1. STIs:Essentials for the Clinician
Kimberly Workowski, M.D, FACP, FIDSA
Professor of Medicine, Division of Infectious
Diseases, Emory University
Division of STD Prevention, CDC

2. Learning Objectives
 Identify the most common infectious causes of
genital ulcers and discuss the diagnostic evaluation
 Describe the epidemiology, diagnosis, and
recommended management of the most common
sexually transmitted infections
 Review various prevention strategies for sexually
transmitted infections
There are no financial relationships to disclose
relevant to this activity.

3. Sexually Transmitted
Bacteria Infections
• Gonorrhea (Neisseria gonorrhoeae)
• Chlamydia (Chlamydia trachomatis)
• Syphilis (Treponema pallidum)
• Chancroid (Haemophilus ducreyi)
Viruses
• Human papillomavirus
• Genital herpes
• Hepatitis A, B, C
Parasites
• Trichomoniasis (Trichomonas vaginalis)
• Pubic lice (Phthirus pubis)

4. Estimated Annual Burden and Cost of
STIs in the U.S.
Estimated Annual
Estimated Annual Direct Costs
Reported Cases, 2009 New Cases** (millions)***
Chlamydia 1,244,180 2.8 million $701
Gonorrhea 301,174 718,000 $138
HIV* 42,959 60,000§ $8,900
Syphilis 13,997 70,000 $25
Hepatitis B* 4,033 80,000 $47
HPV NA 6.2 million $5,800
Genital Herpes NA 1.6 million $1,100
Trichomoniasis NA 7.4 million $198
Total 1,606,343 18.9 million $17 billion
* HIV and Hepatitis B estimates include costs of sexually-acquired cases only
**US annual estimated new cases (Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence
estimates, 2000. Perspect Sex Reprod Health. 2004 Jan-Feb;36(1):6-10.)
§
Annual new HIV cases, 2008 estimate ; all other annual cases are 2004 estimates (1Hall HI, Ruiguang S, Rhodes P, et al. Estimation of HIV incidence in
the United States. JAMA. 2009;300:520-529.)
***Updated to 2010 $US using medical care component of CPI. Total may differ from sum of all diseases due to rounding.
Adapted from: Chesson HW, Blandford JM, Gift TL, Tao G, and Irwin KL. The estimated direct medical cost of sexually transmitted diseases among
American youth, 2000. Perspectives on Sexual and Reproductive Health 2004, 36(1): 11-19.

5. STIs Impact on Women
• Asymptomatic infection
• Symptoms confused with another condition
• Reproductive health consequences
– Infertility, stillbirth, premature birth
• Congenital infection (HSV, syphilis, HIV)
• HPV link with cervical cancer

6. USPSTF Screening Recommendations for Women
Grade Age/Special Considerations
USPSTF
Chlamydia Screening in A Sexually active women < 24 and at-risk women
non-pregnant women > 25
Chlamydia Screening in B All women < 24 and at-risk women > 25
pregnant women
Gonorrhea Screening in B All at-risk sexually active women (including
women pregnant women) - special considerations also
include population risk factors
HIV screening in A All adolescents and adults at increased risk
adolescents and adults
Syphilis Screening A All pregnant women and all persons at risk
www.ahrq.gov
www.cdc.gov/vaccine/recs/acip

7. USPSTF & ACIP Screening Recommendations for
Women
Grade Age/Special Considerations
USPSTF
Cervical Cancer A Sexually active women with a cervix
Hepatitis B Screening A At first prenatal visit
in pregnant women
High-intensity B All adolescents and adults at increased risk
behavioral counseling
to prevent STDs
ACIP
HPV Vaccination -- Recommended for women ages 9 – 26
www.ahrq.gov

8. Screening
• Test all sexually
active women at risk
regardless of sexual
activity
• Retest women with
chlamydia or
gonorrhea 3 months
after treatment
• Screen women for
trichomonasis if
HIV+, high risk, or
vaginal discharge

9. Clinical Prevention Guidance
• High intensity behavioral counseling (USPSTF)
– Partners, pregnancy, protection, practices, past STIs
• Pre-exposure vaccination- HAV, HBV, HPV
• Male latex condom
– HIV, GC, CT, Trichomoniasis
– May reduce HSV-2, HPV and genital warts
• Male circumcision may reduce acquisition of
some STI (HPV, genital HSV)
2010 CDC STD Treatment Guidelines

10. Clinical Presentation
• Genital ulcer: Syphilis, HSV, CT (LGV),
H.ducreyi, Granuloma inguinale
• Urethritis/Cervicitis: GC, CT
• Proctitis: GC, CT(LGV), syphilis, HSV
• Vaginal discharge: Trichomonas, BV
• Genital warts: Papillomavirus

11. Sexually Transmitted Genital Ulcer Disease
Treponema Haemophilus
Herpes simplex pallidum ducreyi
Feature (Syphilis) (Chancroid)
Incubation period 2-7 days 2-4 weeks 1-14 days
estimates
Ulcer Small, Superficial, Deep, small to
appearance superficial, medium size, large;
smooth: well undermined,
erythematous demarcated; ragged edge,
edge, circular elevated edge, irregular
circular/oval shape
Induration None Firm Soft
Pain Exquisitely Typically painless Variable
Lymphadenopathy Firm, tender, Firm, Tender, can
often bilateral nontender, suppurate;
bilateral unilateral:
superinfection

12. Sexually Transmitted Genital Ulcer Disease
Chlamydia trachomatis Calymmatobacterium
Feature (LGV) granulomatis
(Granuloma Inguinale)
Incubation period 3-42 days 8-80 days
estimates
Ulcer appearance Variable depth, small Small to large lesions;
to medium size; with elevated edge and
elevated edge, round/ beefy base, irregular
oval shape
Induration Occasionally firm Firm
Pain Variable Not typical
Lymphadenopathy Large, tender, Pseudobuboes; regional
characteristic unilateral; suppurate lymphadenopathy with
superinfection

14. Genital Ulcer
Evaluation
• Clinical diagnosis often inaccurate
• Multiple agents
• Immunocompromised
• Prevalence of disease; travel history
• Evaluation
– syphilis serology, darkfield microscopy, HSV culture or
PCR, biopsy
• Treat for dx most likely- clinical presentation/epi

15. Herpes Simplex Virus Type 2 (HSV-2)
Highly prevalent, most common cause of genital ulcer
disease worldwide (Corey, JAIDS 2004)
HSV-2
Population Seroprevalence
14-49 year-olds in US 17%
US STD clinic patients 40%
African-American women, 14-49 years 50%
HIV-negative women, southern Africa 70%
HIV-positive persons globally ~80%

16. HSV-2 Seroprevalence by Number of Lifetime
Sex Partners and Race/Ethnicity (Xu, JAMA 2006)
60
1 partner
50
2-4 partners
40 5-9 partners
30 10+ partners
20
10
HSV-2 seroprevalence (%)
0
Non-Hispanic White Non-Hispanic Black Mexican American

17. Herpes Simplex Virus (HSV)
• HSV-1 & HSV-2 cause genital infections
– HSV-2 more likely to reactivate
– HSV-2 associated with risk of HIV acquisition
• Primary infection: fever, HA, myalgias,
itching, vaginal/urethral dc, tender LN
• Majority of infections unrecognized

18. HSV2 Genital Shedding
• Sexual transmission through subclinical shedding
• 498 men and women with HSV2+ self collected
genital swabs x 30 d (Tronstein, JAMA 2011;305(14):1441-9)
Symptomatic Asymptomatic
HSV2 (% of days) 20% 10% <.001
Subclinical 13% 8.8% <.001
shedding
HSV DNA 4.3 log 4.2 log .27

21. HSV Diagnosis
• Cell culture or PCR
• IgM test unreliable
• Type–specific HSV serology (IgG)
– Recurrent/atypical lesions cx neg ulcers
– clinical dx without lab confirmation
– partners
– not indicated for general population screening
2010 CDC STD Treatment Guidelines

22. HSV
• Antiviral efficacy
– Acyclovir, valacyclovir, famciclovir effective
– Acyclovir/valacyclovir effective (suppression)
– Famciclovir slightly less effective (suppression)
• Acyclovir resistance
– Rare in immunocompetent
– Topical cidofovir or imiquimod
– Suppression- less resistance (bone marrow trans)
2010 CDC STD Treatment Guidelines

23. Efficacy of Oral Valacyclovir in Prevention of
HSV-2 Transmission (Corey. NEJM 2004)
4.5
4.0 3.8% P=0.039
Percentage with Infection
3.5 (28/741)
RR: 0.50 (95% CI: 0.26, 0.94)
3.0 50% Reduction
2.5
2.0 1.9%
1.5 (14/743)
1.0
0.5
0.0
Placebo Valaciclovir
500 mg once daily

25. Primary and Secondary Syphilis—Rates by Sex and
Male-to-Female Rate Ratios, United States, 1990–2010
Rate (per 100,000 population) Rate Ratio (log scale)
25 16:1
Male Rate
Female Rate
20 Total Rate
8:1
Male-to-Female Rate Ratio
15
4:1
10
2:1
5
0 1:1
1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010
Year

26. Primary and Secondary Syphilis—Reported Cases* by
Stage, Sex, and Sexual Behavior, United States, 2010
Cases
6,000
Primary
5,000 Secondary
4,000
3,000
2,000
1,000
0
MSW† Women MSM†
* Of the reported male cases of primary and secondary syphilis, 18.3% were missing sex of sex partner information.
†
MSW = men who have sex with women only; MSM = men who have sex with men.

30. Syphilis
• Definitive diagnosis for early syphilis
– darkfield microscopy; PCR
– No commercially available Tp detection tests
• Nontreponemal/treponemal serologic testing
– Reverse serologic screening (trep/nontreponemal)
• CNS involvement can occur at any stage
• Management principles for HIV+ similar

33. Treatment Recommendations
Primary, Secondary, Early Latent
• Penicillin treatment of choice +/-HIV
– Benzathine penicillin 2.4 mu IM x 1
• No benefit of additional therapy
– Enhanced treatment (IM + oral)
• Penicillin alternatives
– Doxycycline, ceftriaxone
– Azithromycin 2 gm (resistance/treatment failure)
• Use only if penicillin or doxycycline not feasible
• Do not use in MSM or pregnancy

34. Cervicitis
• Frequently asymptomatic
- purulent or mucopurulent endocervical exudate
- easily induced endocervical bleeding
• Etiology: CT, GC, Trichomonas, HSV, BV
• Dx: CT/GC NAAT, Trichomonas, BV
• Presumptive therapy:
- azithromycin 1gm PO once OR
- doxycycline 100 mg PO bid for 7d

35. Urethritis
• Bacterial STDs: GC (5-20%), CT (15-40%)
• Nongonoccocal urethritis (NGU)
– Mycoplasma genitalium 5-25%
• Association with NGU, data conflicting in women
– Ureaplasma 0-20%; data inconsistent,biovars
differ
– Trichomonas vaginalis 5-20% (age, geography)
– HSV 15-30%; urethritis in primary infection
– Adenovirus, enterics, Candida, anaerobes

36. Chlamydia Infection in Sexually Active Adolescents/Young Adults
Sexually active people aged 14-24
have about 3x the chlamydia
prevalence of sexually active adults
aged 25-39
Prevalence, %
Age group (years)
NHANES, National Health and Nutrition Examination Survey, 1999-2008
Sexual activity =“yes” response to “Have you ever had sex?”
Sex = vaginal, anal, or oral sex

37. Chlamydia
• Primary focus of screening
– Sexually active women < 25 (USPSTF, Ann Int Med 2007)
• Selective male screening (adolescent clinics,
corrections, national job training program, < 30 yrs,
STD, military)
• Treatment: azithromycin vs doxy
– retest women/men 3 mo post treatment
– CT testing in third trimester (reinfection)
2010 CDC STD Treatment Guidelines

38. Long-term Reproductive
Complications
• Tubal inflammation can result in scarring,
loss of function
• Long-term sequelae
– Tubal factor infertility
– Ectopic pregnancy
– Chronic pelvic pain
• Tubal factor infertility: Normal tubal tissue, 1200x Post-PID, 1200x
Inability to conceive leading preventable cause of
Chlamydia is the
due to fallopian tubal factor infertility
tube
damage
Scanning electron microscopy photos courtesy of Dorothy L. Patton, University of Washington, Seattle, WA

39. Expedited Partner Therapy (EPT)
• Providing prescriptions /medications to take to partner
• Endorsed by CDC, professional organizations
 Two Randomized trials: EPT useful in
assuring partner treatment and reducing
repeat infections in heterosexuals with CT
or GC (Golden NEJM 2006, Schillinger Sex Trans
Dis 2003)
“partner pack”
39

40. Gonorrhea—Rates by Age Among Women Aged 15–44 Years,
United States, 2001–2010
Rate (per 100,000 population)
Age Group
1,000
15–19 30–34
20–24 35–39
800 25–29 40–44
600
400
200
0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Year

41. Testing for GC
• Screening is important component of GC control
• USPSTF (Ann Fam Med 2007)
– sexually active women at risk:< 25, prior GC,
other STI, new/many partners, +/- condom use,
CSW, drugs
• Nucleic acid amplification tests (NAATs)
– superior sensitivity/specificity
– vaginal swabs (women), urine (men)
– asymptomatic infection

42. Neisseria gonorrhoeae
Antibiotic Resistance
 Antibiotic resistance
 Undermines treatment success
 Heightens risk of complications
 Facilitates transmission
 Neisseria gonorrhoeae (NG) has demonstrated ability to
progressively develop antibiotic resistance
Resistance

43. Emergence of Fluoroquinolone-resistant
N. gonorrhoeae (QRNG), United States
FQ not recommended in US‡
Percentage of GISP isolates resistant to ciprofloxacin
Hawaii* MSM†
California**
US
* CDC, MMWR 2000; ** CDC, MMWR, 2002; † CDC, MMWR, 2004.; ‡ CDC, MMWR, 2007.

44. Anogenital GC Treatment
• Decreasing options for treatment
– Cephalosporins MIC increases (SE Asia, Europe,US),
treatment failure, pattern similar to QRNG
• Dual therapy
– Ceftriaxone 250 mg IM (preferred)
• PLUS azithromycin 1 gm or doxy 100 mg bid x 7 d
• Alternatives
– Cefixime 400 mg PO (draft recommendation)
• PLUS azithromycin 1 gm or doxy100 mg bid x 7

45. Trichomoniasis
• Diagnostic evaluation
– T. vaginalis nucleic acid test
– Consider rescreen women at 3 mo
• Tx metronidazole or tinidazole 2 gm
– Resistance 5-10%
• HIV and Trichomoniasis
– Screening at entry into care
– Rx metronidazole 500 mg bid x 7 days (Kissinger, AIDS 2010)
2010 CDC STD Treatment Guidelines, Bachman, CID 2011

46. Tests for Trichomonas
Test Assay Sensitivity (%) Specificity (%)
Wet Preparation* 50-72 100
Culture* 70-78 100
OSOM** 83-99 100
XenoStrip** 77-90 93-99
Affirm VPIII** 80 98
PCR*** 97 98
TMA**** 96.7-98.2 98
*compared to NAATs; ** compared to culture; ***Compared to culture and other primer
sets for trichomonas;-Madico JCM 1998;36:3205-3210; ****Compared to research PCR—
Huppert CID 2007 & Hardick JCM 2006
Gaydos, C. Rapid Tests for STDs Current Infect Dis Reports 2006;8:115-124

47. Bacterial Vaginosis
• Recommended regimen
– Metronidazole 500 mg bid x 7
– Clindamycin cream 2% x 7
– Metrogel 0.75% qday x 5
• New alternative regimen
– Tinidazole 2 g qd x 2 or 1 g qd x 5
• Management of recurrences
– Metronidazole gel 2x weekly x 4-6 mo (Sobel, 2006)
– Oral nitroimidazole followed by intravaginal boric acid
and suppressive metronidazole gel (Reichman 2009)

48. Recurrence
• Persistence of BV-associated organisms and
failure of lactobacillus flora to recolonize (Marrazzo ,
Ann Int Med 2008)
• Risk factors: black, older age, higher Nugent
score, BV hx, regular sex partner, female sex
partner, hormones (Bradshaw, Sobel)
• No evidence of benefit with yogurt or exogenous
oral lactobacillus treatment (CDC Treatment Guidelines)
• Biofilm may increase risk of treatment failure to
G. vaginalis, A.vaginae (Swidsinski 2008)

49. HPV-Associated Disease in
Males and Females
HPV-associated Disease Males Females
Genital precancers and penile, anal cervical, vaginal,
cancers vulvar, anal
Oropharyngeal cancers X X
Recurrent respiratory
X X
papillomatosis
Anogenital warts
X X

50. Association of no. of lifetime sex partners with
prevalent oral HPV – U.S. pop. aged 14-59
Overall
study
prevalence
of oral HPV
infection
was 6.9%
Source: Figure 4. Gillison ML, 2010. JAMA. 2012 Jan 26

51. Projected annual number of patients (ages 30 to 84 years) of
oropharyngeal cancers and cervical cancers
Source: Figure 4B. Chaturvedi AK, Engels EA, Pfeiffer RM et. al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011
Oct 3. [Epub ahead of print]

52. HPV/Genital Warts
• Counseling messages (Dunne, CID 2011)
– Oral transmission
• HPV testing (ASCUS, >30 + PAP)
– Not indicated- +/-vaccinate, STI screen, <21
• GW treatment
– Sinecatechins ointment (15%)
– Imiquimod induced vitiligo
• HPV vaccine
2010 STD Treatment Guidelines

53. HPV Vaccine
• Quadrivalent vaccine licensed in females June
2006; bivalent vaccine October 2009
– Routine rec in girls 11-12; catch up to age 26
– Quadrivalent vaccine licensed for males 9-26 (2009)
• Routine use December 2011
• HPV uptake relatively low in US
– National immunization survey 2010
• 49% of girls 13-17 received 1+ dose/32% all three doses
• 1.4% boys 13-17 received 1+ doses

54. Proportion of eligible age women* with genital
warts, by resident status, Australia, 2004-2010
p-trend=0.96
p-trend=0.84 p-trend=0.06
-25%
p-trend<0.001 -73%
Pre-vaccine period Vaccine period
* Eligible age - <26 years old in July 2007 Donovan B et al. ISSTDR Quebec City, July 2011 54

55. Prevention Guidance
• Education/counseling to reduce risk of STI
acquisition
• Detection of asymptomatic infection
• Effective diagnosis and treatment
• Evaluation, treatment, counseling of sexual
partners
• Pre-exposure vaccination-hepatitis A, B,
HPV

56. Resources for Women
• FindSTDTest.org (HIV/STI testing sites)
• 1-800-CDC-INFO
• http:www.cdc.gov/std for consumer fact sheets
and brochures
• Condoms and STIs
– www.cdc.gov/condomeffectiveness/latex.htm
• Get Yourself Tested
– www.itsyoursexlife.com/gyt

57. Peer Reviewed References
• Workowski KA, Berman S. 2010 CDC Sexually Transmitted Diseases Treatment
Guidelines. MMWR 2010;59(RR-12):1-116.
• Lin JS, Whitlock E, O’Connor E, et al. Behavioral Counseling to prevent sexually
transmitted infections: recommendation statement. Ann Int Med 2008:149:491-6.
• Meyers D, Wolff T, Gregory K, et al. USPSTF recommendations for STI screening. Am
Fam Physician 2008;77:819-24.
• Peterman T, Tian LH, Metcalf CA, et al. High incidence of new sexually transmitted
infections in the year following a sexually transmitted infection: a case for rescreening.
Ann Intern Med 2006;145:564-72.
• CDC. Quadrivalent human papillomavirus vaccine: MMWR 2007;56(No RR-2);
bivalent vaccine and updated recommendations MMWR 2010;59:626-9; licensure of
quadrivalent vaccine in males MMWR 2010;59;630-2..
• Workowski KA, Berman SM, Douglas JM. Emerging Antimicrobial Resistance in
Neisseria gonorrhoeae: Urgent Need to Strengthen Prevention Strategies. Ann Intern
Med 2008;148:606-13.