spirochetes

Question 1

Treponema pallidum microscopy

Answer 1

dark field only

Question 2

Leptospira interrogans microscopy

Answer 2

Leptospira interrogans

Question 3

Borrelia recurrentis microscopy

Answer 3

light microscopy

Question 4

Borrelia burgdorferi microscopy

Answer 4

light microscopy

Question 5

Treponema pallidum vector & reservoir

Answer 5

none

Question 6

Leptospira interrogans vector & reservoir

Answer 6

Rats, mice, wild rodents, dogs, swine, cattle

Question 7

Borrelia recurrentis vector and resevoir

Answer 7

“V. louse,tick

R. Rodents”

Question 8

Borrelia burgdorferi vector and resevoir

Answer 8

V. tick (Ixodes ticks)

R. mouse, deer

Question 9

Treponema pallidum transmission

Answer 9

Intimate sexual contact infective primary or secondary lesion

Passes through placenta resulting in congenital infection

No sexual spread >4 years after acquiring infection

Question 10

Treponema pallidum disease

Answer 10

Syphilis

Question 11

Leptospira interrogans transmission

Answer 11

Contact or ingest infected animal urine- contaminated water

Question 12

Leptospira interrogans disease

Answer 12

Leptospirosis

Question 13

Borrelia recurrentis transmission

Answer 13

Ticks or lice

Question 14

Borrelia recurrentis disease

Answer 14

Relapsing fever

Question 15

Borrelia burgdorferi transmission

Answer 15

Ticks

Question 16

Borrelia burgdorferi disease

Answer 16

Lyme borreliosis

Question 17

Treponema pallidum: Cultural Characteristics

Answer 17

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

Question 18

obliterative endarteritis

Answer 18

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

Question 19

Pathogenesis of Syphilis

Answer 19

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

Question 20

Primary Syphilis

Answer 20

• 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)

Question 21

Secondary syphilis

Answer 21

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

Question 22

Untreated Syphilis

Answer 22

• 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

Question 23

Neurosyphilis

Answer 23

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

Question 24

Congenital Syphilis

Answer 24

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

Question 25

Microscopic Diagnosis of Syphilis

Answer 25

Darkfield Primary and secondary lesions
 Direct Fluorescent Antibody Test Immunofluorescence – monoclonal antibodies Material from lesion or biopsy
 PCR (No cultures)

Question 26

Syphilis Serology – Nontreponemal Tests

Answer 26

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

Question 27

Specific Treponemal Serology

Answer 27

* 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)

Question 28

FTA-Abs

Answer 28

Fluorescent Treponemal Antibody-Absorption Test - Absorbed with non-T. pallidum treponeme - Antigen is killed Reiter strain T. pallidum

Question 29

TPPA – PA = particle agglutination

Answer 29

Treponemal antigens adsorbed onto gelatin particle or RBC | MHA-TP–Microhemagglutination Treponema pallidum

Question 30

EIA and CIA

Answer 30

( 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

Question 31

treatment of T. pallidum

Answer 31

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)

Question 32

Borrelia

Answer 32

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

Question 33

which spirochete can be seen on a blood smear?

Answer 33

B. recurrentis - on a Wright's stained blood smear

Question 34

Borrelia cultures

Answer 34

B. recurrentis – blood, serum or tissue-containing media B. burgdorferi – Barbour, Stoenner, Kelly broth not commonly done - usually rely on serologic tests

Question 35

Relapsing Fever

Answer 35

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

Question 36

Epidemiology – Relapsing Fever

Answer 36

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

Question 37

Relapsing Fever: Clinical Manifestations

Answer 37

``` Fever Chills Muscle pain Headache Relapses – antigenic variation Resolves 3-5 days, remits after 7-9 days Each relapse is less severe ```

Question 38

Diagnosis Relapsing Fever

Answer 38

``` Laboratory Diagnosis Blood smear Culture – rarely performed Serology Cross reactions with other spirochetes ```

Question 39

Treatment of relapsing fever

Answer 39

Tetracycline, Erythromycin | Jarisch-Herxheimer reactions common

Question 40

Epidemiology of Lyme Boreliosis

Answer 40

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

Question 41

Pathogenesis: Lyme Borreliosis

Answer 41

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

Question 42

Erythema migrans

Answer 42

Expanding erythematous lesion at site of tick bite - bulls-eye pattern - Organisms cultured from biopsy - Accompanied by flu-like illness

Question 43

Early Disseminated Lyme Disease

Answer 43

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

Question 44

Late Stage Lyme Disease

Answer 44

Arthritis Recurrent episodes of pain and swelling of large joints especially knees Encephalopathy Fatigue, memory loss, cognitive defects Controversial Skin: acrodermatitis chronica atrophicans

Question 45

Laboratory Diagnosis of Lyme Borreliosis

Answer 45

``` 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%

Question 46

Therapy and Prevention of Lyme Borreliosis

Answer 46

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

Question 47

Leptospira interrogans - Structural and Cultural Characteristics

Answer 47

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

Question 48

Epidemiology – Leptospirosis

Answer 48

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

Question 49

Pathogenesis – Leptospirosis

Answer 49

After infection, spirochetes invade bloodstream and affect endothelial cell integrity causing vasculitis in many organs Immune complexes found in kidney Organisms excreted in urine

Question 50

Leptospirosis first stage

Answer 50

(Bacteremia) | Fever, headache, myalgias, conjunctival suffusion, abdominal pain

Question 51

Leptospirosis second stage

Answer 51

(Immune) | Aseptic meningitis or generalized illness with myalgias, headache, uveitis and rash

Question 52

Leptospirosis severe stages

Answer 52

stages blend Prominent hepatitis, kidney involvement, hemorrhage Mortality 5-10%

Question 53

Leptospirosis: Diagnosis

Answer 53

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

Question 54

Leptospirosis: treatment

Answer 54

Penicillin or doxycycline