ACP medicine, 3rd Edition

Infectious Disease

Vaginitis and Sexually Transmitted Diseases

Matthew R. Golden M.D., M.P.H.1

1Associate Professor of Medicine, Johns Hopkins University School of Medicine

The author has received research support from Roche Diagnostics and Gen-Probe.

April 2003

Sexually transmitted diseases (STDs) are among the most common causes of infectious illness in the world. The United States leads industrialized nations in the occurrence of STDs, with an estimated 12 million new cases annually, three million of them in teenagers.1 In many developing nations, STDs (excluding HIV infection) are the second greatest cause of disability-adjusted years of life lost,2 and highly prevalent bacterial and viral STDs may facilitate HIV transmission.3

STD is an emerging infectious disease problem. Of the more than 30 sexually transmitted pathogens that are currently recognized, eight have been identified since 1980, and it seems likely that the full spectrum of STD remains undefined.4 Antimicrobial resistance has made treatment of some well-established infections (e.g., gonorrhea) more difficult. Finally, decreasing age of menarche, declining median age of populations in developing countries, delayed marriage, increased global travel and trade, urbanization, migration, war and associated social upheaval, and the dissolution of socially restrictive political systems in the former Soviet Union and, to a lesser extent, China all ensure that STDs will remain a major and probably increasing health problem in coming decades.5

For the clinician, the increasing recognition of viral STDs and the emergence of screening for chlamydial infections as a population-based STD control strategy has heightened the importance of familiarity with the management of these common infections. This chapter presents general concepts in the epidemiology and approach to patients with STD and reviews important STD syndromes, including urethritis, vulvovaginitis, mucopurulent cervicitis, pelvic inflammatory disease, and genital ulcer disease. Finally, the approach to STD in men who have sex with men and to sexually transmitted enteric infections will be presented. Specific pathogens, including ChlamydiaNeisseria gonorrhoeae, herpes viruses, and Treponema pallidum, are discussed in other chapters. The Centers for Disease Control and Prevention (CDC) issues guidelines for STD/HIV testing and counseling, as well as STD treatment ( Clinicians are advised to refer to these guidelines for updated recommendations.6,7,8

Epidemiology and Transmission Dynamics

The transmission of an STD through a population can be conceptualized mathematically with the formula R0 = βcD, in which R0 is the average number of secondary cases generated by each primary infection in a population (i.e., the reproductive number); β is the average probability of transmission with each sexual partnership; c is the average number of sexual partnerships formed per unit of time; and D is the mean duration of infection.9 For diseases in which each case generates an average of one additional case, R0 equals 1 and the prevalence remains stable; values less than 1 and greater than 1 are associated with a declining or rising prevalence, respectively.

Although each of the terms in this equation is complex, the simplification that the equation offers can explain a great deal about the distribution of different STDs in a population and provides a framework for conceptualizing STD epidemiology. For example, gonorrhea is thought to be efficiently transmitted (β = 0.5), but it has a relatively short duration of infection, especially in settings in which medical care and therapy are readily available.9,10 Consequently, for the reproductive number to remain 1 or greater, c must be relatively high. Thus, infection tends to concentrate in a population of highly sexually active persons, sometimes referred to as a core group.11 In part because young people tend to be more sexually active than older people, the incidence of gonorrhea, like that of chlamydial infection, is highest among teenagers and persons in their early 20s. (This is less true of men who have sex with men, in whom gonorrhea incidence is less concentrated in the young.) In contrast, herpes simplex virus type 2 (HSV-2) has a very long duration of infection, and R0 may exceed 1 even in populations with very low rates of partnership change. As a result, the prevalence of genital herpes rises with age, peak incidence likely occurs at a somewhat older age than with Chlamydia infection or gonorrhea, and the infection is widely disseminated throughout the population.12

This simple model of STD transmission dynamics focuses on average behavior in a population and the host-parasite relationship as determinants of STD epidemiology. However, it neglects the critical role played by variance in sexual behavior and patterns of sexual mixing (i.e., sexual networks) in defining transmission dynamics. The prevalence of STD in a population is in part a function of the extent to which persons who are more sexually active mix primarily with one another (assortative mixing) versus mixing more randomly with others, including persons who are less sexually active.13 The frequency of concurrent partnerships in a population also exerts a profound influence on STD prevalence; such partnerships allow infections to spread in two directions, connecting groups of people and facilitating rapid transmission of infection.14,15

In eliciting a sexual history, clinicians have traditionally focused on the patient's behavior, asking about the number of sexual partners the patient has had and about the use of condoms. In many cases, however, self-reported behavior is not associated with risk of STD; sexual network factors may be more important in defining risk. For example, virtually all studies of selective screening for chlamydial infection have found that self-reported behavior is an insensitive predictor of infection,16,17,18 whereas demographic factors such as age, race, socioeconomic status, source of clinical care, and geography are strongly associated with a variety of STDs.19,20,21 These factors, which reflect the organization of human society and dictate sexual mixing patterns, play a critical role in defining an individual's risk of infection.22 STDs exist within a social context; therefore, clinicians should base their assessment of risk on their practice setting and the patient's social milieu. Persons whose behavior would suggest a low risk of STD can in fact be at elevated risk simply by virtue of their sexual network, a population that is often socially determined rather than individually chosen. This knowledge should temper any tendency to entertain stigmatizing stereotypes related to sexual behavior and STD.

STD Prevention


What is the best way to elicit a sexual history? Although relatively little research has been done on this question, some general principles can be articulated. In eliciting a sexual history, the clinician must balance the need to collect specific information with the desire to engage the patient in a conversation about sexual risk. Whenever possible, questions should be open ended, allowing the patient to define factors that may have placed him or her at risk for STD (e.g., “What are you doing now, or what have you done in the past, that you think may have put you at risk for a sexually transmitted disease?”). Subsequent questions may be more specific, but the questions should be clear, direct, and phrased nonjudgmentally (e.g., “Do you have sex with men, women, or both men and women?”). Typically, a sexual history should include questions about sexual orientation, the number of sexual partners, the use of condoms, any history of STD, and the sexual repertoire (oral, insertive or receptive anal, and vaginal sex). Persons with HIV or those at high risk for HIV should be asked if they know the HIV status of their sexual partners. Persons with HIV should be asked whether they have informed their partners of their own HIV status.

Clinicians should seek to integrate elicitation of the sexual history with STD prevention counseling. The CDC recommends a client-centered approach to counseling. This approach involves an effort to help patients assess the circumstances and behaviors that place them at risk for STD and then help them commit to a single, defined plan for reducing their risk. Risk-reduction plans should be specific rather than general. For example, a specific goal might be to carry condoms when going out on a date or to ask a specific partner about his or her HIV status, rather than the general goals of using condoms all the time or having safe sex all the time.23 Client-centered counseling has been shown (in a randomized trial of heterosexual STD clinic patients) to reduce the risk of STDs.6,24


By law, gonorrhea, syphilis, chancroid, lymphogranuloma venereum (LGV), donovanosis (granuloma inguinale), and, in most parts of the United States, chlamydial infections must be reported to local health departments. In general, health departments in the United States routinely attempt to ensure the treatment of sexual partners of persons with syphilis; they only sometimes attempt to contact persons reported to have HIV to offer them assistance in notifying their sexual and needle-sharing partners; and they seldom make any routine effort to notify the partners of persons with gonorrhea or chlamydial infection. Some health departments will provide such services if specifically asked to do so by a clinician or a person diagnosed with an STD. Although clinicians should make their patients aware that they may be contacted by public health authorities regarding partner notification, in most instances, it is the responsibility of the diagnosing clinician and the patient to ensure that sexual partners are evaluated and treated. Several recent studies have suggested that giving patients medication to give to their sexual partners is feasible and may reduce chlamydial reinfection rates.25,26,27 However, at present, there are no guidelines that define the circumstances in which this approach to partner management should be employed.


Because STDs are often asymptomatic, screening is a critical component of prevention. Recommendations for screening vary according to population [see Table 1].8 Data in support of STD screening are strongest for chlamydial infection; a randomized trial has demonstrated that chlamydial screening reduces the rate of PID.28

Table 1 Recommended STD Screening8


Screening Measures

All men and women

Retest all patients diagnosed with gonorrhea or Chlamydiainfection 10–18 wk after initial treatment


Annual chlamydial screening

  Sexually active, age ≤ 24 yr

  Age > 24 yr with a new sexual partner or multiple sexual partners

Pregnant women

Test for Chlamydia trachomatisNeisseria gonorrhea, hepatitis B virus infection, and syphilis; offer HIV testing and counseling

Test for bacterial vaginosis in women at high risk (e.g., those with history of preterm delivery)

Perform Pap smear if none was performed in the past year

Men who have sex with men (MSM)*

Perform the following at least annually:
   Serologic testing for HIV and syphilis

   Rectal culture for gonorrhea and chlamydial infection

   Pharyngeal culture for gonorrhea

Consider serologic testing for HSV-2, particularly in HIV-negative MSM

Serologic testing for hepatitis A and B antibodies

*Screening guidelines apply to both HIV-positive and HIV-negative MSM. HIV and hepatitis testing should be performed only for susceptible patients. Current data are insufficient for a recommendation of technologies other than culture to test for rectal gonorrhea or chlamydial infection or pharyngeal gonorrhea. Because herpes simplex virus type 2 (HSV-2) increases the risk of HIV acquisition, HSV-2 screening should be considered to aid in HIV risk assessment and counseling. More frequent screening should be considered for those at highest risk of STD.
Vaccinate for hepatitis A and B if negative.

Urethritis in Men


Urethritis is one of the most common STD syndromes in men, resulting in an estimated 200,000 initial physician visits in the United States in 2000.28 The syndrome is typically divided into urethritis resulting from infection with N. gonorrhoeae and nongonococcal urethritis (NGU). Rates of gonococcal urethritis in most developed nations have declined dramatically over the past 20 years, although rates in the United States and Europe now appear to be rising again, particularly among men who have sex with men.29,30


Since the mid-1970s, Chlamydia trachomatis has been recognized as the most common cause of NGU; C. trachomatis has typically been isolated in 30% to 40% of cases of NGU, although the prevalence of C. trachomatis in men with NGU may now be declining,31 and chlamydial infection is less common in older men with NGU than in younger ones. In areas of the United States where the prevalence of C. trachomatis has declined in recent years, most patients with symptomatic urethritis have no evidence of either gonorrhea or chlamydial infection.32 Other established causes of NGU include Trichomonas vaginalis, HSV-2, and, in men who engage in insertive anal intercourse, enteric pathogens. Approximately one third of men with primary genital herpes have dysuria and a urethral discharge. T. vaginalis is a more common cause of NGU in older men. However, HSV and Trichomonas combined are probably responsible for fewer than 10% of all cases of NGU. Ureaplasma urealyticum and Mycoplasma genitalium have been associated with NGU in case-control studies, but at present no tests for these organisms are commercially available.33,34,35


Clinical Manifestations

Clinical manifestations of urethritis include urethral discharge, dysuria, and itching at the distal urethra. Inguinal adenopathy is unusual. Likewise, fever, chills, perineal pain, scrotal mass, genital pain, and other urinary symptoms (e.g., hematuria, frequency, hesitancy, nocturia, or urgency) are unusual and should prompt consideration of alternative diagnoses, such as urinary tract infection (UTI), epididymitis, orchitis, or prostatitis. Although gonorrhea is generally associated with a more abrupt onset of symptoms and a more copious and purulent discharge than NGU, these distinctions are not reliable.

Asymptomatic and subclinical gonoccocal and chlamydial urethral infections probably play an important role in sustaining endemic levels of these STDs, but their incidence is uncertain. A prospective study of gonococcal urethritis found that only 2% of infections remained asymptomatic in the 14 days after acquisition.36 However, cross-sectional studies have demonstrated that asymptomatic infection is common among the sexual partners of infected women37 and, at least in some parts of the United States that have a high prevalence of gonorrhea, in the general population of young adults.38 Prospective data on the frequency of asymptomatic chlamydial urethritis are not available, but as with gonorrhea, cross-sectional studies have demonstrated that asymptomatic or subclinical chlamydial urethritis is common.38,39

Physical Examination

Objective evidence of urethral inflammation should be sought in men presenting with dysuria or urethral discharge. Physical examination should include a genital examination, preferably conducted several hours after the patient last urinated; the examination should include a search for purulent or mucopurulent discharge. If no discharge is observed, the examiner should strip the urethra from the base of the penis to the urethral meatus to elicit a discharge.

Laboratory Tests

A urethral Gram stain should be performed on all men with symptoms of urethritis, even those with no discharge evident on physical examination. Urethral specimens for Gram stain are obtained by inserting a thin calcium-alginate-tipped swab 3 to 4 cm into the urethra, then rolling the swab over a glass slide. A diagnosis of urethritis is established by the presence of five or more polymorphonuclear neutrophils (PMNs) per 1,000∞ oil-immersion field. Alternatively, the diagnosis can be made through use of a centrifuged 10 to 15 ml first-void urine specimen; the diagnosis is established by the finding of 10 or more PMNs per 400∞ field on at least one of five randomly selected fields. A positive urine leukocyte esterase test is also sufficient for establishing the diagnosis. Among experienced microscopists, the finding of gram-negative intracellular diplococci (GND) is 90% to 95% sensitive and over 95% specific in detecting urethral gonorrhea in symptomatic men,40,41 and the presence of GND establishes the diagnosis of gonorrhea [see Figure 1]. The Gram stain should be considered equivocal if only extracellular organisms are seen. Regardless of Gram stain findings, specific microbiologic testing should be performed forN. gonorrhoeae and C. trachomatis.


Figure 1. Gram Stain in Gonorrhea

This figure shows a Gram stain of a urethral discharge from a man with gonorrhea. The gram-negative intracellular diplococci areNeisseria gonorrhoeae organisms.

Because it provides data on antimicrobial susceptibility, culture remains the preferred microbiologic test for gonorrhea. Nonamplified DNA probes offer the advantage of simplified specimen handling and the ability to perform both gonococcal and chlamydial testing on a single specimen. These tests have a specificity of approximately 99%, and their sensitivity is comparable to that of culture for gonorrhea.42

Nucleic acid amplification tests (NAATs) of urethral specimens or urine (e.g., ligase chain reaction [LCR], polymerase chain reaction [PCR], transcription-mediated amplification [TMA], and strand displacement amplification [SDA]) have sensitivities comparable or superior to that of culture; although typically more costly, these assays offer the advantage of testing without urethral swabs. In low-prevalence populations, positive NAAT results may require confirmatory testing. The sensitivities of tests for C. trachomatis vary widely. Although test performance varies, depending on organism burden and anatomic site of collection, culture has a sensitivity of between 50% and 90%; enzyme immunoassays and nonamplified genetic probes have a sensitivity of 40% to 75%; and NAATs have a sensitivity of more than 90%.43,44 For that reason, NAATs are preferred, when available.


Initial Management

Patients with evidence of gonococcal infection on urethral Gram stain should be treated for gonorrhea. Recommended regimens include single doses of the following agents: (1) cefixime, 400 mg orally; (2) ceftriaxone, 125 mg intramuscularly; (3) ciprofloxacin, 500 mg orally; (4) ofloxacin, 400 mg orally; and (5) levofloxacin, 250 mg orally. Quinolone-resistant N. gonorrhoeae has recently emerged as a problem in Asia, the Pacific Islands, and, most recently, California. Consequently, quinolones are no longer recommended for the empirical treatment of gonorrhea in persons in these areas or in their contacts. Because of the high chlamydial coinfection rate, all patients with gonorrhea should also be treated for Chlamydia, unless that diagnosis has been microbiologically excluded. Treatment for presumptive chlamydial infection in men with NGU is with azithromycin in a single 1 g oral dose or doxycycline, 100 mg orally twice a day for 7 days.

Treatment of Recurrent or Persistent Urethritis

Although recognition of the pathogenic role of C. trachomatis has reduced a major cause of persistent or recurrent urethral symptoms after treatment for gonococcal urethritis, such symptoms continue to affect a minority of patients. Management should include questions regarding adherence to medical therapy and partner treatment, a urethral Gram stain to document evidence of urethral inflammation, and repeat testing for gonorrhea and chlamydial infection. Consideration should be given to possible trichomonal or herpes infection. Erythromycin, 500 mg four times a day for 7 days, with or without a single 2 g dose of metronidazole, is the recommended empirical treatment in patients who are believed to have adhered to their initial regimen and who have not been reexposed to gonorrhea or chlamydial infection.8

Lower Genital Tract Infections in Women

Women with STDs involving the lower genital tract may present with dysuria, urethritis or vulvovaginitis, and abnormal or altered vaginal discharge. The initial evaluation of women with these complaints seeks to differentiate urethritis, cystitis, vulvovaginitis, and cervicitis and to identify women with upper genitourinary tract infections (e.g., pyelonephritis or salpingitis). Subsequent microbiologic testing and treatment are guided by this evaluation.


STDs that can cause dysuria in women include vulvitis resulting from candidal infection and genital herpes and urethritis caused by C. trachomatis or N. gonorrhoeae. Dysuria and sterile pyuria (the presence of leukocytes and the absence of more than 102 organisms/ml of conventional urinary pathogens in a midstream urine specimen) in a woman are consistent with a diagnosis of urethral infection.45 Other factors suggesting urethral infection include the absence of other symptoms and signs typical of UTI; risk factors or risk markers for chlamydial infection (young age, new or multiple sexual partners, failure to consistently use condoms, African-American race); symptoms lasting 7 days or longer; purulent vaginal discharge; pelvic pain or tenderness; and evidence of mucopurulent cervicitis.

Women presenting with a syndrome of dysuria and sterile pyuria should be tested for gonorrhea and chlamydial infection. Because HSV-2 can cause urethritis in women, particularly in women with primary HSV infection, the possibility of genital herpes should also be considered. HSV or candidal vulvitis typically causes external, as opposed to internal, dysuria, which occurs when urine comes in contact with the introitus or labia. Women with these infections typically have vulvar irritation or lesions; vaginal discharge; or a history of either HSV or candidal vaginitis.

In the differential diagnosis of dysuria in women, particular attention should be given to bacterial UTI, which is the most common cause of dysuria. Symptoms, signs, and laboratory findings that support the diagnosis of bacterial cystitis include urinary frequency or urgency, a history of UTI, duration of symptoms of less than 4 days, gross or microscopic hematuria, the patient's belief that she has a UTI, suprapubic tenderness, a positive urine nitrite test, and evidence of typical urinary tract pathogens on Gram stain or urine culture.46,47,48 Fever or flank pain in a woman with dysuria and other findings consistent with UTI suggests pyelonephritis. Vaginal discharge or irritation is not typical of UTI.

Diagnostic testing for gonococcal and chlamydial urethritis in women should be based on specific tests [see Laboratory Tests, above]. In women with no evidence of pelvic inflammatory disease (PID), treatment is identical to that for men [see Treatment, above].


Abnormal vaginal discharge is one of the most common reasons for women to seek medical attention. Since the 1960s, the number of women receiving care for vulvovaginal infections increased approximately threefold. In 2000, an estimated three million initial physician office visits in the United States were prompted by vulvovaginal infections.28

The most common causes of an abnormal vaginal discharge are bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomonal vaginitis (TV) [see Table 2]. Both BV and trichomoniasis have been associated with preterm labor.49,50 However, to date, treatment of these infections has not definitively been shown to decrease preterm delivery.51,52,53,54 BV has been identified as a risk factor for PID, and both BV and trichomoniasis may increase the risk of HIV acquisition and transmission.55,56,57,58,59 Consequently, these diagnoses have assumed new importance in HIV prevention.

Table 2 Clinical Features and Management of Vulvovaginitis


Normal Vaginal Examination

Vulvovaginal Candidiasis

Trichomonal Vaginitis

Bacterial Vaginosis


Uninfected; lactobacilli predominate

Candida albicansmost common; candidiasis caused by species other than C. albicansmay be increasing

Trichomonas vaginalis

Loss of normal vaginal lactobacilli; associated with Gardnerella vaginalis; increased anaerobic bacteria and mycoplasmas



Abnormal vaginal discharge, external dysuria, vulvar itching, pain and/or irritation

Yellow vaginal discharge, external dysuria, vulvar itching

Increased, abnormal, or malodorous vaginal discharge








Clear or white



White or gray


Nonhomogeneous, patchy (floccular)

Clumped; adherent plaques

Homogeneous or frothy

Adherent, homogeneous discharge that uniformly coats vagina

Inflammatory findings


Vulvar erythema, edema, or fissure; erythema of vaginal epithelium; introitus

Erythema of vaginal and vulvar epithelium; colpitis macularis


pH of vaginal fluid*

Usually ≤ 4.5

Usually ≤ 4.5

Usually > 4.5

Usually > 4.5

Amine (fishy) odor with 10% KOH



May be present

May be present


Normal epithelial cells; lactobacilli predominate

Leukocytes, epithelial cells; mycelia or pseudomycelia(50%–85% of cases)

Leukocytes, trichomonads seen in 50%–70% of culture-positive cases

Clue cells (81%–94% of cases); few leukocytes; lactobacilli outnumbered by mixed flora

Recommended treatment

Intravaginal imidazole (butoconazole, clotrimazole, miconazole, terconazole, tioconazole) for 3–7 days; fluconazole, 150 mg p.o. (single dose)

Metronidazole, 2 g p.o. (single dose); metronidazole, 500 mg p.o., b.i.d., for 7 days

Metronidazole, 500 mg p.o., b.i.d., for 7 days; metronidazole gel, 0.75%, 5 g intravaginally each night for 5 nights; clindamycin cream 2%, 5 g intravaginally each night for 7 days

Sexual partner treatment

None if asymptomatic; topical treatment if candidal dermatitis of the penis or balanitis is detected

Metronidazole, 2 g orally (single dose)


*pH determination is not useful if blood is present.
To detect fungal elements, vaginal fluid is digested with 10% KOH before microscopic examination; to examine for other features, fluid is mixed (1:1) with normal saline. Culture may be necessary if microscopy results are negative and the suspicion of Candida is high.

Evaluation of women with vaginal complaints should include a pelvic examination and a directed laboratory evaluation. Although these infections tend to have different clinical features, a study of patients triaged and selectively treated after a telephone assessment found poor agreement between the diagnosis made by nurses and other providers and the diagnoses obtained after examination and testing.60Similarly, a study of women purchasing over-the-counter antifungal therapies found that only one third had vaginal candidiasis, and 53% had a diagnosis other than vulvovaginal candidiasis.61 These findings emphasize the need for a complete evaluation in women complaining of vaginal discharge or discomfort. Less frequent causes of vaginitis include atrophic vaginitis with secondary bacterial infection, vaginitis associated with foreign bodies or toxins, Staphylococcus aureus vaginitis associated with toxic-shock syndrome, group A Streptococcus-associated vaginitis, desquamative vaginitis (clindamycin responsive), erosive lichen planus, allergic vaginitis, vaginitis associated with autoimmune disease, and idiopathic vaginitis.62

Bacterial Vaginosis

BV is the most common cause of vaginal discharge in women of reproductive age. Prevalence studies have found BV in 10% to 40% of women tested, with higher rates of infection in women tested in STD clinics and in African Americans. Douching and use of intrauterine devices (IUDs) have also been associated with BV.63

Pathophysiology and transmission

The etiology of BV is unknown. The syndrome constitutes a disturbance in normal vaginal bacterial flora characterized by a reduction in the concentration of hydrogen peroxide-producing lactobacilli64 and increased growth of mixed bacterial flora that include Gardnerella vaginalis, anaerobes, and Mycoplasma hominis. There is evidence that BV can be transmitted sexually. This evidence includes the following: studies have demonstrated that the inoculation of women with vaginal fluid from another woman with BV can induce the syndrome65,66; there is a high prevalence of BV in patients being treated at STD clinics; there are high rates of concordant BV among lesbian sexual partners67; longitudinal studies have associated BV with having higher numbers of sexual partners and with having new sexual partners68,69,70; and most studies have found that BV is absent in virgins.71 Evidence against sexual transmission includes the lack of benefit from treating sexual partners72,73,74 and inconsistent associations with levels of sexual activity.


Physical examination of women with BV typically reveals a homogeneous, white, uniformly adherent vaginal discharge.63 The Amsel criteria for diagnosis of BV include the following: (1) presence of a homogeneous, thin vaginal discharge; (2) vaginal pH greater than 4.5; (3) clue cells (bacteria attached to vaginal epithelial cells on wet mount); and (4) presence of an amine (fishy) odor when vaginal fluid is mixed with 10% potassium hydroxide (KOH).71,75,76,77 The presence of three of the four criteria establishes the diagnosis [see Table 3].

Table 3 Amsel Criteria for the Diagnosis of Bacterial Vaginosis71,75,77


Sensitivity (%)

Specificity (%)

Homogeneous, thin vaginal discharge



Vaginal pH > 4.5



Clue cells on vaginal wet mount



Amine odor when vaginal fluid is mixed with 10% potassium hydroxide (KOH)



Note: the presence of three of these four criteria establishes the diagnosis of bacterial vaginosis.


BV is treated with metronidazole. A meta-analysis found higher cure rates with a dosage of 1 g a day for 7 days than with a single 2 g dose (82% versus 73%).63 Intravaginal metronidazole and intravaginal clindamycin offer efficacy comparable to 7-day courses of metronidazole, with fewer side effects, but are not effective in the treatment of trichomoniasis and are typically more costly. Recurrence of BV is common, occurring in 50% to 70% of cases. Multiple randomized trials have failed to demonstrate any benefit from treating male partners.72,73,74


  1. vaginalisis a sexually transmitted protozoan. In the United States, the number of women seeking care for trichomonal vaginitis declined by over 50% from 1966 to the mid-1980s; in 2000, physicians in the United States saw an estimated 200,000 patients with TV.28A cross-sectional study of 13,816 pregnant women in the United States found TV in 13%; the vast majority of those infections were subclinical or asymptomatic. Risk factors for TV included African-American ethnicity, cigarette smoking, unmarried status, and lower educational level.77Untreated infections in women are thought to persist for a median of 3 to 5 years.78


Clinical manifestations of trichomonal infection include yellow vaginal discharge and vulvar itching. Neither is highly sensitive or specific. On physical examination, signs associated with Trichomonas infection include frothy or purulent vaginal discharge, which is sometimes profuse; vulvar or vaginal erythema; and cervical mucopus.79,80 All of these signs have far greater specificity than sensitivity. The finding of colpitis macularis—punctate cervical hemorrhages and ulcers, sometimes referred to as strawberry cervix—has a specificity of 99% for TV but is seen in fewer than 5% of patients on unaided physical examination; colpitis macularis is much more readily visible on colposcopy.79 In expert hands, a finding of motile Trichomonas on wet-mount examination has a sensitivity of 50% to 70%, although in clinical practice, wet-mount examination is usually considerably less sensitive. Culture on Diamond medium is the traditional diagnostic gold standard, but this technique is not available in most practice settings. Recently, InPouch, a relatively simple and inexpensive culture method, became available. The sensitivity of InPouch is comparable to that of Diamond medium and superior to that of wet mount.81 PCR has been successfully used in research settings, but no NAAT is commercially available at present. Antigen detection tests are also under investigation.


A single 2 g dose of metronidazole is the treatment of choice for TV. Reported cure rates are 82% to 88%.80 Sexual partners should be treated concurrently, and couples should be advised to abstain from sex for 1 week after treatment. Topical metronidazole is not effective.82Resistance to metronidazole occurs infrequently, and most cases respond to prolonged courses of metronidazole therapy. Some authors have reported successful treatment of metronidazole-resistant cases using either tinidazole or paromomycin cream.83

Vulvovaginal Candidiasis

Because VVC is not a reportable infection, only limited epidemiologic data are available. In the United States, a study of female university students found that over half experienced at least one episode of VVC by 25 years of age,84 and 6.5% of women who participated in a national random-digit-dialing survey reported that a health care provider had told them they had candidal vaginitis at least once in the preceding 2 months.85 Higher rates of VVC have been observed in African Americans and in users of oral contraceptives, vaginal sponges, or IUDs.86 Although VVC is not clearly identified as an STD, it has been associated with the onset of sexual activity in young women and with cunnilingus.84,86 Other predisposing factors include recent use of antibiotics; diabetes mellitus; pregnancy; and immunodeficiency, including that from HIV infection.


Vulvovaginal pruritus is generally the most common symptom of VVC.87 Other findings sometimes associated with VVC include a cottage-cheese-like discharge; external dysuria; external genital burning or pain; perineal edema or erythema; and vulvar erythema, edema, and fissures.87,88 However, several studies have reported the absence of any signs or symptoms significantly associated with VVC.4,89 As a result, the diagnosis requires microscopic and, at times, microbiologic assessment. A 10% KOH preparation of fluid taken from the vagina has a sensitivity of 50% to 85% in the diagnosis of VVC90,91; if this test is negative but the clinical picture is consistent with VVC and there is no alternative diagnosis, culture for yeast should be performed.


Topical azoles (e.g., butoconazole, clotrimazole, miconazole, econazole, tioconazole, and terconazole) are 80% to 90% effective in treating VCC [see Table 2]. Most of these agents are available over the counter. No clear advantage favors one azole over another. Oral azoles (fluconazole or itraconazole) are comparably or slightly more effective and may be more convenient, but these agents also pose a small risk of systemic reactions. Because there are no compelling data favoring any one agent or route of administration, patient preference should guide the choice of treatment. Immunosuppressed patients and those with candidal infections caused by a species other than Candida albicans may require more prolonged therapy (e.g., 14 days).

Long-term therapy is indicated for patients with recurrent VVC, which is defined as four or more episodes of VCC in a year. Approximately 5% of women with VVC experience recurrences. Treatment may require 14 days of induction therapy followed by once-weekly maintenance therapy. Patients with C. glabrata VVC who do not respond to prolonged courses of azole therapy may benefit from topical boric acid (600 mg once a day for 2 weeks) or topical flucytosine.92

Mucopurulent Cervicitis

Mucopurulent cervicitis (MPC) is an inflammatory process affecting the columnar epithelium and subepithelium of the endocervix and adjacent exocervix. As with NGU in men, MPC is common and has most frequently been associated with N. gonorrhoeae or C. trachomatisand, less frequently, with HSV or T. vaginalis. Unlike NGU, MPC typically produces no symptoms; or it may produce nonspecific symptoms, such as a yellow vaginal discharge, that often do not prompt women to seek treatment. In recent years, as the prevalence of gonorrhea and chlamydial infections have decreased in some settings, MPC with no defined microbiologic etiology has come to constitute the majority of cases.4 MPC is important because of its association with known infections and because patients with MPC have an elevated risk of PID and adverse pregnancy outcome.


Different diagnostic criteria have been used for MPC. According to current CDC guidelines, the diagnosis of MPC is made on the basis of a finding of a visible purulent or mucopurulent exudate on cervical examination or on endocervical swab. The finding of cervical mucopus is 28% to 52% sensitive and 82% to 94% specific for the presence of either C. trachomatis or N. gonorrhoeae.88,93,94 Some investigators use additional criteria for MPC, including a finding of from 20 to 30 PMNs per high-power field (hpf) on cervical Gram stain or easily induced cervical bleeding.4,94 These factors have been associated with the likelihood of C. trachomatis or N. gonorrhoeae infection, but they have not consistently been included as diagnostic criteria of MPC; with regard to the use of cervical Gram stain, these findings have not consistently been useful in defining a population in need of empirical therapy.


The decision to treat MPC is based largely on the local prevalence of C. trachomatis or N. gonorrhoeae and on the patient's risk. In areas where both gonorrhea and chlamydial infection are common, empirical therapy should be directed at both pathogens. In areas where gonorrhea rates are low, treating for Chlamydia infection alone is reasonable. Recent evidence suggests that in areas where the prevalence of both infections is low, older patients (i.e., those older than 30 years) suspected of having MPC need not be treated until microbiologic test results are available, provided follow-up care is ensured.94

Pelvic Inflammatory Disease

PID is an inflammatory process involving a variable combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. PID can be blood-borne (e.g., tuberculosis) or result from extension of an intra-abdominal process. At present, however, PID most often develops when bacteria ascend from the vagina or cervix into the endometrium, fallopian tubes, and pelvic peritoneum. Although the number of women seeking care for PID has declined by over 25% since the 1980s, 8% of participants in the 1995 National Survey of Family Growth, a national representative sample of United States women, reported a history of PID.95 Identified risk factors for PID include a previous history of PID, higher numbers of lifetime sex partners, douching, and a history of bacterial STD. In the past, IUD use was identified as a risk factor, but its importance beyond the first 30 days after insertion is now controversial; a recent case-control study found no association between the use of currently available copper IUDs and the occurrence of PID.96 Gynecologic procedures that disrupt the protective cervical barrier (e.g., pregnancy termination, IUD insertion, dilatation and curettage, and hysterosalpingography) elevate the risk of PID and may lead to PID in the absence of classic sexually transmitted pathogens.


Studies of PID conducted in the United States and Europe in the 1980s typically implicated C. trachomatis, N. gonorrhoeae, or both as a cause of PID in approximately half of cases.97 Frequently, these bacteria were part of a polymicrobial infection involving diverse normal vaginal flora, including anaerobic bacteria, facultative anaerobes, and genital mycoplasmas. M. genitalium has been associated with endometritis and PID.98 Actinomyces israelii is a cause of PID in women with IUDs.


The diagnosis of PID is difficult. To date, studies have been unable to identify any single clinical finding or constellation of findings that allow accurate identification of women with PID.99,100 Moreover, PID studies have typically enrolled only women with overt disease and, consequently, have not provided an accurate picture of the full spectrum of the clinical entity. Indeed, most cases of PID probably go undiagnosed. Approximately two thirds of women with postinfectious fallopian tube occlusion report no history of PID, although many have sought care for abdominal pain.101 When the diagnosis is made clinically, it may not be supported by surgical findings. Only 60% to 70% of women with clinically diagnosed PID typically have laparoscopic evidence of PID.102

In clinically detected cases, the cardinal symptom of PID is pelvic or abdominal pain. The pain is typically dull or aching. Onset can be acute or subacute and frequently occurs at the beginning of menses. Typically, patients present after having symptoms for less than 2 weeks. In a Swedish study of 623 patients with PID, all had pelvic or abdominal pain, cervical motion tenderness, and increased inflammatory cells in vaginal or cervical secretions. Other symptoms and laboratory findings included an erythrocyte sedimentation rate (ESR) of 15 mm/hr or higher (75%), leukocytosis greater than 10,000/ml (60%), abnormal vaginal discharge (55%), fever higher than 38° C (100.4° F) (41%), abnormal vaginal bleeding (36%), dysuria (19%), vomiting (10%), and anorectal symptoms (anorectal pain, tenesmus, or rectal bleeding or discharge) (7%).103 A large study showed that only temperatures higher than 38° C (100.4° F) had a specificity of more than 90% for the diagnosis of PID, although its sensitivity was only 11%.103

The differential diagnosis of PID includes other causes of abdominal or pelvic pain. Depending on the clinical circumstances, the physician may need to consider such disorders as appendicitis, endometriosis, bleeding corpus luteum, pelvic adhesions, gastroenteritis, and ectopic pregnancy.

Although laparoscopy has been the traditional gold standard for diagnosing PID, many women with abnormal fimbrial biopsies have normal results on laparoscopy. Moreover, some women have histologic evidence of endometritis without salpingitis,104 which suggests that laparoscopy may be insensitive for the detection of milder cases or of PID that is restricted to the uterus.

Transvaginal ultrasound (TVUS) should be performed when symptoms are severe, when the physical examination reveals a pelvic mass, or when the diagnosis of PID is uncertain. Studies assessing the performance of different imaging modalities in the diagnosis of PID have been small, with no single study enrolling more than 50 patients with the diagnosis.102 Small studies of TVUS have reported sensitivities of 81% to 93%, but specificities have been highly variable, ranging from 5% to 100%, with the test performing best in patients with more severe infection.102 A case-control study of power Doppler TVUS reported a sensitivity of 100% and a specificity of 80%,105 suggesting it may offer advantages over conventional TVUS. In women with tubo-ovarian abscess, repeat TVUS is often indicated to assess response to therapy. Small studies of CT and pelvic MRI have also reported high sensitivity and specificity. Laparoscopy should be performed if appendicitis, ectopic pregnancy, or ruptured abscess is suspected; laparoscopy should also be considered in women who do not respond to antibiotics.


Because the diagnosis of PID can be challenging, the sequelae of PID can be severe, and treatment is safe and inexpensive, all patients suspected of having PID should undergo treatment for PID. The CDC recommends initiating treatment of PID in all sexually active young women with adenexal tenderness or cervical motion tenderness.8 These criteria are likely to be sensitive, but they are also quite nonspecific.100

Treatment for PID is directed against C. trachomatis, N. gonorrhoeae, gram-negative facultative anaerobes, vaginal anaerobes, and streptococci. Numerous regimens have been found acceptable [see Table 4]. A recent randomized trial in women with mild to moderate PID found no advantage of inpatient therapy with intravenous cefoxitin and doxycycline over outpatient therapy with a single intramuscular dose of cefoxitin and probenecid followed by oral doxycycline.106 Indications for hospitalization include the following: (1) inability to exclude a possible surgical emergency (e.g., appendicitis), (2) pregnancy, (3) failure to respond to oral antibiotics, (4) inability to tolerate or adhere to outpatient oral therapy, (5) tubo-ovarian abscess, and (6) inability to reliably ensure follow-up. Patients should show significant improvement within 3 days after starting therapy. Those receiving oral therapy should be reevaluated within 72 hours. Treatment should include efforts to ensure that sexual partners also receive therapy. In addition, patients with Chlamydia or Ngonorrhoeae infections should be rescreened for those infections 10 to 18 weeks after treatment.

Table 4 Treatment Regimens for Pelvic Inflammatory Disease




Cefotetan, 2 g I.V. q. 12 hr


Cefoxitin, 2 g I.V. q. 6 hr


Doxycycline, 100 mg p.o. or I.V. q. 12 hr

Clindamycin, 900 mg I.V. q. 8 hr


Gentamicin, 2 mg/kg I.V. or I.M. once, then 1.5; mg/kg I.V. q. 8 hr (single daily dose may be used)

Ofloxacin, 400 mg I.V. q. 12 hr


Levofloxacin, 500 mg I.V. q.d.


Doxycycline, 100 mg p.o. or I.V. q. 12 hr

with or without

Metronidazole, 500 mg I.V. q. 8 hr


Ampicillin-sulbactam, 3 g I.V. q. 6 hr


Ofloxacin, 400 mg p.o., b.i.d.


Levofloxacin, 500 mg I.V. q.d. for 14 days

with or without

Metronidazole, 500 mg p.o., b.i.d., for 14 days

Ceftriaxone, 250 mg I.M. once


Cefoxitin, 2 g I.M. once with probenecid, 1 g p.o.


Doxycycline, 100 mg b.i.d. for 14 days

with or without

Metronidazole, 500 mg p.o., b.i.d., for 14 days

*Parenteral therapy can be discontinued after the patient improves clinically, but doxycycline should be continued for 14 days.


Although the vast majority of women with PID in developed nations recover fully, long-term sequelae are common; these sequelae include tubal infertility, ectopic pregnancy, and chronic pelvic pain. In the largest study of PID sequelae performed to date, Swedish investigators performed laparoscopy on 1,730 women with suspected PID and then followed them for a mean of 6.9 years. After a single episode of PID, 8% of patients suffered tubal infertility, compared with 1% of control subjects in whom there was no laparoscopic evidence of PID. Of PID patients who subsequently became pregnant, 10% had an ectopic pregnancy, compared with 1% of women without PID. Similarly, pelvic pain lasting longer than 6 months occurred in 17% of women with PID but in only 2% of control subjects.107 Recurrent episodes of PID multiplied the risk of sequelae [see Figure 2], as did more severe PID and longer duration of symptoms before treatment.


Figure 2. Ectopic Pregnancy and Tubal Infertility in PID

Proportion of women experiencing an ectopic pregnancy or tubal infertility by number of episodes of pelvic inflammatory disease (PID) among 1,282 patients with PID and 448 control subjects.97,107

Genital Ulcer Disease

Genital ulcers are a frequent presentation of STDs. Epidemiologic studies, as well as studies measuring HIV shedding, suggest that genital ulcer disease (GUD) increases the risk of both HIV acquisition and HIV transmission.3,108 As a result, the prevention and treatment of GUD is a high public health priority.


Herpes, syphilis, and chancroid are the major causes of genital ulcer disease. Less common causes of GUD include lymphogranuloma venereum (infection with L-serotypes of C. trachomatis), donovanosis (infection with Calymmatobacterium granulomatis), superinfection of ectoparasitic infections, trauma, neoplasm, Behçet syndrome, Reiter syndrome, and fixed drug eruptions (e.g., from doxycycline or sulfonamides).

Herpes is the most common cause of GUD in developed nations. In the United States in 2000, over two million people sought care for genital herpes. In contrast, a total of 5,979 cases of primary and secondary syphilis and 82 cases of chancroid were reported to the CDC.28 A 1996 study of 516 STD clinic patients with genital ulcers found that 62% had HSV, 10% had syphilis, 3% had both syphilis and herpes, 3% had chancroid, and 22% had no identified pathogen.109

Traditionally, chancroid and syphilis have been the most common cause of genital ulcers in most developing nations. However, recent studies undertaken in sub-Saharan Africa have documented the increasing importance of herpes as a cause of GUD, particularly in areas where HIV is highly prevalent.110


Clinical Manifestations

When examining patients with genital ulcers, clinicians should note the number and depth of lesions; the presence of vesicles, induration, necrotic material on the ulcer bed, or an undermined ulcer border (i.e., the ulcer invades beneath the superficial edges); the presence or absence of pain; and any associated adenopathy [see Table 5]. Although physical findings can be helpful, different GUD etiologies cannot be reliably distinguished by physical examination alone.111

Table 5 Clinical Features and Laboratory Diagnosis of Genital Ulcers



Incubation Period

Number of Lesions

Primary Lesion Type

Ulcer Diameter

Ulcer Characteristics

Pain or Tenderness


Laboratory Diagnosis


Treponema pallidum

9–90 days

Usually one


5–15 mm

Superficial or deep; sharply demarcated; indurated; nonvascular, purulent base


Firm, nontender, bilateral

Darkfield microscopy, RPR/VDRL and FTA, MHA-TP


HSV-1 or -2

2–7 days

Multiple, may coalesce


1–2 mm

Superficial; erythematous edges, no induration

Frequently tender

Firm, tender, small; often bilateral with first episode

DFA, culture, serology


Haemophilus ducreyi

1–14 days

Multiple, may coalesce



Deep; irregular, undermined edges; purulent base bleeds easily

Usually tender

Tender, may be fluctuant, loculated; usually unilateral

Culture of ulcer base,*NAAT (e.g., PCR, LCR, TMA, SDA)


L-serotypes ofChlamydia trachomatis

3 days to 6 wk

Usually one

Papule, pustule, or vesicle

2–10 cm

Very rarely seen, because of rapid healing; can be superficial, deep, elevated, round, or oval


Tender, may suppurate or form sinus tracts; loculated, usually unilateral; more common in men than women

Culture, PCR, microimmunofluorescent antibody


Calymmatobacterium granulomatis

1–4 wk (up to 6 mo)




Extensive, indolent ulcer with granulation tissue; elevated, rolled irregular edges on raised ulcer; beefy-red vascular base bleeds easily


None; pseudobuboes

Giemsa or Wright stain of tissue smear

*Culture of material from bubo seldom positive.
Less common variants can be hypertrophic, necrotic, or sclerotic.
DFA—direct fluorescent antibody  HSV—herpes simplex virus  LGV—lymphogranuloma venereum  LCR—ligase chain reaction  MHA-TP—microhemagglutination assay-T. pallidum  NAAT—nucleic acid amplification test  PCR—polymerase chain reaction  RPR—rapid plasma reagin  SDA—strand displacement amplification  TMA—transcription-mediated amplification  VDRL—Venereal Disease Research Laboratory

Laboratory Tests

Because physical findings are unreliable, clinical assessment should be supported by laboratory evaluation. The laboratory evaluation of GUD typically concentrates on herpes and syphilis. Chancroid, donovanosis, or LGV should be considered if the patient lives in or has traveled to an area where one of those infections is common or if the physical findings are highly suggestive of one of those infections.

When possible, laboratory evaluation should include dark-field microscopy, serologic testing for syphilis (e.g., rapid plasma reagin [RPR] or venereal disease research laboratory (VDRL); and fluorescent treponemal antibody [FTA] or microhemagglutination assay for antibody to T. pallidum), and culture for herpes. If available, RPR should be performed. Dark-field microscopy is 70% to 95% sensitive in detecting treponemes, but sensitivity is highly dependent on the expertise of the technician. Culture should seek to distinguish between HSV-1 and HSV-2, because the former typically produces a less severe infection with fewer recurrences. This is particularly important in light of recent data that suggest that HSV-1 is an increasingly common cause of genital herpes.112 If initial evaluation does not establish a cause of genital ulcers and the clinician's suspicion for chancroid, LGV, or donovanosis remains low, further diagnostic efforts should focus on ruling out genital herpes. Several type-specific serologic tests that target the HSV glycoprotein G-2 (gG-2) are now available.113 Patients who have no serologic evidence of HSV-2 may have primary infections. Only limited data are available on how soon seroconversion can be detected by commercially available type-specific tests, but the median time from exposure to seroconversion appears to be 2 to 3 weeks. Patients with a clinical syndrome consistent with genital herpes who test negative for HSV-2 should be retested after 6 to 12 weeks if an intervening recurrence of genital ulcers does not establish the diagnosis of HSV infection and the clinical suspicion for genital herpes is high. Older HSV serologic tests are neither sensitive nor specific and should not be used. Clinicians should be aware that type-specific serologic tests have not been studied extensively for HSV-2 screening. Given the imperfect specificity of these tests, it is likely that widespread testing in populations in which the prevalence of HSV-2 is low will result in large numbers of false positive test results. Because of poor specificity, a positive HSV-2 serologic test result in a patient without signs or symptoms of genital herpes or definite exposure to HSV-2 should be interpreted with caution.


Treatment of patients with genital ulcers is usually empirical [see Table 6]. If patients have physical findings suggestive of syphilis, are residents of or recent travelers to areas where syphilis remains common, or are members of groups at high risk for syphilis (e.g., men who have sex with men, as well as commercial sex workers or their clients), treatment should include benzathine penicillin G, 2.4 million units intramuscularly, and a regimen for genital herpes [see Table 7]. If the suspicion for syphilis is low and follow-up can be ensured, initial empirical treatment can focus on genital herpes alone. The treatment and follow-up of patients with genital herpes and syphilis are discussed in other subsections.

Table 6 Treatment of Genital Ulcers




Benzathine penicillin G, 2.4 million U I.M.*


Azithromycin, 1 g p.o. once


Ceftriaxone, 250 mg I.M. once


Ciprofloxacin, 500 mg p.o., b.i.d., for 3 days


Erythromycin, 500 mg p.o., t.i.d., for 7 days

Lymphogranuloma venereum

Doxycycline, 100 mg p.o., b.i.d., for 21 days


Doxycycline, 100 mg p.o. for at least 3 wk or until lesion is healed


Trimethoprim-sulfamethoxazole, double strength (800 mg/160 mg), one tablet p.o., b.i.d., for at least 3 wk or until lesion is healed


See Table 7

Note: treatment should always include evaluation and treatment of sexual partners.
*For primary or secondary syphillis.

Table 7 Treatment of Genital Herpes in Immunocompetent Patients

Primary herpes

Acyclovir, 400 mg p.o., t.i.d., for 7–10 days


Valacyclovir, 1 g p.o., b.i.d., for 7–10 days


Famciclovir, 250 mg p.o., t.i.d., for 7–10 days

Recurrent herpes

Acyclovir, 800 mg p.o., b.i.d., for 5 days


Acyclovir, 800 mg p.o., t.i.d., for 2 days


Valacyclovir, 1g p.o., q.d., for 5 days


Valacyclovir, 500 mg p.o., b.i.d., for 3–5 days


Famciclovir, 125 mg p.o., t.i.d., for 5 days

Patients with genital herpes should be counseled about the recurrent nature of the infection and advised that subclinical viral shedding is common. The median recurrence rate in the first year after HSV-2 acquisition is 0.33 recurrences monthly.114 During the first 6 months after HSV-2 acquisition, virus can be isolated by culture on 6% of days and by PCR on 20% to 35% of days.115 It is not known to what extent HSV can be transmitted by patients whose cultures are negative and whose PCR results are positive. The American Social Health Association Web site ( is an excellent source of information on STD in general and genital herpes in particular, and it has information on support services for persons with genital herpes.

STDs in Men Who Have Sex with Men and Anorectal STDs in Women

Although surveillance data on STDs in men who have sex with men (MSM) are limited, cases of gonorrhea and syphilis in MSM in selected cities in the United States declined by more than 10-fold in the decade following the first recognition of AIDS.116 More recently, numerous cities in the United States and Europe have reported rising rates of STDs in MSM.30,117 Limited data suggest that HIV transmission may also be increasing.118 Because STDs can enhance HIV transmission, the control of STDs in MSM is a public health priority. Moreover, an STD can be a sentinel event, alerting the clinician to a patient's risk of acquiring HIV infection or transmitting it to others.


Several aspects of the care of MSM merit consideration. First, it is imperative that clinicians adopt a nonjudgmental, direct approach when discussing sexual behavior. In addition to the questions typically included in a sexual history, clinicians should ask patients about the HIV status of their sexual partners and about their anal sexual exposure. The latter can be determined by asking, “Are you a top, a bottom, or both a top and a bottom?” The term top refers to a man who practices insertive anal sex; a bottom practices receptive anal sex.

Second, the spectrum of STD is wider in MSM than in heterosexuals. Several pathogens that are rarely sexually transmitted among heterosexuals are relatively common causes of STD in MSM. These include hepatitis A virus, Shigella species, Salmonella species,Campylobacter species, Giardia lamblia, and Entamoeba histolyticaStrongyloides stercoralis and Enterobius vermicularis are occasionally transmitted sexually in MSM.

Third, the anus is a more common sexual organ for MSM than it is for heterosexuals. Consequently, STD should figure prominently in the differential diagnosis of MSM who present with anorectal symptoms, and rectal screening should be part of standard STD screening in MSM.24 Finally, although there are no guidelines for regular STD screening of heterosexual men, the CDC currently recommends annual STD screening for MSM [see Table 1].8


Although anorectal STD occurs in both men and heterosexual women, anal STD syndromes are more common in MSM. The symptoms of anorectal infection vary, depending on the level and extent of anatomic involvement and on the microbiologic etiology.119 Proctitis is limited to the rectum. It results from direct inoculation of pathogens through anal sex and presents as some combination of rectal pain, constipation, hematochezia, tenesmus, and mucopurulent rectal discharge. Sexually transmitted proctitis is caused by gonorrhea, chlamydial infection (non-LGV), syphilis, or HSV. In proctocolitis, the inflammatory process extends to the colon. As a result, in addition to the symptoms of proctitis, patients may complain of diarrhea, abdominal pain, and bloating or nausea. Most cases of proctocolitis result from oral-genital or oral-anal sex (anilingus, or so-called rimming) and are caused by ShigellaSalmonella, or Campylobacter species; E. histolytica; or LGV serovars of C. trachomatisG. lamblia infection involves the small bowel alone (enteritis) and typically presents as diarrhea, abdominal pain, and bloating or nausea in the absence of rectal symptoms. The differential diagnosis in patients presenting with symptoms of colitis or proctocolitis should include Clostridium difficile infection and inflammatory bowel disease. In persons with HIV infection and CD4+ T cell counts less than 50/mm3, cytomegalovirus infection is also a possibility. Depending on their level of immunosuppression, HIV-infected patients presenting with enteritis should also be evaluated for Mycobacterium avium complex, cryptosporidium, Isospora belli, Cyclospora cayetanensis, and microsporidia organisms.


History and Physical Examination

Evaluation of a patient with anorectal symptoms should include questions about anal, oral-genital, and oral-anal sex and condom use. In the evaluation, an attempt should be made to differentiate symptoms of proctitis, proctocolitis, and enteritis. Physical examination should include a careful anal examination, digital rectal examination, and anoscopy directed toward finding ulcers consistent with HSV or syphilis, condylomata lata, or rectal discharge or bleeding.

Laboratory Tests

If a rectal exudate is present, a Gram stain should be performed to look for gonorrhea. The reported sensitivity of Gram stain is highly variable (30% to 79%).120 In one study, rectal Gram stain specimens obtained by anoscopy were more sensitive in detecting gonorrhea than were those obtained blindly (53% versus 79%).120 In men without rectal symptoms, however, anoscopically obtained rectal cultures do not appear to be more sensitive in detecting gonorrhea than those obtained by blindly inserting a swab 2 to 3 cm into the rectum.121

Laboratory evaluation in patients with suspected proctitis or proctocolitis should include cultures for gonorrhea and chlamydial infection, a serologic test for syphilis, and a rapid syphilis test. Rectal ulcers or lesions should be cultured for HSV; when possible, a specimen should be obtained for dark-field evaluation. If symptoms suggest proctocolitis, stool specimens should be obtained for enteric pathogens and E. histolytica. Patients with recent antibiotic exposures should also be tested for C. difficile. Stool Giardia antigen testing should be performed if enteritis is suspected.


In general, treatment should be directed by laboratory findings. If patients with proctitis have severe symptoms or if follow-up cannot be ensured, empirical therapy should be directed against gonorrhea and chlamydial infection. The CDC recommends treatment with ceftriaxone, 250 mg intramuscularly, and doxycycline, 100 mg a day orally for 7 days. Alternative therapies for gonorrhea (cefixime, 400 mg orally or ciprofloxacin, 500 mg orally once) and chlamydial infection (azithromycin, 1 g orally once) are probably effective but have not been studied. Clinicians should have a low threshold for adding empirical therapy for herpes to this regimen.


  1. Eng TR, Butler WT: The Hidden Epidemic: Confronting Sexually Transmitted Diseases. Committee on Prevention and Control of Sexually Transmitted Diseases, Institute of Medicine (U.S.), National Academy Press, Washington, DC, 1997, p 432
  2. Gerbase AC, Rowley JT, Heymann DH, et al: Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect 74(suppl 1):S12, 1998
  3. Fleming DT, Wasserheit JN: From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 75:3, 1999
  4. Holmes KK: Introduction. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p xi
  5. Holmes KK: Human ecology and behavior and sexually transmitted bacterial infections. Proc Natl Acad Sci U S A 91:2448, 1994
  6. Revised guidelines for HIV counseling, testing and referral. MMWR Recomm Rep 50(RR-19):1, 2001
  7. Revised recommendations for HIV screening of pregnant women. MMWR Recomm Rep 50(RR-19):63, 2001
  8. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep 51(RR-6):1, 2002
  9. Anderson RM: Transmission dynamics of sexually transmitted infections. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 25
  10. Brunham RC, Plummer FA: A general model of sexually transmitted disease epidemiology and its implications for control. Med Clin North Am 74:1339, 1990
  11. Thomas JC, Tucker MJ: The development and use of the concept of a sexually transmitted disease core. J Infect Dis 174 (suppl 2):S134, 1996
  12. Fleming DT, McQuillan GM, Johnson RE, et al: Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med 337:1105, 1997
  13. Garnett GP, Anderson RM: Sexually transmitted diseases and sexual behavior: insights from mathematical models. J Infect Dis 174(suppl 2):S150, 1996
  14. Morris M: Concurrent partnerships and syphilis persistence: new thoughts on an old puzzle. Sex Transm Dis 28:504, 2001
  15. Kretzschmar M: Sexual network structure and sexually transmitted disease prevention: a modeling perspective. Sex Transm Dis 27:627, 2000
  16. Handsfield HH, Jasman LL, Roberts PL, et al: Criteria for selective screening for Chlamydia trachomatisinfection in women attending family planning clinics. JAMA 255:1730, 1986
  17. Marrazzo JM, Fine D, Celum CL, et al: Selective screening for chlamydial infection in women: a comparison of three sets of criteria. Fam Plann Perspect 29:158, 1997
  18. van Valkengoed IG, Morre SA, van den Brule AJ, et al: Low diagnostic accuracy of selective screening criteria for asymptomaticChlamydia trachomatisinfections in the general population. Sex Transm Infect 76:375, 2000
  19. Marrazzo JM, White CL, Krekeler B, et al: Community-based urine screening for Chlamydia trachomatiswith a ligase chain reaction assay. Ann Intern Med 127:796, 1997
  20. Laumann EO, Youm Y: Racial/ethnic group differences in the prevalence of sexually transmitted diseases in the United States: a network explanation. Sex Transm Dis 26:250, 1999
  21. Sucato G, Celum C, Dithmer D, et al: Demographic rather than behavioral risk factors predict herpes simplex virus type 2 infection in sexually active adolescents. Pediatr Infect Dis J 20:422, 2001
  22. Laumann E, Gagnon J, Michaels S: The Social Organization of Sexuality: Sexual Practices in the United States. University of Chicago Press, Chicago, 1994
  23. Sexually transmitted disease and HIV screening guidelines for men who have sex with men. Sex Transm Dis 28:457, 2001
  24. Efficacy of risk-reduction counseling to prevent human immunodeficiency virus and sexually transmitted diseases: a randomized controlled trial. Project RESPECT Study Group. JAMA 280:1161, 1998
  25. Ramstedt K, Forssman L, Johannisson G: Contact tracing in the control of genital Chlamydia trachomatis. Int J STD AIDS 2:116, 1991
  26. Kissinger P, Brown R, Reed K, et al: Effectiveness of patient delivered partner medication for preventing recurrent Chlamydia trachomatis. Sex Transm Infect 74:331, 1998
  27. Golden MR, Whittington WL, Handsfield HH, et al: Partner management for gonococcal and chlamydial infection: expansion of public health services to the private sector and expedited sex partner treatment through a partnership with commercial pharmacies. Sex Transm Dis 28:658, 2001
  28. Scholes D, Stergachis A, Heidrich FE, et al: Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 334:1362, 1996
  29. Gonorrhea among men who have sex with men: selected sexually transmitted disease clinics, 1993–1996. MMWR Morb Mortal Wkly Rep 46:889, 1997
  30. Nicoll A, Hamers FF: Are trends in HIV, gonorrhoea, and syphilis worsening in western Europe? BMJ 324:1324, 2002
  31. Stamm WE, Hicks CB, Martin DH, et al: Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men: a randomized double-blind study. JAMA 274:545, 1995
  32. Marrazzo JM, Whittington WL, Celum CL, et al: Urine-based screening for Chlamydia trachomatisin men attending sexually transmitted disease clinics. Sex Transm Dis 28:219, 2001
  33. Bowie WR, Wang SP, Alexander ER, et al: Etiology of nongonococcal urethritis: evidence for Chlamydia trachomatisand Ureaplasma urealyticum. J Clin Invest 59:735, 1977
  34. Tully JG, Taylor-Robinson D, Cole RM, et al: A newly discovered mycoplasma in the human urogenital tract. Lancet 1:1288, 1981
  35. Totten PA, Schwartz MA, Sjostrom KE, et al: Association of Mycoplasma genitaliumwith nongonococcal urethritis in heterosexual men. J Infect Dis 183:269, 2001
  36. Harrison WO, Hooper RR, Wiesner PJ, et al: A trial of minocycline given after exposure to prevent gonorrhea. N Engl J Med 300:1074, 1979
  37. Handsfield HH, Lipman TO, Harnisch JP, et al: Asymptomatic gonorrhea in men: diagnosis, natural course, prevalence and significance. N Engl J Med 290:117, 1974
  38. Turner CF, Rogers SM, Miller HG, et al: Untreated gonococcal and chlamydial infection in a probability sample of adults. JAMA 287:726, 2002
  39. Klausner JD, McFarland W, Bolan G, et al: Knock-knock: a population-based survey of risk behavior, health care access, andChlamydia trachomatisinfection among low-income women in the San Francisco Bay area. J Infect Dis 183:1087, 2001
  40. Jacobs NF, Kraus SJ: Gonococcal and nongonococcal urethritis in men: clinical and laboratory differentiation. Ann Intern Med 82:7, 1975
  41. Rothenberg RB, Simon R, Chipperfield E, et al: Efficacy of selected diagnostic tests for sexually transmitted diseases. JAMA 235:49, 1976
  42. Koumans EH, Johnson RE, Knapp JS, et al: Laboratory testing for Neisseria gonorrhoeaeby recently introduced nonculture tests: a performance review with clinical and public health considerations. Clin Infect Dis 27:1171, 1998
  43. Marrazzo JM, Stamm WE: New approaches to the diagnosis, treatment, and prevention of chlamydial infection. Curr Clin Top Infect Dis 18:37, 1998
  44. Black CM, Marrazzo J, Johnson RE, et al: Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests forChlamydia trachomatisinfection in women performed with an improved reference standard. J Clin Microbiol 40:3757, 2002
  45. Stamm WE, Wagner KF, Amsel R, et al: Causes of the acute urethral syndrome in women. N Engl J Med 303:409, 1980
  46. Hooton TM, Stamm WE: Diagnosis and treatment of uncomplicated urinary tract infection. Infect Dis Clin North Am 11:551, 1997
  47. Bent S, Nallamothu BK, Simel DL, et al: Does this woman have an acute uncomplicated urinary tract infection? JAMA 287:2701, 2002
  48. Gupta K, Hooton TM, Roberts PL, et al: Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women. Ann Intern Med 135:9, 2001
  49. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 333:1737, 1995
  50. Trichomonas vaginalisassociated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis 24:353, 1997
  51. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 342:534, 2000
  52. Klebanoff MA, Carey JC, Hauth JC, et al: Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalisinfection. N Engl J Med 345:487, 2001
  53. Koumans EH, Kendrick JS: Preventing adverse sequelae of bacterial vaginosis: a public health program and research agenda. Sex Transm Dis 28:292, 2001
  54. Gulmezoglu AM: Interventions for trichomoniasis in pregnancy. Cochrane Database Syst Rev (3):CD000220, 2002
  55. Martin HL, Richardson BA, Nyange PM, et al: Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180:1863, 1999
  56. Taha TE, Hoover DR, Dallabetta GA, et al: Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 12:1699, 1998
  57. Cu-Uvin S, Hogan JW, Caliendo AM, et al: Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract. Clin Infect Dis 33:894, 2001
  58. Sorvillo F, Smith L, Kerndt P, et al: Trichomonas vaginalis, HIV, and African-Americans. Emerg Infect Dis 7:927, 2001
  59. Wang CC, McClelland RS, Reilly M, et al: The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. J Infect Dis 183:1017, 2001
  60. Allen-Davis JT, Beck A, Parker R, et al: Assessment of vulvovaginal complaints: accuracy of telephone triage and in-office diagnosis. Obstet Gynecol 99:18, 2002
  61. Ferris DG, Nyirjesy P, Sobel JD, et al: Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 99:419, 2002
  62. Sobel JD: Vaginitis. N Engl J Med 337:1896, 1997
  63. Hillier S, Holmes K: Bacterial vaginosis. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 563
  64. Eschenbach DA, Davick PR, Williams BL, et al: Prevalence of hydrogen peroxide-producing Lactobacillusspecies in normal women and women with bacterial vaginosis. J Clin Microbiol 27:251, 1989
  65. Gardner H, Dukes C: Haemophilis vaginalisvaginitis: a newly defined specific infection previously classified as “nonspcific” vaginitis. Am J Obstet Gynecol 69:962, 1955
  66. Criswell BS, Ladwig CL, Gardner HL, et al: Haemophilus vaginalis: vaginitis by inoculation from culture. Obstet Gynecol 33:195, 1969
  67. Marrazzo JM, Koutsky LA, Eschenbach DA, et al: Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. J Infect Dis 185:1307, 2002
  68. Avonts D, Sercu M, Heyerick P, et al: Incidence of uncomplicated genital infections in women using oral contraception or an intrauterine device: a prospective study. Sex Transm Dis 17:23, 1990
  69. Barbone F, Austin H, Louv WC, et al: A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis. Am J Obstet Gynecol 163:510, 1990
  70. Hawes SE, Hillier SL, Benedetti J, et al: Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis 174:1058, 1996
  71. Amsel R, Totten PA, Spiegel CA, et al: Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 74:14, 1983
  72. Vejtorp M, Bollerup AC, Vejtorp L, et al: Bacterial vaginosis: a double-blind randomized trial of the effect of treatment of the sexual partner. Br J Obstet Gynaecol 95:920, 1988
  73. Vutyavanich T, Pongsuthirak P, Vannareumol P, et al: A randomized double-blind trial of tinidazole treatment of the sexual partners of females with bacterial vaginosis. Obstet Gynecol 82:550, 1993
  74. Colli E, Landoni M, Parazzini F: Treatment of male partners and recurrence of bacterial vaginosis: a randomised trial. Genitourin Med 73:267, 1997
  75. Eschenbach DA, Hillier S, Critchlow C, et al: Diagnosis and clinical manifestations of bacterial vaginosis. Am J Obstet Gynecol 158:819, 1988
  76. Thomason JL, Gelbart SM, Anderson RJ, et al: Statistical evaluation of diagnostic criteria for bacterial vaginosis. Am J Obstet Gynecol 162:155, 1990
  77. Demographic and behavioral predictors of Trichomonas vaginalisinfection among pregnant women. The Vaginal Infections and Prematurity Study Group. Obstet Gynecol 78:1087, 1991
  78. Bowden FJ, Garnett GP: Trichomonas vaginalisepidemiology: parameterising and analysing a model of treatment interventions. Sex Transm Infect 76:248, 2000
  79. Wolner-Hanssen P, Krieger JN, Stevens CE, et al: Clinical manifestations of vaginal trichomoniasis. JAMA 261:571, 1989
  80. Krieger J, Alderete J: Trichomonas vaginalisand trichomoniasis. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 587
  81. Levi MH, Torres J, Pina C, et al: Comparison of the InPouch TV culture system and Diamond's modified medium for detection ofTrichomonas vaginalis. J Clin Microbiol 35:3308, 1997
  82. Tidwell BH, Lushbaugh WB, Laughlin MD, et al: A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis. J Infect Dis 170:242, 1994
  83. Sobel JD, Nyirjesy P, Brown W: Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clin Infect Dis 33:1341, 2001
  84. Geiger AM, Foxman B, Gillespie BW: The epidemiology of vulvovaginal candidiasis among university students. Am J Public Health 85:1146, 1995
  85. Foxman B, Barlow R, D'Arcy H, et al: Candidavaginitis: self-reported incidence and associated costs. Sex Transm Dis 27:230, 2000
  86. Foxman B: The epidemiology of vulvovaginal candidiasis: risk factors. Am J Public Health 80:329, 1990
  87. Abbott J: Clinical and microscopic diagnosis of vaginal yeast infection: a prospective analysis. Ann Emerg Med 25:587, 1995
  88. Ryan CA, Courtois BN, Hawes SE, et al: Risk assessment, symptoms, and signs as predictors of vulvovaginal and cervical infections in an urban US STD clinic: implications for use of STD algorithms. Sex Transm Infect 74(suppl 1):S59, 1998
  89. Schaaf VM, Perez-Stable EJ, Borchardt K: The limited value of symptoms and signs in the diagnosis of vaginal infections. Arch Intern Med 150:1929, 1990
  90. Sobel J: Vulvovaginal candidiasis. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 629
  91. Bertholf ME, Stafford MJ: Colonization of Candida albicansin vagina, rectum, and mouth. J Fam Pract 16:919, 1983
  92. Sobel JD, Chaim W: Treatment of Torulopsis glabratavaginitis: retrospective review of boric acid therapy. Clin Infect Dis 24:649, 1997
  93. Myziuk L, Romanowski B, Brown M: Endocervical Gram stain smears and their usefulness in the diagnosis of Chlamydia trachomatis. Sex Transm Infect 77:103, 2001
  94. Marrazzo J, Handsfield H, Whittington W: Predicting chlamydial and gonococcal cervical infection: implications for management of cervicitis. Obstet Gynecol 100:579, 2002
  95. Miller HG, Cain VS, Rogers SM, et al: Correlates of sexually transmitted bacterial infections among U.S. women in 1995. Fam Plann Perspect 31:4, 1999
  96. Hubacher D, Lara-Ricalde R, Taylor DJ, et al: Use of copper intrauterine devices and the risk of tubal infertility among nulligravid women. N Engl J Med 345:561, 2001
  97. Westrom L, Eschenbach D: Pelvic inflammatory disease. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 783
  98. Cohen CR, Manhart LE, Bukusi EA, et al: Association between Mycoplasma genitaliumand acute endometritis. Lancet 359:765, 2002
  99. Kahn JG, Walker CK, Washington AE, et al: Diagnosing pelvic inflammatory disease: a comprehensive analysis and considerations for developing a new model. JAMA 266:2594, 1991
  100. Peipert JF, Ness RB, Blume J, et al: Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease. Am J Obstet Gynecol 184:856, 2001
  101. Wolner-Hanssen P: Silent pelvic inflammatory disease: is it overstated? Obstet Gynecol 86:321, 1995
  102. Munday PE: Pelvic inflammatory disease: an evidence-based approach to diagnosis. J Infect 40:31, 2000
  103. Jacobson L, Westrom L: Objectivized diagnosis of acute pelvic inflammatory disease: diagnostic and prognostic value of routine laparoscopy. Am J Obstet Gynecol 105:1088, 1969
  104. Eckert LO, Hawes SE, Wolner-Hanssen PK, et al: Endometritis: the clinical-pathologic syndrome. Am J Obstet Gynecol 186:690, 2002
  105. Molander P, Sjoberg J, Paavonen J, et al: Transvaginal power Doppler findings in laparoscopically proven acute pelvic inflammatory disease. Ultrasound Obstet Gynecol 17:233, 2001
  106. Ness RB, Soper DE, Holley RL, et al: Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol 186:929, 2002
  107. Westrom L, Joesoef R, Reynolds G, et al: Pelvic inflammatory disease and fertility: a cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis 19:185, 1992
  108. Wald A, Link K: Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 185:45, 2002
  109. Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group. J Infect Dis 178:1795, 1998
  110. Korenromp EL, Bakker R, De Vlas SJ, et al: Can behavior change explain increases in the proportion of genital ulcers attributable to herpes in sub-Saharan Africa? A simulation modeling study. Sex Transm Dis 29:228, 2002
  111. DiCarlo RP, Martin DH: The clinical diagnosis of genital ulcer disease in men. Clin Infect Dis 25:292, 1997
  112. Lafferty WE, Downey L, Celum C, et al: Herpes simplex virus type 1 as a cause of genital herpes: impact on surveillance and prevention. J Infect Dis 181:1454, 2000
  113. Ashley RL: Performance and use of HSV type-specific serology test kits. Herpes 9:38, 2002
  114. Benedetti J, Corey L, Ashley R: Recurrence rates in genital herpes after symptomatic first-episode infection. Ann Intern Med 121:847, 1994
  115. Corey L, Wald A: Genital herpes. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 285
  116. Doll L, Ostrow D: Homosexual and bisexual behavior. Sexually Transmitted Diseases, 3rd ed. Holmes KK, Mårdh P-A, Sparling PF, et al, Eds. McGraw-Hill, New York, 1999, p 151
  117. Mayer KH, Klausner JD, Handsfield HH: Intersecting epidemics and educable moments: sexually transmitted disease risk assessment and screening in men who have sex with men. Sex Transm Dis 28:464, 2001
  118. Dukers NH, Spaargaren J, Geskus RB, et al: HIV incidence on the increase among homosexual men attending an Amsterdam sexually transmitted disease clinic: using a novel approach for detecting recent infections. AIDS 16:F19, 2002
  119. Quinn TC, Stamm WE, Goodell SE, et al: The polymicrobial origin of intestinal infections in homosexual men. N Engl J Med 309:576, 1983
  120. William DC, Schapiro CM, Felman YM: Pharyngeal carriage of Neisseria meningitidisand anogenital gonorrhea: evidence for their relationship. Sex Transm Dis 7:175, 1980
  121. Deheragoda P: Diagnosis of rectal gonorrhoea by blind anorectal swabs compared with direct vision swabs taken via a proctoscope. Br J Vener Dis 53:311, 1977

Editors: Dale, David C.; Federman, Daniel D.