Canadian guidelines on sexually transmitted infections (2008 update)
Chlamydial 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 1997.1
• According to preliminary data, over 65,000 cases were reported in Canada in 2006
• Sexual y 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.3–8
• Underscreening is a gap in high-risk males and females. Males, the forgotten reservoir,
have infrequent health-maintenance visits.9–11
• The usual incubation period from time of exposure to onset of symptoms is 2 to 3 weeks,
• In the absence of treatment, infection persists for many months.
• Individuals infected with Neisseria gonorrhoeae are often co-infected with C. trachomatis.12,13
– Sexual contact with a chlamydia-infected person.
– A new sexual partner or more than two sexual partners in the past year.
– Previous sexual y 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 Sexual y 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
• Screening of at-risk groups (as per risk factors listed above):
– Sexual y 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.14,15 While
waiting for such data, it is prudent to screen al sexual y active males under the age of 25 for
Chlamydia trachomatis.7,8,10,16–24
Chlamydial Infections
– 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
• Repeat screening of individuals with chlamydia infection after 6 months.26,32-35
• To prevent reinfection, partners need to be assessed, tested, treated, and counsel ed.
• 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
Manifestations Table 1. Symptoms and signs36 Neonates and Infants Table 2. Major sequelae m s n ra T lly a u x e S n o s e lin e id u G n ia d a n a C Chlamydial Infections Diagnosis Laboratory diagnosis
(See Laboratory Diagnosis of Sexual y Transmitted Infections chapter.)
• Results are highly dependent on the type of test available; specimen col ection and transport;
and laboratory expertise. Consult with your local laboratory regarding available tests and their
• 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
• 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.37 Check with your laboratory to see if this is an option.*
(see Specimen col ection 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 col ection 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
• 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
• Serology is not useful for the diagnosis of acute genital chlamydial infections.
o s e lin e id u G n ia d a n a C Chlamydial Infections Specimen collection
• Cervix in pubertal or older females for NAAT.
– If the cervix has been surgical y removed:
– vaginal swab for culture or NAAT* (see Laboratory Diagnosis section in this chapter).
– 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
• Urine NAAT, vaginal/rectal swab for culture in prepubertal girls.
• Urine NAAT for females and males of any age.
– 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 Sexual y Transmitted Management
• Evaluation should be appropriate for the presenting symptoms, signs and sexual history.
• Treatment for chlamydia is indicated for the fol owing:
– Diagnosis of a syndrome compatible with a chlamydial infection, without waiting for the test
– 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%)12,13
and the possibility of false-negative results, especial y with non-NAAT methods. lin e id u G n ia d a n a C Chlamydial Infections 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.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.48–56
• Erythromycin is associated with significantly higher gastrointestinal side effects than
• Drug resistance is rare but may become an emerging issue.61,62
• In the absence of a contraindication, the fol owing 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,
Table 3. Adults (non-pregnant and non-lactating): urethral, endocervical, rectal, conjunctival infection Preferred Alternative
• Doxycycline 100 mg PO bid for 7 days [A-I]
• Ofloxacin 300 mg PO bid for 7 days [B-I ]
• Azithromycin 1 g PO in a single dose if poor
• Erythromycin 2 g/day PO in divided doses
• Erythromycin 1g/day PO in divided doses
* If vomiting occurs more than 1 hour post-administration, a repeat dose is not required.
† Erythromycin dosages refer to erythromycin base. Equivalent dosages of other formulations may be substituted
(with the exception of the estolate formulation, which is contraindicated in pregnancy). If erythromycin
has been used for treatment, test of cure should be performed 3-4 weeks after completion of therapy. Children
• Topical therapy alone for conjunctivitis is NOT adequate and is unnecessary when systemic
• The use of erythromycin in infants under 6 weeks of age has been associated with
infantile hypertrophic pyloric stenosis (IHPS).63-66 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 fol owing 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. Chlamydial Infections
• 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. Table 4. Children First week of life >1 week to >1 month to 9–18 years <9 years
• Erythromycin
• Azithromycin
• Erythromycin
• Doxycycline 5 mg/
• Erythromycin
• Azithromycin
• Erythromycin
• Sulfamethoxazole
• Erythromycin
• Sulfamethoxazole
* Erythromycin dosages refer to the use of erythromycin base. Equivalent dosages of other formulations may
be substituted (with the exception of the estolate formulation, which is contraindicated in pregnancy).
If erythromycin or sulfamethoxazole has been used for treatment, repeat testing after completion of
• Neonates born to infected mothers need to be tested for C. trachomatis. Neonates should be
treated if their test results are positive. They should be closely monitored for signs of chlamydial infection
(e.g., conjunctivitis, pneumonitis). Prophylaxis is not recommended unless fol ow-up cannot be guaranteed.
• Test of cure should be performed 3-4 weeks after the completion of treatment in al prepubertal children. lin e id u G n ia d a n a C Chlamydial Infections Pregnant women and nursing mothers: urethral, endocervical, rectal infection
• Clinical trials comparing amoxicil in, erythromycin and azithromycin have demonstrated similar
microbiological and clinical cure, but maternal gastrointestinal side effects are more common
• To date, there are limited data col ected on azithromycin in pregnancy, but it is considered to be
safe in this context by many experts.68–70,72–74
• 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* [A-I]
• Erythromycin 2 g/day PO in divided doses for 7 days*† [B-I]
• Erythromycin 1g/day PO in divided doses for 14 days*† [B-I]
• Azithromycin 1 g PO in a single dose, if poor compliance is expected‡ [B-I]
* If erythromycin or amoxicil in 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 amoxicil in.
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 al pregnant women. Consideration for Other STIs
• See Primary Care and Sexual y 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 counsel ing are recommended (see Human Immunodeficiency Virus
• 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 papil omavirus vaccine. u G n ia d a n a C Chlamydial Infections Reporting and Partner Notification
• C. trachomatis infections are reportable by laboratories and physicians to local public health
authorities in al 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 col ection (if asymptomatic) should be tested and empirical y
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,
• 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:
– If an alternative treatment regimen has been used.
• 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 al 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 fol owing:
– Failure to take medication correctly or to finish course of therapy.
– Re-exposure to an untreated partner.
– Infection acquired from a new partner.
• In patients with persistent symptoms, infection with other pathogens and a non-infective etiology
u G n ia d a n a C Chlamydial Infections 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
• Sexual abuse needs to be considered when genital, rectal or pharyngeal chlamydial
infection is diagnosed in any prepubertal child, although perinatal y acquired
C. trachomatis can persist in an infant for up to 3 years. Consultation with a col eague
experienced in such cases should be sought. Siblings and other children possibly
• Sexual abuse of children must be reported to the local child protection agency (See
Sexual Abuse in Peripubertal and Prepubertal Children chapter).
• Al persons named as suspects in child sexual abuse cases should be located and
clinical y 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).
• Fol ow-up cultures for “test of cure” are indicated approximately 3-4 weeks after completion
lic b u P — s n tio c fe In d itte m s n ra T lly a u x e S n o s e lin e id u G n ia d a n a C Chlamydial Infections
The Rise of Antibiotic-Resistant Infections by Ricki Lewis, Ph.D. When penicillin became widely available during the second world war, it was a medical miracle, rapidly vanquishing the biggest wartime killer--infected wounds. Discovered initially by a French medical student, Ernest Duchesne, in 1896, and then rediscovered by Scottish physician Alexander Fleming in 1928, the product of the