Clinical update in sexually transmitted disease –2014
ABSTRACTSexually transmitted diseases (STDs) and their associated syndromes are extremely common in clinical practice. Early diagnosis, appropriate treatment, and partner management are important to ensure sexual, physical, and reproductive health in our patients.
KEY POINTS
- Anyone can have an STD, although the prevalence is higher in some groups, such as younger sexually active people, certain racial and ethnic minorities, men who have sex with men, and people who engage in risky sexual behavior.
- Preexposure vaccination is one of the most effective ways to prevent human papillomavirus, hepatitis A virus, and hepatitis B virus infections.
- The risk of acquiring human immunodeficiency virus is two to five times higher if the patient has a genital ulcerative disease such as syphilis or herpes at the time of exposure.
- Chlamydia trachomatis and Neisseria gonorrhoeae are major players in urethritis, cervicitis, and proctitis.
- The most common conditions associated with vaginitis include bacterial vaginosis, trichomoniasis, and candidiasis.
Which order of testing for syphilis is best?
The CDC recommends that nontreponemal tests be used to screen for syphilis and treponemal tests be used to confirm the diagnosis.36 This traditional algorithm performs well in identifying persons with active infection who require further evaluation and treatment, while minimizing false-positive results in low-prevalence populations.
However, some clinical laboratories have adopted the reverse sequence, using treponemal tests (usually an EIA or a CIA) to screen for syphilis, followed by a nontreponemal test to confirm active infection.36–38 This reverse-sequence testing may result in overdiagnosis and overtreatment of syphilis in some clinical settings.37 When reverse-sequence syphilis screening is used, the CDC recommends reflexively testing all sera that produce reactive EIA or CIA results with a quantitative nontreponemal test and reflexively testing sera with discordant results (ie, a reactive EIA or CIA and a nonreactive RPR or VDRL test) with a different treponemal test.36
Traditionally, the FTA-ABS test had been considered the gold standard treponemal test; however, it has lower specificity than other treponemal tests. Accordingly, TP-PA is the recommended confirmatory treponemal test.8,39 False-negative results, although rare, may occur for biological or technical reasons, such as the prozone phenomenon, resulting in a missed diagnosis. The prozone phenomenon occurs when the antibody titer is high and antigen binding sites are saturated, preventing the cross-linking reaction between antigens and antibodies. In this instance, when syphilis is suspected clinically and the RPR assay is nonreactive, the clinician can request RPR testing at dilutions of sera, ie, diluting the patient’s serum to bring the antibody concentration into the zone equivalence.40
Suspect neurosyphilis if neurologic symptoms arise
Central nervous system involvement can occur at any stage of syphilis. If clinical evidence of neurologic involvement (meningitis, stroke, cranial nerve dysfunction, or auditory or ophthalmic abnormalities) is observed in any patient with syphilis, regardless of stage, a cerebrospinal fluid examination should be performed.8 Laboratory testing can support the diagnosis of neurosyphilis; however, no single laboratory test can be used to diagnose it.
Cerebrospinal fluid abnormalities (ie, mononuclear pleocytosis, increased protein) are common in patients with early syphilis even in the absence of clinical neurologic findings. There is no firm evidence to support diverging from recommended treatment for early syphilis in these patients.35
Cerebrospinal fluid examination is recommended for all patients with serologic evidence of syphilis infection and neurologic symptoms and for patients who do not achieve an adequate serologic decline with stage-appropriate treatment.8
Penicillin is still the mainstay of syphilis treatment
Penicillin is still the mainstay of syphilis treatment.
- Patients with early syphilis (primary, secondary, or early latent) should receive a single intramuscular dose of benzathine penicillin G (2.4 million units).8,35
- Patients with late latent syphilis should receive three intramuscular doses of benzathine penicillin G (2.4 million units each) at 1-week intervals.
- Neurosyphilis should be treated with aqueous crystalline penicillin G 18 to 24 million units daily for 10 to 14 days.8
Doxycycline is the preferred alternative in nonpregnant patients who are allergic to penicillin. The dosage is 100 mg orally twice a day for 14 days (for primary, secondary, or early latent infections) or for 28 days (for late latent infections or those of unknown duration).35,41
Ceftriaxone (1–2 g daily) may be effective for treating early syphilis. However, data are limited, and the optimal dose and duration of therapy are not defined.8,42
Azithromycin in a single 2-g oral dose is effective for treating early syphilis. However, T pallidum chromosomal mutations associated with macrolide resistance are being detected.35,43 In view of this, azithromycin should not be used in men who have sex with men or in pregnant women.
Follow-up of syphilis patients and partners
Close clinical and serologic follow-up is strongly advised in persons who receive an alternate regimen to evaluate for treatment failure.8
Sex partners of patients with primary syphilis should be considered at risk and given treatment if they had sexual contact with the patient within 3 months plus the duration of symptoms, within 6 months plus the duration of symptoms for those with secondary syphilis, or 1 year for patients with early latent syphilis.8
Serologic and clinical evaluation should be repeated at 6, 12, and 24 months after treatment. HIV-infected patients should receive closer follow-up, ie, at 3, 6, 9, 12, and 24 months. The same quantitative nontreponemal serologic test should be used at each visit, with at least a fourfold decrease in titer representing an appropriate serologic decline.
Failure to achieve an appropriate serologic decline in 6 to 12 months may represent treatment failure.8 Optimal management in this instance is unclear; at a minimum, additional clinical and serologic follow-up should be performed.8 If additional follow-up cannot be ensured, retreatment (weekly intramuscular injections of benzathine penicillin G 2.4 million units for 3 weeks) is recommended. Cerebrospinal fluid examination can be considered to exclude unrecognized neurosyphilis.8
URETHRITIS: GONORRHEA, CHLAMYDIA TOP THE LIST
Symptoms of urethritis can include dysuria, discharge (purulent or mucopurulent), and urethral pruritus.26 However, asymptomatic infections are common.8
Several organisms are associated with infectious urethritis, including26:
- Neisseria gonorrhoeae
- Chlamydia trachomatis
- Mycoplasma genitalium
- Trichomonas vaginalis
- Ureaplasma urealyticum.
Diagnosing urethritis: Try to identify the agent
The clinician should attempt to obtain objective evidence of urethral inflammation. Urethral discharge should be examined with microscopy using Gram stain or methylene blue, or a first-void urine sample should be tested with microscopy and leukocyte esterase.26 If clinic-based diagnostic testing is not available, testing for N gonorrhoeae and C trachomatis using nucleic acid amplification can identify additional infections.8
During the clinic visit, either Gram-stain microscopy of a urethral swab or microscopic examination of a first-catch urine sample may identify the causative agent. If gram-negative intracellular diplococci are seen on urethral smear, gonorrhea infection is diagnosed. Nongonococcal urethritis is diagnosed when microscopy or urinalysis displays evidence of inflammation (positive leukocyte esterase or at least 10 white blood cells per high-power field) without gram-negative intracellular diplococci.8
Testing should be performed to determine the specific cause of urethritis, because both chlamydia and gonorrhea are reportable diseases. Nucleic acid amplification tests are the most sensitive tests for C trachomatis and N gonorrhoeae and can be performed on urethral swabs or urine.44 If clinic-based diagnostic tools are unavailable, patients should receive empiric treatment for chlamydia and gonorrhea.8
Treatment of urethritis, by organism
Urethral gonorrhea should be treated with dual therapy: ceftriaxone 250 mg in a single intramuscular dose and either azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice a day for 7 days. Oral cephalosporins are no longer recommended as first-line treatment of gonorrhea.45
Chlamydial urethritis is treated with azithromycin 1 g in a single oral dose or doxycycline 100 mg orally twice a day for 7 days. Although azithromycin provides the advantages of a single-dose regimen administered and directly observed by the provider, some evidence suggests that doxycycline may be more effective than azithromycin for symptomatic chlamydial urethritis.46
All sex partners within the preceding 60 days should be referred for evaluation, testing, and empiric treatment with a drug regimen effective against chlamydia (if nongonococcal urethritis or only C trachomatis was identified) and gonorrhea (if N gonorrhoeae was identified). When patients diagnosed with chlamydia or gonorrhea indicate that their partners are unlikely to seek evaluation, providers can offer patient-delivered partner therapy, a form of expedited partner therapy in which partners of infected persons are treated without previous medical evaluation. Providers should visit www.cdc.gov/std/ept for updated information for their individual jurisdiction, as expedited partner therapy is prohibited in some states. No studies have been published involving patient-delivered partner therapy for chlamydia or gonorrhea in men who have sex with men.8
Patients with recurrent or persistent urethritis can be retreated with the initial regimen if they did not comply with treatment or were reexposed to an untreated sex partner. However, persistent urethritis after doxycycline therapy may suggest the presence of doxycycline-resistant M genitalium or U urealyticum. T vaginalis may also cause urethritis in men. Diagnostic evaluation may include culture or nucleic acid amplification testing of a urethral swab or urine (ie, PCR [Amplicor] or transcription-mediated amplification).8
M genitalium or U urealyticum urethritis. Currently, no commercially available diagnostic test exists for M genitalium or U urealyticum, so clinicians must choose a treatment regimen on the basis of objective evidence of inflammation in the absence of an etiologic agent. If azithromycin was not given during the initial course, metronidazole 2 g orally or tinidazole 2 g orally in a single dose plus azithromycin 1 g orally should be considered.8
M genitalium is one of the most common pathogens in men with persistent urethritis, accounting for 15% to 25% of cases. Several studies have shown that moxifloxacin 400 mg orally daily for 7 days is effective against M genitalium.46–48 Therefore, men for whom an initial regimen of azithromycin fails should be retreated with moxifloxacin 400 mg orally once daily for 7 days.
If men require treatment with a new antibiotic regimen for persistent urethritis and a sexually transmitted agent is the suspected cause, all partners in the past 60 days before the initial diagnosis and any interim partners should be referred for evaluation and appropriate treatment.
