Genital Chlamydia and Gonorrhea Epidemiology, Diagnosis, and Management William M. Geisler M.D., M.P.H. University of Alabama at Birmingham
Chlamydia and Gonorrhea Current Epidemiology
Chlamydia Epidemiology Public health problem worldwide Incidence in the U.S. increasing and at highest rates ever >1 million cases reported in 2006 Estimated >3 million new cases annually Majority of men and women with chlamydia are asymptomatic Highest rates in younger people (age < 30 years) Highest rates in the Southeast U.S Rates 8X higher in African Americans vs. Caucasians Rates higher in women vs. men Reinfection common within months (10-20%) Significant morbidity, especially in women Costly disease CDC STD Surveillance 2006 Report
Estimated New Cases of Chlamydia 1999 North America 4 million Latin America & Caribbean 9.5 million Western Europe 5 million Eastern Europe & Central Asia 6 million North Africa & Middle East 3 million Sub-Saharan Africa 16 million East Asia and Pacific 5.3 million South & Southeast Asia 43 million Australia & New Zealand 340,000 Total 92 million WHO, 2001
Chlamydia Rates: Total and by sex: United States, 1987 2006 Rate (per 100,000 population) 600 480 Men Women Total 360 240 120 0 1987 89 91 93 95 97 99 2001 03 05 Note: As of January 2000, all 50 states and the District of Columbia had regulations requiring the reporting of chlamydia cases.
Chlamydia Age- and sex-specific rates: United States, 2006 Men Rate (per 100,000 population) Women 3000 2400 1800 1200 600 0 Age 0 600 1200 1800 2400 3000 11.6 10-14 121.5 545.1 15-19 2862.7 856.9 20-24 2797.0 480.8 25-29 1141.2 222.2 30-34 415.7 120.8 35-39 174.2 65.1 40-44 69.0 27.8 45-54 25.6 9.1 55-64 6.8 2.8 65+ 2.2 173.4 Total 517.0
Chlamydia Rates by state: United States and outlying areas, 2006 Guam 494 283 283 263 234 279 348 206 376 350 406 510 682 435 286 252 339 365 357 363 283 309 318 420 317 350 285 160 396 318 214 425 387 366 297 525 503 430 651 331 395 275 175 VT 191 NH 152 MA 241 RI 292 CT 312 NJ 232 DE 429 MD 390 DC 612 Rate per 100,000 population <=150 150.1-300 >300 (n= 1) (n= 21) (n= 32) Puerto Rico 130 Virgin Is. 187 Note: The total rate of chlamydia for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 345.0 per 100,000 population.
Chlamydia Rates by race/ethnicity: United States, 1997 2006 Rate (per 100,000 population) 1700 1360 1020 American Indian/AK Native Asian/Pacific Islander Black Hispanic White 680 340 0 1997 98 99 2000 01 02 03 04 05 06
Gonorrhea Epidemiology Incidence in the U.S. declined in the 80 s and 90 s, but has increased in the last 2 years > 350,000 cases reported in 2006 Estimated > 600,000 new cases annually Majority of women with gonorrhea are asymptomatic Significant morbidity, especially in women Highest rates in younger people (age < 30 years) Rates 18X higher in African Americans vs. Caucasians Rates now slightly higher in women Highest rates in the Southeast, and in inner cities Drug use and prostitution are also risk factors Quinolone-resistant N. gonorrhoeae (QNRG) rising nationally CDC STD Surveillance 2006 Report
Estimated New Cases of GC,1999 North America 1.5 million Latin & South America 7.5 million Western Europe 1 million North Africa & Middle East 1.5 million Sub- Saharan Africa 17 million Eastern Europe & Central Asia 3.5 million East Asia & Pacific 3 million South & Southeast Asia 27 million Australia & New Zealand 120,000 Total 62 million WHO, 2001
Gonorrhea Rates: United States, 1941 2006 and the Healthy People 2010 target Rate (per 100,000 population) 500 400 Gonorrhea 2010 Target 300 200 100 0 1941 46 51 56 61 66 71 76 81 86 91 96 2001 06 Note: The Healthy People 2010 target for gonorrhea is 19.0 cases per 100,000 population.
Gonorrhea Rates: Total and by sex: United States, 1987 2006 and the Healthy People 2010 target Rate (per 100,000 population) 400 320 Male Female Total 2010 Target 240 160 80 0 1987 89 91 93 95 97 99 2001 03 05 Note: The Healthy People 2010 target for gonorrhea is 19.0 cases per 100,000 population.
Gonorrhea Age- and sex-specific rates: United States, 2006 Men Rate (per 100,000 population) Women 750 600 450 300 150 0 Age 0 150 300 450 600 750 6.3 10-14 35.1 279.1 15-19 647.9 454.1 20-24 605.7 320.9 25-29 294.9 185.7 30-34 125.5 130.8 35-39 65.7 93.5 40-44 33.9 53.0 45-54 12.9 18.4 55-64 2.9 4.2 65+ 0.7 117.1 Total 124.6
Gonorrhea Rates by state: United States and outlying areas, 2006 Guam 58.1 67.3 20.7 40.1 14.4 23.6 115.6 36.0 93.4 79.2 100.2 89.9 94.9 69.4 24.0 47.3 81.5 80.5 133.2 139.5 64.4 66.3 175.9 154.9 125.1 240.6 154.9 158.2 139.2 162.6 167.4 78.5 52.5 234.0 216.8 257.1 242.5 92.2 85.6 199.4 134.8 90.7 10.4 VT 11.6 NH 13.7 MA 38.0 RI 47.2 CT 74.4 NJ 63.0 DE 176.0 MD 130.8 DC 342.8 Rate per 100,000 population <=19.0 19.1-100.0 >100 (n= 5) (n= 27) (n= 22) Puerto Rico 7.7 Virgin Is. 31.3 Note: The total rate of gonorrhea for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 119.4 per 100,000 population. The Healthy People 2010 target is 19.0 cases per 100,000 population.
Gonorrhea Rates by race/ethnicity: United States, 1997 2006 Rate (per 100,000 population) 900 720 540 360 American Indian/AK Native Asian/Pacific Islander Black Hispanic White 180 0 1997 98 99 2000 01 02 03 04 05 06
Chlamydia and Gonorrhea Clinical Presentation
Uncomplicated Chlamydia or Gonorrhea Males Urethritis Most common manifestation (other uncomplicated manifestations include conjunctivitis, pharyngitis [GC] and proctitis [in MSM]) Chlamydia usually asymptomatic (over 50%) Acute gonorrhea often symptomatic Co-infection with gonorrhea and chlamydia common Symptoms and signs Dysuria Urethral discharge > 5 PMNs/oif on urethral Gram stain Intracellular Gram-negative diplococci on urethral Gram stain (representing GC)
NGU (e.g. chlamydia) Urethral Discharge Gonorrhea Photographed by Dr. James Sizemore
Uncomplicated Chlamydia or Gonorrhea Females Cervicitis Most common manifestation (other uncomplicated manifestations include urethritis, bartholinitis, proctitis, conjunctivitis, and pharyngitis [GC]) Majority are asymptomatic (over 75% for chlamydia) Symptoms nonspecific Vaginal discharge Intermenstrual bleeding Painful sex Abdominal pain Dysuria
Uncomplicated Chlamydia or Gonorrhea Females Cervicitis Signs Cervical examination usually normal Mucopurulent discharge from endocervix Easily induced endocervical bleeding Hypertrophic ectopy Edema Erythema Bleeding
Cervicitis Normal http://www.brooksidepress.org/products/military_obgyn/ Textbook/Discharge/Discharge.htm
Complications Upper Genital Tract Infection Pelvic Inflammatory Disease (PID) in women Epididymitis in men Complications from Upper Genital Tract Infection Infertility (women and men) Ectopic pregnancy Other Complications Reiter s syndrome (Chlamydia) Disseminated infection (Gonorrhea) Increase in HIV transmission/acquisition risk
Chlamydia and Gonorrhea Screening Recommendations Diagnostic Testing
Screening Considerations Annual chlamydia screening for all sexually active females <25yo and those >25yo with risk factors (new or multiple sex partners) is recommended by the CDC Screening 15-25yo females is a HEDIS measure Chlamydia screening recommended for males in high chlamydia prevalence venues or when resources permit Compliance with screening recommendations is low This can be significantly improved with availability of urine-based nucleic acid amplification tests (NAATs) Screening, universal or selective, can have a dramatic impact on prevalence and complications of chlamydia Marrazzo et al. Sex Transm Dis 1997;24 Scholes et al. N Engl J Med 1996;334
Screening Considerations Gonorrhea screening recommended in subjects with risk factors and in areas of high gonorrhea prevalence Most nucleic acid amplification tests include gonorrhea testing along with chlamydia testing
Chlamydia Diagnosis Overview Serology (C. trachomatis IgG) cannot distinguish past from current infection Culture or Direct Fluorescence Antibody (DFA) technically difficult and not widely available only performed on genital swab specimens, not urine DNA Probe or Enzyme Immunoassay least sensitive assays available only performed on genital swab specimens, not urine Nucleic Acid Amplification Test most sensitive tests available (sensitivity >90%) highly specific (98-99.9%) performed on urine (first void) or genital swab specimens can also test for gonorrhea on same specimen cost-effective in most settings facilitates screening, especially when exam not feasible
Gonnorhea Diagnosis Overview Gram Stain of Genital Swab Specimen (presumptive diagnosis) Useful in symptomatic men (95% sensitivity) Limited utility (low sensitivity) in women and asymptomatic men Culture performed on genital swab specimens, not urine useful if antimicrobial susceptibility testing desired DNA probe or Enzyme Immunoassay least sensitive assays available performed on genital swab specimens, not urine Nucleic acid amplification test most sensitive tests available (sensitivity >90%) highly specific (98-99.9%) performed on urine (first void) or genital swab specimens can also test for chlamydia on same specimen facilitates screening, especially when exam not feasible
Nucleic Acid Amplification Tests (NAATs) The new gold standard in chlamydia and gonorrhea testing The preferred diagnostic test for screening Readily available in most commercial diagnostic laboratories Approved NAATs APTIMA TM Combo 2 Assay (Gen-Probe, Inc.) Uses transcription-mediated amplification Genital swabs and first-void urine specimens similar efficacy ProbeTec TM ET Assay (BD Diagnostics) Uses strand displacement amplification Genital swabs and first-void urine specimens similar efficacy COBAS AMPLICOR TM, CT or GC (Roche Diagnostic Systems) Uses polymerase chain reaction For CT testing, genital swabs and first-void urine specimens similar efficacy For GC testing, AMPLICOR TM not approved for female urines or asymptomatic male urethral swabs due to lower sensitivity (< 90%)
Chlamydia and Gonorrhea Treatment
2006 CDC STD Treatment Guidelines Uncomplicated Chlamydia: Nonpregnant Recommended: Azithromycin 1 g PO single dose OR Doxycycline 100 mg BID 7 days Alternative: Erythromycin base 500 mg QID 7 days Ofloxacin 300 mg BID 7 days Levofloxacin 500 mg daily 7 days (Quinolones approved for adolescents >45kg) * New recommendation compared to 1998 CDC guidelines
2006 CDC STD Treatment Guidelines Uncomplicated Chlamydia in Pregnancy Recommended: Azithromycin 1 g PO single dose OR Amoxicillin 500 mg PO TID x 7 days Alternative: Erythromycin base 500 mg QID 7 days * New recommendation compared to 1998 CDC guidelines
2006 CDC STD Treatment Guidelines (Updated for GC in Apr 13, 2007 MMWR) Uncomplicated Gonococcal Infections Recommended: Cefixime 400 mg PO single dose Ceftriaxone 125 mg IM single dose Additionally: Empiric treatment to cover co-infection with chlamydia Quinolones no longer recommended to due an increase in quinolone-resistant Neisseria gonorrhoeae nationwide Alternatives include spectinomycin 2G IM single dose, oral cephalosporin single dose (cefpodoxime 400mg or cefuroxime 500mg), or azithromycin 2G oral single dose * New recommendation compared to 1998 CDC guidelines
Gonococcal Isolate Surveillance Project (GISP) Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990 2006 Percent 16.0 12.0 Resistant Intermediate resistance 8.0 4.0 0.0 1990 91 92 93 94 95 96 97 98 99 2000 01 02 03 04 05 06 Note: Resistant isolates have ciprofloxacin MICs 1 µg/ml. Isolates with intermediate resistance have ciprofloxacin MICs of 0.125-0.5 µg/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990.
Other Treatment Issues No test of cure in nonpregnant persons unless symptoms persist or re-exposed Test of cure with NAATs > 3 weeks post-therapy in pregnant women Rescreen all chlamydia-infected women in about 3 months posttreatment (due to high recurrence rate) Consider rescreening chlamydia-infected men in about 3 months post-treatment Repeat positive tests most likely due to reinfection (untreated or new partner) Sexual partners should be evaluated and treated Recommend abstinence until patient and partner treated
Self-Referral Partner Treatment Expedited Partner Therapy (EPT) Patient-delivered or provider-delivered Consider for partners of heterosexual patients with chlamydia and/or gonorrhea Not yet standard of care Has advantages and disadvantages Legal issues
CDC collaborated with the Center for Law and the Public s Health at Georgetown and Johns Hopkins Universities to assess the legal framework concerning EPT across all 50 states and other jurisdictions (the District of Columbia and Puerto Rico).
Summary Reported rates of chlamydia and gonorrhea are increasing The majority of chlamydia-infected individuals are asymptomatic Sexually active adolescents and young adults are at highest risk for chlamydia Annual chlamydia screening is recommended for this population Chlamydia screening for this population is a HEDIS measure Repeat chlamydia screening recommended 3 months post-therapy Compliance with chlamydia screening is low NAATs are the recommended test Both chlamydia and gonorrhea testing performed Testing can be performed on urine (noninvasive and should improve compliance with screening) In addition to CDC-recommended antibiotic treatment for infected patients, partner treatment is crucial