# Presentation: 448067

## 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

## 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

## 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?

## Approaches to confirmatory testing

| Approach | Barriers to implementation | Barriers to interpretation | Overall |
| --- | --- | --- | --- |
| Test a new specimen +/- different test | Patient needs to return | Which test is correct? – helpful if both are positive | - Good for usual circumstances
 Culture is definitive
 Having patients return is not practical |
| Repeat test using a different test | Incompatible media
 Need for labs to maintain >1 test or send out – turn around time | Which test is correct? – helpful if positive | Best option, but will be tough to implement unless the same testing platform is used |
| Repeat same test | Easy | Two positives still hard to interpret.
Discrepant- Which test is correct? | Easiest, but least definitive |

## Positive predictive value is primarily a function of prevalence & specificity 

- Positive Predictive Value (%)

- Prevalence

- Positive predictive value is primarily a function of prevalence & specificity* *

**1%**

## The absolute risk & number of false positives varies little with prevalence

- _Prevalence_
- 1%
- 4%
- 8%

- # false positives_ per 10,000_
- 98
- 95
- 91

- _PPV_
- 49%
- 80%
- 89%

- Assumes 95% sensitive test and 99% specific

- Absolute risk_  false positive_
- 0.98/100
- 0.95/100
- 0.91/100

## Are NAAT tests good enough?

-  How good do they need to be?
-  PPV >90% in a very low prevalence
-       population (i.e. 0.5%)

## Size, Specificity and Prevalence of Larges NAAT Studies

|  | Largest study | Specificity in largest study | Lowest prevalence studied |
| --- | --- | --- | --- |
| BDProbetec | 3,544  | 99.3 | 3.6% |
| Digene HC-II | 1,370  | 98.5 | 6.3% |
| Aptima | 1,484 | 98.7 | 8.5% |

- Specificity estimates are imprecise.
- Recent studies have avoided discrepant analysis, probably erring on the side of underestimating specificity

## Number of specimens needed to define PPV >90% in a 0.5% prevalent population

**True Specificity (%)**

## Number of specimens needed to define PPV >90% in 0.5% prevalent population

**# tested confirmatory testing design**

**Specificity (%)**

## PPV Aptima for N. gonorrhoeae in a low prevalence population

-  0/194 negative specimens tested positive for *N. gonorrhoeae*

- 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%)

## 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

## 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