Gonorrhea is more common in men that in women, and is more likely to be asymptomatic in women [1]. Men who have sex with men and HIV‐infected individuals are at especially high risk of gonorrhea infection [1]. In women who are symptomatic, vaginal discharge, and abdominal pain are the most common presenting symptoms, with arthralgia, skin lesions, and bartholin gland abscess occurring less commonly [2]. When symptomatic in men, gonorrhea often presents as pyuria or dysuria, and less commonly as epididymitis [3–6].

The vast majority (>95%) of individuals infected with chlamydia are asymptomatic [5, 7, 8]. When symptoms are present, the most common among women is mucopurulent cervicitis or urethritis, and less common is pelvic inflammatory disease [9–11]. Among men, presenting symptoms, when present, can include urethritis and epididymitis [12, 13]. Chlamydia trachomatis has also been identified as the single most common cause of non‐gonococcal reactive arthritis, or Reiter’s syndrome, which typically presents as a single‐site, lower limb arthritis approximately four weeks after genital tract infection occurs [14].

Genital herpes simplex presents with painful ulcers, vesicles, papules, pustules, crusts, fissures along the skin and mucous membranes of the genitals, thighs, or buttocks. However, it can also present with less typical symptoms, such as cystitis, urethritis, cervicitis, and even meningitis [15, 16]. Dysuria can lead to urinary retention, and constitutional symptoms such as headache, fever, malaise, and lymphadenopathy can also be present [16]. These symptoms can be preceded by a prodrome of tingling, burning, or pain in the area where the lesions will appear [16]. While 60% of new HSV‐2 infections are symptomatic, 40% are asymptomatic [15]. In addition, while HSV‐2 is commonly thought to be a genital infection and HSV‐1 an orolabial infection, in fact, new genital HSV‐1 infections are as common as new orolabial HSV‐1 infections, and the incidence of HSV‐1 genital infections appears to be increasing [15, 17]. Primary outbreaks, usually the first outbreak that occurs after acquisition of the virus, are usually significantly more painful and incapacitating, with multiple lesions, while subsequent outbreaks are less painful and demonstrate fewer, more localized lesions or only a single lesion [16, 18].

Trichomonas infections can be asymptomatic in up to 50% of cases and symptoms, when present, can be sufficiently mild that they can be mistaken for normal vaginal discharge, and infections can last for long durations untreated [19, 20]. The most common presenting symptom in women is vaginal discharge and in men, urethral discharge [19, 21]. The vaginal discharge can be yellow or malodorous (“musty”), and a pruritic or irritated sensation can be described [20]. Other symptoms include dyspareunia, dysuria, vulvar erythema, vulvar pruritis, and abdominal pain [20, 22]. Colpitis macularis or “strawberry cervix” is an appearance of the cervix created by punctate hemorrhages on the cervix; however it is difficult to see with the naked eye and is more visible with colposcopy (90%) than with the naked eye (2%) [20, 22]. Mucopurulent discharge is uncommon unless coinfection with chlamydia or gonorrhea is present [20].

The pathological nature of Mycoplasma genitalium is still under investigation. While it is a common cause of non‐gonococcal urethritis in men, it has not been shown to cause them long‐term sequelae, such as infertility [23]. And while mycoplasma has been associated with adverse outcomes in women such as preterm birth, mycoplasma can also be asymptomatic, with over half of women testing positive reporting no symptoms [24]. Among women who do report symptoms, cervicitis and postcoital bleeding are common, and urethritis can also be seen occasionally [23, 24, 25]. While a cervicitis may be seen on presentation, this cervicitis is often asymptomatic [26, 27]. Other pelvic inflammatory disease symptoms are not usually seen with mycoplasma, such as vaginal discharge, pelvic pain, or dyspareunia, though it has been suggested that mycoplasma may increase the risk of developing pelvic inflammatory disease [24].

Genital warts appear as multiple polymorphic lesions, potentially appearing as cauliflower‐like, papular, or keratotic, that can coalesce into larger masses [28, 29]. In men, common locations include the frenum, corona, coronal sulcus, inner surface of the prepuce, and urethra or urinary meatus [28]. In women, warts can appear at the fourchette and adjacent labia, but also other part of the vulva, perineum, groin, and anus [28, 29]. Warts can also be seen inside the vagina and on the cervix, but are rarely seen on the thighs or trunk [28]. Warts usually do not have additional symptoms other than their presence, but may occasionally be accompanied by pruritis, irritation, or pain [29].

1. 2. What is the optimal diagnostic method for gonorrhea, chlamydia, HSV, trichomonas, Mycoplasma genitalium, and genital warts?

The optimal diagnostic test for both N. gonorrhea and C. trachomatis is nucleic acid amplification testing (NAAT) [30]. Previously the gold standard test was culture; however, this method required invasive testing (urethral swabs for men or cervical swabs for women), expedited transportation and maintenance of a cold chain for adequate specimen handling [30]. Additionally, testing required 48–72 hours for bacterial growth in order to provide results [30]. NAAT testing does not require viable organisms; instead detecting infection based on as little as a single copy of DNA or RNA, greatly increases sensitivity [30]. It is estimated that the use of NAAT improves detection of chlamydia by 20–50% over culture or earlier nonculture tests [30]. Sensitivity of NAAT testing for both N. gonorrhea and C. trachomatis is over 90% while specificity is greater than 99% [30]. The improved sensitivity of NAAT testing also permits less invasive methods of testing for gonorrhea and chlamydia, including urine specimens for both men and women, and self‐collected vaginal swabs for women [30]. Self‐collected vaginal swabs have equal sensitivity and specificity when compared with provider‐collected endocervical swabs [31, 32]. While N. gonorrhea and C. trachomatis can be detected in the first void urine for women, the organism load is substantially lower than at other detection sites (cervix, vagina), and evidence indicates that up to 10% of chlamydia or gonorrhea infections may be missed [30, 33, 34]. However, urine testing is a highly convenient and useful diagnostic modality and need not be eliminated as an option for women in the appropriate clinical scenario, especially in patients who are apprehensive about having a pelvic exam or performing a vaginal self‐swab, or who prefer the convenience of a urine sample. NAAT is not FDA‐cleared for rectal, oropharyngeal, or conjunctival diagnosis of gonorrhea or chlamydia, and the specificity may not be as high as with urinary and endocervical samples [23]. When antimicrobial resistance is suspected, such as in cases of treatment failure, culture may still be a useful diagnostic modality despite the logistical challenges [23]. For point‐of‐care testing of symptomatic men, Gram or methylene blue or gentian violet (MB/GV) stain of urethral secretions showing polymorphonuclear leukocytes with intracellular Gram‐negative diplococci can provide high specificity, but does not rule out infection due to low sensitivity [23].

Diagnosis of genital herpes simplex virus can be made clinically, with the appearance of typical lesions as described above. While laboratory diagnosis is not required, it can help confirm the diagnosis and establish the timing of acquisition. If lesions are present, a viral culture can be taken by swabbing the base of an active lesion [16]. Sensitivity of herpes viral culture can be reduced by poor specimen handling, swabbing of healing lesions, or recurrent rather than primary infections; therefore a negative viral culture does not rule out herpes infection [16]. Because of the low sensitivity of viral culture, NAAT tests are becoming more widely available, and are the test of choice for central nervous system and systemic infections [23]. Cytologic detection of herpes cellular changes (Tzanck preparation) and monoclonal antibody detection are insufficiently sensitive [23]. Serum antibodies to herpes rise within a few weeks of exposure, with IgM antibodies rising first, followed by IgG antibodies; the latter remain permanently detectable in the serum [16]. Therefore, serum antibodies may be negative in the setting of an acute primary outbreak, and should be repeated after several weeks [16]. Additionally, presence of HSV‐1 antibodies does not differentiate between oral and genital transmission; HSV‐2 is still rare in the oral cavity and therefore infection is still presumed to occur in the genital tract [23]. While screening with serology in the general population is not recommended, serologic testing may be useful for patients without symptoms whose partners have genital herpes in order to determine immunity status [23].

The mainstay of trichomonas diagnosis is light microscopy with wet mount because it is low cost and widely accessible. T. vaginalis has a classic appearance on wet mount of motile flagellated protozoa [35]. However, sensitivity of light microscopy can be as low as 51–65% [23, 35]. T. vaginalis organisms can be detected on Pap smear, but specificity is low, and therefore clinical correlation is recommended; confirmation via alternative diagnostic method is recommended in patients in whom trichomonas infection is unlikely [36]. NAAT tests are also now available and FDA‐approved for T. vaginalis, and offer the benefit of increased sensitivity and specificity, with the disadvantage of increased cost and precluding immediate diagnosis and treatment [37, 38]. NAAT testing can detect trichomonas three to five times more often than wet mount, and are equally sensitive (95–100%) from urethral swabs or urine in men and from vaginal swabs, endocervical swabs, and urine in women [23]. Rapid tests have been developed, but are not yet FDA approved, and while specificity is high, they have lower sensitivity than NAAT tests. Prior to the widespread availability of NAAT tests, culture offered the highest sensitivity and specificity (75–96% and 100%, respectively) but is less useful now in the era of widespread NAAT availability [23].

Mycoplasma genitalium has only recently been recognized as a sexually transmitted infection, and therefore testing for mycoplasma is not widely commercially available [26, 39, 40]. Culture is not a useful diagnostic tool for mycoplasma because of its slow growth, and the ability to isolate it is limited to few laboratories [23]. Studies of mycoplasma have found that NAAT and PCR‐based detection offers the best sensitivity and specificity, but none have been FDA‐approved [23, 39, 40]. The optimal specimen collection in men is from urine and in women is from cervical or vaginal swabs [39, 40]. While the clinical implications of mycoplasma are still being elucidated [27, 41, 42] development of a commercially available test would further both clinical testing and research into mycoplasma.

Genital warts can be adequately diagnosed by visual inspection of typical lesions as described above [23]. Biopsy is not required unless lesions are atypical or unresponsive to treatment [29]. Atypical appearance can include hyperpigmentation, induration, fixation to underlying tissue, friability, or ulceration [23].

1. 3. What is the recommended treatment of gonorrhea, chlamydia, HSV, trichomonas, Mycoplasma genitalium, and genital warts?

Treatment of gonorrhea is becoming an increasing challenge as the prevalence of antimicrobial resistance rises [23

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