REVIEW 10.1111/j.1469-0691.2008.02647.

Genital Chlamydia trachomatis infections

C. Bébéar and B. de Barbeyrac

Laboratoire de Bactériologie EA 3671, Infections Humaines à Mycoplasmes et Chlamydiae, CNR des Infections à Chlamydiae, Université Victor Segalen
Bordeaux 2, Bordeaux, France

Abstract

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 infec-
tion, 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 diag-
nosis is best made by using nucleic acid amplification tests, because they perform well and do not require invasive procedures for speci-
men collection. Single-dose therapy has been a significant development for treatment of an uncomplicated infection of the patient and
his or her sexual partner.

Keywords: Chlamydia trachomatis, diagnosis, epidemiology, genital infections, review, treatment

Clin Microbiol Infect 2009; 15: 4–10

Corresponding author and reprint requests: C. Bébéar,
Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2,
146 rue Léo Saignat, 33076 Bordeaux cedex, France
E-mail: christiane.bebear@u-bordeaux2.fr
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 transmis-
sion of lymphogranuloma venereum (LGV).

Introduction
Chlamydia trachomatis is an obligate intracellular bacterium.
During its unique developmental cycle, two different forms
are observed, elementary bodies (EBs), which are infec-
tious but not able to divide, and reticulate bodies (RBs),
which are metabolically active and able to multiply. Persis-
tent 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 diagnos-
tic techniques and methods of specimen collection make eas-
ier 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 specific-
ity 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
Epidemiology
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, unpro-
tected sex, and being unmarried [3].
In the USA in 2006, more than one million cases of chla-
mydial 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 asymptom-
atic 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

ª2009 The Authors

Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases
CMI
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 cen-
tres of universities [7]. In 2005, the overall prevalence of
C. trachomatis in the French population was 1.5% in the gen-
eral 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 industrial-
ized 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. Ham-
burg, Paris [10], London, Stockholm, Vienna and Zurich,
and from North America and Australia, indicated the emer-
gence of a new outbreak in this high-risk group. This out-
break was dominated by the C. trachomatis variant L2b, first
described in patients from Amsterdam [11] and sub-
sequently found in France [12], Germany, Canada and
Australia.
Surveillance systems were established in different coun-
tries. 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-rec-
tal samples [14].
170
180 LGV : 551
160 140
Non-LGV : 233
140
No. of strains
117
120 102
100
80 70
54
60
26
40 19
20 3 3 4 perihepatitis
0 (Fitz-Hugh–Curtis syndrome), infertility
2002 2003 2004 2005 2006 2007
FIG. 1. Chlamydia trachomatis proctitis in France, 2002–2007 (lympho-
granuloma venereum (LGV) and non-LGV isolates) (personal data).
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
Bébéar and de Barbeyrac Genital Chlamydia trachomatis infections 5
Clinical Manifestations of C. Trachomatis
Infections
Chlamydial infection can cause cervicitis in women and ure-
thritis 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.
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 incu-
bation, 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 evi-
dence 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 com-
plain of mucopurulent vaginal discharge or postcoital bleed-
ing. 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. Endometri-
tis is frequently associated with this and may produce irregu-
lar 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
TABLE 1. Clinical manifestations of Chlamydia trachomatis
infections
Serovar Clinical manifestation Complication
76
A–C Keratoconjunctivitis Scarring trachoma, blindness
D–K Males: urethritis, proctitis Epididymitis
Females: cervicitis, Endometritis, salpingitis,
urethritis, proctitis pelvic pain, ectopic pregnancy,
Males and females: Reiter’s syndrome, reactive arthritis
conjunctivitis
L1–L3 Lymphogranuloma venereum: Fibrosis, rectal stricture
inguinal syndrome, proctitis
ª2009 The Authors
6 Clinical Microbiology and Infection, Volume 15 Number 1, January 2009
reproductive complications. Two-thirds of all cases of tubal-
factor infertility and one-third of all cases of ectopic preg-
nancy 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 epi-
sodes of PID [19].
Fitz-Hugh–Curtis syndrome, a perihepatitis observed after
or in conjunction with salpingitis, is more commonly associ-
ated with chlamydial than with gonococcal infections.
There is little evidence, and this is conflicting, to implicate
C. trachomatis in chorioamnionitis and adverse pregnancy out-
come [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 secre-
tions 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 devel-
ops 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 high-
lights the importance of the need to control this infection.
Pathogenesis
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 per-
sistent 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 com-
ª2009 The Authors
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
CMI
mon, 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 cyto-
kine system of the host is likely to be central to disease, as
the inflammation following chlamydial infection and exacer-
bated by re-infection leads to tissue damage and scarring.
Moreover, continued chlamydial Hsp60 expression sec-
ondary to the action of interferon-c 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-spe-
cific 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 immu-
nity. Antigenic variation can arise in response to antimicro-
bial 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
There have been major developments during the past
30 years. As C. trachomatis is an obligate intracellular bacte-
rium, cell culture remains a reference method, but many
commercial non-culture-based assays are now available for
diagnosis (Table 2).
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 en-
docervical 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
CMI Bébéar and de Barbeyrac Genital Chlamydia trachomatis infections 7

TABLE 2. Direct detection of Chlamydia trachomatis

Method Turn-around time Advantages Limits

Cell culture 72 h Specificity, strain Sensitivity 80–85%

Antigen detection
DFA 45 min Simple, unit test Sensitivity 75–80%
Subjective reading
EIA 4h Automation Sensitivity 75–80%
Point of care 30 min Low cost, unit test Low specificity (confirmatory test)
Molecular methods
DNA probing 2h Easy to perform Sensitivity 75–80%
Hybrid capture 4h Sensitivity 95% Only for cervical specimens (FDA)
Specificity 99%
NAAT (real-time PCR, SDA, TMA, NASBA) 2–4 h Sensitivity >95% Contamination, costly processing of specimen
Specificity 99%

TABLE 3. Advantages and limits of main urogenital EIA tests can be automated. They are more reproducible
specimens than DFA, and the sensitivity of the best EIA is comparable
Sex Specimen Advantages Limits Usable technique to that of culture and lower than that of NAATs. They can
give false-positive results due to cross-reactions with the
Men Urethral swab High sensitivity Invasive All tests lipopolysaccharide (LPS) of other microorganisms, and all
Urine Non-invasive NAATs
Self-collected Some EIA tests positive EIA results must be confirmed.
Penile swab Non-invasive Low sensitivity NAATs
Self-collected Rapid or ‘point-of-care’ tests are proposed for patients
Women Cervical swab High sensitivity Invasive All tests who are unlikely to return for test results. They are not suit-
Urethral swaba High sensitivity Invasive All tests
Urine Non-invasive Low sensitivity NAATs able for non-invasive specimens, have moderate sensitivity,
Self-collected
Vaginal swab Non-invasive NAATs and are not recommended for laboratory settings. A rapid
Self-collected
test for diagnosis of chlamydial infection, recently developed
NAAT, nucleic acid amplification test; EIA, enzyme immunoassay. by the Wellcome Trust [34,35], is based on a second-genera-
a
Only in association with cervical swabs to improve the diagnosis of infection.
tion signal amplification EIA for chlamydial LPS in a dipstick-
type format. The initial results are promising.

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).
Cell culture
Cell culture has near 100% specificity. However, it is not
recommended for routine use, because of its lack of sensitiv-
ity, 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 anti-
biotic 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].
Nucleic acid hybridization tests
DNA probing (with Pace 2, Gen Probe) was the first molec-
ular 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 hybrid-
ization test that is signal amplification-based. Its sensitivity is
substantially higher than that of the Pace 2 test and is com-
parable to that of PCR [36].
NAATs
Because of their high sensitivity and specificity, and their pos-
sible use for a large range of sample types, including vulvova-
ginal 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 amplifica-
tion (Becton Dickinson, NJ, USA); transcription-mediated
amplification (Gen Probe); and nucleic acid sequence-based

ª2009 The Authors

Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
8 Clinical Microbiology and Infection, Volume 15 Number 1, January 2009
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. tra-
chomatis, 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 Nei-
sseria gonorrhoeae in the same specimen. Their primary disad-
vantage 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 cur-
rently 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 chromo-
somal 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 sex-
ually transmitted infections by using multiplex tests, in partic-
ular DNA microarray technology.
Typing Systems
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, geno-
typing methods exploiting genome variations, e.g. multilocus
sequence [46] and variable-number tandem repeat [47] analy-
sis, have been used to discriminate among strains.
Serology
Serology is useful only in some cases of C. trachomatis infec-
tion and in seroepidemiological studies [48]. It suffers from
several drawbacks, including the serological cross-reactivity
between C. trachomatis and Chlamydophila species, and the
ª2009 The Authors
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
CMI
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 infec-
tions, or for screening in asymptomatic patients, serological
testing may be useful for diagnosing LGV, neonatal pneumo-
nia, and upper genital tract infections, and for the evaluation
of tubal-factor infertility.
The serological methods available are complement fixa-
tion, 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 ref-
erence 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
Screening programmes must be cost-effective and must be
made acceptable to patients by using non-invasive proce-
dures 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
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 fluor-
oquinolones (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 clin-
ical isolates that demonstrated in vitro resistance to macro-
CMI Bébéar and de Barbeyrac
lides 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], sug-
gesting 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 possibil-
ity 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-perfor-
mance NAATs and specimens obtained through non-invasive
procedures, in conjunction with single-dose antimicrobial
therapy, should reduce the consequence of untreated infec-
tions.
Transparency Declaration
C. Bébéar and B. de Barbeyrac declare no conflicts of interest.
References
1. Hatch TP. Developmental biology. In: Stephens RS, ed. Chlamydia.
Washington, DC: ASM Press, 1999; 29–67.
2. Schachter J. Infection and disease epidemiology. In: Stephens RS, ed.
Chlamydia. Washington, DC: ASM Press, 1999; 139–169.
3. Manavi K. A review on infection with Chlamydia trachomatis. Best Pract
Res Clin Obstet Gynaecol 2006; 20: 941–951.
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: 715–720.
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.
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
Genital Chlamydia trachomatis infections 9
6. Warszawski J. Dépistage systématique des infections à Chlamydia tra-
chomatis: il est temps d’agir. Bull Epidémiol Hebd 2006; 38: 275–276.
7. Barbeyrac de B, Raherison S, Bernabeu A et al. Dépistage de l’infetion
à Chlamydia trachomatis dans la population d’étudiantes des universités
de Bordeaux, France, 2004. Bull Epidémiol Hebd 2006; 38: 288–290.
8. van de Laar MJ, Fenton KA, Ison C. Update on the European lympho-
granuloma 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 ven-
ereum proctitis in men who have sex with men is associated with
anal enema use and high-risk behavior. Sex Transm Dis 2008; 35: 203–
208.
10. Herida M, Sednaoui P, Couturier E et al. Rectal lymphogranuloma
venereum, France. Emerg Infect Dis 2005; 11: 505–506.
11. Spaargaren J, Fennema HS, Morre SA, de Vries HJ, Coutinho RA.
New lymphogranuloma venereum Chlamydia trachomatis variant,
Amsterdam. Emerg Infect Dis 2005; 11: 1090–1092.
12. Herida M, de Barbeyrac B, Sednaoui P et al. Rectal lymphogranuloma
venereum surveillance in France 2004–2005. Euro Surveill 2006; 11:
155–156.
13. Ward H, Martin I, Macdonald N et al. Lymphogranuloma venereum
in the United Kingdom. Clin Infect Dis 2007; 44: 26–32.
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: 268–269.
15. van de Laar MJ, Morre SA. Chlamydia: a major challenge for public
health. Euro Surveill 2007; 12: E1–E2. Available at: http://www.eurosur-
veillance.org/em/v12n10/1210-221.asp
16. Peipert JF. Clinical practice. Genital chlamydial infections. N Engl J
Med 2003; 349: 2424–2430.
17. Hicks D. Complications of Chlamydia trachomatis infection in men. In:
Moss TR, ed. International handbook of Chlamydia, 3rd edn. Haslemere,
UK: Alden Press, 2008; 99–109.
18. Barbeyrac de B, Papaxanthos Roche A, Mathieu C et al. Chlamydia tra-
chomatis in subfertile couples undergoing an in vitro fertilization pro-
gram: a prospective study. Eur J Obstet Gynecol Reprod Biol 2006; 129:
46–53.
19. Rogstad K. Complications in the female and their management. In:
Moss T, ed. International handbook of Chlamydia, 3rd edn. Haslemere,
UK: Alden Press, 2008; 111–121.
20. Paavonen J, Eggert-Kruse W. Chlamydia trachomatis: impact on human
reproduction. Hum Reprod Update 1999; 5: 433–447.
21. Hammerschlag MR. Chlamydia trachomatis in children. Pediatr Ann
1994; 23: 349–353.
22. Stenberg K, Mardh PA. Persistent neonatal chlamydial infection in a
6-year-old girl. Lancet 1986; 2: 1278–1279.
23. Darville T. Chlamydia spp. In: Nataro JP, Blaser J, Cunningham-Run-
dles S, eds, Persistent bacterial infections. Washington, DC: ASM Press,
2000; 229–261.
24. Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae: from cell
culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994;
58: 686–699.
25. Ward ME. Mechanisms of Chlamydia-induced disease. In: Stephens RS,
ed. Chlamydia. Washington, DC: ASM Press, 1999; 171–210.
26. Dean D, Suchland RJ, Stamm WE. Evidence for long-term cervical
persistence of Chlamydia trachomatis by omp1 genotyping. J Infect Dis
2000; 182: 909–916.
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: 13984–13989.
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: 1395–1402.
ª2009 The Authors
10 Clinical Microbiology and Infection, Volume 15 Number 1, January 2009
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 AP-
TIMA assays for both infections. Sex Transm Dis 2005; 32: 725–728.
30. Gaydos CA, Ferrero DV, Papp J. Laboratory aspects of screening
men for Chlamydia trachomatis in the new millenium. Sex Transm Dis
2008; 35: 545–550.
31. Essig A. Chlamydia and Chlamydophila. In: Murray PR, Baron EJ, Jorgen-
sen JH, Landry ML, Pfaller MA, eds. Manual of clinical microbiology, 9th
edn. Washington, DC: ASM Press, 2007; 1021–1035.
32. Black CM. Current methods of laboratory diagnosis of Chlamydia tra-
chomatis infections. Clin Microbiol Rev 1997; 10: 160–184.
33. Warford A, Chernesky M, Peterson EM. Laboratory diagnosis of Chla-
mydia trachomatis infections. In: Gleaves CA, ed. Cumitech 19A. Wash-
ington, DC: ASM Press, 1999, pp. 1–18.
34. Michel CE, Solomon AW, Magbanua JP et al. Field evaluation of a
rapid point-of-care assay for targeting antibiotic treatment for tra-
choma control: a comparative study. Lancet 2006; 367: 1585–1590.
35. Mahilum-Tapay L, Laitila V, Wawrzyniak JJ et al. New point of care
Chlamydia Rapid Test—bridging the gap between diagnosis and treat-
ment: performance evaluation study. BMJ 2007; 335: 1190–1194.
36. Leber AL, Hall GS, LeBar WD. Nucleic acid amplification tests for
detection of Chlamydia trachomatis and Neisseria gonorrhoeae. In:
Sharp SE, ed. Cumitech 44. Washington, DC: ASM Press, 2006, pp. 1–
38.
37. Schachter J, Chow JM, Howard H, Bolan G, Moncada J. Detection of
Chlamydia trachomatis by nucleic acid amplification testing: our evalua-
tion suggests that CDC-recommended approaches for confirmatory
testing are ill-advised. J Clin Microbiol 2006; 44: 2512–2517.
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: 1372–
1373.
39. Ripa T, Nilsson P. A variant of Chlamydia trachomatis with deletion in
cryptic plasmid: implications for use of PCR diagnostic tests. Euro Sur-
veill 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, Nor-
way. Euro Surveill 2007; 12: E070301.
42. Hoffmann S, Jensen JS. Mutant Chlamydia trachomatis in Denmark.
Euro Surveill 2007; 12: E7–E8.
43. de Barbeyrac B, Raherison S, Cado S et al. French situation concern-
ing the Swedish Chlamydia trachomatis variant. Euro Surveill 2007; 12:
E11–E12.
44. Frost EH, Deslandes S, Veilleux S, Bourgaux-Ramoisy D. Typing Chla-
mydia trachomatis by detection of restriction fragment length poly-
morphism in the gene encoding the major outer membrane protein. J
Infect Dis 1991; 163: 1103–1107.
45. Rodriguez P, Vekris A, de Barbeyrac B, Dutilh B, Bonnet J, Bebear C.
Typing of Chlamydia trachomatis by restriction endonuclease analysis
ª2009 The Authors
Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 4–10
CMI
of the amplified major outer membrane protein gene. J Clin Microbiol
1991; 29: 1132–1136.
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: 1410–1414.
47. Pedersen LN, Podenphant L, Moller JK. Highly discriminative geno-
typing of Chlamydia trachomatis using omp1 and a set of variable num-
ber tandem repeats. Clin Microbiol Infect 2008; 14: 644–652.
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: 801–814.
49. Jones R, Boag F. Screening for Chlamydia trachomatis—opportunistic
approaches have little evidence to support them. BMJ 2007; 334:
703–704.
50. Low N. Screening programmes for chlamydial infection: when will we
ever learn? BMJ 2007; 334: 725–728.
51. Suchland RJ, Geisler WM, Stamm WE. Methodologies and cell lines
used for antimicrobial susceptibility testing of Chlamydia spp. Antimic-
rob Agents Chemother 2003; 47: 636–642.
52. Mourad A, Sweet RL, Sugg N, Schachter J. Relative resistance to
erythromycin in Chlamydia trachomatis. Antimicrob Agents Chemother
1980; 18: 696–698.
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: 350–352.
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: 1421–1427.
55. Dreses Werringloer U, Padubrin I, Kohler L, Hudson AP. Detection
of nucleotide variability in rpoB in both rifampin-sensitive and rifam-
pin-resistant strains of Chlamydia trachomatis. Antimicrob Agents Chemo-
ther 2003; 47: 2316–2318.
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 Chemo-
ther 1998; 42: 2474–2481.
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: 1347–1349.
58. Wang SA, Papp JR, Stamm WE, Peeling RW, Martin DH, Holmes KK.
Evaluation of antimicrobial resistance and treatment failures for Chla-
mydia trachomatis: a meeting report. J Infect Dis 2005; 191: 917–923.
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: 497–502.
61. Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic
inflammatory disease: the 2006 Centers for Disease Control and Pre-
vention sexually transmitted diseases treatment guidelines. Clin Infect
Dis 2007; 44 (suppl): S111–S122.