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!
what are flocculation tests?
it’s when purified cardiolipin is mixed with dispersants
if there are cardiolipin-specific IgG, IgA or IgM, visible clumps appear
these tests give negative results about a year after successful treatment (unlike specific anti-treponemal Ab tests)
what are the most commonly used floculation tests?
- VDRL = venereal disease research labs
- RPR = rapid plasma reagin
- TRUST = toluidine red unheated serum test
what’s the drawback to cardiolipin-based tests?
MANY diseases that lead to tissue damage can lead to a positive result!
ex. malaria, leprosy, measles, lupus, even pregnancy!
also, these tests can give negative results during the latent phase of syphilis and in 1/3 of tertiary patients
anti-treponemal protein tests are better!
which tests are done to specifically confirm T. pallidum infections?
- FTA = fluorescent treponemal Ab
- EIA = enzyme immunoassay
- TPPA = T. pallidum partilcle aggulination
- PCR
how does an FTA test work?
FTA = fluorescent treponemal Ab
The patient’s serum sample + drop of T. pallidum + fluorescently-labeled 2°Ab
requires flurescnece microscope
how does EIA test work?
EIA = enzyme immunoassay
Patient’s
serum sample into microtiter wells coated
with recombinant treponemal Ags
enzyme-linked anti-human IgG/IgM
how does TPAA test work?
uses gelatin microbeads coated with recombinant treponemal proteins
but be careful people with periodontal disease carry oral treponemes that can
be detected with antibodies to the same antigen used in many tests. These people have detectable antibodies to this and other T. pallidum antigens
also these treponeme-specific tests remain positive for years, even if the patient has been successfully treated; they are useful to confirm that an infection has occurred in the past, but not for assessing current status
how does PCR for T. pallidum work?
T. pallidum can be identified by PCR in the bloodstream of patients with all stages of syphilis
the quantity of treponemes in blood is highest during early syphilis
in latency, treponemes persist in many tissues without causing clinical signs or symptoms; other tests may be negative
what is congenital syphilis?
caused by infection in utero with Treponema pallidum
wide spectrum of severity
kids under 2 may have hepatosplenomegaly, confyloma lata, jaundice, rash, snuffles, anemia
older kids may have interstitial keratitis, mulberry molars, saddle nose, nerve deafness, frontal bossing, Hutchinson teeth etc.
how is congenital syphilis transmitted?
mother-to-child
treponemal reservoir was mother
transplacental infection does not occur in the first ~10 wks of pregnancy, so there was a treatment window
mother was probably infected late in the pregnancy
transplacental infection early in pregnancy generally –> miscarriages and stillbirths
late-pregnancy infections generally –> bone and tooth deformation, heart and brain damage
how do you treat a pregnant woman with syphilis?
only penicillin!!
even if they’re allergic, you should desensitize them and treat them with penicillin
for a nonpregnant patient that’s allergic to penicillin, you can treat with doxycycline
what do you use to treat syphilis?
penicillin G benzathine
it’s the first line treatment for all stages of syphilis except neurosyphilis because it doesn’t cross the BBB
KEY CONCEPTS syphilis
caused by the spirochete treponema pallidum
can be transmitted from mother to fetus = congenital
initial diagnosis via RPR with confirming test for +s
readily treated with penicillin
could be eliminable
three stages:
1. primary = localized to chancre
- secondary = disseminated
- tertiary = immune response –> tissue damage
FLASHCARD: micropathology, pathology, epidemiology, clinical, diagnosis and treatment for treponema pallidum?
MICROBIOLOGY:Spirochete; subsp. pallidum cannot grow on any known culture medium
PATHOLOGY: Extremely invasive (especially subsp. pallidum; affects all tissues with blood supply); “stealth” pathogen with few surface proteins
EPIDEMIOLOGY: (subsp. pallidum) spread sexually and congenitally
CLINICAL: Depends on subsp:
T. p. pallidum – syphilis, chancre –> dissemination / condylomata –> gummas / neurosyphilis
T. p. pertenue – yaws, ulcerating papule –> dissemination to skin & bones
T. p. endemicum – bejel, intertriginous areas & facial bone, destructive lesions of nose & palate
T. carateum – pinta, spread in skin only, local patches of hypo-achromia
DIAGNOSIS: T. p. pallidum – semispecific test for Ab against cardiolipin (Wasserman / VDRL / RPR / TRUST), with positives followed by FTA / TPHA / TPPA (or, increasingly, PCR)
TREATMENT: T. p. pallidum – typically single large dose of benzylpenicillin ( for 1°or 2°syphilis)
