ICL 2.10: Treponema Flashcards
what’s the micriobiology of treponema?
spirochete
NOT all spiral shaped bacteria are spirochetes
what diseases do spirochetes cause?
- gonorrhea
- syphilis
- salmonella
- shigellosis
which bacteria are spirochetes?
- borrelia
- leptospira
- treponema
how is syphilis spread?
sexual contact
~60% of US cases are men who have sex with men (CDC)
no known animal reservior!!
how can syphilis be grown?
It will grow in rabbit testes, and can be isolated that way, but no disease results in the infected rabbit. There is no animal model
is syphilis incidence increasing or decreasing?
increasing…
Easily detected and treated, so no good reason for this situation
where did syphilis come from?
MAY have origins in Africa or South America as a skin disease called Yaws
the causative agents of syphilis and of yaws are nearly indistinguishable
T. pallidum pallidum vs. T. pallidum pertenue
there appears to be cross immunity between the two
what’s the progression of syphilis vs. yaws?
YAWS
primary lesion in yaws –> ulcerating papule (small solid conical elevation of the skin)
localized scarring, even some bone destruction, but almost never involves viscera or nervous system
not transmitted transplacentally
SYPHILIS
primary syphilis –> chancre
MUCH more invasive and damaging
can involve ANY part of the body with a blood supply….
where on the range of bacterial mechanisms of pathogenesis does treponema pallidum fall?
nontoxic
highly invasive
damage from immune system
how many stages of syphilis are there?
3
what is primary syphilis?
painless ulcer with heaped up edges
occur in most indivs. within 3-6 weeks
may be hidden and since they’re painless, sometimes people don’t even know they’re there
high number of spirochetes
vaginal chancres common – whatever the site though, it’s a local infection
disappears after a few weeks
what is the immune response to primary syphilis?
TH1-skewed response
spirochetes surrounded by CD4+ and CD8+ T cells, plasma cells, macrophages producing IL-2 and IFN-γ
chancres disappear after a few weeks
what happens during secondary syphilis?
dissemination from initial site(s) of infection
distribution via blood throughout body because it traverses the tight junctions between endothelial cells
may also use transcytosis to spread through the endothelium
what are the symptoms of secondary syphillis?
fever, malaise, arthralgia
and arthritis common
hepatosplenomegaly
new cutaneous lesions usually after 3 months = condylomata lata
rash includes palms and soles
aka “great pox”
what is tertiary syphilis?
occurs in ~30% of untreated cases, following latent phase
during the latent phase, no symptoms but Ab titers remain high because treponemes are still present
tertiary syphilis has severe consequences = granulomatous lesions called gummas in skin, bones and liver
literally looks like rotting flesh….
you can also get neurosyphilis or cardiovascular syphilis
what is one of the serious side effects of tertiary syphilis?
nerosyphilis with:
- general pareisis: brain damage leads to dementia and paralysis
- tabes dorsalis: loss of myelinated axons in posterior columns of spinal cord which is marked by wasting, pain, lack of coordination and disorders of sensation, nutrition and vision = locomotor ataxia
what is cardiovascular syphilis?
can lead to aortic aneurysm or aortic valve insufficiency
what is one of the main effects of tabes dorsalis?
tabes dorsalis is a condition that is caused by neurosyphilis
Argyll Robertson Pupil
these are small, irregularly shaped pupils that do not react to light but do accommodate
what is the Tuskegee study?
it was a study of syphilis-infected african american men on how the syphilis disease progressed to try and improve AA health
it started before antibiotics when there wasn’t a safe and effective treatment for syphilis
but then when the program went bankrupt it turned into a study of what happens when syphilis is untreated….
they didn’t tell the patients they had syphilis and the patients weren’t told about arsphenamine
even when antibiotics came about in the 40-50s and could safely cure syphilis, the study wasn’t canceled and patients that moved away were denied treatment!
now AA don’t trust doctors…
what did genome sequencing of treponema pallidum tell us?
that treponema pallidum lacks most genes for synthesis of AA, nucleotides, and lipids (LPS)
but it does have genes for large number of transport proteins that is uses for scavenging
how does treponema pallidum evade the immune system?
virtually no protein exposed on the surface for the immune system to detect!!
exposed proteins very rare; called TROMPs = treponemal rare outer membrane proteins
immunodominant proteins are hidden in periplasm (LP1/LP2)
is there a syphilis vaccine?
nope
immunization with recombinant T. pallidum antigens has (so far) yielded only partial protection
what are the different ways we can detect T. pallidum?
culturing is rarely used because doubling time is 33 hours
darkfield microscopy of lesion exudate may show treponemes but some are part of normal flora…
so we tend to rely on serological methods
what’s the main way we detect T. pallidum?
a nonspecific but inexpensive blood test based on a big mistake
Wasserman was looking for an antigen associated with serum from syphilis patients
he found one but it was actually cardiolipin which is from mammalian mitochondrial membranes and gets released when mammalian cells lyse = not specific
so serum cardiolipin levels are usually zero but after widespread tissue damage levels rise
it appears that the treponemes bind cardiolipin and an Ab response follows!