Gonorrhea, Neisseria gonorrhoeae, is one of the most commonly reported infectious diseases in the United States, with 321,849 cases reported in 2011. Gonorrhea is thought to be substantially underdiagnosed and underreported; approximately twice as many new infections are estimated to occur each year as are reported.

Chlamydia, C. trachomatis, is the most frequently reported STI in the United States, with an estimated 4 million new cases each year. In 2011, 1.4 million chlamydia diagnoses were reported, up from 877,478 in 2003. National surveys indicate that chlamydia prevalence among sexually active females aged 14 to 19 is 6.8%, Even so, most chlamydia cases go undiagnosed. The increases in reported cases and rates likely reflect the continued expansion of screening efforts and increased use of more sensitive diagnostic tests, rather than an actual increase in new infections. The availability of urine tests for chlamydia may be contributing to the increased detection of the disease in men and consequently the rising rates of reported chlamydia in men in recent years.

The CDC recommends annual chlamydia screening for sexually active women under age 25, all pregnant women, and older women with risk factors (i.e., new or multiple sex partners). Screening efforts are critical to preventing the serious health consequences of this infection, particularly infertility. Such efforts are linked to a 60% reduction in the incidence of PID. Screening of men who engage in sexual intercourse with other men should be conducted annually, with more frequent screening (every 3 to 6 months) for men involved with multiple partners. If illicit drug use is involved (especially methamphetamine), involved parties are at an even higher risk, and they should receive testing at shorter intervals.

C. trachomatis is an intracellular bacterium with multiple serotypes. Types L1-3 cause LGV. Types D, E, F, G, H, I, J, and K cause urethritis and cervicitis. It is transmitted during vaginal, oral, or anal sexual contact with an infected partner. C. trachomatis accounts for 30% to 50% of cases of nongonococcal urethritis (NGU).

Chlamydial infection in men is generally asymptomatic, but symptoms may include urethritis, epididymitis, and proctitis. Urethritis presents 1 to 3 weeks after infection with a mild to moderate clear urethral discharge and dysuria. Chlamydial urethritis may present as persistent dysuria and/or discharge following a course of treatment for gonorrhea because 15% to 35% of patients with known gonococcal infections are also infected with chlamydia.

Chlamydial epididymitis tends to run a more protracted course than epididymitis because of other organisms; it is also often less severe. Chlamydial proctitis may present with rectal pain and bleeding, but it is often asymptomatic.

Chlamydial infection may disseminate systemically in 1% to 3% of patients. Classically know as Reiter syndrome, it presents with the classic triad of reactive arthritis, urethritis, and conjunctivitis. The Fitz-Hugh-Curtis syndrome may also be seen in about 20% of women with PID secondary to chlamydial infection.

C. trachomatis was the first organism for which there was a commercially available PCR assay. Now there are many published studies using several different types of NAATs and new technologies that are commercially available for detecting chlamydia in urine and urethral, cervical, or vaginal secretions.

Patients who have persistent or recurrent urethritis should be retreated with the initial regimen if they did not comply with the treatment regimen or if they were reexposed to an untreated sex partner. Otherwise, a culture of an intraurethral swab specimen and a first-void urine specimen for Trichomonas vaginalis should be performed. Some cases of recurrent urethritis following doxycycline treatment may be caused by tetracycline-resistant Ureaplasma urealyticum. If the patient was compliant with the initial regimen and reexposure can be excluded, the following regimen is recommended:

Metronidazole 2 g orally in a single dose PLUS erythromycin base 500 mg orally four times a day for 7 days or erythromycin ethylsuccinate 800 mg orally four times a day for 7 days

Patients who have NGU and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.

The etiologies of most cases of nonchlamydial nongonococcal urethritis are unknown. U. urealyticum and Mycoplasma genitalium have been implicated. Specific diagnostic tests for these organisms are not indicated because the detection of these organisms is often difficult and would not alter therapy.

T. vaginalis and HSV sometimes cause urethritis. Diagnostic and treatment procedures for these organisms are reserved for situations in which these infections are suspected (e.g., contact with trichomoniasis and genital lesions suggestive of genital herpes) or when unresponsive to therapy.

HPV is the most common STD with an estimated total of 20 million infected individuals in the United States. HPV vaccination has decreased prevalence by 56% in females aged 14 to 19. HPV, a small, nonenveloped virus containing double-stranded DNA, infects basal epithelial cells and multiplies in the cell nucleus, causing cell death and perinuclear cavitation or koilocytosis, a histologic feature specific to HPV. More than 40 types of HPV can infect the genital tract. Most HPV infections are asymptomatic, unrecognized, or subclinical. Visible genital warts usually are caused by HPV type 6 or 11 (90%). Other HPV types in the anogenital region (e.g., types 16, 18, 31, 33, and 35) have been strongly associated with cervical neoplasia.

Biopsy is recommended under certain clinical conditions:

2. Lesions do not respond to standard therapy.

3. Disease worsens during therapy.

4. Patient is immunocompromised.

5. Warts are pigmented, indurated, fixed, and ulcerated (suggestive of Buschke-Löwenstein tumor).

No data support the use of type-specific HPV nucleic acid tests in the routine diagnosis or management of visible genital warts.

In addition to the external genitalia (i.e., the penis, vulva, scrotum, perineum, perianal skin), genital warts can occur on the uterine cervix and in the vagina, urethra, anus, and mouth.

When urethral lesions occur, 80% are located within the distal 3 cm of urethra. Patients present with dysuria, bloody urethral discharge, and changes in urinary stream. Bladder condyloma are rare. If meatal condyloma are identified, urethroscopy should be performed to look for other urethral lesions. To prevent iatrogenic seeding of the prostatic urethra and bladder, a tourniquet should be placed at the penopubic junction, or urethroscopy should stop at the external sphincter.

Intraanal warts are seen predominantly in patients who have had anal-receptive intercourse; these warts are distinct from perianal warts, which can occur in men and women who do not have a history of anal sex.

HPV types 6 and 11 have been associated with conjunctival, nasal, oral, and laryngeal warts. HPV types 6 and 11 rarely are associated with invasive squamous cell carcinoma of the external genitalia. Depending on the size and anatomic location, genital warts can be painful, friable, and pruritic, although they are commonly asymptomatic.

In the United States, most young, sexually active patients who have genital ulcers have genital herpes, syphilis, or chancroid. Although genital herpes is the most prevalent of these diseases, the relative frequency of each differs by geographic area and patient population. Patients with genital ulcers may have more than one disease. Conversely, not all genital ulcers are caused by STIs. Each disease has been associated with an increased risk for HIV infection.

A diagnosis based only on the patient’s medical history and physical examination often is inaccurate.

Only three ulcer presentations are pathognomonic:

2. A group of vesicles on an erythematous base that does not follow a neural distribution is pathognomonic for herpes simplex infection.

3.