Section 5-2: Canadian Guidelines on Sexually Transmitted Infections – Management and treatment of specific infections – Chlamydial Infections

Section 5 - Management and Treatment of Specific Infections

Chlamydial Infections

(For Lymphogranuloma venereum, see Genital Ulcer Disease and Lymphogranuloma Venereum chapters)

Etiology

• Caused by Chlamydia trachomatis serovars D to K.

Epidemiology

• Reported rate in Canada and elsewhere has been increasing since 1997.^{Footnote 1}
• According to preliminary data, over 65, 000 cases were reported in Canada in 2006 (202 per 100,000 population).^{Footnote 2}
• Sexually active youth and young adults are disproportionately represented in the case reports for Chlamydia. The reported rate in 2004 was highest in youth/young adults 15 to 24 years of age, accounting for approximately 2/3 of the national reported cases.
• Chlamydia is underdiagnosed because the majority of infected individuals are asymptomatic.^{Footnote 3–Footnote 8}
• Underscreening is a gap in high-risk males and females. Males, the forgotten reservoir, have infrequent health-maintenance visits.^{Footnote 9–Footnote 11}
• The usual incubation period from time of exposure to onset of symptoms is 2 to 3 weeks, but can be as long as 6 weeks.
• In the absence of treatment, infection persists for many months.
• Individuals infected with Neisseria gonorrhoeae are often co-infected with C. trachomatis.^{Footnote 12,Footnote 13}
• Risk factors:
  • Sexual contact with a chlamydia-infected person.
  • A new sexual partner or more than two sexual partners in the past year.
  • Previous sexually transmitted infections (STIs).
  • Vulnerable populations (e.g., injection drug users, incarcerated individuals, sex trade workers, street youth etc.) (see Specific Populations section).

Prevention and Control

Infection and its sequelae can be prevented by:

• Consistent practice of safer sex (see Primary Care and Sexually Transmitted Infections chapter).
• Identifying barriers to prevention practices and the means to overcome them.
• Increased acceptance of testing by using a non-invasive urine-based nucleic acid amplification test (NAAT).
• Screening of at-risk groups (as per risk factors listed above):
  • Sexually active females under 25 years of age.
  • Infected men under the age of 25 are a hidden reservoir for infections and re-infections of their partners. There is an evidence gap to determine whether routine screening of asymptomatic young males decreases the incidence of anogenital Chlamydia infection in women.^{Footnote 14,Footnote 15} While waiting for such data, it is prudent to screen all sexually active males under the age of 25 for Chlamydia trachomatis. ^{Footnote 7,Footnote 8,Footnote 10,Footnote 16–Footnote 24}
  • Pregnant women. All pregnant women should be screened at the first prenatal visit. For those who are positive or who are at high risk for reinfection, rescreening at third trimester is indicated.^{Footnote 25–Footnote 31}
• Repeat screening of individuals with chlamydia infection after 6 months.^{Footnote 26,Footnote 32-Footnote 35}
• To prevent reinfection, partners need to be assessed, tested, treated, and counselled.
• Patients and contacts should abstain from unprotected intercourse until treatment of both partners is complete (i.e., after completion of a multiple-dose treatment or for 7 days after single-dose therapy).

Manifestations

Diagnosis

Laboratory diagnosis

(See Laboratory Diagnosis of Sexually Transmitted Infections chapter).

• Results are highly dependent on the type of test available; specimen collection and transport; and laboratory expertise. Consult with your local laboratory regarding available tests and their test performance.
• NAATs (e.g., polymerase chain reaction [PCR], transcription-mediated amplification [TMA]) are more sensitive and specific than culture, enzyme immunoassay (EIA) and direct fluorescent antibody assay (DFA). For non–medico-legal purposes, NAATs should be used whenever possible for urine, urethral or cervical specimens. Blood and mucus interfere with NAAT performance and can result in false-negative results, therefore culture is recommended in such situations.
• Although some NAATs have not been approved in Canada for use with vaginal or rectal specimens, recent data show that NAATs for C. trachomatis, N. gonorrhoeae and Trichomonas vaginalis may identify as many or more infected women using vaginal swabs than cervical swabs, urethral swabs or urine.^{Footnote 37} Check with your laboratory to see if this is an option. (see Specimen collection in this chapter).
• There are promising data on the use of rectal and oral swabs for C. trachomatis and N. gonorrhoeae tested by NAATs and current clinical trials are underway through the U.S. National Institutes of Health. (see Specimen collection in this chapter).
• Currently, only culture is recommended for throat specimens.
• Due to its non-invasive nature a urine-based NAAT is ideal for screening asymptomatic females when a pelvic examination is not warranted for other reasons. However, a physical examination remains essential, and more invasive specimens may be needed for diagnostic purposes in symptomatic individuals.
• Post exposure NAAT testing can be taken at the time of presentation without waiting for 48 hours; this is based on expert opinion, which assumes that NAATs are able to detect inoculum (DNA or RNA).
• Both chlamydia and gonorrhea can be detected from a single specimen by some NAATs.
• Culture is the preferred method for medico-legal purposes, but NAATs may be suitable, provided that positive results are confirmed. Confirmation of positive results can be done with a NAAT using a different set of primers or by DNA sequencing techniques.
• C. trachomatis IgM serology is useful for diagnosing C. trachomatis pneumonia in infants less than 3 months of age.
• Serology is not useful for the diagnosis of acute genital chlamydial infections.

Specimen collection

Potential specimen sites:

• Cervix in pubertal or older females for NAAT.
  • If the cervix has been surgically removed:
    • urine or urethral swab for NAAT
      
      or
    • vaginal swab for culture or NAAT* (see Laboratory Diagnosis section in this chapter).
      
      or
    • rectal swab for culture or NAAT** (see Laboratory Diagnosis section in this chapter).
• Urethral swab in males for NAAT (preferably not have voided for at least 2 hours, but this does not preclude testing).
• Urine NAAT, vaginal/rectal swab for culture in prepubertal girls.
• Urine NAAT for females and males of any age.
  • Any time of day.
  • Initial 10 to 20 mL of the urine stream (not mid-stream).
  • Preferably not having voided for at least 2 hours, but this does not preclude testing.
• Endometrial or fimbrial biopsy specimens for NAAT in women undergoing laparoscopy for investigation of pelvic inflammatory disease.
• Conjunctival swab for culture, EIA, DFA.
• Nasopharyngeal aspirate for culture in infants <6 months of age.
• Oropharyngeal and rectal specimens as required.

For information on specimen transport, see Laboratory Diagnosis of Sexually Transmitted Infections chapter.

Management

• Evaluation should be appropriate for the presenting symptoms, signs and sexual history.
• Treatment for chlamydia is indicated for the following:
  • A positive chlamydia test.
  • Diagnosis of a syndrome compatible with a chlamydial infection, without waiting for the test results of C. trachomatis.
  • Diagnosis of chlamydial infection in a sexual partner.
  • Empirical co-treatment when a diagnosis of N. gonorrhoeae is made without waiting for test results of C. trachomatis due to the significant probability of co-infection (20–42%)^{Footnote 12,Footnote 13} and the possibility of false-negative results, especially with non-NAAT methods.

Treatment

• Efficacy and use-effectiveness studies evaluating single-dose azithromycin and a 7-day course of doxycycline have demonstrated similarly high cure rates; azithromycin is much more expensive.^{Footnote 38-47}
• Ofloxacin has an efficacy similar to doxycycline and azithromycin, but it is more expensive and needs to be taken as a multiple-dose course.^{Footnote 48–Footnote 56}
• Erythromycin is associated with significantly higher gastrointestinal side effects than other regimens.^{Footnote 56–Footnote 60}
• Drug resistance is rare but may become an emerging issue.^{Footnote 61,Footnote 62}
• In the absence of a contraindication, the following treatment options are recommended.

Adults (non-pregnant and non-lactating): urethral, endocervical, rectal, conjunctival infection

(For pelvic inflammatory disease, see Pelvic Inflammatory Disease chapter; for epididymitis, see Epididymitis chapter.)

Children

• Topical therapy alone for conjunctivitis is NOT adequate and is unnecessary when systemic treatment is used.
• The use of erythromycin in infants under 6 weeks of age has been associated with infantile hypertrophic pyloric stenosis (IHPS).^{Footnote 63-Footnote 66} The risk of IHPS with other macrolides (e.g., azithromycin, clarithromycin) is unknown. The risks and benefits of using erythromycin in such infants should be explained to parents. When erythromycin is used in such infants, it is important to monitor for signs and symptoms of IHPS. IHPS following erythromycin use should be reported to the Canadian Adverse Drug Reaction Monitoring Program at 1-866-234-2345.
• The need to treat infants less than 6 weeks of age for C. trachomatis can be avoided by screening pregnant women and treating before delivery.
• Doxycycline is contraindicated in children under 9 years of age.
• Quinolones have been associated with articular damage in young animals. Such joint changes have not been clearly attributable to quinolone use in children. Its safety in children has not been established. Quinolones should not be used in prepubertal patients. Experience in pubertal patients under 18 years of age is limited.

Pregnant women and nursing mothers: urethral, endocervical, rectal infection

• Clinical trials comparing amoxicillin, erythromycin and azithromycin have demonstrated similar microbiological and clinical cure, but maternal gastrointestinal side effects are more common with erythromycin.^{Footnote 67–Footnote 75}
• To date, there are limited data collected on azithromycin in pregnancy, but it is considered to be safe in this context by many experts.^{Footnote 68–Footnote 70,Footnote 72–Footnote 74}
• Doxycycline and quinolones are contraindicated in pregnancy and in lactating women.
• Clindamycin requires dosing three to four times a day for 10-14 days and does not offer any advantage. In addition, it is even more expensive than azithromycin and is thus not being listed as an option.
• Data on neonatal outcomes are limited.

Table 5. Pregnant women and nursing mothers: urethral, endocervical, rectal infection

• Amoxicillin 500 mg PO tid for 7 days^{Table 5 - Footnote *} [A-l]
  
  OR
• Erythromycin 2 g/day PO in divided doses for 7 days^{Table 5 - Footnote *Table 5 - Footnote †} [B-l]
  
  OR
• Erythromycin 1g/day PO in divided doses for 14 days^{Table 5 - Footnote *Table 5 - Footnote †} [B-l]
  
  OR
• Azithromycin 1 g PO in a single dose, if poor compliance is expected ^{Table 5 - Footnote ‡ [B-l]}

*If erythromycin or amoxicillin has been used for treatment in nursing mothers, test of cure should be performed 3- 4 weeks after the completion of treatment.

†Erythromycin dosage refers to the use of erythromycin base. Equivalent dosages of other formulations may be substituted ( with the exception of the estolate formulation being contraindicated in pregnancy).
Gastrointestinal side effects are more severe with erythromycin than amoxicillin.

‡If vomiting occurs more than 1 hour post-administration, a repeat dose is not required.

Note: Test of cure should be performed 3-4 weeks after the completion of treatment in all pregnant women.

Consideration for other STIs

• See Primary Care and Sexually Transmitted Infections chapter.
• Obtain specimen(s) for the diagnosis of N. gonorrhoeae.
• Obtain a blood sample for serologic testing for syphilis (see Syphilis chapter).
• HIV testing and counselling are recommended (see Human Immunodeficiency Virus Infections chapter).
• Immunization against hepatitis B is recommended in non-immune non-immunized individuals (see Hepatitis B Virus Infections chapter).
• Discuss HPV vaccine with women as per the recommendations outlined in the Canada Communicable Disease Report, Volume 33 ACS-2, (2007) National Advisory Committee on Immunization (NACI) statement on Human papillomavirus vaccine.

Reporting and Partner Notification

• C. trachomatis infections are reportable by laboratories and physicians to local public health authorities in all provinces and territories.
• All partners who have had sexual contact with the index case within 60 days prior to symptom onset or date of specimen collection (if asymptomatic) should be tested and empirically treated regardless of clinical findings and without waiting for test results.
  • The length of time for the trace-back period should be extended:
    1. to include additional time up to the date of treatment
    2. if the index case states that there were no partners during the recommended trace-back period, then the last partner should be notified
    3. if all partners traced (according to recommended trace-back period) test negative, then the partner prior to the trace-back period should be notified.
• Parents of infected neonates (i.e., mother and her sexual partner[s]) should be located, clinically evaluated and treated.
• Local public health authorities are available to assist with partner notification and help with appropriate referral for clinical evaluation, testing, treatment and health education. If resources for local public health authority support are limited, priority for partner notification should be directed toward youth/young adults <25 years of age.

Follow-up

• Test of cure for C. trachomatis is not routinely indicated if a recommended treatment is taken AND symptoms and signs disappear AND there is no re-exposure to an untreated partner except:
  • Where compliance is suboptimal.
  • If an alternative treatment regimen has been used.
  • In all prepubertal children.
  • In all pregnant women.
• Test of cure using a NAAT, if needed, should be performed at 3-4 weeks after the completion of effective treatment to avoid false-positive results due to the presence of non-viable organisms.
• Repeat testing in all individuals with C. trachomatis infection is recommended 6 months post-treatment, as reinfection risk is high.
• In patients with apparent treatment failure, possibilities include the following:
  • Failure to take medication correctly or to finish course of therapy.
  • Re-exposure to an untreated partner.
  • Infection acquired from a new partner.
  • A false-positive result.
  • Rarely, resistance is an issue.
• In patients with persistent symptoms, infection with other pathogens and a non-infective etiology should also be considered.

Special Considerations

Children

• It is essential that neonates born to infected mothers be tested for C. trachomatis. Neonates should be treated if test results are positive. They should be closely monitored for signs of chlamydial infection (e.g., conjunctivitis, pneumonitis). Prophylaxis is not recommended unless follow-up cannot be guaranteed.
• Sexual abuse needs to be considered when genital, rectal or pharyngeal chlamydial infection is diagnosed in any prepubertal child, although perinatally acquired C. trachomatis can persist in an infant for up to 3 years. Consultation with a colleague experienced in such cases should be sought. Siblings and other children possibly at risk should also be evaluated.
• Sexual abuse of children must be reported to the local child protection agency (See Sexual Abuse in Peripubertal and Prepubertal Children chapter).
• All persons named as suspects in child sexual abuse cases should be located and clinically evaluated; prophylactic treatment may or may not be offered and the decision to treat or not should be based on history, clinical findings and test results (See Sexual abuse in Peripubertal and Prepubertal Children chapter).
• Follow-up cultures for “test of cure” are indicated approximately 3-4 weeks after completion of therapy in prepubertal children.

References