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Keywords:

  • Chlamydia trachomatis;
  • diagnosis;
  • epidemiology;
  • genital infections;
  • review;
  • treatment

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Chlamydia trachomatis infections affect young, sexually active persons. Risk factors include multiple partners and failure to use condoms. The incidence of infection has increased in the past 10 years. Untreated C. trachomatis infections are responsible for a large proportion of salpingitis, ectopic pregnancy, infertility and, to a lesser extent, epididymitis. Screening is a possible intervention to control the infection, which is often asymptomatic. The emergence of lymphogranuloma venereum proctitis in men who have sex with men, in Europe, and of a variant with a deletion in the cryptic plasmid, in Sweden, are new features of C. trachomatis infections in the last years. A diagnosis is best made by using nucleic acid amplification tests, because they perform well and do not require invasive procedures for specimen collection. Single-dose therapy has been a significant development for treatment of an uncomplicated infection of the patient and his or her sexual partner.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Chlamydia trachomatis is an obligate intracellular bacterium. During its unique developmental cycle, two different forms are observed, elementary bodies (EBs), which are infectious but not able to divide, and reticulate bodies (RBs), which are metabolically active and able to multiply. Persistent forms can also be present under particular conditions [1].

C. trachomatis is the most common bacterium responsible for sexually transmitted infections. Most of these infections are asymptomatic and, if not treated, can lead to severe complications, mainly in young women. Advances in diagnostic techniques and methods of specimen collection make easier the detection, treatment and prevention of these infections of global public health significance.

C. trachomatis, a bacterium specifically found in humans, is currently divided into 19 serovars, according to the specificity of major outer membrane protein (MOMP) epitopes [2]. Serovars A, B, Ba and C are the agents of trachoma, a major cause of blindness in Africa, the Middle East, Asia and South America. Serovars D–K, including D, Da, E, F, G, Ga, H, I, Ia, J and K, are the most common sexually transmitted bacteria, and serovars L1, L2, L2a and L3 are the agents of transmission of lymphogranuloma venereum (LGV).

Epidemiology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

With the exception of LGV, chlamydial infections are widely diffused among the general population, affecting mainly young people between 16 and 24 years of age. Risk factors include high frequency of partner change, multiple partners, unprotected sex, and being unmarried [3].

In the USA in 2006, more than one million cases of chlamydial infection, which is a notifiable disease, were reported to the CDC, corresponding to a rate of 347.8 cases/100 000, an increase of 5.6% as compared with the rate in 2005 (http://www.cdc.gov/std/stats/chlamydia.htm).

In Europe also, the incidence of chlamydial infections has increased in the past 10 years. In 2005, over 200 000 cases were reported in 17 European countries, (http://www.ecdc.europa.eu/en/Health_Topics/chlamydia_infection/aer_07.aspx), and this is probably an underestimate. Prevalence rates have been shown to range from 2% to 17% in asymptomatic women, depending on the setting, population and country.

In Denmark, the overall prevalence rate of infection was 456 cases/100 000 in 2007. In the UK, it has been reported that 10.3% of women and 13.3% of men <25 years of age are infected [3]. In comparison with other countries, the prevalence is lower in Switzerland, ranging from 2.8% in women [4] to 1.2% in men [5]. In France, where chlamydial infection is not a notifiable disease, screening studies showed large differences according to the population tested, ranging from 6–11% in individuals attending family planning centres [6] to 1–3% in individuals attending preventive medical centres of universities [7]. In 2005, the overall prevalence of C. trachomatis in the French population was 1.5% in the general population and 3% among 18–24-year-old individuals (6th Meeting of the European Society for Chlamydia Research, abstract P71, Goulet V, 2008).

LGV, endemic in tropical regions, was rare in industrialized countries until 2003. It presented as a genital ulcer with secondary lymphoid proliferation. In 2004, a cluster of cases presenting with proctitis was reported in Rotterdam [8,9]; these were cases of men who had sex with men, most being human immunodeficiency virus-seropositive. Subsequent reports from other European cities, e.g. Hamburg, Paris [10], London, Stockholm, Vienna and Zurich, and from North America and Australia, indicated the emergence of a new outbreak in this high-risk group. This outbreak was dominated by the C. trachomatis variant L2b, first described in patients from Amsterdam [11] and subsequently found in France [12], Germany, Canada and Australia.

Surveillance systems were established in different countries. In the UK, through February 2006, 327 cases of LGV (96% with proctitis) were reported [13]. In France, between 2002 and 2007, among 784 C. trachomatis-positive rectal specimens, 551 (71%) were from cases of LGV and 29% were positive for non-LGV serovars. Despite the information available, the number of LGV cases increased every year (Fig. 1). In 11 cases, LGV strains were isolated from non-rectal samples [14].

image

Figure 1. Chlamydia trachomatis proctitis in France, 2002–2007 (lymphogranuloma venereum (LGV) and non-LGV isolates) (personal data).

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Clinical Manifestations of C. Trachomatis Infections

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Chlamydial infection can cause cervicitis in women and urethritis in men (Table 1). However, these infections produce few or no symptoms in approximately 70% of women and 50% of men [15] and thus remain undetected.

Table 1.   Clinical manifestations of Chlamydia trachomatis infections
SerovarClinical manifestationComplication
A–CKeratoconjunctivitisScarring trachoma, blindness
D–KMales: urethritis, proctitisEpididymitis
 Females: cervicitis, urethritis, proctitisEndometritis, salpingitis, pelvic pain, ectopic pregnancy, perihepatitis (Fitz-Hugh–Curtis syndrome), infertility
Males and females: conjunctivitisReiter’s syndrome, reactive arthritis
L1–L3Lymphogranuloma venereum: inguinal syndrome, proctitisFibrosis, rectal stricture

Infections in men

C. trachomatis is the major cause of non-gonococcal urethritis and post-gonococcal urethritis. Urethritis can be complicated by acute epididymitis in young men. After 7–21 days of incubation, the symptoms include dysuria, and a moderate clear or whitish urethral discharge [16]. Acute proctitis can be associated with oculo-genital serovars, but is usually milder than that associated with LGV serovars. There is no evidence of the role of C. trachomatis in prostatitis [17], and chlamydial infection does not significantly contribute to male infertility [18].

Reiter’s syndrome (urethritis, conjunctivitis, arthritis and mucocutaneous lesions) or reactive arthritis have also been associated with genital C. trachomatis infections, with a high male/female ratio [17].

Infections in women

Women with cervicitis can be asymptomatic or may complain of mucopurulent vaginal discharge or postcoital bleeding. Oedema, congestion and bleeding of the cervix have been observed. Urethral infection can be associated with cervicitis. A culture-negative leucocyturia finding is suggestive of C. trachomatis infection.

Ascending infections can result from cervicitis. Endometritis is frequently associated with this and may produce irregular uterine bleeding. Salpingitis or pelvic inflammatory disease (PID) is often subclinical. It seems possible that, in Europe, C. trachomatis is the cause of at least 60% of cases of acute PID [19]. Salpingitis may lead to tubal scarring and severe reproductive complications. Two-thirds of all cases of tubal-factor infertility and one-third of all cases of ectopic pregnancy could be due to chlamydial infection [16,20]. Chronic pelvic pain linked to the presence of peritoneal adhesions may occur in more than 15% of women with previous episodes of PID [19].

Fitz-Hugh–Curtis syndrome, a perihepatitis observed after or in conjunction with salpingitis, is more commonly associated with chlamydial than with gonococcal infections.

There is little evidence, and this is conflicting, to implicate C. trachomatis in chorioamnionitis and adverse pregnancy outcome [19]. Postpartum endometritis occurs in 30% of women with antenatal chlamydial infection. In both men and women, C. trachomatis may be involved in conjunctivitis by auto-inoculation from the genital tract.

Neonatal infections

Infants of mothers with chlamydial infections can be infected at delivery. The transmission rate via infected vaginal secretions is high (50–70%). Approximately 30–50% of infants of infected mothers will have conjunctivitis 5–10 days after delivery. At least 50% of infants with conjunctivitis will have nasopharyngeal infection [16]. Chlamydial pneumonia develops in c. 30% of these cases, after 2–3 weeks of incubation. The untreated infection acquired at birth can persist for months or years [21,22].

LGV

LGV is associated with L serovars, which are more invasive than D–K serovars, affecting submucosal connective tissue layers, and being able to disseminate to locoregional lymph nodes. LGV proctitis can be misdiagnosed as inflammatory bowel disease [3], and lead to rectal stricture.

The persistence of LGV cases that may contribute to the transmission of human immunodeficiency virus infection highlights the importance of the need to control this infection.

Pathogenesis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Chlamydiae exhibit a unique biphasic developmental cycle consisting of the conversion of EBs to RBs, the division of RBs, and the reorganization of RBs back into EBs. The persistent cycle seems to be the norm.

Chlamydial persistence [23] has been described as a long-term association between chlamydiae and their host cells in which these bacteria remain in a viable but culture-negative state [24].

Characteristically, C. trachomatis infection is frequently low-grade or asymptomatic, and repeated infection is common, indicating that natural immunity is limited. The major sequelae arise as a result of inflammation and fibrosis. A key question is whether persistent forms of chlamydiae play a role in the immunopathology of disease. In vitro, some factors inducing the development of aberrant persistent forms of chlamydiae, e.g. nutrient depletion, antibiotics and cytokines, have been identified. Chlamydial interaction with the cytokine system of the host is likely to be central to disease, as the inflammation following chlamydial infection and exacerbated by re-infection leads to tissue damage and scarring.

Moreover, continued chlamydial Hsp60 expression secondary to the action of interferon-γ produced by the cell-mediated immune response might ultimately drive chronic inflammatory responses associated with the severe sequelae of chlamydial infection [25]. The presence of Chlamydia-specific anti-Hsp antibodies has been proposed as a marker of chronic C. trachomatis infection. Antibody response to the surface antigen, MOMP, is an important mediator of immunity. Antigenic variation can arise in response to antimicrobial and/or immune pressure, and may play a role in persistence and disease pathogenesis [26].

A cytotoxin and a type III secretion system have been described as virulence factors, but very little is known about this, due to the absence of genetic tools [27].

Direct Diagnosis

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

There have been major developments during the past 30 years. As C. trachomatis is an obligate intracellular bacterium, cell culture remains a reference method, but many commercial non-culture-based assays are now available for diagnosis (Table 2).

Table 2.   Direct detection of Chlamydia trachomatis
MethodTurn-around timeAdvantagesLimits
  1. DFA, direct fluorescent staining with monoclonal antibodies; EIA, enzyme immunoassay; NAAT, nucleic acid amplification test; SDA, strand displacement amplification; TMA, transcription-mediated amplification; NASBA, nucleic acid sequence-based amplification.

Cell culture72 hSpecificity, strainSensitivity 80–85%
Antigen detection
 DFA45 minSimple, unit testSensitivity 75–80% Subjective reading
 EIA4 hAutomationSensitivity 75–80% Low specificity (confirmatory test)
 Point of care30 minLow cost, unit test
Molecular methods
 DNA probing2 hEasy to performSensitivity 75–80%
 Hybrid capture4 hSensitivity 95% Specificity 99%Only for cervical specimens (FDA)
 NAAT (real-time PCR, SDA, TMA, NASBA)2–4 hSensitivity >95% Specificity 99%Contamination, costly processing of specimen

Specimens

The type of specimen depends on the clinical picture, the diagnosis conditions, and the laboratory technique used for detection, with the conditions of transport and storage being adapted to the particular technique.

Invasive specimens include urethral swabs in men, and endocervical or urethral swabs, and specimens taken from the upper genital tract, in women (liquid from Douglas’s pouch, endometrium and tubal specimens). Other sites include the conjunctiva, nasopharynx or deeper respiratory tract.

Non-invasive self-collected specimens include first-void urine (FVU), vulvovaginal swabs, anal swabs and penile swabs (Table 3). The bacterial load of these specimens is a major aspect of their suitability for the diagnosis, which can be made only by using nucleic acid amplification tests (NAATs) [28]. Self-collected vaginal swabs have a lower bacterial load than endocervical swabs, but a higher load than FVU, and are very well adapted to screening programmes [29]. FVU is a suitable sample type for men [30]. The sensitivity of the results obtained with penile swabs is lower than that with FVU, and the results are not reproducible in our experience (6th Meeting of the European Society for Chlamydia Research, abstract P10, Barbeyrac de B, 2008).

Table 3.   Advantages and limits of main urogenital specimens
SexSpecimenAdvantagesLimitsUsable technique
  1. NAAT, nucleic acid amplification test; EIA, enzyme immunoassay.

  2. aOnly in association with cervical swabs to improve the diagnosis of infection.

MenUrethral swabHigh sensitivityInvasiveAll tests
UrineNon-invasive NAATs
Self-collected Some EIA tests
Penile swabNon-invasiveLow sensitivityNAATs
Self-collected  
WomenCervical swabHigh sensitivityInvasiveAll tests
Urethral swabaHigh sensitivityInvasiveAll tests
UrineNon-invasiveLow sensitivityNAATs
Self-collected  
Vaginal swabNon-invasive NAATs
Self-collected  

Cell culture

Cell culture has near 100% specificity. However, it is not recommended for routine use, because of its lack of sensitivity, its technical complexity, the long turn-around time, the requirements concerning transport and storage of specimens, and the limited number of appropriate specimens [31,32]. Owing to the detection of only viable organisms, it remains the method of choice in medico-legal situations and for antibiotic susceptibility testing [33].

Antigen-based detection methods (direct fluorescent staining with monoclonal antibodies (DFA) and enzyme immunoassay (EIA))

DFA is rapid to perform and specific, but is subjective, and not suitable for a large number of specimens [32].

EIA tests can be automated. They are more reproducible than DFA, and the sensitivity of the best EIA is comparable to that of culture and lower than that of NAATs. They can give false-positive results due to cross-reactions with the lipopolysaccharide (LPS) of other microorganisms, and all positive EIA results must be confirmed.

Rapid or ‘point-of-care’ tests are proposed for patients who are unlikely to return for test results. They are not suitable for non-invasive specimens, have moderate sensitivity, and are not recommended for laboratory settings. A rapid test for diagnosis of chlamydial infection, recently developed by the Wellcome Trust [34,35], is based on a second-generation signal amplification EIA for chlamydial LPS in a dipstick-type format. The initial results are promising.

Nucleic acid hybridization tests

DNA probing (with Pace 2, Gen  Probe) was the first molecular DNA test for C. trachomatis, and was largely used before the advent of NAATs. The performance of these tests is comparable to that of the better antigen detection and cell culture methods. Pace 2 can be used with endocervical or urethral swabs, but is not recommended for use with non-invasive specimens [29].

The Digene Hybrid Capture II test is a nucleic acid hybridization test that is signal amplification-based. Its sensitivity is substantially higher than that of the Pace 2 test and is comparable to that of PCR [36].

NAATs

Because of their high sensitivity and specificity, and their possible use for a large range of sample types, including vulvovaginal swabs and FVU, NAATs are the tests of choice for the diagnosis of C. trachomatis genital infections.

Several commercial NAATs are available [36], and make use of different technologies: PCR and real-time PCR (Roche Diagnostics, Abbott, IL, USA); strand displacement amplification (Becton Dickinson, NJ, USA); transcription-mediated amplification (Gen  Probe); and nucleic acid sequence-based amplification (bioMerieux, Nancy L’Etoile, France). The major targets for amplification-based tests are generally multiple-copy genes, e.g. those carried by the cryptic plasmid of C. trachomatis, or gene products such as rRNAs.

These assays are automated and can be used for screening programmes and for the detection of C. trachomatis and Neisseria gonorrhoeae in the same specimen. Their primary disadvantage is the cost, which could be reduced by pooling specimens. Another drawback is the presence of inhibitors in specimens, which can be overcome by different procedures. Their specificity is very high. The necessity of confirmatory testing of positive specimens, previously recommended in low-prevalence populations, is controversial [37,38].

In 2006, a new C. trachomatis variant belonging to serovar E, with a 377-bp deletion in the cryptic plasmid, was described in Sweden [39], where it was reported in high proportions (10–65%) of the infected patients. There is currently no evidence that the variant has spread widely across Europe [40–43]. This new variant can obviously not be detected by amplification tests targeting the deleted area, but can be detected by amplification targeting a chromosomal gene, e.g. ompA or a rRNA gene. New versions of the COBAS Taqman v2.0 test and of the Abbott test allow simultaneous detection of the cryptic plasmid and of ompA, and simultaneous detection of two different regions of the cryptic plasmid, respectively.

The goal for the future is to improve the diagnosis of sexually transmitted infections by using multiplex tests, in particular DNA microarray technology.

Typing Systems

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

C. trachomatis strains are discriminated by serotyping based on the antigenic differences among the major MOMP epitopes. Genotypes corresponding to serovars can be separated by omp1 PCR–restriction fragment length polymorphism typing [44,45], which can be used directly on specimens. Sequencing of the omp1 gene can be more discriminating. Recently, genotyping methods exploiting genome variations, e.g. multilocus sequence [46] and variable-number tandem repeat [47] analysis, have been used to discriminate among strains.

Serology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Serology is useful only in some cases of C. trachomatis infection and in seroepidemiological studies [48]. It suffers from several drawbacks, including the serological cross-reactivity between C. trachomatis and Chlamydophila species, and the persistence of antibodies, which prevents a distinction being made between past and present infection. Although it is not recommended for the diagnosis of lower genital tract infections, or for screening in asymptomatic patients, serological testing may be useful for diagnosing LGV, neonatal pneumonia, and upper genital tract infections, and for the evaluation of tubal-factor infertility.

The serological methods available are complement fixation, microimmunofluorescence and EIA. The latter two allow the distinction among IgG, IgA and IgM.

The microimmunofluorescence method, which is species- and serovar-specific, and which is considered to be the reference method, was a complex technology in its original form. EIAs, which can make use of synthetic peptides from the variable domains of the MOMP or recombinant LPS, can be automated.

Screening

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Screening programmes must be cost-effective and must be made acceptable to patients by using non-invasive procedures that allow sample collection at the patient’s home.

There are two main approaches to the design of screening programmes: proactive, consisting of screening the entire target population; and opportunistic, targeting individuals who attend a healthcare setting [49]. The opportunistic approach, targeting sexually active individuals under 25 years of age within a variety of healthcare settings, is used in most Chlamydia screening programmes in the USA, the UK and France. At this time, research studies are needed to establish the benefits and the disadvantages of Chlamydia screening programmes [50].

Treatment

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References

Antimicrobial susceptibility

Evaluation of in vitro susceptibility is not currently performed, because a standardized method is lacking and MIC results are not consistently reproducible [51].

In vitro, the most active drug is rifampin, with the lowest MIC, followed by tetracyclines, macrolides, and some fluoroquinolones (ofloxacin and the newer compounds).

The potential of C. trachomatis to develop antimicrobial resistance has not been well studied, although some case reports [52–54] suggest resistance as a cause of treatment failure. However, mutants resistant to fluoroquinolones and to rifampin have been produced in vitro [55,56], and four clinical isolates that demonstrated in vitro resistance to macrolides were shown to carry mutations in a 23S rRNA gene [57].

Heterotypic resistance can be observed when cells are inoculated with a large number of organisms. It affects only a small proportion of organisms that are difficult to propagate and eventually lost through continued cell culture [58], suggesting that they may be ‘less fit’. Acquired antimicrobial resistance seems to be exceptional.

Management of infections

Both patients and their sexual partners must be treated. For treatment of uncomplicated lower genital tract infections in adults, major progress has been made in the use of single-dose therapy with azithromycin (1 g) [59]. A 7-day course of doxycycline gives comparable results, but with lower rates of compliance [60].

Guidelines have been proposed in different countries for the treatment of upper genital tract infections [61]. These require a longer treatment period (14–21 days), and the combination of several antibiotics to control other bacteria involved. The same duration of treatment is proposed for LGV. The possibility of persistence of the infection after treatment may justify the use of a test of cure (5 weeks post-treatment) in cases of presumptive treatment failure or during pregnancy.

In conclusion, the available opportunities for diagnosis of C. trachomatis infections of the genital tract using high-performance NAATs and specimens obtained through non-invasive procedures, in conjunction with single-dose antimicrobial therapy, should reduce the consequence of untreated infections.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Epidemiology
  5. Clinical Manifestations of C. Trachomatis Infections
  6. Pathogenesis
  7. Direct Diagnosis
  8. Typing Systems
  9. Serology
  10. Screening
  11. Treatment
  12. Transparency Declaration
  13. References
  • 1
    Hatch TP. Developmental biology. In: StephensRS, ed. Chlamydia. Washington, DC: ASM Press, 1999; 2967.
  • 2
    Schachter J. Infection and disease epidemiology. In: StephensRS, ed. Chlamydia. Washington, DC: ASM Press, 1999; 139169.
  • 3
    Manavi K. A review on infection with Chlamydia trachomatis. Best Pract Res Clin Obstet Gynaecol 2006; 20: 941951.
  • 4
    Paget WJ, Zbinden R, Ritzler E et al. National laboratory reports of Chlamydia trachomatis seriously underestimate the frequency of genital chlamydial infections among women in Switzerland. Sex Transm Dis 2002; 29: 715720.
  • 5
    Baud D, Jaton K, Bertelli C, Kulling JP, Greub G. Low prevalence of Chlamydia trachomatis infection in asymptomatic young Swiss men. BMC Infect Dis 2008; 8: 45.
  • 6
    Warszawski J. Dépistage systématique des infections àChlamydia trachomatis: il est temps d’agir. Bull Epidémiol Hebd 2006; 38: 275276.
  • 7
    Barbeyrac de B, Raherison S, Bernabeu A et al. Dépistage de l’infetion àChlamydia trachomatis dans la population d’étudiantes des universités de Bordeaux, France, 2004. Bull Epidémiol Hebd 2006; 38: 288290.
  • 8
    Van De Laar MJ, Fenton KA, Ison C. Update on the European lymphogranuloma venereum epidemic among men who have sex with men. Euro Surveill 2005; 10: E050602.
  • 9
    De Vries HJ, Van Der Bij AK, Fennema JS et al. Lymphogranuloma venereum proctitis in men who have sex with men is associated with anal enema use and high-risk behavior. Sex Transm Dis 2008; 35: 203208.
  • 10
    Herida M, Sednaoui P, Couturier E et al. Rectal lymphogranuloma venereum, France. Emerg Infect Dis 2005; 11: 505506.
  • 11
    Spaargaren J, Fennema HS, Morre SA, De Vries HJ, Coutinho RA. New lymphogranuloma venereum Chlamydia trachomatis variant, Amsterdam. Emerg Infect Dis 2005; 11: 10901092.
  • 12
    Herida M, De Barbeyrac B, Sednaoui P et al. Rectal lymphogranuloma venereum surveillance in France 2004–2005. Euro Surveill 2006; 11: 155156.
  • 13
    Ward H, Martin I, Macdonald N et al. Lymphogranuloma venereum in the United Kingdom. Clin Infect Dis 2007; 44: 2632.
  • 14
    Herida M, Kreplack G, Cardon B, Desenclos JC, De Barbeyrac B. First case of urethritis due to Chlamydia trachomatis genovar L2b. Clin Infect Dis 2006; 43: 268269.
  • 15
    Van De Laar MJ, Morre SA. Chlamydia: a major challenge for public health. Euro Surveill 2007; 12: E1E2. Available at: http://www.eurosurveillance.org/em/v12n10/1210-221.asp
  • 16
    Peipert JF. Clinical practice. Genital chlamydial infections. N Engl J Med 2003; 349: 24242430.
  • 17
    Hicks D. Complications of Chlamydia trachomatis infection in men. In: MossTR, ed. International handbook of Chlamydia, 3rd edn. Haslemere, UK: Alden Press, 2008; 99109.
  • 18
    Barbeyrac de B, Papaxanthos Roche A, Mathieu C et al. Chlamydia trachomatis in subfertile couples undergoing an in vitro fertilization program: a prospective study. Eur J Obstet Gynecol Reprod Biol 2006; 129: 4653.
  • 19
    Rogstad K. Complications in the female and their management. In: MossT, ed. International handbook of Chlamydia, 3rd edn. Haslemere, UK: Alden Press, 2008; 111121.
  • 20
    Paavonen J, Eggert-Kruse W. Chlamydia trachomatis: impact on human reproduction. Hum Reprod Update 1999; 5: 433447.
  • 21
    Hammerschlag MR. Chlamydia trachomatis in children. Pediatr Ann 1994; 23: 349353.
  • 22
    Stenberg K, Mardh PA. Persistent neonatal chlamydial infection in a 6-year-old girl. Lancet 1986; 2: 12781279.
  • 23
    Darville T. Chlamydia spp. In: NataroJP, BlaserJ, Cunningham-RundlesS, eds, Persistent bacterial infections. Washington, DC: ASM Press, 2000; 229261.
  • 24
    Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994; 58: 686699.
  • 25
    Ward ME. Mechanisms of Chlamydia-induced disease. In: StephensRS, ed. Chlamydia. Washington, DC: ASM Press, 1999; 171210.
  • 26
    Dean D, Suchland RJ, Stamm WE. Evidence for long-term cervical persistence of Chlamydia trachomatis by omp1 genotyping. J Infect Dis 2000; 182: 909916.
  • 27
    Belland RS, Sudmoze MA, Carne DD et al. Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes. Proc Natl Acad Sci USA 2007; 98: 1398413989.
  • 28
    Michel CEC, Sonnex C, Carne CA et al. Chlamydia trachomatis load at matched anatomic sites: implications for screening strategies. J Clin Microbiol 2007; 45: 13951402.
  • 29
    Schachter J, Chernesky MA, Willis DE et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis 2005; 32: 725728.
  • 30
    Gaydos CA, Ferrero DV, Papp J. Laboratory aspects of screening men for Chlamydia trachomatis in the new millenium. Sex Transm Dis 2008; 35: 545550.
  • 31
    Essig A. Chlamydia and Chlamydophila. In: MurrayPR, BaronEJ, JorgensenJH, LandryML, PfallerMA, eds. Manual of clinical microbiology, 9th edn. Washington, DC: ASM Press, 2007; 10211035.
  • 32
    Black CM. Current methods of laboratory diagnosis of Chlamydia trachomatis infections. Clin Microbiol Rev 1997; 10: 160184.
  • 33
    Warford A, Chernesky M, Peterson EM. Laboratory diagnosis of Chlamydia trachomatis infections. In: GleavesCA, ed. Cumitech 19A. Washington, DC: ASM Press, 1999, pp. 118.
  • 34
    Michel CE, Solomon AW, Magbanua JP et al. Field evaluation of a rapid point-of-care assay for targeting antibiotic treatment for trachoma control: a comparative study. Lancet 2006; 367: 15851590.
  • 35
    Mahilum-Tapay L, Laitila V, Wawrzyniak JJ et al. New point of care Chlamydia Rapid Test—bridging the gap between diagnosis and treatment: performance evaluation study. BMJ 2007; 335: 11901194.
  • 36
    Leber AL, Hall GS, LeBar WD. Nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. In: SharpSE, ed. Cumitech 44. Washington, DC: ASM Press, 2006, pp. 138.
  • 37
    Schachter J, Chow JM, Howard H, Bolan G, Moncada J. Detection of Chlamydia trachomatis by nucleic acid amplification testing: our evaluation suggests that CDC-recommended approaches for confirmatory testing are ill-advised. J Clin Microbiol 2006; 44: 25122517.
  • 38
    Schachter J, Hook EW, Martin DH et al. Confirming positive results of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis: all NAATs are not created equal. J Clin Microbiol 2005; 43: 13721373.
  • 39
    Ripa T, Nilsson P. A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications for use of PCR diagnostic tests. Euro Surveill 2006; 11: E061109.
  • 40
    Lynagh Y, Walsh A, Crowley B. First report of the new variant strain of Chlamydia trachomatis in Ireland. Epi-Insight 2007; 8: 4.
  • 41
    Moghaddam A, Reinton N. Identification of the Swedish Chlamydia trachomatis variant among patients attending a STI clinic in Oslo, Norway. Euro Surveill 2007; 12: E070301.
  • 42
    Hoffmann S, Jensen JS. Mutant Chlamydia trachomatis in Denmark. Euro Surveill 2007; 12: E7E8.
  • 43
    De Barbeyrac B, Raherison S, Cado S et al. French situation concerning the Swedish Chlamydia trachomatis variant. Euro Surveill 2007; 12: E11E12.
  • 44
    Frost EH, Deslandes S, Veilleux S, Bourgaux-Ramoisy D. Typing Chlamydia trachomatis by detection of restriction fragment length polymorphism in the gene encoding the major outer membrane protein. J Infect Dis 1991; 163: 11031107.
  • 45
    Rodriguez P, Vekris A, De Barbeyrac B, Dutilh B, Bonnet J, Bebear C. Typing of Chlamydia trachomatis by restriction endonuclease analysis of the amplified major outer membrane protein gene. J Clin Microbiol 1991; 29: 11321136.
  • 46
    Klint M, Fuxelius HH, Goldkuhl RR et al. High-resolution genotyping of Chlamydia trachomatis strains by multilocus sequence analysis. J Clin Microbiol 2007; 45: 14101414.
  • 47
    Pedersen LN, Podenphant L, Moller JK. Highly discriminative genotyping of Chlamydia trachomatis using omp1 and a set of variable number tandem repeats. Clin Microbiol Infect 2008; 14: 644652.
  • 48
    Persson K. The role of serology, antibiotic susceptibility testing and serovar determination in genital chlamydial infections. Best Pract Res Clin Obstet Gynaecol 2002; 16: 801814.
  • 49
    Jones R, Boag F. Screening for Chlamydia trachomatis—opportunistic approaches have little evidence to support them. BMJ 2007; 334: 703704.
  • 50
    Low N. Screening programmes for chlamydial infection: when will we ever learn? BMJ 2007; 334: 725728.
  • 51
    Suchland RJ, Geisler WM, Stamm WE. Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp. Antimicrob Agents Chemother 2003; 47: 636642.
  • 52
    Mourad A, Sweet RL, Sugg N, Schachter J. Relative resistance to erythromycin in Chlamydia trachomatis. Antimicrob Agents Chemother 1980; 18: 696698.
  • 53
    Lefevre JC, Lepargneur JP. Comparative in vitro susceptibility of a tetracycline-resistant Chlamydia trachomatis strain isolated in Toulouse (France). Sex Transm Dis 1998; 25: 350352.
  • 54
    Somani J, Bhullar VB, Workowski KA, Farshy CE, Black CM. Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure. J Infect Dis 2000; 181: 14211427.
  • 55
    Dreses Werringloer U, Padubrin I, Kohler L, Hudson AP. Detection of nucleotide variability in rpoB in both rifampin-sensitive and rifampin-resistant strains of Chlamydia trachomatis. Antimicrob Agents Chemother 2003; 47: 23162318.
  • 56
    Dessus-Babus S, Bébéar CM, Charron A, Bébéar C, De Barbeyrac B. Sequencing of gyrase and topoisomerase  IV quinolone-resistance-determining regions of Chlamydia trachomatis and characterization of quinolone-resistant mutants obtained in vitro. Antimicrob Agents Chemother 1998; 42: 24742481.
  • 57
    Misyurina OY, Chipitsyna EV, Finashutina YP et al. Mutations in a 23S rRNA gene of Chlamydia trachomatis associated with resistance to macrolides. Antimicrob Agents Chemother 2004; 48: 13471349.
  • 58
    Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH, Holmes KK. Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis: a meeting report. J Infect Dis 2005; 191: 917923.
  • 59
    CDC. Sexually transmitted diseases treatment guidelines. MMWR 2006; Report No. 55 (RR-11).
  • 60
    Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections—a meta-analysis of randomized clinical trials. Sex Transm Dis 2002; 29: 497502.
  • 61
    Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis 2007; 44 (suppl): S111S122.