Sexually Transmitted Infections and Increased Risk of Co-Infection with Human Immunodeficiency Virus

REVIEW ARTICLE

Sexually Transmitted Infections and Increased Risk of Co-infection with Human Immunodeficiency Virus

Margaret R.H. Nusbaum, DO, MPH; Robin R. Wallace, MD; Lisa M. Slatt, MEd; Elin C. Kondrad, MD

The incidence of trichomoniasis (Trichomonas vaginalis) Clinical Presentation in the United States is estimated at 5 million cases annu- Urethritis, Epididymitis, and Proctitis ally; chlamydia (Chlamydia trachomatis) at 3 million; gon- In men, STIs usually remain confined to the urethra. Symptoms orrhea (Neisseria gonorrhoeae), 650,000; and syphilis (Tre- of urethritis include urethral discharge, dysuria, or urethral ponema pallidum), 70,000. However, most sexually itching. The discharge of nongonococcal urethritis (NGU) is transmitted infections (STIs) are asymptomatic—con- often slight, and may not be apparent without massaging the tributing to underdiagnosis estimated at 50% or more. urethra. Discharge of NGU is usually minimal and gray, white, Diagnosis of an STI signals sexual health risk because an or mucoid rather than yellow. Discharge that is yellow and pre- STI facilitates the transmission and acquisition of other sent in greater volume most often signals infection with N STIs, including human immunodeficiency virus (HIV). gonorrhoeae. In fact, comorbid STIs increase patients’ susceptibility of Epididymitis presents as acute unilateral testicular pain acquiring and transmitting HIV by two- to fivefold. Sev- and swelling. Clinical findings include tenderness of the epi- eral studies have shown that aggressive STI prevention, didymis and ductus deferens, erythema and edema of the testing, and treatment reduces the transmission of HIV. overlying scrotal skin, urethral discharge, and dysuria. Swelling The authors discuss common clinical presentations, and tenderness may be localized or may extend to the entire screening, diagnosis, and treatment for trichomoniasis, epididymis and surrounding areas, making the epididymis less chlamydia, gonorrhea, syphilis, and herpes simplex virus. distinct in the inflammatory mass. Proctitis presents as anorectal or perineal itching, anorectal iagnosis of a sexually transmitted infection (STI) sig- pain, and discharge. Dnals sexual health risk. STIs facilitate the transmission Trichomoniasis tends to be asymptomatic in men, while and acquisition of other STIs, including human immunode- chlamydia and gonorrhea present as acute urethritis or epi- ficiency virus (HIV). Coexisting STIs increase susceptibility of didymitis. In sexually active men, however, C trachomatiscauses acquiring and transmitting HIV by two- to fivefold.1 Studies 30% to 50% of cases of NGU,4 an even higher proportion of post- show that aggressive STI prevention, testing, and treatment gonococcal urethritis, and the majority of cases of epididymitis. reduces transmission of HIV.1 Ureaplasma urealyticum appears to be causative in the remaining Most STIs are asymptomatic, contributing to widespread cases, although the cause is undetermined in approximately one underdiagnosis estimated at 50% or higher.2 In the United third of men who have NGU. Routine screening for U ure- States, the annual incidence of trichomoniasis (Trichomonas alyticum is not recommended as NGU is often associated with vaginalis) is estimated at 5 million; chlamydia (Chlamydia tra- infection from C trachomatis and N gonorrhoeae. chomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000, Other urinary tract pathogens, including Escherichia coli and syphilis (Treponema pallidum), 70,000. 3 This article dis- and Pseudomonas aeruginosa, can be causative agents in men cusses the common clinical presentations, screening, diagnosis, who are older, have structural abnormalities of the urethra, and treatment for trichomoniasis, chlamydia, gonorrhea, have recently undergone a urinary tract procedure or manip- syphilis, and herpes simplex virus. ulation, or engage in anal intercourse. Although ascending infection to the epididymis is rare, most cases of epididymitis are caused by STIs. In addition to infectious causes, differential diagnoses should also include trauma, testicular torsion, and tumor. From the Department of Family Medicine in the School of Medicine at the Positive results for leukocyte esterase on urinalysis can University of North Carolina at Chapel Hill. Address correspondence to: Margaret R.H. Nusbaum, DO, MPH, Asso- indicate C trachomatis, N gonorrhoeae, or other urinary tract ciate Professor, Department of Family Medicine, 101 Manning Dr, CB 7595, pathogens. Chlamydia trachomatis or T vaginalis should be sus- Chapel Hill, NC 27514-7595. pected in the absence of gram negative intracellular diplo- E-mail: [email protected]

Nusbaum et al • Review Article JAOA • Vol 104 • No 12 • December 2004 • 527 REVIEW ARTICLE cocci on Gram stain. Patients presenting with epididymitis Leukocytosis and elevated erythrocyte sedimentation rate also should be examined and tested for chlamydia and gonorrhea. support a diagnosis of PID. In the case of proctitis, cultures should be taken from the Pelvic inflammatory disease can lead to infertility, ectopic symptomatic area. pregnancy, and chronic pelvic pain. Because PID can poten- In women, urethritis can be a manifestation of C tra- tially cause significant damage to women’s reproductive health, chomatis, herpes simplex virus (HSV), N gonorrhoeae, or T vagi- clinicians should have a low threshold for diagnosis and treat- nalis. As in men, proctitis in women presents as anorectal or ment of PID. perineal itching, or anorectal pain and discharge. Genital Ulcerative Disease Vaginitis and Cervicitis Herpes simplex virus is the most common single cause of Etiologic agents of vaginitis and cervicitis include C trachomatis, genital ulcers in the United States. Herpetic ulcers appear on N gonorrhoeae, HSV, and T vaginalis. More than half of endo- the external genital, urethral, and anorectal areas as well as in cervical infections do not cause sufficient inflammation to the vagina and on the cervix. About 10% of ulcers are the result in clinical signs and symptoms, however. When pre- result of more than one etiologic agent, however. The clinical sent, symptoms can include dysuria, vaginal discharge, dys- features of ulcers can be altered in immunosuppressed indi- pareunia, perineal itching, and pelvic discomfort or pain. Ery- viduals. Differential diagnosis includes syphilis and herpes thema multiforme and swelling of the vulva or labia suggest zoster as well as noninfectious causes such as trauma, con- trichomonal or HSV infection. tact dermatitis, lichen sclerosis, and Behçet’s syndrome. Trichomonal discharge is usually copius, frothy, and The primary lesion of syphilis, the chancre, is usually yellow-green or occasionally gray. The vaginal walls are often painless. It is a solitary ulcer with raised, well-defined bor- erythematous and granular in appearance, while punctate ders and a clean, indurated base. The chancre occurs at the site hemorrhages of the cervix give it the classic “strawberry” of infection and is usually associated with nontender regional appearance. lymphadenopathy and heals spontaneously and without scar- Perineal swelling, cervical vesicles, or venereal (or den- ring in 3 to 6 weeks. driform) ulcers, suggest HSV infection. Alternatively, swelling, Secondary syphilis occurs 4 to 10 weeks after the primary tenderness, and drainage in glandula vestibularis major lesion of syphilis appears—and goes untreated. Symptoms of (ie, Bartholin’s gland) sites suggest gonorrheal infection. A secondary syphilis include myalgia, arthralgia, malaise, low- friable cervix and mucopurulent vaginal discharge can be grade fever, and generalized lymphadenopathy. A nonpruritic, seen with gonorrhea and chlamydia. maculopapular eruption affecting the trunk, limbs, palms, Because chlamydia, gonorrhea, and trichomoniasis, may and soles is present in 10% to 75% of patients. Condylomata present similarly with mucopurulent vaginal discharge, lata, fleshy lesions that may be broad-based, flat, or raised, drainage from the cervix, or a friable cervix, physicians should may be seen in the mucous membranes (eg, anus, external screen for all three—as well as for bacterial vaginosis. Ulcer- genitals, mouth). ative lesions should be tested for HSV. A definitive diagnosis In up to one third of patients with secondary syphilis, of trichomoniasis requires identifying T vaginalis on a Tri- the primary chancre is still present, increasing the likelihood chomonas wet prep test. of transmission to any additional sexual contacts. Left untreated, syphilis becomes latent with no readily Pelvic Inflammatory Disease apparent clinical findings. Without therapy, approximately With the exceptions of T vaginalis and HSV, pathogens in the one third of those infected will develop tertiary syphilis 10 to lower genital tract in women frequently and rapidly ascend to 30 years after the initial infection. The manifestations of tertiary the endometrium and adnex uteri, causing pelvic inflamma- syphilis include gummas, aortitis and other cardiovascular tory disease (PID) and pelvic adhesive disease. Manifestations disease, and neurosyphilis. of PID include endometritis, salpingitis, tuboovarian abscess, and pelvic peritonitis. Suspected Exposure to Sexually Transmitted Infections Physical symptoms of PID include perineal and urethral Patients may initially present to physicians’ offices with con- itching or burning, vaginal discharge and odor, spotting with cerns about STI exposure for numerous reasons. Some patients intercourse, insertional or deep dyspareunia, pelvic pain, abdom- fear the results of not using protective barriers with a new inal pain, worsening dysmenorrhea, or systemic symptoms sexual partner or they are apprehensive about the failure of including chills, fever, malaise, or myalgia. Cervical motion such barriers during sexual contact. Some patients seek tenderness on bimanual pelvic examination can indicate PID. screening and medical care after they have been informed by Fitz-Hugh–Curtis syndrome presents as PID with pain in a sexual partner or public health official of their possible con- the right upper quadrant and hepatic tenderness with palpa- tact with an STI. Still other patients may have recently dis- tion. Fever, increased pulse rate and blood pressure, and covered that their intimate relationship was not mutually enlarged, painful inguinal lymph nodes can also be present. monogamous.

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Table 1 Sexually Transmitted Infections: Screening by Risk Group and Properties of Commercially Used Diagnostic Tests*

Likelihood Ratio† Infection (Pathogen) and Diagnostic Test(s)‡ Sensitivity, % Specificity, % Positive Negative

Trichomoniasis (Trichomoniasis vaginalis) ▫ DFA 80–86 98 .43 .04 ▫ Trichomonas wet prep 50–75 70–98 .50 .25

Chlamydia (Chlamydia trachomatis) ▫ ANA Men: urethra 70–90 97–99 .90 .10 Women: cervix 70–90 97–99 .90 .10 ▫ Chlamydia culture§ 70–90 100 .90 .10 ▫ DFA 70–90 97–99 .99 .99 ▫ DNA probe 60–95 95–99 .19 .05 ▫ Ligase chain reaction ...... 19 .05 Men: urethra 95 95 ...... Women: vagina, cervix 95 95 ...... Urine 95–99 ...... ▫ Papanicolaou smear 10 4.5 .11 .20 ▫ Polymerase chain reaction . . . 95 .19 .05 Men: urethra 60–95 ...... Women: vagina, cervix 60–95 ...... Urine 95–99 ...... ▫ ULE 40–100 ...... ▫ Urine 77–91 97–100 .92 .09

Gonorrhea (Neisseria gonorrhoeae) ▫ ANA Men: urethra 95 95 .19 .05 Women: endocervix 60–100 70–98 .50 .01 ▫ DNA probe 97–99 97–99 .99 .01 ▫ Gonorrhea culture§ 80–95 ...... ▫ Gram stain// Men: urethra 70–99 97–99 .99 .01 Women: cervix 30–65 90–97 .66 .36 ▫ ULE 46–60 93–96 .15 .41 (continued)

* Data used to compile this table are from several sources. (1) US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;287-302,325-346. Available at: http://www.ahcpr.gov/clinic/cpsix.htm. Accessed September 27, 2004. (2) Bickley LS. Acute vaginitis. In: Panzer RJ, Black ER, Griner PF, eds. Diagnostic Strategies for Common Medical Problems. Philadelphia, PA: American College of Physicians; 1991:249-259. (3) Caudill JL, Humphrey SK, Goellner JR. Cervicovaginal cytology and the diagnosis of Chlamydia trachomatis: a comparison with immunofluorescent results. Diagn Cytopathol. 1994;11:20-22.

Many screening techniques listed here are reader dependent. Check supporting laboratory to obtain local sensitivity, specificity, and prevalence data. Where data are unavailable for sensitivities and specificities, comments are made in the chart and likelihood ratios are not reported. † Positive likelihood ratio is defined as the likelihood that a positive test result would be expected in a patient with the infection compared to the likelihood that that same result would be expected in a patient without the infection, ie, positive likelihood ratio 2 Sensitivity/(1-Specificity). Negative likelihood ratio is defined as the likelihood that a negative test result would be expected in a patient with the infection compared to the likelihood that that same result would be expected in a patient without the infection, ie, negative likelihood ratio 2 (1-Sensitivity)/Specificity. Where ranges are given for sensitivity and specificity, the highest reported value was used to calculate likelihood ratios, except that 99% is used for any values of 100%. ‡ ANA indicates antinuclear antibody test (enzyme immunoassay); DFA, direct fluorescent antibody; ULE, urine leukocyte esterase. § Culture (chlamydia and gonorrhea) is the preferred diagnostic testing method for patients who are the victims of sexual abuse or sexual asault. // Gram stain testing using pharyngeal and rectal samples is not clinically effective. ¶ The specificity of syphilis testing may be reduced with the presence of human immunodeficiency virus (HIV) infection. When HIV infection is present, nontreponemal test results may remain persistently positive after treatment, thus making treatment difficult to assess. Further, treponemal test results may become nonreactive after treatment, making documentation of past infection difficult. # The specificity of the darkfield microsopy diagnostic test in establishing a diagnosis of syphilis is technician dependent. Consult your local laboratory. ** Testing does not differentiate herpes simplex virus type 1 (HSV-1) from type 2 (HSV-2) or herpes zoster.

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Table 1 (continued) Sexually Transmitted Infections: Screening by Risk Group and Properties of Commercially Used Diagnostic Tests*

Likelihood Ratio† Infection (Pathogen) and Diagnostic Test(s)‡ Sensitivity, % Specificity, % Positive Negative

Syphilis (Treponema pallidum)¶ ▫ Darkfield microscopy (treponemal) Primary 80 # ...... ▫ Fluorescent treponemal antibody absorption test and microhemaglutination assay for antibodies to Treponema pallidum (treponemal) Primary 84 96 .21 .17 Other stages of infection 100 . . . .75 .01 ▫ Rapid plasma reagin and Venereal Disease Research Laboratory (nontreponemal) Early or primary 62–76 75–85 .76 .01 Secondary 100 . . . .24 .70 Late 70 100 .99 .30

Herpes simplex virus** ▫ ANA 59–93 ...... ▫ Cytology 30–80 ...... ▫ Direct fluorescent antibody 70–90 ...... ▫ Herpes culture Lesions ▪ Crusted 27 ...... ▪ Primary 82 ...... ▪ Recurrent 43 ...... Ulcers 72 ...... Vesicles 93 ...... ▫ Polymerase chain reaction 93–100 ...... ▫ Tzanck test (herpes zoster) 65 85 .33 .41

The practitioner should test for all STIs from all sites of con- exposures, assess if the patient is a candidate for emergency tact, begin treatment for any known exposure to STIs, and contraception. It is important for physicians to be fully prepared offer hepatitis A and B vaccinations. Physicians should also con- to provide patient education and supportive counseling. sider retesting patients for T pallidum and review HIV serology For victims of sexual assault when no condom was used, 12 weeks after most recent sexual contact. For all suspected STI consider presumptive treatment for chlamydia, gonorrhea,

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Table 2 Sexually Transmitted Infections: Screening and Confirmation Methods

Infection (Pathogen) Screening Method(s) Confirmation(s)

Chlamydia (Chlamydia trachomatis) Antinuclear antibody test Chlamydia culture*

Gonorrhea (Neisseria gonorrhoeae) Gram stain Gonorrhea culture*

Herpes simplex virus type 1 (HSV-1) Antinuclear antibody test Herpes culture and type 2 (HSV-2) and HSV antibody testing and HSV DNA testing*

Syphilis (Treponema pallidum) Rapid plasma reagin test and MHA-TP (microhemaglutination assay VDRL (Venereal Disease Research for antibodies to Treponema pallidum) Laboratory) test test and FTA-abs (fluorescent treponemal antibody absorption) test

* This confirmation method is the “gold standard” in verifying the etiology of this sexually transmitted infection. and trichomoniasis. Presumptive treatment, although contro- dations on screening for C trachomatis, N gonorrhoeae, T pal- versial, can alleviate patients’ fears while they await the results lidum, and HIV. The positive predictive value of STI testing of cultures. As pathogens may not be present in sufficient increases with the prevalence and risk of STIs. In asymptomatic quantities on initial testing, physicians should consider repeat persons, where prevalence and sexual health risk is low, very examinations and serology 12 weeks after the assault. The sensitive nonculture tests, such as the antinuclear antibody test risk of acquiring HIV is less than 0.1% for mucous membrane (ANA) or the direct fluorescent antibody test (DFA) can return exposure to blood. false positive results. Sexually active adults aged 25 years and For drug injection–related or sexual contact exposures to younger are at the highest risk for chlamydial infection. HIV, there is no conclusive data on the effectiveness of post- Properties of available tests for the most prevalent STI exposure therapy. The physician should consider postexposure pathogens are summarized in Table 1. As noted, clinicians therapy if the source is HIV positive, if there is a high risk of should check with their supporting laboratory as to preferred transmission (eg, no condom or a torn one, vaginal or anal methods of testing. Culture is often the preferred testing penetration), or if other factors increase the risk of transmission method when screening for chlamydia and gonorrhea in vic- (eg, anal or vaginal tears, bleeding, ulcers on the anus or tims of sexual assault and abuse. Screening, confirmations, external genitals, or evidence of an STI). and gold standards in testing patients for chlamydia, gonor- Therapy is probably most effective when initiated within rhea, HSV, and syphilis are listed in Table 2. 1 to 2 hours after contact and is probably not effective by 24 to 36 hours after exposure. Therapy is difficult, required for at least Treatment 30 days, and expensive. Side effects are common, but adher- Table 3 summarizes treatment for the STIs covered in this ence to therapy is critical for both effectiveness and prevention review. Treatment failures are usually due to reinfection, of drug-resistance. failure to treat infected sexual partners, or nonadherence to therapy. When STIs are suspected by history, physical exam- Screening and Diagnostic Testing ination, or preliminary laboratory test results, therapy should Because the majority of STIs are asymptomatic, deciding when be administered while awaiting laboratory confirmation. to screen patients is critical. People often underestimate their Because of the potential for significant damage to women’s risk of exposure to STIs and HIV and don’t understand safe reproductive health, physicians are encouraged to maintain a sexual practices. One third of all sexually active adults have low threshold for diagnosis and treatment. never been tested for HIV.5 Because self-reported sexual his- Very ill-appearing women may require intravenous antibi- tory is often an unreliable indicator of the actual risk of infec- otics, fluids, and pain management. Additionally, nonsteroidal tion, consider broader screening of populations in which preva- anti-inflammatory medications are helpful for controlling the lence of STIs is high. inflammation and pain associated with epididymoorchitis In general, all patients with one STI should be considered (level of evidence, B). A summary of levels of evidence by candidates for additional screening, and all patients at risk for risk group for clinical effectiveness in the screening and treat- STIs should be offered testing in accordance with recommen- ment of patients for STIs is provided in Table 4.

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Table 3 Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods*

Treatment Methods

Infection (Pathogen) Primary Alternative Comment(s)

Chlamydia Doxycycline, 100 mg Erythromycin (base), 500 mg Screen and treat patients (Chlamydia trachomatis) twice daily for 7 days OR four times daily for 7 days OR for gonorrhea. azithromycin dihydrate, ofloxacin, 300 mg twice daily single dose 1 g for 7 days OR levofloxacin, If patient is pregnant or 500 mg daily for 7 days lactating, use azithromycin.

Gonorrhea Ceftriaxone sodium, 125 mg Spectinomycin, 2 g Screen and treat patients (Neisseria gonorrhoeae) intramuscularly OR cefixime, intramuscularly OR cefotaxime for chlamydia. single dose 400 mg OR sodium, single dose 500 mg ciprofloxacin, single dose intramuscularly OR Note that fluoroquinolones 500 mg OR ofloxacin, single ceftizoxime sodium, 500 mg are contraindicated for dose 400 mg OR levofloxacin, intramuscularly OR cefoxitin patients who are younger single dose 250 mg OR sodium, 2 g intramuscularly than 18 years and patients gatifloxacin, single dose with probenecid, 1 g OR who are pregnant or 400 mg OR azithromycin, lemofloxacin, single dose lactating. single dose 1 g OR doxycycline, 400 mg OR norfloxacin, 100 mg twice daily for 7 days single dose 800 mg

Herpes simplex virus† ▫ Primary HSV Acyclovir, 200 mg five . . . Physicians treat herpes (episodic treatment) times daily for 10 days simplex virus with a tiered (or 400 mg three times daily approach, first attempting for 7 to 10 days) OR valacyclovir to control episodes or hydrochloride, 1 g twice “flare-ups” with episodic daily for 7 to 10 days OR treatment. Patients who have more than six episodes famciclovir, 125 mg per year, however, require three times daily for more aggressive treatment 7 to 10 days and are given daily suppressive treatment. ▫ Recurrent HSV In either situation, patients’ (episodic treatment for Acyclovir, 400 mg . . . infection status should be 6 episodes per year) three times daily for reassessed after 1 year of 5 days and 800 mg three times continuous treatment. daily for 3 days OR famciclovir, 125 mg twice daily for Twenty percent of patients 5 days OR valacyclovir, have a reduction in 500 mg twice daily for recurrence frequency after 3 days 1 year of treatment for this sexually transmitted infection.‡ ▫ Recurrent HSV (suppressive treatment for Acyclovir, 400 mg . . . Patients with recurrent HSV 6 episodes per year) twice daily OR valacyclovir, proctitis may be treated with 1 g daily OR famciclovir, acyclovir, 400 mg five times daily for 10 days. 250 mg twice daily (continued)

* Unless otherwise specified, delivery method for all medications listed is tablets, capsules, or caplets by mouth. † Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). ‡ Keep up to date with changing regimens via your local public health authorities or infectious disease consultant. § Nonspecific cervicitis or urethritis describes sexually transmitted infections caused by Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma. // Syphilis is classified as being early or late; primary, secondary, or tertiary; and latent. ¶ For patients with a hypersensitivity to pencillin, physicians should prescribe doxycycline, 100 mg twice daily for 28 days OR tretracycline, 500 mg four times daily for 28 days.

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Table 3 (continued) Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods*

Treatment Methods

Infection (Pathogen) Primary Alternative Comment(s)

Nonspecific urethritis Doxycycline, 100 mg Erythromycin (base), 500 mg Screen patients for or cervicitis§ twice daily for 7 days OR four times daily for 7 days OR chlamydia. azithromycin, single dose 1 g ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, If patient is pregnant or 500 mg daily for 7 days lactating, use azithromycin.

Syphilis Penicillin G benzathine, For patients who are hyper- For patients with latent syphilis (Treponema pallidum)// single dose, 2.4 million units sensitive to penicillin: (1 year), syphilis of unknown intramuscularly Doxycycline,100 mg twice daily duration, syphilis with for14 days OR tetracycline, cardiovascular involvement, or 500 mg four times daily tertiary syphilis, use weekly for 14 days OR ceftriaxone, treatment of 2.4 million units 1 g daily intramuscularly or of penicillin G benzathine intraveneously for 8 to 10 days delivered intramuscularly for 3 weeks.¶

If serologic test results do not show improvement 3 months after treatment, consider a lumbar puncture to rule out involvement of cerebrospinal fluid.

Trichomoniasis Metronidazole, single dose . . . Metronidazole is (Trichomonas vaginalis)2g OR metronidazole, 500 mg contraindicated in the first twice daily for 7 days trimester of pregnancy. If a diagnosis is made during this period, delay treatment until after the first trimester, when patients can be treated with metronidazole.

* Unless otherwise specified, delivery method for all medications listed is tablets, capsules, or caplets by mouth. † Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). ‡ Keep up to date with changing regimens via your local public health authorities or infectious disease consultant. § Nonspecific cervicitis or urethritis describes sexually transmitted infections caused by Mycoplasma genitalium, Mycoplasma hominis, or Ureaplasma. // Syphilis is classified as being early or late; primary, secondary, or tertiary; and latent. ¶ For patients with a hypersensitivity to pencillin, physicians should prescribe doxycycline, 100 mg twice daily for 28 days OR tetracycline, 500 mg four times daily for 28 days.

Hepatitis B vaccine is recommended for patients diag- should be administered within 14 days of sexual contact with nosed with any STI as well as for those in groups at high risk persons infected with hepatitis B. Hepatitis A immunoglobulin for STIs, including persons with multiple partners within the should be administered intramuscularly at a dose of 0.02 mL previous six months, intravenous drug users and their sexual per kilogram of body weight within 14 days of sexual exposure partners, and men who have anal intercourse with men (level to persons with hepatitis A; hepatitis A vaccination is not rec- of evidence, A).4 Hepatitis A vaccine is recommended for men ommended as postexposure prophylaxis, however.7 who have anal intercourse with men, and all intravenous and street drug users (level of evidence, B).4 The combined hep- Patient Education atitis A and B vaccine has similar efficacy to the individual vac- Because STIs are commonly asymptomatic and can go undi- cines.6 Hepatitis B immunoglobulin and hepatitis B vaccine agnosed for many years, physicians who must inform patients

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Table 4 Sexually Transmitted Infections: Levels of Evidence for Clinical Effectiveness of Screening and Treatment

Risk Group Infection (Pathogen)

Level of Evidence: A, Strong or moderate research-based evidence that is consistent across several studies, including at least two randomized controlled trials. ▫ Women At risk (all), including asymptomatic* Chlamydia (Chlamydia trachomatis), Syphilis (Treponema pallidum), Sexually active, age 25 y and younger Chlamydia (C trachomatis) ▫ Men, at risk (all) Syphilis (T pallidum) ▫ Newborns, ocular prophylaxis Gonorrhea (Neisseria gonorrhoeae)

Level of Evidence: B, Limited research-based evidence. The evidence in this level is less consistent or extensive than in the preceding group, but the preponderance of evidence supports the use of screening and treatment. ▫ Women Asymptomatic, age 25 y and younger Chlamydia (C trachomatis) At risk Gonorrhea (N gonorrhoeae) Pregnant, at risk Chlamydia (C trachomatis), gonorrhea (N gonorrhoeae)

Level of Evidence: C, Established common medical practice with little or no research-based evidence to support it. ▫ Women, pregnant Chlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus,† syphilis (T pallidum) ▫ Men, at risk Gonorrhea (N gonorrhoeae) ▫ Newborns, ocular prophylaxis Chlamydia (C trachomatis)

Level of Evidence: X, Moderate or strong research-based evidence suggests that this use of screening and treatment is not effective. ▫ Women, pregnant (asymptomatic) Herpes simplex virus ▫ General Screening (asymptomatic) Chlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus, syphilis (T pallidum) Level of Evidence: I, Insufficient evidence for or against this use of screening and treatment. ▫ Men, asymptomatic Chlamydia (C trachomatis)

* Repeat testing for syphilis should be ordered for at-risk women who are in their third trimester of pregnancy and then again at delivery.

† When a pregnant woman’s partner has tested positive for herpes simplex virus (HSV), physicians recommend abstinence or condoms during intercourse. Additionally, physicians examine pregnant women for signs of active genital lesions associated with HSV and recommend cesarean deliveries for women with lesions present. Use of acyclovir in pregnancy is commonly recommended for patients with recurrent HSV to prevent reactivation during pregnancy and delivery. Again, there is little or no research-based evidence to support these established common practices. of a new STI diagnosis should be extremely careful not to should discuss sexual health risks—including the risks inherent implicate the patient’s current or most recent sexual partner in choices of new sexual partners—and emphasize the impor- (often a spouse); a different sexual partner could have trans- tance of developing and adhering to safe sexual practices. mitted the STI many years ago. Patient education includes informing patients about the Improved patient education is crucial to reducing the diagnosis and transmission of STIs, use of medication, and transmission of STIs. When speaking to patients, physicians the responsibility and importance of notifying past sexual

534 • JAOA • Vol 104 • No 12 • December 2004 Nusbaum et al • Review Article REVIEW ARTICLE partners when an infection is diagnosed. Although patients are Comment often afraid or ashamed to notify past sexual partners, they Sexually transmitted infections are commonly asymptomatic. should be counseled regarding the risks of untreated infection Individuals tend to underestimate their risk for exposure to and strongly encouraged to help former partners avoid further STIs, including HIV. Sexually transmitted infections, espe- spread of infection and long-term health effects. cially gential ulcerative disease, increase the probability of Reviewing safer sexual practices in a professional and acquiring HIV by altering tissue integrity. Symptomatic infec- empathetic manner is imperative for patient confidence and tions present as genitourinary, anal, skin, and systemic signs compliance. Physicians should aim to empower patients to and symptoms. Diagnostic tests are reliable. Presumptive negotiate safer sexual practices with their partners and to treatment for concurrent STIs is prudent given long-term negotiate the kinds of sexual activity they are willing to par- sequela. Thorough treatment includes patient education and ticipate in with their partners. supportive counseling. Latex condoms reduce transmission of many STI pathogens when used during vaginal, anal, and oral sexual References activities. Physicians should ask if patients are hypersensitive 1. HIV prevention through early detection and treatment of other sexually trans- to latex or spermicide and be ready to provide alternative mitted diseases—United States. Recommendations of the Advisory Committee suggestions for protective barriers if such “allergies” exists. for HIV and STD Prevention. MMWR Recomm Rep. 1998;47(RR-12);1-24. Although condom availability and/or sexual health edu- 2. Turner CF, Rogers SM, Miller HG, Miller WC, Gribble JN, Chromy JR, et al. cation does not promote increased sexual activity, availability Untreated gonococcal and chlamydial infection in a probability sample of adults. JAMA. 2002;287:726-733. of condoms has been shown to increase the likelihood of 8 3. Centers for Disease Control and Prevention. Tracking the hidden epi- condom use. Explain that the correct use of condoms (see demics. Trends in STDs in the United States 2000. April 2001. Available at: http://www.plannedparenthood.org/bc/condom.htm for more infor- http://www.cdc.gov/nchstp/dstd/Stats_Trends/Trends2000.pdf. Accessed mation) includes the use of water-based lubricants instead of September 27, 2004. petroleum-based lubricants, which can result in latex break- 4. Centers for Disease Control and Prevention. HIV counseling and testing in down and reduced efficacy.8 publicly funded sites. Annual report 1997 and 1998. 2001. Available at: http://www.cdc.gov/hiv/pubs/cts98.pdf. Accessed September 27, 2004. The female condom should be used when the male 5. US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd condom will not be used, and, additionally, appears effective ed. Baltimore, Md: Williams & Wilkins; 1996;287-302,325-346. Available at: in reducing STIs for receptive anal intercourse.9 http://www.ahcpr.gov/clinic/cpsix.htm. Accessed September 27, 2004. Testing for HIV infection should be done before the ini- 6. FDA approval for a combined hepatitis A and B vaccine. MMWR Morb tiation of sexual activity with a new partner and barrier Mortal Wkly Rep. 2001;50:806-807. Available at: http://www.cdc.gov/mmwr/pre- methods should be continued until both partners are able to view/mmwrhtml/mm5037a4.htm. Accessed September 24, 2004. repeat HIV testing at least 6 months into a mutually monog- 7. National Guideline Clearinghouse. Vaccine preventable STDs. Sexually transmitted diseases treatment guidelines 2002. Available at: amous relationship and test results prove both partners to be http://www.ngc.gov/summary/summary.aspx?doc_id=3242&nbr=2468&string=h seronegative. epatitis. Accessed September 24, 2004. It is important for physicians to be prepared to provide 8. Kaplan DW, Feinstein RA, Fisher MM, Klein JD, Olmedo LF, Rome ES, et al; supportive counseling for patients’ emotional responses. People Committee on Adolescence. Condom use by adolescents. Pediatrics. 2001;107:1463-1469. with STIs often have to deal with feelings of guilt, anxiety, 9. Gross M, Buchbinder SP, Holte S, Celum CL, Koblin BA, Douglas JM Jr. anger, tension, and preoccupation. The diagnosis of an STI Use of reality “female condoms” for anal sex by US men who have sex with can be traumatic, altering self-image and affecting the dynamics men. HIVNET Vaccine Preparedness Study Protocol Team. Am J Public Health. of current and future relationships. 1999;89:1739-1741.

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