Positive NAAT test results for Neisseria gonorrhoeae do not require routine confirmatory testing

1. Positive NAAT test results for Neisseria gonorrhoeae do not require routine confirmatory testing Matthew R. Golden MD, MPH Center for AIDS & STD, University of WA Public Health - Seattle & King County

2. Objectives • To demonstrate that NAAT for gonorrhea do not require universal confirmatory testing when used in low prevalence environments. • Issues I will not argue • Should low prevalence populations be screened • Selective screening – currently do not exist • PCR can be used in very low prevalence • populations without confirmatory testing

3. Problems with an argument based on PPV • Routine confirmatory testing is impractical • Need for routine testing reflects a hyperbolic sense of risk, and excessive attention to relative rather than absolute risk • Perceived need is based on notion that true test performance in a very low prevalence population can’t be known. It’s cynical. • Maybe some tests are OK?

4. Approaches to confirmatory testing

5. Positive predictive value is primarily a function of prevalence & specificity Positive Predictive Value (%) 1% Prevalence

6. The absolute risk & number of false positives varies little with prevalence Absolute risk false positive 0.98/100 0.95/100 0.91/100 # false positives per 10,000 98 95 91 Prevalence 1% 4% 8% PPV 49% 80% 89% Assumes 95% sensitive test and 99% specific

7. Are NAAT tests good enough? • How good do they need to be? • PPV >90% in a very low prevalence • population (i.e. 0.5%)

8. Size, Specificity and Prevalence of Larges NAAT Studies Specificity estimates are imprecise. Recent studies have avoided discrepant analysis, probably erring on the side of underestimating specificity

9. Number of specimens needed to define PPV >90% in a 0.5% prevalent population True Specificity (%)

10. Number of specimens needed to define PPV >90% in 0.5% prevalent population # tested confirmatory testing design Specificity (%)

11. PPV Aptima for N. gonorrhoeae in a low prevalence population 4 Labs in WA state test 59,664 specimens 280 (0.5%) GC+ 265 Tested using alternative set rRNA primers 258 GC+ PPV= 97.4 (95% CI 95.1%-98.8%) • 0/194 negative specimens tested positive for N. gonorrhoeae

12. Limitations to Confirmatory Testing • Using a NAAT for confirmatory testing assumes that the confirmatory NAAT is specific. If an organism other than N. gonorrhoeae has nucleic acid amplification sequences amplified by both tests, then a confirmatory NAAT results will not be valid. • Routine confirmatory testing doesn’t solve this problem unless all the patients come back for culture. • This is not practical and culture is somewhat less sensitive than NAATs, so interpreting results will still be difficult. • There is still a need for judgment in ordering and interpreting tests

13. Conclusions • Confirmatory testing is not indicated for all specimens that test positive for N. gonorrhoeae using NAATs in low prevalence populations • Confirmatory testing is not practical • Perceived need based on low threshold for absolute risk of false positive • Assumes test performance cannot be defined • Need for confirmation depends on the test • Aptima performs well and that confirmatory testing is not needed. • PCR does not perform adequately and confirmatory testing is • needed. • Data are inadequate to assess the need for confirmatory • testing with SDA & Probetec – some data low positive SDA may • be more likely to be false positive