Monitoring therapy success of Chlamydia trachomatis infections using culture
A prospective observational cohort study.

Clinicians may use a one-time follow-up test, a so-called test-of-cure (TOC),
in order to confirm success of treatment of a Chlamydia trachomatis (Ct)
infection. The value of a TOC using a nucleic acid amplification test (NAAT)
after treatment is subject to discussion, as the presence of Ct-nucleic acids
after treatment may be prolonged and intermittent. This applies to both DNA and
RNA tests, which can not differentiate between dead or living Chlamydia
bacteria. It has been shown that the number of NAAT-positive patients does not
reach zero at any time point after considered adequate treatment and starts
increasing before day 51 after treatment. It is unknown whether this is due to
failure of therapy, re-infections or other reasons. Despite the lower
sensitivity compared to NAAT, a positive culture (after treatment) can exclude
false positive molecular remnants of successfully treated infections and prove
a persistent infection or re-infection with Ct.

Primary objective: To demonstrate that Positive Ct NAAT results 7, 21 and 49
days after (considered adequate) treatment of urogenital Ct with azithromycin
is due to slow clearance of Ct RNA/DNA remnants (Ct culture negative) and not
to therapy resistant viable Ct (Ct culture positive).

Secondary objectives: 1) To estimate the sensitivity of Ct culture in a
head-to-head comparison with the Aptima Combo 2 assay and the COBAS® 4800 CT/NG
Test in urogenital samples from untreated patients. 2) To distinguish
recurrent or persistent infections from new infections by determining if
persistent Ct NAAT and/or culture positive results after treatment are caused
by the same Ct strain defined by a high resolution multilocus sequence typing
method (CT-MLST). 3) To collect data and samples that can be used subsequently
for the evaluation of more practical TOC that do not require culture.

A prospective observational cohort study involving female STI Outpatient Clinic
patients with a urogenital Ct infection, objectified by routine Ct NAAT (Aptima
Combo 2 assay). Upon consent, participants are asked to complete a
questionnaire and undergo four extra speculum examinations to obtain a cervical
swab for Ct culture and NAAT on days 0 and 7, 21 and 49 days after treatment.

Participants are asked to revisit the STI Outpatient Clinic at days 7, 21 and
49 after treatment and to have an extra endocervical specimen collected by
speculum examination at each timepoint. Another inconvenience for patients is
our request to practice safe sex or refrain from sexual contact during the
study period and refrain from vaginal douching. The treatment that patients
receive in this study will not pose any other or additional risks than standard
of care. The treatment itself is not a point of investigation in this study. We
classify this study as having a low chance of possible risks and a low degree
of harm, leading to a negligible risk to patients.