Emergence and spread of Chlamydia trachomatis variant, Sweden.A variant of Chlamydia trachomatis Chlamydia tra·cho·ma·tis n. A species of Chlamydia that causes trachoma, inclusion conjunctivitis, lymphogranuloma venereum, nonspecific urethritis, and proctitis in humans. that had escaped detection by commonly used systems was discovered in Sweden in 2006. In a nationwide study, we found that it is now prevalent across Sweden, irrespective of irrespective of prep. Without consideration of; regardless of. irrespective of preposition despite the detection system used. Genetic analysis by multilocus sequence typing Multilocus sequence typing (MLST) is a technique in molecular biology for the typing of multiple loci. The procedure characterizes isolates of bacterial species using the DNA sequences of internal fragments of multiple (usually seven) housekeeping genes. identified a predominant variant, suggesting recent emergence. ********** In 2006 a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden (1). Because of a 377-bp deletion in the target sequence for amplification, the variant had escaped detection by 2 widely used nucleic acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. amplification tests, Abbott m2000 (Abbott Laboratories Abbott Laboratories (NYSE: ABT) is a diversified pharmaceuticals and health care company. It has over 65,000 employees and operates in 130 countries. The corporate headquarters are in Abbott Park, Illinois, a neighborhood of North Chicago, Illinois. , Abbott Park, IL, USA) and Cobas Amplicor/TaqMan48 (Roche Diagnostics Roche Diagnostics Division is a subsidiary of Hoffmann-La Roche which manufactures equipment and reagents for research and medical diagnostic applications. Internally, it is organized into six major business areas: Roche Applied Science, Roche Centralized Diagnostics, Roche , Basel, Switzerland) (1,2). The other test commonly used in Sweden, ProbeTec ET (Becton Dickinson BD (NYSE: BDX), is a medical technology company that manufactures and sells medical devices, instrument systems and reagents. Founded in 1897 and headquartered in Franklin Lakes, New Jersey, BD employs 27,000 people in nearly 50 countries. [BD], Franklin Lakes, NJ, USA), detects the new variant because it uses a different DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. target sequence in the cryptic plasmid (3). The nvCT has now been reported from several of Sweden's 21 counties (Figure 1). The aim of this study was to provide a national overview of the characteristics and extent of the new chlamydia chlamydia (kləmĭd`ēə), genus of microorganisms that cause a variety of diseases in humans and other animals. Psittacosis, or parrot fever, caused by the species Chlamydia psittaci, variant through examination of surveillance trends, microbiologic laboratory data, and genetic analysis of new variant strains. The Study We examined national surveillance data reported to the Swedish Institute The Swedish Institute (Svenska Institutet, SI) is a Swedish government agency with the responsibility to spread information about Sweden abroad, to promote Swedish interests, and to organise exchanges with other countries in different areas of public life, in particular in for Infectious Disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. Control (Smittskyddsinstitutet) about chlamydia cases detected and the number of chlamydia tests performed. Trend analysis from 2004 to 2006 included only data for the first 6 months of each year to avoid any influence of changes in detection systems; some counties introduced different detection systems in late 2006 in response to the emergence of nvCT. The statistical methods are described in the online Technical Appendix (available from http://www.cdc.gov/ EID/content/14/9/1462-Techapp.pdf). The total number of chlamydia cases detected in Sweden in the first 6 months of 2006 was lower than that in 2005, and the proportion of tests that were positive also fell (Table 1). In 2004, the proportion of positive chlamydia tests was similar whether laboratories used Abbott/Roche or BD test systems. From 2004 to 2005, there was a relative reduction of 3.4% (95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [CI] 5.8-1.0) in chlamydia positivity in laboratories using the Abbott or Roche methods (p = 0.006) but no change in the proportion of positive samples in laboratories using the BD test system (-0.4%, 95% CI -4.2 to +3.5). During the first 6 months of 2005 and 2006, the positivity rates of samples tested by Abbott or Roche systems fell further; samples tested that used the BD system remained stable. The estimated difference in proportions of chlamydia-positive samples in counties that used Abbott or Roche tests compared with counties that used the BD method was -9.5 % (95% CI -14.1 to -4.7, p = 0.0005), after baseline differences and county differences in testing were controlled for. We conducted microbiologic analyses on consecutive samples that were collected from 12 counties in late 2006 and early 2007. Cases of nvCT were identified by testing specimens with additional methods using alternative sequence targets (online Technical Appendix). The proportion of nvCT ranged from 20% to 64% in the 8 counties that used Abbott or Roche detection systems, compared with 7% to 19%, respectively, for counties that used BD tests (Figure 1). Additional data about gender, age, and clinical setting of diagnoses were available for 600 chlamydia-positive patients in the 4 counties using the BD system (Table 2). The proportion of nvCT cases varied between clinics (p = 0.020) and was higher at youth and venereal disease venereal disease (vənēr`ēəl): see sexually transmitted disease. clinics than at antenatal an·te·na·tal adj. See prenatal. antenatal before parturition. Called also prenatal, antepartal. and gynecology clinics. This variance might be because persons seeking treatment in these settings have higher levels of risk taking and more frequent changes in partners (4). There was no evidence of differences in the proportion of cases by gender (p = 0.103) or age (p = 0.558) because of nvCT. [FIGURE 1 OMITTED] Genetic characterization with a new high-resolution genotyping Genotyping refers to the process of determining the genotype of an individual with a biological assay. Current methods of doing this include PCR, DNA sequencing, and hybridization to DNA microarrays or beads. system (5) was performed on 48 specimens of nvCT from 2 counties that used the BD test system (n = 21); 2 counties that used Roche and Abbott systems (n = 18); and 9 specimens from Norway, Ireland, and France (online Technical Appendix). The nvCT showed a new genetic variant in the chromosomal target region hctB compared with previous findings in wild-type strains and thus constitutes a separate clone with the designation 21 (hctB), 19 (CT058), 1 (CT144), 2 (CT172), and 1 (pbpB) in our system. All 48 specimens tested were of genotype genotype (jēn`ətīp'): see genetics. genotype Genetic makeup of an organism. The genotype determines the hereditary potentials and limitations of an individual. E, and 46 were identical in the ompA gene to the reference strain E/ Bour. The divergent specimens were from 2 persons known to be sexual partners and differed in a single nucleotide position. In the other 5 target genes, altogether comprising some 5,500 bp, all 48 specimens were identical. Conclusions Our study was a national systematic overview including surveillance, demographic, microbiologic, and genetic data about the emergence and spread of a mutant strain of C. trachomatis Noun 1. C. trachomatis - bacteria responsible for the sexually transmitted diseases chlamydia and lymphogranuloma venereum Chlamydia trachomatis chlamydia - coccoid rickettsia infesting birds and mammals; cause infections of eyes and lungs and genitourinary in Sweden. A fall in the proportion of positive chlamydia test results in counties using Abbott or Roche test systems began in 2005 and continued in 2006, whereas positivity rates in counties using BD tests did not change. The mutant strain has now spread throughout Sweden. Notably, the new variant has scarcely been found outside Sweden (or), indicating that we need to improve our understanding of the sexual networks through which chlamydiae Chlamydiae is a bacterial phylum whose members are obligate intracellular pathogens.[1] Many Chlamydiae coexist in an asymptomatic state within specific hosts, and it is widely believed that these hosts provide a natural reservoir for these species. spread (7). Our analysis suggests that widespread transmission of nvCT is recent, even if the mutation itself occurred some time ago, because 46 of 48 specimens from different places had identical sequences when we used a highly discriminatory multilocus sequence typing system (5). This hypothesis is supported by the lack of diversification in the mutant strains compared with the high degree of sequence variation in other sample collections that we have analyzed (5; and unpub, data). We expect new nucleotide substitutions to occur over time. The area in Sweden in which nvCT originated is not known, but the consistently high proportion of nvCT found in the county of Dalarna suggests that the mutant might have been present in this region for longer than in other counties studied, nvCT comprised 64% of chlamydia-positive specimens over the study period in Dalarna as a whole, and up to 78% in some localities (7); elsewhere in Sweden (8-10) and worldwide (11,12), genotype E strains of different subvariants comprise [approximately equal to] 40% of chlamydia-positive speciments in heterosexual populations. These data might indicate that the high proportion of nvCT is not only a result of accumulation of chlamydia cases when diagnostics failed and treatment and contact tracing In epidemiology, contact tracing is the identification and diagnosis of persons who may have come into contact with an infected person. For sexually transmitted diseases, this is generally limited to sexual partners but for highly virulent diseases such as Ebola and tuberculosis, a were inadequate. Further studies will be needed to determine whether nvCT also has a selective advantage that might outcompete the wild-type bacterium over time. The emergence of this mutant strain of a sexually transmitted pathogen Pathogen Any agent capable of causing disease. The term pathogen is usually restricted to living agents, which include viruses, rickettsia, bacteria, fungi, yeasts, protozoa, helminths, and certain insect larval stages. has implications for public health practice. A recent study estimates that some 8,000 chlamydia cases escaped detection in 2006 (7). This would have resulted in an [approximately equal to] 20% increase in reported chlamydia cases. Actual national figures for 2007 confirm such an increase, and the number of reported chlamydia cases has reached an all-time high in Sweden (Figure 2). Chlamydia infections, caused not only by nvCT, continue to rise (13,14), but the areas most heavily affected by the spread of nvCT have been in much the same situation as before chlamydia was first recognized as a pathogen. Failure to detect the nvCT over time have resulted in episodes of complicated infection all over the country, leading to ectopic pregnancies ectopic pregnancy or extrauterine pregnancy Condition in which a fertilized egg is imbedded outside the uterus (see fertilization). Early on, it may resemble a normal pregnancy, with hormonal changes, amenorrhea, and development of a placenta. and infertility. Research is now needed to determine whether sequelae sequelae Clinical medicine The consequences of a particular condition or therapeutic intervention associated with chlamydia occur disproportionately in counties where test systems fail to diagnose the nvCT. The ability of this new variant to escape detection for so long shows that developers of future diagnostic tests need to take into account the structure and function of genomes when selecting appropriate target nucleic acid sequences in microorganisms. Currently, there are unique opportunities for research that could lead to insights into the immunobiology, transmission, and consequences of C. trachomatis. [FIGURE 2 OMITTED] DOI (Digital Object Identifier) A method of applying a persistent name to documents, publications and other resources on the Internet rather than using a URL, which can change over time. : 10.3201/eid 1409.080153 Acknowledgments Prevalence data on the new variant of C. trachomatis or samples for analysis were provided from different counties. We thank Kenneth Persson, Ida Bjorklund, Torvald Ripa, Jens Bjrrkman, Andreas Mattussek, Christina Lundberg, Hans Fredlund, Mafia Rotzen Ostlund, Britta Lore, and Barbro Almqvist. Amir Moghaddam generously contributed 6 specimens from Oslo, Norway, Yvonne Lynagh kindly provided 2 specimens from Ireland, and Bertille Barbeyrac provided 1 sample from France. Research on the new variant of C. trachomatis was supported by grants from Roche Molecular Diagnostics and Becton Dickinson. References (1.) Ripa T, Nilsson P. A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications for use of PCR PCR polymerase chain reaction. PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) diagnostic tests. Euro Surveill. 2006;11(11) [cited 2008 Apr 29]. Available from http://www.eurosurveillance.org/ew/2006/061207.asp (2.) 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;34:255-6.. (3.) Dellone B, Shank shank (shangk) 1. leg (1). 2. crus ( 2). shank n. The part of the human leg between the knee and ankle. DD, Price JA. Analytical detection with the BD ProbeTec ET CT amplified DNA assay of a variant of Chlamydia trachomatis with a deletion in the cryptic plasmid. Presented at: 17th international Society for STD (Subscriber Trunk Dialing) Long distance dialing outside of the U.S. that does not require operator intervention. STD prefix codes are required and billing is based on call units, which are a fixed amount of money in the currency of that country. Research/10th International Union against Sexually Transmitted Infections Congress; 2007 Jul 29-Aug 1; Seattle, Washington  This page is protected from moves until disputes have been resolved on the .The reason for its protection is listed on the protection policy page. , USA. Poster 144. (4.) Herlitz C. HIV/AIDS HIV/AIDS Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and society: knowledge, attitudes and behaviour, 1987-2007 [in Swedish]. Article no. 2008:123-1. Stockholm: National Board of Health and Welfare; 2008. (5.) Klint M, Fuxelius HH, Goldkuhl RR, Skarin H, Rutemark C, Andersson SG, et al. High-resolution genotyping of Chlamydia trachomatis strains by multilocus sequence analysis. J Clin Microbiol. 2007;45:1410-4. DOI: 10.1128/JCM.02301-06 (6.) Savage EJ, Ison CA, van de Laar MJ. Results of a Europe-wide investigation to assess the presence of a new variant of Chlamydia trachomatis. Euro Surveill. 2007 12(10) [cited 2008 Apr 29]. Available from http://www, euro surveillance, org/em/v12n10/1210-222.asp (7.) Herrmann B. A new genetic variant of Chlamydia trachomatis: a thrilling story in Sweden with global impact. Sex Transm Infect. 2007;83:253-4. DOI: 10.1136/sti.2007.026260 (8.) Jurstrand M, Falk L, Fredlund H, Lindberg M, Olcen P, Andersson S, et al. Characterization of Chlamydia trachomatis ompl genotypes among sexually transmitted disease sexually transmitted disease (STD) or venereal disease, term for infections acquired mainly through sexual contact. Five diseases were traditionally known as venereal diseases: gonorrhea, syphilis, and the less common granuloma inguinale, patients in Sweden. J Clin Microbiol. 2001;39:3915-9. DOI: 10.1128/JCM.39.11.3915-3919.2001 (9.) Lysen M, Osterlund A, Rubin C J, Persson T, Persson I, Herrmann B. Characterization of ompA genotypes by sequence analysis of DNA from all detected cases of Chlamydia trachomatis infections during 1 year of contact tracing in a Swedish county. J Clin Microbiol. 2004;42:1641-7. DOI: 10.1128/JCM.42.4.1641-1647.2004 (10.) Persson K. Epidemiology of serovars of Chlamydia trachomatis. In: Bowie WR, Caldwell HD, Jones RB, Mardh PA, Ridgway GL, Schachter J, et al., editors. Chlamydial chlamydial pertaining to members of the family Chlamydiaceae. chlamydial abortion abortion in cows, ewes, sows and goat does caused by Chlamydophila abortus and C. pecorum. See enzootic abortion of ewes. infections. Proceedings of the Seventh International Symposium on Human Chlamydial Infections. Cambridge (UK): Cambridge University Press Cambridge University Press (known colloquially as CUP) is a publisher given a Royal Charter by Henry VIII in 1534, and one of the two privileged presses (the other being Oxford University Press). ; 1990. p. 559-62. (11.) Geisler WM, Suchland RJ, Whittington WL, Stamm WE. The relationship of serovar to clinical manifestations of urogenital urogenital /uro·gen·i·tal/ (-jen´i-tal) genitourinary. u·ro·gen·i·tal or u·ri·no·gen·i·tal adj. Genitourinary. Chlamydia trachomatis infection. Sex Transm Dis. 2003 ;30:160-5. DOI: 10.1097/00007435-200302000-00013 (12.) van Duynhoven YT, Ossewaarde JM, Derksen-Nawrocki RP, van der Meijden WI, van de Laar MJ. Chlamydia trachomatis genotypes: correlation with clinical manifestations of infection and patients' characteristics. Clin Infect Dis. 1998;26:314-22. DOI: 10.1086/516291 (13.) Velicko I, Kuhlmann-Berenzon S, Blaxhult A. Reasons for the sharp increase of genital chlamydia infections reported in the first months of 2007 in Sweden. Euro Surveill. 2007;12(10) [cited 2008 Apr 29]. Available from: http://www.eurosurveillance.org/em/v12n10/1210223.asp (14.) Swedish Institute for Infectious Disease Control. Chlamydia infection, 2007 [cited 2008 Apr 8]. Available from http://www.smittsky ddsinstitutet.se/in-english/statistics/chlamydia-infection Address for correspondence: Bjorn Herrmann, Department of Clinical Microbiology Clinical microbiology The adaptation of microbiological techniques to the study of the etiological agents of infectious disease. Clinical microbiologists determine the nature of infectious disease and test the ability of various antibiotics to inhibit or kill , Uppsala University Hospital Uppsala University Hospital (Swedish: Akademiska sjukhuset, often referred to colloquially as "Akademiska" or "Ackis" , S-751 85 Uppsala, Sweden; email: bjorn.herrmann@medsci.uu.se Uppsala University Hospital, Uppsala, Sweden (B. Herrmann, M. Klint, A. Nilsson); Swedish Institute for Infectious Disease Control, Solna, Sweden (A.Torner, I. Velicko, T. Soderblom, A. Blaxhult); and University of Bern The University of Bern is a university in the Swiss capital of Bern. It was founded in 1834. As one of the German-speaking universities in Switzerland its official name is Universität Bern, although it is frequently referred to in the French form, Université de Berne. , Bern, Switzerland (N. Low) Dr Herrmann is a microbiologist and associate professor at the University Hospital in Uppsala, Sweden. His major research interests are diagnostics and epidemiology of Chlamydia infections and the development of molecular methods for detecting different bacteria and viruses.
Table 1. Numbers of chlamydia tests, positive results, and change
in positivity rates, Sweden, 2004-2006
No. positive
results/total no.
tests (%) to first 6
mo
Diagnostic test * No. counties 2004
Abbott/Roche 14 11,721/150,080 (7.8)
Becton Dickinson 8 4,262/54,260 (7.9)
All tests 21 15,983/204,340 (7.8)
No. positive results/total no. tests (%)
to first 6 mo
Diagnostic test * 2005 2006
Abbott/Roche 11,111/147,311 (7.5) 10,236/152,960 (6.7)
Becton Dickinson 5,220/66,728 (7.8) 3,363/43,189 (7.8)
All tests 16,331/214,039 (7.6) 13,599/196,149 (6.9)
* One county used both Roche and Becton Dickinson tests.
Table 2. Distribution of cases of nvCT by gender, age, and clinic
category in 4 selected counties that used the Becton Dickinson
system *
Factor % nvCT (n/N) p value
([dagger])
Gender
Male 16 (45/273) 0.103
Female 12 (39/327)
Age, y
15-19 14 (23/162) 0.558
20-24 16 (44/279)
25-29 11 (11/98)
[greater than or equal to] 30 10 (6/59)
Clinic
Venereal disease 15 (19/129) 0.020
Youth clinics 19 (39/210)
Gynecology 9 (13/150)
Antenatal/general practice 8 (6/77)
Others 21 (7/34)
* nvCT, new variant of Chlamydia trachomatis; n, number of nvCT cases
detected; N, total number of C. trachomatis cases detected.
([dagger]) Determined by [chi square] test.
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