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Eurosurveillance, Volume 12, Issue 10, 01 October 2007
Editorial
Chlamydia: a major challenge for public health

Citation style for this article: Van de Laar MJ, Morré SA. Chlamydia: a major challenge for public health. Euro Surveill. 2007;12(10):pii=735. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=735

 

Marita JW van de Laar1, Servaas A Morré2,3,4

1. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden
2. VU University Medical Center, Amsterdam, the Netherlands
3. University Hospital Maastricht, Maastricht, the Netherlands
4. City of Hope Medical Center, Duarte, California, United States


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.


References

  1. Annual Epidemiological Report on Communicable Diseases in Europe. Report on the status of communicable diseases in the EU and EEA/EFTA countries. Ed. Amato-Gauci A, Ammon A. European Centre for Disease Prevention and Control. June 2007. Available from: http://www.ecdc.europa.eu/pdf/Epi_report_2007.pdf
  2. Wilson JS, Honey E, Templeton A, Paavonen J, Mårdh PA, et al. A systematic review of the prevalence of Chlamydia trachomatis among European women. Human Reproduction Update 2002;8:385–94.
  3. Fenton KA, Lowndes CM, for the European Surveillance of Sexually Transmitted Infections (ESSTI) Network. Recent trends in the epidemiology of sexually transmitted infections in the European Union. Sex Transm Infect 2004; 80: 255-263.
  4. Boer IM de, Op de Coul ELM, Koedijk FDH, van Veen MG, van Sighem AI, van de Laar MJW. HIV and Sexually Transmitted Infections in the Netherlands in 2005. RIVM rapport 441100024. Available from: http://www.rivm.nl/bibliotheek/rapporten/441100024.html
  5. Health Protection Agency. Annual Report. A Complex Picture. HIV and other Sexually Transmitted Infections in the United Kingdom: 2006. Available from: http://www.hpa.org.uk/publications/2006/hiv_sti_2006/default.htm
  6. Halberstädter L, von Prowazek S. Über Zelleinschlüsse parasitärer Natur beim Trachom. Arbeiten aus dem Kaiserlichen Gesundheitsamte, Berlin, 1907, 26: 44-47.
  7. Jespersen DJ, Flatten KS, Jones MF, Smith TF. Prospective Comparison of Cell Cultures and Nucleic Acid Amplification Tests for Laboratory Diagnosis of Chlamydia trachomatis Infections. Journal of Clinical Microbiology, October 2005, p. 5324-5326, Vol. 43, No. 10
  8. Ripa T, Nilsson PA. A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications for use of PCR diagnostic tests. Euro Surveill 2006;11(11):E061109.2. Available from: http://www.eurosurveillance.org/ew/2006/061109.asp#2
  9. Unemo M, Olcén P, Agné-Stadling I, Feldt A, Jurstrand M, Herrmann B, and al. Experiences with the new genetic variant of Chlamydia trachomatis in Örebro county, Sweden – proportion, characteristics and effective diagnostic solution in an emergent situation. Euro Surveill 2007;12(4). Available online: http://www.eurosurveillance.org/em/v12n04/1204-223.asp
  10. Ripa T, Nilsson PA. A Chlamydia trachomatis strain with a 377-bp deletion in the cryptic plasmid causing false-negative nucleic acid amplification tests. Sex Transm Dis. 2007 May;34(5):255-6.
  11. Björkman J, Jonsson L, Nilsson P. Prevalence of the new genetic variant of Chlamydia trachomatis in Södra Älvsborg County, Västra Götaland Region, Sweden. Euro Surveill 2007;12(6):E070614.4. Available from: http://www.eurosurveillance.org/ew/2007/070614.asp#4
  12. Herrmann B. A new genetic variant of Chlamydia trachomatis. Sex Transm Infect. 2007 Jul;83(4):253-4.
  13. Moghaddam A, Reinton N. Identification of the Swedish Chlamydia trachomatis variant among patients attending a STI clinic in Oslo, Norway. Euro Surveill 2007;12(3):E070301.3. Available from: http://www.eurosurveillance.org/ew/2007/070301.asp#3
  14. Lynagh Y, Walsh A, Crowley B. First report of the new variant strain of Chlamydia trachomatis in Ireland. Epi-Insight 2007;8(7):4. Available from: http://www.ndsc.ie/hpsc/EPI-Insight/Volume82007/File,2424,en.pdf
  15. Schachter J. The Chlamydia trachomatis plasmid deletion mutant – what does it mean to us? Sex Transm Dis. 2007 May;34(5):257.
  16. Marions L, Rotzen-Ostlund M, Grillner L, Edgardh K, Tiveljung-Lindell A, Wikstrom A, Lidbrink P. High Occurrence of a New Variant of Chlamydia trachomatis Escaping Diagnostic Tests Among STI Clinic Patients in Stockholm, Sweden. Sex Transm Dis. 2007 Aug 29 [Epub ahead of print].
  17. De Vries H, Catsburg A, van der Helm J, Beukelaar E, Morré S, Fennema J, Thiesbrumme H. No indication of Swedish Chlamydia trachomatis variant among STI clinic visitors in Amsterdam. Euro Surveill 2007; 12(2). Available from: http://www.eurosurveillance.org/ew/2007/070208.asp#3
  18. Van de Laar M, Ison C. Europe-wide investigation to assess the presence of new variant of Chlamydia trachomatis in Europe. Euro Surveill 2007;12(2):E070208.4. Available from: http://www.eurosurveillance.org/ew/2007/070208.asp#4
  19. Catsburg A, van Dommelen L, Smelov V, de Vries HJC, Savitcheva A, Domeika M, Herrmann B, Ouburg S, Hoebe CJPA, Nilsson A, Savelkoul PHM, Morré SA. TaqMan Assay for Swedish Chlamydia trachomatis Variant. Emerg Infect Dis. Sept 2007;13(9):1432-1434
  20. An Q, Radcliffe G, Vassallo R, Buxton D, O'Brien WJ, Pelletier DA, Weisburg WG, Klinger JD, Olive DM. Infection with a plasmid-free variant Chlamydia related to Chlamydia trachomatis identified by using multiple assays for nucleic acid detection. J Clin Microbiol. 1992 Nov;30(11):2814-21.
  21. Magbanua JP, Goh BT, Michel CE, Aguirre-Andreasen A, Alexander S, Ushiro-Lumb I, Ison C, Lee H. Chlamydia trachomatis variant not detected by plasmid based nucleic acid amplification tests: molecular characterisation and failure of single dose azithromycin. Sex Transm Infect. 2007 Jul;83(4):339-43.
  22. Söderblom T, Blaxhult A, Fredlund H, Herrmann B. Impact of a genetic variant of Chlamydia trachomatis on national detection rates in Sweden. Euro Surveill 2006;11(12):E061207.1. Available from: http://www.eurosurveillance.org/ew/2006/061207.asp#1

 



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Disclamer:The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the Editorial team or the institutions with which the authors are affiliated. Neither the ECDC nor any person acting on behalf of the ECDC is responsible for the use which might be made of the information in this journal.
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