Sexually Transmitted Diseases

1. Sexually Transmitted Diseases 2005-02

2. Sexually Transmitted Diseases • Impact • Common Infectious Agents • Symptoms • Pathogenesis • Diagnosis • Treatment

3. Impact • 19 million new cases/yr in USA • Major part of health care budget • Major part of medical practice • Serious side effects • Infertility • Premature birth • Cesarian sections • Birth defects • Neonatal disease • Death

4. Incidence and Prevalence • STD Incidence Prevalence • Chlamydia 2,800,000 N.R. • Gonorrhea 700,000 N.R. • Syphilis 32,000 N.R. • Herpes (HSV) 1,000,000 45,000,000 • Hepatitis B 60,000 1,250,000 • Genital Warts (HPV) 6,200,000 20,000,000 • Trichomoniasis 7,400,000 N.R. • 15-24 year-old

5. Common Features • Human only • Transmission • Virulence Mechanism • Inapparent Infection • Prevention • Abstinence • Monogamy

6. “Drips” Urethritis Gonorrhea Non-gonoccal urethritis Vaginal discharge Trichomoniasis “Bumps” Warts Swollen lymph glands AIDS Chancroid Lymphogranuloma venereum (LGV) Genital ulcer disease Herpes Syphilis Chancroid LGV Two Major Presentations

7. STD’s • Most commont • Non-gonococcal urethritis • Gonorrhea • Genital herpes • Genital warts • Trichomoniasis • Less common • AIDS • Syphilis • Uncommon • Chancroid • LGV

8. STD overview • Encounter • Genital contact • Blood • Entry • External genitalia • Mucosal membrane (genital, anal or oral) • Spread • Mucosal surface (local) • Systemic • Multiplication - most fastidious • Neisseria gonorrhoeae: Thayer-Martin • Chlamydia trachomatis: obligate intracellular • Treponema pallidum: can not be cultured in vitro

9. STD overview • Host defenses • Non-specific mucosal defense • Recruit phagocyte during infection • sIgA • Phagocyte and complement (systemic) • Damage • Inflammation leading to scarring • Intracellular cytotoxicity (Chlamydia) • Spread to new hosts • Sexual contact • Neonatal or congenital • Blood

10. Gonorrhea • Many asymptomatic • Reason for spread • Male- Urethritis, urethral discharge • Female - Endocervicitis, discharge, dysuria, bleeding • Pharyngitis • Proctitis • Disseminated gonococcal infection (DGI) • Pustular skin lesions • Septic arthritis • Pelvic inflammatory disease (PID) • Endometritis, salpingitis, peritinitis • Infertility, ectopic pregnancy • Ophthalmia neonatorum

11. Neisseria gonorrhoeae • Gram-, diplococcus • Gram stain pus, intracellular diplococcus • Virulence factors • Pili • Initial attachment • Antigenic and phase variation • Opacity protein (Opa) • Tighter contact and invasion • Antigenic variation • LOS (lipooligosaccharide, lack O-Ag) • Inflammatory, major cause of symptom • IgA protease

13. Pili antigenic variation

14. Phase variation PilC Opa

15. N. gonorrhoeae

16. Gonorrhea • Diagnosis • Intracellular Gram negative diplococci in discharge • Growth on selective media, oxidase positive colonies • Fluorescent antibody • Treatment • Cover for probable association with C. trachomatis

17. Non-gonococcal Urethritis • Infectious agents • Chlamydia trachomatis • Ureaplasma urealyticum • Symptoms of Chlamydial infection • Often inapparent in men • Watery or mucopurulent discharge • Dysuria • In women, mucopurulent cervicitis, salpingitis, premature labor • In newborns may cause conjunctivitis or pneumonia

18. Chlamydia trachomatis • G- type, no peptidoglycan • Obligate intracellular • Energy parasite - ATP • Evade phagocytosis and complement • Disease resembles neisseriae • Urethritis • Cervicitis, salpingitis, PID • Infant pneumonia • Conjunctivitis • Lymphogranuloma venereum (LGV) • Damage • Cytotoxicity, necrosis, scarring

19. C. trachomatis • Life cycle • Elementary body • Resistant to extracellular environment • Do not reproduce in this form • Infectious • Reticulate body • Replicative form • Form inclusion body in vacuole • Not infectious • Converts into EB and release

20. C. trachomatis • Infection of epithelial cells • Male - Urethra • Female - cervix, endometrium or fallopian tubes • LPS mediated inflammation • Alternative complement pathway • Activate macrophage to produce TNFa and IL-8 which is chemotactic to PMNs • Tissue damage • Tissue repair after the infection is resolved • Scarring

21. C. trachomatis • Diagnosis • – grow in fibroblasts, detect with flourescein-labeled antibody • PCR • Treatment • Keep in mind – no peptidoglycan

22. Other Common STD’s • Genital herpes • Caused by HHV 1 • Causes painful ulcers and (with a primary infection) asceptic meningitis • Can be treated with acyclovir • Genital warts • Caused by papilloma virus • May cause cervical cancer • Trichomoniasis • Caused by Trichomonas vaginalis • Asymptomatic in men • Causes severe vaginal itching and a blood-tinged discharge in women • Treated with metronidazole

23. Haemophilus ducreyi • G- cocco-bacillus • Genital ulcers • Chancroid - soft chancre • Painful • Unindurated • Potentiates the spread of HIV • Uni- or bilateral lymphadenopathy

24. Treponema pallidum • Spirochetes that do not Gram stain • Dark field or fluorescent microscopy • Endoflagellum

25. Stages of Syphilis

26. Syphilis • Primary syphilis • Chancre on primary infection sites • External genitalia, perianal, lips or gums • Secondary syphilis • Generalized skin rash - palm and sole • Fever, malaise and headache • Latent syphilis • Asymptomatic and non-infectious • Tertiary syphilis (4-10 years after secondary) • Gumma (granulomatous dermal lesions) • Neurosyphilis • Paresis, blindness, neurological signs • Cardiovascular syphilis • Delayed type hypersensitivity - immune response

27. Primary Syphilis -- chancre

28. Secondary Syphilis -- rash

29. Syphilis • Congenital syphilis • Infection via blood and placenta • Similar to secondary syphilis • Mortality rate 25% • Treatment • Primary and secondary • Penicillin or doxycycline • Tertiary syphilis • Antimicrobial not effective • Congenital syphilis • Penicillin treatment

30. Diagnosis • Detection of the organism in lesions • Serology • Indirect: anti-cardiolipin • VDRL: Venereal Disease Research Laboratory • RPR: Rapid Plasma Reagin • Direct: anti-treponemal Ab • FTA-ABS: Fluorescent treponemal antibody adsorption • MHA-TP: Microhemagglutination test for T. pallidum • Nucleic acid amplification tests