LETTER

First, do not harm: also an issue in NAA assay diagnostics for chlamydial infection

V Verhoeven, M Ieven, A Meheus, D Avonts and H Goossens

University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

Correspondence to:
Correspondence to:
Veronique Verhoeven;
verover{at}uia.ua.ac.be

Accepted 17 October 2002

Keywords: nucleic acid amplification assay; chlamydial infection

In his update on Chlamydia trachomatis diagnostics,¹ Chernesky emphasises that nucleic acid amplification (NAA) assays can be useful for screening purposes, because of their increased sensitivity and the possibility of non-invasive sample collection. Since the introduction of these assays, many screening interventions have been undertaken and evaluated mostly in an optimal research context. However, a number of problems can be expected if these diagnostics are implemented in large scale routine clinical practice or in community screening programmes.

Firstly, multiple testing sites may be needed for accurate results,¹ but cannot be realised for reasons of cost and inconvenience.

Secondly, the positive predictive value of a test is low in low prevalence populations. To avoid false positive diagnoses in these situations repeat testing of the sample, preferably by a different technique, is highly recommended. However, in clinical practice a single positive result is often considered to indicate that a patient is infected.²

Thirdly, reproducibility problems do occur and are varying in time,³ and confirmatory testing is required when test results are intermediate or near the cut-off value. A low positive test result that is not caused by the presence of amplification inhibitors points to a low number of target organisms in the sample. Repeat testing is then a matter of statistical chance of the second portion of the sample containing detectable numbers of target organisms. Such results should be transmitted to the clinician accompanied by interpretative comments.

Fourthly, diagnostic accuracy may be affected by contamination of the specimen during laboratory processing.

Fifthly, it is not clear whether detection of a very small amount of chlamydial DNA always reflects clinically significant infection: NAA assays might identify residual DNA from a cleared or treated infection, DNA of non-viable organisms, or DNA of levels of pathogens which are too low to be infectious.^4,5

For this reasons it is likely that in routine practice a number of results will be interpreted as positive in patients who are not truly infected.

However, the impact of a chlamydia diagnosis on people’s lives is considerable,⁶ and can include stigmatisation, anxiety about reproductive health, and potential partner discord. Pre-test and post-test counselling has been shown to be labour intensive for healthcare providers too, since most infections in asymptomatic patients will be unexpected.

To overcome these problems, rigid diagnostic protocols must be developed before introducing any screening programme. Not only should infected people be identified but false positive diagnoses should be avoided. Laboratories should participate in quality control programmes, and test runs should include multiple controls. Healthcare providers should be offered agreed standards to which they can manage the different aspects of screening and counselling for chlamydial infection.

1. Chernesky MA. Chlamydia trachomatis diagnostics. Sex Transm Infect 2002;78:232–4.[Abstract/Free Full Text]
2. Garrow SC, Smith DW, Harnett GB. The diagnosis of chlamydia, gonorrhea, and trichomonas infections by self obtained low vaginal swabs, in remote northern Australian clinical practice. Sex Transm Infect 2002;78:278–81.[Abstract/Free Full Text]
3. Mallinson H, Hopwood J, Mutton K. Resolution of the recent performance problem of Abbott LCx Chlamydia trachomatis assay. Issues of repeat testing for confirmation of chlamydial infection. Sex Transm Infect 2002;78: 225–6.[Free Full Text]
4. Louie M, Louie L, Simor AE. The role of DNA amplification technology in the diagnosis of infectious diseases. CMAJ 2000;163:301–9.[Abstract/Free Full Text]
5. Turner CF, Rogers SM, Miller HG, et al. Untreated gonococcal and chlamydia infection in a probability sample of adults. JAMA 2002;287:726–33.[Abstract/Free Full Text]
6. Duncan B, Hart G, Scoular A, et al. Qualitative analysis of psychosocial impact of diagnosis of Chlamydia trachomatis: implications for screening. BMJ 2001;322:195–9.[Abstract/Free Full Text]

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