CHAPTER 35: SEXUALLY TRANSMITTED INFECTIONS: OVERVIEW AND CLINICAL APPROACH

Worldwide, most adults acquire at least one sexually transmitted infection (STI), and many remain at risk for complications. Each year, for example, an estimated 14 million persons in the United States acquire a new genital human papillomavirus (HPV) infection, and many of these individuals are at risk for genital neoplasias. Certain STIs, such as syphilis, gonorrhea, HIV infection, hepatitis B, and chancroid, are most concentrated within “core populations” characterized by high rates of partner change, multiple concurrent partners, or “dense,” highly connected sexual networks—e.g., involving sex workers and their clients, some men who have sex with men (MSM), and persons involved in the use of illicit drugs, particularly crack cocaine and methamphetamine. Other STIs are distributed more evenly throughout societies. For example, chlamydial infections, genital infections with HPV, and genital herpes can spread widely, even in relatively low-risk populations.

In general, the product of three factors determines the initial rate of spread of any STI within a population: rate of sexual exposure of susceptible to infectious people, efficiency of transmission per exposure, and duration of infectivity of those infected. Accordingly, efforts to prevent and control STIs aim to decrease the rate of sexual exposure of susceptibles to infected persons (e.g., through individual counseling and efforts to change the norms of sexual behavior and through a variety of STI control efforts aimed at reducing the proportion of the population infected), to decrease the duration of infectivity (through early diagnosis and curative or suppressive treatment), and to decrease the efficiency of transmission (e.g., through promotion of condom use and safer sexual practices, through use of effective vaccines, and recently through male circumcision).

In all societies, STIs rank among the most common of all infectious diseases, with >30 infections now classified as predominantly sexually transmitted or as frequently sexually transmissible (Table 35-1). In developing countries, with three-quarters of the world’s population and 90% of the world’s STIs, factors such as population growth (especially in adolescent and young-adult age groups), rural-to-urban migration, wars, limited or no provision of reproductive health services for women, and poverty create exceptional vulnerability to disease resulting from unprotected sex. During the 1990s in China, Russia, the other states of the former Soviet Union, and South Africa, internal social structures changed rapidly as borders opened to the West, unleashing enormous new epidemics of HIV infection and other STIs. Despite advances in the provision of highly effective antiretroviral therapy worldwide, HIV remains the leading cause of death in some developing countries, and HPV and hepatitis B virus (HBV) remain important causes of cervical and hepatocellular carcinoma, respectively—two of the most common malignancies in the developing world. Sexually transmitted herpes simplex virus (HSV) infections now cause most genital ulcer disease throughout the world and an increasing proportion of cases of genital herpes in developing countries with generalized HIV epidemics, where the positive-feedback loop between HSV and HIV transmission is a growing, intractable problem. Despite this consistent link, randomized trials evaluating the efficacy of antiviral therapy in suppressing HSV in both HIV-uninfected and HIV-infected persons have not demonstrated a protective effect against acquisition or transmission of HIV. The World Health Organization estimated that 448 million new cases of four curable STIs—gonorrhea, chlamydial infection, syphilis, and trichomoniasis—occurred in 2005. Up to 50% of women of reproductive age in developing countries have bacterial vaginosis (arguably acquired sexually). All of these curable infections have been associated with increased risk of HIV transmission or acquisition.

In the United States, the prevalence of antibody to HSV-2 began to fall in the late 1990s, especially among adolescents and young adults; the decline is presumably due to delayed sexual debut, increased condom use, and lower rates of multiple (four or more) sex partners, as is well documented by the U.S. Youth Risk Behavior Surveillance System. The estimated annual incidence of HBV infection has also declined dramatically since the mid-1980s; this decrease is probably attributable more to adoption of safer sexual practices and reduced needle sharing among injection drug users than to use of hepatitis B vaccine, for which coverage among young adults (including those at high risk for this infection) initially was very limited. Genital HPV remains the most common sexually transmitted pathogen in this country, infecting 60% of a cohort of initially HPV-negative, sexually active Washington state college women within 5 years in a study conducted from 1990 to 2000. The scale-up of HPV vaccine coverage among young women has already shown promise in reducing the incidence of infection with the HPV types included in the vaccines and of conditions associated with these viruses.

In industrialized countries, fear of HIV infection since the mid-1980s, coupled with widespread behavioral interventions and better-organized systems of care for the curable STIs, initially helped curb the transmission of the latter diseases. However, foci of hyperendemic transmission persist in the southeastern United States and in most large U.S. cities. Rates of gonorrhea and syphilis remain higher in the United States than in any other Western industrialized country.

In the United States, the Centers for Disease Control and Prevention (CDC) has compiled reported rates of STIs since 1941. The incidence of reported gonorrhea peaked at 468 cases per 100,000 population in the mid-1970s and fell to a low of 98 cases per 100,000 in 2012. With increased testing and more sensitive tests, the incidence of reported Chlamydia trachomatis infection has been increasing steadily since reporting began in 1984, reaching an all-time peak of 457.6 cases per 100,000 in 2011. The incidence of primary and secondary syphilis per 100,000 peaked at 71 cases in 1946, fell rapidly to 3.9 cases in 1956, ranged from ~10 to 15 cases through 1987 (with markedly increased rates among MSM and African Americans), and then fell to a nadir of 2.1 cases in 2000–2001 (with rates falling most rapidly among heterosexual African Americans). Unfortunately, since 1996, with the introduction of highly active antiretroviral therapy, the increased use of “serosorting” (i.e., the avoidance of unprotected sex with HIV-serodiscordant partners but not with HIV-seroconcordant partners, a strategy that provides no protection against STIs other than HIV infection), and an ongoing epidemic of methamphetamine use, gonorrhea, syphilis, and chlamydial infection have had a remarkable resurgence among MSM in North America and Europe, where outbreaks of a rare type of chlamydial infection (lymphogranuloma venereum [LGV]) that had virtually disappeared during the AIDS era have occurred. In 2012, ~75% of primary and secondary syphilis cases reported to the CDC were in MSM. These developments have resulted in a high degree of co-infection with HIV and other sexually transmitted pathogens (particularly syphilis and LGV), primarily among MSM.

Although other chapters discuss management of specific STIs, delineating treatment based on diagnosis of a specific infection, most patients are actually managed (at least initially) on the basis of presenting symptoms and signs and associated risk factors, even in industrialized countries. Table 35-2 lists some of the most common clinical STD syndromes and their microbial etiologies. Strategies for their management are outlined below. Chapter 97 addresses the management of infections with human retroviruses.

STD care and management begin with risk assessment and proceed to clinical assessment, diagnostic testing or screening, treatment, and prevention. Indeed, the routine care of any patient begins with risk assessment (e.g., for risk of heart disease, cancer). STD/HIV risk assessment is important in primary care, urgent care, and emergency care settings as well as in specialty clinics providing adolescent, HIV/AIDS, prenatal, and family planning services. STD/HIV risk assessment guides detection and interpretation of symptoms that could reflect an STD; decisions on screening or prophylactic/preventive treatment; risk reduction counseling and intervention (e.g., hepatitis B vaccination); and treatment of partners of patients with known infections. Consideration of routine demographic data (e.g., gender, age, area of residence) is a simple first step in STD/HIV risk assessment. For example, national guidelines strongly recommend routine screening of sexually active females ≤25 years of age for C. trachomatis infection. Table 35-3 provides a set of 11 STD/HIV risk-assessment questions that clinicians can pose verbally or that health care systems can adapt (with yes/no responses) into a routine self-administered questionnaire for use in clinics. The initial framing statement gives permission to discuss topics that may be perceived as sensitive or socially unacceptable by providers and patients alike.

Risk assessment is followed by clinical assessment (elicitation of information on specific current symptoms and signs of STDs). Confirmatory diagnostic tests (for persons with symptoms or signs) or screening tests (for those without symptoms or signs) may involve microscopic examination, culture, antigen detection tests, nucleic acid amplification tests (NAATs), or serology. Initial syndrome-based treatment should cover the most likely causes. For certain syndromes, results of rapid tests can narrow the spectrum of this initial therapy (e.g., saline microscopy of vaginal fluid for women with vaginal discharge, Gram’s stain of urethral discharge for men with urethral discharge, rapid plasma reagin test for genital ulcer). After the institution of treatment, STD management proceeds to the “4 Cs” of prevention and control: contact tracing (see “Prevention and Control of STIs,” below), ensuring compliance with therapy, and counseling on risk reduction, including condom promotion and provision.

Consistent with current guidelines, all adults should be screened for infection with HIV-1 at least once and more frequently if they are at elevated risk for acquisition of this infection.

URETHRITIS IN MEN

Urethritis in men produces urethral discharge, dysuria, or both, usually without frequency of urination. Causes include Neisseria gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis, HSV, and adenovirus.

Until recently, C. trachomatis caused ~30–40% of cases of nongonococcal urethritis (NGU), particularly in heterosexual men; however, the proportion of cases due to this organism has probably declined in some populations served by effective chlamydial-control programs, and older men with urethritis appear less likely to have chlamydial infection. HSV and T. vaginalis each cause a small proportion of NGU cases in the United States. Recently, multiple studies have consistently implicated M. genitalium as a probable cause of many Chlamydia-negative cases. Fewer studies than in the past have implicated Ureaplasma; the ureaplasmas have been differentiated into U. urealyticum and Ureaplasma parvum, and a few studies suggest that U. urealyticum—but not U. parvum—is associated with NGU. Coliform bacteria can cause urethritis in men who practice insertive anal intercourse. The initial diagnosis of urethritis in men currently includes specific tests only for N. gonorrhoeae and C. trachomatis; it does not yet include testing for Mycoplasma or Ureaplasma species. The following summarizes the approach to the patient with suspected urethritis:

1. Establish the presence of urethritis. If proximal-to-distal “milking” of the urethra does not express a purulent or mucopurulent discharge, even after the patient has not voided for several hours (or preferably overnight), a Gram’s-stained smear of an anterior urethral specimen obtained by passage of a small urethrogenital swab 2–3 cm into the urethra usually reveals ≥5 neutrophils per 1000× field in areas containing cells; in gonococcal infection, such a smear usually reveals gram-negative intracellular diplococci as well. Alternatively, the centrifuged sediment of the first 20–30 mL of voided urine—ideally collected as the first morning specimen—can be examined for inflammatory cells, either by microscopy showing ≥10 leukocytes per high-power field or by the leukocyte esterase test. Patients with symptoms who lack objective evidence of urethritis may have functional rather than organic problems and generally do not benefit from repeated courses of antibiotics.

2. Evaluate for complications or alternative diagnoses. A brief history and examination will exclude epididymitis and systemic complications, such as disseminated gonococcal infection (DGI) and reactive arthritis. Although digital examination of the prostate gland seldom contributes to the evaluation of sexually active young men with urethritis, men with dysuria who lack evidence of urethritis as well as sexually inactive men with urethritis should undergo prostate palpation, urinalysis, and urine culture to exclude bacterial prostatitis and cystitis.

3. Evaluate for gonococcal and chlamydial infection. An absence of typical gram-negative diplococci on Gram’s-stained smear of urethral exudate containing inflammatory cells warrants a preliminary diagnosis of NGU, as this test is 98% sensitive for the diagnosis of gonococcal urethral infection. However, an increasing proportion of men with symptoms and/or signs of urethritis are simultaneously assessed for infection with N. gonorrhoeae and C. trachomatis by “multiplex” NAATs of first-voided urine. The urine specimen tested should consist of the first 10–15 mL of the stream, and, if possible, patients should not have voided for the prior 2 h. Culture or NAAT for N. gonorrhoeae may yield positive results when Gram’s staining is negative; certain strains of N. gonorrhoeae can result in negative urethral Gram’s stains in up to 30% of cases of urethral infection. Results of tests for gonococcal and chlamydial infection predict the patient’s prognosis (with greater risk for recurrent NGU if neither chlamydiae nor gonococci are found than if either is detected) and can guide both the counseling given to the patient and the management of the patient’s sexual partner(s).

4. Treat urethritis promptly while test results are pending.

TREATMENT

EPIDIDYMITIS

Acute epididymitis, almost always unilateral, produces pain, swelling, and tenderness of the epididymis, with or without symptoms or signs of urethritis. This condition must be differentiated from testicular torsion, tumor, and trauma. Torsion, a surgical emergency, usually occurs in the second or third decade of life and produces a sudden onset of pain, elevation of the testicle within the scrotal sac, rotation of the epididymis from a posterior to an anterior position, and absence of blood flow on Doppler examination or ^99mTc scan. Persistence of symptoms after a course of therapy for epididymitis suggests the possibility of testicular tumor or of a chronic granulomatous disease, such as tuberculosis. In sexually active men under age 35, acute epididymitis is caused most frequently by C. trachomatis and less commonly by N. gonorrhoeae and is usually associated with overt or subclinical urethritis. Acute epididymitis occurring in older men or following urinary tract instrumentation is usually caused by urinary pathogens. Similarly, epididymitis in men who have practiced insertive rectal intercourse is often caused by Enterobacteriaceae. These older men usually have no urethritis but do have bacteriuria.

TREATMENT

URETHRITIS AND THE URETHRAL SYNDROME IN WOMEN

C. trachomatis, N. gonorrhoeae, and occasionally HSV cause symptomatic urethritis—known as the urethral syndrome in women—that is characterized by “internal” dysuria (usually without urinary urgency or frequency), pyuria, and an absence of Escherichia coli and other uropathogens at counts of ≥10²/mL in urine. In contrast, the dysuria associated with vulvar herpes or vulvovaginal candidiasis (and perhaps with trichomoniasis) is often described as “external,” being caused by painful contact of urine with the inflamed or ulcerated labia or introitus. Acute onset, association with urinary urgency or frequency, hematuria, or suprapubic bladder tenderness suggests bacterial cystitis. Among women with symptoms of acute bacterial cystitis, costovertebral pain and tenderness or fever suggests acute pyelonephritis. The management of bacterial urinary tract infection (UTI) is discussed in Chap. 33.

Signs of vulvovaginitis, coupled with symptoms of external dysuria, suggest vulvar infection (e.g., with HSV or Candida albicans). Among dysuric women without signs of vulvovaginitis, bacterial UTI must be differentiated from the urethral syndrome by assessment of risk, evaluation of the pattern of symptoms and signs, and specific microbiologic testing. An STI etiology of the urethral syndrome is suggested by young age, more than one current sexual partner, a new partner within the past month, a partner with urethritis, or coexisting mucopurulent cervicitis (see below). The finding of a single urinary pathogen, such as E. coli or Staphylococcus saprophyticus, at a concentration of ≥10²/mL in a properly collected specimen of midstream urine from a dysuric woman with pyuria indicates probable bacterial UTI, whereas pyuria with <10² conventional uropathogens per milliliter of urine (“sterile” pyuria) suggests acute urethral syndrome due to C. trachomatis or N. gonorrhoeae. Gonorrhea and chlamydial infection should be sought by specific tests (e.g., NAATs of vaginal secretions collected with a swab). Among dysuric women with sterile pyuria caused by infection with N. gonorrhoeae or C. trachomatis, appropriate treatment alleviates dysuria. The role of M. genitalium in the urethral syndrome in women remains undefined.

VULVOVAGINAL INFECTIONS

Abnormal vaginal discharge

If directly questioned about vaginal discharge during routine health checkups, many women acknowledge having nonspecific symptoms of vaginal discharge that do not correlate with objective signs of inflammation or with actual infection. However, unsolicited reporting of abnormal vaginal discharge does suggest bacterial vaginosis or trichomoniasis. Specifically, an abnormally increased amount or an abnormal odor of the discharge is associated with one or both of these conditions. Cervical infection with N. gonorrhoeae or C. trachomatis does not often cause an increased amount or abnormal odor of discharge; however, when these pathogens cause cervicitis, they—like T. vaginalis—often result in an increased number of neutrophils in vaginal fluid, which thus takes on a yellow color. Vulvar conditions such as genital herpes or vulvovaginal candidiasis can cause vulvar pruritus, burning, irritation, or lesions as well as external dysuria (as urine passes over the inflamed vulva or areas of epithelial disruption) or vulvar dyspareunia.

Certain vulvovaginal infections may have serious sequelae. Trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis have all been associated with increased risk of acquisition of HIV infection; bacterial vaginosis may promote HIV transmission from HIV-infected women to their male sex partners. Vaginal trichomoniasis and bacterial vaginosis early in pregnancy independently predict premature onset of labor. Bacterial vaginosis can also lead to anaerobic bacterial infection of the endometrium and salpinges. Vaginitis may be an early and prominent feature of toxic shock syndrome, and recurrent or chronic vulvovaginal candidiasis develops with increased frequency among women who have systemic illnesses, such as diabetes mellitus or HIV-related immunosuppression (although only a very small proportion of women with recurrent vulvovaginal candidiasis in industrialized countries actually have a serious predisposing illness).

Thus vulvovaginal symptoms or signs warrant careful evaluation, including speculum and pelvic examination, simple rapid diagnostic tests, and appropriate therapy specific for the anatomic site and type of infection. Unfortunately, a survey in the United States indicated that clinicians seldom perform the tests required to establish the cause of such symptoms. Further, comparison of telephone and office management of vulvovaginal symptoms has documented the inaccuracy of the former, and comparison of evaluations by nurse-midwives with those by physician-practitioners showed that the practitioners’ clinical evaluations correlated poorly both with the nurses’ evaluations and with diagnostic tests. The diagnosis and treatment of the three most common types of vaginal infection are summarized in Table 35-5.

Inspection of the vulva and perineum may reveal tender genital ulcerations or fissures (typically due to HSV infection or vulvovaginal candidiasis) or discharge visible at the introitus before insertion of a speculum (suggestive of bacterial vaginosis or trichomoniasis). Speculum examination permits the clinician to discern whether the discharge in fact looks abnormal and whether any abnormal discharge in the vagina emanates from the cervical os (mucoid and, if abnormal, yellow) or from the vagina (not mucoid, since the vaginal epithelium does not produce mucus). Symptoms or signs of abnormal vaginal discharge should prompt testing of vaginal fluid for pH, for a fishy odor when mixed with 10% KOH, and for certain microscopic features when mixed with saline (motile trichomonads and/or “clue cells”) and with 10% KOH (pseudohyphae or hyphae indicative of vulvovaginal candidiasis). Additional objective laboratory tests useful for establishing the cause of abnormal vaginal discharge include rapid point-of-care tests for bacterial vaginosis and T. vaginalis, as described below; a DNA probe test (the Affirm test) to detect T. vaginalis and C. albicans as well as the increased concentrations of Gardnerella vaginalis associated with bacterial vaginosis; and a NAAT for T. vaginalis. Gram’s staining of vaginal fluid can be used to score alterations in the vaginal microbiota but is used primarily for research purposes and requires familiarity with the morphotypes and scale involved.

TREATMENT

Vaginal trichomoniasis

(See also Chap. 129) Symptomatic trichomoniasis characteristically produces a profuse, yellow, purulent, homogeneous vaginal discharge and vulvar irritation, sometimes with visible inflammation of the vaginal and vulvar epithelium and petechial lesions on the cervix (the so-called strawberry cervix, usually evident only by colposcopy). The pH of vaginal fluid—normally <4.7—usually rises to ≥5. In women with typical symptoms and signs of trichomoniasis, microscopic examination of vaginal discharge mixed with saline reveals motile trichomonads in most culture-positive cases. However, saline microscopy probably detects only one-half of all cases, and, especially in the absence of symptoms or signs, culture or NAAT is usually required for detection of the organism. NAAT for T. vaginalis is as sensitive as or more sensitive than culture, and NAAT of urine has disclosed surprisingly high prevalences of this pathogen among men at several STD clinics in the United States. Treatment of asymptomatic as well as symptomatic cases reduces rates of transmission and prevents later development of symptoms.

TREATMENT

Bacterial vaginosis

Bacterial vaginosis (formerly termed nonspecific vaginitis, Haemophilus vaginitis, anaerobic vaginitis, or Gardnerella-associated vaginal discharge) is a syndrome of complex etiology that is characterized by symptoms of vaginal malodor and a slightly to moderately increased white discharge, which appears homogeneous, is low in viscosity, and evenly coats the vaginal mucosa. Bacterial vaginosis has been associated with increased risk of acquiring several other genital infections, including those caused by HIV, C. trachomatis, and N. gonorrhoeae. Other risk factors include recent unprotected vaginal intercourse, having a female sex partner, and vaginal douching. Although bacteria associated with bacterial vaginosis have been detected under the foreskin of uncircumcised men, metronidazole treatment of male partners has not reduced the rate of recurrence among affected women.

Among women with bacterial vaginosis, culture of vaginal fluid has shown markedly increased prevalences and concentrations of G. vaginalis, Mycoplasma hominis, and several anaerobic bacteria (e.g., Mobiluncus, Prevotella [formerly Bacteroides], and some Peptostreptococcus species) as well as an absence of hydrogen peroxide–producing Lactobacillus species that constitute most of the normal vaginal microbiota and help protect against certain cervical and vaginal infections. Broad-range polymerase chain reaction (PCR) amplification of 16S rDNA in vaginal fluid, with subsequent identification of specific bacterial species by various methods, has documented an even greater and unexpected bacterial diversity, including several unique species not previously cultivated (e.g., three species in the order Clostridiales that appear to be specific for bacterial vaginosis and are associated with metronidazole treatment failure [Fig. 35-2]). Also detected are DNA sequences related to Atopobium vaginae, an organism that is strongly associated with bacterial vaginosis, is resistant to metronidazole, and is also associated with recurrent bacterial vaginosis after metronidazole treatment. Other genera newly implicated in bacterial vaginosis include Megasphaera, Leptotrichia, Eggerthella, and Dialister.

Bacterial vaginosis is conventionally diagnosed clinically with the Amsel criteria, which include any three of the following four clinical abnormalities: (1) objective signs of increased white homogeneous vaginal discharge; (2) a vaginal discharge pH of >4.5; (3) liberation of a distinct fishy odor (attributable to volatile amines such as trimethylamine) immediately after vaginal secretions are mixed with a 10% solution of KOH; and (4) microscopic demonstration of “clue cells” (vaginal epithelial cells coated with coccobacillary organisms, which have a granular appearance and indistinct borders; Fig. 35-3) on a wet mount prepared by mixing vaginal secretions with normal saline in a ratio of ~1:1.

TREATMENT

Vulvovaginal pruritus, burning, or irritation

Vulvovaginal candidiasis produces vulvar pruritus, burning, or irritation, generally without symptoms of increased vaginal discharge or malodor. Genital herpes can produce similar symptoms, with lesions sometimes difficult to distinguish from the fissures and inflammation caused by candidiasis. Signs of vulvovaginal candidiasis include vulvar erythema, edema, fissures, and tenderness. With candidiasis, a white scanty vaginal discharge sometimes takes the form of white thrush-like plaques or cottage cheese–like curds adhering loosely to the vaginal epithelium. C. albicans accounts for nearly all cases of symptomatic vulvovaginal candidiasis, which probably arise from endogenous strains of C. albicans that have colonized the vagina or the intestinal tract. Complicated vulvovaginal candidiasis includes cases that recur four or more times per year; are unusually severe; are caused by non-albicans Candida species; or occur in women with uncontrolled diabetes, debilitation, immunosuppression, or pregnancy.

In addition to compatible clinical symptoms, the diagnosis of vulvovaginal candidiasis usually involves the demonstration of pseudohyphae or hyphae by microscopic examination of vaginal fluid mixed with saline or 10% KOH or subjected to Gram’s staining. Microscopic examination is less sensitive than culture but correlates better with symptoms. Culture is typically reserved for cases that do not respond to standard first-line antimycotic agents and is undertaken to rule out imidazole or azole resistance (often associated with Candida glabrata) or before the initiation of suppressive antifungal therapy for recurrent disease.

TREATMENT

Other causes of vaginal discharge or vaginitis

In the ulcerative vaginitis associated with staphylococcal toxic shock syndrome, Staphylococcus aureus should be promptly identified in vaginal fluid by Gram’s stain and by culture. In desquamative inflammatory vaginitis, smears of vaginal fluid reveal neutrophils, massive vaginal epithelial-cell exfoliation with increased numbers of parabasal cells, and gram-positive cocci; this syndrome may respond to treatment with 2% clindamycin cream, often given in combination with topical steroid preparations for several weeks. Additional causes of vaginitis and vulvovaginal symptoms include retained foreign bodies (e.g., tampons), cervical caps, vaginal spermicides, vaginal antiseptic preparations or douches, vaginal epithelial atrophy (in postmenopausal women or during prolonged breast-feeding in the postpartum period), allergic reactions to latex condoms, vaginal aphthae associated with HIV infection or Behçet’s syndrome, and vestibulitis (a poorly understood syndrome).

MUCOPURULENT CERVICITIS

Mucopurulent cervicitis (MPC) refers to inflammation of the columnar epithelium and subepithelium of the endocervix and of any contiguous columnar epithelium that lies exposed in an ectopic position on the ectocervix. MPC in women represents the “silent partner” of urethritis in men, being equally common and often caused by the same agents (N. gonorrhoeae, C. trachomatis, or—as shown by case–control studies—M. genitalium); however, MPC is more difficult than urethritis to recognize. As the most common manifestation of these serious bacterial infections in women, MPC can be a harbinger or sign of upper genital tract infection, also known as pelvic inflammatory disease (PID; see below). In pregnant women, MPC can lead to obstetric complications. In a prospective study in Seattle of 167 consecutive patients with MPC (defined on the basis of yellow endocervical mucopus or ≥30 polymorphonuclear leukocytes [PMNs]/1000× microscopic field) who were seen at STD clinics during the 1980s, slightly more than one-third of cervicovaginal specimens tested for C. trachomatis, N. gonorrhoeae, M. genitalium, HSV, and T. vaginalis revealed no identifiable etiology (Fig. 35-4). More recently, a study in Baltimore using NAATs for these pathogens still failed to identify a microbiologic etiology in nearly one-half of the 133 women with MPC.

The diagnosis of MPC rests on the detection of cardinal signs at the cervix, including yellow mucopurulent discharge from the cervical os, endocervical bleeding upon gentle swabbing, and edematous cervical ectopy (see below); the latter two findings are somewhat more common with MPC due to chlamydial infection, but signs alone do not allow a distinction between the causative pathogens. Unlike the endocervicitis produced by gonococcal or chlamydial infection, cervicitis caused by HSV produces ulcerative lesions on the stratified squamous epithelium of the ectocervix as well as on the columnar epithelium. Yellow cervical mucus on a white swab removed from the endocervix indicates the presence of PMNs. Gram’s staining may confirm their presence, although it adds relatively little to the diagnostic value of assessment for cervical signs. The presence of ≥20 PMNs/1000× microscopic field within strands of cervical mucus not contaminated by vaginal squamous epithelial cells or vaginal bacteria indicates endocervicitis. Detection of intracellular gram-negative diplococci in carefully collected endocervical mucus is quite specific but ≤50% sensitive for gonorrhea. Therefore, specific and sensitive tests for N. gonorrhoeae as well as for C. trachomatis (e.g., NAATs) are always indicated in the evaluation of MPC.

TREATMENT

CERVICAL ECTOPY

Cervical ectopy, often mislabeled “cervical erosion,” is easily confused with infectious endocervicitis. Ectopy represents the presence of the one-cell-thick columnar epithelium extending from the endocervix out onto the visible ectocervix. In ectopy, the cervical os may contain clear or slightly cloudy mucus but usually not yellow mucopus. Colposcopy shows intact epithelium. Normally found during adolescence and early adulthood, ectopy gradually recedes through the second and third decades of life, as squamous metaplasia replaces the ectopic columnar epithelium. Oral contraceptive use favors the persistence or reappearance of ectopy, while smoking apparently accelerates squamous metaplasia. Cauterization of ectopy is not warranted. Ectopy may render the cervix more susceptible to infection with N. gonorrhoeae, C. trachomatis, or HIV.

PELVIC INFLAMMATORY DISEASE

The term pelvic inflammatory disease usually refers to infection that ascends from the cervix or vagina to involve the endometrium and/or fallopian tubes. Infection can extend beyond the reproductive tract to cause pelvic peritonitis, generalized peritonitis, perihepatitis, perisplenitis, or pelvic abscess. Rarely, infection not related to specific sexually transmitted pathogens extends secondarily to the pelvic organs (1) from adjacent foci of inflammation (e.g., appendicitis, regional ileitis, or diverticulitis) or bacterial vaginosis, (2) as a result of hematogenous dissemination (e.g., of tuberculosis or staphylococcal bacteremia), or (3) as a complication of certain tropical diseases (e.g., schistosomiasis). Intrauterine infection can be primary (spontaneously occurring and usually sexually transmitted) or secondary to invasive intrauterine surgical procedures (e.g., dilation and curettage, termination of pregnancy, insertion of an intrauterine device [IUD], or hysterosalpingography) or to parturition.

Etiology

The agents most often implicated in acute PID include the primary causes of endocervicitis (e.g., N. gonorrhoeae and C. trachomatis) and organisms that can be regarded as components of an altered vaginal microbiota. In general, PID is most often caused by N. gonorrhoeae where there is a high incidence of gonorrhea—e.g., in inner-city populations in the United States. In case–control studies, M. genitalium has also been significantly associated with histopathologic diagnoses of endometritis and with salpingitis.

Anaerobic and facultative organisms (especially Prevotella species, peptostreptococci, E. coli, Haemophilus influenzae, and group B streptococci) as well as genital mycoplasmas have been isolated from the peritoneal fluid or fallopian tubes in a varying proportion (typically one-fourth to one-third) of women with PID studied in the United States. The difficulty of determining the exact microbial etiology of an individual case of PID—short of using invasive procedures for specimen collection—has implications for the approach to empirical antimicrobial treatment of this infection.

Epidemiology

In the United States, the estimated annual number of initial visits to physicians’ offices for PID by women 15–44 years of age fell from an average of 400,000 during the 1980s to 250,000 in 1999 and then to 90,000 in 2011. Hospitalizations for acute PID in the United States also declined steadily throughout the 1980s and early 1990s but have remained fairly constant at 70,000–100,000 per year since 1995. Important risk factors for acute PID include the presence of endocervical infection or bacterial vaginosis, a history of salpingitis or of recent vaginal douching, and recent insertion of an IUD. Certain other iatrogenic factors, such as dilation and curettage or cesarean section, can increase the risk of PID, especially among women with endocervical gonococcal or chlamydial infection or bacterial vaginosis. Symptoms of N. gonorrhoeae–associated and C. trachomatis–associated PID often begin during or soon after the menstrual period; this timing suggests that menstruation is a risk factor for ascending infection from the cervix and vagina. Experimental inoculation of the fallopian tubes of nonhuman primates has shown that repeated exposure to C. trachomatis leads to the greatest degree of tissue inflammation and damage; thus, immunopathology probably contributes to the pathogenesis of chlamydial salpingitis. Women using oral contraceptives appear to be at decreased risk of symptomatic PID, and tubal sterilization reduces the risk of salpingitis by preventing intraluminal spread of infection into the tubes.

Clinical manifestations

Endometritis: a clinical pathologic syndrome

A study of women with clinically suspected PID who were undergoing both endometrial biopsy and laparoscopy showed that those with endometritis alone differed from those who also had salpingitis in significantly less often having lower-quadrant, adnexal, or cervical motion or abdominal rebound tenderness; fever; or elevated C-reactive protein levels. In addition, women with endometritis alone differed from those with neither endometritis nor salpingitis in more often having gonorrhea, chlamydial infection, and risk factors such as douching or IUD use. Thus, women with endometritis alone were intermediate between those with neither endometritis nor salpingitis and those with salpingitis with respect to risk factors, clinical manifestations, cervical infection prevalence, and elevated C-reactive protein level. Women with endometritis alone are at lower risk of subsequent tubal occlusion and resulting infertility than are those with salpingitis.

Salpingitis

Symptoms of nontuberculous salpingitis classically evolve from a yellow or malodorous vaginal discharge caused by MPC and/or bacterial vaginosis to midline abdominal pain and abnormal vaginal bleeding caused by endometritis and then to bilateral lower abdominal and pelvic pain caused by salpingitis, with nausea, vomiting, and increased abdominal tenderness if peritonitis develops.

The abdominal pain in nontuberculous salpingitis is usually described as dull or aching. In some cases, pain is lacking or atypical, but active inflammatory changes are found in the course of an unrelated evaluation or procedure, such as a laparoscopic evaluation for infertility. Abnormal uterine bleeding precedes or coincides with the onset of pain in ~40% of women with PID, symptoms of urethritis (dysuria) occur in 20%, and symptoms of proctitis (anorectal pain, tenesmus, and rectal discharge or bleeding) are occasionally seen in women with gonococcal or chlamydial infection.

Speculum examination shows evidence of MPC (yellow endocervical discharge, easily induced endocervical bleeding) in the majority of women with gonococcal or chlamydial PID. Cervical motion tenderness is produced by stretching of the adnexal attachments on the side toward which the cervix is pushed. Bimanual examination reveals uterine fundal tenderness due to endometritis and abnormal adnexal tenderness due to salpingitis that is usually, but not necessarily, bilateral. Adnexal swelling is palpable in about one-half of women with acute salpingitis, but evaluation of the adnexae in a patient with marked tenderness is not reliable. The initial temperature is >38°C in only about one-third of patients with acute salpingitis. Laboratory findings include elevation of the erythrocyte sedimentation rate (ESR) in 75% of patients with acute salpingitis and elevation of the peripheral white blood cell count in up to 60%.

Unlike nontuberculous salpingitis, genital tuberculosis often occurs in older women, many of whom are postmenopausal. Presenting symptoms include abnormal vaginal bleeding, pain (including dysmenorrhea), and infertility. About one-quarter of these women have had adnexal masses. Endometrial biopsy shows tuberculous granulomas and provides optimal specimens for culture.

Perihepatitis and periappendicitis

Pleuritic upper-abdominal pain and tenderness, usually localized to the right upper quadrant (RUQ), develop in 3–10% of women with acute PID. Symptoms of perihepatitis arise during or after the onset of symptoms of PID and may overshadow lower abdominal symptoms, thereby leading to a mistaken diagnosis of cholecystitis. In perhaps 5% of cases of acute salpingitis, early laparoscopy reveals perihepatic inflammation ranging from edema and erythema of the liver capsule to exudate with fibrinous adhesions between the visceral and parietal peritoneum. When treatment is delayed and laparoscopy is performed late, dense “violin-string” adhesions can be seen over the liver; chronic exertional or positional RUQ pain ensues when traction is placed on the adhesions. Although perihepatitis, also known as the Fitz-Hugh–Curtis syndrome, was for many years specifically attributed to gonococcal salpingitis, most cases are now attributed to chlamydial salpingitis. In patients with chlamydial salpingitis, serum titers of microimmunofluorescent antibody to C. trachomatis are typically much higher when perihepatitis is present than when it is absent.

Physical findings include RUQ tenderness and usually include adnexal tenderness and cervicitis, even in patients whose symptoms do not suggest salpingitis. Results of liver function tests and RUQ ultrasonography are nearly always normal. The presence of MPC and pelvic tenderness in a young woman with subacute pleuritic RUQ pain and normal ultrasonography of the gallbladder points to a diagnosis of perihepatitis.

Periappendicitis (appendiceal serositis without involvement of the intestinal mucosa) has been found in ~5% of patients undergoing appendectomy for suspected appendicitis and can occur as a complication of gonococcal or chlamydial salpingitis.

Among women with salpingitis, HIV infection is associated with increased severity of salpingitis and with tuboovarian abscess requiring hospitalization and surgical drainage. Nonetheless, among women with HIV infection and salpingitis, the clinical response to conventional antimicrobial therapy (coupled with drainage of tuboovarian abscess, when found) has usually been satisfactory.

Diagnosis

Treatment appropriate for PID must not be withheld from patients who have an equivocal diagnosis; it is better to err on the side of overdiagnosis and overtreatment. On the other hand, it is essential to differentiate between salpingitis and other pelvic pathology, particularly surgical emergencies such as appendicitis and ectopic pregnancy.

Nothing short of laparoscopy definitively identifies salpingitis, but routine laparoscopy to confirm suspected salpingitis is generally impractical. Most patients with acute PID have lower abdominal pain of <3 weeks’ duration, pelvic tenderness on bimanual pelvic examination, and evidence of lower genital tract infection (e.g., MPC). Approximately 60% of such patients have salpingitis at laparoscopy, and perhaps 10–20% have endometritis alone. Among the patients with these findings, a rectal temperature >38°C, a palpable adnexal mass, and elevation of the ESR to >15 mm/h also raise the probability of salpingitis, which has been found at laparoscopy in 68% of patients with one of these additional findings, 90% of patients with two, and 96% of patients with three. However, only 17% of all patients with laparoscopy-confirmed salpingitis have had all three additional findings.

In a woman with pelvic pain and tenderness, increased numbers of PMNs (30 per 1000× microscopic field in strands of cervical mucus) or leukocytes outnumbering epithelial cells in vaginal fluid (in the absence of trichomonal vaginitis, which also produces PMNs in vaginal discharge) increase the predictive value of a clinical diagnosis of acute PID, as do onset with menses, history of recent abnormal menstrual bleeding, presence of an IUD, history of salpingitis, and sexual exposure to a male with urethritis. Appendicitis or another disorder of the gut is favored by the early onset of anorexia, nausea, or vomiting; the onset of pain later than day 14 of the menstrual cycle; or unilateral pain limited to the right or left lower quadrant. Whenever the diagnosis of PID is being considered, serum assays for human β-chorionic gonadotropin should be performed; these tests are usually positive with ectopic pregnancy. Ultrasonography and magnetic resonance imaging (MRI) can be useful for the identification of tuboovarian or pelvic abscess. MRI of the tubes can also show increased tubal diameter, intratubal fluid, or tubal wall thickening in cases of salpingitis.

The primary and uncontested value of laparoscopy in women with lower abdominal pain is for the exclusion of other surgical problems. Some of the most common or serious problems that may be confused with salpingitis (e.g., acute appendicitis, ectopic pregnancy, corpus luteum bleeding, ovarian tumor) are unilateral. Unilateral pain or pelvic mass, although not incompatible with PID, is a strong indication for laparoscopy unless the clinical picture warrants laparotomy instead. Atypical clinical findings such as the absence of lower genital tract infection, a missed menstrual period, a positive pregnancy test, or failure to respond to appropriate therapy are other common indications for laparoscopy. Endometrial biopsy is relatively sensitive and specific for the diagnosis of endometritis, which correlates well with the presence of salpingitis.

Vaginal or endocervical swab specimens should be examined by NAATs for N. gonorrhoeae and C. trachomatis. At a minimum, vaginal fluid should be evaluated for the presence of PMNs, and endocervical secretions ideally should be assessed by Gram’s staining for PMNs and gram-negative diplococci, which indicate gonococcal infection. The clinical diagnosis of PID made by expert gynecologists is confirmed by laparoscopy or endometrial biopsy in ~90% of women who also have cultures positive for N. gonorrhoeae or C. trachomatis. Even among women with no symptoms suggestive of acute PID who were attending an STD clinic or a gynecology clinic in Pittsburgh, endometritis was significantly associated with endocervical gonorrhea or chlamydial infection or with bacterial vaginosis, being detected in 26%, 27%, and 15% of women with these conditions, respectively.

TREATMENT

Prognosis

Late sequelae include infertility due to bilateral tubal occlusion, ectopic pregnancy due to tubal scarring without occlusion, chronic pelvic pain, and recurrent salpingitis. The overall post-salpingitis risk of infertility due to tubal occlusion in a large study in Sweden was 11% after one episode of salpingitis, 23% after two episodes, and 54% after three or more episodes. A University of Washington study found a sevenfold increase in the risk of ectopic pregnancy and an eightfold increase in the rate of hysterectomy after PID.

Prevention

A randomized controlled trial designed to determine whether selective screening for chlamydial infection reduces the risk of subsequent PID showed that women randomized to undergo screening had a 56% lower rate of PID over the following year than did women receiving the usual care without screening. This report helped prompt U.S. national guidelines for risk-based chlamydial screening of young women to reduce the incidence of PID and the prevalence of post-PID sequelae, while also reducing sexual transmission of C. trachomatis. The CDC and the U.S. Preventive Services Task Force recommend that sexually active women ≤25 years of age be screened for genital chlamydial infection annually. Despite this recommendation, screening coverage in many primary care settings remains low.

ULCERATIVE GENITAL OR PERIANAL LESIONS

Genital ulceration reflects a set of important STIs, most of which sharply increase the risk of sexual acquisition and shedding of HIV. In a 1996 study of genital ulcers in 10 of the U.S. cities with the highest rates of primary syphilis, PCR testing of ulcer specimens demonstrated HSV in 62% of patients, Treponema pallidum (the cause of syphilis) in 13%, and Haemophilus ducreyi (the cause of chancroid) in 12–20%. Today, genital herpes represents an even higher proportion of genital ulcers in the United States and other industrialized countries.

In Asia and Africa, chancroid (Fig. 35-5) was once considered the most common type of genital ulcer, followed in frequency by primary syphilis and then genital herpes (Fig. 35-6). With increased efforts to control chancroid and syphilis and widespread use of broad-spectrum antibiotics to treat STI-related syndromes, together with more frequent recurrences or persistence of genital herpes attributable to HIV infection, PCR testing of genital ulcers now clearly implicates genital herpes as by far the most common cause of genital ulceration in most developing countries. LGV due to C. trachomatis (Fig. 35-7) and donovanosis (granuloma inguinale, due to Klebsiella granulomatis; see Fig. 70-1) continue to cause genital ulceration in some developing countries. LGV virtually disappeared in industrialized countries during the first 20 years of the HIV pandemic, but outbreaks are again occurring in Europe (including the United Kingdom), in North America, and in Australia. In these outbreaks, LGV typically presents as proctitis, with or without anal lesions, in men who report unprotected receptive anal intercourse, very often in association with HIV and/or hepatitis C virus infection; the latter may be an acute infection acquired through the same exposure. Other causes of genital ulcers include (1) candidiasis and traumatized genital warts—both readily recognized; (2) lesions due to genital involvement by more widespread dermatoses; (3) cutaneous manifestations of systemic diseases such as genital mucosal ulceration in Stevens-Johnson syndrome or Behçet’s disease; (4) superinfections of lesions that may originally have been sexually acquired (for example, methicillin-resistant S. aureus complicating a genital ulcer due to HSV-2); and (5) localized drug reactions, such as the ulcers occasionally seen with topical paromomycin cream or boric acid preparations.

Diagnosis

Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings (Table 35-7) and epidemiologic considerations can usually guide initial management (Table 35-8) pending results of specific tests. Clinicians should order a rapid serologic test for syphilis in all cases of genital ulcer. To evaluate lesions except those highly characteristic of infection with HSV (i.e., those with herpetic vesicles), dark-field microscopy, direct immunofluorescence, and PCR for T. pallidum can be useful but are rarely available today in most countries. It is important to note that 30% of syphilitic chancres—the primary ulcer of syphilis—are associated with an initially nonreactive syphilis serology. All patients presenting with genital ulceration should be counseled and tested for HIV infection.

Typical vesicles or pustules or a cluster of painful ulcers preceded by vesiculopustular lesions suggests genital herpes. These typical clinical manifestations make detection of the virus optional; however, many patients want confirmation of the diagnosis, and differentiation of HSV-1 from HSV-2 has prognostic implications, because the latter causes more frequent genital recurrences.

Painless, nontender, indurated ulcers with firm, nontender inguinal adenopathy suggest primary syphilis. If results of dark-field examination and a rapid serologic test for syphilis are initially negative, presumptive therapy should be provided on the basis of the individual’s risk. For example, with increasing rates of syphilis among MSM in the United States, most experts would not withhold therapy for this infection pending watchful waiting and/or subsequent detection of seroconversion. Repeated serologic testing for syphilis 1 or 2 weeks after treatment of seronegative primary syphilis usually demonstrates seroconversion.

“Atypical” or clinically trivial ulcers may be more common manifestations of genital herpes than classic vesiculopustular lesions. Specific tests for HSV in such lesions are therefore indicated (Chap. 88). Commercially available type-specific serologic tests for serum antibody to HSV-2 may give negative results, especially when patients present early with the initial episode of genital herpes or when HSV-1 is the cause of genital herpes (as is often the case today). Furthermore, a positive test for antibody to HSV-2 does not prove that the current lesions are herpetic, because nearly one-fifth of the general population of the United States (and no doubt a higher proportion of those at risk for other STIs) becomes seropositive for HSV-2 during early adulthood. Although even “type-specific” tests for HSV-2 that are commercially available in the United States are not 100% specific, a positive HSV-2 serology does enable the clinician to tell the patient that he or she has probably had genital herpes, should learn to recognize symptoms, and should avoid sex during recurrences. In addition, because genital shedding and sexual transmission of HSV-2 often occur in the absence of symptoms and signs of recurrent herpetic lesions, persons who have a history of genital herpes or who are seropositive for HSV-2 should consider the use of condoms or suppressive antiviral therapy, both of which can reduce the risk of HSV-2 transmission to a sexual partner.

Demonstration of H. ducreyi by culture (or by PCR, where available) is most useful when ulcers are painful and purulent, especially if inguinal lymphadenopathy with fluctuance or overlying erythema is noted; if chancroid is prevalent in the community; or if the patient has recently had a sexual exposure elsewhere in a chancroid-endemic area (e.g., a developing country). Enlarged, fluctuant lymph nodes should be aspirated for culture or PCR to detect H. ducreyi as well as for Gram’s staining and culture to rule out the presence of other pyogenic bacteria.

When genital ulcers persist beyond the natural history of initial episodes of herpes (2–3 weeks) or of chancroid or syphilis (up to 6 weeks) and do not resolve with syndrome-based antimicrobial therapy, then—in addition to the usual tests for herpes, syphilis, and chancroid—biopsy is indicated to exclude donovanosis, carcinoma, and other nonvenereal dermatoses. If not performed previously, HIV serology should be standard because chronic, persistent genital herpes is common in AIDS.

TREATMENT

PROCTITIS, PROCTOCOLITIS, ENTEROCOLITIS, AND ENTERITIS

Sexually acquired proctitis, with inflammation limited to the rectal mucosa (the distal 10–12 cm), results from direct rectal inoculation of typical STD pathogens. In contrast, inflammation extending from the rectum to the colon (proctocolitis), involving both the small and the large bowel (enterocolitis), or involving the small bowel alone (enteritis) can result from ingestion of typical intestinal pathogens through oral–anal exposure during sexual contact. Anorectal pain and mucopurulent, bloody rectal discharge suggest proctitis or protocolitis. Proctitis commonly produces tenesmus (causing frequent attempts to defecate, but not true diarrhea) and constipation, whereas proctocolitis and enterocolitis more often cause true diarrhea. In all three conditions, anoscopy usually shows mucosal exudate and easily induced mucosal bleeding (i.e., a positive “wipe test”), sometimes with petechiae or mucosal ulcers. Exudate should be sampled for Gram’s staining and other microbiologic studies. Sigmoidoscopy or colonoscopy shows inflammation limited to the rectum in proctitis or disease extending at least up into the sigmoid colon in proctocolitis.

The AIDS era brought an extraordinary shift in the clinical and etiologic spectrum of intestinal infections among MSM. The number of cases of the acute intestinal STIs described above fell as high-risk sexual behaviors became less common in this group. At the same time, the number of AIDS-related opportunistic intestinal infections increased rapidly, many associated with chronic or recurrent symptoms. The incidence of these opportunistic infections has since fallen with increasingly widespread coverage of HIV-infected persons with effective antiretroviral therapy. Two species initially isolated in association with intestinal symptoms in MSM—now known as Helicobacter cinaedi and H. fennelliae—have both been isolated from the blood of HIV-infected men and other immunosuppressed persons, often in association with a syndrome of multifocal dermatitis and arthritis.

Acquisition of HSV, N. gonorrhoeae, or C. trachomatis (including LGV strains of C. trachomatis) during receptive anorectal intercourse causes most cases of infectious proctitis in women and MSM. Primary and secondary syphilis can also produce anal or anorectal lesions, with or without symptoms. Gonococcal or chlamydial proctitis typically involves the most distal rectal mucosa and the anal crypts and is clinically mild, without systemic manifestations. In contrast, primary proctitis due to HSV and proctocolitis due to the strains of C. trachomatis that cause LGV usually produce severe anorectal pain and often cause fever. Perianal ulcers and inguinal lymphadenopathy, most commonly due to HSV, can also occur with LGV or syphilis. Sacral nerve root radiculopathies, usually presenting as urinary retention, laxity of the anal sphincter, or constipation, may complicate primary herpetic proctitis. In LGV, rectal biopsy typically shows crypt abscesses, granulomas, and giant cells—findings resembling those in Crohn’s disease; such findings should always prompt rectal culture and serology for LGV, which is a curable infection. Syphilis can also produce rectal granulomas, usually in association with infiltration by plasma cells or other mononuclear cells. Syphilis, LGV, and HSV infection involving the rectum can produce perirectal adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal lymph nodes.

Diarrhea and abdominal bloating or cramping pain without anorectal symptoms and with normal findings on anoscopy and sigmoidoscopy occur with inflammation of the small intestine (enteritis) or with proximal colitis. In MSM without HIV infection, enteritis is often attributable to Giardia lamblia. Sexually acquired proctocolitis is most often due to Campylobacter or Shigella species.

TREATMENT

Prevention and control of STIs require the following:

1. Reduction of the average rate of sexual exposure to STIs through alteration of sexual risk behaviors and behavioral norms among both susceptible and infected persons in all population groups. The necessary changes include reduction in the total number of sexual partners and the number of concurrent sexual partners.

2. Reduction of the efficiency of transmission through the promotion of safer sexual practices, the use of condoms during casual or commercial sex, vaccination against HBV and HPV infection, male circumcision (which reduces risk of acquisition of HIV infection, chancroid, and perhaps other STIs), and a growing number of other approaches (e.g., early detection and treatment of other STIs to reduce the efficiency of sexual transmission of HIV). Longitudinal studies have shown that consistent condom use is associated with significant protection of both males and females against all STIs that have been examined, including HIV, HPV, and HSV infections as well as gonorrhea and chlamydial infection. The only exceptions are probably sexually transmitted Pthirus pubis and Sarcoptes scabiei infestations.

3. Shortening of the duration of infectivity of STIs through early detection and curative or suppressive treatment of patients and their sexual partners.

Financial and time constraints imposed by many clinical practices, along with the reluctance of some clinicians to ask questions about stigmatized sexual behaviors, often curtail screening and prevention services. As outlined in Fig. 35-8, the success of clinicians’ efforts to detect and treat STIs depends in part on societal efforts to teach young people how to recognize symptoms of STIs; to motivate individuals with symptoms to seek care promptly; to educate persons who are at risk but have no symptoms about what tests they should undergo routinely; and to make high-quality, appropriate care accessible, affordable, and acceptable, especially to the young indigent patients most likely to acquire an STI.

Because many infected individuals develop no symptoms or fail to recognize and report symptoms, clinicians should routinely perform an STI risk assessment for teenagers and young adults as a guide to selective screening. As stated earlier, U.S. Preventive Services Task Force Guidelines recommend screening sexually active female patients ≤25 years of age for C. trachomatis whenever they present for health care (at least once a year); older women should be tested if they have more than one sexual partner, have begun a new sexual relationship since the previous test, or have another STI diagnosed. In women 25–29 years of age, chlamydial infection is uncommon but still may reach a prevalence of 3–5% in some settings; information provided by women in this age group on a sex partner’s concurrency (whether a male partner has had another sex partner during the time they have been together) is helpful in identifying women at increased risk. In some regions of the United States, widespread selective screening and treatment of young women for cervical C. trachomatis infection have been associated with a 50–60% drop in prevalence. Such screening and treatment also protect the individual woman from PID. Sensitive urine-based genetic amplification tests permit expansion of screening to men, teenage boys, and girls in settings where examination is not planned or is impractical (e.g., during preparticipation sports examinations or during initial medical evaluation of adolescent girls). Vaginal swabs—collected either by the health care provider at a pelvic examination or by the woman herself—are highly sensitive and specific for the diagnosis of chlamydial and gonococcal infection; they are now the preferred type of specimen for screening and diagnosis of these infections.

Although gonorrhea is now substantially less common than chlamydial infection in industrialized countries, screening tests for N. gonorrhoeae are still appropriate for women and teenage girls attending STD clinics and for sexually active teens and young women from areas of high gonorrhea prevalence. Multiplex NAATs that combine screening for N. gonorrhoeae and C. trachomatis—and, more recently, for T. vaginalis—in a single low-cost assay now facilitate the prevention and control of these infections for populations at high risk.

All patients who have newly detected STIs or are at high risk for STIs according to routine risk assessment as well as all pregnant women should be encouraged to undergo serologic testing for syphilis and HIV infection, with appropriate HIV counseling before and after testing. Randomized trials have shown that risk-reduction counseling of patients with STIs significantly lowers subsequent risk of acquiring an STI; such counseling should now be considered a standard component of STI management. Preimmunization serologic testing for antibody to HBV is indicated for unvaccinated persons who are known to be at high risk, such as MSM and people who use injection drugs. In most young persons, however, it is more cost-effective to vaccinate against HBV without serologic screening. It is important to recognize that, while immunization against HBV has contributed to marked reductions in the incidence of infection with this virus, the majority of new cases that do occur are acquired through sex. In 2006, the Advisory Committee on Immunization Practices (ACIP) of the CDC recommended the following: (1) Universal hepatitis B vaccination should be implemented for all unvaccinated adults in settings in which a high proportion of adults have risk factors for HBV infection (e.g., STD clinics, HIV testing and treatment facilities, drug-abuse treatment and prevention settings, health care settings targeting services to injection drug users or MSM, and correctional facilities). (2) In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health care providers should inform all patients about the health benefits of vaccination, the risk factors for HBV infection, and the persons for whom vaccination is recommended and should vaccinate adults who report risk factors for HBV infection as well as any adult who requests protection from HBV infection. To promote vaccination in all settings, health care providers should implement standing orders to identify adults recommended for hepatitis B vaccination, should administer hepatitis B vaccine as part of routine clinical services, should not require acknowledgment of an HBV infection risk factor for adult vaccination, and should use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination.

In 2007, the ACIP recommended routine immunization of 9- to 26-year-old girls and women with the quadrivalent HPV vaccine (against HPV types 6, 11, 16, and 18) approved by the U.S. Food and Drug Administration; the optimal age for recommended vaccination is 11–12 years because of the very high risk of HPV infection after sexual debut. In 2009, the ACIP added bivalent HPV vaccine (against types 6 and 11) as an option and expanded the groups in which immunization (with either quadrivalent or bivalent vaccine) is safe and effective to include boys and men 9–26 years old. HPV vaccines offering broader protection against additional oncogenic HPV types are anticipated. Since 2011, the ACIP has recommended routine administration of quadrivalent HPV vaccine to boys at 11 or 12 years of age and to males 13–21 years of age who have not yet been vaccinated or who have not completed the three-dose vaccine series; men 22–26 years of age may also be vaccinated.

Partner notification is the process of identifying and informing partners of infected patients about possible exposure to an STI and of examining, testing, and treating partners as appropriate. In a series of 22 reports concerning partner notification during the 1990s, index patients with gonorrhea or chlamydial infection named a mean of 0.75–1.6 partners, of whom one-fourth to one-third were infected; those with syphilis named 1.8–6.3 partners, with one-third to one-half infected; and those with HIV infection named 0.76–5.31 partners, with up to one-fourth infected. Persons who transmit infection or who have recently been infected and are still in the incubation period usually have no symptoms or only mild symptoms and seek medical attention only when notified of their exposure. Therefore, the clinician must encourage patients to participate in partner notification, must ensure that exposed persons are notified and treated, and must guarantee confidentiality to all involved. In the United States, local health departments often offer assistance in partner notification, treatment, and/or counseling. It seems both feasible and most useful to notify those partners exposed within the patient’s likely period of infectiousness, which is often considered the preceding 1 month for gonorrhea, 1–2 months for chlamydial infection, and up to 3 months for early syphilis.

Persons with a new-onset STI always have a source contact who gave them the infection; in addition, they may have a secondary (spread or exposed) contact with whom they had sex after becoming infected. The identification and treatment of these two types of contacts have different objectives. Treatment of the source contact (often a casual contact) benefits the community by preventing further transmission and benefits the source contact; treatment of the recently exposed secondary contact (typically a spouse or another steady sexual partner) prevents the development of serious complications (such as PID) in the partner, reinfection of the index patient, and further spread of infection. A survey of a random sample of U.S. physicians found that most instructed patients to abstain from sex during treatment, to use condoms, and to inform their sex partners after being diagnosed with gonorrhea, chlamydial infection, or syphilis; physicians sometimes gave the patients drugs for their partners. However, follow-up of the partners by physicians was infrequent. A randomized trial compared patients’ delivery of therapy to partners exposed to gonorrhea or chlamydial infection with conventional notification and advice to partners to seek evaluation for STD; patients’ delivery of partners’ therapy, also known as expedited partner therapy (EPT), significantly reduced combined rates of reinfection of the index patient with N. gonorrhoeae or C. trachomatis. State-by-state variations in regulations governing this approach have not been well defined, but the 2010 CDC STD treatment guidelines and the EPT final report of 2006 (http://www.cdc.gov/std/treatment/EPTFinalReport2006.pdf) describe its potential use. Currently, EPT is commonly used by many practicing physicians. Its legal status varies by state, but EPT is now permissible in 38 states and potentially allowable in another 9. (Updated information on the legal status of EPT is available at http://www.cdc.gov/std/ept.)

In summary, clinicians and public health agencies share responsibility for the prevention and control of STIs. In the current health care environment, the role of primary care clinicians has become increasingly important in STI prevention as well as in diagnosis and treatment, and the resurgence of bacterial STIs like syphilis and LGV among MSM—particularly those co-infected with HIV—emphasizes the need for risk assessment and routine screening.