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
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.
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 topic presents general concepts in the epidemiology and approach to patients with STD and reviews important STD syndromes, including urethritis, vulvovagini-tis, 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 Chlamydia, Neisseria gonorrhoeae, herpes viruses, and Treponema pallidum, are discussed in other topics. The Centers for Disease Control and Prevention (CDC) issues guidelines for STD/HIV testing and counseling, as well as STD treatment (http://www.cdc.gov/ hiv/dhap.htm). Clinicians are advised to refer to these guidelines for updated recommendations.6-8
Epidemiology and Transmission Dynamics
The transmission of an STD through a population can be conceptualized mathematically with the formula Rq = ficD, in which Rq is the average number of secondary cases generated by each primary infection in a population (i.e., the reproductive number); p 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, Rq 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 (p = 0.5), but it has a relatively short duration of infection, especially in settings in which medical care and therapy are readily avail-able.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 Rq 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 (assorta-tive 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.
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,16-18 whereas demographic factors such as age, race, socioeconomic status, source of clinical care, and geography are strongly associated with a variety of STDs.19-21 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 in-fection.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
Sexual history and counseling
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.
Table 1 Recommended STD Screening8
|
Population |
Screening Measures |
|
All men and women |
Retest all patients diagnosed with gonorrhea or Chlamydia infection 10-18 wk after initial treatment |
|
Women Sexually active, age s 24 yr Age > 24 yr with a new sexual partner or multiple sexual partners |
Annual chlamydial screening |
|
Pregnant women |
Test for Chlamydia trachomatis, Neisseria gonorrhoea, 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.
Std reporting and sexual partner management
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.25-27 However, at present, there are no guidelines that define the circumstances in which this approach to partner management should be employed.
Std screening
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
Urethritis in Men
Epidemiology
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
Etiology and microbiology
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 My-coplasma genitalium have been associated with NGU in case-control studies, but at present no tests for these organisms are commercially available.
Diagnosis
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 1,000x 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 400x field on at least one of five randomly selected fields.
Figure 1 This figure shows a Gram stain of a urethral discharge from a man with gonorrhea. The gram-negative intracellular diplococci are Neisseria gonorrhoeae organisms.
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 ureth-ral 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 micro-biologic testing should be performed for N. gonorrhoeae and C. trachomatis.
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.
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 ure-thral 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 im-munoassays 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.
Treatment
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 mi-crobiologically excluded. Treatment for presumptive chlamydi-al 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.
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, vulvo-vaginitis, 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.
Syndromes causing dysuria and urethritis
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 vul-vitis 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.4648 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].
