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Review  |   December 2004
Sexually Transmitted Infections and Increased Risk of Co-infection with Human Immunodeficiency Virus
Author Notes
  • From the Department of Family Medicine in the School of Medicine at the University of North Carolina at Chapel Hill. 
  • Address correspondence to: Margaret R.H. Nusbaum, DO, MPH, Associate Professor, Department of Family Medicine, 101 Manning Dr, CB 7595, Chapel Hill, NC 27514-7595.E-mail: mnusbaum@med.unc.edu 
Article Information
Gastroenterology / Obstetrics and Gynecology / Urological Disorders
Review   |   December 2004
Sexually Transmitted Infections and Increased Risk of Co-infection with Human Immunodeficiency Virus
The Journal of the American Osteopathic Association, December 2004, Vol. 104, 527-535. doi:10.7556/jaoa.2004.104.12.527
The Journal of the American Osteopathic Association, December 2004, Vol. 104, 527-535. doi:10.7556/jaoa.2004.104.12.527
Abstract

The incidence of trichomoniasis (Trichomonas vaginalis) in the United States is estimated at 5 million cases annually; chlamydia (Chlamydia trachomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000; and syphilis (Treponema pallidum), 70,000. However, most sexually transmitted infections (STIs) are asymptomatic—contributing to underdiagnosis estimated at 50% or more. Diagnosis of an STI signals sexual health risk because an STI facilitates the transmission and acquisition of other STIs, including human immunodeficiency virus (HIV). In fact, comorbid STIs increase patients' susceptibility of acquiring and transmitting HIV by two- to fivefold. Several studies have shown that aggressive STI prevention, testing, and treatment reduces the transmission of HIV. The authors discuss common clinical presentations, screening, diagnosis, and treatment for trichomoniasis, chlamydia, gonorrhea, syphilis, and herpes simplex virus.

Diagnosis of a sexually transmitted infection (STI) signals sexual health risk. STIs facilitate the transmission and acquisition of other STIs, including human immunodeficiency virus (HIV). Coexisting STIs increase susceptibility of acquiring and transmitting HIV by two- to fivefold.1 Studies show that aggressive STI prevention, testing, and treatment reduces transmission of HIV.1 
Most STIs are asymptomatic, contributing to widespread underdiagnosis estimated at 50% or higher.2 In the United States, the annual incidence of trichomoniasis (Trichomonas vaginalis) is estimated at 5 million; chlamydia (Chlamydia trachomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000, and syphilis (Treponema pallidum), 70,000.3 This article discusses the common clinical presentations, screening, diagnosis, and treatment for trichomoniasis, chlamydia, gonorrhea, syphilis, and herpes simplex virus. 
Clinical Presentation
Urethritis, Epididymitis, and Proctitis
In men, STIs usually remain confined to the urethra. Symptoms of urethritis include urethral discharge, dysuria, or urethral itching. The discharge of nongonococcal urethritis (NGU) is often slight, and may not be apparent without massaging the urethra. Discharge of NGU is usually minimal and gray, white, or mucoid rather than yellow. Discharge that is yellow and present in greater volume most often signals infection with N gonorrhoeae. 
Epididymitis presents as acute unilateral testicular pain and swelling. Clinical findings include tenderness of the epididymis and ductus deferens, erythema and edema of the overlying scrotal skin, urethral discharge, and dysuria. Swelling and tenderness may be localized or may extend to the entire epididymis and surrounding areas, making the epididymis less distinct in the inflammatory mass. 
Proctitis presents as anorectal or perineal itching, anorectal pain, and discharge. 
Trichomoniasis tends to be asymptomatic in men, while chlamydia and gonorrhea present as acute urethritis or epididymitis. In sexually active men, however, C trachomatiscauses 30% to 50% of cases of NGU,4 an even higher proportion of postgonococcal urethritis, and the majority of cases of epididymitis. Ureaplasma urealyticum appears to be causative in the remaining cases, although the cause is undetermined in approximately one third of men who have NGU. Routine screening for U urealyticum is not recommended as NGU is often associated with infection from C trachomatis and N gonorrhoeae. 
Other urinary tract pathogens, including Escherichia coli and Pseudomonas aeruginosa, can be causative agents in men who are older, have structural abnormalities of the urethra, have recently undergone a urinary tract procedure or manipulation, 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. 
Positive results for leukocyte esterase on urinalysis can indicate C trachomatis, N gonorrhoeae, or other urinary tract pathogens. Chlamydia trachomatis or T vaginalis should be suspected in the absence of gram negative intracellular diplococci on Gram stain. Patients presenting with epididymitis should be examined and tested for chlamydia and gonorrhea. In the case of proctitis, cultures should be taken from the symptomatic area. 
In women, urethritis can be a manifestation of C trachomatis, herpes simplex virus (HSV), N gonorrhoeae, or T vaginalis. As in men, proctitis in women presents as anorectal or perineal itching, or anorectal pain and discharge. 
Vaginitis and Cervicitis
Etiologic agents of vaginitis and cervicitis include C trachomatis, N gonorrhoeae, HSV, and T vaginalis. More than half of endocervical infections do not cause sufficient inflammation to result in clinical signs and symptoms, however. When present, symptoms can include dysuria, vaginal discharge, dyspareunia, perineal itching, and pelvic discomfort or pain. Erythema multiforme and swelling of the vulva or labia suggest trichomonal or HSV infection. 
Trichomonal discharge is usually copius, frothy, and yellow-green or occasionally gray. The vaginal walls are often erythematous and granular in appearance, while punctate hemorrhages of the cervix give it the classic “strawberry” appearance. 
Perineal swelling, cervical vesicles, or venereal (or dendriform) ulcers, suggest HSV infection. Alternatively, swelling, tenderness, and drainage in glandula vestibularis major (ie, Bartholin's gland) sites suggest gonorrheal infection. A friable cervix and mucopurulent vaginal discharge can be seen with gonorrhea and chlamydia. 
Because chlamydia, gonorrhea, and trichomoniasis, may present similarly with mucopurulent vaginal discharge, drainage from the cervix, or a friable cervix, physicians should screen for all three—as well as for bacterial vaginosis. Ulcerative lesions should be tested for HSV. A definitive diagnosis of trichomoniasis requires identifying T vaginalis on a Trichomonas wet prep test. 
Pelvic Inflammatory Disease
With the exceptions of T vaginalis and HSV, pathogens in the lower genital tract in women frequently and rapidly ascend to the endometrium and adnex uteri, causing pelvic inflammatory disease (PID) and pelvic adhesive disease. Manifestations of PID include endometritis, salpingitis, tuboovarian abscess, and pelvic peritonitis. 
Physical symptoms of PID include perineal and urethral itching or burning, vaginal discharge and odor, spotting with intercourse, insertional or deep dyspareunia, pelvic pain, abdominal pain, worsening dysmenorrhea, or systemic symptoms including chills, fever, malaise, or myalgia. Cervical motion tenderness on bimanual pelvic examination can indicate PID. 
Fitz-Hugh–Curtis syndrome presents as PID with pain in the right upper quadrant and hepatic tenderness with palpation. Fever, increased pulse rate and blood pressure, and enlarged, painful inguinal lymph nodes can also be present. Leukocytosis and elevated erythrocyte sedimentation rate also support a diagnosis of PID. 
Pelvic inflammatory disease can lead to infertility, ectopic pregnancy, and chronic pelvic pain. Because PID can potentially cause significant damage to women's reproductive health, clinicians should have a low threshold for diagnosis and treatment of PID. 
Genital Ulcerative Disease
Herpes simplex virus is the most common single cause of genital ulcers in the United States. Herpetic ulcers appear on the external genital, urethral, and anorectal areas as well as in the vagina and on the cervix. About 10% of ulcers are the result of more than one etiologic agent, however. The clinical features of ulcers can be altered in immunosuppressed individuals. Differential diagnosis includes syphilis and herpes zoster as well as noninfectious causes such as trauma, contact dermatitis, lichen sclerosis, and Behçet's syndrome. 
The primary lesion of syphilis, the chancre, is usually painless. It is a solitary ulcer with raised, well-defined borders and a clean, indurated base. The chancre occurs at the site of infection and is usually associated with nontender regional lymphadenopathy and heals spontaneously and without scarring in 3 to 6 weeks. 
Secondary syphilis occurs 4 to 10 weeks after the primary lesion of syphilis appears—and goes untreated. Symptoms of secondary syphilis include myalgia, arthralgia, malaise, low-grade fever, and generalized lymphadenopathy. A nonpruritic, maculopapular eruption affecting the trunk, limbs, palms, and soles is present in 10% to 75% of patients. Condylomata lata, fleshy lesions that may be broad-based, flat, or raised, may be seen in the mucous membranes (eg, anus, external genitals, mouth). 
In up to one third of patients with secondary syphilis, the primary chancre is still present, increasing the likelihood of transmission to any additional sexual contacts. 
Left untreated, syphilis becomes latent with no readily apparent clinical findings. Without therapy, approximately one third of those infected will develop tertiary syphilis 10 to 30 years after the initial infection. The manifestations of tertiary syphilis include gummas, aortitis and other cardiovascular disease, and neurosyphilis. 
Suspected Exposure to Sexually Transmitted Infections
Patients may initially present to physicians' offices with concerns about STI exposure for numerous reasons. Some patients fear the results of not using protective barriers with a new sexual partner or they are apprehensive about the failure of such barriers during sexual contact. Some patients seek screening and medical care after they have been informed by a sexual partner or public health official of their possible contact with an STI. Still other patients may have recently discovered that their intimate relationship was not mutually monogamous. 
The practitioner should test for all STIs from all sites of contact, begin treatment for any known exposure to STIs, and offer hepatitis A and B vaccinations. Physicians should also consider retesting patients for T pallidum and review HIV serology 12 weeks after most recent sexual contact. For all suspected STI exposures, assess if the patient is a candidate for emergency contraception. It is important for physicians to be fully prepared to provide patient education and supportive counseling. 
For victims of sexual assault when no condom was used, consider presumptive treatment for chlamydia, gonorrhea, and trichomoniasis. Presumptive treatment, although controversial, can alleviate patients' fears while they await the results of cultures. As pathogens may not be present in sufficient quantities on initial testing, physicians should consider repeat examinations and serology 12 weeks after the assault. The risk of acquiring HIV is less than 0.1% for mucous membrane exposure to blood. 
For drug injection–related or sexual contact exposures to HIV, there is no conclusive data on the effectiveness of postexposure therapy. The physician should consider postexposure therapy if the source is HIV positive, if there is a high risk of transmission (eg, no condom or a torn one, vaginal or anal penetration), or if other factors increase the risk of transmission (eg, anal or vaginal tears, bleeding, ulcers on the anus or external genitals, or evidence of an STI). 
Therapy is probably most effective when initiated within 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 30 days, and expensive. Side effects are common, but adherence to therapy is critical for both effectiveness and prevention of drug-resistance. 
Screening and Diagnostic Testing
Because the majority of STIs are asymptomatic, deciding when to screen patients is critical. People often underestimate their risk of exposure to STIs and HIV and don't understand safe sexual practices. One third of all sexually active adults have never been tested for HIV.5 Because self-reported sexual history is often an unreliable indicator of the actual risk of infection, consider broader screening of populations in which prevalence of STIs is high. 
In general, all patients with one STI should be considered candidates for additional screening, and all patients at risk for STIs should be offered testing in accordance with recommendations on screening for C trachomatis, N gonorrhoeae, T pallidum, and HIV. The positive predictive value of STI testing increases with the prevalence and risk of STIs. In asymptomatic persons, where prevalence and sexual health risk is low, very sensitive nonculture tests, such as the antinuclear antibody test (ANA) or the direct fluorescent antibody test (DFA) can return false positive results. Sexually active adults aged 25 years and younger are at the highest risk for chlamydial infection. 
Properties of available tests for the most prevalent STI pathogens are summarized in Table 1. As noted, clinicians should check with their supporting laboratory as to preferred methods of testing. Culture is often the preferred testing method when screening for chlamydia and gonorrhea in victims of sexual assault and abuse. Screening, confirmations, and gold standards in testing patients for chlamydia, gonorrhea, HSV, and syphilis are listed in Table 2. 
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)
□ DFA80-8698.43.04
□ Trichomonas wet prep50-7570-98.50.25
Chlamydia (Chlamydia trachomatis)
□ ANA
- Men: urethra70-9097-99.90.10
- Women: cervix70-9097-99.90.10
□ Chlamydia culture§70-90100.90.10
□ DFA70-9097-99.99.99
□ DNA probe60-9595-99.19.05
□ Ligase chain reaction.......19.05
- Men: urethra9595......
- Women: vagina, cervix9595......
- Urine95-99.........
□ Papanicolaou smear104.5.11.20
□ Polymerase chain reaction...95.19.05
- Men: urethra60-95.........
- Women: vagina, cervix60-95.........
- Urine95-99.........
□ ULE40-100.........
□ Urine77-9197-100.92.09
Gonorrhea (Neisseria gonorrhoeae)
□ ANA
- Men: urethra9595.19.05
- Women: endocervix60-10070-98.50.01
□ DNA probe97-9997-99.99.01
□ Gonorrhea culture§80-95.........
□ Gram stain
- Men: urethra70-9997-99.99.01
- Women: cervix30-6590-97.66.36
□ ULE46-6093-96.15.41
Syphilis (Treponema pallidum
□ Darkfield microscopy (treponemal)
— Primary80 # ......
□ Fluorescent treponemal antibody absorption test and microhemaglutination assay for antibodies to Treponema pallidum (treponemal)
— Primary8496.21.17
— Other stages of infection100....75.01
□ Rapid plasma reagin and Venereal Disease Research Laboratory (nontreponemal)
— Early or primary62-7675-85.76.01
— Secondary100....24.70
— Late70100.99.30
Herpes simplex virus**
□ ANA59-93.........
□ Cytology30-80.........
□ Direct fluorescent antibody70-90.........
□ Herpes culture
— Lesions
▪ Crusted27.........
▪ Primary82.........
▪ Recurrent43.........
— Ulcers72.........
— Vesicles93.........
□ Polymerase chain reaction93-100.........
□ Tzanck test (herpes zoster)
65
85
.33
.41
 *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.
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)
□ DFA80-8698.43.04
□ Trichomonas wet prep50-7570-98.50.25
Chlamydia (Chlamydia trachomatis)
□ ANA
- Men: urethra70-9097-99.90.10
- Women: cervix70-9097-99.90.10
□ Chlamydia culture§70-90100.90.10
□ DFA70-9097-99.99.99
□ DNA probe60-9595-99.19.05
□ Ligase chain reaction.......19.05
- Men: urethra9595......
- Women: vagina, cervix9595......
- Urine95-99.........
□ Papanicolaou smear104.5.11.20
□ Polymerase chain reaction...95.19.05
- Men: urethra60-95.........
- Women: vagina, cervix60-95.........
- Urine95-99.........
□ ULE40-100.........
□ Urine77-9197-100.92.09
Gonorrhea (Neisseria gonorrhoeae)
□ ANA
- Men: urethra9595.19.05
- Women: endocervix60-10070-98.50.01
□ DNA probe97-9997-99.99.01
□ Gonorrhea culture§80-95.........
□ Gram stain
- Men: urethra70-9997-99.99.01
- Women: cervix30-6590-97.66.36
□ ULE46-6093-96.15.41
Syphilis (Treponema pallidum
□ Darkfield microscopy (treponemal)
— Primary80 # ......
□ Fluorescent treponemal antibody absorption test and microhemaglutination assay for antibodies to Treponema pallidum (treponemal)
— Primary8496.21.17
— Other stages of infection100....75.01
□ Rapid plasma reagin and Venereal Disease Research Laboratory (nontreponemal)
— Early or primary62-7675-85.76.01
— Secondary100....24.70
— Late70100.99.30
Herpes simplex virus**
□ ANA59-93.........
□ Cytology30-80.........
□ Direct fluorescent antibody70-90.........
□ Herpes culture
— Lesions
▪ Crusted27.........
▪ Primary82.........
▪ Recurrent43.........
— Ulcers72.........
— Vesicles93.........
□ Polymerase chain reaction93-100.........
□ Tzanck test (herpes zoster)
65
85
.33
.41
 *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.
×
Table 2
Sexually Transmitted Infections: Screening and Confirmation Methods
Infection (Pathogen) Screening Method(s) Confirmation(s)
Chlamydia (Chlamydia trachomatis)Antinuclear antibody testChlamydia culture*
Gonorrhea (Neisseria gonorrhoeae)Gram stainGonorrhea culture*
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)Antinuclear antibody test and HSV antibody testingHerpes culture and HSV DNA testing*
Syphilis (Treponema pallidum)Rapid plasma reagin test and VDRL (Venereal Disease Research Laboratory) testMHA-TP (microhemaglutination assay for antibodies to Treponema pallidum) 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.
Table 2
Sexually Transmitted Infections: Screening and Confirmation Methods
Infection (Pathogen) Screening Method(s) Confirmation(s)
Chlamydia (Chlamydia trachomatis)Antinuclear antibody testChlamydia culture*
Gonorrhea (Neisseria gonorrhoeae)Gram stainGonorrhea culture*
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)Antinuclear antibody test and HSV antibody testingHerpes culture and HSV DNA testing*
Syphilis (Treponema pallidum)Rapid plasma reagin test and VDRL (Venereal Disease Research Laboratory) testMHA-TP (microhemaglutination assay for antibodies to Treponema pallidum) 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.
×
Treatment
Table 3 summarizes treatment for the STIs covered in this review. Treatment failures are usually due to reinfection, failure to treat infected sexual partners, or nonadherence to therapy. When STIs are suspected by history, physical examination, or preliminary laboratory test results, therapy should be administered while awaiting laboratory confirmation. Because of the potential for significant damage to women's reproductive health, physicians are encouraged to maintain a low threshold for diagnosis and treatment. 
Table 3
Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods *
Treatment Methods
Infection (Pathogen) Primary Alternative Comment(s)
Chlamydia (Chlamydia trachomatis)Doxycycline, 100 mg twice daily for 7 days OR azithromycin dihydrate, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen and treat patients for gonorrhea.
If patient is pregnant or lactating, use azithromycin.
Gonorrhea (Neisseria gonorrhoeae)Ceftriaxone sodium, 125 mg intramuscularly OR cefixime, single dose 400 mg OR ciprofloxacin, single dose 500 mg OR ofloxacin, single dose 400 mg OR levofloxacin, single dose 250 mg OR gatifloxacin, single dose 400 mg OR azithromycin, single dose 1 g OR doxycycline, 100 mg twice daily for 7 daysSpectinomycin, 2 g intramuscularly OR cefotaxime sodium, single dose 500 mg intramuscularly OR ceftizoxime sodium, 500 mg intramuscularly OR cefoxitin sodium, 2 g intramuscularly with probenecid, 1 g OR lemofloxacin, single dose 400 mg OR norfloxacin, single dose 800 mgScreen and treat patients for chlamydia.
Note that fluoroquinolones are contraindicated for patients who are younger than 18 years and patients who are pregnant or lactating.
Herpes simplex virus
Primary HSV (episodic treatment)Acyclovir, 200 mg five times daily for 10 days (or 400 mg three times daily for 7 to 10 days) OR valacyclovir hydrochloride, 1 g twice daily for 7 to 10 days OR famciclovir, 125 mg three times daily for 7 to 10 days...Physicians treat herpes simplex virus with a tiered approach, first attempting to control episodes or “flare-ups” with episodic treatment. Patients who have more than six episodes per year, however, require more aggressive treatment and are given daily suppressive treatment.
Recurrent HSV (episodic treatment for < 6 episodes per year)Acyclovir, 400 mg three times daily for 5 days and 800 mg three times daily for 3 days OR famciclovir, 125 mg twice daily for 5 days OR valacyclovir, 500 mg twice daily for 3 days...In either situation, patients' infection status should be reassessed after 1 year of continuous treatment.
Twenty percent of patients have a reduction in recurrence frequency after 1 year of treatment for this sexually transmitted infection.
Recurrent HSV (suppressive treatment for ≥ 6 episodes per year)Acyclovir, 400 mg twice daily OR valacyclovir, 1 g daily OR famciclovir, 250 mg twice daily...Patients with recurrent HSV proctitis may be treated with acyclovir, 400 mg five times daily for 10 days.
Nonspecific urethritis or cervicitis§Doxycycline, 100 mg twice daily for 7 days OR azithromycin, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen patients for chlamydia.
If patient is pregnant or lactating, use azithromycin.
Syphilis (Treponema pallidum)Penicillin G benzathine, single dose, 2.4 million units intramuscularlyFor patients who are hypersensitive to penicillin: Doxycycline, 100 mg twice daily for 14 days OR tetracycline, 500 mg four times daily for 14 days OR ceftriaxone, 1 g daily intramuscularly or intraveneously for 8 to 10 daysFor patients with latent syphilis (>1 year), syphilis of unknown duration, syphilis with cardiovascular involvement, or tertiary syphilis, use weekly treatment of 2.4 million units of penicillin G benzathine 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 (Trichomonas vaginalis)Metronidazole, single dose 2 g OR metronidazole, 500 mg twice daily for 7 days...Metronidazole is contraindicated in the first 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.
Table 3
Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods *
Treatment Methods
Infection (Pathogen) Primary Alternative Comment(s)
Chlamydia (Chlamydia trachomatis)Doxycycline, 100 mg twice daily for 7 days OR azithromycin dihydrate, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen and treat patients for gonorrhea.
If patient is pregnant or lactating, use azithromycin.
Gonorrhea (Neisseria gonorrhoeae)Ceftriaxone sodium, 125 mg intramuscularly OR cefixime, single dose 400 mg OR ciprofloxacin, single dose 500 mg OR ofloxacin, single dose 400 mg OR levofloxacin, single dose 250 mg OR gatifloxacin, single dose 400 mg OR azithromycin, single dose 1 g OR doxycycline, 100 mg twice daily for 7 daysSpectinomycin, 2 g intramuscularly OR cefotaxime sodium, single dose 500 mg intramuscularly OR ceftizoxime sodium, 500 mg intramuscularly OR cefoxitin sodium, 2 g intramuscularly with probenecid, 1 g OR lemofloxacin, single dose 400 mg OR norfloxacin, single dose 800 mgScreen and treat patients for chlamydia.
Note that fluoroquinolones are contraindicated for patients who are younger than 18 years and patients who are pregnant or lactating.
Herpes simplex virus
Primary HSV (episodic treatment)Acyclovir, 200 mg five times daily for 10 days (or 400 mg three times daily for 7 to 10 days) OR valacyclovir hydrochloride, 1 g twice daily for 7 to 10 days OR famciclovir, 125 mg three times daily for 7 to 10 days...Physicians treat herpes simplex virus with a tiered approach, first attempting to control episodes or “flare-ups” with episodic treatment. Patients who have more than six episodes per year, however, require more aggressive treatment and are given daily suppressive treatment.
Recurrent HSV (episodic treatment for < 6 episodes per year)Acyclovir, 400 mg three times daily for 5 days and 800 mg three times daily for 3 days OR famciclovir, 125 mg twice daily for 5 days OR valacyclovir, 500 mg twice daily for 3 days...In either situation, patients' infection status should be reassessed after 1 year of continuous treatment.
Twenty percent of patients have a reduction in recurrence frequency after 1 year of treatment for this sexually transmitted infection.
Recurrent HSV (suppressive treatment for ≥ 6 episodes per year)Acyclovir, 400 mg twice daily OR valacyclovir, 1 g daily OR famciclovir, 250 mg twice daily...Patients with recurrent HSV proctitis may be treated with acyclovir, 400 mg five times daily for 10 days.
Nonspecific urethritis or cervicitis§Doxycycline, 100 mg twice daily for 7 days OR azithromycin, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen patients for chlamydia.
If patient is pregnant or lactating, use azithromycin.
Syphilis (Treponema pallidum)Penicillin G benzathine, single dose, 2.4 million units intramuscularlyFor patients who are hypersensitive to penicillin: Doxycycline, 100 mg twice daily for 14 days OR tetracycline, 500 mg four times daily for 14 days OR ceftriaxone, 1 g daily intramuscularly or intraveneously for 8 to 10 daysFor patients with latent syphilis (>1 year), syphilis of unknown duration, syphilis with cardiovascular involvement, or tertiary syphilis, use weekly treatment of 2.4 million units of penicillin G benzathine 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 (Trichomonas vaginalis)Metronidazole, single dose 2 g OR metronidazole, 500 mg twice daily for 7 days...Metronidazole is contraindicated in the first 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.
×
Very ill-appearing women may require intravenous antibiotics, fluids, and pain management. Additionally, nonsteroidal anti-inflammatory medications are helpful for controlling the inflammation and pain associated with epididymoorchitis (level of evidence, B). A summary of levels of evidence by risk group for clinical effectiveness in the screening and treatment of patients for STIs is provided in Table 4. 
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 youngerChlamydia (C trachomatis)
□ Men, at risk (all)Syphilis (T pallidum)
□ Newborns, ocular prophylaxisGonorrhea (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 youngerChlamydia (C trachomatis)
- At riskGonorrhea (N gonorrhoeae)
- Pregnant, at riskChlamydia (C trachomatis), gonorrhea (N gonorrhoeae)
Level of Evidence: C, Established common medical practice with little or no research-based evidence to support it.
□ Women, pregnantChlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus, syphilis (T pallidum)
□ Men, at riskGonorrhea (N gonorrhoeae)
□ Newborns, ocular prophylaxisChlamydia (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.
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 youngerChlamydia (C trachomatis)
□ Men, at risk (all)Syphilis (T pallidum)
□ Newborns, ocular prophylaxisGonorrhea (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 youngerChlamydia (C trachomatis)
- At riskGonorrhea (N gonorrhoeae)
- Pregnant, at riskChlamydia (C trachomatis), gonorrhea (N gonorrhoeae)
Level of Evidence: C, Established common medical practice with little or no research-based evidence to support it.
□ Women, pregnantChlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus, syphilis (T pallidum)
□ Men, at riskGonorrhea (N gonorrhoeae)
□ Newborns, ocular prophylaxisChlamydia (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.
×
Hepatitis B vaccine is recommended for patients diagnosed with any STI as well as for those in groups at high risk for STIs, including persons with multiple partners within the previous six months, intravenous drug users and their sexual partners, and men who have anal intercourse with men (level of evidence, A).4 Hepatitis A vaccine is recommended for men who have anal intercourse with men, and all intravenous and street drug users (level of evidence, B).4 The combined hepatitis A and B vaccine has similar efficacy to the individual vaccines.6 Hepatitis B immunoglobulin and hepatitis B vaccine should be administered within 14 days of sexual contact with persons infected with hepatitis B. Hepatitis A immunoglobulin should be administered intramuscularly at a dose of 0.02 mL per kilogram of body weight within 14 days of sexual exposure to persons with hepatitis A; hepatitis A vaccination is not recommended as postexposure prophylaxis, however.7 
Patient Education
Because STIs are commonly asymptomatic and can go undiagnosed for many years, physicians who must inform patients of a new STI diagnosis should be extremely careful not to implicate the patient's current or most recent sexual partner (often a spouse); a different sexual partner could have transmitted the STI many years ago. 
Improved patient education is crucial to reducing the transmission of STIs. When speaking to patients, physicians should discuss sexual health risks—including the risks inherent in choices of new sexual partners—and emphasize the importance of developing and adhering to safe sexual practices. 
Patient education includes informing patients about the diagnosis and transmission of STIs, use of medication, and the responsibility and importance of notifying past sexual partners when an infection is diagnosed. Although patients are often afraid or ashamed to notify past sexual partners, they should be counseled regarding the risks of untreated infection and strongly encouraged to help former partners avoid further spread of infection and long-term health effects. 
Reviewing safer sexual practices in a professional and empathetic manner is imperative for patient confidence and compliance. Physicians should aim to empower patients to negotiate safer sexual practices with their partners and to negotiate the kinds of sexual activity they are willing to participate in with their partners. 
Latex condoms reduce transmission of many STI pathogens when used during vaginal, anal, and oral sexual activities. Physicians should ask if patients are hypersensitive to latex or spermicide and be ready to provide alternative suggestions for protective barriers if such “allergies” exists. 
Although condom availability and/or sexual health education does not promote increased sexual activity, availability of condoms has been shown to increase the likelihood of condom use.8 Explain that the correct use of condoms (see http://www.plannedparenthood.org/bc/condom.htm for more information) includes the use of water-based lubricants instead of petroleum-based lubricants, which can result in latex breakdown and reduced efficacy.8 
The female condom should be used when the male condom will not be used, and, additionally, appears effective in reducing STIs for receptive anal intercourse.9 
Testing for HIV infection should be done before the initiation of sexual activity with a new partner and barrier methods should be continued until both partners are able to repeat HIV testing at least 6 months into a mutually monogamous relationship and test results prove both partners to be seronegative. 
It is important for physicians to be prepared to provide supportive counseling for patients' emotional responses. People with STIs often have to deal with feelings of guilt, anxiety, anger, tension, and preoccupation. The diagnosis of an STI can be traumatic, altering self-image and affecting the dynamics of current and future relationships. 
Comment
Sexually transmitted infections are commonly asymptomatic. Individuals tend to underestimate their risk for exposure to STIs, including HIV. Sexually transmitted infections, especially gential ulcerative disease, increase the probability of acquiring HIV by altering tissue integrity. Symptomatic infections present as genitourinary, anal, skin, and systemic signs and symptoms. Diagnostic tests are reliable. Presumptive treatment for concurrent STIs is prudent given long-term sequela. Thorough treatment includes patient education and supportive counseling. 
HIV prevention through early detection and treatment of other sexually transmitted diseases—United States. Recommendations of the Advisory Committee for HIV and STD Prevention. MMWR Recomm Rep. 1998;47(RR-12);1-24.
Turner CF, Rogers SM, Miller HG, Miller WC, Gribble JN, Chromy JR, et al. Untreated gonococcal and chlamydial infection in a probability sample of adults. JAMA. 2002;287:726-733.
Centers for Disease Control and Prevention. Tracking the hidden epidemics. Trends in STDs in the United States 2000. April 2001. Available at: http://www.cdc.gov/nchstp/dstd/Stats_Trends/Trends2000.pdf. Accessed September 27, 2004.
Centers for Disease Control and Prevention. HIV counseling and testing in publicly funded sites. Annual report 1997 and 1998. 2001. Available at: http://www.cdc.gov/hiv/pubs/cts98.pdf. Accessed September 27, 2004.
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.
FDA approval for a combined hepatitis A and B vaccine. MMWR Morb Mortal Wkly Rep. 2001;50:806-807. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5037a4.htm. Accessed September 24, 2004.
National Guideline Clearinghouse. Vaccine preventable STDs. Sexually transmitted diseases treatment guidelines 2002. Available at: http://www.ngc.gov/summary/summary.aspx?doc_id=3242&nbr=2468&string=hepatitis. Accessed September 24, 2004.
Kaplan DW, Feinstein RA, Fisher MM, Klein JD, Olmedo LF, Rome ES, et al; Committee on Adolescence. Condom use by adolescents. Pediatrics. 2001;107:1463-1469.
Gross M, Buchbinder SP, Holte S, Celum CL, Koblin BA, Douglas JM Jr. Use of reality “female condoms” for anal sex by US men who have sex with men. HIVNET Vaccine Preparedness Study Protocol Team. Am J Public Health. 1999;89:1739-1741.
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)
□ DFA80-8698.43.04
□ Trichomonas wet prep50-7570-98.50.25
Chlamydia (Chlamydia trachomatis)
□ ANA
- Men: urethra70-9097-99.90.10
- Women: cervix70-9097-99.90.10
□ Chlamydia culture§70-90100.90.10
□ DFA70-9097-99.99.99
□ DNA probe60-9595-99.19.05
□ Ligase chain reaction.......19.05
- Men: urethra9595......
- Women: vagina, cervix9595......
- Urine95-99.........
□ Papanicolaou smear104.5.11.20
□ Polymerase chain reaction...95.19.05
- Men: urethra60-95.........
- Women: vagina, cervix60-95.........
- Urine95-99.........
□ ULE40-100.........
□ Urine77-9197-100.92.09
Gonorrhea (Neisseria gonorrhoeae)
□ ANA
- Men: urethra9595.19.05
- Women: endocervix60-10070-98.50.01
□ DNA probe97-9997-99.99.01
□ Gonorrhea culture§80-95.........
□ Gram stain
- Men: urethra70-9997-99.99.01
- Women: cervix30-6590-97.66.36
□ ULE46-6093-96.15.41
Syphilis (Treponema pallidum
□ Darkfield microscopy (treponemal)
— Primary80 # ......
□ Fluorescent treponemal antibody absorption test and microhemaglutination assay for antibodies to Treponema pallidum (treponemal)
— Primary8496.21.17
— Other stages of infection100....75.01
□ Rapid plasma reagin and Venereal Disease Research Laboratory (nontreponemal)
— Early or primary62-7675-85.76.01
— Secondary100....24.70
— Late70100.99.30
Herpes simplex virus**
□ ANA59-93.........
□ Cytology30-80.........
□ Direct fluorescent antibody70-90.........
□ Herpes culture
— Lesions
▪ Crusted27.........
▪ Primary82.........
▪ Recurrent43.........
— Ulcers72.........
— Vesicles93.........
□ Polymerase chain reaction93-100.........
□ Tzanck test (herpes zoster)
65
85
.33
.41
 *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.
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)
□ DFA80-8698.43.04
□ Trichomonas wet prep50-7570-98.50.25
Chlamydia (Chlamydia trachomatis)
□ ANA
- Men: urethra70-9097-99.90.10
- Women: cervix70-9097-99.90.10
□ Chlamydia culture§70-90100.90.10
□ DFA70-9097-99.99.99
□ DNA probe60-9595-99.19.05
□ Ligase chain reaction.......19.05
- Men: urethra9595......
- Women: vagina, cervix9595......
- Urine95-99.........
□ Papanicolaou smear104.5.11.20
□ Polymerase chain reaction...95.19.05
- Men: urethra60-95.........
- Women: vagina, cervix60-95.........
- Urine95-99.........
□ ULE40-100.........
□ Urine77-9197-100.92.09
Gonorrhea (Neisseria gonorrhoeae)
□ ANA
- Men: urethra9595.19.05
- Women: endocervix60-10070-98.50.01
□ DNA probe97-9997-99.99.01
□ Gonorrhea culture§80-95.........
□ Gram stain
- Men: urethra70-9997-99.99.01
- Women: cervix30-6590-97.66.36
□ ULE46-6093-96.15.41
Syphilis (Treponema pallidum
□ Darkfield microscopy (treponemal)
— Primary80 # ......
□ Fluorescent treponemal antibody absorption test and microhemaglutination assay for antibodies to Treponema pallidum (treponemal)
— Primary8496.21.17
— Other stages of infection100....75.01
□ Rapid plasma reagin and Venereal Disease Research Laboratory (nontreponemal)
— Early or primary62-7675-85.76.01
— Secondary100....24.70
— Late70100.99.30
Herpes simplex virus**
□ ANA59-93.........
□ Cytology30-80.........
□ Direct fluorescent antibody70-90.........
□ Herpes culture
— Lesions
▪ Crusted27.........
▪ Primary82.........
▪ Recurrent43.........
— Ulcers72.........
— Vesicles93.........
□ Polymerase chain reaction93-100.........
□ Tzanck test (herpes zoster)
65
85
.33
.41
 *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.
×
Table 2
Sexually Transmitted Infections: Screening and Confirmation Methods
Infection (Pathogen) Screening Method(s) Confirmation(s)
Chlamydia (Chlamydia trachomatis)Antinuclear antibody testChlamydia culture*
Gonorrhea (Neisseria gonorrhoeae)Gram stainGonorrhea culture*
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)Antinuclear antibody test and HSV antibody testingHerpes culture and HSV DNA testing*
Syphilis (Treponema pallidum)Rapid plasma reagin test and VDRL (Venereal Disease Research Laboratory) testMHA-TP (microhemaglutination assay for antibodies to Treponema pallidum) 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.
Table 2
Sexually Transmitted Infections: Screening and Confirmation Methods
Infection (Pathogen) Screening Method(s) Confirmation(s)
Chlamydia (Chlamydia trachomatis)Antinuclear antibody testChlamydia culture*
Gonorrhea (Neisseria gonorrhoeae)Gram stainGonorrhea culture*
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2)Antinuclear antibody test and HSV antibody testingHerpes culture and HSV DNA testing*
Syphilis (Treponema pallidum)Rapid plasma reagin test and VDRL (Venereal Disease Research Laboratory) testMHA-TP (microhemaglutination assay for antibodies to Treponema pallidum) 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.
×
Table 3
Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods *
Treatment Methods
Infection (Pathogen) Primary Alternative Comment(s)
Chlamydia (Chlamydia trachomatis)Doxycycline, 100 mg twice daily for 7 days OR azithromycin dihydrate, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen and treat patients for gonorrhea.
If patient is pregnant or lactating, use azithromycin.
Gonorrhea (Neisseria gonorrhoeae)Ceftriaxone sodium, 125 mg intramuscularly OR cefixime, single dose 400 mg OR ciprofloxacin, single dose 500 mg OR ofloxacin, single dose 400 mg OR levofloxacin, single dose 250 mg OR gatifloxacin, single dose 400 mg OR azithromycin, single dose 1 g OR doxycycline, 100 mg twice daily for 7 daysSpectinomycin, 2 g intramuscularly OR cefotaxime sodium, single dose 500 mg intramuscularly OR ceftizoxime sodium, 500 mg intramuscularly OR cefoxitin sodium, 2 g intramuscularly with probenecid, 1 g OR lemofloxacin, single dose 400 mg OR norfloxacin, single dose 800 mgScreen and treat patients for chlamydia.
Note that fluoroquinolones are contraindicated for patients who are younger than 18 years and patients who are pregnant or lactating.
Herpes simplex virus
Primary HSV (episodic treatment)Acyclovir, 200 mg five times daily for 10 days (or 400 mg three times daily for 7 to 10 days) OR valacyclovir hydrochloride, 1 g twice daily for 7 to 10 days OR famciclovir, 125 mg three times daily for 7 to 10 days...Physicians treat herpes simplex virus with a tiered approach, first attempting to control episodes or “flare-ups” with episodic treatment. Patients who have more than six episodes per year, however, require more aggressive treatment and are given daily suppressive treatment.
Recurrent HSV (episodic treatment for < 6 episodes per year)Acyclovir, 400 mg three times daily for 5 days and 800 mg three times daily for 3 days OR famciclovir, 125 mg twice daily for 5 days OR valacyclovir, 500 mg twice daily for 3 days...In either situation, patients' infection status should be reassessed after 1 year of continuous treatment.
Twenty percent of patients have a reduction in recurrence frequency after 1 year of treatment for this sexually transmitted infection.
Recurrent HSV (suppressive treatment for ≥ 6 episodes per year)Acyclovir, 400 mg twice daily OR valacyclovir, 1 g daily OR famciclovir, 250 mg twice daily...Patients with recurrent HSV proctitis may be treated with acyclovir, 400 mg five times daily for 10 days.
Nonspecific urethritis or cervicitis§Doxycycline, 100 mg twice daily for 7 days OR azithromycin, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen patients for chlamydia.
If patient is pregnant or lactating, use azithromycin.
Syphilis (Treponema pallidum)Penicillin G benzathine, single dose, 2.4 million units intramuscularlyFor patients who are hypersensitive to penicillin: Doxycycline, 100 mg twice daily for 14 days OR tetracycline, 500 mg four times daily for 14 days OR ceftriaxone, 1 g daily intramuscularly or intraveneously for 8 to 10 daysFor patients with latent syphilis (>1 year), syphilis of unknown duration, syphilis with cardiovascular involvement, or tertiary syphilis, use weekly treatment of 2.4 million units of penicillin G benzathine 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 (Trichomonas vaginalis)Metronidazole, single dose 2 g OR metronidazole, 500 mg twice daily for 7 days...Metronidazole is contraindicated in the first 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.
Table 3
Sexually Transmitted Infections: Primary and Alternative Pharmacologic Treatment Methods *
Treatment Methods
Infection (Pathogen) Primary Alternative Comment(s)
Chlamydia (Chlamydia trachomatis)Doxycycline, 100 mg twice daily for 7 days OR azithromycin dihydrate, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen and treat patients for gonorrhea.
If patient is pregnant or lactating, use azithromycin.
Gonorrhea (Neisseria gonorrhoeae)Ceftriaxone sodium, 125 mg intramuscularly OR cefixime, single dose 400 mg OR ciprofloxacin, single dose 500 mg OR ofloxacin, single dose 400 mg OR levofloxacin, single dose 250 mg OR gatifloxacin, single dose 400 mg OR azithromycin, single dose 1 g OR doxycycline, 100 mg twice daily for 7 daysSpectinomycin, 2 g intramuscularly OR cefotaxime sodium, single dose 500 mg intramuscularly OR ceftizoxime sodium, 500 mg intramuscularly OR cefoxitin sodium, 2 g intramuscularly with probenecid, 1 g OR lemofloxacin, single dose 400 mg OR norfloxacin, single dose 800 mgScreen and treat patients for chlamydia.
Note that fluoroquinolones are contraindicated for patients who are younger than 18 years and patients who are pregnant or lactating.
Herpes simplex virus
Primary HSV (episodic treatment)Acyclovir, 200 mg five times daily for 10 days (or 400 mg three times daily for 7 to 10 days) OR valacyclovir hydrochloride, 1 g twice daily for 7 to 10 days OR famciclovir, 125 mg three times daily for 7 to 10 days...Physicians treat herpes simplex virus with a tiered approach, first attempting to control episodes or “flare-ups” with episodic treatment. Patients who have more than six episodes per year, however, require more aggressive treatment and are given daily suppressive treatment.
Recurrent HSV (episodic treatment for < 6 episodes per year)Acyclovir, 400 mg three times daily for 5 days and 800 mg three times daily for 3 days OR famciclovir, 125 mg twice daily for 5 days OR valacyclovir, 500 mg twice daily for 3 days...In either situation, patients' infection status should be reassessed after 1 year of continuous treatment.
Twenty percent of patients have a reduction in recurrence frequency after 1 year of treatment for this sexually transmitted infection.
Recurrent HSV (suppressive treatment for ≥ 6 episodes per year)Acyclovir, 400 mg twice daily OR valacyclovir, 1 g daily OR famciclovir, 250 mg twice daily...Patients with recurrent HSV proctitis may be treated with acyclovir, 400 mg five times daily for 10 days.
Nonspecific urethritis or cervicitis§Doxycycline, 100 mg twice daily for 7 days OR azithromycin, single dose 1 gErythromycin (base), 500 mg four times daily for 7 days OR ofloxacin, 300 mg twice daily for 7 days OR levofloxacin, 500 mg daily for 7 daysScreen patients for chlamydia.
If patient is pregnant or lactating, use azithromycin.
Syphilis (Treponema pallidum)Penicillin G benzathine, single dose, 2.4 million units intramuscularlyFor patients who are hypersensitive to penicillin: Doxycycline, 100 mg twice daily for 14 days OR tetracycline, 500 mg four times daily for 14 days OR ceftriaxone, 1 g daily intramuscularly or intraveneously for 8 to 10 daysFor patients with latent syphilis (>1 year), syphilis of unknown duration, syphilis with cardiovascular involvement, or tertiary syphilis, use weekly treatment of 2.4 million units of penicillin G benzathine 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 (Trichomonas vaginalis)Metronidazole, single dose 2 g OR metronidazole, 500 mg twice daily for 7 days...Metronidazole is contraindicated in the first 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.
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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 youngerChlamydia (C trachomatis)
□ Men, at risk (all)Syphilis (T pallidum)
□ Newborns, ocular prophylaxisGonorrhea (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 youngerChlamydia (C trachomatis)
- At riskGonorrhea (N gonorrhoeae)
- Pregnant, at riskChlamydia (C trachomatis), gonorrhea (N gonorrhoeae)
Level of Evidence: C, Established common medical practice with little or no research-based evidence to support it.
□ Women, pregnantChlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus, syphilis (T pallidum)
□ Men, at riskGonorrhea (N gonorrhoeae)
□ Newborns, ocular prophylaxisChlamydia (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.
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 youngerChlamydia (C trachomatis)
□ Men, at risk (all)Syphilis (T pallidum)
□ Newborns, ocular prophylaxisGonorrhea (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 youngerChlamydia (C trachomatis)
- At riskGonorrhea (N gonorrhoeae)
- Pregnant, at riskChlamydia (C trachomatis), gonorrhea (N gonorrhoeae)
Level of Evidence: C, Established common medical practice with little or no research-based evidence to support it.
□ Women, pregnantChlamydia (C trachomatis), gonorrhea (N gonorrhoeae), herpes simplex virus, syphilis (T pallidum)
□ Men, at riskGonorrhea (N gonorrhoeae)
□ Newborns, ocular prophylaxisChlamydia (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.
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