Chlamydia, Rickettsial Diseases and Spirochetes (3/8/18) Flashcards
morphology of chlamydia
Small (.3-1micrometer)
gram-
how does chlamydia act as a pathogen
obligate intracellular bacteria relying on host amino acids and atp
cell wall of chlamydia
no peptidoglycan
life cycle of chlamydia
biphasic: Elementrary bodies (EB)-small rigid cell wall, infectious form Reticulate bodies (RB)- large fragile, metabolically active replicative form
where can chlamydia live
diverse tissue tropism and disease
major difference between EB and RB chlamydia
EB: isolated orgnism infectious, adaptived for extracellular survival
RB: Isolated organisms not infectious, adapted for intracellular growth
lifecycle of C. trachomatis
Attaches and induces endocytosis (TARP-translocated actin recruiting protein)
Using stored ATP, EB converts to replicative RB
Inhibition lysosomal fusion in host cell by forming its own membrane-bound vesicle (the inclusion where replication takes place)
Once a threshold of RB, convert to EB
CPAF (Chlamydia protease-like activity factor)- regulated cellular apoptosis signals
EBs are released
where replication takes place for RB CC. trachomatis
in an inclusion
reservoid for C. trachomatis
humans
where does C. trachomatis cuase disease
conjunctiva (eye and Genitals
commonality of C. trachomatis
most common disease in world (100 mill new cases)
most common bacterial STI worldwild
what is the commmon cause of neonatal conjunctivitis
contact with C. trachomatis with infected cervical secretions during vaginal delivery
how many does Chronic follicular conjunctivites affect
500 mill world wide
blinds 7-9 million (africa)
when does one get chronic follicular conjunctivities
in infancy or early childhood from mom vis contact with infected secretions (fomites, fingers, flies)
Chlamydia affects how much in urethral infection
5% general pop in US men and women
Conagiousness of Urethral chlamydia
Very (1/3 of male sex contacts of women with chlamydia cervicitis develop urethritis)
Asymptotic infection in men are more common than with gonorrhea
incubation period for urethral infection via chlamydia
2-6 weeks
tissue tropism of chlamydiae
columnar epithelial cells of endocervic and upper Genital tract of women
urethra, rectum, and onjunctiva of both sexes
depending on biovar other cell types can also be infected: endothelium, S. muscle, lymph, and macrophages
what mediates initial attachment of chlamydiae
MOMP (major outer membrane protein) followed by endocytosis
how can chlamydia enter
LGV biovars enter through breaks in skin/mucosa or endocytosis
what is the source of primary injury due to chlamydia
inflammation: (also cuased by Chlamydial LPS
what are the pro-inflammatory cytokines for chlamydia inflammation
IL-8 releasedby epithelial cells
inflammation by chlamydia leads to
early tissue inasion by PMN, then lymphocytes, macrophages, plasma cels, and eosinophils
If the immune system fails to control chlamydia infection what happens
aggregates of lymphocytes and macrophages in submucosa leading to necrosis and fibrosis and scarring: lead to infertility and blingness of eye
immuniy to chlamydia
incomplete (50% of women still shedd aftera a year)
what response is the most protective for chlamydia
TH1 response (CD4+ t cells) also Th2 directed at MOMP may participate, but antibody is associated with injury in chronic forms of the disease trachoma
chronic inflammation of eyelids that can lead to scaring of cornea often leading to blindness
Trachoma
acute infection presnt in newborns as mucopurulent eye discharge, but does not lead to blindness
Inclusion conjuctivitis
how does inclusion conjunctivities get to baby
from morther to infant at birth to affect newborns and adults
what may inclusion conjunctivies turn into
can lead to infant pneumonia sydrome (cough and difficulty feeding)
eye infections of chlamydia trachomatis
trachoma and inclusion conjunctivites
Genital infections of chlamydia trachomatis
Urethritis and epididymitis in men
cervicitis, salpingitis, and urethral syndrom in women
Lymphogranuloma venereum (LGV)
characteristics of urethritis and epididymitis
dysuria(diffficult urination) and thin urethral dischage
characteristics of cervicits, salpingitis, and urethral syndrome
asymptomatic Vaginal dischage
5-30 of women get pelvic inflammatory disease leading to sterility and ectopic pregnancy
inflamed fallopian tubes
salpingitis
where is LGV found
STD of S. america, africa, SE asia, india and caribbean
what causes LGV
invasice biovars: L1, L2 or L3
how does LGV get into body and what does it cause
entery through breaks in skin causing transient genital lesion, invades inguindal lymph notes to create bubos(swollen gland in groin)
also cuases hemorrhagic ulcerative proctitis
How to diagnose Chlamydia historically
collect epithelial cells from site of infection (urethral swab collection hurts men)
how do we diagnose chlamydia now?
Nucleic acid Amplifcation test (NAAT) to detect chlamydia and N gonorrhoeae DNA using first void urin sample for genital infections
treating C. trachomatis
Azithromycin for non-LGV (oral)
Doxycyclin for LGV
morphology of Rickettsiae
small with small genone
Gram-negative
aerobic coccobacilli
non-motile
parasite type for rickettsiae
obligate intracellular parasites
how do we get Rickettsiae
arthropod-borne to humans via arthrodpod vectors (ticks, fleas, mites, and sandflies)
cell envelope of Rickettsiae
LPS and 2 other OM proteins
Cell wall of peptidoglycan
why does Rickettsiae need to depend on host
reductive evolution requires host co-factors, amino acids, phosphorylated sugars, and ATP
how does Rickettsiae metabolize host glutamate
aerobic respiration and TCA cycle
grwoth of Rickettsiae
slow- in host cytoplasm or nucleus
entery of Rickettsiae
enter host via endocytosis-attachment of OMP
escape phagosome using phopholipase
grow in host cell cytoplasm
where is Rickettsiae transmitted from
trick salivary glands
locatl spread of rickettsiae leads to
necrotic eschar (Black sore)
tissue tropism for Rickettsiae leading to
vascular endothelium infection leads to vasculitis(inflammation of Blood vessel)
vascular lesions
increase vascular permeability: hypopvolemai and hypotension
Thrombosis cuase by
focal areas of endothelial proliferation and perivascualr infiltration
leakage of rBC by Rickettsiae leads to
rash and petechial lesions
CAtegories of Rickettsiosis
Spottered Fever group- US
typhus group- EU
symptoms of both types of Rickettsiosis
Fever, headache, myalgia, and rash
may be fatal due to severe vascular collapse
where spotted fever group comes from
Tick -borne rickettsia
what causes Rocky Mountain spotted fever
Rickettsia rickettsii
who does Rickettsia Rickettsii SF normally parasite
ticks, spreading to tick offspring
only slightly more than 500 cases a year in the US
when is Rickettsia Rickettii SF highest
between april and september, betwween age 60-69 and killing in children less than 10
what type of tick transmitts R. Rickett SFi?
Adult feamle ticks(but diff speicies) transmit because they need blood meal to lays egs
how long can infected adult tricks live without blood meal
4 years
R. Ricketti SF ticks across the US
- Western states - wood tick
- Eastern states - dog tick
- Southwest and Midwest- lone star tick
- Ubiquitous- Brown dog tick
incubation period for R. rickettsii SF
6-7 days
symptoms of R. rickettsii SF
fever headache, RASH, toxicity, mental confusion, Myalgia (muscle pain)
travel of rash from Rickettsia Rickettsii SF
begins on arm and ankles, spreads to extremities of trunk within hours
what parts of the rach from Rickettsi aSF are used for diagnostic test
rash on palsm an d soles
complications if RMSF is leaft untreated
Intravascular coagulatoin thrombocytopenia (low platelets) Encephalitis (brain inflammation Vascular collapse Renal and heart failure
diagnosis of Rickettsia SF
hard/hazardous to culture
how to diagnosis in early stages (antibodies appear 6-7 days after illness onset)
clinical signs
serologic diagnosis is perferred
when to start therapy for Rickettsia SF
based on clinicl sings and aymptoms and epidemiologic considerastions
how is seologic diagnoisis of Rickettisa SF done
Indirect fluoresent antibody(IFA)-reference labs
skin lesion biopsy- immunofluorescent antibody used for rapid confirmation
treating Rickettisae SF
Doxycyclin-first wek of illness
if delayed, can’t use it (complications
Sulfonamides make the situation worse
disease caused by Typhus group
Epidemic Thyphus fever
Endemic (murine) Typhus
Scrub typhus
how to get epidemic typhus fever
R. prowazekii spread by body lice(often by times of misery where lots of people get lice)
how to get Endemic (murine) typhus
R. typhi spread by rat flease
how get Scrub typhus
orintia tsutsugamush spread by chiggers
the only epidemic ricketsial disease
Typhus fever
where is typhus found
africa, latin america and asia, homeless population
NOT in the US for 50 years
typhus fever pathogenisis
R. Prowazekii circulates in patients blood during aute febril infection
human body louse gets infected during feeding (Blood meal)
louse die 7-21 days after infection
lice poop has R. prowazekii after 5-10 days
how does humans eveutally get typhus fever
louse poop while they food, so bacteria enter blood stratm when a human scratches the bite ( can also infect through mucous membrane of eyes and respiratory tract
Incubation period of Epidemic Typhus
1-2 weeks
symptoms of epidemic Typhus
maculopapular rash: on trunk then to extremities (opposite from RMSF)
headache, Malaise, and Myalgia common
complication: myocarditis and CNS dysfunction
fatality rate of Epidemic Typhus if untreated
10-60%(increases with age)
diagnosising Epidemic typhus
serology used to confirm, clinicla history to justify
treating Epidemic Typhus
immeidate with Doxycyclien
how to prevent Epidemic Typhus
louse control
no vaccine
how humans get Endemic(Murine) typhus
incidental - urban rodents are natural reservoir (rat flea with R. typhi)
occurange of Endemic (murine typhus
world wide (50-100 case in US)
pathogenesis of endemic (Murine) typhus
similar to louse-orne typhus but with expose to rats and rat flease
serologic tests to separate Endemic and Epidemic Typhus
can’t separate
what does intital lesion of scrub typhus decelop as at the bite
necrotic eschar
symptomes of scrub typhus
fever slowing increase
headache Maculopapular rash, mental change, general lymphadenopathy
length of maculopapular rash
shorter duration than louse borne or murine typhus
trating scrub typhus
Doxycycline
Morphology of Bartonella
Gram-neg coccobacili
parasite of bartonella
facultative intraceullar parasite as an opportunistic pathogen
primary niche and infection of bartonella
endothelial cells to be released into the blood stream to infect eryhtocytes
eventually taken up by arthropod
vectors for bartonella
ticks, fleas, sand flies, and mosquitoes
what can bartonella casuse co-infections with
lyme’s disease
Bartonella henselae
Cat-scratch disease
cases of Bartonella henselae (cat-scratch disease)
25k in the US mostly children
how is Bartonella henselae (cat-scratch disease) spread
cat scratch, bites, or cat flease
preventing Bartonella henselae (cat-scratch disease)
flea control
symptomes of Bartonella henselae (cat-scratch disease)
swollen lymph nodes skinrash, conjunctivites, encephalities, prolongued fever
how is affected by bartonella quintana (trench fever)
homeless alcoholic me in france and US by body louse
bartonella quintana (trench fever) severity
mild subclinical diease
symptomes of bartonella quintana (trench fever)
- sudden onset of chills, headache, relapsing fever, maculopapular rash
morphology of spirchetes
spirals (loose coils to rigid corkscrew)
Motile via rotation and flexion
fexible peptidoglycan cell wall with axial fibrils
outer bi-layered membrane (like gram neg)
seeing spirochetes
hard to see with routing microscopy
medically important genera of spirochetes
trponema
leptopria
borrelia
normal flora for spirchetes
oral cavity and dental crevice
Trench mouth (Vincent infection or ANUG-acuter necrotixing ulcerative gingivites) gets it name from
WWI
how does Trench mouth (Vincent infection or ANUG-acuter necrotixing ulcerative gingivites) infect
opportunistic, correltaed with immunocompromised sever malnutrition and neglect of basic oral hydien
what do spirochetes and anaerobic flora cuase
necrotizing, ulceration infection of the gums, oral cavity, or pharynx (bleeding gums, bad breath, metallic taste, sudden onset, pain)
Morphology of treponema pallidum
motile
Slim spirochete
corkscrew shape
no lps
how to kill treponema pallidum
easy: dry, heat, detergenet, disinfected
what odes Trponema pallidum cuse
syphilis
studying treponema pallidum
hard to culutre and can only be grown in animals
what does T. Pallidum need from host
Minimalist pathogen: basic nutreitns and metabolites
can T. Pallidum detox O2
no (no catalse or oxidase)
Energy pathways for T. pallidum
lacks : no TCA of Electron transport
growth speed of T. pallidum
slo (30 hours)
who does syphilis pathogen
only human
how do you get syphilis
sexual contact with person with active primary or seconday lesion
also non-genital contact
how to get syphilis without touching genitals
congenital syphilis - transplacental transmission
Needles
is tertiary syphilis contagious
no
problwm of syphilis
world wide, as lesions cause HIV to enter
rise of syphilis
on the riase (Up 18% in the US) 27,814 primary and secondary syphilis in US most with dudes who bang dudes)
628 people with congenital syphilis (minorities)
Pathogeneisis of spirochete
reaches subepithelial tissue via small breaks in skin or mucous membranes
multiplty in submucos iwthout detection
spread to bloodstreat and establish infection in distant tissues
the primary lesions of T. Pallidum is what and results in what
endarteritis-inflammation of inner lining of an artery and a necrotic ulceration forms
dense granulomatous cuffs of lymphocytes, monocytes, and plasms sound vessels
how does T. pallidum evade
unkown
when does Primary syphilis occure
3-90 days after exposure
what first appears from primary syphilis
primary lesion (chancre) at point of contact
single painless, non-itchy skin ulceration
lymph node englangement 7-10 days after chancre
heals after 4-6 weeks
when does secondary syphilis occure
2-8 weeks after primary infection in 1/3 of patients
what does secondary syphilis involve
skin ,mucous membranes, and lymph nodes
gives a symmetrical, red-pink, non-itchy rask on trunk and extremities, including palms and soles
what fills the lesion of seconadry syphilis
bacteria (highly infectious)
after xeconday syphilis what occures
latent syphilis (1/3 spontanously clear infection)
symptoms of latenet syphilis
no clinical symptoms but serolgical tests are positive
what can happen with latent syphilis
relapse to secondary
transmit to others or feus
what odes tertiary syphilis result in
tissue distrcution
how common is tertiary syphilis
1/3 of untreated secondar syphilis, after infection 15-20 ears
how tertiary syphilis manifests itself
neeurosyphils
Ocular syphilis
Cardiovascular syphilis
GUmma
when syphilis invades the nervous system
neurosyphilis
symptomes of neuosyphilis
headache, altered behavior, loss of coordination, paralysis, Tabes dorsalis,
sensory deficits and dementia (most common in HIV positive patients)
symptomes of ocular syphilis
vision change
symptomes of cardiovascular syphils
aortis - leads to aneurysms
where is gumma
in skin, bone, joints, organs
diagnosis of syphilis
serologically: detection of antibodies aginst treponeal antigens
treponemal vs non-treponemal
looks for treponemal antigen (FTA- ABD, MHA-TP)
cardiolipin based test that is non-specific and cross reaction possible when autoimmune disaes present
treating ssyphilis
penicillin at all stages
morphilogy of borrelia burgdorferi
long slender psirochetes axial flagella (many) outer membrane without LPS stains with Giemsa or Write Microaerophilic
grow speed of Borrelia Burgdorferi
slow (24-48 doubleing time hours)
what genes does Borrelia Burgdorferi lack
essential nutrients(amino acids, fatty acids, nucleic acids
genome type of Borrelia burgdorferi
partitioned genome- many circular and linear plasmids
disease from borrelia burgdorferi
Lyme
other Borrelia cause relapseing fever
species of Borrelia burgdorferi
18 diff subspecies: differ in geographic distribution and clinical manifestation
OMP’S OF bORRELIA BURGDORFERI
MULTIPLE CLASSES,that undergo antigenic variation (outer surface proteins)(Osps)
what do Osps do
OspA and OspC are differentially expressed dpening on state of tick or mammalian infection
other bind fibrongectin and serum factor H
the primary reservoid of B. burgdorferi
rodernts
how do ticks get B. burgdorferi
tick larvae food on mice
when lyme’s disaes occures
in spring and summer when nymphs feed on vertebrate hosts as part of life cycle
inoculum of B burgdorferi
low (less than 20)
enxootic cycle of B. Burgdorferi
larve hatch fro m uninfected eggs and feed on infected host
larve molt into myphs, feed and transmited B. Burgdorferi to vertebrae host
Nymphs mold into adults which feed on deer and mate
where is lyme disease present
where deer are present
symptomes of primary lyme diease
bull’s eye pattern -macule or papule rash at bite site (erythema migrans)
Fever, Fatigue, Myalgia, headache, joint pain, mild neck stiffness
who doesnt get seconday lyme disease
50% of patietns develop like primary
when does secondary(Chronic) lyme disease occure
days to months after primary rash
what happens in seconary lyme diease
Fluctuating meningitis, cranial nerve palsies, and peripherneuropathay
heart conducting problems - atrioventricular block - myocarditis leading to caridac englandment
arthrits
what is chronic lyme diease from
autoimmune state
diagnosis of Lyme diease
expose and clinical finds
later statge can use serology for antibodies
how to culture Lyme disease
from erythema migrans skin lesion, blod, joins, CSF.
but very hard
can you see lymes disease with a microcope
no
treating lyme’s diase
Doxycycline and BEta- lactam: early lyme and arthristis
but slow response
preventing lymes disease
wear protective clothing
remove tick fast (ned 48-72 hours to reansmit bacteria
