Clinical Manifestations

Chlamydia is the most frequently reported infectious disease in the United States and is the second most common STI in US adolescents after human papillomavirus (HPV). Although most infections are asymptomatic, clinical manifestations include urethritis, epididymitis, cervicitis, proctitis, pelvic inflammatory disease (PID), and conjunctivitis and pneumonia among infants. Chlamydia is one of the leading causes of tubal factor infertility in females, which is preventable with early detection and treatment. Although the clinical significance of oropharyngeal infection is unclear, available evidence suggests that C trachomatis can be sexually transmitted from oral to genital sites.

Diagnosis and Screening

Nucleic acid amplification tests (NAATs) have superior sensitivity and adequate specificity compared with older nonculture and non-NAAT methods for the diagnosis of C trachomatis genital tract infections in males and females. These US Food and Drug Administration (FDA)-cleared and recommended tests can be collected via vaginal or cervical swabs from females and first-catch urine from females or males. Compared with vaginal and cervical specimens, first-catch urine may detect up to 10% fewer infections among females. Vaginal swabs are preferred for female screening, although urine is still recommended. Urine is preferred for male urethral screening. Rectal and oropharyngeal NAATs are not FDA cleared, but are recommended by the CDC based on increased sensitivity and ease of specimen transport and processing. This testing is available commercially and most reference laboratories have already performed internal validation for Clinical Laboratory Improvement Amendments (CLIA) approval; clinicians should discuss testing availability with their local laboratories.

The use and acceptability for self-collected swab testing has been described in females as young as 12 years of age and is potentially cost saving in this group. In a recent study of STI testing using clinic-based, self-collected vaginal swabs among 310 first-year female college students, 98% of students found it easy or very easy to understand collection instructions and 93% found it easy or very easy to collect the specimen. Among all females, self-collected specimens were preferred over clinician-collected specimens, and the majority of females noted that self-collection made them feel comfortable and in control and that they were taking care of their health. Currently, multiple FDA-cleared NAAT platforms can be used for patient-collected vaginal swabs in a clinical setting.

The CDC, the US Preventive Services Task Force (USPSTF), and the American Academy of Pediatrics (AAP) recommend routine annual chlamydia screening for sexually active females less than 25 years of age. The CDC and AAP also recommend that clinicians should consider chlamydia screening in sexually active, heterosexual young males in clinical settings with higher chlamydia prevalence (including adolescent primary care clinics, correctional facilities, and STI clinics).

The recommendation for routine chlamydia screening remains unchanged for MSM based on most current guidelines, but more frequent screening at 3- to 6-month intervals is indicated for MSM, including those with human immunodeficiency virus (HIV) infection, based on risk factors in patients or their partners (see Special Populations: Men Who Have Sex With Men).

Treatment and Management

Recommended and alternative chlamydia treatments are outlined in Table 1 . Recent studies suggest that doxycycline is marginally superior to azithromycin in treating genital chlamydia. Data from several studies and a metaanalysis show pooled cure rates of 97.5% for doxycycline versus 94.4% for azithromycin. A recent randomized, controlled trial of males and females 12 to 21 years of age in a youth detention setting evaluated chlamydia directly observed therapy with doxycycline versus azithromycin. Treatment failure occurred in 5 of 155 individuals treated with azithromycin and none of the 155 individuals treated with doxycycline (cure rates of 97% and 100%, respectively.) However, in settings in which directly observed therapy would not be feasible, that is, an office setting, single-dose azithromycin is still a highly effective and appropriate treatment option with a high cure rate.

As mentioned, although routine oropharyngeal screening is not recommended, chlamydia can be transmitted sexually from oral to genital sites and should be treated if detected. The efficacy of any of the alternative regimens is unknown for this indication. Last, more recent retrospective studies including a systematic review and metaanalysis have raised some concern about the efficacy of single-dose azithromycin compared with doxycycline for rectal chlamydia infections. More studies are needed comparing the 2 regimens before definitive recommendations can be made.

Secondary to high reinfection rates, retesting in 3 months after chlamydia treatment is indicated in males and females. NAAT testing should not be performed any sooner than approximately 1 month postinfection secondary to residual chlamydial DNA or RNA despite appropriate therapy. Sexual partners in the past 60 days before diagnosis should be evaluated and treated. Or, if the last sexual exposure was more than 60 days before the onset of symptoms or diagnosis, the most recent sex partner should be treated. Partners should avoid sexual intercourse for at least 7 days after treatment to avoid reinfection.

Clinical Manifestations

N gonorrhoeae typically infects mucous membranes and may remain localized but can disseminate. Manifestations include urethritis, epididymitis, proctitis, conjunctivitis, cervicitis, PID, pharyngitis, and disseminated infection. Vertical transmission from infected mothers to their infants occurs. Gonorrhea can also increase rates of HIV sexual transmission up to 5-fold.

Oral sex is highly prevalent among youth and prevalence of pharyngeal gonorrhea has increased in parallel. In 2 Los Angeles STI clinics, 65% of patients 15 to 24 years of age reported having oral sex and prevalence of pharyngeal gonorrhea in this group was 6%, compared with 7% for urogenital gonorrhea.

Diagnosis and Screening

Similar to that for C trachomatis (see Chlamydia trachomatis infections), optimal detection of genital tract infections caused by N gonorrhoeae in males and females is achieved with NAATs collected via cervical or vaginal swabs (either clinician or patient collected in a clinical setting) from females and first-catch urine from females or males. Clinicians should discuss testing availability with their local laboratories. Similar to chlamydia, the CDC, AAP, and USPSTF recommend routine gonorrhea screening for sexually active females less than 25 years of age.

The recommendation for routine gonorrhea screening remains unchanged for MSM based on most current guidelines, but more frequent screening at 3- to 6-month intervals is indicated for MSM, including those with HIV infection, based on risk factors in patients or their partners (see Special Populations: Men Who Have Sex With Men).

Treatment and Management

Recommended and alternative gonorrhea treatments are outlined in Table 1 . Dual therapy is recommended to improve treatment efficacy and potentially slow the emergence and spread of cephalosporin resistance. Importantly, doxycycline is no longer recommended as part of dual therapy based on the substantially higher prevalence of gonococcal resistance to tetracycline. Ideally, patients should receive dual therapy simultaneously and under direct observation in the clinic. If a prescription is given for azithromycin, it is critical to review with the patient the importance of dual therapy and that the azithromycin prescription should be filled and taken as soon as possible. If ceftriaxone is not available, then single-dose oral cefixime can be given in addition to azithromycin; however, this regimen is not appropriate for pharyngeal infections because cefixime has limited treatment efficacy for oral infections (92.3% cure [95% confidence interval, 74.9%–99.1%] compared with 97.5% cure [95% confidence interval, 95.4%–99.8%] in anogenital infections).

A test of cure is only needed for individuals with pharyngeal gonorrhea treated with an alternative regimen; either culture or NAAT should be performed 14 days after treatment and any positive testing should be followed by antimicrobial susceptibility testing. Secondary to high reinfection rates, retesting in 3 months after therapy is indicated. Sexual partners in the past 60 days before diagnosis should be evaluated and treated. Or, if the last sexual exposure was more than 60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated. Partners should avoid sexual intercourse for at least 7 days after treatment to avoid reinfection.

For those with cephalosporin or immunoglobulin E–mediated penicillin allergy, options are limited but include intramuscular gentamicin or oral gemifloxacin plus azithromycin based on a noncomparative randomized trial and in vitro studies. Unfortunately, there is a current shortage of gemifloxacin in the United States; although the FDA approved a generic formulation in June 2015, it is unclear when this will become more available. Clinicians can find updates on the availability of gemifloxacin online via the CDC.

Treatment Failures

Treatment failure should be considered in (1) persons whose symptoms do not resolve within 3 to 5 days after appropriate treatment and report no sexual contact during the posttreatment follow-up period and (2) persons with a positive test-of-cure (ie, positive culture ≥72 hours or positive NAAT ≥7 days after receiving recommended treatment) when no sexual contact is reported during the posttreatment follow-up period. In the adolescent population, a patient who is reinfected from an untreated or partially treated partner is the most commonly encountered situation rather than a case of resistant gonorrhea. If this situation is suspected, a careful history should be obtained and the patient should be retreated with ceftriaxone and azithromycin. Clinicians should ensure that the patient’s sex partners from the preceding 60 days are evaluated promptly with culture and presumptively treated using the same regimen used for the patient. A test of cure with a simultaneous NAAT at relevant clinical sites should be obtained 7 to 14 days after retreatment. It should be emphasized with the patient that he or she should abstain from sex for at least 1 week after treatment to avoid reinfection or transmission to a new partner.

In contrast, if treatment failure is truly suspected, clinicians should obtain relevant clinical specimens, including both NAAT and culture, and contact the local health department for guidance before retreatment.

Clinical Manifestations

Symptoms of syphilis depend on the stage and duration of infection; asymptomatic patients may only be diagnosed via screening. Patients with primary syphilis may present with painless ulcers or chancres on the genitalia, extremities, or oral mucosa depending on the location of exposure. Secondary syphilis symptoms can include skin rash, mucocutaneous lesions, and lymphadenopathy; tertiary syphilis presents with cardiac, neurologic, or gummatous manifestations decades after initial infection. Neurosyphilis can occur at any stage of disease.

As mentioned, 12 cases of ocular syphilis (including uveitis associated with rapidly progressive ocular symptoms and blindness) were initially identified in Seattle, Washington, and San Francisco, California, between December 2014 and March 2015. As of the latest update in March 2016, more than 200 cases have been reported from a total of 20 states. Most cases have been among HIV-positive MSM with a few cases in HIV-negative patients including heterosexual males and females. Although this outbreak has not yet affected adolescents, considering the syphilis epidemic in young MSM of color, clinicians should remain vigilant for this manifestation.

Diagnosis and Screening

Syphilis diagnosis requires both nontreponemal (eg, Venereal Disease Research Laboratory or rapid plasma reagin) and treponemal (eg, fluorescent treponemal antibody absorbed tests, the T pallidum passive particle agglutination assay, or enzyme immunoassay) testing. Because false-positive nontreponemal testing occurs in some situations (including pregnancy, autoimmune disease, HIV, and others), patients should always receive confirmatory treponemal testing.

A growing number of clinical laboratories are screening samples initially using treponemal rather than nontreponemal tests, typically by enzyme immunoassay or chemiluminescence immunoassays, called the reverse screening algorithm. Such testing can be automated (in contrast, rapid plasma reagin is a manual test), has high sensitivity, and is optimal for populations with high prevalence of disease. In contrast, reverse screening cannot distinguish previous from new disease or treated from untreated disease, and secondary treponemal confirmation is required. False-positive initial treponemal results can occur in low-prevalence populations. Clinicians should be aware of the testing options at their institutions, and if reverse algorithm screening is available, they must be able to receive all treponemal and nontreponemal testing results to interpret the test results appropriately. Of note, in 2014, the FDA granted a CLIA waiver for the Syphilis Health Check, a point-of-care test allowing for rapid screening in multiple clinical settings. Local health departments and infectious diseases specialists can be contacted for discussion regarding testing availability and the most appropriate testing methodologies based on local epidemiology.

Patients with ocular symptoms consistent with syphilis should have serologic testing for syphilis in addition to immediate ophthalmologic evaluation and examination of the cerebrospinal fluid. Clinicians should contact their local health departments for guidance regarding suspected ocular syphilis cases.

Treatment and Management

Syphilis treatments are outlined in Table 1 . Of note, no adolescent or young adult-specific data exist. Primary and secondary syphilis-infected patients should be evaluated clinically and serologically for treatment failure at 6 and 12 months; those with latent syphilis should be evaluated clinically and serologically for treatment failure at 6, 12, and 24 months. Those with suspected neurosyphilis should be managed in collaboration with an infectious diseases specialist. In cases of suspected ocular syphilis, clinicians should contact their local health departments for discussion and guidance within 24 hours of diagnosis.