Molecular Diagnosis of Gonorrhoea

1. Molecular Diagnosis of Gonorrhoea “The pros and cons from a clinical perspective” Michael Addidle

2. Molecular Testing of Gonorrhoea • Most of the newer molecular tests now combine the diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis.

3. Advantages of Molecular Testing for N. gonorrhoeae • Increased sensitivity • Decreased TAT • One swab/urine for both Chlamydia and Gono testing • Cost:-

4. Advantages of Molecular gono testing: Increased sensitivity • When compared with N. gonorrhoeae NAATs, culture methods have sensitivity of 85-95%. For females with chronic infection, this may fall as low as 50% (Whiley et al, Journal Molecular Diag. 2006) • Culture methods for N. gonorrhoeae suffer when there are significant delays in specimen transport. Once you go beyond 24 hrs transport the survival of N. gonorrhoeae starts to drop off exponentially.

5. Advantages of Molecular gono testing :Decreased TATs • Less anxiety for the patient • Potential for quicker treatment and reduced window for transmission.

6. Advantages of Molecular gono testing: One sample for both NG and CT • Trying to explain to GPs the correct swabs for STD screening is a bit of a nightmare. • Pathlab have had numerous changes in this area recently (partially cost driven) • GPs would definitely welcome this: would make the scientists life easier also. • For men, urine is validated as a suitable specimen type, big advantage over the traditional and much disliked urethral swab.

7. Advantages of Molecular gono testing: Cost issues • Traditionally molecular more expensive. • Because of the multiplex nature of the assay, (combining both chlamydia and gono) clear incentives for laboratories to look at this very carefully. • Potential labour savings also.

8. Disadvantages of molecular testing • No susceptibility profile • Not validated for certain types of samples • May not stand up in a medico-legal situation • Specificity?? (or is this historical) • Molecular expertise within the laboratory, particularly for troubleshooting.

9. Disadvantages of molecular testing: No susceptibility profile • ?repeat sampling on molecular positives for C&S • Makes empirical Ceftriaxone a necessity (or oral Cefixime if we had it in NZ) • Resistance rates for ciprofloxacin and penicillin are such that they are no longer appropriate for empirical treatment. • GPs do not always have access to IM Ceftriaxone • Would probably require referral of most positive cases to Sexual Health Clinics (which is not a bad thing….)

10. Disadvantages of molecular testing for gonorrhoea:Not validated for certain types of sample sites • Generally rectal and pharyngeal sites not validated for most molecular NG assays. (CDC recommends that culture still be used for these sites) • High incidence of commensal Neisserias in these sites. • Numbers of these types of samples often not sufficient in trials to validate these sites. • (However sensitivity for these sites significantly greater compared with gonorrhoea culture)

11. Disadvantages of molecular testing for gonorrhoea: ?Specificity • These tests need to have seriously high specificity if used to screen for gono in a low prevalence pop. • Serious diagnosis, not so much from clinical point of view but from the psycho-social implications (and implications for me if we get it wrong!).

12. Disadvantages of molecular testing for gonorrhoea: ?Specificity Ie let us assume the sensitivity and specificity of a gono test are both 99%. In our lab approx 1% of our genital swabs are positive for gono. • This gives a PPV of 0.5 Ie half of our results will be false positive. • Even if specificity is 99.5%, in a 1% prevalence situation, PPV is only 0.67

13. What I don’t want… • GP phoning me with….“I have a lady who has been diagnosed with gonorrhoea by your lab, who swears blind that there is no way she could have gonorrhoea. What are the chances that your test is falsely positive.” • Kit manufacturers (should)show assay performance in terms of sensitivity and specificity …but Scientists, Clinicians and Clinical Microbiologists need to think about it in terms of Positive Predictive Value (PPV) Is it necessary to confirm a molecular positive gonorrhoea ?

14. Medico-legal issues • Traditionally a positive culture under strict chain of evidence is acceptable as evidence. • Now difficult for a court to refute positive molecular test by two different assays. Legal interpretation of Neisseria gonorrhoeae results may vary from country to country.

15. The future • Will molecular testing for gonorrhoea be common practice in NZ in 10 years time?? (almost certainly) • For me the biggest issue is minimising false positives. I can live with the lack of antimicrobial susceptibility profile. • Time to look at it seriously, don’t be scared to ask the assay manufacturers the difficult questions. • If a lab decides to go ahead with molecular testing for Neisseria gonorrhoeae …any test change needs to be communicated effectively to the users, who when kept in the loop are often very understanding of need to innovate and work within a tight budget. (They will be doing exactly the same thing in their particular field) Any questions around the issues raised?