1. Review screening recommendations and treatment guidelines for STDs.

2. List the differential diagnosis of vaginitis and cervicitis and describe the work-up of the patient with vaginal discharge.

3. Discuss the diagnostic work-up and current drug treatment of chlamydia, human papillomavirus (HPV) infection, trichomoniasis, and syphilis, as well as vaccination recommendations for prevention of HPV infection.

4. Differentiate between treponemal and nontreponemal tests for syphilis and state how these are used.

5. Describe various presentations of syphilis and explain when cerebrospinal fluid testing is indicated for patients with syphilis .

Diagnosis and Management of Sexually Transmitted Diseases
Jeffrey D. Klausner, MD, MPH, Associate Professor of Medicine, Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, School of Medicine; Deputy Health Officer and Director, STD Prevention and Control Services, San Francisco Department of Public Health

Incidence of sexually transmitted disease (STD): 20 million STD cases per year in United States (2000); half occur in young adults; human papillomavirus (HPV), Chlamydia trachomatis, and trichomoniasis comprise 88% of new cases among young adults; societal cost $6 billion per year; Centers for Disease Control and Prevention (CDC) report 26% of teens 14 to 19 yr of age have STDs; of these, 18% have HPV; C trachomatis next most common (long asymptomatic period); then herpes simplex virus II (HSV-II), then trichomoniasis

Screening and treatment guidelines: CDC recommends screening for certain asymptomatic STD infections; specifically recommend young sexually active women have annual C trachomatis screening; many STDs reportable to local public health department (PHD); for most effective patient and partner treatment, coordinate with local PHD; standard of care includes expedited partner therapy; treat partner if patient brings him or her into clinic; or prescribe double treatment to patient, or write prescription directly for partners without seeing them; California state laws enacted in 2001 and 2006 specifically authorize providing therapy for partner(s); need to rescreen and differentiate treatment failure from re-exposure; counsel patient on risky behaviors; reinfection rate 10% to 30%

HPV infection: case presentation—sexually active woman 22 yr of age; new partner in past 3 mo; presented with bumps on introitus; physical examination revealed bumpy warty lesions; typical HPV presentation; diagnosis by visual inspection 80% accurate and adequate; HPV subtypes 6 and 11 cause 90% of external genital warts; Gardasil vaccine includes subtypes 6 and 11; external genital warts affect vagina, urethra, penis, cervix, anus, and rectum; plantar warts caused by different subtypes; recent studies explore possible link between genital wart subtypes and oral cancer; advise patient that HPV common; 70% of sexually active adults have had exposure to HPV, as seen by presence of antibodies; counsel that HPV can be spread by nonsexual contact, eg, genital-hand contact

HPV treatment: in-office—topical liquid nitrogen, podophyllin resin, trichloroacetic acid, surgical excision; all remove superficial wart but do not clear virus from basal cells; patient-applied —2 Food and Drug Administration (FDA) approved modalities; typically have higher cure rates than in-office treatments (possibly patient applies more product and thereby increases ablation); podofilox gel applied twice daily 3 days per wk for 4 wk; imiquimod (Aldara) applied 3 nights per week for 12 to 16 wk; counsel patient that overapplication of Aldara onto normal tissue causes erythema and pain

CDC guidelines for HPV: do not recommend change in Papanicolaou (Pap) test frequency or colposcopy; do not recommend partner examination; do encourage condom use (not recommendation as evidence slightly weaker)

Condom use by patients with HPV: 2003 study randomized women with cervical intraepithelial neoplasia (CIN) to consistent condom use vs no condom use; condom use group had 50% increase in regression of abnormal Pap test at 2 yr and more rapid clearance of HPV; men with penile warts consistent condom use group had faster regression of warts; counsel patients that regular condom use reduces re-exposure to HPV and has impact on disease process; study of university women initiating first sexual activity and reporting 100% condom use showed 70% reduction in acquisition of HPV infection and decreased frequency of development of CIN

HPV vaccination: principal study randomized 2400 women to vaccine against HPV 16; 0% of vaccinated group vs 3.8% of placebo group acquired HPV 16; 2006 Gardasil licensed; contains HPV subtypes 6 and 11 (low-risk types) with 16 and 18 (high-risk types); evidence for some cross protection in reduced acquisition of high-risk family-related subtypes 31, 33, and 45; too expensive to produce vaccine with additional types; vaccine recommended for girls 11 to 12 yr of age and approved for any girl 9 to 26 yr of age; licensed and approved for boys in New Zealand and Australia; in 2009, expect further data on use in boys in United States; may not be as effective for boys, due to differences in penile vs cervical tissue

HPV screening and anal cancer: anal cancer rates in gay men ≈50 per 100000, double that in gay men infected with HIV (compare with cervical cancer rates of 5 to 10 per 100000); no national recommendation for routine anal Pap tests; no evidence that screening reduces bad outcomes of anal cancer; anal cancer differs from cervical cancer, ie, less invasive and less likely to metastasize; local screening practices vary

Vaginitis and cervicitis: case presentation—woman, 32 yr of age presents with new frothy bubbly vaginal discharge; reported monogamy for 5 yr and no new sexual partners; infectious vaginitis can be sexually associated, eg, trichomoniasis, bacterial vaginosis (no pathogen identified, not considered sexually transmitted, but more frequently seen in those with new partners and less condom use), or nonsexually associated, eg, candidiasis; cervicitis can cause vaginal discharge, particularly Neisseria gonorrhea and C trachomatis infections; HSV can cause cervicitis in primary infection (cervical ulcers, mucopurulence) as well as in recurrences; noninfectious causes include foreign body and chemical or allergic irritation; above case typical for trichomoniasis

Work-up of vaginal discharge: sexual history; speculum examination differentiates vaginitis from cervicitis; standard of care includes vaginal fluid analysis for pH, microscopy, and whiff test; normal vaginal pH <4.5 (acidic environment protective); elevated pH (5 to 6.5) suggests infection, bacterial vaginosis, or other abnormality of vaginal ecosystem; microscopy for parasites (eg, trichomonads) and to identify yeast (with potassium hydroxide ); whiff test detects amine production from anaerobe overgrowth (eg, bacterial vaginosis); target gonococcal and chlamydial testing to those with new partners or potential multiple partners, and age <30 yr; false positives more common with newer sensitive testing technology; apply to correct populations and interpret in clinical context

Trichomoniasis: trichomonads same size as white blood cells (WBCs), but have flagella and move faster around wet mount field; in 2001 to 2004, frequency of trichomoniasis studied in women recruited from home and tested in mobile medical van; study showed increased prevalence in black women, with current prevalent infection in 15% to 20% of black women >30 yr of age, and 2% in nonblack women; no current screening recommendations, not reportable to PHD, and not part of most STD-control programs; health impact still unknown; study of effects of screening and treating pregnant women with trichomoniasis showed associated harm in treated group (increased incidence of premature delivery); associated with increased risk for HIV infection, so may be appropriate to screen and treat in populations at high risk for HIV transmission

Testing for trichomoniasis: wet mount moderately sensitive and most frequent method of diagnosis in United States; enzyme immunoassay (EIA) test can be done in office; laboratory culture done with special swab, needs 5 days, and more sensitive than wet mount; consider culture for patients with persistent symptoms or treatment resistance; need culture to determine susceptibility of isolate to metronidazole

Treatment of trichomoniasis: single-dose oral metronidazole (2 g); cure rate comparable to treatment over 5 to 7 days; known since early 1980s that partners need treatment, which led to other STD partner-treatment programs; metronidazole-resistant trichomoniasis emerging (prevalence unknown); no routine monitoring done but consider if symptoms persist and organism identified on wet mount; must rule out reinfection or re-exposure to infected partner, as well as nonadherence to treatment (eg, did not take drug or unable to tolerate side effects); tinidazole new approved drug therapy; more expensive, equally efficacious, and may be better tolerated than metronidazole; tinidazole not recommended over metronidazole in routine care; may be utilized in metronidazole resistance, although data not fully supportive of this

Screening guidelines: case presentation—woman 17 yr of age presented with questions on recommended screening tests; history of sexual activity for 1 yr; one partner for 6 mo; no issues or symptoms; only recommended test for this patient at this time is annual screening for chlamydia, which is recommended annually for recently sexually active women up to age ≤25 yr; asymptomatic C trachomatis prevalence, 4%; N gonorrhea screening—recommended for high-risk groups, but not routinely recommended, as prevalence of asymptomatic N gonorrhea 0.7%; American Cancer Society recommends Pap test after 3 yr of sexual activity, or annually age 20 to 30 yr, then reduce frequency if previous results normal; before age 30 yr, most abnormal cytology clears on its own; in Europ, Pap tests for screening do not begin until age 30 yr; HSV screening— recommended for those with partners who have HSV, in pregnancy complicated by HSV, or in patients with HIV; HSV testing offered in many STD clinics on patient request, but not routine; syphilis screening—not recommended as routine in young women, as prevalence in heterosexual population very low; slight increase in prevalence in gay men; recommended in pregnancy, patients with HIV infection, and men who have sex with men

Prevalence of C trachomatis: national survey— whites showed 2% prevalence in 14- to 19-yr of age, 2% in 20- to 29- yr of age, then decrease; C trachomatis should be considered pediatric disease; immature cervix more susceptible to infection; more common in younger women due to their social networks; proportion higher in blacks in every age group because of sustained community prevalence, not PHD reporting disparity; gay men—chlamydia present in 15% to 20% of gay men with urethritis; in men who practice anal intercourse, 5% to 10% have asymptomatic rectal chlamydial infection (common cause of proctitis); recommend chlamydia testing for gay men every 3 to 6 mo, as 5% to 10% consistently positive across variety of test groups; positivity 5% in those presenting for HIV testing

Case presentation: HIV-infected gay man 33 yr of age presented with persistent penile ulcer 1 wk after receiving initial drug therapy with single-dose oral azithromycin 2g for presumed syphilis; patient given partner pack of same therapy, which patient took himself 12 hr after first treatment (should have cleared infection); differential diagnosis—primary syphilis with slow resolution; HSV with resultant bacterially infected ulcer; chancroid (very uncommon); treatment-resistant syphilis; drug reaction (eg, tetracyclines, trimethoprim sulfamethazole, can cause genital ulceration); pyogenic infection; autoimmune reaction; work-up—review medication history; examine oral and anal mucous membranes; perform darkfield microscopy; obtain serum rapid plasma reagin (RPR) or VDRL, plus Treponema pallidum particle agglutination (TP-PA) test; because HSV common cause of penile ulcers, perform polymerase chain reaction (PCR) test (cheaper, easier, and slightly more sensitive than culture) and serology; case patient had positive RPR test and spirochetes on darkfield microscopy; this patient had first documented case of azithromycin-resistant syphilis (2004) due to 23s ribosomal RNA point mutation conferring resistance to macrolides

Treatment of syphilis: penicillin G treatment of choice (2.4 million units); no resistance ever documented; in San Francisco 80% of patients with syphilis resistant to macrolides; when giving penicillin G, advise patient of possible Jarisch- Herxheimer reaction (as organisms die, they elicit immune response with fevers, headache, unwell feeling) differentiate from penicillin allergy; doxycycline reasonable alternative in penicillin-allergic nonpregnant patients; perform follow-up serologies every 3 mo; patient cured when titer declines 4-fold (eg, 1:64 to 1:16) consistent with serologic response; ceftriaxone may be considered for neurologic presentations;

Case presentation: patient with paronychia presented to STD clinic; initially treated with cephalexin (Keflex) but not responding; sexual history revealed digital penetration of rectum; diagnosed with syphilitic chancre; counsel patients who practice sexual fisting to use gloves to prevent disease transmission

Syphilis testing: nontreponemal testing—RPR or VDRL (measure nonspecific response to cardiolipin lecithin phospholipid antigen) equally sensitive; always use one of theseto obtain titer levels; treponemal specific—most sensitive and positive for life; TP-PA and EIA available; recommended to test one nontreponemal test with TP-PA to improve sensitivity; always treat if unsure about timing of initial infection ; treatment clears lesion in 24 to 48 hr and interrupts spread of infection

Other presentations of syphilis: mucous patches—(hypopigmented lesions on tongue) typical of secondary syphilis; can be confused with oral candidiasis or atypical oral hairy leukoplakia; patches resolve within 1 day of treatment; syphilis easily spread by oral sexual activity; recent study in Chicago showed 20% of new syphilis cases acquired this way; men who have sex with men should be routinely tested; condylomata lata—secondary syphilis; highly infectious lesions teeming with spirochetes; appear moist and shiny; differentiate from condyloma acuminata (warts of HPV); other lesions—palmar rash with circular annular lesions; nodular raised lesions common on scrotum (may resemble scabies); maculopapular rash (resembles viral exanthem or drug reaction); comprehensive sexual history critical; ask if sexually active with men, women, or both; how many male or female partners; any drug use associated with sexual activity (especially methamphetamine); how met partner, eg, Internet; always keep syphilis in differential diagnosis

Cerebrospinal fluid (CSF) examination: 4 indications in patients with syphilis; neurologic signs and symptoms— especially auditory or balance disorders, since neurosyphilis affects eighth and ninth cranial nerves and may manifest as basilar meningitis; treatment failure—rule out CSF harboring organisms; HIV infection—if late or unknown stage (>1 yr; do not routinely perform on HIV patients); tertiary syphilis—especially if aortic aneurysm or tissue gumma present

Ciprofloxacin-resistant N gonorrhea: 40% of men who have sex with men and 8% of heterosexual men with gonococcal infection ciprofloxacin-resistant; fluoroquinolones not recommended for N gonorrhea treatment

Question and answer: duration of treatment of syphilis—treat with one injection penicillin G if syphilis recently acquired (in past year), chancre present, secondary rash, or documentation of prior negative test in past year; treat with one injection, regardless of HIV status; if unable to document how long syphilis present, or if patient asymptomatic and no prior testing done, treat with 3 injections