Spontaneous clearance of asymptomatic anogenital and pharyngeal Neisseria gonorrhoeae: A secondary analysis from the NABOGO trial

Introduction: Spontaneous clearance of asymptomatic Neisseria gonorrhoeae (NG) does occur, but data are scarce. We aimed to assess spontaneous clearance among patients with asymptomatic anal, pharyngeal, vaginal and urethral NG infections who participated in the New AntiBiotic treatment Options for uncomplicated GOnorrhoea (NABOGO) trial. In addition, we assessed the determinants associated with spontaneous clearance. Methods: The NABOGO trial (Trial registration number: NCT03294395) was a randomised controlled, double-blind, single-centre trial assessing non-inferiority of ertapenem, gentamicin and fosfomycin to ceftriaxone for treatment of uncomplicated gonorrhoea. For asymptomatic NABOGO participants, we collected pre-enrolment and enrolment visit samples before trial medication was given. Spontaneous clearance was defined as a positive pre-enrolment nucleic acid amplification test (NAAT) result, followed by a negative NAAT at enrolment. We compared the median time between pre-enrolment and enrolment visits for patients who cleared spontaneously and for those who did not. Determinants of spontaneous clearance were assessed using logistic regression. Results: Thirty-two of 221 (14.5%) anal NG infections cleared spontaneously, 17 of 91 (18.7%) pharyngeal, 3 of 13 (23.1%) vaginal and 9 of 28 (32.1%) urethral NG infections. The median time between the pre-enrolment and enrolment visit was longer for patients who cleared their pharyngeal infection spontaneously compared with those who did not (median 8 days (IQR=7-11) vs 6 days (IQR=4-8), p=0.012); no determinants of clearance at other sites were identified. Overall, patients with more days between the pre-enrolment and enrolment visit were more likely to clear spontaneously (adjusted OR=1.06 per additional day, 95% CI 1.01 to 1.12). No association between location of NG infection and spontaneous clearance was found. Conclusions: A significant proportion of asymptomatic patients cleared their NG infections spontaneously. Given these results, treatment of all NG infections after a one-time NAAT may be excessive, and more research on the natural history of NG is needed to improve antibiotic stewardship.