Lecture 10 Flashcards
syphilis organism
Treponema Pallidum
Treponema Pallidum shape
long, very thin spirochete
Treponema Pallidum motility
endoflagella - within periplasm (3 at each end)
Treponema Pallidum covering
has glycosaminoglycan sheath surrounding whole cell
unusual envelope
-no LPS: very loosely anchored OM with cardiolipin in membrane -mostly IM lipoproteins; OM proteins very few
Treponema Pallidum culture
-cultivate in rabbit testes
Treponema Pallidum oxygen
has microaerophilic metabolism
Treponema Pallidum primary
ulcerated, defined papule at site of infection =
chancre; regional lymph nodes swell
-usually genital site, but 10-20% oral or anal or . . . -heals spontaneously, but organisms remain
Treponema Pallidum secondary
red maculopapular rash-anywhere on body, including soles and palms
condylomas-white warts in moist areas
Treponema Pallidum tertiary
lesions in tissues throughout the body (due to immune response, not bacteria)
- skin: gummas
- bones: porous, easily bent, fragile
- heart: aorta swells, ruptures
- liver
- CNS: brain = general paresis; spine = tabes dorsalis
- neurosyphilis is hard to diagnose, and may occur at 2o or 3o stage
Treponema Pallidum and infants
May also cross placenta to infect fetus in utero (few bact. do) -~20% abortion or stillbirth
-~80% congenital defects, which may not appear immediately
-Hutchinson’s triad: interstitial keratitis - blindness : VIII nerve deafness
: Hutchinson’s teeth
-also saddlenose, neural defects, bone deformation
after any stillbirth, mother should be tested for syphilis
Treponema Pallidum epidemiology
- Exclusively human, exclusively STD
- can artificially infect rabbits, but they never go beyond 1o stage
- Contagious for first 3-5 years after infection, not thereafter -Incidence in US increasing from 2005 – now (10,000 / yr)
Treponema Pallidum pathogenesis
- highly infectious (10 organisms)
- hyaluronidase facilitates spread and invasion of tissues
- rapid motility also a spread mechanism
- few surface proteins means hiding from immune system - may explain long latent period
Treponema Pallidum control
- includes finding and testing sexual contacts
- can scrape chancres to look for spirochetes, but not if latent -Serologic Tests for Syphilis (STS) (aka VDRL)
- Indirect: T. pallidum induces formation of “reagin” in host (IgM + IgA)
- add cardiolipin to patient’s serum
- if +, reagin causes cardiolipin to clump - lots of false positives (other infections)
- Direct: Fluorescent Treponema Antibody (FTA) test
- bind T. pallidum to slide and add serum from patient
- add fluorescent anti-human 2o Ab to detect 1o Ab in serum
Treponema Pallidum treatment
- treat with Penicillin G (0.003 U/ml): very sensitive -one i.m. injection for early disease (< 1 year)
- 3 injections for later disease
- in use since 1940 without resistance developing -before 1940 treatment was Salvorsan (arsenic paste)
Neisseria gonorrhea shape and stain
Gram neg, coffee-bean shaped diplococcus
Neisseria gonorrhea environment and metabolism
- fastidious (grow on MTM or Chocolate blood)
- better with selective media (vanco, colistin, etc.)
- aerobic, but prefer 5% CO2 (candle jar)
- cytochrome c oxidase positive
Neisseria gonorrhea symptoms in general
- Invades mucus membranes of UGT, rectum, eye and throat
- proctitis (fem usu from vagina, male usu from anal sex) -pharyngitis (oral sex)
- arthritis (esp of thumbs), dermatitis (rare)
Neisseria gonorrhea in males
-urethritis: painful urination, drip of pus from urethra -40% asymptomatic
Neisseria gonorrhea in females
- urethritis, vaginitis
- cervicitis, salpingitis, PID, peritonitis
- Fallopian tube scarring, sterility (15% after 1 infection, 80% after 3)
- 60% asymptomatic
Neisseria gonorrhea in infants
conjunctivitis from infected birth canal
Neisseria gonorrhea Epidemiological
-Exclusively a human STD
~75% of people who have sex with infected person get infected, ~50% after one encounter
-other co-infections contribute to symptoms (40% Chlamydia+)
-large number of asymptomatic carriers allow continued spread
-major problem in US (0.2 to 0.5% infection prevalence, 600,000 new cases / yr. reported)
Neisseria gonorrhea diagnosis
-diagnosis in males is by gram stain of urethral drip, in females by culture of cervical or vaginal swab
Neisseria gonorrhea adhesion
- initial - pili:
- pilus antigenic variation by recombinational “cassette switching” – very common, >2% of pop with variant pili
- one promoter (pilE), many genes (pilS)
- recombine new pilS gene or part of gene with pilE to make new pili (note the advantage of being diploid)
- avoid host immune response -tight - Opa (Protein II)
- named for opacity phenotype of colonies on petri dish -antigenic variation by DNA slippage of repeats
- infections in females change Opas during menstrual cycle
Neisseria gonorrhea evasion
- Por (Protein I): outer membrane porin, but also prevents phagolysosome fusion in host
- Rmp (Protein III): Host Abs bind to it, prevents Ab binding to Por and LOS in outer membrane
- IgA protease: IgA is the bactericidal, complement activating, first response Ab
Neisseria gonorrhea toxicity
- LOS rather than LPS:
- lipid A part is toxic as in all G- bacteria (endotoxin) -oligosaccharide mimics host cell membrane structure
- NANA transferase to sialylate bacterial LOS with host NANA
- PG released by autolysins at low temp or alkaline pH -typical PG inflammatory effects
Neisseria gonorrhea other virulence factors
-Fbp: scavenges Fe from human lactoferrin and transferrin
Neisseria gonorrhea Tx
- resistance acquired very easily
- PPNG produce β-lactamases, make penicillin less effective
- Pan-resistant (to all available antibiotics) Ng from Sweden reported in 2011 – in North America 2012
- preferred treatment is ceftriaxone (i.m.) or cefixime (oral) for the N.g. PLUS doxycycline or erythromycin (not doxy in pregnancy) for Chlamydial co-infections
- must locate and treat sexual contacts, too (expedited partner therapy with cefixime)
- tetracycline drops in eyes of newborns (used to use AgNO3)
N. Meningitidis structure
Antiphagocytic capsule (about 12 types) B type with sialic acid very hard to detect
Where does N. meningitidis first attack?
Blood stream
How does N. meningitidis first present?
Purpura (75%)
Small hemorrhages
In response to LOS
What are the second and third infections associated with N. meningitides?
- Meningitis
3. DIC and circulatory collapse (Waterhouse-Friderichsen syndrome)
When does N. meningitides become virulent?
Pilin modification
Phosphatidylglycerol disrupts colonies and allows organisms to spread
How does N. meningitidis spread?
Respiratory droplets
Most epidemics of N. meningitidis are due to what?
Specific capsular antigen type (B, C, Y in North America)
How does N. meningitidis breach BBB?
Special pili recruit tight junctions and open
How can you treat N. meningitidis and why?
PCN G
BBB is permeable at this point
3rd gen Cephalosporins if allergy to PCN
What is prophylactic treatment for N. meningitidis in epidemic setting?
Rifampin
Moraxella catarrhalis belongs to what family?
Neisseria
Moraxella catarrhalis causes what?
Opportunistic OM in children Sinusitis Bronchitis Pneumonia
Moraxella catarrhalis in adults specifically causes what?
Exacerbates COPD symptoms
Moraxella catarrhalis treatment and why?
Most have beta-lactamases
Treat with 3rd gen cephalosporins or cipro
Chlamydia trachomatis metabolism
Obligate intracellular parasite
lacks many metabolic genes, steals ATP from host
What is distinct about Chlamydia trachomatis cell wall?
Lacks MurNAc
but still has PBPs
Chlamydia trachomatis mostly resemble what, GramPos or GramNeg?
GramNeg
What are the two life cycles of Chlamydia trachomatis?
Elementary bodies-infective (small)
Reticulate bodies-replicative (large)
Chlamydia trachomatis enters the cell during what phase of life cycle?
Elementary (this is the infective stage)
What are the five manifestations of Chlamydia trachomatis?
- Trachoma (eyes)
- Inclusion conjunctivitis (eyes, newborns)
- Neonatal pneumonia
- Chlamydia
- Latent infection (lymphogranuloma venereum)
How does one get trachoma?
Infected birth canal Or vectors (such as from flies)
Trachoma symptoms?
Pus in eyes Keratinized corneas (pannus formation) Corneal obscuration Eyelid involvement (trichiasis) May lead to eventual blindness
Trachoma Tx?
Maybe azithromycin
How does one get inclusion conjunctivitis?
Mostly from infected birth canal
What can be sequela to inclusion conjunctivitis?
Respiratory problems
“Neonatal pneumonia” can be secondary
Male chlamydia symptoms?
- nongonococcal urethritis!
- epididymitis!
- prostatitis!
- usually self-limiting!
Female chlamydia symptoms?
!-urethritis!
! !-cervicitis!
! !-salpingitis / PID (invasive)!
What is the most common cause of PID?
Chlamydia
Latent infection caused by Chlamydia trachomatis symptoms (lymphogranuloma venereum)?
May begin as a small abscess that heals quickly
Can get inguinal buboes which can turn black
Associated with fever and pain
What is a long term complication of lymphogranumoa venereum?
May form fibrous restrictions:
Can lead to elephantiasis or bowel obstruction
Trachoma has what epidemiological implication?
Leading cause of infectious blindness in the world
Chlamydia trachomatis mechanism for invading cells (during elementary body phase)?
Bind host receptors
Induce pathogen-mediated endocytosis
(T3SS effectors remodel cytoskeleton)
How does Chlamydia trachomatis survive in a cell?
Inhibit phagolysosome fusion
How does Chlamydia trachomatis induce inflammation once residing in a cell?
Induce cytokines
Especially IL-1
Why are vaccines ineffective against Chlamydia trachomatis?
Intracellular location
What is most common test for Chlamydia trachomatis?
PCR
How can you prevent corneal keratinization with trachoma?
Pull out eyelashes
Treatment for Chlamydia trachomatis?
One does azithromycin
tetracycline or macrolides also work
Chlamydia pneumoniae is found in what percentage of population?
Almost 100%
Most asymptomatic
Chlamydia pneumoniae may be implicated in what diseases?
Atherosclerosis CAD Asthma Stroke Alzheimers
Chlamydia psittaci causes what disease?
Parrot fever
Parrot fever symptoms?
Acute, severe pneumonia and sepsis
Patchy, well-defined lung involvement
How is Chlamydia psittaci transmitted?
Always via psittacine birds
Chlamydia psittaci treatment?
Tetracycline
Rickettsiae shape and stain
Small rods
GramNeg
Rickettsiae metabolism
Obligate intracellular parasite (cultured in yolk sac of eggs)
What are the four groups of Rickettsiae?
- Typhus
- Spotted fever
- Ehrlichia/anaplasma
- Coxiella burnetti (actually genetically related to Legionella)
