Chlamydia trachomatis is the most commonly reported bacterial sexually transmitted infection (STI) in Europe [1]. Genital chlamydial infection causes cervicitis and salpingitis in women and urethritis and conjunctivitis in both men and women. However, chlamydial infections often produce few or no symptoms (in approximately 70% of women and 50% of men) and may remain undetected and untreated. If left untreated, this STI can progress to cause complications with serious consequences on women’s reproductive health, including pelvic inflammatory disease (PID) that may lead to ectopic pregnancy and tubal infertility. Chlamydial infection is easily treated with a single dose of antibiotics and is a preventable disease (safe sex, condom use). An important aspect of prevention involves the evaluation of sexual partners to prevent re-infection and further spread of disease.
In many European countries, the incidence rates of chlamydia infection have increased in the past 10 years. In 2005, over 200,000 cases were reported in 17 European countries (known to be an underestimate) [1]. However, in most European countries it is not a notifiable disease. Because of the asymptomatic nature of infections, screening studies contribute largely to our knowledge of chlamydia. In Europe, prevalence rates have shown to range between 2 and 17% in asymptomatic women, depending on setting, population and country [2,3].
Chlamydia infections are widely diffused in the general population and – unlike gonorrhoea and syphilis – appear not to be restricted to a particular risk group, mainly affecting young people, especially young women. The highest incidence is usually reported in the age group 15–24 years, accounting for more than 60% of all cases, as described in this issue in the article of D. Whyte et al., and also in annual STI reports in the Netherlands and United Kingdom [4,5]. In order to control the chlamydial infection disease burden in Europe, screening programmes targeting young people are crucial for early detection and treatment of all infected individuals and their partners.
Chlamydial infection was detected for the first time in 1907 by Giemsa staining by Halberstaedter and von Prowazek [6]. Ever since, the detection has been improved with respect to sensitivity, specificity, time per assay and the laboratory standardisation. The technical development from culture, enzyme-immuno assay (EIA) and direct fluorescent-antibody assay (DFA) to the more recently developed nucleic acid amplification tests (NAATs) have resulted in easy and quick diagnostics for chlamydial infection both in clinical and screening settings. As of today, NAATs (including polymerase chain reaction – PCR) are regarded as the gold standard for chlamydial infection [7]. Current NAATs are usually targeting genes which are present in multiple copies, like all genes on the cryptic plasmid which is present in 10 copies as compared to the chromosomal genes.
In 2006, a new variant of C. trachomatis was reported in and by Sweden, designated either as Swedish CT variant (swCT variant) or new variant of C. trachomatis (nvCT) [8-12]. It had been detected following an unexpected 25% decrease in the number of infections observed in Halland county, southwest Sweden. The variant contains a 377 base pair deletion in the cryptic plasmid which is the region targeted by the NAATs manufactured by both Roche and Abbott [8]. Patients infected with this variant of C. trachomatis would therefore be given a false negative result if tested by a laboratory that used either of these assays as its diagnostic test. Several other diagnostic kits do not target the deleted region and are therefore able to detect the swCT variant (e.g. Becton Dickinson ProbeTec, GenProbe Aptima Combo2 & Aptima CT).
In Sweden, the swCT variant could spread easily in the counties that primarily used the NAATs unable to detect the swCT variant. As described in this issue of Eurosurveillance (article of I. Velicko et al.), chlamydia infection rates have increased considerably since the diagnostic methods were changed. At the same time, the authors argue that the diagnostics may not have been the only factor that contributed to the recently observed increase.
What does this mean for Europe? Given the increasing amount of international travel, the recent growth of STI rates in young people and sexual activity persisting, a further spread of this variant has been anticipated in countries that used diagnostic assays unable to detect the swCT variant. It is of public health importance to assess the risk of possibly widespread undetected chlamydial infections in Europe. The detection of this swCT variant puts an extra burden on chlamydia control programmes in many countries that already have to face continuous increasing trends.
At the moment, the spread of the swCT variant seems to be restricted to Sweden, as presented in this issue in the article by the European network for the surveillance of STI (ESSTI) and the European Centre for Disease Prevention and Control (ECDC) (article of E.J. Savage et al.). There are a number of single case reports from other Scandinavian countries – Denmark (article of S. Hoffmann et al. in this issue) and Norway [13] – as well as Ireland [14]. In this issue, France also reports a new case of swCT that had an unknown link with Scandinavia (article of B. de Barbeyrac et al. in this issue). The emergence of the swCT variant was followed by individual rapid endeavours of the STI expert community to assess the presence of this variant in other countries (dual-testing, re-testing of samples retrospectively or prospectively (article of S.A. Morré et al. in this issue) [15-17]. Rapid dissemination and the exchange of information and strains were facilitated through the network of ESSTI epidemiologists and microbiologists (http://www.essti.org) and the ECDC [18]. However, despite these many efforts no evidence has yet been found in many other European countries (article of E.J. Savage et al. in this issue) [19]. Most of the identified patients with swCT variant seem to be linked with Sweden or crucial information on epidemiological characteristics is not available. Given the on-going investigations the news of another discovery will travel fast.
In addition, several diagnostic lessons can be learned. Firstly, cryptic plasmid free strains of C. trachomatis were reported in the early 1990s, and in 2007 a plasmid free strain was reported again [20,21]. Developing diagnostic assays based on essential genes only will reduce the chance of diagnostically escaped new CT variants. Secondly, dual target NAATs (in part based on essential genes), could also circumvent the problem of missing new variants and, lastly, as is shown in Sweden, the use of different tests in one country in combination with incidence and prevalence monitoring can also be helpful in identifying potential diagnostic problems [8,12,22].
Although the articles included in this issue raise various questions, in particular why the new variant has so far been confined to Sweden, the collaboration and rapid reaction of the STI community to this possible emerging threat to public health can serve as a good example. The sharing of information facilitates action and inventing solutions of the problem.
Finally, it is worth pointing out that the current situation in Sweden provides the possibility of studying in a unique setting the transmission dynamics and network identification of chlamydial infection. However, to date no initiatives have been undertaken to address these topics.