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Gonorrhoea notifications and nucleic acid amplification testing in a very low-prevalence Australian female population

Eric P F Chow, Glenda Fehler, Tim R H Read, Sepehr N Tabrizi, Jane S Hocking, Ian Denham, Catriona S Bradshaw, Marcus Y Chen and Christopher K Fairley
Med J Aust 2015; 202 (6): 321-323. || doi: 10.5694/mja14.00780

Summary

Objectives: To examine whether the rapid increase of gonorrhoea notifications in Victoria, Australia, identified by nucleic acid amplification test (NAAT) is supported by similar changes in diagnoses by culture, which has higher specificity, and to determine the proportion of tests positive among women tested.

Design, setting and participants: Retrospective analysis of Medicare reporting of dual NAATs in Victoria, Victorian Department of Health gonorrhoea notifications, and gonorrhoea culture data at the Melbourne Sexual Health Centre (MSHC), among women, 2008 to 2013.

Main outcome measures: Gonorrhoea notifications and testing methods.

Results: Gonorrhoea cases identified by NAAT increased from 98 to 343 cases over the study period. Notifications by culture alone decreased from 19 to five cases. The proportion of NAATs positive for gonorrhoea in Victoria was low (0.2%–0.3%) and did not change over time (P for trend, 0.66). Similarly, the proportion of women tested at the MSHC for gonorrhoea who tested positive (0.4%–0.6%) did not change over time (P for trend, 0.70). Of untreated women who had a positive NAAT result for gonorrhoea and were referred to the MSHC, 10/25 were confirmed by culture.

Conclusions: The positivity of gonorrhoea in women identified by culture remains stable over time. Using NAAT for gonorrhoea screening in low-prevalence populations will result in many false positives. Positive NAAT results among low-risk women should be regarded as doubtful, and confirmatory cultures should be performed.

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  • Eric P F Chow1,2
  • Glenda Fehler1
  • Tim R H Read1,2
  • Sepehr N Tabrizi3
  • Jane S Hocking4
  • Ian Denham1
  • Catriona S Bradshaw1,2
  • Marcus Y Chen1,2
  • Christopher K Fairley1,2

  • 1 Melbourne Sexual Health Centre, Melbourne, VIC.
  • 2 Monash University, Melbourne, VIC.
  • 3 Royal Women's Hospital Melbourne, Melbourne, VIC.
  • 4 University of Melbourne, Melbourne, VIC.

Correspondence: echow@mshc.org.au

Acknowledgements: 

We acknowledge A Afrizal for his assistance with data extraction. This work was supported by the National Health and Medical Research Council (grant 568971).

Competing interests:

No relevant disclosures

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access_time 04:08, 25 May 2015
Sarah Garner

We disagree that many false positives are reported due to Neisseria gonorrhoeae NAAT testing locally.

Difficulties with gonorrhoea molecular testing were recognised early due to the way genetic information is easily transferred between commensal and pathogenic Neisseria species. Consequently, in Victoria all laboratories confirm positive NAATs with one or more targets or culture (1), as per national requirements (2). The specificity of testing by National Neisseria Network laboratories is 99.96% (3). The PPV will be much higher than quoted.

As blind screening is prohibited outside pregnancy under MBS rules, laboratories must assume requests are diagnostic and the overwhelming majority of requests include gonorrhoea. For logistic and test validation reasons commercial assays cannot be modified for chlamydia only detection (most detect both). Pathologists discuss rare unrequested but positive gonorrhoea NAAT tests with referring clinicians and recommend repeat cervical samples for gonorrhoea PCR/culture. Previously unidentified risk factors are often uncovered on further questioning.

We agree it is important to continue to collect susceptibility data on gonorrhoea, especially in Victoria where resistance to ciprofloxacin is 38% and decreased susceptibility to ceftriaxone is 6.5% (4). Culture collection techniques of MHSC are admirable but not readily reproduceable.

Two incompatible datasets have been used to estimate gonorrhoea incidence in women: DoH data is a patient notification system and does not take account of methods. The Medicare data quoted as a denominator for tests perfomed is inaccurate as it only reflects what tests Medicare has paid for, not total number of tests. The true number ordered is higher.

Medical Microbiologists Victoria.


1. Personal communication – Melbourne Microbiologists Meeting representing all Victorian private and public microbiology laboratories.
2. Lum G et al. Supplemental testing is still required in Australia for samples positive for Neisseria gonorrhoeae by nucleic acid detection tests. J Clin Microbiol 2006 44(11):4292-4293
3. Trembizki E et al. A national quality assurance survey of Neisseria gonorrhoeae testing. J Med Microbiol 2014 Jan 63(Pt 1):45-9
4. Stevens K et al. Antimicrobial resistance trends in Neisseria gonorrhoeae isolates from Victoria, 2000-2014. Australian Society for Antimicrobials poster presentation, 2015.

Competing Interests: No relevant disclosures

Dr Sarah Garner
Dorevitch Pathology, West Gippsland Healthcare Group

access_time 05:27, 12 June 2015
Eric P.F. Chow

The proportion of tests that are false positives is very important and we acknowledge that ‘substantial proportion’ would be a better description than ‘many’. The specificity of 99.96% [1] that Garner cite used only N. gonorrhoeae culture isolates and cannot determine the true specificity because other species of Neisseria or clinical samples negative for N. gonorrohoeae were not included. The specificity should be based on studies such as those detailed in the product insert. This specificity is lower and varies from 98.8% to 99.7%. Using the highest specificity cited of 99.7% (prevalence 0.2%), 60% would be false positives. Using the inappropriate figure of 99.96%, 20% would be false positives. If confirmatory testing is done then this will be reduced but there is substantial concerns about discrepant analysis which accepts that because a second NAAT is positive, the result must be positive [2]. This is why the US, the UK and Australia recommend only using gonorrhoea when it is suspected on clinical grounds or the true prevalence is more than about 1% [3-5]. It is much lower.

We agree that most of the commercial assays cannot be modified for the detection of chlamydia and gonorrhoea, however some like the Roche Cobas 4800, can suppress the gonorrhoea result. We would recommend laboratories suppress the gonorrhoea results if it is not requested.

We agree that the denominator for the number of tests through Medicare was conservative. However using a higher number would reduce the prevalence further and only strengthen the argument to restrict testing to those at significant risk.


References:
1. Trembizki E, Lahra M, Stevens K, Freeman K, Hogan T, Hogg G, et al. A national quality assurance survey of Neisseria gonorrhoeae testing. J Med Microbiol. 2014;63(Pt 1):45-9.
2. Hadgu A, Sternberg M. Reproducibility and specificity concerns associated with nucleic acid amplification tests for detecting Chlamydia trachomatis. Eur J Clin Microbiol Infect Dis. 2009;28(1):9-15.
3. Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep. 2014;63(RR-02):1-19.
4. Hughes G, Ison C, Field N, Folkard K, Kennedy I, Alexander S, et al. Guidance for the detection of gonorrhoea in England - Including guidance on the use of dual nucleic acid amplification tests (NAATs) for chlamydia and gonorrhoea. London: Public Health England, 2014.
5. Smith DW, Tapsall JW, Lum G. Guidelines for the use and interpretation of nucleic acid detection tests for Neisseria gonorrhoeae in Australia: a position paper on behalf of the Public Health Laboratory Network. Commun Dis Intell Q Rep. 2005;29(4):358-65.

Competing Interests: No relevant disclosures

Dr Eric P.F. Chow
Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia

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