Catherine A. Miller
Mary-Ann B. Shafer
Genital infections caused by Chlamydia trachomatis represent the most prevalent bacterial sexually transmitted disease (STD) in the United States and the most frequently reported infectious disease. An estimated 3 million new cases occur annually, with most identified among patients younger than 25 years. Chlamydial infections and their sequelae have a large impact on health care expenditures, resulting in more than $2 billion in health care costs per year in the United States alone (Eng and Butler, 1997). Chlamydial infections pose a major public health threat because of associated harmful sequelae in females; the most serious of these include pelvic inflammatory disease (PID), ectopic pregnancy, and infertility.
The genus Chlamydia is divided into four species: Chlamydia psittaci, C. pecorum, C. pneumoniae, and C. trachomatis.
Developmental Cycle and Pathogenesis
which is 50% homologous to human HSP60. This homology could potentially cause cross-reactive immune responses with healthy human tissues and could help explain the apparent tissue immune-mediated destruction associated with C. trachomatis infections, such as the scarring of the fallopian tubes as a result of PID.
FIGURE 62.1 Life cycle of C. trachomatis. (Courtesy of California STD/HIV Prevention Training Center.)
Overall, national rates reported by the CDC in 2005 are as follows:
FIGURE 62.2 C. trachomatis—United States age- and sex-specific rates: Centers for Disease Control and Prevention, STD Surveillance, National Profile, 2005: http://www.cdc.gov/std/stats/natprointro.htm (Figure 7 in the CDC report.)
female-to-male transmission after multiple sexual encounters may actually be equivalent (Quinn et al., 1996).
The clinical manifestations of C. trachomatis are similar to those of Neisseria gonorrhoeae (Table 62.3). Both organisms preferentially infect columnar or transitional epithelium of the urethra, with extension to the epididymis; the endocervix, with extension to the endometrium, salpinx, and peritoneum; and the rectum. Both organisms can invade deeper tissue, causing extensive subepithelial inflammation, epithelial ulceration, scarring, and PID. PID is responsible for most of the acute illness and long-term economic cost related to chlamydial infections. Most infections caused by C. trachomatis are asymptomatic or have few or no symptoms, unlike N. gonorrhoeae infections. An estimated 70% to 90% of C. trachomatis endocervical infections have no symptoms (Brunham and Peeling, 1994).
Studies of infected male patients have historically been limited to those who were largely adult symptomatic clients attending STD clinics and who were diagnosed with nongonococcal urethritis (NGU). Complications other than urethritis, epididymitis, proctitis, and Reiter syndrome are unusual in males. However, there is some evidence, although still controversial, that C. trachomatis infection may affect male fertility (Eley et al., 2005).
Despite continued study, the role of C. trachomatis in causing nonbacterial prostatitis remains
controversial. Although definitive studies are lacking, C. trachomatis has been isolated from prostatic secretions and prostatic biopsies from some patients with prostatitis.
Most of the information about C. trachomatis and proctitis is derived from studies of homosexual men. Either the lymphogranuloma venereum (LGV) strains or the genital strains D through K are responsible for the development of proctitis. The LGV strains can produce a primary ulcerative proctitis and a histopathological picture of giant cell formation and granulomas similar to those seen in acute Crohn disease, whereas the non-LGV immunotypes produce more mild disease, from no symptoms present to rectal bleeding, diarrhea, and rectal discharge.
Pelvic Inflammatory Disease
See Chapter 63 on PID.
Perihepatitis (Fitz-Hugh-Curtis Syndrome)
This syndrome can occur in up to 25% of those individuals with PID and may be associated with chlamydial (70% of cases) and gonococcal salpingitis. Signs and symptoms include right-upper-quadrant pain and tenderness, fever, nausea, and vomiting. Women may also have signs of PID. Although usually related to STD infections in females, perihepatitis has been described in males in rare cases.
Pregnancy-Related Chlamydial Infections
Other Infections and Complications, Male and Female
Direct contact with infectious secretions during sexual activity or from autoinoculation can result in conjunctivitis. Of patients with urogenital infections, approximately 1% have a concurrent ophthalmologic
infection. Symptoms usually include unilateral eye discharge, hyperemia, and pain.
Rare cardiac complications include endocarditis (Dimmitt et al., 1985; Jones et al., 1982b) and myocarditis.
Reiter syndrome, or reactive arthritis, is a disease characterized by a prolonged immune response focused mainly on the skin and joints. The syndrome of conjunctivitis, dermatitis, urethritis, and arthritis occurs most frequently after a bacterial infection of the genital tract or gastrointestinal tract. The common organisms implicated in Reiter syndrome are C. trachomatis (post–genital tract infection), and Salmonella enteritidis and S. typhimurium in the postdysenteric form. Most individuals who develop Reiter syndrome are HLA-B27 positive and it occurs more commonly in males. C. trachomatis infection can also be associated with an arthritis or reactive tenosynovitis without the other characteristics of Reiter syndrome.
The differential diagnosis of a reproductive-related problem is dependent on the symptom complex of the patient (e.g., urethritis, cervicitis, epididymitis, or PID). The reader is also directed to the chapters in this book dealing with these individual problems.
Although most cases of C. trachomatis in female patients are asymptomatic, a common problem in those with chlamydial infection is MPC or urethritis, which can also be caused by the following:
The most common problem in males is urethritis, which can also be caused by the following:
In males presenting with symptoms of acute epididymitis or orchitis, it is important to consider the following in the differential diagnosis:
The introduction of NAATs for the diagnosis of C. trachomatis infections now provides readily available, highly sensitive, inexpensive, and noninvasive screening tests. In comparison to the former cell culture testing, which required cervical or urethral sampling, the newer testing technology allows noninvasive sampling of first-void urine and self-administered vaginal swabs to collect specimens. The focus for testing has broadened from testing symptomatic individuals to also screening at-risk asymptomatic individuals. The noninvasive testing is preferred by patients and also allows for testing in nontraditional, nonclinical sites, potentially leading to earlier detection and screening of populations not utilizing clinics.
Collection of Specimens
Correct specimen collection and handling are essential for all testing methods. As C. trachomatis is an obligate intracellular organism infecting columnar epithelium, the presence of columnar epithelial cells has been associated with increased sensitivity in most studies evaluating various screening tests. The preferred method of collection is dictated by the particular test manufacturer's directives.
If a pelvic examination is performed, the endocervix can be used as the site for specimen collection. Before
obtaining a specimen, a large swab should be used to remove secretions and discharge from the cervical os. After cleaning the cervix, the physician inserts a small swab approximately 1 cm into the os and rotates it several times to collect the specimen. All types of chlamydial testing techniques can be applied to the cervix.
This is the main site of infection in the male patient but is also a site of infection in females either alone or in conjunction with an endocervical infection. The urogenital swab should be gently inserted into the urethra, in males 2 to 3 cm and in females 1 to 2 cm. All types of C. trachomatis tests have been applied successfully to urethral specimens. Urethral swabs for chlamydial testing are being replaced by the noninvasive urine sampling.
Noninvasive urine-based testing is becoming widely used to screen adolescent males and females for chlamydial infection. To optimize the urine sample—first-void “dirty” sample (first 15–20 mL of micturition) should be used, and if possible, specimen collection should be delayed until more than 1 hour after prior urination.
The U.S. Food and Drug Administration (FDA) recently approved the transcription-mediated amplification assay for chlamydial testing of vaginal samples (Cook et al., 2005). Recent studies of other types of assays have also shown that results obtained with vaginal specimens are identical if not superior to the results obtained with cervical specimens. Vaginal swabs can be accurately self-collected by patients and do not require a pelvic examination.
For conjunctival samples, culture is preferred because of high sensitivity and specificity. Enzyme immunoassay (EIA), nucleic acid probe, and direct fluorescent antibody (DFA) tests are also FDA cleared for use with conjunctival specimens. Rectal specimens have not proved to be amenable to NAATs because of inhibitors present in rectal specimens. Culture isolation is acceptable for detecting C. trachomatis in rectal or pharyngeal swab specimens. DFA can also be performed on rectal or pharyngeal swab specimens.
It must be remembered that a lower prevalence rate, particularly less than 5%, increases the potential for a false-positive test result among the nonculture testing techniques. Testing technologies are summarized in Table 62.4.
The CDC recommends culture as one option for legal evidence collection in sexual assault cases (Centers for Disease Control and Prevention, 2006). See discussion regarding testing in sexual assault cases in subsequent section Testing after Sexual Assault.
Who Should Be Tested for Chlamydial Infection?
The approach recommended by the CDC and most professional health services and policy organizations (e.g., the American Academy of Pediatrics, the American Medical Association, Health Plan Employer Data and Information Set [HEDIS], American College of Obstetricians and Gynecologists, among others) is that all sexually active adolescent females aged 25 and younger should be screened for C. trachomatis at least once a year, with some calling for more frequent screening. National guidelines do not yet specify a screening recommendation for adolescent males, but screening programs for males are currently being explored, and are particularly useful in settings with high prevalence. In addition to the obvious teenage male or female who has genitourinary symptoms, adolescents on the street, in detention, who are paid for sex, who use intravenous drugs, who are pregnant, who are victims of sexual assault, who have chosen to have a therapeutic abortion, who have had prior STDs, who have new and multiple partners, and who do not use barrier contraception consistently should be considered for screening.
Testing after Sexual Assault
Testing for C. trachomatis, with culture or FDA-cleared NAATs, should be performed from specimens collected from any site of penetration or attempted penetration (Centers for Disease Control and Prevention, 2006). Testing should be repeated within 1 to 2 weeks of the assault unless prophylactic treatment was provided at the time of the initial testing.
Principles of Chlamydial Treatment
Treatment guidelines and recommendations were derived from the 2006 CDC guidelines. The following general principles can help guide the treatment of C. trachomatis in adolescents and young adults:
Definitive testing and subsequent appropriate disease-specific treatment should be the rule regarding chlamydial treatment. Empirical treatment is reserved for the following specific situations in the adolescent client:
partners, and unprotected sex) who are unlikely to return for follow-up evaluation.
Uncomplicated Urethral, Cervical, or Rectal Infection
Uncomplicated urethral, endocervical, or rectal infection in adults and adolescents should be treated with one of the following:
Alternative regimens are as follows:
The results of clinical trials indicate that azithromycin and doxycycline are equally efficacious (microbial cure rates of 97% and 98% respectively). However, azithromycin has the advantage of single-dose administration and the price is becoming competitive with other traditionally cheaper regimes. In addition, because of higher compliance with azithromycin it might be more cost-effective as it enables the provision of a single dose of directly observed therapy. Ofloxacin is also very effective but may be more expensive and should not be used during pregnancy. Nonpregnant adolescents who weigh >45 kg can be treated with adult doses of quinolones. Now that quinolones are not recommended for gonorrhea treatment, testing with culture or NAAT for gonorrhea is essential when treating Chlamydia. Erythromycin is less efficacious and has more gastrointestinal toxicity, but is inexpensive and can be used during pregnancy.
When taken as directed, azithromycin or alternative regimens are highly effective (>95%). If one of these regimens is used, posttreatment tests of cure are not recommended unless symptoms persist, reinfection is suspected, therapeutic compliance is in question, or the patient is pregnant. Posttreatment testing 3 weeks after completion of treatment should be considered if erythromycin is used. Retesting before 3 weeks after completion of therapy can lead to false-positive results. Patients with positive posttreatment test results should be re-treated with one of the preceding regimens, because resistant chlamydiae have not been described. Partners should also be re-treated.
Adolescents with chlamydial infections appear to be twice as likely to have a recurrent chlamydial infection as compared with young women. Because of the concern about increased tissue damage with increased numbers of infections in female patients, health care providers should consider advising all women with chlamydial infection to be screened for reinfection 3 to 4 months after treatment. Providers are also strongly encouraged to rescreen all women treated for chlamydial infection whenever they next present for care within the following 12 months.
All sex partners should be referred for evaluation and treatment. The exact time intervals for exposure have not been well evaluated. The CDC recommends that sex partners should be evaluated, tested, and treated if they had sexual contact with the patient during the 60 days preceding onset of symptoms in the patient or diagnosis of C. trachomatis. The most recent sex partner should be treated even if the time interval is more than 60 days. Sex partners of mothers with infected newborns should also be evaluated and treated.
Delivery of antibiotic therapy by heterosexual female or male patients to their partners might be an option if there is concern that partners will not seek evaluation and treatment. Written information for female partners regarding the importance of seeking evaluation for PID should be given with patient-delivered partner therapy. Because of the high risk for coexisting infections in males engaging in sex with males, patient-delivered partner therapy is not recommended in this patient population.
Patients should avoid sexual contact until they and their partners are treated and are assumed cured—7 days after completing single-dose treatment or following a 7-day antibiotic course.
Recommended Regimen During Pregnancy
Doxycycline, ofloxacin, levofloxacin, and erythromycin estolate are contraindicated during pregnancy. Three weeks after completion of therapy, repeat testing is recommended for all pregnant women.
Human Immunodeficiency Virus Infection
Adolescents with human immunodeficiency virus (HIV) and chlamydial infections should receive the same treatments listed for those without HIV infection.
Pelvic Inflammatory Disease
Because many cases of PID are caused by more than one organism, treatment regimens must include broad coverage. Evaluation and treatment of PID are discussed in detail inChapter 63.
Regimen of Choice
Bed rest and elevation of the scrotum are also recommended.
For acute epididymitis most likely caused by enteric organisms or for patients allergic to cephalosporins and/or tetracyclines:
These regimens are similar in HIV-infected teens. However, in immunocompromised adolescents fungal and mycobacterial causes are more common. Those teens who fail to respond within 3 days require close reevaluation of the diagnosis and therapy.
Sex partners should be examined for an STD and treated with a regimen effective against uncomplicated gonococcal and chlamydial infections. Both partners should avoid sexual contact until therapy is completed and both individuals are asymptomatic.
Behavioral changes include reduction of the number of sex partners, delaying age at first intercourse, and the use of condoms. C. trachomatis is often neglected in discussions of HIV risk and sexual behaviors. Information about C. trachomatis should be incorporated into educational materials and discussions regarding risk behaviors. Specific areas to cover include the following:
A high prevalence of C. trachomatis infection is found in women who have had chlamydial infection in the preceding several months. Most posttreatment infections result from reinfection, often occurring because patient's sex partners were not treated or because the patient resumed sex among a network of persons with a high prevalence of infection. Repeat infection confers an elevated risk of PID and other complications when compared with initial infection.
For Teenagers and Parents
http://www.cdc.gov/std/Chlamydia/STDFact-Chlamydia.htm. CDC fact sheet on chlamydia.
http://www.niaid.nih.gov/factsheets/stdclam.htm. National Institutes of Health (NIH) fact sheet on chlamydia.
http://www.plannedparenthood.org/sexual-health/std/chlamydia.htm. Planned Parenthood frequently asked questions sheet on chlamydia.
http://www.kidshealth.org/teen/infections/stds/std chlamydia.html. Teen health site information sheet on chlamydia.
http://www.4woman.gov/faq/stdchlam.htm. National Women's Health Information Center facts about Chlamydia.
http://www.youngwomenshealth.org/chlamydia.html. Health information for teens from the Center for Young Women's Health, Children's Hospital Boston.
For Health Professionals
http://www.emedicine.com/emerg/topic925.htm. E-medicine article on chlamydia.
http://www.cdc.gov/std/chlamydia/. CDC link to chlamydia facts, 2003 surveillance statistics, and treatment guide-lines.
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