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Abstract

The focus on Chlamydia trachomatis in gynecologic practice 20 years ago was in treating its potential consequences: pelvic inflammatory disease, infertility and ectopic pregnancy. Although these conditions are still important, the current focus of C. trachomatis management for the obstetrician and gynecologist is early detection and treatment. The majority of women with C. trachomatis are asymptomatic, therefore, screening programs are being devised so that C. trachomatis can be treated prior to the occurence of any adverse consequences. Novel tests have allowed the use of urine samples and self-collected vulvovaginal swabs in the detection of C. trachomatis. This article will review the consequences of C. trachomatis infection in women, methods of identification of the organism, the prevalence in various populations, and treatment and screening strategies.

Keywords

chlamydia trachomatis ectopic pregnancy infertility mass screening nucleic acid amplification test pelvic inflammatory disease

What is Chlamydia?

Chlamydia trachomatis is a nonmotile Gram-negative bacterium that survives within cells [1]. There are two other species of Chlamydia that infect humans: Chlamydia psittaci and Chlamydia pneumonia; however, these other species will not be discussed further in this article. C. trachomatis is implicated in diseases of trachoma and lymphogranuloma venerum, inclusion conjunctivitis and urogenital tract disease. This review will focus on urogenital disease in women, which is normally associated with the serovars D–K (strains determined by the major outer membrane protein characteristics). C. trachomatis has an unusual biphasic lifestyle. In the first phase, the bacteria enters cells (probably by receptor-mediated endocytosis) as a chlamydial elementary body. Next, the elementary body is reorganized into the reticulate body, which replicates to generate a large number of infectious units. The reticulate bodies condense into elementary bodies, which mature and are extruded with the release of infectious elementary bodies, and the cycle begins again. The intracellular location of C. trachomatis means that the organism can only be identified (by culture) in samples that contain tissue or cells. Until the development of nucleic acid amplification tests (NAATs), this meant that either an endocervical swab for genital tract infection or a urethral swab for the less common urethral C. trachomatis infection had to be performed. Taking an endocervical swab involves a vaginal speculum examination by a trained clinician, with consequent limited patient acceptability. The introduction of NAATs, which are much more sensitive than culture, has revolutionized the detection of C. trachomatis, and allows a first-void urine sample or self-collected vaginal swab to be used in the detection of female C. trachomatis. These samples can be produced by the woman herself without any medical intervention, and the method even allows remote (e.g., home based) testing. Mass screening to identify asymptomatic women with C. trachomatis has thus become a realistic option. This issue will be discussed in more detail later in this article.

Clinical consequences of C. trachomatis

Symptoms

C. trachomatis infection is asymptomatic in up to 80% of women. The remaining 20% may present either with nonspecific symptoms, for example, vaginal discharge and intermenstrual bleeding, or with symptoms of some of the consequences, such as pelvic inflammatory disease (PID) (e.g., lower abdominal pain or irregular menses). Rarely, in the UK, extragenital spread occurs and may cause site-specific symptoms (e.g., pain, redness and discharge from the eye in ocular infections). Although a detailed description of male C. trachomatis infection is out of the scope of this review, it should be noted that, in men, C. trachomatis causes urethritis or epididymitis that may be asymptomatic in over 50% of individuals.

Spontaneous resolution

Although failure to treat C. trachomatis infection cannot be justified, it is clear that, in some women, the infection resolves spontaneously, an effect presumably mediated by the host immune response. For example, 28% (21/75) of women in whom an endocervical swab was culture positive for C. trachomatis were found to be negative on repeat testing within 45 days [2]. In another study using polymerase chain reaction (PCR), 22% (13/58) of women were found to have a negative result on repeat testing 10 days later [3]. In a company health check, the rate of clearance of asymptomatic C. trachomatis infection (diagnosed by urine DNA analysis) was 45% within 1 year [4]. Natural resolution of the infection has also been demonstrated in pregnancy. In a subset of a larger study, a cohort of 1547 asymptomatic women provided urine samples between 16 and 24 weeks of pregnancy, and then again between 24 and 30 weeks gestation [5]. None had received antibiotics active against C. trachomatis. A total of 140 (9%) tested positive using ligase chain reaction (LCR) on the first occasion, with only 74 (56% of previously positive women) testing positive on the second occasion. In this, as in previous studies, being older and having a longer interval between infections was associated with an increased likelihood of spontaneous resolution, suggesting that this phenomenon is mediated by the host immune response. Perhaps surprisingly, having a greater number of previous sexual partners was also associated with a greater likelihood of spontaneous resolution. This has been interpreted to mean that second and subsequent infections are more likely to resolve spontaneously than the first episode of infection, presumably due to the development of protective immunity.

Ascending infection & pelvic inflammatory disease

If C. trachomatis does not resolve spontaneously, potentially the most serious consequences occur when it ascends the genital tract to cause upper genital tract infection and PID. There is little information that accurately defines the risk of developing PID in women with lower genital tract C. trachomatis infection. Most authorities have assumed the risk of clinically apparent PID in women with untreated lower genital tract C. trachomatis infection to be in the order of 6–20% [6,7]. Some of the best evidence comes from a randomized, controlled trial in which women were randomized either to screening and treatment of asymptomatic C. trachomatis or to no treatment, with the rates of PID in each group ascertained over the following year [8]. The rate of PID was 9.6%/year in the unscreened and untreated group, and 2.16%/year in the screened group. If one assumes that the difference in PID rates is due to treated lower genital tract C. trachomatis infection, the rate of PID associated with untreated infection is 7.5%/year (in practice, only 64% of the women assigned to the screening group actually attended for screening, so the true rate of PID associated with untreated C. trachomatis infection is likely to be higher). Although these data are generally accepted, a recent paper has argued that these projected rates of PID are only related to high-risk populations and suggests that in the general population, where the prevalence of C. trachomatis is lower, the probability of a woman with untreated genital tract C. trachomatis infection developing PID is likely to be 0.43% (calculation derived from the incidence of PID and the prevalence of C. trachomatis on a population basis) [9]. This calculation is supported by a prospective study of 30 women with untreated asymptomatic C. trachomatis infection, none of whom developed clinical PID during a 1-year follow-up [4].

In women who have clinical evidence of PID, the prevalence of infection with C. trachomatis ranges from 27% [10] to 61% [11]. Therefore, C. trachomatis is one of the major contributors to PID. Interestingly, having C. trachomatis PID rather than PID from any other cause seems to reduce the likelihood of developing chronic pelvic pain [12]. Clearly, there are other adverse consequence of C. trachomatis PID infection, such as ectopic pregnancy and infertility, and these will be discussed in more detail below.

Ectopic pregnancy

C. trachomatis is clearly implicated in the pathophysiology of tubal ectopic pregnancy. The presumptive mechanism is that C. trachomatis damages the tubal epithelium either alone or in conjunction with other microbes. The host immune response may also, paradoxically, contribute to tubal damage via autoimmunity induced by C. trachomatis antigens to endogenous heat shock protein 60.

In a case–control study of women in France between 1998–1991, the attributable fraction of ectopic pregnancy due to C. trachomatis seropositivity was 25% [13]. The odds ratios (ORs) for the risk factors positive C. trachomatis serology and confirmed PID were 4.9 (95% confidence interval [CI]: 3.5–5.7) and 5.6 (3.5–9.2), respectively, in women with ectopic pregnancy were greater than the OR for the other risk factors such as maternal smoking and lack of contraceptive pill use. In a more recent ecologic analysis from Sweden, where rates of both C. trachomatis and ectopic pregnancy are declining, a very strong correlation between C. trachomatis infection and ectopic pregnancy rates were found in all age groups [14]. In older women (35–39 years), the correlation was strongest between current rates of ectopic pregnancy and C. trachomatis infection 2 years earlier (p < 0.001). In young women (20–24 years), correlation was strongest between current rates of C. trachomatis; indeed, variations in the concurrent rate of C. trachomatis explained 86% of the variation in ectopic pregnancy rates [14].

In the last 10–20 years, a decline in ectopic pregnancy rates in the UK and many Western countries has been noted [15]. Coste and colleagues have differentiated ectopic pregnancy arising from contraceptive failure, where the woman was using contraception at the time of pregnancy, and ectopic pregnancy arising from reproductive failure, where contraception was not used. They demonstrate that ectopic pregnancy due to contraceptive failure is decreasing (presumably due to more effective contraception or a change in contraceptive usage); however, ectopic pregnancy due to reproductive failure has actually increased by 17% over the past 10 years [16]. Therefore, in women planning (or at least not avoiding) pregnancy, the problem of ectopic pregnancy is growing. The authors suggest that this is due to a 23% increase in the prevalence of C. trachomatis and an 8.2% increase in cigarette smoking among women over this period, both highly important risk factors for ectopic pregnancy in this population [17].

Infertility

The association between tubal infertility and current or past C. trachomatis infection has been comprehensively described [18]. In a World Health Organization (WHO) multicenter case–control study, 70% of women with bilateral tubal occlusion had antibodies either to C. trachomatis alone or to C. trachomatis and Neisseria gonorrohoea, compared with only 32% who presented with other causes of infertility [19]. Furthermore, the distribution of C. trachomatis immunoglobulin G antibodies was similar in fertile controls and infertile controls without tubal occlusion, but markedly different (stronger and more prevalent) in women with bilateral tubal occlusion [19]. This study was conducted in Thailand, Hungary and Slovenia, and therefore may not be relevant for all developed countries. However, studies in the Netherlands [20] and the UK [21] have shown a prevalence of C. trachomatis antibodies of 54% (32/59) and 36% (23/63), respectively, in infertile women with demonstrable tubal disease, compared with only 8% (20/254) and 12% (17/144), respectively, in infertile women without tubal disease. Taken together, these studies demonstrate that past C. trachomatis infection is strongly associated with the development of tubal infertility and, taking into account the current knowledge of the pathophysiology of C. trachomatis infection, it seems highly likely that it is causally implicated in tubal-factor infertility.

Effects on mother & baby in pregnancy

Infection with C. trachomatis in pregnancy is associated with an increased risk of preterm delivery, low birth weight and premature rupture of the membranes [22 –26]. In a recent study in the USA, where C. trachomatis was detected in urine samples by LCR, women with C. trachomatis infection at 24 weeks gestation were twice as likely as uninfected women to have a spontaneous preterm birth at less than 37 weeks gestation (OR: 2.2; 95% CI: 1.03–4.78) and three times as likely to have a spontaneous preterm birth at less than 35 weeks gestation (OR: 3.2; 95% CI: 1.08–9.57), after adjustment for risk factors for spontaneous preterm birth [26]. There are other potential adverse neonatal effects, since babies born to women with C. trachomatis have an 18–50% risk of developing C. trachomatis conjunctivitis and a 10–16% risk of developing C. trachomatis pneumonia [27]. Therefore, C. trachomatis poses a risk to pregnant women and their babies, although the risks of ascending infection are generally lower in this group.

Identifying C. trachomatis infection

Laboratory tests

Tests for C. trachomatis can be categorized as culture-based methods, nonculture methods and serologic testing [28]. Previously, culture was considered the gold standard for testing of C. trachomatis due to its high specificity; however, it is limited by the relatively long interval between sampling and result (3–7 days), the requirement for careful transportation of specimens and the insensitivity of the method compared with NAATs. Culture is still considered to be the optimum test where medicolegal issues may arise.

Of the nonculture methods, the NAATs are the most sensitive. As their name suggests, these tests use C. trachomatis DNA or RNA in the test sample as a template to generate more C. trachomatis DNA/RNA fragments, using either PCR or LCR. These amplified copies of the relevant C. trachomatis nucleic acid fragment are then stained and visualized. The amplification strategy crucially relies on at least one copy of C. trachomatis DNA/RNA in the test sample, although the powerful nature of the amplification process allows detection down to this very low concentration of C. trachomatis DNA/RNA. Thus, the NAATs are both exquisitely sensitive and (if conducted correctly in surroundings that minimize contamination) highly specific. They allow samples that would previously have been considered unsuitable due to the low concentration of C. trachomatis (e.g., urine) to be used in diagnosis. Both the PCR and LCR technologies have been automated. PCR is available commercially for the analysis of many samples simultaneously and most regional laboratories in the UK and the Western world have now moved over to this technology as their primary test for C. trachomatis. The commmercial LCR test was withdrawn in 2003. There was a concern that around 10% of urine samples from pregnant and nonpregnant women contained inhibitors to nucleic acid amplification, thus decreasing the sensitivity of the test. However, further studies have shown that these inhibitors are destroyed by relatively simple measures such as refrigerating samples overnight [29] and do not appear to be a problem with modern NAATs.

Further developments in NAAT technology include transcription mediated amplification (TMA) tests, marketed commercially as the Gen-Probe AMP-CT® and the newer Gen-Probe APTIMA Combo2®. This latter test appears to be at least as sensitive in urine as the other NAATs, with the advantage that once the specimen has been placed in transport media, it is stable at room temperature for up to 30 days [30]. Finally, strand displacement amplification (SDA) (e.g., ProbeTecET®) is an alternative NAAT, which appears to have a similar performance to other NAATs except when the specimen is female urine, where the sensitivity appears to be inadequate. The potential advantage of the technology is that it is a relatively easy to perform and rapid assay; however, laboratories that use this test should promote vulvovaginal swabs rather than first-void urine as the self-collected specimen of choice in female patients.

The performance of a variety of tests for the detection of C. trachomatis was comprehensively evaluated in a recent meta-analysis [31]. Studies that compared a test to a gold standard (of either culture or two nonculture tests) in asymptomatic women were reviewed. The mean sensitivity of PCR and LCR in urine was found to be 87 and 93%, respectively, compared with only 56% using culture. Even when an endocervical swab was used, the sensitivity of culture was only 86% of the gold standard used in comparison.

An alternative testing strategy for C. trachomatis involves staining and visualization of the organism without further amplification. The stain may either be a fluorescently labelled antibody (as with direct immunofluorescence [DFA]) or another label (such as enzyme immunohistochemistry [EIA]). These testing methods have the advantage of being easier to perform and standardize, with a lower requirement for stringency of transport than culture, but have markedly inferior sensitivity. The OR of a false negative test in urine was 1.86 (95% CI: 0.39–8.75) for EIA, and in the cervix was 4.10 (95% CI: 1.15–14.59) for EIA and 1.05 (95% CI: 0.09–12.93) for DFA.

Finally, some tests use DNA hybridization without amplification. These tests are commercially available as the Gen-Probe PACE-2® test or the newer Digene Hybrid Capture® test (Digene, Maryland, USA). The Gen-Probe PACE-2 test is widely used in the USA. As one might expect, it performs as well as enzyme immunoassay tests; however, it is generally less sensitive than the best NAATs when similar specimens are used [28,31]. The Digene test appears to be at least as good and possibly superior to the PACE-2 test, although further work is required before firm conclusions can be drawn [32].

Specimens for C. trachomatis testing

The systematic review referred to above indicates that an endocervical swab is superior to a first-void urine test when PCR is the test used: OR of false negative test is 0.26 (95% CI: 0.12–0.56) and 0.84 (95% CI: 0.37–1.89), respectively [31]. However, the performance of urine LCR is similar to that of endocervical swab PCR: OR of a false negative test is 0.33 (95% CI: 0.13–0.8). Therefore, provided the correct test is performed, urine tests appear to be as sensitive as endocervical swabs for the detection of C. trachomatis in women. The ideal urine test is a first-void urine that allows urethral, vaginal and perineal cells to be flushed out by the urine stream into the sample bottle and provides the cells within which the C. trachomatis organism resides. There are several advantages of urine tests over endocervical swabs. Not only do they minimize staff time (and thus expense), but they are generally more acceptable to women and allow remote testing. Furthermore, in low prevalence populations, pooling of urine samples reduces the cost of testing [33].

Alternative specimens that have been evaluated include self-collected vulval/vaginal or perineal swabs. These are also sensitive in the detection of C. trachomatis [34], acceptable to women [35], and are thought by some authorities to represent the ideal specimen in this scenario [36].

Prevalence of C. trachomatis

Secular trends

Diagnoses rates of C. trachomatis infection are continuing to rise in the Western world. For example, in the UK, the rate of diagnosis of uncomplicated genital C. trachomatis infection increased from around 400/100,000 in women in the 16–19 and 20–24 year age group, to around 1300 and 1100/100,000, respectively, in these age groups in 2003 [101]. It is hoped that some of the increased proportion of diagnoses is due to greater detection rates (resulting from better access to services and improved diagnostic tests); however, it is possible that the underlying prevalence of infection is also increasing. Similar findings are reported in the USA, with a prevalence of 400/100,000 in women (all age groups combined) in 2003 [37]. In contrast, in some European countries where C. trachomatis is a notifiable disease, rates have fallen [14,38].

Risk factors for infection

Young age, having a new sexual partner or having multiple sexual partners, being of black race, lack of condom use and attendance at genitourinary medicine (GUM), rather than family planning clinics, are consistent predictors of increased risk of C. trachomatis infection [39]. These risk factors should be borne in mind when determing screening strategies. For the gynecologist, there is a persuasive argument for offering young, sexually active women screening for C. trachomatis on an opportunistic basis when they present to clinics.

Prevalence of C. trachomatis in obstetric & gynecologic clinic populations.

A meta-analysis/systematic review of prevalence of C. trachomatis in a variety of UK clinic populations was published by Adams and colleagues in 2004 [40]. Table 1 summarizes the prevalence of C. trachomatis in clinic populations seen by obstetricians and gynecologists. In a multivariate logistic regression model, age and clinic setting were found to be important predictors of the prevalence of C. trachomatis. The prevalences in antenatal clinics, at 12.6% (95% CI: 6.4–23.2) in the under 20 years age group and 8.3% (95% CI: 4.2–15.7) in the 20–24 years age group, were similar to those found in the author's study, which was published too late to be included in the meta-analysis: 12.1% (95% CI: 8.6–16.7) in the under 20 years age group and 4.4% (95% CI: 2.6–6.9) in the 20–24 years age group, respectively [41]. In the meta-analysis, prevalences in termination-of-pregnancy (TOP) clinics were similar to those in antenatal clinics (OR of infection in a TOP clinic of 1.6 [compared with the reference general practice clinic], and infection rates in an antenatal clinic of 1.64). In contrast, in the author's study, where women were recruited from two hospitals (in Aberdeen and Glasgow), the adjusted OR of prevalence in the TOP clinic was 2.2 (95% CI: 1.23–3.99) compared with the prevalence in the antenatal clinic [41]. The actual prevalences found in the authors' study in TOP clinics were 12.6% (95% CI: 8.5–18.3) and 11.4% (95% CI: 7.7–16.5) in the under 20 years and the 20–24 years age groups, respectively.

Table 1.

Prevalence of C. trachomatis in obstetric & gynecologic clinic populations (%).

Setting	Age group (years)				Ref.

	<20	20–24	25–29	>30
Antenatal clinic	12.6 (6.4–23.2)	8.3 (4.2–15.7)	4.1 (2.0–8.2)	2.2 (1.1–4.6)	[40]
TOP clinic	12.3 (9.8–15.3)	8.1 (6.4–10.1)	4.0 (3.0–5.4)	2.2 (1.6–3.1)	[40]
Colposcopy clinic		8.9 (5.2–14.5)	3.9 (1.7–8.6)	4.4 (2.3–8.4)	[41]

95% CI; CI: Confidence interval; TOP: Termination-of-pregnancy.

In the Adams study, the date of testing, diagnostic test and specimen tested did not have a significant effect on C. trachomatis prevalence [40]. However, 63% of the observations were obtained between 1995 and 2002, with the remainder between 1973 and 1995, and the tests and specimens in all but one of the studies were the same (NAAT on urine). Thus, this meta-analysis is probably not powered or appropriately designed to refute conclusions from other studies suggesting that the prevalence of C. trachomatis infection is increasing and that NAATs are superior to other diagnostic tests.

The prevalence of C. trachomatis infection by age group in colposcopy clinics in the author's study is shown in Table 1 [41]. Unlike other clinics, there was no age-related decline in the prevalence of infection with age in this setting [41]. If these data are confirmed by other groups, they imply that where screening in colposcopy clinics is routinely employed, all age groups should be screened.

The remaining clinic scenario where C. trachomatis screening has been recommended by some groups is in infertility clinics. There is an association between C. trachomatis and infection and infertility (as described previously), therefore screening in infertility clinics appears to be advantageous. However, in prospective studies, the prevalence of C. trachomatis infection in women presenting to infertility clinics was low [42]. In infertile women undergoing uterine instrumentation, prophylaxis to prevent ascending infection with C. trachomatis and other organisms may be worthwhile, although the frequency of C. trachomatis infections detected in a screening program is likely to be low.

Prevalence of C. trachomatis in other clinic populations

In nongynecologic clinics where asymptomatic women have been screened for C. trachomatis, prevalences of 1.7–17% have been observed in European studies [43]. The NATional survey of Sexual Attitudes and Lifestyles (NATSAL) 2000 sampled UK residents of reproductive age and sought to assess C. trachomatis prevalence among those respondents who indicated that they were sexually active [44]. Over 2000 women were tested. The age-related prevalence of infection in women is shown in Table 2. Risk factors for infection (other than age) included single or cohabiting marital status, the number of new partners in the last year and having sex with two or more heterosexual partners without a condom in the last year.

Table 2.

C. trachomatis prevalence in women participating in the NATSAL survey (%).

Setting	Age group (years)			Ref.

	18–24	25–34	35–44
NATSAL 2000	3.0 (1.7–5.0)	1.7 (1.0–2.8)	0.6 (0.3–1.4)	[44]

95% CI; CI: Confidence interval; NATSAL: NATional Survey of sexual Attitudes and Lifestyle.

Screening for C. trachomatis

Does screening for C. trachomatis improve health outcomes?

It is an accepted dogma that screening for C. trachomatis in asymptomatic women and the treatment of those who test positive is beneficial to women's health (and the health of the wider community). However, the evidence for this is limited to only two randomized trials [8,45], with some supporting evidence from other types of study.

Honey and Templeton have pointed out that the evidence that C. trachomatis screening is effective is grade 2 evidence (leading to a level B recommendation that screening strategies should be instituted) [46]. Again, although many authors have found screening to be cost effective if the prevalence of infection is greater than 4% [7,47,48], others have disputed this, arguing that it is based on incorrect assumptions on the risks of outcomes [9]. More information on the efficacy of screening programmes using newer NAATs, the likelihood and consequences of reinfection and the outcomes in low-risk populations would be helpful, although a randomized trial to address this issue is likely to be extremely expensive.

National guidelines & screening strategies

Most screening programmes focus on opportunistic screening of those attending selected (usually healthcare) settings. Postal screening has been tried with some success in both Denmark [49] and the UK [50]. Several groups have produced guidelines for the management of C. trachomatis and strategies for screening. A full list with web addresses is shown in Table 3. Common themes are that screening should be targeted at young, sexually active women (an age of 25 years is often used as a cut-off point). The use of NAATs is endorsed. Most authorities do not recommend a routine test of cure if the patient has been given and complied with appropriate treatment; however, some do [51]. The importance of partner notification and screening is highlighted. Many authorities suggest that women undergoing uterine instrumentation who have risk factors for C. trachomatis should either be tested before the procedure (and administered treatment if found to test positive) or should receive antibiotic prophylaxis.

Table 3.

Guidelines on management of C. trachomatis.

Organization	Issue	Date of guideline	Ref./web address
Health Protection Agency, UK	C. trachomatis managment	2004	www.hpa.org.uk/infections/topics_az/hiv_and_sti/stichlamydia/guidelines/guidelines.htm (Accessed October 2005)
Centers for Disease Control, USA	C. trachomatis testing	2002	www.cdc.gov/STD/LabGuidelines/default.htm (Accessed October 2005)
Centers for Disease Control, USA	C. trachomatis treatment	2002	www.cdc.gov/std/treatment/4–2002TG.htm# Chlamydia (Accessed October 2005)
British Association for Sexual Health	C. trachomatis management	2002	www.bashh.org/guidelines/2002/c4a_0901c.pdf (Accessed October 2005)
US Preventive Services Task Force	C. trachomatis screening	2001	[62]
Scottish Intercollegiate Guideline Network	C. trachomatis management	2000	www.sign.ac.uk/pdf/sign42.pdf (Accessed October 2005)
Chief Medical Officer's Expert Advisory Group, UK	C. trachomatis management	1998	http://crawl04.archive.org/ukgov/20030731072839/www.doh.gov.uk/pub/docs/doh/chlamyd.pdf (Accessed October 2005)

Treatment of C. trachomatis infection Antibiotics

Standard treatment regimens for C. trachomatis infection include 1 g azithromycin (Zithromax®) orally once and 100 mg doxycycline (Doxy®) twice daily for 7 days. Both are highly effective, with cure rates of 97 and 98%, respectively. A meta-analysis found no significant difference in cure rates and adverse effects between the two treatments [52]. Azithromycin is normally more expensive, although since it is a single-dose treatment it may have some advantages for patients. In pregnancy, doxycycline is not recommended, and erythromycin (E-mycin®) (500 mg four-times daily for 7 days) or amoxicillin (Amoxil®) (500 mg three-times daily for 7 days) are both appropriate treatments in this case [53]. Although azithromycin use in pregnancy is not recommended as first-line treatment by the manufacturer, the Center for Disease Control (CDC) guidelines indicate it may be used as an alternative agent in pregnancy.

Partner notification & treatment

An important and often neglected part of C. trachomatis infection management is that of partner notification and testing/treatment. If the partner is not treated and is infected, then women may become reinfected. Indeed, a recent study has demonstrated that expedited treatment of partners of individuals with C. trachomatis reduces the risk of persistent or recurrent infection in the index individual [54]. The optimum strategy for partner notification and treatment in C. trachomatis infection is still not clear. Some successes have been found with patient delivered partner treatment (PDPT) [55], although direct contact with healthcare providers or a choice between patient or provider referral has been found to work best with other sexually transmitted diseases [56]. If PDPT is to be widely adopted, its legal status needs to be addressed [55]. Ethically, there are concerns with respect to administering antibiotic drugs to individuals without a formal clinical consultation to ascertain allergies and coexisting disease and treatments. In addition, there are concerns about treating contacts of patients with a sexually transmitted infection (STI) without testing for other coinfections. This latter issue may not be a significant concern, since a recent study has shown that such coinfections are likely to be infrequent in partners of women with C. trachomatis [57]. Whatever the strategy adopted, most obstetricians and gynecologists are likely to find the expertise of GUM services invaluable in this context.

Prevention of C. trachomatis infection

Although the screening and treatment of C. trachomatis infection is important and the focus of much effort, prevention is the ideal method of infection control. Condom use (especially when correct and consistent) has been shown to play a major role in reducing infection, with ORs for infection of 0.1–0.4 in users versus nonusers [58,59].

Implications for the obstetrician & gynecologist

The obstetrician and gynecologist should consider opportunistic screening for C. trachomatis infection in asymptomatic, young, sexually active women. All women presenting with symptoms should be tested. Women who test positive for C. trachomatis should be counseled and treated with antibiotics. Partner notification and treatment should be undertaken, usually in collaboration with local GUM services. A first-void urine, vaginal swab or (in women requiring pelvic examination for other reasons) an endocervical swab are appropriate specimens for testing. Clinicians should be aware that NAATs are more sensitive than alternatives for the detection of C. trachomatis. Where antibiotic prophylaxis is administered to women undergoing uterine instrumentation, they should be effective against C. trachomatis infection for women at risk. Since C. trachomatis is implicated in the pathophysiology of PID, women presenting with this condition should be treated with antibiotics active against this organism, and testing and partner notification of C. trachomatis-positive women should be included in management protocols for this condition.

Future perspective

C. trachomatis is likely to remain an important cause of female reproductive morbidity for the foreseeable future. However, vaccines for C. trachomatis are being sought and may become available in due course [60,61]. Tests for C. trachomatis are likely to continue to improve, and although point-of-care tests for C. trachomatis are, at present, constrained by their lack of sensitivity, this situation is likely to improve. Healthcare providers will continue to roll out mass screening programmes for the detection of asymptomatic C. trachomatis infection in women and men [102], and it is hoped that these strategies will result in a decline in the prevalence of C. trachomatis infection.

Executive summary

Epidemiology

Chlamydia trachomatis is a common sexually transmitted infection of young (mainly < 25 years) men and women.

Mean prevalences in this age group attending obstetric and gynecologic clinic settings are 8–12%.

Clinical presentation

C. trachomatis is asymptomatic in 80% of women.

Consequences of C. trachomatis infection

Risk of pelvic inflammatory disease, ectopic pregnancy, infertility and (in pregnancy) preterm delivery.

Spontaneous resolution may occur.

Diagnosis

C. trachomatis infection can be diagnosed in a first-void urine sample or an endocervical or vaginal swab.

Nucleic acid amplification tests are the most sensitive.

Treatment

Antibiotics: either azithromycin or doxycycline or, in pregnant women, erythromycin or amoxicillin.

Partner notification and treatment is recommended to reduce the risk of reinfection.

Screening strategies

Opportunistic screening of young women is recommended to prevent adverse sequelae.

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Chlamydia in Gynecologic Practice

Abstract

Keywords

What is Chlamydia?

Clinical consequences of C. trachomatis

Symptoms

Spontaneous resolution

Ascending infection & pelvic inflammatory disease

Ectopic pregnancy

Infertility

Effects on mother & baby in pregnancy

Identifying C. trachomatis infection

Laboratory tests

Specimens for C. trachomatis testing

Prevalence of C. trachomatis

Secular trends

Risk factors for infection

Prevalence of C. trachomatis in obstetric & gynecologic clinic populations.

Prevalence of C. trachomatis in other clinic populations

Screening for C. trachomatis

Does screening for C. trachomatis improve health outcomes?

National guidelines & screening strategies

Treatment of C. trachomatis infection Antibiotics

Partner notification & treatment

Prevention of C. trachomatis infection

Implications for the obstetrician & gynecologist

Future perspective

References