Chapter 44: Sexually Transmitted Infections

The rate of sexually transmitted infections (STIs) acquired during adolescence remains high despite widespread educational programs and increased access to health care. By senior year in high school, over half of youth will have had sexual intercourse. The highest age-specific rates for gonorrhea, chlamydia, and human papillomavirus (HPV) infection occur in adolescents and young adults (15–24 years of age). While this age group accounts for only 25% of the sexually active population, it accounts for almost half of the incident STIs. Adolescents contract STIs at a higher rate than adults because of sexual risk taking, age-related biologic factors, and barriers to health care access. In every state and the District of Columbia, adolescents can provide consent for the diagnosis and treatment of STIs without parental consent; 18 states allow for the disclosure to a parent. In many states, adolescents can also provide consent for human immunodeficiency virus (HIV) counseling and testing. Since individual state laws vary, health care providers should be knowledgeable about the legal definitions regarding age of consent and confidentiality requirements in their state.

Providers should screen sexually experienced adolescents for STIs and use this opportunity to discuss risk reduction. Since not all adolescents receive regular preventive care, providers should use acute care visits to offer screening and education. Health education counseling should be nonjudgmental and appropriate for the developmental level, yet sufficiently thorough to identify risk behaviors because many adolescents may not readily acknowledge engaging in these behaviors.

The spectrum of sexual behavior includes holding hands and kissing, touching, mutual masturbation, oral-genital contact, and vaginal and anal intercourse. Each has its associated risks. A small, but statistically significant, trend has occurred in the epidemiology of sexual risk taking toward less sexual involvement and later onset of vaginal intercourse. The most recent Youth Risk Behavior Survey (2017) reports that 40% of high school students have had sexual intercourse; 3.4% of teenagers initiated sex by age 13. Racial and gender differences exist; non-Hispanic black adolescents report a higher prevalence of sexual activity and an earlier age of initiation. Twenty-nine percent of students had sex in the 3 months prior to the survey—44% of twelfth-graders and 13% of ninth-graders. 10% of students reported having had four or more lifetime sexual intercourse partners. Among those youths currently sexually active, 54% reported that either they or their partner had used a condom during their last sexual intercourse. Paradoxically, condom use decreases with age—58% of tenth-graders reported condom use at their last intercourse compared with 50% of twelfth-graders. Substance use contributes to an increase in risky sexual activity; 19% of sexually active youth report that they used alcohol or drugs prior to their last intercourse.

Although there may be variations among groups of teens, oral sex is relatively common in adolescents with approximately two-thirds of 15–24-year-olds reporting oral sexual activity. Anal intercourse occurs in both hetero- and homosexual populations. Adolescent development is a time of exploration, including one’s sexual orientation. Frequently, teenagers may not identify themselves as gay, lesbian, or bisexual; thus, sensitive, nonjudgmental history taking is necessary to elicit a history of same-sex partners. Adolescents struggling with their emerging sexual orientation and associated stigma may engage in sexual activity with partners of both sexes or may use substances to cope, thereby impairing their decision-making abilities.

Certain behaviors and experiences are risk factors for an adolescent to develop STIs. These include early age at sexual debut, lack of condom use, multiple partners, prior STI, history of STI in a partner, and sex with a partner who is 3 or more years older. The type of sex affects risk as well, with intercourse being riskier than oral sex. Other risk factors associated with STIs in adolescents are smoking, alcohol use, drug use, dropping out of school, pregnancy, and depression.

The adolescent female is especially predisposed to chlamydia, gonorrhea, and HPV infection because the cervix during adolescence has an exposed squamocolumnar junction. The rapidly dividing cells in this area are especially susceptible to microorganism attachment and infection. During early to mid-puberty, this junction slowly invaginates as the uterus and cervix mature, and by the late teens to early 20s the squamocolumnar junction is inside the cervix.

Efforts to reduce STI risk behavior should begin before the onset of sexual experimentation: first by helping youth personalize their risk for STIs and encouraging positive behaviors that minimize these risks, and then by enhancing communication skills with sexual partners about STI prevention, abstinence, and condom use.

Primary prevention focuses largely on education and risk-reduction techniques. It is essential to recognize that a key task of adolescence is developing a sexual identity. Teenagers are sexual beings that will decide if, when, and how they are going to initiate sexual involvement. Health care providers should routinely address sexuality as part of well-adolescent checkups. Being open and frank about the risks and benefits of each specific type of sexual activity will help youth think about their decision and the consequences. Although more than 90% of students have been taught about HIV infection and other STIs in school, adolescents still have a difficult time personalizing risk. Discussing prevalence, symptoms, and sequelae of STIs can raise awareness and help teenagers make informed decisions about initiating sexual activity and the use of safer sex techniques. Abstinence is theoretically an effective method of preventing STIs. However, many studies have failed to show sustainable protection. Making condoms available reiterates the message that safer sex is vital to health. Discussing condoms, dental dams, and the proper use of lubrication also facilitates safer sex practices. Condoms prevent infections with HIV, HPV, gonorrhea, Chlamydia, and herpes simplex virus (HSV). They are probably effective in preventing other STIs as well.

Secondary prevention requires identifying and treating STIs (see the next section Screening for Sexually Transmitted Infections) before infected individuals transmit infection to others. Access to confidential medical care is critical to this objective. Identifying and treating STIs in partners is essential to limit the spread of these infections. Cooperation with the state or county health departments is valuable, because these agencies assume responsibility for locating the contacts of infected persons and ensuring appropriate treatment.

Tertiary prevention is directed toward complications of a specific illness. Examples of tertiary prevention would be treating pelvic inflammatory disease (PID) before infertility develops, following the serologic response to syphilis to prevent late-stage syphilis, treating cervicitis to prevent PID, or treating a chlamydial infection before epididymitis ensues.

Finally, preexposure vaccination against hepatitis B, hepatitis A, and HPV reduces the risk of acquiring these preventable STIs. All adolescents should have prior or current immunization against hepatitis B (see Chapter 10). However, because hepatitis B infection is frequently sexually transmitted, this vaccine is especially critical for all unvaccinated patients being evaluated for an STI. Hepatitis A vaccination is recommended for all individuals. Preexposure vaccination for HPV will decrease the risk for cervical dysplasia and cervical cancer in females, and decreases the risk for genital warts and both anal and oropharyngeal cancers in males and females, which typically occur decades later (see Chapter 10).

The ability of the health care provider to obtain an accurate sexual history is crucial in prevention and control efforts. Teenagers should be asked open-ended questions about their sexual experiences to assess their risk for STIs. Questions must be clear to the youth, so choose language that the adolescent will understand. If the adolescent has ever engaged in sexual activity, the provider needs to determine what kind of sexual activity (mutual masturbation or oral, anal, or vaginal sex); whether it has been opposite sex, same sex, or both; whether birth control and condoms were used; and whether it has been consensual or forced. During the interview, the clinician should take the opportunity to discuss risk-reduction techniques regardless of the history obtained from the youth.

A routine laboratory screening process is warranted if the patient has engaged in intercourse, presents with STI symptoms, or reports a partner with an STI. The availability of nucleic acid amplification tests (NAATs), primarily for Chlamydia and Neisseria gonorrhoeae, has changed the nature of STI screening and intervention. NAATs are more than 95% sensitive and more than 99% specific, using either urine or cervical/urethral or vaginal swabs. Annual screening of all sexually active females aged 25 years or younger is recommended for Chlamydia trachomatis and N gonorrhoeae. Routine chlamydial testing should be considered for all adolescent males, especially for males who have sex with men (MSM), have new or multiple sex partners, or are in correctional facilities. For men who have sex with men, consideration should be given to testing oropharyngeal and rectal sites, as asymptomatic infections are common. Use of NAAT is recommended for samples from these sites, but such tests are not currently FDA-approved and providers must locate a laboratory that has performed the necessary validation studies.

Initial screening for urethritis in males begins with a physical examination. A first-catch urine sample (the first 10–20 mL of voided urine collected after not voiding for 2 hours) should be sent for Chlamydia and N gonorrhoeae testing if there are no signs (urethral discharge or lesions) or symptoms. With signs or symptoms of urethritis, a urethral swab should be sent to test for both N gonorrhoeae and Chlamydia. A wet mount preparation should then be done on a spun urine sample or from urethral discharge, evaluating for the presence of Trichomonas vaginalis. Newer technologies, such as enzyme-linked immunoassays (EIA) and NAATs, allow greater sensitivity and specificity in making the diagnosis of T vaginalis in males and females.

Screening asymptomatic females is more complicated because a variety of approaches are available. Generally, either a first-void urine specimen, a cervical swab, or a vaginal swab is used to screen for Chlamydia and N gonorrhoeae by NAAT. Any vaginal discharge should be evaluated with a wet mount of vaginal secretions to check for bacterial vaginosis and trichomoniasis, and a potassium hydroxide (KOH) preparation to screen for yeast infections. The Papanicolaou (Pap) smear serves to evaluate the cervix for the presence of dysplasia. The first Pap smear should be performed at age 21 years and then every 3 years. HPV typing is not recommended before age 30.

In urban areas with a relatively high rate of syphilis and in MSM, a screening test should be drawn yearly or more frequently if higher risk encounters are more frequent. Rapid plasma reagin (RPR) antibody tests should be done in all individuals in whom a concomitant STI is present. HIV antibody testing is recommended at least once for all patients and repeat testing undertaken when an STI is present or the history includes multiple partners and high-risk behaviors.

The most common symptoms in males are dysuria and penile discharge resulting from urethral inflammation. However, providers should be aware that many urethral infections are asymptomatic. Less common symptoms are scrotal pain, hematuria, proctitis, and pruritus in the pubic region. Signs include epididymitis, orchitis, and urethral discharge. Rarely do males develop systemic symptoms. Acute HIV seroconversion illness should be considered in the differential diagnoses for any sexually active adolescent at risk for HIV infection who presents with nonspecific viral symptoms. This is especially true for MSM, for females, the most common symptoms are vaginal discharge and dysuria. Again, infection may be asymptomatic. Vaginal itching and irregular menses or spotting are also common. Abdominal pain, fever, and vomiting, although less common and specific, are signs of PID. Pain in the genital region and dyspareunia may be present.

Signs that can be found in both males and females with an STI include genital ulcerations, adenopathy, and genital warts.

CHLAMYDIA TRACHOMATIS INFECTION

General Considerations

C trachomatis is the most common bacterial cause of STIs in the United States. In 2017, over 1.05 million cases in adolescents and young adults were reported to the CDC, representing 63% of reported chlamydia cases. C trachomatis is an obligate intracellular bacterium that replicates within the cytoplasm of host cells. Destruction of Chlamydia-infected cells is mediated by host immune responses.

Clinical Findings

A. Symptoms and Signs

Clinical infection in females manifests as dysuria, urethritis, vaginal discharge, cervicitis, irregular vaginal bleeding, or PID. The presence of mucopus at the cervical os (mucopurulent cervicitis) is a sign of chlamydial infection or gonorrhea. Chlamydial infection is asymptomatic in 75% of females.

Chlamydial infection may be asymptomatic in 70% of males or manifest as dysuria, urethritis, or epididymitis. Some patients complain of urethral discharge. On clinical examination, a clear white discharge may be found after milking the penis. Proctitis or proctocolitis from Chlamydia may occur in adolescents practicing receptive anal intercourse.

B. Laboratory Findings

NAAT is the most sensitive (92%–99%) way to detect Chlamydia. Enzyme-linked immunosorbent assay (ELISA) or direct fluorescent antibody (DFA) tests are less sensitive, but may be the only testing option in some centers.

A cervical or vaginal swab, using the manufacturer’s swab provided with the specific test, or first-void urine specimen, should be obtained. For urine screening, yields of testing are maximized when collecting between 10 and 20 mL of urine and ensuring that patient has not voided for 2 hours. Often a single swab can be used to collect both the Chlamydia and N gonorrhoeae specimen. To optimize detection of Chlamydia from the cervix, columnar cells need to be collected by inserting the swab in the os and rotating it 360 degrees. NAAT is not licensed for rectal samples but some laboratories have validated testing on rectal specimens for C trachomatis. Thus, when a rectal specimen is obtained, this must often be evaluated by less sensitive culture methods unless there is access to a laboratory that has validated Chlamydia NAAT for nongenital sites.

A first-void urine sample, or urethral swab for NAAT, should be obtained at least annually. Some studies suggest that more frequent screenings—every 6 months—in higher-prevalence populations will decrease endemic chlamydial infection. For both males and females, testing urine allows for more frequent screening and simplifies screening in large group settings, such as schools and correctional facilities.

Complications

Epididymitis is a complication in males. Reiter syndrome occurs in association with chlamydial urethritis. This should be suspected in male patients who are sexually active and present with low back pain (sacroiliitis), arthritis (polyarticular), characteristic mucocutaneous lesions, and conjunctivitis. PID is an important complication in females.

Treatment

Infected patients and their contacts, regardless of the extent of signs or symptoms, need to receive treatment (Table 44–1). Reinfection caused by failure of contacts to receive treatment or the initiation of sexual activity with a newly infected partner puts the adolescent at high risk of acquiring a repeat chlamydial infection within several months of the first infection. Because of this increased risk, all infected females and males should be retested approximately 3 months after treatment.

NEISSERIA GONORRHOEAE INFECTION

General Considerations

Gonorrhea is the second most prevalent bacterial STI in the United States, where over 556,000 new N gonorrhoeae infections were reported in 2017. Among 15–19-year-olds the rate of gonorrhea infections increased 15.5% in 2016–2017. During this same time rates increased 12.8% among those aged 20–24 years.

Sites of infection include the cervix, urethra, rectum, and pharynx. In addition, gonorrhea is a cause of PID. Humans are the natural reservoir. Gonococci are present in the exudate and secretions of infected mucous membranes.

Clinical Findings

A. Symptoms and Signs

In uncomplicated gonococcal cervicitis, females are symptomatic 23%–57% of the time, presenting with vaginal discharge and dysuria. Urethritis and pyuria may also be present. Mucopurulent cervicitis with a yellowish discharge may be found, and the cervix may be edematous and friable. Other symptoms include abnormal menstrual periods and dyspareunia. Approximately 15% of females with endocervical gonorrhea have signs of involvement of the upper genital tract. Compared with chlamydial infection, pelvic inflammation with gonorrhea has a shorter duration, but an increased intensity of symptoms, and is more often associated with fever. Symptomatic males usually have a yellowish-green urethral discharge and burning on urination, but most males (55%–67%) with N gonorrhoeae are asymptomatic. Both males and females can develop gonococcal proctitis and pharyngitis after appropriate exposure.

B. Laboratory Findings

A first-void urine sample or cervical or vaginal swab from females should be sent for NAAT. Culture or NAAT for N gonorrhoeae in males can be achieved with a swab of the urethra or first-void urine. Urethral culture is less sensitive (85%) compared with the 95%–99% sensitivity using NAAT methods on either urethral or urine specimens. Gram stain of urethral discharge showing gram-negative intracellular diplococci indicates gonorrhea in a male.

If proctitis is present, appropriate cultures should be obtained and treatment for both gonorrhea and chlamydial infection given. If oral exposure to gonorrhea is suspected, cultures should be taken and the patient given empiric treatment. If there is access to a laboratory that has validated NAAT for oropharyngeal or rectal specimens, this will substantially increase detection over culture methods.

Differential Diagnosis

Gonococcal pharyngitis needs to be differentiated from pharyngitis caused by streptococcal infection, herpes simplex, adenovirus, and infectious mononucleosis (EBV). Chlamydial infection needs to be differentiated from gonococcal infection.

Complications

Disseminated gonococcal infection occurs in a minority (0.5%–3%) of patients with untreated gonorrhea. Hematogenous spread most commonly causes arthritis and dermatitis. The joints most frequently involved are the wrist, metacarpophalangeal joints, knee, and ankle. Skin lesions are typically tender, with hemorrhagic or necrotic pustules or bullae on an erythematous base occurring on the distal extremities. Disseminated disease occurs more frequently in females than in males. Risk factors include pregnancy and gonococcal pharyngitis. Gonorrhea is complicated occasionally by perihepatitis.

Treatment

Since 2010, the CDC made two significant changes to gonorrhea treatment recommendations: dual treatment with azithromycin and ceftriaxone regardless of anatomic site involved and removal of the recommendation of oral cefixime treatment of gonorrhea (see Table 44–1). These changes reflect increasing resistance to cephalosporins, the frequency of coinfection with Chlamydia, and the need to increase consistency of treatment regimens.

CDC guidelines also state that N gonorrhoeae and C trachomatis do not require tests of cure when they are treated with first-line medications, unless the patient remains symptomatic. If retesting is indicated, it should be delayed for 1 month after completion of therapy if NAATs are used. Retesting might also be considered for sexually active adolescents likely to be reinfected. Due to increasing resistance of N gonorrhoeae to cephalosporins, providers considering treatment failure should also obtain a gonorrhea culture to assess for antibiotic resistance. Patients should be advised to abstain from sexual intercourse until both they and their partners have completed a course of treatment. Treatment for disseminated disease may require hospitalization. Quinolones should no longer be used to treat gonorrhea due to high levels of quinolone resistance in the United States. Failure of initial treatment should prompt reevaluation of the patient and consideration of retreatment with ceftriaxone.

The patient presenting with an STI usually has one or more of the signs or symptoms described in this section. Management considerations for STIs include assessing the patient’s adherence to therapy and ensuring follow-up, treating STIs in partners, and determining pregnancy risk. Treatment of each STI is detailed in Table 44–1.

CERVICITIS

General Considerations

In most cases of cervicitis no organism is isolated. The most common causes include C trachomatis or N gonorrhoeae. HSV, T vaginalis, and Mycoplasma genitalium are less common causes. Bacterial vaginosis is now recognized as a cause of cervicitis. Cervicitis can also be present without an STI.

Clinical Findings

A. Symptoms and Signs

Two major diagnostic signs characterize cervicitis: (1) purulent or mucopurulent endocervical exudate visible in the endocervical canal or on an endocervical swab and (2) easily induced bleeding with the passage of a cotton swab through the cervical os. Cervicitis is often asymptomatic, but many patients with cervicitis have an abnormal vaginal discharge or postcoital bleeding.

B. Laboratory Findings

Although endocervical Gram stain may show an increased number of polymorphonuclear leukocytes, this finding has a low positive predictive value and is not recommended for diagnosis. Patients with cervicitis should be tested for C trachomatis, N gonorrhoeae, and trichomoniasis by using the most sensitive and specific tests available at the site.

Complications

Persistent cervicitis is difficult to manage and requires reassessment of the initial diagnosis and reevaluation for possible re-exposure to an STI. Cervicitis can persist despite repeated courses of antimicrobial therapy. Presence of a large ectropion can contribute to persistent cervicitis.

Treatment

Empiric treatment for both gonorrhea and chlamydial infection is recommended because coinfection is common. If the patient is asymptomatic except for cervicitis, then treatment may wait until diagnostic test results are available (see Table 44–1). Follow-up is recommended if symptoms persist. Patients should be instructed to abstain from sexual intercourse until they and their sex partners are cured and treatment is completed.

PELVIC INFLAMMATORY DISEASE

General Considerations

Pelvic inflammatory disease (PID) is defined as inflammation of the upper female genital tract and may include endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. It is the most common gynecologic disorder necessitating hospitalization for female patients of reproductive age in the United States. The incidence is highest in teenage girls. Those who are sexually active have a high risk (1 in 8) of developing PID, whereas women in their 20s have one-tenth the risk. Predisposing risk factors include multiple sexual partners, younger age of initiating sexual intercourse, prior history of PID, and lack of condom use. Lack of protective antibody from previous exposure to sexually transmitted organisms and cervical ectopy contribute to the development of PID. Many adolescents with subacute or asymptomatic PID are never identified.

PID is a polymicrobial infection. Causative agents include N gonorrhoeae, C trachomatis, anaerobic bacteria that reside in the vagina, and genital mycoplasmas. Vaginal douching and other mechanical factors such as intrauterine devices in place for multiple years or prior gynecologic surgery increase the risk of PID by providing access of lower genital tract organisms to pelvic organs. Recent menses and bacterial vaginosis have been associated with the development of PID.

Clinical Findings

A. Symptoms and Signs

PID may be challenging to diagnose because of the wide variation in the symptoms and signs. No single historical, clinical, or laboratory finding has both high sensitivity and specificity for the diagnosis. Diagnosis of PID is usually made clinically (Table 44–2). Typical patients have lower abdominal pain, pelvic pain, or dyspareunia. Systemic symptoms such fever, nausea, or vomiting may be present. Vaginal discharge is variable. Cervical motion tenderness, uterine or adnexal tenderness, or signs of peritonitis are often present. Mucopurulent cervicitis is present in 50% of patients. Tubo-ovarian abscesses can often be detected by careful physical examination (feeling a mass or fullness in the adnexa).

B. Laboratory Findings

Laboratory findings may include elevated WBCs with a left shift and elevated acute-phase reactants (erythrocyte sedimentation rate or C-reactive protein). A positive test for N gonorrhoeae or C trachomatis is supportive, although 25% of the time neither of these bacteria is detected. Pregnancy needs to be ruled out, because patients with an ectopic pregnancy can present with abdominal pain and concomitant pregnancy will affect management.

C. Diagnostic Studies

Laparoscopy is the gold standard for detecting salpingitis. It is used if the diagnosis is in question or to help differentiate PID from an ectopic pregnancy, ovarian cysts, or adnexal torsion. Endometrial biopsy should be performed in women undergoing laparoscopy who do not have visual evidence of salpingitis because some women may have isolated endometritis. The clinical diagnosis of PID has a positive predictive value for salpingitis of 65%–90% in comparison with laparoscopy. Pelvic ultrasonography also is helpful in detecting tubo-ovarian abscesses, which are found in almost 20% of teens with PID. Transvaginal ultrasound is more sensitive than abdominal ultrasound. All women who have acute PID should be tested for N gonorrhoeae and C trachomatis and should be screened for HIV infection.

Differential Diagnosis

Differential diagnosis includes other gynecologic illnesses (ectopic pregnancy, threatened or septic abortion, adnexal torsion, ruptured and hemorrhagic ovarian cysts, dysmenorrhea, endometriosis, or mittelschmerz), gastrointestinal illnesses (appendicitis, cholecystitis, hepatitis, gastroenteritis, or inflammatory bowel disease), and urinary tract illnesses (cystitis, pyelonephritis, or urinary calculi).

Complications

Scarring of the fallopian tubes is one of the major sequelae of PID. After one episode of PID, 17% of patients become infertile, 17% develop chronic pelvic pain, and 10% will have an ectopic pregnancy. Infertility rates increase with each episode of PID; three episodes of PID result in a 73% infertility rate. Duration of symptoms appears to be the largest determinant of infertility. Hematogenous or lymphatic spread of organisms from the fallopian tubes rarely causes inflammation of the liver capsule (perihepatitis) resulting in symptoms of pleuritic right upper quadrant pain and elevation of liver function tests.

Treatment

The objectives of treatment are both to achieve a clinical cure and to prevent long-term sequelae. There are no differences in short- and long-term clinical and microbiologic response rates resulting from parenteral or oral therapy. PID is frequently managed at the outpatient level, although some clinicians argue that all adolescents with PID should be hospitalized because of the frequency of complications. Severe systemic symptoms and toxicity, signs of peritonitis, inability to take fluids, pregnancy, nonresponse or intolerance of oral antimicrobial therapy, and tubo-ovarian abscess favor hospitalization. In addition, if the health care provider believes that the patient will not adhere to treatment, hospitalization is warranted. Pregnant women with PID should be admitted to hospital and treated with parental antibiotics to reduce the risk of increased morbidity. Surgical drainage may be required for adequate treatment of tubo-ovarian abscesses.

The broad-spectrum antibiotic regimens described in Table 44–1 cover the numerous microorganisms associated with PID. All treatment regimens should be effective against N gonorrhoeae and C trachomatis because negative endocervical screening tests do not rule out upper reproductive tract infection with these organisms. Outpatient treatment should be reserved for compliant patients who have classic signs of PID without systemic symptoms. Patients with PID who receive outpatient treatment should be reexamined within 24–48 hours, with phone contact in the interim, to assess persistent disease or treatment failure. Patients should have substantial improvement within 48–72 hours. An adolescent should be reexamined 7–10 days after the completion of therapy to ensure the resolution of symptoms.

URETHRITIS

General Considerations

The most common bacterial causes of urethritis in males are N gonorrhoeae and C trachomatis. Additionally, T vaginalis, HSV, Ureaplasma urealyticum, and M genitalium cause urethritis. Approximately 15%–25% of nongonococcal, nonchlamydial urethritis can be attributed to either M genitalium or U urealyticum. Coliforms may cause urethritis in males practicing insertive anal intercourse. Mechanical manipulation or contact with irritants can also cause transient urethritis. It is important to recognize that urethritis in both males and females are frequently asymptomatic.

Females often present with symptoms of a urinary tract infection and “sterile pyuria” (no enteric bacterial pathogens isolated), which reflects urethritis caused by the organisms described above.

Clinical Findings

A. Symptoms and Signs

If symptomatic, males present most commonly with a clear or purulent discharge from the urethra, dysuria, or urethral pruritus. Hematuria and inguinal adenopathy can occur. Most infections caused by C trachomatis and T vaginalis are asymptomatic, while 70% of males with M genitalium and 23%–90% with gonococcal urethritis are symptomatic.

B. Laboratory Findings

In a symptomatic male a positive leukocyte esterase test on first-void urine, or microscopic examination of first-void urine demonstrating more than 10 WBCs per high-power field, is suggestive of urethritis. Gram stain of urethral secretions demonstrating more than 5 WBCs per high-power field is also suggestive. Gonococcal urethritis is established by documenting the presence of WBCs containing intracellular gram-negative diplococci. Urethral swab or first-void urine for NAAT should be sent to the laboratory to detect N gonorrhoeae and C trachomatis. Evaluation for T vaginalis should be considered as newer technologies increase the sensitivity and specificity of detecting T vaginalis over wet mount. Microscopic examination of urethral discharge is not a sensitive test. Specific NAAT testing of urine is available for Mycoplasma and Ureaplasma, though it is not often clinically utilized.

Complications

Complications include recurrent or persistent urethritis, epididymitis, prostatitis, or Reiter syndrome.

Treatment

Patients with objective evidence of urethritis should receive empiric treatment for gonorrhea and chlamydial infection, ideally directly observed in the office (see Table 44–1). Some data suggest better outcomes for treatment of M genitalium with azithromycin. If the infection is unresponsive to initial treatment and the infection is NAAT-negative, trichomoniasis should be ruled out and nongonococcal, nonchlamydial urethritis should be suspected and treated appropriately. Patients should be instructed to return for evaluation if symptoms persist or recur after completion of initial empiric therapy. Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not a sufficient basis for retreatment. Sexual partners should either be evaluated or treated for gonorrhea and chlamydial infection.

EPIDIDYMITIS

General Considerations

Epididymitis in a male who is sexually active is most often caused by C trachomatis or N gonorrhoeae. Epididymitis caused by Escherichia coli occurs among males who are the insertive partners during anal intercourse and in males who have urinary tract abnormalities.

Clinical Findings

A. Symptoms and Signs

Epididymitis presents as a constellation of pain, swelling, and inflammation of the epididymis. In many cases, the testis is also involved.

B. Laboratory and Diagnostic Studies

Diagnosis is generally made clinically. Color Doppler ultrasound can help make the diagnosis. Although often not available, radionuclide scanning of the scrotum is the most accurate method of diagnosis. Laboratory evaluation is the same as for suspected urethritis and should include urine culture if NAAT is negative.

Differential Diagnosis

Acute epididymitis must be distinguished from orchitis due to infarct, testicular torsion, or viral infection. Less common and more chronic illnesses include testicular cancer, tuberculosis, or fungal infection.

Complications

Infertility is rare, and chronic local pain is uncommon.

Treatment

Empiric therapy (see Table 44–1) is indicated before culture results are available. As an adjunct to therapy, bed rest, scrotal elevation, and analgesics are recommended until fever and local inflammation subside. Lack of improvement of swelling and tenderness within 3 days requires reevaluation of both the diagnosis and therapy. Sex partners should be evaluated and treated for gonorrhea and chlamydial infections.

PROCTITIS, PROCTOCOLITIS, & ENTERITIS

General Considerations

Proctitis occurs predominantly among persons who participate in anal intercourse. Enteritis occurs among those whose sexual practices include oral-fecal contact. Proctocolitis can be acquired by either route depending on the pathogen. Common sexually transmitted pathogens causing proctitis or proctocolitis include C trachomatis (including lymphogranuloma venereum [LGV] serovars), Treponema pallidum, HSV, N gonorrhoeae, Giardia lamblia, and enteric organisms. As many as 85% of rectal infections with N gonorrhoeae and C trachomatis are asymptomatic. The presence of symptomatic or asymptomatic proctitis may facilitate the transmission of HIV infection.

Clinical Findings

A. Symptoms and Signs

Proctitis, defined as inflammation limited to the distal 10–12 cm of the rectum, is associated with anorectal pain, tenesmus, and rectal discharge. Acute proctitis among persons who have recently practiced receptive anal intercourse is most often sexually transmitted. The symptoms of proctocolitis combine those of proctitis, plus diarrhea or abdominal cramps (or both), because of inflamed colonic mucosa more than 12 cm from the anus. Enteritis usually results in diarrhea and abdominal cramping without signs of proctitis or proctocolitis.

B. Laboratory and Diagnostic Studies

Evaluation may include anoscopy or sigmoidoscopy, stool examination, culture or NAAT for appropriate organisms, and serology for syphilis.

Treatment

Management will be determined by the etiologic agent (see Table 44–1 and Chapter 42). Reinfection may be difficult to distinguish from treatment failure.

VAGINAL DISCHARGE

Adolescent girls may have a normal physiologic leukorrhea, secondary to turnover of vaginal epithelium. Infectious causes of discharge include T vaginalis, C trachomatis, N gonorrhoeae, and bacterial vaginosis pathogens. Candidiasis is a yeast infection that produces vaginal discharge, but is not usually sexually transmitted. Vaginitis in general may cause vaginal discharge, vulvar itching, and irritation. Discharge may be white, gray, or yellow. Physiologic leukorrhea is usually white, homogeneous, and not associated with itching, irritation, or foul odor. Mechanical, chemical, allergic, or other noninfectious irritants of the vagina may cause vaginal discharge.

1. Bacterial Vaginosis

General Considerations

Bacterial vaginosis is a polymicrobial infection of the vagina caused by an imbalance of the normal bacterial vaginal flora. The altered flora has a paucity of hydrogen peroxide-producing lactobacilli and increased concentrations of anaerobic bacteria (Prevotella spp and Mobiluncus spp), Gardnerella vaginalis, Ureaplasma, and Mycoplasma. It is unclear whether bacterial vaginosis is sexually transmitted, but it is associated with having multiple sex partners and women with bacterial vaginosis are at increased risk for other STIs.

Clinical Findings

A. Symptoms and signs

The most common symptom is a copious, malodorous, homogeneous thin gray-white vaginal discharge. Patients may report vaginal itching or dysuria. A fishy odor may be most noticeable after intercourse or during menses, when the high pH of blood or semen volatilizes the amines.

B. Laboratory Findings

Bacterial vaginosis is most often diagnosed by the use of clinical criteria, which include: (1) presence of thin, white discharge that smoothly coats the vaginal walls; (2) fishy (amine) odor before or after the addition of 10% KOH (whiff test); (3) pH of vaginal fluid greater than 4.5 determined with narrow-range pH paper; and (4) presence of “clue cells” on microscopic examination. Clue cells are squamous epithelial cells that have multiple bacteria adhering to them, making their borders irregular and giving them a speckled appearance. Diagnosis requires three out of four criteria, although many female patients who fulfill these criteria have no discharge or other symptoms.

Complications

Bacterial vaginosis during pregnancy is associated with adverse outcomes such as premature labor, preterm delivery, intra-amniotic infection, and postpartum endometritis. In the nonpregnant individual, it may be associated with PID and urinary tract infections.

Treatment

All female patients who have symptomatic disease should receive treatment to relieve vaginal symptoms and signs of infection (see Table 44–1). Pregnant patients should receive treatment to prevent adverse outcomes of pregnancy. Treatment for patients who do not complain of vaginal discharge or itching, but who demonstrate bacterial vaginosis on routine pelvic examination, is unclear. Because some studies associate bacterial vaginosis and PID, the recommendation is to have a low threshold for treating asymptomatic bacterial vaginosis. Follow-up visits are unnecessary if symptoms resolve. Recurrence of bacterial vaginosis is not unusual. Follow-up examination 1 month after treatment for high-risk pregnant patients is recommended.

Males do not develop infection equivalent to bacterial vaginosis and are often asymptomatic. Treatment of male partners has no effect on the course of infection in females but treatment is recommended for women who have sex with women.

2. Trichomoniasis

General Considerations

Trichomoniasis is caused by T vaginalis, a flagellated protozoan that infects 3.7 million people annually in the United States.

Clinical Findings

A. Symptoms and Signs

Fifty percent of females with trichomoniasis develop a symptomatic vaginitis with vaginal itching, a green-gray malodorous frothy discharge, and dysuria. Occasionally postcoital bleeding and dyspareunia may be present. The vulva may be erythematous and the cervix friable.

B. Laboratory Findings

Mixing the discharge with normal saline facilitates detection of the flagellated protozoan on microscopic examination (wet preparation). This has a sensitivity of only 60%–70% even with immediate evaluation of the slide to achieve optimal results. Culture and NAAT testing are available when the diagnosis is unclear. NAAT tests are sensitive, but expensive, and not readily available. Two FDA-approved, point-of-care antigen-based detection assays for T vaginalis are available, but false positive results are problematic in low disease prevalence populations. Both antigen assays are performed on vaginal secretions and have a sensitivity greater than 83% and a specificity greater than 97%. Trichomonal urethritis frequently causes a positive urine leukocyte esterase test and WBCs on urethral smear.

Complications

Trichomonas infection in females has been associated with adverse pregnancy outcomes. Male partners of females diagnosed with trichomoniasis have a 22% chance of having trichomoniasis. Half of males with trichomoniasis will have urethritis. Male partners should receive empiric therapy for trichomoniasis. Rescreening for T vaginalis at 3 months following initial infection is recommended for women due to the high rate of reinfection.

Treatment

See Table 44–1 for treatment recommendations.

3. Vulvovaginal Candidiasis

General Considerations

Vulvovaginal candidiasis is caused by Candida albicans in 85%–90% of cases. Most females will have at least one episode of vulvovaginal candidiasis in their lifetime, and almost half will have two or more episodes. The highest incidence is between ages 16 and 30 years. Predisposing factors include recent use of antibiotics, diabetes, pregnancy, and HIV. Risk factors include vaginal intercourse, especially with a new sexual partner, use of oral contraceptives, and use of spermicide. This disease is usually caused by unrestrained growth of Candida that normally colonizes the vagina asymptomatically or is infected secondarily from Candida present in the GI tract. Recurrences reflect reactivation of colonization.

Clinical Findings

A. Symptoms and Signs

Typical symptoms include pruritus and a white, cottage cheese-like vaginal discharge without odor. The itching is more common midcycle and shortly after menses. Other symptoms include vaginal soreness, vulvar burning, vulvar edema and redness, dyspareunia, and dysuria (especially after intercourse).

B. Laboratory Findings

The diagnosis is usually made by visualizing yeast or pseudohyphae with 10% KOH (90% sensitive) or Gram stain (77% sensitive) in the vaginal discharge. Fungal culture can be used if symptoms and microscopy are not definitive or if disease is unresponsive or recurrent. However, culture is not very specific as colonization is common in asymptomatic females. Vaginal pH is normal with yeast infections.

Complications

The only complication of vulvovaginal candidiasis is recurrent infections. Most females with recurrent infection have no apparent predisposing or underlying conditions.

Treatment

Short-course topical formulations effectively treat uncomplicated vaginal yeast infections (see Table 44–1). The topically applied azole drugs are more effective than nystatin. Treatment with azoles results in relief of symptoms and negative cultures in 80%–90% of patients who complete therapy. Oral fluconazole as a one-time dose is an effective oral treatment. Patients should be instructed to return for follow-up visits only if symptoms persist or recur. Six-month prophylaxis regimens have been effective in many female patients with persistent or recurrent yeast infection. Recurrent disease is usually due to C albicans that remains susceptible to azoles, and should be treated for 14 days with oral azoles. Some nonalbicans Candida will respond to itraconazole or boric acid gelatin capsules (600 mg daily for 14 days) intravaginally. Treatment of sex partners is not recommended, but may be considered for females who have recurrent infection.

GENITAL ULCERATIONS

In the United States, young, sexually active patients who have genital ulcers have genital herpes or syphilis. The relative frequency of each disease differs by geographic area and patient population; however, in most areas, genital herpes is the most prevalent of these diseases. More than one of these diseases could be present in a patient with genital ulcers. All ulcerative diseases are associated with an increased risk for HIV infection. Primary HIV infection (acute retroviral syndrome) may present with oral and genital lesions. Less common causes of genital ulceration include chancroid and donovanosis.

Location of the ulcers is dependent on the specific type of sexual behavior. Ulcers may be vaginal, vulvar, cervical, penile, or rectal. Oral lesions may occur concomitantly with genital ulcerations. Each etiologic agent has specific characteristics that are described in the following sections. Lesion pain, inguinal lymphadenopathy, and urethritis may be found in association with the ulcers.

1. Herpes Simplex Virus Infection

(See Also Chapter 40)

General Considerations

HSV is the most common cause of visible genital ulcers. HSV-1 is commonly associated with infections of the face, including the eyes, pharynx, and mouth. However, each serotype is capable of infecting either region. HSV-1 infections are frequently established in children by age 5 through oral acquisition; lower socioeconomic groups have higher infection rates. Both HSV-1 and HSV-2 cause STIs. The prevalence of both infections in the United States increases during teen years. In this age group and young adults, HSV-1 has become the predominant cause of genital infection. Rates of HSV-2 seroprevalence reach 20%–40% in 40-year-olds. HSV infections are lifelong as a result of latent infection of sensory ganglia, although many individuals infected with either type of HSV infection, may not be aware of their infection because of mild or nonspecific symptoms. Nevertheless, these individuals can still asymptomatically shed virus and thereby unknowingly transmit the infection, and they can reactivate the virus to cause clinical infection in themselves.

Clinical Findings

A. Symptoms and Signs

Symptomatic initial genital HSV infection causes vesicles of the vulva, vagina, cervix, penis, rectum, or urethra, which are quickly followed by shallow, painful ulcerations. Atypical presentation of HSV infection includes vulvar erythema and fissures. Urethritis may occur. Initial infection can be severe, lasting up to 3 weeks, and be associated with fever and malaise, as well as localized tender adenopathy. The pain and dysuria can be extremely uncomfortable, requiring sitz baths, topical anesthetics, and occasionally catheterization for urinary retention.

Symptoms tend to be more severe in females. Recurrence in the genital area with HSV-2 is likely (65%–90%). Approximately 40% of individuals infected with HSV-2 will experience at least six recurrences per year in the early years after initial infection. Prodromal pain in the genital, buttock, or pelvic region is common prior to recurrences. Recurrent genital HSV is of shorter duration (5–7 days), with fewer lesions and usually no systemic symptoms. Commonly, the frequency of recurrences decreases over time, although approximately one-third of individuals fail to demonstrate this improvement. First-episode genital herpes infection caused by HSV-1 is usually the consequence of oral-genital sex. Primary HSV-1 infection generally is as severe as HSV-2 infection, and treatment is the same. Recurrence of genital HSV-1 is less frequent than genital HSV-2. Genital HSV-1 occurs in less than 50% of patients.

B. Laboratory Findings

Diagnosis of genital HSV infection is often made presumptively, but in one large series this diagnosis was incorrect for 20% of cases. Cell culture and PCR testing are the CDC’s preferred methods of testing. NAAT is more sensitive. Direct immunofluorescence assays are available, but lack sensitivity.

Differential Diagnosis

Genital HSV infections must be distinguished from other ulcerative STI lesions, including syphilis, chancroid, and lymphogranuloma venereum (LGV). Non-STIs might include herpes zoster, Behçet syndrome, or lichen sclerosis. (See next two sections Syphilis and Chancroid.)

Complications

Complications, almost always only with the first episode of genital HSV infection, include viral meningitis, urinary retention, transmission to newborns at birth, and pharyngitis. Infection with genital HSV, whether active or not, greatly increases the likelihood of transmitting or acquiring HIV infection within couples discordant for HIV.

Prevention

All patients with active lesions should be counseled to abstain from sexual contact. Almost all patients have very frequent periodic asymptomatic shedding of HSV, and most cases of genital HSV infection are transmitted by persons who are unaware that they have the infection or are asymptomatic when transmission occurs. Reactivation with asymptomatic shedding occurs even in individuals who were asymptomatically infected. Individuals with prior HSV infection should be encouraged to use condoms to protect susceptible partners. Antiviral prophylaxis of infected individuals reduces shedding and significantly reduces the chance of transmission to their sexual partners.

Treatment

Antiviral drugs administered within the first 5 days of primary infection decrease the duration and severity of HSV infection (see Table 44–1). The effect of antivirals on the severity or duration of recurrent disease is limited. For best results with recurrent disease, therapy should be started with the prodrome or during the first day of the recurrence. Patients should have a prescription at home to initiate treatment. If recurrences are frequent and cause significant physical or emotional discomfort, patients may elect to take antiviral prophylaxis on a daily basis to reduce the frequency (70% decrease) and duration of recurrences. Treatment of first or subsequent attacks will not prevent future attacks.

2. Syphilis

General Considerations

Syphilis is an acute and chronic STI caused by infection with T pallidum. The national rate of syphilis has increased annually since reaching an all-time low in 2000. Increases have been observed in both genders, but predominantly in MSM, who now account for 58% of primary and secondary cases reported to the CDC. In 2017, the CDC reported an increase of 21% in new cases of primary and secondary syphilis among women with subsequent increases in the rate of congenital syphilis. Men between the ages of 25 and 29 years have the highest rates of syphilis. Nearly 50% of the cases of syphilis in MSM in 2017 were also living with HIV.

Clinical Findings

A. Symptoms and Signs

Skin and mucous membrane lesions characterize the acute phase of primary and secondary syphilis. Lesions of the bone, viscera, aorta, and central nervous system predominate in the chronic phase (tertiary syphilis) (see Chapter 42). Prevention of syphilis is also important because syphilitic mucosal lesions facilitate transmission of HIV.

Primary syphilis usually presents as a solitary chancre at the point of inoculation. Characteristically, the chancre presents as a painless, indurated, nonpurulent ulcer with a clean base and associated nontender, firm adenopathy. The chancre appears on average 21 days (range: 3–90 days) after exposure and resolves spontaneously 4–8 weeks later. Because it is painless, it may go undetected, especially if the lesion is within the vagina, oropharynx, urethra, or rectum. Chancres may occur on the genitalia, anus, or oropharynx. Secondary syphilis occurs 4–10 weeks after the chancre appears, with generalized malaise, painless adenopathy, and a nonpruritic maculopapular rash that often includes the palms and soles. Secondary syphilis resolves in 1–3 months, but can recur. Verrucous lesions known as condylomata lata may develop on the genitalia. These must be distinguished from genital warts.

B. Laboratory Findings

If the patient has a suspect primary lesion, is at high risk, is a contact, or may have secondary syphilis, a nontreponemal serum screen—either RPR or VDRL—should be performed. If the nontreponemal test is positive, then a specific treponemal test—a fluorescent treponemal antibody-absorbed (FTA-ABS) or microhemagglutination–T pallidum (MHA-TP) test—is done to confirm the diagnosis.

If a patient is engaging in high-risk sexual behavior or is living in an area in which syphilis is endemic, RPRs should be drawn yearly to screen for asymptomatic infection. Annual RPR testing among high-risk groups is essential to distinguish between early latent syphilis (1 year or less postinfection), late latent syphilis (> 1 year postinfection), or syphilis of unknown duration, as treatment recommendations vary. Syphilis is reportable to state health departments, and all sexual contacts need to be evaluated. Patients also need to be evaluated for other STIs, especially HIV. People with HIV have increased rates of failure with some treatment regimens and treatment of the HIV infection should occur as soon as indicated after diagnosis.

Complications

Untreated syphilis can lead to tertiary complications with serious multiorgan involvement, including aortitis and neurosyphilis. Transmission to the fetus can occur from an untreated pregnant woman (see Chapters 2 and 42).

Treatment

See Table 44–1 for treatment recommendations. Patients should be reexamined and serologically evaluated with nontreponemal tests at 6 and 12 months after treatment. If signs or symptoms persist or recur, or patients do not have a fourfold decrease in their nontreponemal test titer, they should be considered to have failed treatment or be reinfected and need retreatment.

3. Chancroid

General Considerations

Chancroid is caused by Haemophilus ducreyi. It is relatively rare outside of the tropics and subtropics, but is endemic in some urban areas in the United States, and has been associated with HIV infection, drug use, and prostitution. Coinfection with syphilis or HSV occurs in as many as 17% of patients. A detailed history, including travel, may prove to be important in identifying this infection.

Clinical Findings

A. Symptoms and Signs

The typical lesion begins as a papule that erodes after 24–48 hours into an ulcer. The ulcer is painful and has ragged, sharply demarcated edges and a purulent base (unlike syphilis). The ulcer is typically solitary and somewhat deeper than HSV infection. The lesions may occur anywhere on the genitals and are more common in men than in women. Tender, fluctuant (unlike syphilis and HSV) inguinal adenopathy is present in 50% of patients. A painful ulcer in combination with suppurative inguinal adenopathy is very often chancroid.

B. Laboratory Findings

Gram stain shows gram-positive cocci arranged in a boxcar formation. Culture, which has a sensitivity of less than 80%, can be performed on a special medium that is available in academic centers. NAAT testing may improve laboratory diagnosis in areas where such testing is available.

Differential Diagnosis

Chancroid is distinguished from syphilis by the painful nature of the ulcer and the associated tender suppurative adenopathy. HSV vesicles often produce painful ulcers, but these are multiple, smaller, and shallower than chancroid ulcers. Adenopathy associated with initial HSV infection does not suppurate. A presumptive diagnosis of chancroid should be considered in a patient with typical painful genital ulcers and regional adenopathy when the test results for syphilis and HSV are negative.

Treatment

Symptoms improve within 3 days after therapy (see Table 44–1). Most ulcers resolve in 7 days, although large ulcers may take 2 weeks to heal. All sexual contacts need to be examined and given treatment, even if asymptomatic. Individuals with HIV coinfection may have slower rates of healing or treatment failures.

4. Lymphogranuloma Venereum

General Considerations

Lymphogranuloma venereum (LGV), caused by C trachomatis serovars L1, L2, or L3, is generally rare in the United States. The disease is endemic in Southeast Asia, the Caribbean, Latin America, and areas of Africa. Since 2003, an increased number of cases in the United States, Western Europe, and Canada have occurred primarily among MSM and has been associated with HIV coinfection.

Clinical Findings

A. Symptoms and Signs

Patients with LGV present with a painless vesicle or ulcer that heals spontaneously, followed by the development of tender adenopathy that is typically unilateral. A classic finding is the groove sign—an inguinal crease created by concomitant involvement of inguinal and femoral nodes. These nodes become matted and fluctuant and may rupture. LGV can cause proctocolitis with rectal ulceration, purulent anal discharge, fever, tenesmus, and lower abdominal pain, primarily in MSM.

B. Laboratory Findings

Diagnosis of LGV can be difficult. It generally requires a clinical suspicion based on physical examination findings. Lesion swabs and lymph node aspirates can be tested for Chlamydia by culture, DFA, or NAAT. NAAT is not FDA cleared for rectal specimens. Additional genotyping is necessary to differentiate LGV from non-LGV serovars of Chlamydia. In the absence of laboratory testing to confirm the diagnosis, one should treat for LGV if clinical suspicion is high.

Differential Diagnosis

Differential diagnosis during the adenopathy phase includes bacterial adenitis, lymphoma, and cat-scratch disease. Differential diagnosis during the ulcerative phase encompasses all causes of genital ulcers.

Treatment

See Table 44–1 for treatment recommendations. Despite the effectiveness of azithromycin for non-LGV chlamydial infections, there have been no controlled treatment trials to recommend its use in LGV. HIV-infected individuals are treated the same as non–HIV-infected individuals, but should be monitored closely to assess response to treatment.

5. Other Ulcerations

Granuloma inguinale, or donovanosis, is caused by Klebsiella granulomatis, a gram-negative bacillus that is rare in the United States, but is endemic in India, the Caribbean, and southern Africa. An indurated subcutaneous nodule erodes to form a painless, friable ulcer with granulation tissue. Diagnosis is based on clinical suspicion and supported by a Wright or Giemsa stain of the granulation tissue that reveals intracytoplasmic rods (Donovan bodies) in mononuclear cells. See Table 44–1 for treatment recommendations. Relapse may occur 6–18 months after apparently effective treatment with a 3-week course of doxycycline.

GENITAL WARTS & HUMAN PAPILLOMAVIRUS

General Considerations

Condylomata acuminata, or genital warts, are caused by HPV, which can also cause cervical dysplasia and cervical cancer, and oropharyngeal and anal cancers. HPV is transmitted sexually. An estimated 20 million people in the United States are infected annually with HPV, including approximately more than 9 million sexually active adolescents and young adults 15–24 years of age. The majority (74%) of new HPV infections occurs among those 15–24 years of age; in females younger than age 25 years, the prevalence ranges between 28% and 46%. It is estimated that 32%–50% of adolescent females having sexual intercourse in the United States have HPV infections, though only 1% may have visible lesions. Thirty to 60% of males whose partners have HPV have evidence of genital warts on examination. An estimated 1 million new cases of genital warts occur every year in the United States.

Although there are almost 100 serotypes of HPV, types 6 and 11 cause approximately 90% of genital warts, and HPV types 16 and 18 cause more than 70% of cervical dysplasia and cervical cancer. The infection is more common in persons with multiple partners and in those who initiate sexual intercourse at an early age.

Pap smears should be obtained starting at age 21 and then every 3 years. More frequent and earlier evaluations are recommended if there are additional risk factors such as coinfection with HIV.

Clinical Findings

A. Symptoms and Signs

For males, verrucous lesions are found on the shaft or corona of the penis. Lesions also may develop in the urethra or rectum. Lesions do not produce discomfort. They may be single or found in clusters. Females develop verrucous lesions on any genital mucosal surface, either internally or externally, and often develop perianal lesions.

B. Laboratory Findings

External, visible lesions have unique characteristics that make the diagnosis straightforward. Condylomata acuminata can be distinguished from condylomata lata (syphilis), skin tags, and molluscum contagiosum by application of 5% acetic acid solution. Blanching of skin or mucous membranes, after application of 3%–5% acetic acid solution, acetowhitening, is used to indicate the extent of cervical infection.

Pap smears detect cervical abnormalities. HPV infection is the most frequent cause of an abnormal smear. Pap smear findings are graded by the atypical nature of the cervical cells. These changes range from atypical squamous cells of undetermined significance (ASCUS) to low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). LSIL encompasses cellular changes associated with HPV and mild dysplasia. HSIL includes moderate dysplasia, severe dysplasia, and carcinoma in situ.

Follow-up for ASCUS is controversial, as only 25% progress to dysplasia, and the remainder is stable or regress. Updated recommendations prefer repeat cytology in 12 months with no HPV DNA testing. If a test for HPV DNA is performed and is positive, then repeat cytology in 12 months is recommended. If the grade of the atypical squamous cells remains uncertain or if there is HSIL, colposcopy is recommended. If LSIL is detected, colposcopy is not needed, but a repeat Pap smear should be done in 1 year, and if LSIL or HSIL are subsequently detected, the patient should be referred for colposcopy for direct visualization or biopsy of the cervix (or both). If a Pap smear shows signs of inflammation only, and concomitant infection such as vaginitis or cervicitis is present, the smear should be repeated after the inflammation has cleared.

Differential Diagnosis

The differential diagnosis includes normal anatomic structures (pearly penile papules, vestibular papillae, and sebaceous glands), molluscum contagiosum, seborrheic keratosis, and syphilis.

Complications

Because genital warts can proliferate and become friable during pregnancy, many experts advocate their removal during pregnancy. HPV types 6 and 11 can cause laryngeal papillomatosis in infants and children. Complications of appropriate treatment include scarring with changes in skin pigmentation or pain at the treatment site. Pap smears with persistent or high-grade dysplasia require biopsy and/or resection, which may result in cervical abnormalities that complicate pregnancy. Cervical cancer is the most common and important sequelae of HPV and persistent cervical dysplasia.

Prevention

The use of condoms significantly reduces, but does not eliminate, the risk for transmission to uninfected partners. The 9-valent HPV vaccine is 96%–100% effective in preventing HPV-6 and 11-related genital warts and HPV-16 and 18-related cervical dysplasia and many of the cervical lesions caused by less common serotypes. It is recommended for females and males aged 9–26 years. Males are protected against genital warts and anal cancer, which has a significantly increased incidence in males who practice anal sex (see Chapter 10).

Treatment

Penile and external vaginal or vulvar lesions can be treated topically. Treatment may need to occur weekly for 4–6 weeks. An experienced practitioner should treat internal and cervical lesions (see Table 44–1). Treatment may clear the visible lesions, but not reduce the presence of virus, nor is it clear whether transmission of HPV is reduced by treatment.

Warts may resolve or remain unchanged if left untreated or they may increase in size or number. Treatment can induce wart-free periods in most patients. Most recurrences occur within the 3 months following completion of a treatment regimen. Appropriate follow-up of abnormal Pap smears is essential to detect any progression to malignancy.

OTHER VIRAL INFECTIONS

1. Hepatitis

(See also Chapter 22)

General Considerations

In the United States, viral hepatitis is linked primarily to three viruses: hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV). Each virus has the potential to be spread through sexual activity. HAV is spread via fecal-oral transmission and oral-anal contact. Both HBV and HCV are spread through contact with blood or body fluids. Sexual transmission of HBV is believed to be much more efficient than that of HCV although recent data have suggested increased transmission of HCV in MSM.

Universal immunization recommendations for HAV and HBV have contributed to the decline in the prevalence of these diseases. However, individuals born before implementation of routine vaccination, especially those in high-risk groups (multiple sexual partners or MSM should receive vaccination).

2. Human Immunodeficiency Virus

(See also Chapter 41)

General Considerations

In 2017, 21% of new HIV infections in the United States occurred in youth and young adults aged 13–24 years. Data suggest that adolescents and young adults are less likely to be aware of their HIV infection than older individuals with HIV. Because of the long latency period between infection with HIV and progression to AIDS, it is felt that many HIV-positive young adults contracted HIV during adolescence. CDC incidence data indicate that young men who have sex with men continue to be the highest-risk group, particularly young men of color. Young women account for approximately 13% of the infections in this age group with black and Hispanic women bearing a disproportionate burden of the disease. Risk factors for contracting HIV include a prior STI, infrequent condom use, practicing insertive or receptive anal sex (both males and females), prior genital HSV infection, practicing survival sex (ie, trading sex for money or drugs), intravenous drug or crack cocaine or crystal methamphetamine use, homelessness, and being the victim of sexual abuse (males).

HIV infection should be considered in all sexually active youth, whether they have sex with males, females, or both. The CDC and the United States Preventative Services Task Force recommend adolescents be offered HIV testing at least once. Individual risk factors should then be used to determine the frequency of repeat testing. Opportunities for HIV screening in adolescents should include STI screening or treatment, pregnancy testing, or routine health evaluations. Most states allow adolescents to consent to HIV testing and treatment, but providers should be aware of their particular State’s laws.

Clinical Findings

A. Symptoms and Signs

Adolescents may be asymptomatic with recent HIV infection or may present with the acute retroviral syndrome, which is evident 2–6 weeks after exposure. The acute clinical syndrome, which occurs in about 50% of patients, is generally indistinguishable from other viral illnesses with respect to fever, malaise, and upper respiratory symptoms. Distinguishing features include generalized lymphadenopathy, rash, oral and genital ulcerations, aseptic meningitis, and thrush. After the acute illness, signs and symptoms may be absent for many years.

B. Laboratory Findings

In 2014, the CDC updated its recommendations for HIV screening. The new recommendations are based on the availability of technologies that allow for earlier detection of HIV infection than offered by ELISA followed by Western Blot confirmation. The new testing algorithm for serum or plasma recommends the use of an HIV 1/2 antigen/antibody combination immunoassay for initial testing. This test detects antibodies to both HIV-1 and HIV-2 and the HIV-1 p24 antigen, which can occur approximately 3 weeks following HIV infection. This detects both established infections and more recent infections.

If acute HIV infection is suspected, HIV testing should be done by HIV RNA PCR testing or HIV DNA PCR testing. Routine serological testing may not be positive for 2–3 weeks or longer. Viral load values of less than 3000 copies/mL by RNA PCR may indicate a false positive in this setting and repeat testing would be indicated.

Treatment

The most important aspect of identifying adolescents and young adults with HIV infection is linking them to care. Data support the treatment of youth with HIV infection in care settings that provide comprehensive, multidisciplinary care. These settings will be best equipped to provide emotional support, preventative care, risk reduction for contacts, access to research, and guidance on the appropriate timing of antiretroviral therapies.

3. HIV Postsexual Exposure Prophylaxis

Adolescents may present to health care providers seeking nonoccupational HIV postexposure prophylaxis (nPEP) following an assault or a high-risk sexual encounter. The risk of acquiring HIV infection through sexual assault or abuse is low but present. The risk for HIV transmission from a positive contact per episode of receptive penile-anal sexual exposure is estimated at 0.5%–3%; the risk per episode of receptive vaginal exposure is estimated at less than 0.1%–0.2%. HIV transmission also occurs from receptive oral exposure, but the risk is unknown. The risk of HIV transmission may be increased in certain conditions: traumatic vaginal, anal, or oral penetration; site of exposure to ejaculate; HIV viral load in ejaculate; duration of HIV infection in the assailant or partner; and presence of an STI, prior genital HSV infection or genital lesions in either partner. The risk is greatly reduced if the contact is successfully receiving antiretroviral therapy.

Health care providers that consider offering nPEP should take into account the likelihood that exposure to HIV occurred, the potential benefits and risks of such therapy, and the interval between the exposure and initiation of therapy. It will be helpful to know the HIV status of the sexual contact. The CDC provides an algorithm for consideration of nPEP. In general, nPEP is not recommended when more than 72 hours have passed since exposure. If the patient decides to take nPEP, clinical management should be implemented according to published CDC guidelines. Providers should be aware that structural barriers exist to obtaining nPEP, and that adolescent assault victims have a high discontinuation rate due to adverse effects from the medication.

4. HIV Preexposure Prophylaxis

In 2014, the U.S. Public Health Service released guidance on the use of preexposure prophylaxis (PrEP) in the United States. The guidance followed the Food and Drug Administration’s approval of a coformulated HIV antiretroviral (tenofovir and emtricitabine [TDF-FTC]) for use as PrEP based on data from two large international trials. In 2018, the Food and Drug Administration approved TDF-FTC as PrEP for individuals greater than or equal to 35 kg, without renal impairment. Initial studies to determine safety and acceptability in younger individuals at high risk for HIV acquisition revealed high rates of acceptability but adherence dropped as intervals between study visits lengthened, suggesting that increased adherence support may be needed. Providers considering the use of PrEP in a minor at risk of infection should consult with an experienced prescriber and know the laws of their particular state with respect to providing preventive HIV medication without parental consent.

ECTOPARASITIC INFECTIONS

1. Pubic Lice

Pthirus pubis, the pubic louse, lives in pubic hair. The louse or the nits can be transmitted by close contact from person to person. Patients complain of itching and may report having seen the insect. Examination of the pubic hair may reveal the louse crawling around or attached to the hair. Closer inspection may reveal the nit or sac of eggs, which is a gelatinous material (1–2 mm) stuck to the hair shaft. See Table 44–1 for treatment recommendations.

2. Scabies

Sarcoptes scabiei, the causative organism in scabies, is smaller than the louse. It can be identified by the classic burrow, which is created by the organism laying eggs and traveling just below the skin surface. Scabies can be sexually transmitted by close skin-to-skin contact and can be found in the pubic region, groin, lower abdomen, or upper thighs. The rash is intensely pruritic, especially at night, erythematous, and scaly. See Table 44–1 for treatment options. Ivermectin is an oral therapeutic option for scabies that may hold particular promise in the treatment of severe infestations or in epidemic situations. When treating with lotion or shampoo, the entire area needs to be covered for the time specified by the manufacturer. One treatment usually clears the infestation, although a second treatment may be necessary. Bed sheets and clothes must be washed in hot water. Both sexual and close personal or household contacts within the preceding month should be examined and treated.