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Nobody in their right mind would want to confirm a chlamydial infection by isolation of the organism in tissue culture, if they didn't have to. The only really justification these days is for research, or for the diagnosis of chlamydial infection for medico-legal cases - judicial authorities have not yet caught up with the excellent specificity of modern nucleic acid amplification-based tests for C. trachomatis infection. Antigen detection tests generally lack the sensitivity for screening low to middle prevalence populations. However direct immunofluorescence is still a valuable test for resolving a problem result and the Dako IDEIA PCE warrants further characterisation.

In general, nucleic acid amplification-based tests are most useful where the organism is difficult or tedious to isolate (e.g. C. trachomatis) or is slow to grow (M. tuberculosis). PCR combined with sequencing gives the research lab the opportunity to further characterise the infecting organism's genotype. As far as C. trachomatis is concerned, we are fortunate indeed that there are now a number of nucleic acid amplification based-tests with sufficient sensitivity and specificity to give reasonable predictive values, even when screening low prevalence asymptomatic populations. Urine and self-collected vulval introital specimens are evaluated and acceptable alternatives to an endocervical swab when screening for chlamydial genital tract infection in women. For men, urine testing is an acceptable and humane alternative to the endourethral swab. 

The emphasis of control strategies is likely to shift in the future to the asymptomatic population, using self-collected samples taken at home and mailed to the appropriate laboratory. In this respect, it will be just as important to detect infection in men as in women. Laboratories will increasingly be looking at ease of assay and the flexibility of the format with respect to their own needs. Many of the early nucleic acid amplification-based tests were quite restricted with respect to specimen throughput. The more recent tests place greater emphasis on ease of use and flexibility. Tests have still to become sufficiently rapid and facile to be taken from the laboratory professional to the patient's side. More tests based on different nucleic acid amplification protocols, for example Q-beta replicase [Shah et al., 1994; An et al., 1995; Stefano et al., 1997] or isothermal ramification amplification [Zhang et al., 2002] are likely to be introduced.

All existing commercial nucleic acid amplification-based tests have one major disadvantage; they require a clinician to be able to 'best guess' the likely infecting organism. This is different to conventional bacteriology, where a 'look see' culture swab is often taken, either to diagnose the infection or to perform antibiotic susceptibility tests. This is rarely a problem in the setting of a sexually transmitted infection clinic, particularly now that duoplex techniques for both C. trachomatis and gonococci are available. However, in a general medical setting, it may still be a problem when trying to assess, for example, abdominal pain in a young woman. The increasing use of multiplex tests, in particular DNA micro-array technology, is likely to go some way to addressing this problem. Methods have already been developed for the in situ anchored strand displacement amplification of suspect targets [including the chlamydial plasmid] on microelectronic chips, with discrimination of the relevant bacterial species and even genotype on the same platform [Westin et al., 2000; 2001].  Microchip arrays additionally offer the possibility of assessing the associated host response, [as demonstrated for C. pneumoniae by Coombes & Mahony, 2001], and genotype [Edman 2000]. 

Looking at the array of nucleic acid amplification-based tests for C. trachomatis infection, one is tempted to build the dream test out of different components, just as football enthusiasts dream of putting together players from individual teams into one star team. Patent law precludes this. In chlamydial diagnostics we are fortunate that we have so many good tests. While basic science has and will continue to be central to this process, it is commercial competition and know-how in the market place that has been crucial in delivering the products we have in a timely manner. 

[MEW] May 2002

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