ingestion of or direct contact with food or water contaminated with infected animal urine
Pathogenesis – Leptospirosis
After infection, spirochetes invade bloodstream and affect endothelial cell integrity causing vasculitis in many organs
Immune complexes found in kidney
Organisms excreted in urine
Leptospirosis first stage
(Bacteremia)
Fever, headache, myalgias, conjunctival suffusion, abdominal pain
Leptospirosis second stage
(Immune)
Aseptic meningitis or generalized illness with myalgias, headache, uveitis and rash
Leptospirosis severe stages
stages blend
Prominent hepatitis, kidney involvement, hemorrhage
Mortality 5-10%
Leptospirosis: Diagnosis
Culture blood and CSF (early), urine (late)
Serology – Microscopic agglutination test (MAT) after first week (difficult)
ELISA and IHA tests less standardized (but easier)
PCR very sensitive in research laboratories
Leptospirosis: treatment
Penicillin or doxycycline
