Leveraging whole genome sequence data to evaluate Neisseria gonorrhoeae molecular diagnostic assays

Summary

Neisseria gonorrhoeae (Ng) is a leading cause of sexually transmitted infections (STIs) worldwide, responsible for >87 million cases annually. Ng isolates extensively resistant to last-line antibiotics have been reported globally limiting treatment options. This makes combatting Ng a global public health priority.

In high-income settings, most gonorrhoea infections are diagnosed using commercially available nucleic acid amplification tests (NAATs) that target genetic determinants harboured by Ng. Most NAATs have been validated using defined isolate collections representative of the Neisseria genus with further validation undertaken in clinical settings where results from multiple NAATs are compared. To-date, however, whole genome sequence data (WGS) have not been exploited to assess the specificity and sensitivity of genetic targets in silico. This project therefore aims to leverage WGS to evaluate Ng NAATs and potentially identify alternative genetic targets.

Work will consist of:

1. Perform literature searches to refine and identify the genetic targets used in commercial Ng NAATs
2. Evaluate the specificity and sensitivity of each NAATs using WGS belonging to >60,000 Neisseria isolates that span the Neisseria genus including WGS from >39,000 N.meningitidis isolates, >20,000 Ng isolates, and >1,600 other Neisseria species. Following genome quality control checks, WGS will be screened for genetic targets used in NAATS using in silico PCR tools.
3. Undertake statistical analyses to calculate positive predictive values, negative predictive values, sensitivity and specificity for each NAATs evaluated.

Outcome: first study to leverage WGS to evaluate STI NAATs; publication of results and methodology.