Spirochetes

-Long, thin flexible w/ characteristic spirals

-Possess cytoplasmic & outer membranes
-Thin peptidoglycan wall
-Motile
**periplasmic flagella**: attached at ends of bacteria, wrap around cell body, e& end near middle of bug
--> rotation of periplasmic flagella --> typical cork-screw motility of spirochetes (involv. in disseminiation throughout body)

Treponema pallidum pallidum

Other Treponema:

Borrelia recurrentis & hermsii

Borellia burgdorferi

Leptospira interrogans

Shape

Helical bacillus (very long and thin, too thin to see)

Helical bacillus (visible)

Helical bacillus

Helical bacillus

Aerobicity

Microaerophilic

Microaerophilic

Microaerophilic

Aerobe

-visible by light microscopy w/ aniline dyes

-seen in blood smear

Characteristics

Optimal temp 30C

Variable Major Protein:

--> antigenic variants cause cycles/relapses
--> each bacterium has ~30 genes for VMP (major surface
protein)
--> Each VMP gene diff, so Ab directed vs. one VMP won't kill
bacteria expressing another VMP
Virulence Factors

Expression Plasmid (EP)

--> contains expression site of VMP, w/ single VMP gene
Storage Plasmid (SP):
--> contains library of ~30 unexpressed VMP genes, which can
be switched into EP expression site --> cause Ag variation

Pathophys

Reservoir

Coming into contact with urine or water

contaminated by urine of infected animals

T. pallidum (pallidum): syphilis

T. pallidum (pertunue): yaws
T. pallidum (endemicum): endemic syphilis
Trepnoma carateum: pinta

-High bacteremia

**Obligate parasite of humans**

-Transmission: arthropods (ticks & lice)

-Transmission: small, hard-bodied ticks

Non-pathogens found in oral cavity & perianal

From rodents to humans via ticks (hermsii)

Human to Human via lice (recurrentis)

To humans via ticks

--> DEER req. for adult tick phase

-Transmission: mucuous embranes or breaks in

skin
Rodents, Dogs, Cattle, Swine

Transmission (syphilis): direct, sexual contact

Urine - may contaminate water

Primary Syphilis: **CHANCRE** (days to weeks) - local infection

--> Penetrates epidermis/mucous membrane & estab. local infection = chancre
--> chancre = round, painless lesion 1-2 cm in diameter, often ulcerated; contains large #s of bugs
--> spontaneously heals after ~1-5 weeks

T. pallidum endemicum
Endemic (nonvenereal) syphilis
Tropics of Africa & Asia
Spread by direct contact

Secondary Syphilis: **RASH** (weeks to months) - disseminated infection

--> ~6 weeks after chancre occurs
--> multiple skin lesions & lymphadenopathy w/ fatigue & malaise
--> may have involv. of internal organs (ex: meningovascular syphilis)
--> large #s of bugs in skin lesions
--> spontaneously heals after ~2-6 wks, but can recur

T. carateum:
Pinta
Contagious, non-venereal dz
Primitive Latin America
Chronic depigmenting skin lesions on distal extremities

Latent Syphilis: (asymptomatic)

--> (1/3 patients): persist for life w/no further complications
--> (1/3 patients): "spontaneous" biological cure: no signs of infection, loses serological reactivity
Diseases

Tertiary Syphilis "late": (Persistent infection with severe sequelae) (months to years later)
Gummatous:
--> granulomatous lesions w/ accumulations of lymphocytes & macrophages reacting to few # of bugs
--> immune response --> marked tissue destruction & pathology
--> can occur anywhere in body
Neurosyphilis:
--> long-term infection of CNS
--> paresis: infection of brain w/ psych effects
--> tabes dorsalis: infection of lower spinal column w/ loss of sensory & motor fcn in lower extremities
Cardiovascular syphilis:
--> esp aorta --> aortic aneurisms

T. pallidum pertenue
Yaws
Non-venereal, communicable dz in Africa & Asia
Nondestructive skin lesion, bad bone deformities

Relapsing fever:
Louse borne (B. recurrentis):
--> Epidemic human to human by lice
-->more severe & more relapses
--> severe damage to internal organs: liver necrosis, miliary
splenic abscesses, CNS hemorrhage, myocariditis, GIT & renal
lesions
Tick-borne (B. hermsii):
--> Endemic rodents primary host and is spread by ticks
Both Diseases:
-Cyclic dz w/ relapses d/t Ag variation of bugs
--> Each cycle rep. a new Ag variant w. diff. VMP
-Patient improves after 3-5 days, then undergoes RELAPSE
--> cycle repeat 2-5x

Stage 1: Local infection (days to weeks)

--> Erythema migrans = red rash with expanding margin
-->Fever, malaise, swollen nodes
--> lasts 3-4 wks
Stage 2: Disseminated infection (weeks to months)
--> Severe malaise, multiple skin lesions, myalgia/ arthralgia,
lymphadenopathy
--> Neurologic- Bell's pals, neuritis, enhephalitis
--> Cardiovascular- cardiac arrhythmias
Stage 3: Persistent infection (months to years)
***Arthritis***
--> Chronic neurologic dz
--> Raised skin lesions (in Europe)
--> 10% have persistent sx

Periodontal Disease
Accumulation of normal flora, incl. oral spirochetes &
fusiform anaerobic bugs in gingivial crevices around teeth [sx]: Fever, headache, rigors, muscle& joint pain, conjunctivitis,
Inflamm, reraction of gums, exposure of tooth root
macular &/or petechial rash
Acute necrotizing gingivitis/ Trench Mouth

[mild - fatal]
-Incubation: 7-14 days
[onset sx]:
-High fever, chills
-HA
-Severe myalgias of legs & back
-Confusion
-Conjunctival suffusion
-Skin rash (maculopapular, petechial, purpuric,
peripheral gangrene)
-lymphadenopathy, haptomegaly, acalculous
cholecystitis
Secondary phase/ Immune phase
(leptospires gone from blood & CSF, but persist in
urine & aqueous humor)
-Recurrence of fever
-Meningismus
-CSF pleocytosis
Weil's syndrome:
-Severe illness w/ hemorrhage, azotemia,
jaundice
-Associated w/ L. interrogans serovar
icterohaemorrhagiae

Congenital:
--> infection of fetus by transplacental passage of bug by mother in early stages of syphilis (<1 yr duration)
--> miscarriage, stillbirth & earlyor late sx in live born children

Specimen

Exudate from skin

Blood

Serum, skin biopsy

Blood, CSF, urine

Visualized via:
Darkfield microscopy **definitive dx**
Silver impregnation stains
Immunofluorescence

Blood smears:
-Shows spirochetes w/ broad spirals
-Animal inoculation to verify infection

**Clinical dx backed by serological tests**

**Urine is positive for weeks to months**

Nontreponemal tests: Detect Ig against cardiolipin (VDRL, RPR)

--> titer decr & turns (-) after effective therapy
--> false (+) d/t: autoimmune dz, pregnancy, IVDA

Some have:
--> Proteus agglutinin OX-K titers
--> (+) serologic tests for syphilis (STS)
--> Bugs in CSF (10-15%) w/CNS sx

Lab Diagnosis
Treponemal tests: Detect Ig against T. pallidum (FTA-ABS, MHA-TP)
--> confirmatory test for syphillis
--> (+) for life

Treatment

-Characteristic hx & sx: tick bite followed by erythema migrans Culture of blood may be positive 1st week, but
may require weeks to grow
-Serological tests:
--> anti-B. burgdorferi Ab in serum
Serology: Ab agglutination of Leptospira
-- "2-tiered":
1. ELISA
2. Western Blot
-Culture
--> not reliable, req. special medium, take weeks

Dx confirmed by any of the following:

-characteristic lesions + (+) darkfield microscopy exam
-characteristic lesions & history (+) RPR
-reactive RPR + reactive treponemal test

-PCR
--> not used routinely

**PCN**
--> In fulminant 2 syphilis this treatment can cause Jarisch-Herxheimer reaction: fever, chills

Doxycycline
Amoxicillin

tetracycline

Long-term infections/severe cases:

Amoxicillin
PCN
Ceftriaxone

Dogs are vaccinated but still can shed it

Prevention/
Control

Notes

Doxycycline?
B-lactams?
Streptomycin?

Congenital syphilis is 100% preventable:

TX LAW: says a RPR test must be done @ 1st maternity visit & within 24 hr of delivery
(early sx): fulminant T. pallidum infection w/ many bugs present --> multiple manifestations
--> skin & mucous membrane lesions, lung, liver, bone involv.
(late sx): [early teens]: bone & tooth deformities, rhagades, interstitial keratitis, deafness, mental
impairment

-Highest in NE US & Great Lake states

Other dz that mimic relapsing fever:
leptospirosis, typhus, typhoid fever, dengue fever, malaria, &
typhoid

Southern Tick Associated Rash Illness (STARI)

--> Acts like normal lyme disease and is all over SE US
--> Amblyomma americanum (lone star) tick
--> Borelia lonestari

Occupational disease (formerly):

Sewer workers, veterinarians, dairy farmers who
have contact with urine of infected dogs and rats
Organism may live for weeks or more after being
shed in urine if stagnant water