Sexually Transmitted Diseases (STDs)

Chlamydial Infections

Chlamydial Infections in Adolescents and Adults

Chlamydial genital infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged ≤25 years (93). Several important sequelae can result from C. trachomatis infection in women, the most serious of which include PID, ectopic pregnancy, and infertility. Some women who have uncomplicated cervical infection already have subclinical upper-reproductive–tract infection upon diagnosis.

Asymptomatic infection is common among both men and women. To detect chlamydial infections, health-care providers frequently rely on screening tests. Annual screening of all sexually active women aged ≤25 years is recommended, as is screening of older women with risk factors (e.g., those who have a new sex partner or multiple sex partners). In June 2007, USPSTF reviewed and updated their chlamydia screening guidance and found that the epidemiology of chlamydial infection in the United States had not changed since the last review (81,271). In issuing recommendations, USPSTF made the decision to alter the age groups used to demonstrate disease incidence (i.e., from persons aged ≤25 years to those aged ≤24 years). CDC has not changed its age cutoff, and thus continues to recommend annual chlamydia screening of sexually active women aged ≤25 years.

Screening programs have been demonstrated to reduce both the prevalence of C. trachomatis infection and rates of PID in women (272,273). Although evidence is insufficient to recommend routine screening for C. trachomatis in sexually active young men because of several factors (including feasibility, efficacy, and cost-effectiveness) (94), the screening of sexually active young men should be considered in clinical settings with a high prevalence of chlamydia (e.g., adolescent clinics, correctional facilities, and STD clinics). Among women, the primary focus of chlamydia screening efforts should be to detect chlamydia and prevent complications, whereas targeted chlamydia screening in men should only be considered when resources permit and do not hinder chlamydia screening efforts in women (274,275). An appropriate sexual risk assessment should be conducted for all persons and might indicate more frequent screening for some women or certain men (see MSM).

Diagnostic Considerations

C. trachomatis urogenital infection in women can be diagnosed by testing urine or by collecting swab specimens from the endocervix or vagina. Diagnosis of C. trachomatis urethral infection in men can be made by testing a urethral swab or urine specimen. Rectal C. trachomatis infections in persons that engage in receptive anal intercourse can be diagnosed by testing a rectal swab specimen. NAATs, cell culture, direct immunofluorescence, EIA, and nucleic acid hybridization tests are available for the detection of C. trachomatis on endocervical specimens and urethral swab specimens from men (197). NAATs are the most sensitive tests for these specimens and are FDA-cleared for use with urine. Some NAATs are cleared for use with vaginal swab specimens, which can be collected by a provider or self-collected by a patient. Self-collected vaginal swab specimens perform at least as well as with other approved specimens using NAATs (276,277), and women find this screening strategy highly acceptable. Rectal and oropharyngeal C. trachomatis infection in persons engaging in receptive anal or oral intercourse can be diagnosed by testing at the anatomic site of exposure. Most tests, including NAAT and nucleic acid hybridization tests, are not FDA-cleared for use with rectal or oropharyngeal swab specimens, and chlamydia culture is not widely available for this purpose. However, NAATs have demonstrated improved sensitivity and specificity compared with culture for the detection of C. trachomatis at rectal sites (278–280) and at oropharyngeal sites among men (278–281). Some laboratories have met CLIA requirements and have validated NAAT testing on rectal swab specimens for C. trachomatis. Recent evidence suggests that the liquid-based cytology specimens collected for Pap smears might be acceptable specimens for NAAT testing, although test sensitivity using these specimens might be lower than those resulting from the use of cervical swab specimens (282); regardless, certain NAATs have been FDA-cleared for use on liquid-based cytology specimens. Persons who undergo testing and are diagnosed with chlamydia should be tested for other STDs.

Treatment

Treating infected patients prevents sexual transmission of the disease, and treating all sex partners of those testing positive for chlamydia can prevent reinfection of the index patient and infection of other partners. Treating pregnant women usually prevents transmission of C. trachomatis to infants during birth. Chlamydia treatment should be provided promptly for all persons testing positive for infection; delays in receiving chlamydia treatment have been associated with complications (e.g., PID) in a limited proportion of chlamydia-infected subjects (283). Coinfection with C. trachomatis frequently occurs among patients who have gonococcal infection; therefore, presumptive treatment of such patients for chlamydia is appropriate (see Gonococcal Infection, Dual Therapy for Gonococcal and Chlamydial Infections). The following recommended treatment regimens and alternative regimens cure infection and usually relieve symptoms.

A meta-analysis of 12 randomized clinical trials of azithromycin versus doxycycline for the treatment of genital chlamydial infection demonstrated that the treatments were equally efficacious, with microbial cure rates of 97% and 98%, respectively (284). These studies were conducted primarily in populations in which follow-up was encouraged, adherence to a 7-day regimen was effective, and culture or EIA (rather than the more sensitive NAAT) was used for determining microbiological outcome. Azithromycin should always be available to treat patients for whom compliance with multiday dosing is uncertain. The clinical significance and transmissibility of C. trachomatis detected at oropharyngeal sites is unclear (285), and the efficacy of different antibiotic regimens in resolving oropharyngeal chlamydia remains unknown.

In patients who have erratic health-care–seeking behavior, poor treatment compliance, or unpredictable follow-up, azithromycin might be more cost-effective in treating chlamydia because it enables the provision of a single-dose of directly observed therapy (284). Erythromycin might be less efficacious than either azithromycin or doxycycline, mainly because of the frequent occurrence of gastrointestinal side effects that can lead to noncompliance. Levofloxacin and ofloxacin are effective treatment alternatives but are more expensive and offer no advantage in the dosage regimen. Other quinolones either are not reliably effective against chlamydial infection or have not been evaluated adequately.

To maximize compliance with recommended therapies, medications for chlamydial infections should be dispensed on site, and the first dose should be directly observed. To minimize disease transmission to sex partners, persons treated for chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen. To minimize the risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all of their sex partners are treated.

Follow-Up

Except in pregnant women, test-of-cure (i.e., repeat testing 3–4 weeks after completing therapy) is not advised for persons treated with the recommended or alterative regimens, unless therapeutic compliance is in question, symptoms persist, or reinfection is suspected. Moreover, the validity of chlamydial diagnostic testing at <3 weeks after completion of therapy (to identify patients who did not respond to therapy) has not been established. False-negative results might occur in the presence of persistent infections involving limited numbers of chlamydial organisms. In addition, NAAT conducted at <3 weeks after completion of therapy in persons who were treated successfully could yield false-positive results because of the continued presence of nonviable organisms (197).

A high prevalence of C. trachomatis infection has been observed in women and men who were treated for chlamydial infection during the preceding several months (251,267,286–288). Most post-treatment infections result from reinfection caused by failure of sex partners to receive treatment or the initiation of sexual activity with a new infected partner. Repeat infections confer an elevated risk for PID and other complications. Unlike the test-of-cure, which is not recommended, repeat C. trachomatis testing of recently infected women or men should be a priority for providers. Chlamydia-infected women and men should be retested approximately 3 months after treatment, regardless of whether they believe that their sex partners were treated (251,267). If retesting at 3 months is not possible, clinicians should retest whenever persons next present for medical care in the 12 months following initial treatment.

Management of Sex Partners

Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient’s symptoms or chlamydia diagnosis. Although the exposure intervals defined for the identification of at-risk sex partners are based on limited evaluation, the most recent sex partner should be evaluated and treated, even if the time of the last sexual contact was >60 days before symptom onset or diagnosis.

Among heterosexual patients, if concerns exist that sex partners who are referred to evaluation and treatment will not seek these services (or if other management strategies are impractical or unsuccessful), patient delivery of antibiotic therapy to their partners can be considered (see Partner Management). Compared with standard partner referral, this approach, which involves delivering a prescription or the medication itself, has been associated with a trend toward a decrease in rates of persistent or recurrent chlamydia (68,69,71). Patients must also inform their partners of their infection and provide them with written materials about the importance of seeking evaluation for any symptoms suggestive of complications (e.g., testicular pain in men and pelvic or abdominal pain in women). Patient-delivered partner therapy is not routinely recommended for MSM because of a high risk for coexisting infections, especially undiagnosed HIV infection, in their partners.

Patients should be instructed to abstain from sexual intercourse until they and their sex partners have completed treatment. Abstinence should be continued until 7 days after a single-dose regimen or after completion of a multiple-dose regimen. Timely treatment of sex partners is essential for decreasing the risk for reinfecting the index patient.

Special Considerations

Pregnancy

Doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnant women. However, clinical experience and published studies suggest that azithromycin is safe and effective (289–291). Repeat testing to document chlamydial eradication (preferably by NAAT) 3 weeks after completion of therapy with the following regimens is recommended for all pregnant women to ensure therapeutic cure, considering the severe sequelae that might occur in mothers and neonates if the infection persists. Women aged <25 years and those at increased risk for chlamydia (i.e., women who have a new or more than one sex partner) also should be retested during the third trimester to prevent maternal postnatal complications and chlamydial infection in the infant (81). Pregnant women diagnosed with a chlamydial infection during the first trimester should not only receive a test to document chlamydial eradication, but be retested 3 months after treatment.

The frequent gastrointestinal side effects associated with erythromycin can result in noncompliance with the alternative regimens. Although erythromycin estolate is contraindicated during pregnancy because of drug-related hepatotoxicity, the lower dose 14-day erythromycin regimens can be considered if gastrointestinal tolerance is a concern.

HIV Infection

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

Chlamydial Infections Among Infants

Prenatal screening and treatment of pregnant women can prevent chlamydial infection among neonates. Pregnant women aged <25 years are at high risk for infection.

C. trachomatis infection of neonates results from perinatal exposure to the mother’s infected cervix. Although neonatal ocular prophylaxis with silver nitrate solution or antibiotic ointments does not prevent perinatal transmission of C. trachomatis from mother to infant, ocular prophylaxis with these agents does prevent gonococcal ophthalmia and therefore should be administered (see Ophthalmia Neonatorum Prophylaxis).

Initial C. trachomatis perinatal infection involves the mucous membranes of the eye, oropharynx, urogenital tract, and rectum, although infection might be asymptomatic in these locations. Instead, C. trachomatis infection in neonates is most frequently recognized by conjunctivitis that develops 5–12 days after birth. C. trachomatis also can cause a subacute, afebrile pneumonia with onset at ages 1–3 months. Although C. trachomatis has been the most frequent identifiable infectious cause of ophthalmia neonatorum, perinatal chlamydial infections (including ophthalmia and pneumonia) have occurred less frequently because of the institution of widespread prenatal screening and treatment of pregnant women.

Ophthalmia Neonatorum Caused by C. trachomatis

A chlamydial etiology should be considered for all infants aged ≤30 days who have conjunctivitis, especially if the mother has a history of untreated chlamydia infection.

Diagnostic Considerations

Sensitive and specific methods used to diagnose chlamydial ophthalmia in the neonate include both tissue culture and nonculture tests (e.g., direct fluorescence antibody [DFA] tests, EIA, and NAAT). Most nonculture tests are not FDA-cleared for the detection of chlamydia from conjunctival swabs, and clinical laboratories must verify the procedure according to CLIA regulations. Specimens for culture isolation and nonculture tests should be obtained from the everted eyelid using a dacron-tipped swab or the swab specified by the manufacturer’s test kit, and they must contain conjunctival cells, not exudate alone. Specific diagnosis of C. trachomatis infection confirms the need for treatment not only for the neonate, but also for the mother and her sex partner(s). Ocular specimens from infants being evaluated for chlamydial conjunctivitis also should be tested for N. gonorrhoeae.

Topical antibiotic therapy alone is inadequate for treatment of chlamydial infection and is unnecessary when systemic treatment is administered.

Follow-Up

Because the efficacy of erythromycin treatment is only approximately 80%, a second course of therapy might be required. Therefore, follow-up of infants is recommended to determine whether initial treatment was effective. The possibility of concomitant chlamydial pneumonia should be considered.

Management of Mothers and Their Sex Partners

The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated (see Chlamydial Infection in Adolescents and Adults).

Infant Pneumonia Caused by C. trachomatis

Characteristic signs of chlamydial pneumonia in infants include 1) a repetitive staccato cough with tachypnea and 2) hyperinflation and bilateral diffuse infiltrates on a chest radiograph. In addition, peripheral eosinophilia (≥400 cells/mm³) occurs frequently. Wheezing is rare, and infants are typically afebrile. Because clinical presentations differ, initial treatment and diagnostic tests should include C. trachomatis for all infants aged 1–3 months who are suspected of having pneumonia (especially those whose mothers have untreated chlamydial infection).

Diagnostic Considerations

Specimens for chlamydial testing should be collected from the nasopharynx. Tissue culture is the definitive standard for chlamydial pneumonia. Nonculture tests (e.g., EIA, DFA, and NAAT) can be used, although nonculture tests of nasopharyngeal specimens have a lower sensitivity and specificity than nonculture tests of ocular specimens. DFA is the only FDA-cleared test for the detection of C. trachomatis from nasopharyngeal specimens. Tracheal aspirates and lung biopsy specimens, if collected, should be tested for C. trachomatis.

Because test results for chlamydia often are not available in a timely manner, the decision to provide treatment for C. trachomatis pneumonia must frequently be based on clinical and radiologic findings. The results of tests for chlamydial infection assist in the management of an infant’s illness and can help determine the need for treating the mother and her sex partner(s).

Follow-Up

The effectiveness of erythromycin in treating pneumonia caused by C. trachomatis is approximately 80%; a second course of therapy might be required. Follow-up of infants is recommended to determine whether the pneumonia has resolved, although some infants with chlamydial pneumonia continue to have abnormal pulmonary function tests later in childhood.

Management of Mothers and Their Sex Partners

Mothers of infants who have chlamydia pneumonia and the sex partners of these women should be evaluated and treated according to the recommended treatment of adults for chlamydial infections (see Chlamydial Infection in Adolescents and Adults).

Infants Born to Mothers Who Have Chlamydial Infection

Infants born to mothers who have untreated chlamydia are at high risk for infection; however, prophylatic antibiotic treatment is not indicated, and the efficacy of such treatment is unknown. Infants should be monitored to ensure appropriate treatment if symptoms develop.

Chlamydial Infections Among Children

Sexual abuse must be considered a cause of chlamydial infection in preadolescent children, although perinatally transmitted C. trachomatis infection of the nasopharynx, urogenital tract, and rectum might persist for >1 year (see Sexual Assault or Abuse of Children).

Diagnostic Considerations

Nonculture, nonamplified probe tests for chlamydia (EIA and DFA) should not be used because of the possibility of false-positive test results. With respiratory-tract specimens, false-positive results can occur because of cross-reaction of test reagents with C. pneumoniae; with genital and anal specimens, false-positive results might occur as a result of cross-reaction with fecal flora.

Other Management Considerations

See Sexual Assault or Abuse of Children.

Follow-Up

Follow-up cultures are necessary to ensure that treatment has been effective.