Lecture 20: Sexually Transmitted Infections STIs

(Sexually Transmitted Infections STIs) Lecture 20 STI Diseases of Reproductive Tract: · PID = pelvic inflammatory disease (chlamydia or gonorrhoeae) · cervicitis, vaginitis, urethritis · HSV herpes simplex · genital warts (HPV) · vaginosis (not always transmitted sexually) · NGU = nongonococcal urethritis (Chlamydia) · arthropod manifestations (eg. lice) Lecture Focus: · Chlamydia trachomatis · Neisseria gonorrhoeae · Treponema pallidum · Haemophilus ducreyi · HPV (human papillomavirus) · HSV Cherpes simplex) STI Characteristics · no vaccines available except for HPV · produces negligible symptoms initially · may persist if untreated and symptoms may reoccur (eg. Herpes latent) · lack of immunity: agents are poorly antigenic or have immune evasion ability ↳ lack of antigens or antigenic variability · finicky, adapted to be spread from mucous membranes to mucous membranes (sensitive to drying) PID (pelvic inflammatory disease) · extensive infection: cervix, uterus, fallopian tubes, ovaries · can spread to peritoneal cavity and cause hepatitis · over 50% of women are asymptomatic but can have complications · symptoms: lower abdominal pain radiating to back, slightly more discharge from vagina · Chlamydia trachomatis is the dominating cause, then Neisseria gonorrhoeae · inflammation leads to scarring in fallopian tubes that can make you sterile or lead to ectopic pregnancy Chlamydia trachomatis · most common bacterial STD · Gram-, but cannot use gram stain because it must live in host cells and the stain won't penetrate and particles are too small · unique developmental cycle ↳ infectious form (EB): elementary body like an infectious spore, package with thick layer of proteins and genetic material inside ↳ metabolically active form (RB): reticulate body, divides to make RBC · obligate intracellular parasites · must get ATP (energy) from the host cell Three Species of Chlamydia Infect Humans · C. trachomatis serotypes A-C cause trachoma (eye infections) serotypes D-K cause genital infection and inclusion conjunctivitis serotypes L1, L2, L3 cause LGV · C. psittaci zoonosis from birds (parrots), respiratory infection (pneumonia) · C. pneumoniae respiratory infection associated with cardiovascular disease Pathogenicity of Chlamydia · elementary bodies (EB) bind host cell receptors, internalized in a host cell membrane bound vacuole · Chlamydia vacuole (inclusion) does not fuse with host lysosome · Chlamydia then replicates in the host cell and can lyse the host cell, causing inflammation ↳ no exotoxins, inflammation causes the damage · LGV (lymphogranuloma venereum) is invasive, causing systemic disease Genital Infection with C. trachomatis D-K · endemic (always present) · highest frequency in 15-25 year olds (b/c more sexually active) · 50% asymptomatic in women · PID (pelvic inflammatory disease) ↳ scarring of fallopian tubes ↳ ectopic pregnancy Infertility · cause of NGU (non-gonococcal urethritis in men) LGV (lymphogranuloma venereum) · C. trachomatis L1, L2, L3 · characterized by supparative inguinal adenitis ↳ inflammation of lymph glands in groin and sores with pus · most common in tropics · untreated can result in tissue damage, fibrosis, elephantasis · Laboratory diagnosis: ↳ DNA probes, PCR (urine and secretions) · Treatment: ↳ tetracycline or macrolides (inhibits protein synthesis) eg. azithromysin ↳ partner tracing ↳ NO VACCINE Penis Gonorrhea Gonorrhea (GC) or "The Clap" · caused by Neisseria gonorrhoeae · symptoms: painful urination with pus (or white discharge) · G- aerobic diplococci · twitching motility (don't move well with pili) · no capsule · humans are only reservoir · transmission: direct contact (sexual contact) ↳ pregnant women can transmit infection to their child resulting in opthalmia neonatorum - · virulence factors: ↳ pili: adhesin and invasin, bind to non-ciliated epithelial cells ↳ Opa: outer membrane proteins, adhesins and invasins - adhere to a variety of eukaryotic cells - one strain can express 0-11 Opa proteins, on average 3 (antigenic variation does not allow immune response to keep up) ↳ Lipooligosaccharide (LOS) - lipid A in long chain of sugars - sialic acid residues, giving capsule like properties (can hide from immune system) - inflammation is induced by Lipid A ↳ IgA protease - destroys IgA antibodies on mucosal surfaces - allows adherence of bacteria to the basement membrane Immune Evasion · sialic acid attached to LOS ↳ "self-identification" · phase variation ↳ can turn off the OPA and LOS · antigenic variation urethral smear (pus) ↳ N. gonorrhoea inside neutrophils No lifelong immunity Clinical Features of Gonorrhea Males: · much more likely to show symptoms · symptoms Females: · majority are asymptomatic (50-80%) · symptoms ↳ Vaginal discharge ↳ painful urination ↳ purulent (pus) urethral discharge ↳ vaginal bleeding ↳ painful urination · uncommon, but can lead to epididymitis and reactive arthritis ↳ lower abdominal pain · 10-20% acquire pelvic inflammatory disease (PID) Clinical Features of Gonorrhea · Rectal gonorrhea (anal intercourse) ↳ majority asymptomatic ↳ discharge, rectal bleeding · Pharyngeal gonorrhea ↳ majority asymptomatic ↳ sore throat and cervical adenitis Diagnosis · finding G- diplococci in WBC from pus, or urethral discharge (men only) · culture, DNA probes, PCR · antibiotic susceptibility tests as there is increasing antibiotic resistance · Disseminated Gonococcal Infection (DGI) ↳ systemic infection with lots of cytokines ↳ primary symptom is fever ↳ bacteremia may lead to endocarditis and meningitis, but majority result in monoarticular arthritis Prevention · case finding and partner notification · abstinence · safe sex Treatment · treat patients with antibiotics for all bacterial STI's b/c its likely you have more than one ↳ Chlamydia trachomatis, Neisseria Gonorrnoeae, Treponema pallidum · partner tracing and treatment important · penicillin WAS drug of choice until GC produced beta-lactamase · No vaccine Syphilis (Treponema pallidum) · Spirochaete, cell wall contains lipids (no LPS and not visible in Gram stain) · cannot be cultured without host · closely related to other Treponema species causing tropical diseases eg. T. pertenue (yaws), T. carateum (pinta) · bad complications: congenital disease in babies, dementia etc. · incubation period: usually 3 weeks (10-90 days) Three Stages of Disease ① Primary: initial sign is hard painless chancre (highly infectious) ↳ bacteria enter body and lymph ② Secondary: occurs weeks after chancre disappears, characterized by infectious rash on skin and mucous membranes latent period: may last months or years ③ Tertiary: 50% of patients enter chronic stage ↳ dementia, tissue deformation, gumma Pathogenesis · portal of entry: breaks in skin or mucous membranes · poorly antigenic: due to lipid content in cell walls, only dead Treponema can activate immune system and induce antibody formation · endoflagella (axial filament): helps to move through tissues · spread of the spirochaete systemically before immune defenses can activate · inflammatory responses cause "gumma" formation in tertiary syphilis ↳ thickened scar tissue due to chronic inflammation or appears as tissue deformities Diagnosis: · serology (antibodies specific to T. pallidum) · wet mount direct microscopy (only used with fresh chancre) Complications: Treatment · penicillin is drug of choice · no immunity, no vaccine · aortic aneurism · CNS damage (paresis), blindness, seizures, dementia · congenital syphylis Haemophilus ducreyi · small aerobic G- rods · causes chancroid HSV 1/2 · DNA virus, enveloped · incubation 1 week · soft chancre, painful · treated with ceftriazone · no permanent immunity · primary lesions are vesicles which breakdown to form shallow ulcers causing pain and discomfort in the genital area and on urination · chronic infection, latent infection in ganglia · most infectious when vesicles are apparent but can infect asymptomatic · complications: encephalitis, or disseminated herpes in fetus (fatal) HPV (genital warts) · papillomavirus, DNA virus, nonenveloped · certain genotypes are associated with cervical cancer and cancer of the penis (and anus, even pharangeal cancer possible) eg. types 16, 18 for cervical cancer · warts of the genital tract may be either flat or raised ("condylomata accuminata") · cervical (usually flat) warts removed by laser or podophyllin, visualized by acetic acid · vaccine for nine genotypes · gardasil and cervarix (16, 18)