What are the bugs that cause non-ulcerative sexually transmitted bacterial infections? How do they present differently in males vs. females?
Chlamydia, gonorrhea and mycoplasma. In women they present with cervicitis, urethritis, endometritis, salpingitis and PID. In males they present as urethritis, epididymitis and proctitis.
What are the bugs that cause non-ulcerative sexually transmitted bacterial infections? How do their physical characteristics differ?
Neisseria gonorrhoeae is a gram-negative diplococcus that lives extra-cellularly. Chlamydia is an obligate intra-cellular pathogen. Mycoplasma does not have a cell wall.
Which non-ulcerative sexually transmitted bacteria are gram-negative, require CO2 for growth, are pyogenic and have increasing rates of antibiotic resistance?
Neisseria gonorrhoeae. Bacteria can transfer antibiotic resistance via conjugation (exchanging material) and transformation (taking up single stranded DNA).
Primary site of infection of gonorrhea in women?
Males: mucopurulent discharge in urethra, characterized by frequent, urgent and painful urination. Women: mucopurulent discharge in cervix, 50% is asymptomatic in women. Can also spread into paracervical glands and Bartholin glands.
How does site of infection differ by age in women with gonorrhea?
Prepubertal and post-menopausal women have vulvovaginitis. Non-pregnant women in reproductive years have infection that correlates with menstrual cycle (culture negative window after ovulation)
Why might a woman have vague symptoms of gonorrhea as they go through their cycle?
Progesterone causes a decrease in TLRs, which decreases the immune response to gonorrhea.
Where does the majority of antibiotic resistance in gonorrhea come from?
Genetic material exchange with commensal organisms in the pharynx when people have oral sex.
What can babies get when they are delivered by a mother who has gonorrhea?
Opthalmia neonatorum: acute purulent conjunctivitis (PMNs with gram negative diplococci) -> common cause of blindness in the U.S.
Characteristic histology of cervicitis, endometritis or salpingitis from gonorrhea infection?
Robust neutrophil response
Dissemination of gonorrhea into the peritoneum from the fallopian tubes that causes perihepatitis.
How do you diagnose PID in a woman who has been infected with chlamydia or gonorrhea?
Endocervical smear w/gram negative extracellular diplococci = gonorrhea. Monocolonal antibody smear for chlamydia (because it is intracellular).
A 25 year old man presents with unilateral testicular pain and swelling. He complains of painful urination, urethral discharge and blood in the semen. He states that ejaculation is painful and that he has had a low-grade fever and chills for the past week. What has happened if he later complains of papillary lesions around the fingers/toes and migratory polyarthritis?
He is originally complaining of epididymitis from gonorrhea or chlamydia. Gonorrhea does not have a capsule which makes it able to evade the immune system and cause disseminated gonococcal infection, which he is presenting with (dermatitis and gonococcal arthritis).
Leading cause of septic arthritis in young adults. How do you make the diagnosis?
Gonococcal arthritis. Synovial fluid will have a positive culture 30% of the time.
Why might a gonococcal vaccine be easier to develop for males than for females?
Gonorrhea needs lactoferrin, transferrin and Hgb-binding proteins in order to obtain iron from the host. In males there is not a lot of iron supply for the bacteria unless it binds to these structures. In women, regular menese makes it easier for these bacteria to get iron without binding to these receptors.
Why can you continue to get gonorrhea even if you’ve been infected previously?
It has an IgA1 protease and can invade epithelial cells with Opa proteins and live intracellularly. It has porins (P1A and P1B) that bind complement regulatory proteins (C4bp and factor H). It coats its LOS with sialic acid with sialyltransferase. Finally, it doesn’t have a capsule which downregulates complement.
How does N. gonorrhoeae damage fallopian tubes?
It releases blebs of LOS and peptidoglycan fragments that causes cilia to slough off and damages the cells. (Direct gonococcal toxicity).
How does gonorrhea have so much antigenic variation?
It can change pilin types that make up pili. This ensures that the host does not have antibodies for the specific pilin types expressed on new infections.
Why does gonorrhea increase the risk for other STIs like HIV and chlamydia?
Although N. gonorrhoeae induces a strong Th17 response, there is a poor adaptive response and can induce immunosuppression in the host. This is part of the reason it is difficult to make a successful vaccine for the bacteria.
Lab diagnosis for gonorrhea
Gram stain is pretty sensitive and specific for men. Not as much for women because they have lots of bacteria in their reproductive tract. NAAT (nucleic acid amplification tests) are the best means of diagnosis.
How do you culture a suspected gonococcal infection?
5% CO2 required, chocolate agar for sample from sterile source, Thayer Martin (most used) or Martin Lewis agar for contaminated sources.
How did N. gonorrhoeae become resistant to penicillin?
Porin mutations (drugs can't get in), altered penicillin binding proteins (don't bind penicillin, maintaining transpeptidase activity) and overexpression of MDR active efflux pumps due to mutation in mtr pump repressor gene.
What is the current recommendation for treatment of gonorrhea?
Dual therapy: ceftriaxone with azithromycin or doxycycline. This will also treat for chlamydia.
Serovars of chlamydia that cause urethritis, cervicitis and conjunctivitis
Male non-gonococcal urethritis in men vs. gonococcal urethritis in men
Non-gonococcal urethritis presents with the same urgency and painful urination, but discharge is usually clear and not purulent.
Chlamydia presentation in females
Usually asymptomatic and clear discharge. Note that this is associated with migratory polyarthritis (Reiter’s syndrome).
Aside from the urogenital tract, what other regions are affected by Chlamydia trachomatis D-K?
Rectum, pharynx and follicular conjunctivitis that can lead to blindness.
What is the lifecycle of chlamydia?
Elementary body (infectious body) invaded epithelial cells -> Multiply within epithelial cells and form inclusions and reticulate body -> Cell lyses and elementary bodies infect other cells.
What causes damage in c. trachomatis infection?
Host response causes scarring in the fallopian tubes and conjunctiva. This differs from gonococcal infections where damage is due to direct bacterial toxicity.
A homosexual male presents with a painless necrotic abscesses on his penis and proctitis. He was also recently diagnosed with HIV. Physical exam reveals swollen lymph nodes. What is the most likely diagnosis?
This is C. trachomatis LGV infection.
How does the laboratory diagnose chlamydia?
Urine NAAT or urethral/cervical swab NAAT or culture + immunohistochemistry.
Treatment of c. trachomatis
Genital: azithromycin or doxycycline Babies: azithromycin
What bug makes up 20% of non-gonococcal urethritis?
How do we culture mycoplasma?
PPLO (fried egg colonies)
Top 2 most common infections reported to the CDC each year?
#1) Chlamydia (1 million per year) #2) Gonorrhea (350,000 cases per year, heavy in South)
Why are people with ulcerative STDs at higher risk for HIV?
Lots of cells in the ulcers are susceptible to HIV infection
What are younger women at increased risk for chlamydia or gonorrhea?
Cervical ectopy: the columnar epithelial cells are most susceptible to C. trachomatis or N. gonorrhoeae. With age the outside of the cervix becomes more squamous and less susceptible to infection.
Core groups STIs that travel around a network of people
Gonorrhea, HIV and syphillis. Stopping the infection in one person can stop the spread to many other people.
What antibiotic has most gonorrhea become resistant to most recently?
Why is nonoxynol-9 a bad drug?
It is a detergent damages epithelial cells, causes inflammation and makes people more susceptible to STIs.