Treponema pallidum shape and visualization techniques
- Visualized in fixed tissues by silver stain
- Visualized live by dark field microscope
*Not visible using light microscopy
Treponema has a _____ that surrounds the whole cell
It is motile due to.....
It has a GAG sheath surrounding the whole cell
Motile due to endoflagella within periplasm (THREE at each end)
Treponema envelope composition
- No LPS
- Loosely anchored OM containing cardiolipin
- Mostly IM lipoproteins (OM few)
Lab culture technique for treponema
Can't culture in lab!
Cultivate in rabbit testes
*has microaerophilic metabolism
Primary treponema presentation
- Chancre = Ulcerated defined papule at infection site
- Regional lymph node swelling
- heals spontaneously, but organisms remain
Secondary treponema presentation
Maculopapular rash anywhere on body (palms/soles)
Condylomas in moist areas
- Heals spontaneously, recurs for 8 months, then latent for 20 years
How many patients progress to tertiary syphillis?
Tertiary syphillis: where's the lesion?
throughout the body
*due to immune response, not bacteria
How does tertiary treponema affect particular tissues?
Bones: porous, fragile
Heart: aorta swells, ruptures
CNS: paresis in brain, tabes dorsalis in spinal cord
Neurosyphillis can occur...
during secondary or tertiary stages
Vertical transmission of treponema?
Yes, it can cross the placenta
- 20% aborted, stillbirth
- 80% congenital defects
What does congenital syphillis present as?
- Interstitial keratitis (blindness)
- 8th nerve deafness
- Hutchinson's teeth
*also saddlenose, cognitive deficits, and bone deformation
Treponema reservoirs and transmission?
Only human, only STD
(can artificially infect rabbits, but they don't progress beyond the Primary stage
When is treponema contagious?
Only for the first 3-5 years
Who should be tested for syphilis?
High risk populations
Pregnant women at 28 weeks and at delivery
After any stillbirth
Pathogenic factors (4) for treponema
Highly infectious (10 organisms)
Hyaluronidase (facilitates spread and invasion)
Few surface proteins (hide from immune system)
______ lesions are full of treponema organisms
Primary and secondary
(General) control measures for treponema
ID sexual contacts
Scrape chancres (only if active infection, not latent)
Indirect serologic tests for treponema
induce formation of reagin in host (IgM+IgA)
- add cardiolipin to patients serum
- If positive, the reagin will cause cardiolipin to clump
- ****False positives possible***
FTA test (detect anti-treponema antibodies)
- bind treponema to slide and add patient's serum
- add a fluorescent anti-human 2' antibody to detect the 1' antibody
Direct serological tests for treponema
FTA test (can also be indirect)
- Fix anti-treponema antibodies to slide, and add patients serum
- Add fluorescent anti-treponema antibodies to detect organisms
Pen G (2.4 MU)
Early disease = One injection
Latent disease = Three injections
*Salvorsan (arsenic) was used before 1940
Neisseria gonorrhea organism shape and location (in cells)
Gram (-) , Coffee-bean shaped diplococcus
Intracellular and inside PMN's
N. gonorrhea growth characteristics
Fastidious (grow on MTMor chocolate blood agar)......better with selective media (vanco,colistin)
Aerobic growth but prefers 5% CO2 (candle jar)
Cytochrome C oxidase ++
Ox+, Gram(-) diplococcus =
Two identical chromosomes (diploid) -- never heterozygous
Neisseria invades what tissues?
What are the infections that this causes?
invades mucus membranes of the UGT, rectum, eye, throat
Proctitis, pharyngitis, arthritis, dermatitis (rare)
Male N. gonorrhea infections
N. gonorrhea female infections
- Urethritis, vaginitis
- Cervicitis, salpingitis, PID, peritonitis
-->> fallopian tube scarring and infertility (even if asymptomatic...60%)
Neonatal N. gonorrhea infection
(from infected birth canal)
Animal carriers of N. gonorrhea
None. Exclusively human
Infection and coinfectino rates of N. gonorrhea
75% of people who sex an infected person (50% after one time)
40% coinfect with Chlamydia
N. gonorrhea diagnosis
Males = gram stain of urethral discharge
Females = culture of cervical/vaginal swab
N. gonorrhea virulence factors
- IgA protease
- Peptidoglycan release
N. gonorrhea virulence factors for ATTACHMENT
- Antigenic variation via cassette switching -- avoid host immune response
- One promoter (PiliE), many genes (PiliS)
- recombine new piliS gene or part of gene with piliE
OPA protein = "Protein 2" (tight attachment)
- antigenic variation by DNA slippage of repeats
- infections in females change Opas during menstrual cycles
N. gonorrhea virulence factors for EVASION (3)
Por = protein 1
- Outer membrane porin
- Prevents phagolysosome fusion
Rmp = protein 3
- Prevents antibody binding to Por and LOS in the outer membrane
- prevents complement activation
- Stops IgA response (first-response Ab in mucus membranes)
N. gonorrhea virulence factors for TOXICITY (2)
Lipooligosaccharide (rather than LPS)
- Lipid A = toxic in all Gram (-) bacteria (endotoxin)
- Oligosaccharide mimics hist cell membrane structure
- NANA transferase = sialylates bacterial LOS with host NANA
Peptidoglycan release by autolysins
- At low temperature or alkaline pH
"Other" N. gonorrhea virulence factor
Scavenges iron from human lactoferrin and transferrin
What is PPNG?
Penicillinase-producing N. gonnorhea
* produces beta-lactamases
Other type of resistant gonorrhea?
**to ALL available antibiotics
Tx for N. gonorrhea
Ceptriaxone (i.m.) + Cefixime (oral)
Doxy or erythromycin for chlamydia co-infection
**NO DOXY DURING PREGNANCY
Treat N. gonorrhea sexual partners with...
Neonatal N. gonorrhea infection treatment?
Tetracycline drops (for conjunctivitis)
**no longer use AgNO3
Neisseria meningitidis structure
Like the gonococcus, but has polysaccharide capsule
Types of N. meningitidis
Common: A, B, C, Y, W135
N. meningitidis initially invades ______, causing ________ (infection)
It presents as ________ and small hemorrhages. Why?
Invades bloodstream--> meningococcemia
Purpura (75%) -- because blood vessels become more permeable in response to the toxic effects of LOS and soluble peptidoglycan
15% of N. meningitidis cases involve
meninges (meningococcal meningitis)
- acute headache, vomiting, stiff neck
Cellular findings in meningococcal meningitis?
This may progress to...
PMN lymphocytes in CSF (d/t increased vascular permeability)
Brain covered in purulent exudate with PMNL's and N. meningitidis
--> may progress to DIC and circulatory collapse = meningococcal septicemia
N. meningitidis is ______ in 10% of people
N. meningitidis spread is helped by __________
--disrupts microcolony and spreads the organism
N. meningitidis is chiefly spread by
respiratory droplets, especially in crowded areas and with susceptible populations
Common environments (examples) for spread of N. meningitidis
College dorms and military barracks
Once N. meningitidis epidemic begins, there is a ____ carrier rate. This necessitates ________
80% carrier rate
Prophylaxis for control of epidemic
Most N. meningitidis epidemics are due to...
specific capsular antigen types
N. meningitidis virulence factors...
all of the ones from N. g.
Antiphagocytic polysaccharide capsule
- Antigen B is sialylated = much more disguised
- Special Pili that attach to BBB and recruit junction complexes, depleting them in other areas of the BBB (increasing permeability)
- Additional Adhesins (in outer membrane)
N. meningitidis vaccines
(current and newly approved)
NmA vaccine = general prophylaxis
ACWY conjugate vaccine = US use (dorms, army, etc)
NmB vaccines = recently approved
- Bexsero = 3Nm proteins + PorA
- Trumenba = 1 recombinant lipidated proteinfrom 2 NmB strains
Preferred N. meningitidis treatment
3rd gen Ceph
(may include acyclovir too if CSF suggests herpes present (RBC/WBC)
Initial treatment of N. meningitidis should be...
broad spectrum antibiotic
including Vancomycin (will penetrate BBB)
_____ or ______ can be used for prophylactic N. meningitidis treatment in epidemic settings. Why these in particular?
Rifampin or 3rd gen Ceph
** they cross the BBB
**can also use high-dose ciprofloxacin
(Carrier rate, infections in kids and adults, and Tx)
- 50% carrier in school aged kids
- infections = opportunistic sinusitis, bronchitis, PNA
- May also present as Otitis Media (3rd most common cause)
- Exacerbates COPD in adults (attach to ECM)
- Produce BETA LACTAMASES = Treat wth Ceph3 or with Cipro (or not at all?)
Chlamydia trachomatis organism, genome,and structure
- Obligate intracellular parasite
- Small genome (lacks metabolic genes, steals ATP from host)
- Cell wall lacks MurNAC, but has PBP's
- Susceptible to Penicillin but not to lysozyme (PEN NOT USED TO TREAT)
- Susceptible to Penicillin but not to lysozyme (PEN NOT USED TO TREAT)
Chlamydia trachomatis has ___ serovariants, baed on ____
based on LPS antigens
Must cultivate Chlamydia trachomatis on ________
eukaryotic host cells
(embryonated chicken eggs, McCoy cells in monolayer tissue cultures, mouse brains)
Two life cycle forms of Chlamydia trachomatis
- .3um in diameter, electron dense nucleoid tough membrane (S-S)
- INFECTIVE FORM (the form that enters cell)
- 1um diameter, diffuse EM staining, fragile (SH-HS), more ribosomes
- REPLICATIVE FORM (the one that divides)
Chlamydia trachomatis life cycle (7 steps)
- Initial attachment (surface sugars), actin remodeling, induced uptake
- Elementary body metabolism
- Develops into RB
- RB matures
Eye infection of Chlamydia trachomatis
(Aquisition and symptoms/pathology)
- infection at birth or early childhood via flies
- mucopurulent discharge --> pannus forms (keratinized cornea)
- Corneal obscuration and trichiasis
- Permanent blindness
Tx = oral Azithromycin (mass trial showed reduced infective rate by 50%)
Other eye infection of Chlamydia trachomatis (the less severe one)
(who does it infect, and possible complications)
- mostly in neonate (adult from self-innoculation of conjunctiva)
- may be respiratory complications
Chlamydia trachomatis neonatal (non-eye) infection
(Symptoms and Dx?)
- Shortness of breath
- NO FEVER
- suspect if infant has inclusion conjunctivitis
STD version of Chlamydia trachomatis?
Male Chlamydia STD symptoms
- non-gonococcal urethritis
Female chlamydia STD symptoms
- salpingitis/PID (most common cause)
(**Fallopian scarring may lead to infertility or predispose to ectopic pregnancies -- 10 fold increase in likelihood)
Most common cause of acquired infertility in females?
Chlamydia induced PID
Latent infection of Chlamydia trachomatis?
General infection timeline?
(small abcess--> heals quickly --> inguinal buboes later)
**must Ddx from PLAGUE buboes
Latent Chlamydia infection may become ______. This could lead to ______ or ______ due to fibrous restrictions of lymphatic system.
elephantiasis or bowel obstruction
Specific manifestation of latent Chlamydia depends on...
Serovar of the organism
Probability of infection by sex with partner who is infected with Chlamydia trachomatis?
Most common Chlamydia trachomatis infections in North/South America and Europe?
What about Asia and Africa?
NA/SA/Eur = STD
Asia/Africa = Trachoma
Why do we need to treat both epidemiological localizations of Chlamydia trachomatis the same?
They can cross-infect
Chlamydia trachomatis infectiveness is caused by _______
--binding to a host receptor and inducing Pathogen-mediated endocytosis
_____ remodels the host cytoskeleton in Chlamydia trachomatis pathogenesis
Chlamydia inhibits ______ so it can proliferate intracellularly
Chlamydia trachomatis induces _______
Cytokine (IL-1) production
What is the preferred treatment? Prevention?
Vax = ineffective d/t intracellular location
Tx = Azithromycin (one dose oral)
- Can also treat with Tetracycline or macrolides
Prevention = surgery or epilation for trichiasis to prevent keratinization of the cornea
** ID partners -- expidited partner therapy, legal in 35 states
C. pneumoniae may have originated as a _____ from what?
zoonosis from koalas
C. pneumoniae infection rate
100%, but mostly asymptomatic
C. pneumoniae may progres to....
Walking PNA (like mycoplasma)
C. pneumoniae is found in ______, which suggests...
suggests link to atherosclerosis and coronary artery disease
** also associated with asthma, stroke, and late-onset Alzheimer's
C. pneumoniae Tx
Tetracycline may help
C. psittaci presentation, transmission, and Tx/control