Sexually Transmitted Diseases

Sexually Transmitted Diseases Impact Common Infectious Agents Symptoms Pathogenesis Diagnosis Treatment

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

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 year-old

Common Features Human only Transmission Virulence Mechanism  Inapparent Infection Prevention  Abstinence  Monogamy

Two Major Presentations “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

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

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

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

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

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

Pili antigenic variation

Phase variation Opa PilC

N. gonorrhoeae

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

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

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

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

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

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

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

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

Treponema pallidum Spirochetes that do not Gram stain  Dark field or fluorescent microscopy  Endoflagellum

Stages of Syphilis

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

Primary Syphilis -- chancre

Secondary Syphilis -- rash

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

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