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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) Sexually-transmitted Diseases Denise Kirschner,PhD Dept of Micro/Immuno MICRO 532 Nov 29, 2001 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) 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) Sexually-transmitted Diseases Mucosal infections • gonorrhea • chlamydia Ulcerative infections • herpes simplex • syphilis • chancroid • LGV Proliferative infections • papillomavirus Systemic infections • HIV • hepatitis B Epidemiologic Principles of STDs Occurrence of STDs in the U.S. Disease Incidence Prevalence -Chlamydia 4,000,000 -Gonorrhea 1,400,000 Papillomavirus 800,000 45,000,000 Herpes simplex 300,000 30,000,000 Syphilis (primary) 50,000 (all stages) 100,000 100,000 HIV 70,000 1,500,000 Chancroid ~4,000 ? Trends in common STDs 500 400 chlamydia gonorrhea syphilis chancroid 300 200 60 40 100 20 0 1950 1960 1970 1980 Year 1990 1995 1980 1990 1995 Note: 60% of all N. gonorrhea infection are ages 15-24 Determinants of STD Morbidity Rate of transmission Sexual behavior (rate of new partner acquisition) Duration of infectivity Factors That Affect the Transmission of STDs: • Age • Gender • Genetic susceptibility • Sexual practices • Contraceptive and "hygienic" practices • Circumcision 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 Theoretical Structure of an STD Core Group PPNG in Colorado Springs, Dec. 1989 - Dec. 1991 - not gang-related - gang-related C A S E S 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 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 CO-INFECTIONS Relevance of STD Co-infections May identify a core group member STDs increase transmission of HIV ulcerative and mucosal infections only Effect of HIV on expression of STDs i.e., a "sentinel event" 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) Infections of mucosal surfaces Infections caused by gonococci and chlamydiae urethritis cervicitis epididymitis proctitis pharyngitis eye infection + + > + >> Epidemiologic characteristics of chlamydial and gonococcal infections GONOCOCCUS PATIENT AGE teenagers > young adults CHLAMYDIA teenagers > young adults SEXUAL HISTORY usually acquired from a recent contact may have been acquired in the remote past ASX INFECTION (male) ~ 50% of infected sexual partners ~ 5% of infected males ( higher in some areas) ASX INFECTION (female) ASX=asymptomatic 50 - 80% of infected females ~ 50% of infected sexual partners 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) 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? 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 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?) Chlamydial infections urethritis (NGU) epididymitis proctitis mucopurulent cervicitis pelvic inflammatory disease trachoma (serotypes A-C) LGV (L1, L2, L3) 50-60% of women with infertility have serologic evidence of chlamydia or gonococcus, but no history of symptoms! Ulcerative infections Frequency of genital ulcer infections HSV>>syphilis>>chancroid Distinguishing features of genital ulcers anatomical location multiplicity pain induration Microbiology of syphilis Treponema pallidum spirochete -- labile spiral bacterium with axial filaments man is the only recognized host non-cultivable Gram-negative like T. pallidum darkfield examination % reactive cases iary ge 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 Natural history of secondary syphilis 1/3 Secondary infection 1/3 1/3 spontaneous resolution infected without clinical disease tertiary syphilis: Neurosyphilis DTH Organisms rare Syphilis- principles of treatment T. pallidum is exquisitely sensitive to penicillin Dosing and penicillin formulation used depends on the stage of the disease Microbiology of chancroid Haemophilus ducreyi Gram-negative coccobacilli fastidious and labile Diagnosis is usually clinical, by exclusion of other agents of genital ulcers 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