1. Sexually Transmitted Diseases Part 2
Edward L. Goodman, MD
February 9, 2004

2. Background Information

3. Knowledge About STDs Among Americans
Background
Knowledge About STDs Among Americans
Source: Kaiser Family Foundation, 1996

4. Where Do People Go for STD Treatment?
Background
Where Do People Go for STD Treatment?
Population-based estimates from National Health and Social Life Survey
Private provider 59%
Other clinic 15%
Emergency room 10%
STD clinic 9%
Family planning clinic 7%
Source: Brackbill et al. Where do people go for treatment of sexually transmitted diseases? Family Planning Perspectives. 31(1):10-5, 1999

5. Background
Percent of Women Who Said Topic Was Discussed During First Visit With New Gynecological or Obstetrical Doctor/Health Care Professional
Percentages may not total to 100% because of rounding or respondents answering “Don’t know” to the question “Who initiated this conversation?”
Source: Kaiser Family Foundation/Glamour National Survey on STDs, 1997

6. Estimated Burden of STD in U.S. - 1996
Background
Estimated Burden of STD in U.S
STD
Incidence
Prevalence
Chlamydia
3 million
2 million
Gonorrhea
650,000
---
Syphilis
70,000
Trichomoniasis
5 million
HSV
1 million
45 million
HPV
5.5 million
20 million
Hepatitis B
77,000
750,000
HIV
20,000
560,000
Source: The Tip of the Iceberg: How Big Is the STD Epidemic in the U.S.? Kaiser Family Foundation 1998

7. Background
“...the scope and impact of the STD epidemic are under-appreciated and the STD epidemic is largely hidden from public discourse.”
IOM Report 1997

8. STD Prevention and Control
Education and counseling to reduce risk of STD acquisition
Detection of asymptomatic and/or symptomatic persons unlikely to seek evaluation
Effective diagnosis and treatment
Evaluation, treatment, and counseling of sexual partners
Preexposure vaccination--hepatitis A, B

9. Prevention Messages
Prevention messages tailored to the client’s personal risk; interactive counseling approaches are effective
Despite adolescents greater risk of STDs, providers often fail to inquire about sexual behavior, assess risk, counsel about risk reduction, screen for asx infection
Specific actions necessary to avoid acquisition or transmission of STDs
Clients seeking evaluation or treatment for STDs should be informed which specific tests will be performed

10. Prevention Methods Male Condoms
Consistent/correct use of latex condoms are effective in preventing sexual transmission of HIV infection and can reduce risk of other STDs
Likely to be more effective in prevention of infections transmitted by fluids from mucosal surfaces (GC,CT, trichomonas, HIV) than those transmitted by skin-skin contact (HSV,HPV, syphilis, chancroid)

11. Prevention Methods Spermicides
N-9 vaginal spermicides are not effective in preventing CT, GC, or HIV infection
Frequent use of spermicides/N-9 have been associated with genital lesions
Spermicides alone are not recommended for STD/HIV prevention
N-9 should not be used a microbicide or lubricant during anal intercourse

12. MSM
STD/HIV sexual risk assessment and client-centered prevention counseling
Annual STD screening for MSM at risk
-HIV and syphilis serology
-Urethral cx or NAAT, GC/CT
-Pharyngeal cx, GC (oro-genital)
-Rectal cx, GC/CT (receptive anal IC)

13. STDs of Concern Actually, all of them “Sores” (ulcers) Syphilis
Background
STDs of Concern
Actually, all of them
“Sores” (ulcers)
Syphilis
Genital herpes (HSV-2, HSV-1)
Others uncommon in the U.S.
Lymphogranuloma venereum
Chancroid
Granuloma inguinale

14. STDs of Concern (continued)
Background
STDs of Concern (continued)
“Drips” (discharges)
Gonorrhea
Chlamydia
Nongonococcal urethritis / mucopurulent cervicitis
Trichomonas vaginitis / urethritis
Candidiasis (vulvovaginal, less problems in men)
Other major concerns
Genital HPV (especially type 16, 18) and Cervical Cancer

15. “Drips” Gonorrhea Nongonococcal urethritis Chlamydia
Mucopurulent cervicitis
Trichomonas vaginitis and urethritis
Candidiasis

16. Empiric treatment in those with high risk who are unlikely to return
Urethritis
Mucopurulent or purulent discharge
Gram stain of urethral secretions > 5 WBC per oil immersion field
Positive leukocyte esterase on first void urine or >10 WBC per high power field
Empiric treatment in those with high risk who are unlikely to return

17. Gonorrhea - Clinical Manifestations
Drips
Gonorrhea - Clinical Manifestations
Urethritis - male
Incubation: d (usually 2-5 d)
Sx: Dysuria and urethral discharge (5% asymptomatic)
Dx: Gram stain urethral smear (+) > 98% culture
Complications
Urogenital infection - female
Endocervical canal primary site
70-90% also colonize urethra
Incubation: unclear; sx usually in l0 d
Sx: majority asymptomatic; may have vaginal discharge, dysuria, urination, labial pain/swelling, abd. pain
Dx: Gram stain smear (+) 50-70% culture

18. Epidemiology of Gonorrhea
Proportion of gonococcal infections caused by resistant organisms is increasing
Incidence remains high in some groups defined by geography, age and race/ethnicity, or sexual orientation
Gonorrhea associated with increased susceptibility to HIV infection

19. Gonorrhea
Gonorrhea — Reported rates: United States, 1970–2001 and the Healthy People year 2010 objective
Note: The Healthy People 2010 (HP2010) objective for gonorrhea is 19.0 cases per 100,000 population.
Source: CDC/NCHSTP 2001 STD Surveillance Report

20. Gonorrhea — Rates by state: United States and outlying areas, 2001
Note: The total rate of gonorrhea for the United States and outlying areas (including Guam, Puerto Rico and Virgin Islands) was per 100,000 population. The Healthy People year 2010 objective is 19.0 per 100,000 population.
Source: CDC/NCHSTP 2001 STD Surveillance Report

21. Gonorrhea
Gonorrhea — Rates by gender: United States, 1981–2001 and the Healthy People year 2010 objective
Source: CDC/NCHSTP 2001 STD Surveillance Report

22. Gonorrhea — Age- and gender-specific rates: United States, 2001
Source: CDC/NCHSTP 2001 STD Surveillance Report

23. Drips
Gonorrhea
Source: Florida STD/HIV Prevention Training Center

24. Gonorrhea Gram Stain Drips
Source: Cincinnati STD/HIV Prevention Training Center

25. Neisseria gonorrhoeae Cervix, Urethra, Rectum
Cefixime 400 mg or
Ceftriaxone 125 IM
Ciprofloxacin 500 mg
Ofloxacin 400 mg/Levofloxacin 250 mg
PLUS Chlamydial therapy if infection not ruled out

26. Neisseria gonorrhoeae Cervix, Urethra, Rectum
Alternative regimens
Spectinomycin 2 grams IM in a single dose or
Single dose cephalosporin (cefotaxime 500 mg)
Single dose quinolone (gatifloxacin 400 mg, lomefloxacin 400 mg, norfloxacin 800 mg)
PLUS Chlamydial therapy if infection not ruled out

27. Neisseria gonorrhoeae Pharynx
Ceftriaxone 125 IM in a single dose or
Ciprofloxacin 500 mg in a single dose
PLUS Chlamydial therapy if infection not ruled out

28. Neisseria gonorrhoeae Treatment in Pregnancy
Cephalosporin regimen
Women who can’t tolerate cephalosporin regimen may receive 2 g spectinomycin IM
No quinolone or tetracycline regimen
Erythromycin or amoxicillin for presumptive or diagnosed chlamydial infection

29. Disseminated Gonococcal Infection
Recommended regimen
Ceftriaxone 1 gm IM or IV q 24 hr
Alternative regimens
Cefotaxime or Ceftizoxime 1 gm IV q8 hr or
Ciprofloxacin 400 mg IV q 12
Ofloxacin 400 mg IV q 12
Levofloxacin 250 mg IV daily

30. Neisseria gonorrhoeae Antimicrobial Resistance
Geographic variation in resistance to penicillin and tetracycline
No significant resistance to ceftriaxone
Fluoroquinolone resistance in SE Asia, Pacific, Hawaii, California
Surveillance is crucial for guiding therapy recommendations

31. Gonococcal Isolate Surveillance Project (GISP) — Penicillin and tetracycline resistance among GISP isolates, 2002
Note: PPNG=penicillinase-producing N. gonorrhoeae; TRNG=plasmid-mediated tetracycline resistant N. gonorrhoeae; PPNG-TRNG=plasmid-mediated penicillin and tetracycline resistant N. gonorrhoeae; PenR=chromosomally mediated penicillin resistant N. gonorrhoeae; TetR=chromosomally mediated tetracycline resistant N. gonorrhoeae; CMRNG=chromosomally mediated penicillin and tetracycline resistant N. gonorrhoeae.

32. Gonococcal Isolate Surveillance Project (GISP) — Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990–2002
Note: Resistant isolates have ciprofloxacin MICs > 1 g/ml. Isolates with intermediate resistance have ciprofloxacin MICs of g/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990.

33. Nongonococcal Urethritis
Drips
Nongonococcal Urethritis
Source: Diepgen TL, Yihune G et al. Dermatology Online Atlas

34. Nongonococcal Urethritis
Drips
Nongonococcal Urethritis
Etiology:
20-40% C. trachomatis
20-30% genital mycoplasmas (Ureaplasma urealyticum, Mycoplasma genitalium)
Occasional Trichomonas vaginalis, HSV
Unknown in ~50% cases
Sx: Mild dysuria, mucoid discharge
Dx: Urethral smear  5 PMNs (usually 15)/OI field Urine microscopic  10 PMNs/HPF Leukocyte esterase (+)

35. Epidemiology of Chlamydia
Incidence: Approximately 4 million estimated cases in U.S. per annum
Most frequently reported STD in U.S.
Rates 4x higher in females
Decreasing prevalence in selected areas with control programs that include clinic-based screening
High prevalence of coinfection in partners (>50%)
Perinatal transmission results in neonatal conjunctivitis in 30-50% of exposed babies

36. Chlamydia — Rates by gender: United States, 1984–2001
Source: CDC/NCHSTP 2001 STD Surveillance Report

37. Chlamydia — Age- and sex-specific rates: United States, 2001
Source: CDC/NCHSTP 2001 STD Surveillance Report

38. Chlamydia — Rates by state: United States and outlying areas, 2001
Note: The total rate of chlamydia for the United States and outlying areas (including Guam, Puerto Rico and Virgin Islands) was per 100,000 population.
Source: CDC/NCHSTP 2001 STD Surveillance Report

39. Nongonococcal Urethritis
Azithromycin 1 gm in a single dose or
Doxycycline 100 mg bid x 7 days

40. Nongonococcal Urethritis Alternative regimens
Erythromycin base 500 mg qid for 7 days or
Erythromycin ethylsuccinate 800 mg qid for 7 days
Ofloxacin 300 mg twice daily for 7 days
Levofloxacin 500 mg daily for 7 days

41. Recurrent/Persistent Urethritis
Objective signs of urethritis
Re-treat with initial regimen if non-compliant or re-exposure occurs
Intraurethral culture for trichomonas
Effective regimens not identified in those with persistent symptoms without signs

42. Recurrent/Persistent Urethritis
Metronidazole 2 gm single dose
PLUS
Erythromycin base 500 mg qid x 7d or
Erythromycin ethylsuccinate 800 mg qid x 7d

43. Chlamydia trachomatis
Drips
Chlamydia trachomatis
More than three million new cases annually
Responsible for causing cervicitis, urethritis, proctitis, lymphogranuloma venereum, and pelvic inflammatory disease
Direct and indirect cost of chlamydial infections run into billions of dollars
Potential to transmit to newborn during delivery
Conjunctivitis, pneumonia

44. Drips
Normal Cervix
Source: Claire E. Stevens, Seattle STD/HIV Prevention Training Center

45. Chlamydia Cervicitis Drips
Source: St. Louis STD/HIV Prevention Training Center

46. Mucopurulent Cervicitis
Drips
Mucopurulent Cervicitis
Source: Seattle STD/HIV Prevention Training Center

47. Chlamydia Life Cycle Drips
Source: California STD/HIV Prevention Training Center

48. Laboratory Tests for Chlamydia
Drips
Laboratory Tests for Chlamydia
Tissue culture has been the standard
Specificity approaching 100%
Sensitivity ranges from 60% to 90%
Non-amplified tests
Enzyme Immunoassay (EIA), e.g. Chlamydiazyme
sensitivity and specificity of 85% and 97% respectively
useful for high volume screening
false positives
Nucleic Acid Hybridization (NA Probe), e.g. Gen-Probe Pace-2
sensitivities ranging from 75% to 100%; specificities greater than 95%
detects chlamydial ribosomal RNA
able to detect gonorrhea and chlamydia from one swab
need for large amounts of sample DNA

49. Laboratory Tests for Chlamydia (continued)
Drips
Laboratory Tests for Chlamydia (continued)
DNA amplification assays
polymerase chain reaction (PCR)
ligase chain reaction (LCR)
Sensitivities with PCR and LCR 95% and 85-98% respectively; specificity approaches 100%
LCR ability to detect chlamydia in first void urine

50. Chlamydia Direct Fluorescent Antibody (DFA)
Drips
Chlamydia Direct Fluorescent Antibody (DFA)
Source: Centers for Disease Control and Prevention

51. Pelvic Inflammatory Disease (PID)
Drips
Pelvic Inflammatory Disease (PID)
l0%-20% women with GC develop PID
In Europe and North America, higher proportion of C. trachomatis than N. gonorrhoeae in women with symptoms of PID
CDC minimal criteria
uterine adnexal tenderness, cervical motion tenderness
Other symptoms include
endocervical discharge, fever, lower abd. pain
Complications:
Infertility: 15%-24% with 1 episode PID secondary to GC or chlamydia
7X risk of ectopic pregnancy with 1 episode PID
chronic pelvic pain in 18%

52. Pelvic Inflammatory Disease
Drips
Pelvic Inflammatory Disease
Source: Cincinnati STD/HIV Prevention Training Center

53. C. trachomatis Infection (PID)
Drips
C. trachomatis Infection (PID)
Normal Human
Fallopian Tube Tissue
PID Infection
Source: Patton, D.L. University of Washington, Seattle, Washington

54. Pelvic Inflammatory Disease
Minimum Diagnostic Criteria
Uterine/adnexal tenderness or cervical motion tenderness
Additional Diagnostic Criteria
Oral temperature >38.3 C Elevated ESR
Cervical CT or GC Elevated CRP
WBCs/saline microscopy Cx discharge

55. Pelvic Inflammatory Disease Definitive Diagnostic Criteria
Endometrial biopsy with histopathologic evidence of endometritis
Transvaginal sonography or MRI showing thick fluid-filled tubes
Laparoscopic abnormalities consistent with PID

56. Pelvic Inflammatory Disease Hospitalization
Surgical emergencies not excluded
Pregnancy
Clinical failure of oral antimicrobials
Inability to follow or tolerate oral regimen
Severe illness, nausea/vomiting, high fever
Tubo-ovarian abscess

57. Pelvic Inflammatory Disease
No efficacy data compare parenteral with oral regimens
Clinical experience should guide decisions regarding transition to oral therapy
Until regimens that do not adequately cover anaerobes have been demonstrated to prevent sequelae as successfully as regimens active against these microbes, regimens should provide anaerobic coverage

58. Pelvic Inflammatory Disease Parenteral Regimen A
Cefotetan 2 g IV q 12 hours or
Cefoxitin 2 g IV q 6 hours
PLUS
Doxycycline 100 mg orally/IV
q 12 hrs

59. Pelvic Inflammatory Disease Parenteral Regimen B
Clindamycin 900 mg IV q 8 hours
PLUS
Gentamicin loading dose IV/IM (2 mg/kg) followed by maintenance dose (1.5 mg/kg) q 8 hours. Single daily dosing may be substituted.

60. Pelvic Inflammatory Disease Alternative Parenteral Regimens
Ofloxacin 400 mg IV q 12 hours or
Levofloxacin 500 mg IV once daily
WITH OR WITHOUT
Metronidazole 500 mg IV q 8 hours
Ampicillin/Sulbactam 3 g IV q 6 hrs
PLUS
Doxycycline 100 mg orally/IV q 12 hrs

61. Pelvic Inflammatory Disease Oral Regimen A
Ofloxacin 400 mg twice daily for 14 days or
Levofloxacin 500 mg once daily for 14 days
WITH OR WITHOUT
Metronidazole 500 mg twice daily for 14 days

62. Pelvic Inflammatory Disease Oral Regimen B
Ceftriaxone 250 mg IM in a single dose or
Cefoxitin 2 g IM in a single dose and Probenecid 1 g administered concurrently
PLUS
Doxycycline 100 mg twice daily for 14 days
WITH or WITHOUT
Metronidazole 500 mg twice daily for 14 days

63. Pelvic Inflammatory Disease Management of Sex Partners
Male sex partners of women with PID should be examined and treated for sexual contact 60 days preceding pt’s onset of symptoms
Sex partners should be treated empirically with regimens effective against CT and GC