Follow-up after treatment of Neisseria gonorrhoeae infections, when and how is a test-of-cure to be included in routine? A prospective observational cohort study

Gonorrhoea, caused by Neisseria gonorrhoeae (Ng), is the most prevalent
bacterial sexually transmitted infection (STI) globally. If left untreated
infection with Ng can result in complications including pelvic inflammatory
disease, ectopic pregnancy, infertility, epididymitis or prostatitis. To
diagnose Ng national and international guidelines increasingly recommend the
use of a nucleic acid amplification test (NAAT). This method has very high
sensitivity and specificity for Ng, but lacks the possibility to determine
antimicrobial resistance (AMR), which is done by direct cultivation.
Surveillance of AMR is important as Ng has shown a remarkable ability for rapid
development of resistance to any type of antimicrobials that have been used to
treat it so far. Recently multidrug-resistance and treatment failures even with
the last available type of antibiotics (extended-spectrum cephalosporins, ESC)
have been reported, making Ng possibly untreatable in the near future.
In the light of increasing AMR and necessary surveillance a test-of-cure (TOC)
is strongly advocated by e.g. WHO. Yet information on the appropriate timing of
TOC with a NAAT is highly limited and inconsistent.

The primary objective is: The minimum time in days after treatment for Ng to
perform a TOC using NAAT and DNA PCR. Secondary objectives are: Time to
clearance per infected location. Host and pathogen related factors associated
with time to clearance. Occurrence of intermittent bacterial DNA or RNA
positivity after treatment.

In this prospective observational cohort study 60 patients visiting the STI
outpatient clinic will be included. Inclusion criteria are: 18 years of age or
older, Ng infection confirmed at the STI Outpatient Clinic: anorectal or
urethral in males, endocervical, vaginal or anorectal in females, accepting
routine treatment. Included patients will self-sample daily for 28 consecutive
days following treatment. The collected samples will be analysed by NAAT
(APTIMA Combo 2® assay) and DNA PCR (cobas® 4800) to evaluate time to clearance
and provide answers regarding the time and place of TOC in routine practice.

This study will require patients to take daily samples, fill out a short diary,
use condoms consistently or abstain from sexual contact during the study
period, abstain from vaginal/rectal douching during the study period and return
to the STI clinic for an end of study visit.
No risks or harms are involved in this study. Benefit of the individual patient
is the monitoring of their therapy effect and clearance of the Ng infection.