Lecture 17: Bacterial STIs Flashcards
Neisseria Characteristics
- Gram neg.
- diplococci w. adj. sides flattened together
- polysaccharide capsule on meningitidis, but not gonorrheae
- 13 serogroups
Does N. gonorrheae or N. meningitidis have a polysaccharide capsule?
what does this capsule help do?
N. meningitidis
- helps the org. move deeper into the host to get into the meninges and brain to cause inflammation
what serogroups are we concerned with and why?
A, B, C, W-135, and Y
- these cause human disease
Virulence factors of N. Meningitidis
- polysaccharide capsule
- pili
- PorA and PorB expression
- Opa proteins
- Rmp (reduction-modifiable proteins)
- Lipooligosaccharide (LOS)
- release “blebs” during growth
- IgA1 protease
Virulence factors of N. gonorrhoeae
- pili
- PorB expression
- Opa proteins
- Rmp (reduction-modifiable proteins)
- Lipooligosaccharide (LOS)
- release “blebs” during growth
- IgA1 protease
how do pili help Neisseria spp.?
- attachment, genetic transfer, and motility
- expression ass. w/ virulence: attachment to non-ciliated epithelial cells, resistance to neutrophils
- conserved N-terminal, variable C-terminal
- pilC contributes to antigenic diversity
how do Porin proteins A and B help Neisseria pathogenesis?
- antigenic variation make them poor vx targets
- they interfere with neutrophil degranulation
- they facilitate invasion into epithelial cells and intracellular survival
- Resistance to C’ mediated killing
how do Opacity proteins (opa proteins) help Neisseria pathogenesis?
- they mediate intimate binding to epithelial and phagocytic cells
- important for cell-cell signalling
- multiple alleles
how do Rmp proteins help Neisseria Spp. affect the host?
they stimulate antibody production that blocks complement
What makes Neisseria a human-specific pathogen?
they bind to host transferrin, lactoferrin, and hemoglobin to scavenge for iron from the host
How is LOS different from LPS?
- only has Lipid A and core oligosaccharide
- Lacks O-antigen polysaccharide
- endotoxin activity present, but not as strong as LPS
What is important about the bleb release with Neisseria spp.?
- they contain LOS and surface proteins
- they enhance endotoxin activity and provide decoys
T/F
IgA1 protease cleaves hinge region to inactivate
true
Pathogenesis of Neisseria spp.
- attached to non-ciliated columnar epithelial cells
- invade:
- -> type IV pili induce endocytosis (pili, PorB, Opa involved)
- transcytosis to reach macrophages
- LOS induces TNFa
- antibodies to LOS activate C’ but Rmp antibodies block C’
- bacterial killing occurs mostly by neutrophils
- MAC complex is effective
Clinical disease of N. meningitidis
- meningitis
- meningococcemia
clinical signs of meningitis
- abrupt onset headache, stiff neck, photophobia, fever
- mortality ~100% if untreated, <10% with antibiotics
- Death can occur within 12 hrs of 1st symptoms
- neurologic sequellae low in survivors, with hearing deficits and arthritis most common, although amputations are often necessary due to damage of the extremities
clinical signs of meningococcemia
- septicemia with or without meningitis
- thrombosis of small blood vessels, multorgan involvement
- small petechial skin lesions on trunk and lower extremities, coalesce to hemorrhagic lesions
- DIC with shock and bilateral destruction of adrenal glands
Strong Diff Dx test for N. meningitidis for those with meningococcemia
pressing down on one of the lesions, and it not disappearing
epidemiology of N. meningitidis
- commonly colonizes nasopharynx of school age and young adults, particularly college students in dorms
- carriage is transient
- humans are only natural carrier
transmission of N. meningitidis
respiratory droplets to close contacts
when is N. meningitidis dz most common?
in dry cold months
N. meningitidis is the ___ most common cause of ____
2nd; community acquired meningitis in adults
Clinical disease of Gonorrhea in men
- purulent urethral discharge an dburning sensation during urination, sometimes painful swollen testicles
percentage of men w/ gonorrhea who have acute symptoms
95%
complications of gonorrhea in men
- epididymitis
- prostatitis
- periurethral abscess
Clinical disease of Gonorrhea in women
most women asymptomatic
where is the primary site of infection for women with gonorrhea
the cervix
why can’t N. gonorrhoeae invade the vagina
they can’t penetrate the squamous epithelial cells there
symptoms of gonorrhea in women
- mostly asymptomatic, but:
- vaginal discharge, pain, or burning during urination
- vaginal bleeding between periods
- abdominal pain
what percentage of gonorrheal infections ascend to the uterus and fallopian tubes, causing pelvic inflammatory disease
10-20%
symptoms of rectal gonorrhea
- discharge
- anal itching
- soreness
- bleeding
- painful bowel movements
What is Ophthalmis neonatorum?
- vertical transmission of gonorrhea from mother to child
- causes purulent conjunctivitis
can also be in adults but is transmitted by direct contact in this case
what is gonococcemia?
disseminated infections with septicemia and infection of skin and joints
results from untreated asymptomatic infections
prevalence of gonococcemia
1-3% of infected women, less in men
clinical signs of gonoccemia
fever, arthralgia, suppurative arthritis in wrists, knees, ankles
pustular rash on erythematous base of extremities
may also present as redness and purulent of the eyes after dissemination through the body
N. gonorrhoeae epidemiology
- only occurs in humans
- 2nd most common STD in US
- ~700K infections / yr (US)
- same infection rate in males and females
- higher rate in blacks and hispanics
- men: 20% risk from single exposures
- women: 50% risk from single exposure
- asymptomatic infection more likely in women
which age group is mostly likely to be infected w/ gonorrhea
adolescents and young adults
Diagnosis of Neisseria
- PCR (gold standard)
- gram stain-sensitive for men with symptoms
- N. meningitidis can be found in CSF prior to tx
- culture: chocolate agar and selective media to suppress commensal growth
treatment of Neisseria
- penicillin (if susceptible)
- fluoroquinolones or ceftriaxone if resistant
- silver nitrate/erythromycin ointment on newborn eyes after birth
Neisseria vx facts
- polyvalent polysaccharide-protein conjugate vx effective against N. meningitidis serogroups A, C, Y, W-135
routine vx: 11-18 Yr olds
characteristics of Chlamydia
- Obligate intracellular
- similar to G(-) but do not stain w/ gram stain
what is the unique development cycle of chlamydia
- elementary bodies (infectious)
- reticulate bodies
EBs infect columnar epithelial cells, differentiate into RBs, replicate, and then revert to EBs. When the cell ruptures, the EBs are released to infect other cells. RBs die.
3 species of chlamydia
- c. trachomatis
- C. psittaci
- C. pneumoniae
Chlamydia Virulence factors and pathogenesis
- LPS w/ weak endotoxin activity
- no peptidoglycan layer
- host range limited
- major outer membrane protein
- outer membrane protein 2
what is the host range of Chlamydia
non-ciliated columnar, cuboidal, and transitional epithelial cells of mucous membranes
urethra, endocervix, endometrum, fallopian tubes, anorectum, resp. tract, conjunctiva
clinical symptoms of chlamydia are caused by _____ during replication and _____
- destruction of cells
- proinflammatory cytokine response
epidemiology of genital Chlamydia
- most common STD in US
- estimated 2.8 million infections per yr in US
epidemiology of Chlamydial conjunctivitis
- leading cause of preventable blindness worldwide
- infections occur predominantly in children
- transmitted eye to eye by droplet, hands, contaminated clothing, eye-seeking flies
- endemic in communities with crowded living conditions, poor sanitation, poor hygiene
Chlamydial conjunctivitis occurs when ____
what is the rate of conjunctivitis? of pneumonia?
mothers have active genital infection at time of birth
- 25%
- 10-20%
who is more likely to be infected with Chlamydia?
- overall women
- younger women more likely than most
clinical disease of genital chlamydia in women
- 80% asymptomatic
- cervicitis, endometritis, salpingitis, urethritis
- mucopurulent discharge from cervix, frequent need to urinate, painful sex, bleeding after sex
clinical disease of genital chlamydia in men
- ~25% asymptomatic
- mucopurulent discharge from penis, burning when urinating, swollen, painful testicles
what is Lymphogranuloma Venerium (LGV)
- condition of Chlamydia
- primary lesion at site of infection
- painless
- inflammation and swelling of draining lymph nodes, buboes that enlarge and can rupture, fever, chills, anorexia, headache, meningismus, myalgia
- occurs when C. trachomatis enters into breaks, tears, or other lesions in the mucosa or skin
ocular infections of Chlamydia
Trachoma
adult inclusion conjunctivitis
neonatal conjunctivitis
clinical signs of trachoma
- chronic disease, occurs in stages
- initially follicular conjunctivitis with diffuse inflammation –> intense inflammation
- conjunctiva becomes scarred, eyelids turn in (trichiasis), eyelashes abrade the cornea, corneal vascularization, and opacity, vision loss
clinical signs of adult inclusion conjunctivitis
- acute follicular conjunctivitis ass. with genital infections
thought to be caused by dissemination or from self-inoculation with contaminated fingers
mucopurulent discharge, keratitis, corneal infiltrates, corneal vascularization, scarring
clinical signs of neonatal conjunctivitis
- infants exposed during birth
- swollen eyelids, copious purulent discharge
if left untreated, corneal vascularization and conjunctival scarring
timing of neonatal conjunctivitis after birth. differentiate gonorrhea and chlamydia
gonorrhea: 2-5 days
chlamydia: 5-15 days
diagnosis of chlamydia
- PCR (gold standard)
- cytologic, culture (specimen must be collected from site. Giemsa stain on cervical scraping shows inclusions)
- microimmunofluorescence (MIF)
treatment of Chlamydia
LGV: doxycycline for 21 days
- ocular / genital: azythromycin (single dose)
- neonatal ocular: erythromycin 10-14 days
- neonatal gonococcal conjunctivitis: topical antibiotic prophylaxis (not applicable to neonatal chlamydial conjunctivitis)
T/F
elementary bodies are resistant to antibiotics
true
Haemophilus Ducreyi factoids
- ass. w/ sexual transmission of HIV
- not prevalent in US
H. ducreyi symptoms
- one or more sores or raised bumps on genitals, surrounded by narrow red border
- becomes filled w/ pus and ruptures, leaving a painful open sore that can persist for weeks/months
- men are 3-25x more likely to have the infection