Version May 2024
INTRODUCTION — Chlamydia trachomatis is a sexually transmitted gram-negative bacterium that causes infection worldwide. In the United States, it is the most commonly reported bacterial infection and a common cause of urethritis in males and cervicitis in females [1]. The largely asymptomatic reservoir of infections provides an ongoing source for efficient disease transmission and also allows for silent disease. C. trachomatis infection can result in scarring of the Fallopian tubes, ovaries, endometrial lining, and occasionally, the adjacent perineum, which increases the risk of future ectopic pregnancy and tubal infertility [2]. These consequences are the main reason that C. trachomatis is estimated to be the most costly nonviral sexually transmitted infection [3]. With this in mind, screening programs aimed at preventing pelvic inflammatory disease (PID) in females began in the late 1980s in the US, and were formally endorsed by the US Preventive Screening Task Force (USPSTF) and other major organization in the mid-1990s [4]. Other countries also have national chlamydia screening programs [5].
The epidemiology of C. trachomatis infection in adolescents and adults is discussed in this topic. The screening, clinical manifestations, diagnosis, and treatment of chlamydial infections in adolescents and adults are discussed in detail elsewhere. (See "Screening for sexually transmitted infections", section on 'Chlamydia and gonorrhea' and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections" and "Treatment of Chlamydia trachomatis infection".)
Lymphogranuloma venereum, endemic trachoma, and chlamydia infections in the newborn are discussed in detail elsewhere. (See "Lymphogranuloma venereum" and "Trachoma" and "Chlamydia trachomatis infections in the newborn".)
MICROBIOLOGY — C. trachomatis is a small gram-negative bacterium that is an obligate intracellular parasite. It has a distinct life-cycle consisting of two major phases:
●The small elementary bodies attach and penetrate into cells, changing into the metabolically active form, called the reticulate body, within six to eight hours. These forms create large inclusions within cells.
●The reticulate bodies then reorganize into small elementary bodies, and within two to three days the cell ruptures, releasing newly formed elementary bodies. Release of the elementary bodies initiates the replicative process, since this is the form that can infect new epithelial cells. The long growth cycle explains why treatment with agents with long half-lives or a prolonged course of antibiotics is necessary to eradicate infection. (See "Treatment of Chlamydia trachomatis infection".)
Chlamydia cannot be cultured on artificial media; tissue culture is required to grow the organism. Culture methods are now limited to research and reference laboratories in favor of more sensitive and practical diagnostic methods. (See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Diagnosis of chlamydial infections'.)
One critical feature of chlamydial organisms is that immunity to infection is not long-lived. As a result, reinfection or persistent infection is common.
TRANSMISSION — In most countries, C. trachomatis infections among adults and adolescents are virtually all sexually transmitted. The risk of transmitting C. trachomatis from an infected individual to an uninfected one has been difficult to establish.
In a study that included 290 heterosexual couples using a strand displacement assay to detect chlamydia infection, 76 percent of male partners of female cases and 77 percent of female partners of male cases also tested positive [6]. In a study of male-male couples, among the 30 males who had urethral chlamydia, 14 (47 percent) had a partner with rectal chlamydia, and among the 46 males with rectal chlamydia, 14 (30 percent) had a partner with urethral chlamydia [7] These findings suggest that transmission of chlamydia between the urethra and the rectum is less efficient than transmission between the urethra and cervix in heterosexual couples, and transmission from urethra to rectum is more efficient than vice versa.
Unfortunately, data on the likelihood of infection after a known exposure or rates of transmission from symptomatic versus asymptomatic persons are not available.
PREVALENCE AND INCIDENCE
United States
Incidence — C. trachomatis is the most commonly reported bacterial infection in the United States. In 2021, 1,644,416 chlamydial infections were reported to the Centers for Disease Control and Prevention (CDC), reflecting an incidence rate of 495.5 cases per 100,000 people [1], which represented an increase over the prior year. The rate of infection among females has remained much higher than that among males (629 versus 357 cases per 100,000 persons), probably because females are considerably more likely to be screened than males (figure 1).
Race, ethnicity, economic disadvantage, and geographic region also modify the likelihood of infection being detected [1,8,9]. As an example, the reported incidence among Black individuals in 2021 was five and seven times that among White individuals, for females and males, respectively [1]. In a separate analysis from 2015, American Indian or Alaska Native persons were estimated to have an incidence of chlamydia 3.8 times higher than the rate among White individuals in the United States [10].
Since the majority of urogenital C. trachomatis infections are asymptomatic, these rates undoubtedly underestimate the true burden of disease. Moreover, there has been considerable debate as to how much of the apparent increase in disease burden is related to enhanced screening efforts and whether there is a true increase in the incidence of infection.
Prevalence — Some features of chlamydia epidemiology have remained constant since surveillance was initiated in the US. Prevalence is consistently highest among young females and males (14 to 24 years of age) [1]. In one prospective study of 14,322 individuals between the ages of 18 and 26 years, the prevalence of chlamydia was 4.2 percent and, overall, was higher among females than males [11]. The highest prevalence rates were in African American females (14 percent). In a study of a sample of households in the US conducted from 2007 to 2012 as a part of the National Health and Nutrition Examination Survey (NHANES), the prevalence of chlamydia was 1.7 percent among participants ranging in age from 14 to 39 years; this corresponded to 1.8 million prevalent infections [12]. The overall prevalence in this study was slightly higher among females than males (2 versus 1.4 percent). Among sexually active females, the prevalence increased with decreasing age.
As with incidence, prevalence varies by race, ethnicity, economic disadvantage, and geographic region. Prevalence is also higher among incarcerated populations, military recruits, and patients receiving care at public sexually transmitted infection (STI) clinics [13].
Worldwide — Chlamydia is a common infection worldwide. In general, the age-specific prevalence described in the US, with younger individuals bearing the brunt of the disease, also appears evident in other countries, although systematically collected, nationally representative data are limited in lower resource countries. The World Health Organization (WHO) has estimated the global prevalence of several STIs among individuals aged 15 to 49 years based on data from regions that have good case-based surveillance systems as well as data from population-based studies [14]. In 2016, chlamydia prevalence was estimated to be 3.8 percent, and an estimated 127.2 million incident cases of chlamydia occurred worldwide. The degree to which improved diagnostics and increased availability of chlamydia diagnostics in resource-limited settings have influenced this reported increase is unknown.
However, in support of the general increasing global trend in genital chlamydia, population-based studies in certain regions also demonstrate a surprisingly high prevalence of C. trachomatis. In an observational study of almost 3500 individuals in China randomly selected by region to provide a nationally representative sampling, the estimated prevalence of C. trachomatis infection was 2.1 percent [15]. In a population-based screening study in the Netherlands, in which 21,000 males and females ages 15 to 29 years underwent home based urine testing, the prevalence of chlamydia was 2.6 percent in females and 2.0 percent in males [16].
One interesting feature of C. trachomatis global epidemiology is the so-called Swedish new variant, first reported in 2006 in Sweden [17]. This variant contained a mutation so that nucleic acid amplification testing (NAAT) used at the time of its emergence did not detect the microorganism. This diagnostic test failure allowed infections caused by this strain to go undiagnosed, leading to a nationwide network of related infections. Subsequent modification of testing protocols has resulted in a relatively lower proportion of chlamydial infections due to this strain, and it remains rarely reported beyond the Nordic countries.
Subsequently, newer mutations have allowed C. trachomatis specimens to be falsely negative in certain NAAT platforms in Finland, Sweden, Norway, Denmark, and England, raising the concern that mutations escaping detection are more common than previously realized [18-22].
Extragenital infections — Extragenital sites are not typically specified in surveillance studies of C. trachomatis in heterosexual populations, but may serve as reservoirs for ongoing transmission [23].
As an example, in a study of Kansas City, Missouri STI clinic attendees who reported exposure at extragenital sites, the prevalence of rectally detected C. trachomatis was 11.8 percent, and the prevalence of orally detected C. trachomatis was 2 percent amongst women who had sex with men; between 23 and 33 percent of chlamydia infections in women would have been missed if extragenital testing were not performed [24]. Younger age was a strong predictor of extragenital infections in women.
These data have not yet prompted recommendations to screen women at the rectal site [23]. (See 'Selective screening' below.)
COINFECTION WITH OTHER PATHOGENS — Co-infections with C. trachomatis and other urogenital sexually transmitted pathogens have frequently been reported among high-risk individuals. As an example, in a study of males with urethritis, 35 percent of those with C. trachomatis were also infected with Mycoplasma genitalium [25]. In certain high-risk populations, such as adolescents entering juvenile detention centers, reported rates of coinfection with C. trachomatis and Neisseria gonorrhoeae have been as high as 50 percent, but appear to be considerably lower in the general population [11,26,27]. Trichomoniasis is especially prevalent in sexually active females, and may also occur with C. trachomatis [28]. These findings highlight the importance of evaluation for other sexually transmitted infections, particularly N. gonorrhoeae in patients with known C. trachomatis infection. (See "Mycoplasma genitalium infection" and "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents", section on 'Diagnostic approach'.)
RISK OF INFECTION
General risk factors — In both females and males, general features that are consistently associated with a higher likelihood of C. trachomatis infection include the following [12]:
●Young age – Individuals less than 25 years of age tend to have the highest prevalence of chlamydia. Some experts believe that a decline in prevalence with age may be related to development of partial immunity through periodic repeated exposures, in addition to changes in behavior [29,30].
●Report of a new sex partner or more than one sex partner in the prior three months – These are not specific for C. trachomatis, but denote a risk for common sexually transmitted infections.
●History of previous C. trachomatis infection – This is a highly predictive factor for newly detected infection, probably because it identifies persons at high risk for reinfection from a previously untreated sex partner or from a new partner involved in the same sexual network as the original source partner [31]. (See 'Risk of repeat infection' below.)
●Inconsistent use of condoms – Although report of inconsistent condom use is often associated epidemiologically with increased likelihood of infection, the utility of this history to assess risk for the individual is limited.
History of a different sexually transmitted infection (STI), including HIV, is also associated with a higher risk of chlamydia. (See 'Risk of repeat infection' below.)
Socioeconomic and racial disparities also exist with chlamydia prevalence, with higher prevalences noted among certain ethnic populations, certain clinical settings, and among socioeconomically disadvantaged youth. (See 'Prevalence' above.)
In general, less is known about the risk factors for chlamydia in males than in females. There is a high prevalence of both genital and extragenital chlamydia among men who have sex with men (MSM) (see 'Risk in men who have sex with men' below). Other risk factors may be similar to those in females. In a population-based study from the Netherlands, infection in males was associated with young age, multiple sex partners, low/intermediate education status, and infrequent condom use [16]. In a population-based study from China, unprotected sex with a commercial sex worker was a significant risk factor for infection among males aged 20 to 44 years [15].
Risk of repeat infection — Several prospective studies and systematic reviews have documented high rates of repeat infection in the months after an initial chlamydial infection [32-36]. In a systematic review of 38 studies, the overall median proportion of females reinfected with chlamydia was 13.9 percent [35]. In a systematic review of eight studies, the median proportion of males reinfected with chlamydia was 11.3 percent [36].
In one rigorous study, participants with C. trachomatis infection underwent a test-of-cure approximately 30 days after antibiotic treatment in order to document successful therapy before returning at three months for repeat screening. In this way, repeat infection could be distinguished from treatment failure. In a study of 272 males aged 15 to 35 years, diagnosed with chlamydia, and subsequently followed for four months in three urban sites in the US (Baltimore, Denver, and San Francisco), repeat infection occurred in 13 percent (an estimated incidence of 45 infections per 100 person-years) [32]. Among 897 female adolescents diagnosed with an initial C. trachomatis infection at school-based health centers, 236 (26 percent) had one or more subsequent positive tests over the next year [33].
A prior history of any urogenital STI also appears to be associated with a risk of future C. trachomatis infection. An analysis of data on individuals who visited an STI clinic and participated in a counseling trial (Project RESPECT) estimated the incidence of repeat infection during the subsequent year [34]. Among 1236 females, 25.8 percent had one or more new infections (11.9 percent C. trachomatis, 6.3 percent N. gonorrhoeae, and 12.8 percent Trichomonas vaginalis), and among 1183 men, 14.7 percent had one or more new infections (9.4 percent acquired C. trachomatis and 7.1 percent N. gonorrhoeae).
Risk in men who have sex with men — There is a high incidence and prevalence of STIs, including C. trachomatis, among men who have sex with men (MSM). As an example, in 2021, approximately 17 percent of MSM evaluated at select STI clinics in the United States tested positive for C. trachomatis [1]. In a study of nearly 3000 MSM in Australia who were initiating pre-exposure prophylaxis for HIV, the incidence of new C. trachomatis infections (urogenital, rectal, and pharyngeal) was 45 cases per 100 person-years [37]. These figures reflect sampling of high-risk MSM populations. Furthermore, among such high-risk populations, there may be subgroups at especially high risk who account for much of the disease burden. In the Australian study, 25 percent of the study population accounted for 75 percent of all STIs diagnosed [37].
Some prevalence estimates underestimate the total burden of infection because they do not take into account rectal C. trachomatis infections, which are common among MSM, asymptomatic, and not frequently sought using recommended diagnostic tests [38,39]. In one study of nearly 22,000 MSM included in a United States national STI clinic surveillance network, only 46 percent were tested for rectal chlamydia infection, but 14 percent of those tested were positive [38]. Similarly, in another study of MSM screened for chlamydia at urethral, rectal, and pharyngeal sites, rectal infections accounted for 53 percent of chlamydial infections, and 86 percent of them were asymptomatic [39]. In both studies, the majority of males with rectal infections did not have concurrent urethral infection and thus would have been missed had urethral testing only been performed. In the first community-based (non-clinic-based) study of site-specific chlamydia prevalence in the United States, in which over 2000 MSM in five cities provided self-collected specimens for screening, rectal C. trachomatis infection was identified in 7 percent; oral C. trachomatis prevalence was 1.4 percent [40].
In addition to asymptomatic rectal infections, which are most commonly caused by C. trachomatis serovars D-K, lymphogranuloma venereum (LGV), caused by serovars L1, L2, and L3, can cause symptomatic proctitis in men who engage in receptive anal intercourse with other men. LGV-causing strains of C. trachomatis continue to cause discrete outbreaks of ulcerative proctitis in resource-rich countries [41-43]. LGV can also be asymptomatic. LGV is discussed in detail elsewhere. (See "Lymphogranuloma venereum".)
Risk in women who have sex with women — According to data reported by the 2017-2019 National Survey of Family Growth, 20.8 percent of women aged 18 to 49 years reported same sex behavior in their lifetime [44]. Few data inform the risk of sexually transmitted infections (STIs) in women who have sex with women (WSW). Transmission risk probably varies by the specific STI and sexual practice (eg, oral-genital sex; vaginal or anal sex using hands, fingers, or penetrative sex items; and oral-anal sex) [45,46]. Data indicate that C. trachomatis infection among WSW can occur [47-50]. Although the rate of transmission of C. trachomatis between women is unknown, infection also might be acquired from past or current male partners, as many WSW have previously had and continue to have sex with men [51]. Additionally, in some studies, a higher proportion of women who have sex with both women and men report high-risk sexual behavior, such as multiple lifetime and recent sexual partners and sex with injection drug users, compared with women who have sex with only men. Nevertheless, even women who have sex exclusively with women remain at risk for STIs, including C. trachomatis.
In a study of women aged 15 to 24 years attending family planning clinics in the US Pacific Northwest during 1997 through 2005, the rate of C. trachomatis infection was unexpectedly higher among those who reported same sex behavior compared with those who reported exclusively heterosexual behavior (7.1 versus 5.3 percent) [47]. Over the study period, women who have sex exclusively with women and reported risky sexual behavioral (new, multiple, or symptomatic sexual partners) had higher chlamydia rates than women who reported similar behavioral risks but have sex with only men or with both men and women. Possible explanations for these observations relate to differences in use of reproductive health care services (including chlamydia screening) by WSW, altered biological susceptibility to lower genital tract infection, infrequent use of barrier methods to prevent STI transmission with female partners, trends towards higher risk behaviors in WSW, and particular characteristics of their respective sexual networks.
Of note, there were also high chlamydia rates among American Indian and Native Alaskan WSW relative to other races, a finding that is consistent with racial/ethnic disparities among women in general. (See 'Prevalence' above.)
SELECTIVE SCREENING — Because only the minority of chlamydial infections present as syndromes, including cervicitis, urethritis, proctitis, or pelvic inflammatory disease (PID), screening of asymptomatic persons plays a critical role in detecting the majority of infections. Screening for chlamydia is discussed in detail elsewhere. (See "Screening for sexually transmitted infections", section on 'Chlamydia and gonorrhea'.)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Chlamydia and gonorrhea (The Basics)")
●Beyond the Basics topic (see "Patient education: Chlamydia (Beyond the Basics)")
SUMMARY
●Incidence and prevalence – Infection with C. trachomatis is common worldwide; in the US, it is the most frequently reported bacterial infection. Prevalence is consistently highest among young individuals (15 to 24 years of age) (figure 1). (See 'Prevalence and incidence' above.)
●Risk factors – Other important risk factors include sexual behavior (eg, a new sex partner or more than one sex partner in the prior three months), history of C. trachomatis infection or other sexually transmitted infection (STI), and inconsistent condom use. The risk of subsequent C. trachomatis infection is particularly high in the few months following a diagnosis of chlamydia or other STI. (See 'General risk factors' above and 'Risk of repeat infection' above.)
●Men who have sex with men – There is a high prevalence and incidence of chlamydia among men who have sex with men (MSM), including both urogenital and rectal infections. (See 'Risk in men who have sex with men' above.)
●Women who have sex with women – Women who have sex with exclusively women also remain at risk for chlamydia, particularly in the setting of a new, multiple, or symptomatic partners. (See 'Risk in women who have sex with women' above.)
●Importance of screening – Because only the minority of C. trachomatis infections present as syndromes, screening of asymptomatic persons plays a critical role in detecting the majority of infections. (See 'Selective screening' above and "Screening for sexually transmitted infections", section on 'Chlamydia and gonorrhea'.)
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