1. Review from last lecture Skin Infections: Contrasting Staph aureus with Strep pyogenes Folliculitis, boils and carbuncles Rocky mountain spotted fever (R. rickettsii) Lyme disease (B. burgdorferi) Anthrax (Bacillus anthracis) Bacterial infections of Wounds: Tetanus (C. tetani) Gangrene (C. perfringens) Burn infections (P. auerginosa) Actinomycosis (A. israelii)

3. Sexually-transmitted Diseases Denise Kirschner,PhD Dept of Micro/Immuno MICRO 532 Nov 29, 2001

4. Outline Epidemiological principles of STDs UTI/Bladder infections Infections of mucosal surfaces Neisseria gonorrhea and Chlamydia trachomatis Ulcerative Infections Syphilis (T. pallidium) and Chancroid (H. ducreyi)

6. General uro-genital tract information More female infections that males Urine is sterile Above bladder entrance-sterile, below lots of IM: Lactobacillus, Staphylococcus, Cornybacterium, Haemophilus, Streptococcus, Bacteriodes Urinary tract infections (UTI): More than 100,000 bacteria/ml indicated Bladder infection Catherization is the major cause of infection (usually IM) Intercourse (for women)

7. Mucosal infections Ulcerative infections Proliferative infections Sexually-transmitted Diseases gonorrhea chlamydia herpes simplex syphilis chancroid LGV papillomavirus Systemic infections HIV hepatitis B

8. Epidemiologic Principles of STDs

9. Disease Incidence Prevalence Chlamydia Gonorrhea Papillomavirus Herpes simplex Syphilis (primary) (all stages) HIV Chancroid 4,000,000 1,400,000 800,000 300,000 50,000 100,000 70,000 ~4,000 -- 45,000,000 30,000,000 100,000 1,500,000 ? Occurrence of STDs in the U.S.

10. Trends in common STDs Year 0 100 200 300 400 500 195019601970198019901995 chlamydia gonorrhea syphilis chancroid 20 40 60 198019901995 Note: 60% of all N. gonorrhea infection are ages 15-24

11. Determinants of STD Morbidity Rate of transmission Sexual behavior (rate of new partner acquisition) Duration of infectivity

12. Factors That Affect the Transmission of STDs: Age Gender Genetic susceptibility Sexual practices Contraceptive and "hygienic" practices Circumcision

13. Determinants of the Duration of Infectivity in STDs Etiologic agent tendency to asymptomatic carriage antimicrobial resistance Access and utilization of the health care system Compliance with therapy Contact tracing

15. Theoretical Structure of an STD Core Group

16. PPNG in Colorado Springs, Dec. 1989 - Dec. 1991 D J F M A M J J A S O N D J F M A M J J A S O N D CASESCASES - not gang-related - gang-related

17. PPNG Outbreak, Colorado Spgs., 1989-91 56 cases in a 2-year period Traced to a network of 578 persons 410 (218 males and 192 females) were affiliated with a street gang that moved to the area in May 1988. Mean age: females (19.7 yrs); males (21.5 yrs) Prominent behaviors among females: multiple partners, heavy crack use, drugs for sex

18. CO-INFECTIONS

19. Relevance of STD Co-infections May identify a core group member i.e., a "sentinel event" STDs increase transmission of HIV ulcerative and mucosal infections only Effect of HIV on expression of STDs accelerates HPV-associated tumors facilitates spread of gonococcus alters the natural course of syphilis Presumptive therapy 80-90% of college men with 1 STD have others (50% with Chlamydia) May identify a core group member i.e., a "sentinel event" STDs increase transmission of HIV ulcerative and mucosal infections only Effect of HIV on expression of STDs accelerates HPV-associated tumors facilitates spread of gonococcus alters the natural course of syphilis Presumptive therapy 80-90% of college men with 1 STD have others (50% with Chlamydia)

20. Infections of mucosal surfaces

21. Infections caused by gonococci and chlamydiae urethritis cervicitis epididymitis proctitis pharyngitis eye infection > >> + + +

22. Epidemiologic characteristics of chlamydial and gonococcal infections GONOCOCCUS CHLAMYDIA PATIENT AGE SEXUAL HISTORY ASX INFECTION (male) ASX INFECTION (female) teenagers > young adults usually acquired from a recent contact ~ 5% of infected males ( higher in some areas) 50 - 80% of infected females teenagers > young adults may have been acquired in the remote past ~ 50% of infected sexual partners ~ 50% of infected sexual partners ASX=asymptomatic

23. Microbiology of gonorrhea Strict human pathogen Gram-negative diplococcus Adherent- pilus (antigenic variation) IgA protease (cleaves IgA) Oxidase-positive Fastidious growth Modified Thayer-Martin media (VCN)

25. Virulence determinants of Neisseria gonorrhoeae  pilus colonization factor--> antigenic variation  opa proteins-------------------> phase variation  lipooligosaccharide--------->antigenic variation  IgA1 protease  transferrin/lactoferrin binding proteins  intracellular environment?

26. Treatment of gonococcal infections PPNG Tetracycline resistance Quinolone resistance Single-dose treatment options for uncomplicated disease: 1944 10^5 units of penicillin 1970 10^7 units Resistance (R plasmids) PPNG strain PPNG Tetracycline resistance Quinolone resistance Single-dose treatment options for uncomplicated disease: 1944 10^5 units of penicillin 1970 10^7 units Resistance (R plasmids) PPNG strain

28. Microbiology of Chlamydia trachomatis Obligate intracellular bacteria Not G+/G- (lacks part of LPS) Complex, 2-stage life cycle Elementary body (spore like) Reticulated body (vegetative like) Treatment: antibiotics: tetracyclines (not penicillin-why?) Obligate intracellular bacteria Not G+/G- (lacks part of LPS) Complex, 2-stage life cycle Elementary body (spore like) Reticulated body (vegetative like) Treatment: antibiotics: tetracyclines (not penicillin-why?)

31. Chlamydial infections urethritis (NGU) epididymitis proctitis mucopurulent cervicitis pelvic inflammatory disease trachoma (serotypes A-C) LGV (L1, L2, L3)

32. 50-60% of women with infertility have serologic evidence of chlamydia or gonococcus, but no history of symptoms!

33. Ulcerative infections

34. Frequency of genital ulcer infections HSV>>syphilis>>chancroid

35. Distinguishing features of genital ulcers anatomical location multiplicity pain induration

36. Microbiology of syphilis Treponema pallidum spirochete -- labile spiral bacterium with axial filaments man is the only recognized host non-cultivable Gram-negative like Treponema pallidum spirochete -- labile spiral bacterium with axial filaments man is the only recognized host non-cultivable Gram-negative like

37. T. pallidum darkfield examination

38. % reactive cases iary ge

39. Manifestations of 1° Syphilis Chancre (may be unnoticed) painless, but tender indurated highly contagious rapid dissemination motility of the organism? Congenital MANIFESTATIONS OF SECONDARY SYPHILIS Rash Lesions mucous patches Fever

40. Natural history of secondary syphilis Secondary infection spontaneous resolution infected without clinical disease tertiary syphilis: Neurosyphilis DTH Organisms rare 1/3

41. Syphilis- principles of treatment T. pallidum is exquisitely sensitive to penicillin Dosing and penicillin formulation used depends on the stage of the disease

42. Microbiology of chancroid Haemophilus ducreyi Gram-negative coccobacilli fastidious and labile Diagnosis is usually clinical, by exclusion of other agents of genital ulcers Haemophilus ducreyi Gram-negative coccobacilli fastidious and labile Diagnosis is usually clinical, by exclusion of other agents of genital ulcers

43. Epidemiology and treatment of chancroid CDC reported a 10-fold increase in incidence from 1978 - 1987 10% of patients are co-infected with either HSV or T. pallidum Males >> females Occurs in sustained, urban outbreaks Associated with female commercial sex workers and “sex-for-drugs” trade TREATMENT: sensitive to ceftriaxone or azithromycin in single dose