Chapter 14: Sexually Transmitted Diseases

General Considerations

Sexually transmitted diseases (STDs) include sexually transmitted infections and the clinical syndromes they cause. There are an estimated 20 million new STDs in the United States annually, almost half of them among persons aged 15–24 years.

Although all sexually active individuals are susceptible to infection, adolescents and young adults are most commonly affected. Reasons for this include: (1) an attitude of invincibility, (2) lack of knowledge about the risks and consequences of STDs, and (3) barriers to health care access.

This chapter emphasizes the clinical presentation, diagnostic evaluation, and treatment of STDs commonly found in the United States. Readers of this chapter should be able to:

• Differentiate common STDs on the basis of clinical information and laboratory testing.

• Treat STDs according to current guidelines.

• Intervene in patients’ lives to reduce risk of future STD acquisition.

The discussion draws greatly from the most recent Centers for Disease Control and Prevention (CDC) guidelines for treatment of STDs. The authors are indebted to the individuals who worked to develop these recommendations.

Federal and state laws create disease-reporting requirements for many STDs. Gonorrhea; Chlamydia; chanchroid; syphilis; Hepatitis A, B, C; and HIV (including AIDS) are all nationally notifiable. Clinicians should contact their local health department for pertinent reporting information.

Privacy and confidentiality concerns are different for STDs than for general medical information. Patients generally experience greater anxiety about information pertaining to a possible diagnosis of an STD, and this may limit their willingness to disclose clinically pertinent information. Conversely, legal requirements for disease reporting and health department partner notification programs can inadvertently compromise patient confidentiality if not handled with the utmost professionalism. Furthermore, although minors generally require parental consent for nonemergent medical care in all states, minors can be diagnosed and treated for STDs without parental consent. Additionally, many US states’ legislations may permit physicians to prescribe treatment for the heterosexual partners of men or women with Chlamydia or gonorrhea without examining the partner. Thus, laws in different jurisdictions create additional options and complexities in treating STDs. Practitioners need to be familiar with local requirements.

Prevention

Intervening in patients’ lives to reduce their risk of disease due to STDs is no less important than reducing risk due to smoking, inadequate exercise, poor nutrition, and other health risks. STD risk assessment should prompt providers to undertake discussion of risk reduction, and thus disease prevention. Physicians’ effectiveness depends on their ability to obtain an accurate sexual history employing effective counseling skills. Specific techniques include creating a trusting, confidential environment; obtaining permission to ask questions about STDs; demonstrating a nonjudgmental, optimistic attitude; and combining information collection with patient education, using clear, mutually understandable language (see Chapter 17). Prevention is facilitated by an environment of open, honest communication about sexuality.

A. Counseling

The US Preventive Services Task Force (USPSTF) recommends high-intensity behavioral counseling to prevent sexually transmitted infections (STIs) for all sexually active adolescents and for adults at increased risk for STIs, for example, adults with current STIs or infections within the past year who have multiple current sexual partners, or who are members of a population with a high rate of STIs. Recommendations for changes in behavior should be tailored to the patient’s specific risks and needs; simple suggestions such as keeping condoms available have been shown to be effective. Brief counseling using personalized risk reduction plans and culturally appropriate videos can significantly increase condom use and prevent new STDs, and can be conducted even in busy public clinics with minimal disruption to clinic operations. Effective interventions to reduce STDs in adolescents can extend beyond the examination room and include school-based and community-based education programs. Characteristics of successful interventions include multiple sessions, most often in groups, with total duration from 3 to 9 hours, or two 20-minute counseling sessions before and after HIV testing. Individuals with chronic infections [eg, herpes simplex virus (HSV) and HPV] will need counseling tailored to help them accurately understand their infection and effectively manage symptoms and transmission risk.

B. Condoms

For sexually active patients, male condoms are effective in reducing the sexual transmission of HIV infection. When used correctly and consistently, male latex condoms can reduce the risk of other STIs, including Chlamydia, gonorrhea, and Trichomonas. Condoms may afford some protection against transmission of HSV, and may mitigate some adverse consequences of infection with HPV, as their use has been associated with higher rates of regression of cervical intraepithelial neoplasia and clearance of HPV in women.

Effectiveness depends on correct, consistent use. Patients should be instructed to use only water-based lubricants. Providers may need to demonstrate how to place a condom on the penis via a suitable model, especially for persons who may be inexperienced with condom use.

Spermicide is not recommended for STI/HIV prevention. Some may confuse contraception with disease prevention; nonbarrier methods of contraception such as hormonal contraceptives or surgical sterilization do not protect against STDs. Women employing these methods should be counseled about the role of condoms in prevention of STDs.

C. Vaccination

Vaccination for hepatitis B virus (HBV) is indicated for all unvaccinated adolescents, all unvaccinated adults at risk for HBV infection, and all adults seeking protection from HBV infection. Other settings where all unvaccinated persons should receive vaccination include correctional facilities, drug abuse treatment and prevention services centers, health care settings serving men who have sex with men, and HIV testing and treatment facilities. Additionally, individuals with chronic liver disease (including chronic HBV or hepatitis C infection), end-stage renal disease, diabetes mellitus, and potential occupational or travel exposure should be vaccinated. The prevalence of past exposure to HBV in homosexual men and injection drug users may render prevaccination testing cost effective, although it may lower compliance. For this reason, if prevaccination testing is employed, patients should receive their first vaccination dose when tested. If employed, HBV core antibody testing is an effective screen for immunity.

Vaccination for hepatitis A virus (HAV) is indicated for homosexual or bisexual men, persons with chronic liver disease (including hepatitis B and C), and IV drug users; additionally, some individuals with occupational or travel exposure should be vaccinated. In cases of sexual or household contact with someone with HAV, hepatitis A vaccine or immune globulin should be administered as soon as possible after exposure. (For additional information on hepatitis A and B, see Chapter 31.)

Two HPV vaccines are available and licensed for females aged 9-26 years to prevent cervical precancers and cancers, the quadrivalent HPV (Gardasil) and the bivalent HPV vaccine (Cervarix). Universal vaccination of females aged 11–12 years is recommended with either vaccine, as is catchup vaccination for females aged 13–26 years. In order to prevent genital warts and anal cancers, all males may receive the quadrivalent HPV vaccine at ages 9–26. The quadrivalent HPV vaccine (Gardasil) is universally recommended for males aged 11–12 years, as is catchup vaccination for males aged 13–21 years. Gardasil is also recommended for high risk males (men who have sex with men and those who are immunocompromised) ages 22–26. Experimental vaccines are also being explored for other STDs.

Society of Teachers of Family Medicine. Shots by STFM 2013 (available at http://www.immunizationed.org/shotsonline.aspx; accessed April 6, 2013).

D. Partner Treatment

Following treatment of an individual patient, treatment of asymptomatic partners of a diagnosed patient is commonly employed in STD treatment. For patients with multiple partners, it may be difficult to identify the source of infection. Partner treatment should be recommended for sexual contacts occurring prior to diagnosis within the time intervals indicated for each disease:

• Chancroid, 10 days

• Granuloma inguinale, 60 days

• Lymphogranuloma venereum, 60 days

• Syphilis, 3 months plus the duration of symptoms for patients diagnosed with primary syphilis (even if the contact tests seronegative); 6 months plus the duration of symptoms for patients diagnosed with secondary syphilis, and 1 year for patients with early latent syphilis

• Chlamydial infection, 60 days

• Gonorrhea, 60 days

• Epididymitis, 60 days

• Pelvic inflammatory disease (PID), 60 days

• Pediculosis pubis, 30 days

• Scabies, 30 days

Although in general physicians must examine a patient directly before prescribing treatment, when prior medical evaluation and counseling is not feasible, or resource limitations constrain evaluation and diagnosis, other partner management options may be considered. One of these is partner-delivered therapy, in which patients diagnosed with Chlamydia or gonorrhea deliver the prescribed treatment to their partners; this option is affected by state laws and regulations.

Repeat testing at 3 months following treatment is indicated for persons with Chlamydia or gonorrhea, due to the increased incidence of reinfection. Patients should also be instructed to avoid sexual contact for the duration of therapy to prevent further transmission. Patients taking single-dose azithromycin for Chlamydia infection should be instructed to avoid sexual contact for 7 days. Patients must also be instructed to avoid contact with their previous partner(s) until both patient and partner complete treatment.

E. Screening

Some form of STD screening, such as questions asked during the history interview or included in routine history forms, should be a universal practice for all patients, with periodic and regular updating. Content, frequency, and additional screening should be determined by individual patient circumstances, local disease prevalence, and research documenting effectiveness and cost-benefit. Table 14-1 summarizes current recommendations for STD screening from the USPSTF.

1. Chlamydia and gonorrhea

Annual screening of all sexually active women aged <25 years is recommended, as is screening of older women with risk factors (eg, those who have a new sex partner or multiple sex partners).

The benefits of Chlamydia trachomatis screening in women have been demonstrated in areas where screening programs have reduced both the prevalence of infection and rates of PID. Evidence is insufficient to recommend routine screening for C. trachomatis in sexually active young men, based on feasibility, efficacy, and cost-effectiveness. However, screening of sexually active young men should be considered in clinical settings with a high prevalence of Chlamydia (eg, adolescent clinics, correctional facilities, and STD clinics).

2. Pregnancy

Recommendations for screening pregnant women vary somewhat depending on the source. According to the CDC, pregnant women should receive a serologic test for syphilis, Hepatitis B surface antigen, and HIV at the onset of prenatal care. High-risk women should repeat HIV and syphilis testing early in the third trimester, and should repeat hepatitis B surface antigen and syphilis testing again at delivery. Furthermore, pregnant women at risk for HBV infection should be vaccinated for hepatitis B.

Providers of obstetric care should test for Neisseria gonorrhoeae at the onset of care if local prevalence of gonorrhea is high or if the woman is at increased risk, and testing should be repeated in the third trimester if the woman is at continued risk. Providers should test for Chlamydia at the first prenatal visit. Women aged <25 years and those at increased risk for chlamydial infection (ie, those who have multiple partners or who have a partner with multiple partners) should also be tested again in the third trimester. Evidence does not support routine testing for bacterial vaginosis. For asymptomatic pregnant women at high risk for preterm delivery, the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis. Symptomatic women should be evaluated and treated.

3. HIV

HIV screening is recommended for patients aged 15–65 years in all health care settings after the patient is notified that testing will be performed unless the patient declines. CDC recommends that younger adolescents and older adults at increased risk also be screened. Repeat annual testing for HIV is indicated for any high-risk patient, including patients with a diagnosed STD or with a history of behaviors that could expose them to HIV. Testing is also indicated for patients who present with a history and findings consistent with the acute retroviral syndrome (ARS), symptoms of which are listed in Table 14-2. Appropriate testing regimens include an HIV1 screening antibody test such as enzyme immunoassay, with a confirmatory test such as the Western immunoblot. HIV2 prevalence in the United States is very low, so routine testing is not indicated, although several commercial antibody tests screen for both HIV1 and HIV2; HIV2 should be considered for persons coming from areas of high HIV2 prevalence (eg, parts of West Africa, particularly Cape Verde, Ivory Coast, Gambia, Guinea-Bissau, Mali, Mauritania, Nigeria, and Sierra Leone).

Early diagnosis of ARS may present a very narrow window of opportunity to alter the course of HIV infection in the recently infected patient, and to block the source of most presumed new HIV transmission. Symptoms are common and nonspecific, rendering diagnosis difficult without a high index of suspicion; they include fever, malaise, lymphadenopathy, pharyngitis, and skin rash. Appropriate testing should include a nucleic acid test for HIV such as HIV-RNA polymerase chain reaction (PCR); routine HIV antibody tests are not sufficient, because they seldom will have become positive during ARS. Individuals with positive HIV tests should be referred immediately to an expert in HIV care.

All HIV-infected individuals pose particular challenges for STD risk reduction. Reducing high-risk behaviors of known HIV-infected patients is a top priority, both to decrease the further spread of HIV and to limit the exposure of HIV patients to additional STDs. Persons with HIV also have substantial medical, psychological, and legal needs that are beyond the scope of this chapter.

4. Other STDs

Accepted national guidelines directing screening for other STDs do not exist. If undertaken, additional screening should be guided by local disease prevalence and an individual patient’s risk behaviors.

Patients who are infected with STDs rarely present with accurate knowledge of their microbiological diagnosis. More commonly, patients present with clinical syndromes consistent with one or more diagnoses, so that providers frequently employ syndromic evaluation and treatment. This approach is useful for several reasons, including the fact that more than one disease may be present, and has been employed commonly in resource-poor settings with limited access to advanced diagnostic technology. The following recommendations for testing strategies and use of empiric treatment pending laboratory results should be adapted to take into consideration local availability of specific tests, the probability of the diagnosis based on the history and examination, disease-associated morbidity, the risk of further transmission while awaiting diagnosis, and the likelihood that an untreated patient will return for laboratory test results and treatment. Treatment information is summarized in Table 14-3, and additional treatment information appears within the text description of specific diseases where applicable.

General Considerations

In the United States, herpes simplex is the most common cause of genital ulcer disease (GUD); syphilis is less common, and other causes such as chancroid, lymphogranuloma venereum, and granuloma inguinale are very uncommon. Because this is not true throughout the world, physicians treating international travelers or recent arrivals to the United States may need to consider a broad spectrum of potential etiologies. The approach to diagnosis needs to include consideration of the likelihood of the different etiologies based on the patient’s history, physical examination, and local epidemiology. Furthermore, all types of GUD are associated with increased risk of HIV transmission, making HIV testing a necessary part of GUD evaluation.

Herpes Simplex

At least 50 million persons in the United States have genital HSV2 infection.

The majority of persons infected with HSV2 have not been diagnosed with genital herpes. Many such persons have mild or unrecognized infections but shed virus intermittently in the genital tract. The majority of genital herpes infections are transmitted by persons unaware that they have the infection or who are asymptomatic when transmission occurs. Herpes simplex virus type 1 is causing an increasing proportion of anogenital herpes and in some populations, such as young women and men who have sex with men (MSM), may now account for the majority of first episode anogenital infections.

Clinical Findings

A. Symptoms and Signs

A first episode of genital herpes classically presents with blisters and sores, with local tingling and discomfort. Visible lesions may be preceded by a prodrome of tingling or burning. Some patients also report dysesthesia or neuralgic pain in the buttocks or legs and malaise with fever. The clinical spectrum of disease can include atypical rashes, fissuring, excoriation, and discomfort of the anogenital area, cervical lesions, urinary symptoms, and extragenital lesions. Recent data suggest that a minority of patients who acquire HSV2 have symptoms associated with initial infection, although overt disease may follow. In immunocomprised persons, HSV can manifest as large, chronic, hyperkeratotic ulcers. If lesions persist despite antiviral therapy, acyclovir-resistant HSV should be suspected.

Both HSV1 and HSV2 cause genital disease, although HSV1 produces fewer clinical recurrences and may be less severe. Symptoms during recurrences are generally less intense and shorter in duration. Infectious virus is shed intermittently and unpredictably in some asymptomatic patients. Latex condoms, when used correctly and consistently, may reduce the risk of genital HSV transmission.

B. Laboratory Findings

Diagnosis of HSV is based on either culture of the vesicle base or ulcer, or PCR test for HSV DNA. PCR assays for HSV DNA are more sensitive and have been increasingly used. Cytologic detection of cellular changes of herpes virus infection is insensitive and nonspecific, both in genital lesions (Tzanck smear) and cervical Papanicolaou (Pap) smears, and so should not be relied on. Type-specific serologic assays may be useful in patients with recurrent symptoms and negative HSV cultures, those with a clinical diagnosis of genital herpes without laboratory confirmation, or in patients who have a partner with genital herpes.

Treatment

Treatment of HSV can be episodic (ie, in response to an episode of disease) or suppressive, with daily medication continuing for months or years. Treatment for an initial outbreak consists of 7–10 days of oral medication (see Table 14-3). Episodic treatment is effective when medication is started during the prodrome or on the first symptomatic day. No benefit will be seen if treatment of recurrences is delayed; thus, patients should be given a prescription to have available for use when needed.

Suppressive therapy is traditionally indicated for patients with frequent recurrences, although this may be individualized with respect to the stress and disability caused by recurrences. Available experience suggests that long-term suppression is safe and is not associated with development of antiviral resistance. Suppressive therapy seems to reduce but not eliminate asymptomatic shedding. Daily treatment with valacyclovir (500 mg) has been shown to decrease the rate of HSV2 transmission in discordant heterosexual couples in which the source partner has a history of genital HSV2 infection. Suppression does not change the natural history of a patient’s infection; however, because the frequency of recurrences diminishes with time, suppression may be particularly useful during the time period immediately following initial infection. Available therapies appear to be safe in pregnant women, although data for valacyclovir and famciclovir are limited.

Syphilis

General Considerations

Syphilis cases reported to the CDC had declined since the early 1950s until a resurgence was noted in the 1990s. In 1999, the CDC launched “The National Plan to Eliminate Syphilis from the United States.” In 2011, 13,970 cases of primary and secondary syphilis were reported. National numbers increased every year from 2000 to 2009, and have largely held steady since then. Men who have sex with men now account for more than two-thirds of new cases of primary and secondary syphilis. More recent resurgences of syphilis in some populations and geographic areas indicate the need for continued vigilance.

Clinical Findings

A. Symptoms and Signs

Syphilis infection is characterized by stages, and accurate staging is vital to determine appropriate therapy. Primary syphilis is characterized by the appearance of a painless, indurated ulcer—the chancre—occurring 10 days to 3 months after infection with Treponema pallidum. The chancre usually heals by 4–6 weeks, although associated painless bilateral lymphadenopathy may persist for months.

Secondary syphilis has variable manifestations, but usually includes symmetric mucocutaneous macular, papular, papulosquamous, or pustular lesions with generalized nontender lymphadenopathy. In moist skin areas such as the perianal or vulvar regions, papules may become superficially eroded to form pink or whitish condylomata lata. Constitutional symptoms such as fever, malaise, and weight loss occur commonly. Less common complications include meningitis, hepatitis, arthritis, nephropathy, and iridocyclitis.

Latent syphilis is diagnosed in persons with serologic evidence of syphilis infection without other current evidence of disease. “Early” latent syphilis is defined as infection for less than 1 year. A diagnosis of early latent syphilis is demonstrated by seroconversion, a definitive history of primary or secondary syphilis findings within the past year, or documented exposure to primary or secondary syphilis in the past year. Asymptomatic patients with known infection of >1 year or in whom infection of <1 year cannot be conclusively demonstrated are classified as having late latent syphilis or latent syphilis of unknown duration, respectively. These two categories of syphilis are treated equivalently. The magnitude of serologic test titers cannot reliably differentiate early from late latent syphilis.

Neurosyphilis can occur at any stage of infection and is difficult to diagnose, as no single test can be used in all instances. The cerebrospinal fluid (CSF) VDRL test is highly specific but insensitive. The diagnosis depends on a combination of serologic tests, elevated CSF cell count or protein, or a reactive VDRL. CSF fluorescent treponemal antibody absorption (FTA-abs) is less specific, but highly sensitive. CSF pleocytosis [>5 white blood cells (WBCs)/mm³] is usually evident, although HIV infection and other conditions may also cause increased WBCs in the CSF.

Tertiary syphilis is characterized by a self-destructive immune response to a persistent low level of pathogens. It can manifest as neurosyphilis, cardiovascular syphilis including aortitis, or in the form of gummas, granulomas, or psoriasiform plaques.

Patients are infectious during primary, secondary, and early latent stages of syphilis.

B. Laboratory Findings

Positive darkfield examination or direct fluorescent antibody tests of lesion exudates definitively diagnose primary syphilis. More typically, syphilis is diagnosed by positive serologic results of both a nontreponemal test (VDRL or RPR) and a treponemal test [Treponema pallidum particle agglutination (TPPA) or FTA-abs].

Nontreponemal tests may be falsely positive because of other medical conditions (eg, some collagen vascular diseases). When positive because of syphilis, their titers generally rise and fall in response to T. pallidum infection and treatment, respectively, and usually return to normal (negative) following treatment, although some individuals remain “serofast” and have persistent low positive titers. Treponemal tests usually yield persistent positive results throughout the patient’s life following infection with T. pallidum. Treponemal test titers do not correlate with disease activity or treatment.

Lumbar puncture is indicated for: (1) neurologic or ophthalmologic signs or symptoms, (2) active aortitis or gumma, or (3) treatment failure (a fourfold increase in titer or a failure to decline fourfold or more within 12–24 months).

Treatment

Treatment for syphilis as described in Table 14-3 is based on current CDC guidelines. Follow-up testing of patients diagnosed with syphilis is a vital part of care, as it determines the effectiveness of therapy and provides useful information to differentiate potential future serofast patients from those with recurrent infection.

The nontreponemal test titer should have fallen fourfold or more (eg, from 1:32 to ≤1:8) for persons with primary or secondary syphilis in 6–12 months post therapy. If it does not, consider this a treatment failure or an indication of reinfection. In evaluating such a potential treatment failure, the patient should, at minimum, receive continued serologic follow-up and repeat HIV serology if previously negative. Lumbar puncture should also be considered, and if the results are normal, the patient should be treated with 2.4 million units of benzathine penicillin weekly for 3 weeks and followed as described previously.

Chancroid

Chancroid has declined in the United States and worldwide. In 2011, a total of eight cases of chancroid were reported in only six states in the United States. These data should be interpreted with caution, however, because Haemophilus ducreyi is difficult to culture, and thus this condition may be substantially underdiagnosed.

Definitive diagnosis is difficult, requiring identification of H. ducreyi on special culture medium that is seldom readily available. Presumptive diagnosis rests on the presence of painful genital ulcer(s) with a negative HSV test and negative syphilis serology, with or without regional lymphadenopathy.

Treatment consists of oral antibiotics as listed in Table 14-3. Healing of large ulcers may require >2 weeks. If patients do not show clinical improvement after 7 days, consider the accuracy of the diagnosis, medication nonadherence, antibacterial resistance, or a combination of these. Fluctuant lymphadenopathy may require drainage via aspiration or incision.

Although definitive diagnosis generally rests on laboratory testing, history and examination (H&PE) often lead to a presumptive diagnosis. Table 14-4 summarizes findings for different causes of GUD.

Other Causes of GUD

Granuloma inguinale or donovanosis is caused by Calymmatobacterium granulomatis, which is endemic in some tropical nonindustrialized parts of the world and is rarely reported in the United States. The bacterium does not grow on standard culture media; diagnosis rests on demonstration of so-called Donovan bodies in a tissue specimen. Infection causes painless, progressive, beefy red, highly vascular lesions without lymphadenopathy. Treatment is often prolonged, and relapse can occur months after initial treatment and apparent cure.

Lymphogranuloma venereum is caused by serovars L1, L2, and L3 of C. trachomatis. The small ulcer arising at the site of infection is often unnoticed or unreported. The most common clinical presentation is painful unilateral lymphadenopathy. Rectal exposure in women and in MSMs may result in proctocolitis (mucus or hemorrhagic rectal discharge, anal pain, constipation, fever, or tenesmus). Diagnosis rests on clinical suspicion, epidemiologic information, exclusion of other etiologies, and C. trachomatis tests. In addition to antibiotics, treatment may require aspiration or incision and drainage of buboes; nevertheless, patients may still experience scarring.

In 2011, population studies showed a rate of Chlamydia infection of 457.6 cases per 100,000 and a rate of gonorrhea infection of 104.2 cases per 100,000 in the United States. Rates for both of these pathogens are higher in females than males, and are highest in the adolescent and young adult age groups.

Sexually transmitted diseases causing urethritis are typically diagnosed in men, although women may also experience urethritis as a consequence of an STD. For clinical management, urethritis can be divided into nongonococcal urethritis (NGU) and urethritis due to N. gonorrhoeae infection.

Nongonococcal Urethritis

One frequent cause of NGU is C. trachomatis. In 2011, 1,412,791 Chlamydia cases were reported, and although significant, these numbers likely dramatically underestimate actual cases of C. trachomatis infection. The spectrum of C. trachomatis–caused disease includes extragenital manifestations, among them ophthalmic infection and a reactive arthritis.

Causes of nonchlamydial NGU may include Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis, herpes simplex, and adenovirus. Diagnosis of NGU can be based on: (1) purulent urethral discharge; (2) Gram stain of urethral secretions with ≥5 WBCs per high-power field (HPF) and no gram-negative intracellular diplococci (which, if present, would indicate gonorrhea); (3) first-void urine with positive leukocyte esterase, or >10 WBCs/HPF. Nucleic acid amplification tests (Chlamydia or gonorrhea) offer greater convenience and better sensitivity than culture and represent the best tests currently available.

In patients presenting with recurrent urethritis, diagnostic evaluation may be necessary to identify the etiology. In evaluating recurrent urethritis, the physician should assess medication compliance and potential reexposure; perform wet mount, culture, or both, for T. vaginalis; and treat as indicated by findings, or empirically as per Table 14-3.

Treatment of NGU generally employs azithromycin or doxycycline, with alternatives as listed in Table 14-3. If findings of urethritis are present, treatment is generally indicated pending results of diagnostic tests. Because diagnostic testing typically does not look for all potential causes of urethritis, patients with negative tests for gonorrhea and C. trachomatis may also benefit from treatment. Empiric treatment of symptoms without documentation of urethritis findings is recommended only for patients at high risk for infection who are unlikely to return for a follow-up evaluation. Such patients should be treated for gonorrhea and Chlamydia. Partners of patients treated empirically should be evaluated and treated. If treatment is not offered at the initial visit, diagnostic testing should employ the most sensitive test available, with follow-up treatment as indicated by test results and symptom persistence.

Gonorrhea

General Considerations

In 2011, 321,849 cases of gonorrhea were reported in the United States. Rates have been moderately stable since 2004, more common in the South (135.5 cases per 100,000 population vs 104.2 cases per 100,000 for the country), and somewhat more common in women than in men (108.9 vs 98.7 cases per 100,000, respectively).

Clinical Findings

A. Symptoms and Signs

If symptomatic, gonorrhea typically causes dysuria and a purulent urethral discharge; however, it may also cause asymptomatic infection or disseminated systemic disease, including pharyngitis, skin lesions, septic arthritis, tenosynovitis, arthralgias, proctitis, perihepatitis, endocarditis, and meningitis. In these cases, there is usually minimal genital inflammation.

Clinical differentiation between gonorrhea and Chlamydia may be difficult. Characteristically, urethral exudate in gonorrhea is thicker, more profuse, and more purulent in appearance than the exudate caused by C. trachomatis, which is often watery with mucus strands. However, differentiation of etiology based on clinical appearance is notoriously unreliable.

B. Laboratory Findings

Nucleic acid amplification technology (NAAT, including PCR) has largely supplanted culture for diagnosis because of enhanced sensitivity and excellent specificity. NAAT tests can be performed on endocervical swabs, vaginal swabs, urethral swabs, and urine samples. In addition, some laboratories have established performance specifications for the use of NAAT testing for gonorrhea on rectal and pharyngeal swabs. However, the use of NAAT testing in nongenital sites is rendered more challenging by the potential for cross-reactivity with nongonorrheal Neisseria species. In addition, gonorrhea PCR test sensitivity is quite poor in women’s urine specimens—as low as 55%, and therefore endocervial swab NAAT testing is to be preferred in this population.

Diagnostic evaluation identifies disease etiology and may facilitate the public health missions of contact tracing and disease eradication. For an individual patient, however, the physician may treat empirically if follow-up cannot be ensured and test methodology is insensitive. Decisions about diagnostic testing should consider both public health goals and how information obtained will influence patient (and partner) treatment.

Treatment

When treating for gonorrhea, practitioners should treat also for C. trachomatis, as coinfection is common. Quinolone-resistant N. gonorrhoeae strains are now widely disseminated throughout United States and the world. Since April 2007, quinolones have no longer been recommended in the United States for treatment of gonorrhea and associated conditions such as PID. As of October 2012, oral cephalosporins are no longer a recommended treatment for gonorrheal infection. Decreased susceptibility of N gonorrhoeae to cephalosporins and other antimicrobials is expected to continue to spread; therefore, state and local surveillance for antimicrobial resistance is crucial for guiding local therapy recommendations. Ceftriaxone 250 mg IM is currently effective for the treatment of uncomplicated gonorrhea at all anatomic sites.

Treatment failures should be followed by (repeat) culture and sensitivity testing, and any resistance should be reported to the public health department.

The cause of epididymitis varies with age. In men aged ≤35 years, it is most commonly due to gonorrhea or C. trachomatis, or to gram-negative enteric organisms in men who engage in unprotected insertive anal intercourse. In men aged >35 years, epididymitis is seldom sexually transmitted, and is more likely caused by gram-negative enteric organisms; increased risk in this case is found in patients who have undergone recent urologic surgery, or who have anatomic abnormalities. Patients usually present with unilateral testicular pain and inflammation with onset over several days. The clinician must differentiate epididymitis from testicular torsion, since the latter is a surgical emergency requiring immediate correction. The laboratory evaluation of suspected epididymitis includes Gram stain, nucleic acid amplification test, and serologic testing for HIV and syphilis.

Proctitis, proctocolitis, and enteritis may arise from anal intercourse or oral-anal contact. Depending on organism and anatomic location of infection and inflammation, symptoms can include pain, tenesmus, rectal discharge, and diarrhea. Etiologic agents of proctitis include C. trachomatis (lymphogranuloma venereum), N. gonorrhea, T. pallidum, and HSV. Other agents may cause proctitis or enteritis including Giardia lamblia, Campylobacter, Shigella, and Entamoeba histolytica. In HIV-infected patients, additional etiologic agents include cytomegalovirus, Mycobacterium avium intracellulare, Salmonella, Cryptosporidium, Microsporidium, and Isospora. Symptoms may also arise as a primary effect of HIV infection.

Diagnosis involves examination of stool for ova, parasites, occult blood, and WBCs; stool culture; and anoscopy or sigmoidoscopy.

Treatment should generally be based on results of diagnostic studies. However, if the onset of symptoms occurs within 1–2 weeks of receptive anal intercourse, and there is evidence of purulent exudates or polymorphonuclear neutrophils on Gram stain of anorectal smear, the patient can be treated presumptively for gonorrhea and chlamydial infection. If painful perianal ulcers are present or mucosal ulcers are detected on anoscopy, presumptive therapy should include a regimen for genital herpes and lymphogranuloma venereum.

Patients with vaginitis may present with vaginal discharge, vulvar itching, irritation, or all of these, and sometimes with complaints of abnormal vaginal odor. Common etiologies include Candida albicans, T. vaginalis, and bacterial vaginosis. Diagnostic evaluation typically includes physical examination and evaluation of a saline wet mount and potassium hydroxide (KOH) preparation. Differences between common causes of vaginitis are summarized in Table 14-5 and described next.

Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is typically caused by C. albicans, although occasionally other species are identified. More than 75% of all women will have at least one episode of VVC during their lifetime. The diagnosis is presumed if the patient has vulvovaginal pruritus and erythema with or without a white discharge, and is confirmed by wet mount or KOH preparation showing yeast or pseudohyphae, or culture showing a yeast species.

Vulvovaginal candidiasis can be classified as uncomplicated, complicated, or recurrent. Uncomplicated VVC encompasses sporadic, nonrecurrent, mild to moderate symptoms due to C. albicans that, in an otherwise healthy patient, are responsive to routine therapy. Complicated VVC implies recurrent or severe local disease in a patient with impaired immune function (eg, diabetes or HIV), or infection with resistant yeast species. Recurrent VVC is defined as four or more symptomatic episodes annually.

Treatment is summarized in Table 14-3. Uncomplicated candidiasis should respond to short-term or single-dose therapies as listed. Complicated VVC may require prolonged treatment. Treatment of women with recurrent vulvovaginal candidiasis should begin with an intensive regimen (7–14 days of topical therapy or a multidose fluconazole regimen) followed by 6 months of maintenance therapy to reduce the likelihood of subsequent recurrence. Symptomatic candidal vaginitis is more frequent in HIV-infected women and correlates with severity of immunodeficiency.

Vulvovaginal candidiasis is seldom acquired through sexual intercourse. There are no data to support treatment of sex partners. Some male sex partners have balanitis and may benefit from topical antifungal agents.

Trichomoniasis

Vaginitis due to T. vaginalis presents with a thin, yellow, or yellow-green frothy malodorous discharge and vulvar irritation that may worsen following menstruation. However, many women have minimal or no symptoms at all. Diagnosis can often be made via prompt examination of a freshly obtained wet mount, which reveals the motile trichomonads. Although culture is more sensitive, it may not be as readily available, and results are delayed. Point-of-care tests (eg, Osom Trichomonas Rapid Test and Affirm VPIII) are also available and tend to be more sensitive than vaginal wet prep. Partners of women with Trichomonas infection require treatment.

Bacterial Vaginosis

Bacterial vaginosis arises when normal vaginal bacteria are replaced with an overgrowth of anaerobic bacteria. Although not thought to be an STD, it is associated with having multiple sex partners or a new sex partner.

Diagnosis can be based on the presence of three of four clinical criteria: (1) a thin, homogeneous vaginal discharge; (2) a vaginal pH value of >4.5; (3) a positive “whiff” test (fishy odor when KOH is added to vaginal discharge); and (4) the presence of clue cells in a wet mount preparation.

Treatment is recommended for women with symtoms. Potential benefits of therapy include reducing the risk for infectious complications associated with bacterial vaginosis during pregnancy and reducing the risk for other infections. Routine treatment of sex partners is not recommended.

Cervicitis

Cervicitis is characterized by purulent discharge from the endocervix, which may or may not be associated with vaginal discharge or cervical bleeding. The diagnostic evaluation should include testing for Chlamydia, gonorrhea, bacterial vaginosis, and Trichomonas. Absence of symptoms should not preclude additional evaluation and treatment, as approximately 70% of chlamydial infections and 50% of gonococcal infections in women are asymptomatic.

Nucleic acid amplification tests are the preferred diagnostic test for gonorrhea and Chlamydia and can be performed on vaginal, cervical, or urine specimens (although, urine testing for gonorrhea has only 55% sensitivity and so cervical specimens are preferred). Empiric treatment should be considered in areas with high prevalence of C. trachomatis or gonorrhea, or if follow-up is unlikely.

Pelvic inflammatory disease (PID) is defined as inflammation of the upper genital tract, including pelvic peritonitis, endometritis, salpingitis, and tuboovarian abscess due to infection with gonorrhea, C. trachomatis, or vaginal or bowel flora; etiology is often polymicrobial. Diagnosis is challenging because of often vague symptoms, lack of a single diagnostic test, and the invasive nature of technologies needed to make a definitive diagnosis. Lower abdominal tenderness and uterine, adnexal, or cervical motion tenderness with signs of lower genital tract inflammation increase the specificity of a PID diagnosis. Other criteria enhance the specificity of the diagnosis (but reduce diagnostic sensitivity):

• Fever >38.3°C (>101°F)

• Abnormal cervical or vaginal discharge

• Abundant WBCs in saline microscopy of vaginal secretions

• Elevated sedimentation rate

• Elevated C-reactive protein

• Cervical infection with gonorrhea or C trachomatis

Definitive diagnosis rests on techniques that are not always readily available and that are rarely used to make the diagnosis. These include laparoscopic findings consistent with PID, evidence of endometritis on endometrial biopsy, and ultrasonographic findings showing thickened fluid-filled tubes with or without free pelvic fluid or tuboovarian complex.

Determination of appropriate therapy should consider pregnancy status, severity of illness, and patient compliance. Less severe disease can generally be treated with oral antibiotics in an ambulatory setting, whereas pregnant patients and those with severe disease may need hospitalization. Options are listed in Table 14-3.

General Considerations

It is estimated that >79 million Americans are infected with HPV, with 15 million new infections and 453,000 initial visits to physicians for genital warts occurring annually. Even this estimate may be low; overall HPV prevalence among US females aged 14–59 years was estimated to be 42.5%, based on 2003–2006 National Health and Nutrition Examination Survey (NHANES) data. Over 100 types of HPV have been identified, and over 40 types cause genital lesions. Types 6, 11, and others typically produce benign exophytic warts, whereas types 16, 18, 31, 33, 35, and others are associated with dysplasia and neoplasia. Thus, cervical and anogenital squamous cancer can be considered STDs; other cancers may also be sexually transmitted.

Clinical Findings

Diagnosis is almost always based on physical examination with bright light and magnification, and rarely requires biopsy. If the diagnosis is uncertain, consider referral to a physician with extensive experience in external genital warts. Biopsy should be considered for >1-cm warts; indurated, ulcerated, or fixed to underlying structures; atypical in appearance; pigmented; or resistant to therapy. Application of 3–5% acetic acid as an aid to visualization is seldom useful, and the resulting nonspecific acetowhite reaction may lead to overdiagnosis of genital warts.

Human papillomavirus is the primary cause of cervical cancer, and screening guidelines for cervical cancer screening including the use of HPV testing, are reviewed in Chapter 26. Genital warts are not an indication for screening more frequently.

Because of the increased incidence of anal cancer in HIV-infected homosexual and bisexual men and high-risk women, screening for anal cytologic abnormalities may be considered. However, there are limited data on the natural history of anal intraepithelial neoplasias, the reliability of screening methods, the safety of and response to treatments, and the programmatic considerations that would support this screening approach.

Treatment

The therapeutic goal in treatment of external genital warts is elimination of warts. Treatment strives to eliminate symptoms, and a potential theoretical benefit is reduced likelihood of transmission. Clinicians should be certain of the diagnosis prior to instituting therapy, and should not apply treatments to skin tags, pearly penile papules, sebaceous glands, or other benign findings that do not require (and will not respond to) genital wart treatment.

No evidence suggests any treatment is superior to others. The possibility of spontaneous resolution may justify no treatment, if that is the patient’s wish.

Treatments can be categorized as provider-applied or patient-applied. Physicians should familiarize themselves with at least one or two treatments in each category, as described in Table 14-3. Most treatments work via tissue destruction. Imiquimod uses a different mechanism; by inducing production of interferon, it may be more effective than other therapies in treating some genital warts or other skin conditions, including molluscum contagiosum. Patients unresponsive to an initial course of treatment may require another round of treatment, more aggressive treatment, or referral to a specialist.

Although most HPV infections will clear spontaneously within 2 years and cause no harm, patients with HPV need to understand the possibility of chronic infection, including its natural history and treatment options, and should receive adequate education and counseling to achieve optimal treatment outcomes. The chronic nature of HPV infection combined with the serious, albeit relatively infrequent, complication of cancer creates significant challenges to patient coping and provider counseling.

Molluscum contagiosum appears in individuals of all ages and from all races, but has been reported more commonly in the white population and in males. Lesions are due to infection with poxvirus, which is transmitted through direct skin contact, as occurs among children in a nursery school and among adults during sexual activity. Diagnosis is typically based on inspection, which reveals dimpled or umbilicated flesh-colored or pearly papules several millimeters in diameter; if needed, a smear of the core stained with Giemsa reveals cytoplasmic inclusion bodies. Lesions usually number fewer than 10–30, but may exceed 100, especially in HIV-infected patients who may have verrucous, warty papules, as well as mollusca of >1 cm diameter. Lesions usually resolve spontaneously within months of appearance, but can be treated with cryotherapy, cautery, curettage, or removal of the lesion’s core, with or without local anesthesia.

Vaccines for prevention of viral hepatitis and indications were described previously. Diagnostic and treatment considerations of viral hepatitis are reviewed in Chapter 32.

Pediculosis pubis results from infestation with “crab lice” or Phthirus pubis. Affected patients usually present with pubic or anogenital pruritus, and may have identified lice or nits. The physician should be able to identify lice or nits with careful examination, and their absence calls into question the diagnosis despite compatible history.

Scabies, resulting from infestation with Sarcoptes scabiei, usually presents with pruritus not necessarily limited to the genital region. The intensity of pruritus may be increased at bedtime, and may be out of proportion to modest physical findings of erythematous papules, burrows, or excoriation from scratching. A classic finding on physical examination is the serpiginous burrow present in the web space between fingers, although this finding is frequently absent in individuals with scabies.

Scabies can be sexually transmitted in adults; sexual contact is not the usual route of transmission in children. Pruritus may persist for weeks after treatment. Retreatment should be deferred if intensity of symptoms is diminishing and no new findings appear. In HIV-infected patients with uncomplicated scabies, treatment is the same as for HIV-uninfected patients. However, HIV-infected patients are at risk for a more severe infestation with Norwegian scabies, which should be managed with expert consultation.

Treatments may be empirically targeted to agents most likely causing the presenting clinical syndrome, or targeted to a specific infection diagnosed definitively. Regardless, there are overarching concerns affecting STD treatment that pertain to adherence and treatment success, HIV status, partner treatment, test of cure, and pregnancy.

Adherence considerations may favor shorter or single-dose regimens. For example, although single-dose azithromycin is more expensive than 7-day doxycycline therapy, reduced medication compliance and attendant costs of follow-up evaluation for patients treated with doxycycline may favor the use of azithromycin.

With HIV coinfection, treatments are generally the same as for uninfected patients unless stated otherwise. One potential difference is that HSV often causes more significant and prolonged symptoms in HIV-infected than in uninfected patients, so that HIV-infected patients may require longer treatment or higher medication dosages, or both. Syphilis treatment is the same as for HIV-uninfected patients regardless of stage. However, careful follow-up is important, as treatment failure or progression to neurosyphilis may be more common in the presence of HIV.

Ulcerative and nonulcerative STDs can increase the risk of HIV transmission approximately three- to fivefold.

Pregnancy imposes constraints and special considerations for therapy. Where applicable, these are noted in the treatment recommendations in Table 14-3.

As described previously, patients often present with a clinical syndrome potentially attributable to more than one infectious agent, and optimally focused therapy depends on microbiological identification. However, delaying therapy may allow symptoms to continue, resulting in untreated infection or continued spread (if the patient fails to return for follow-up or heed advice to avoid sexual contact until cured), and contribute to increased long-term morbidity. Consequently, it may be desirable to treat at the initial presentation for the infectious agents considered most likely.

Management of victims of sexual assault encompasses much more than treatment or prevention of STDs. Providers must heed legal requirements and effectively manage the psychological trauma, while not compromising the best course of medical care.

Proper medical management of sexual assault victims includes collection of evidence, diagnostic evaluation, counseling, and medical therapies to treat infection and unintended pregnancy. The diagnostic evaluation should include the following:

• Nucleic acid amplification tests for Neiserria gonorrhoeae and C. trachomatis from specimens collected from any sites of penetration or attempted penetration.

• Vaginal wet mount and culture for T. vaginalis; wet mount can also detect sperm which are motile for ~6 hours.

• Serum tests for syphilis, hepatitis B, and HIV.

• Pregnancy testing.

Evaluation for STDs may be repeated in 1–2 weeks after the initial evaluation to detect organisms that may have been undetected, unless the patient was treated prophylactically. Repeat testing for syphilis and HIV should be performed at 6 weeks, 3 months, and 6 months. Providers should also consider testing for hepatitis C virus, transmission of which has been documented following sexual assault.

Prophylactic treatment for STDs may be offered or recommended as compliance with follow-up visits is poor. Hepatitis B vaccine should be administered according to the routine schedule; hepatitis B immune globulin is not necessary unless the perpetrator is known to be infected with HBV. Azithromycin, 1 g orally, plus ceftriaxone 250 mg intramuscularly, plus metronidazole 2 g orally, may be offered to treat C. trachomatis, N. gonorrhea, and Trichomonas. Gastrointestinal side effects, especially when combined with postcoital oral contraceptive pills, may make this regimen intolerable, and alternative therapies or watchful waiting may be preferable.

Need for and benefit from HIV postexposure prophylaxis is difficult to predict. If instituted, the greatest benefit results from initiation of therapy as soon after exposure as possible. For guidance in deciding whether to begin postexposure HIV prophylaxis and in selecting appropriate treatment and monitoring, providers may contact the National Clinician’s Post-Exposure Prophylaxis Hotline (PEPline) at 888-HIV-4911 (888-448 4911).

After the neonatal period, STDs in children most commonly result from sexual abuse. In addition to vaginal gonococcal infection, pharyngeal and anorectal infection may occur and are often asymptomatic. Specific diagnostic techniques should rely only on existing guidelines as data on nucleic acid amplification tests for Chlamydia and gonorrhea are limited and performance may be test-dependent. Specimen preservation is essential for future testing when needed.