Objectives In UK Microbiology laboratories there is widespread use of nucleic acid amplification tests (NAATs) which allow the simultaneous ‘dual’ detection of Neisseria gonorrhoeae and Chlamydia trachomatis, although the prevalence of gonorrhoea in most areas is low and this may lead to high numbers of false positive results. The aim of this study was to examine the evidence base for unselected testing for gonorrhoea in the community.
Methods A literature search was performed to review the use of dual testing in low prevalence settings by searching PubMed for appropriate terms linked to gonorrhoea diagnosis up to 1 December 2013 but without restriction of publication date. All publications with a prevalence of <1% were defined as low prevalence and included in this review.
Results The publication search found data in low prevalence settings from three sources; genitourinary medicine clinics, laboratories outside the UK and from the National Chlamydia Screening Programme. The evidence base to support widespread screening for gonorrhoea was found to be limited and of variable quality.
Conclusions We were unable to find an evidence base to support widespread screening for gonorrhoea in the community. However, the increasing availability of dual NAATs may lead to more testing but this should be tempered by the public health need. Pilot studies and development of robust testing algorithms should be encouraged.
- DNA AMPLIFICATION
- MOLECULAR TECHNIQUES
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Nucleic acid amplification tests (NAAT) for the detection of Neisseria gonorrhoeae have become the method of choice for testing asymptomatic individuals for urethral or endocervical infection. The ability to use non-invasive specimens (urine or self-taken vulvo-vaginal swabs) facilitates screening in both clinics specialising in sexually transmitted infections (genitourinary medicine (GUM) clinics) and non-GUM settings. However, the testing algorithm should give a positive predictive value (PPV) of >90%, and in low prevalence populations it is advised to use a confirmatory test using a different nucleic acid target to achieve an acceptable PPV.1
NAAT platforms allow the simultaneous ‘dual’ detection of N. gonorrhoeae and Chlamydia trachomatis from the same sample. It should be noted that there are marked differences in the epidemiology between chlamydia and gonorrhoea, with the latter being much rarer and in a more concentrated distribution, geographically and by risk group. Almost 50% of all UK gonorrhoea cases are diagnosed in London, and infection is strongly associated with deprived urban areas. The key risk groups are men who have sex with men, black Caribbean populations, and young heterosexuals with complex sexual networks.2
In 2010, the ‘Guidance for gonorrhoea testing in England and Wales’ concluded that there was limited information regarding the prevalence of gonorrhoea among individuals attending non-GUM settings, and that there was no evidence base to support widespread unselected testing for gonorrhoea in the community.1 However, there has been an increased use of dual NAATs among microbiology laboratories in recent years (Toby et al, 2014 unpublished data); we performed a literature review to determine if there was any change in the evidence base to support this increased use of dual NAAT testing.
PubMed was searched up to 1 December 2013 without a restriction on publication date. Our search included all types of articles published in English. Search terms included: gonorrhoea; chlamydia; dual testing; NAAT; molecular; prevalence; community; clinics; screening. All potentially relevant articles were retrieved as full manuscripts and then reviewed for inclusion. The reference lists of all relevant articles were also reviewed for additional studies. We included all studies reporting original data on NAATs for gonorrhoea in low prevalence settings. ‘Low prevalence’ was defined as less than 1%, and this was used as a cut-off for inclusion. Eligible papers included those analysing genital or non-genital samples, and specimens sourced from all patient demographic groups (age, sex, race, sexual orientation).
Results and discussion
Our literature search found that data describing the use of NAATs in low prevalence settings was reported from three main sources (table 1): GUM clinics serving low prevalence areas3–5; laboratories outside the UK6–9; and from National Chlamydia Screening Programme areas (NCSP) where dual chlamydia and gonorrhoea testing is being offered.10–14 Several different NAAT platforms were used in the studies reviewed. In every study, an initial positive NAAT underwent supplementary testing, although there were differences in the method used. In most laboratories, a positive sample was retested using another NAAT detecting a different target.3 ,4 ,6–10 ,12 Some repeated the test on residual samples using the original assay11 ,13 ,14 which, in fact, demonstrates reproducibility rather than confirmation. In one small study,5 a low PPV of 43% may be explained by the use of culture alone to confirm a positive NAAT. It is difficult to draw comparisons between the studies when the ‘gold standard’ for the diagnosis of infection is the isolation of N. gonorrhoeae, which can have a poor sensitivity. Significantly, many of the studies did not report the number of positive NAATs which were not confirmed, the false positive rates, nor calculated a PPV. One of the NCSP studies found a much lower PPV than expected, of 3.8% for women, and ‘incalculable’ for men.10 However, the authors made the incorrect assumption when estimating the PPV, that sensitivity and specificity may vary by prevalence, which is not substantiated in the context of asymptomatic gonorrhoea testing.
Of five NCSP studies, all but one reported a low prevalence of gonorrhoea infection (less than 1%), and approximately half the individuals with gonorrhoea were coinfected with chlamydia. The one NCSP study which found a much higher rate of gonorrhoea of 4.1% was from Lewisham, an area of South London which probably does not represent a ‘low prevalence’ population, as discussed above.13 The papers from outside the UK described data from community laboratories serving low prevalence populations. The study from Seattle Washington, USA,9 specifically excluded samples from specialist sexual health clinics. The study from Canada8 and the two from New Zealand6 ,7 were based in low prevalence community settings, but did not provide further details on the source of the specimens.
The evidence base to support widespread screening for gonorrhoea in the community is limited and of poor quality. Indeed, the recent National Survey of Sexual Attitudes and Lifestyles (NATSAL), found that the prevalence of gonorrhoea in the UK general population was <0.1%, and those with infection had recognised high-risk factors.15 However, the widespread availability of dual NAAT technology may lead to increased opportunistic testing for N. gonorrhoeae. This should be tempered by the public health need and be restricted to areas with higher prevalence, such as inner cities, or following pilot studies that indicate the usefulness of more widespread testing. We would support the development of an algorithm to calculate local prevalence and PPV in order to help inform whether selected screening should be implemented.
Nucleic acid amplification tests (NAATs) that detect both N. gonorrhoeae and C. trachomatis (dual NAATs) are widely used.
Gonorrhoea is at low prevalence in many areas of the UK and use of dual NAATs may lead to high numbers of false positive results.
A literature review was unable to find an evidence base to support widespread testing for gonorrhoea.
There should be a clear public health need, supported by pilot studies and robust testing algorithms, before testing for gonorrhoea is initiated.
Handling editor Jackie A Cassell
Contributors CAI initiated and supervised the review of the literature, HF carried out the review and prepared the first draft of the manuscript and CAI and HF both edited and approved the final draft.
Funding This work was internally funded by Public Health England.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.