Agent-based modelling study of antimicrobial resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment

Introduction:
Antimicrobial resistant (AMR) gonorrhoea is a global public health threat. In London, diagnoses of gonorrhoea in men who have sex with men (MSM) have increased year on year since 2010. Importantly, our last-line treatment (ceftriaxone) is used in first-line therapy. However, over half of tested isolates are still sensitive to previously recommended drugs, e.g. ciprofloxacin. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised resistance guided therapy. Static models have been used previously to evaluate the cost-effectiveness of POCT, but these are limited in not accounting for dynamic changes in disease epidemiology resulting from changes to testing and treatment practice.

Methods:
We developed an individual-based dynamic transmission model of gonorrhoea infection in MSM living in London, incorporating ciprofloxacin-sensitive and resistant strains. The time-dependent sexual contact network is captured by periodically restructuring active connections to reflect the transience of contacts. We explored different strategies to improve treatment selection, including discriminatory POCT, and selecting partner treatment based on either index case or partner susceptibility. Outcomes included population prevalence of gonorrhoea and drug dose counts.

Results:
The new model is flexible and fast and is able to capture essential elements of gonorrhoea epidemiology (low prevalence, heterogeneous behaviour, dynamic sexual network). In this case study we show that using POCT to detect ciprofloxacin-sensitive infections could result in a large decrease in ceftriaxone doses (by 70% compared to the reference case in our simulations). It also suggests that ceftriaxone use can be reduced with existing technologies, albeit to a lesser degree: either using index case sensitivity profiles to direct treatment of partners, or testing notified partners with strain discriminatory laboratory tests prior to treatment, reduced ceftriaxone use in our model (by 27% and 47% respectively).

Conclusion:
POCT to detect ciprofloxacin-sensitive gonorrhoea are likely to dramatically reduce reliance on ceftriaxone but requires the implementation of new technology. In the meantime, we could significantly reduce the proportion of unnecessary ceftriaxone treatment by testing partners before treatment. Alternatively, index case sensitivity profiles could be used to select effective treatments for partners.