The family Chlamydiaceae, obligate intracellular
bacteria, is comprised of four species:
C. trachomatis, C. pneumoniae, C. psittaci and
C. pecorum, which cause many types of diseases.
Species are divided according to host range,
biochemical, biologic, and molecular properties1.
C. trachomatis has 15 serovars which are divided
into the trachoma serotypes A-C, the occulo-
genital serovars D-K, and the lymphogranuloma
venerum (LGV) serovars L -L (Table1). The serovars can be distinguished by serological typing which uses monoclonal antibodies or by Species of Chlamydiae and the diseases with which Species
Sequelae or
Chronic Disease
C. trachomatis is the etiologic agent of a RB utilizies the host nutrient resources and wide variety of diseases. Trachoma is a sequela adenosine triphosphate (ATP) for its energy of ocular disease in developing countries and source to divide by binary fission within the continues to be a leading cause of preventable inclusion body of the infected cell. This blindness. Urogenital, ocular, and pneumonic phagosome resists fusion with host lysozymes, infections are caused by the serovars D-K. The thus allowing the chlamydia to evade destruction urogenital infections are sexually transmitted and by the host cell. In 48-72 hours, at the end of may be transmitted to infants born to infected the life cycle, the RBs condense back to EBs, the inclusion body and cell rupture to release neonatal pneumonia. C. pneumoniae, exclusively new infective EBs, and the life cycles continues.
a human pathogen thus far, has been associatedwith respiratory diseases, including pneumonia.
Epidemiology and Diseases
Antibody prevalence studies demonstrate that it There is a heavy burden of disease for society is highly prevalent in man, with approximately due to chlamydial diseases world wide. It is 50% or more of adults having antibodies to the estimated that there are 7 million cases of organism. It has recently been associated with blindness worldwide due to scarring from trachoma with as many as 500 million active C. psittaci is the cause of psittacosis in cases of trachoma.1 The remainder of this psittacine and nonpsittacine birds, including report focuses on urogenital infections and parrots, canaries, turkeys, pigeons, and ducks, as their sequelae caused by C. trachomatis.
well as in other animals such as cats, cattle, and C. trachomatis infections are among the most sheep. Man can be an accidental host, infected common sexually transmitted diseases among through aerosolized droplet transmission to the young adults and adolescents.3, 4 More than 50 respiratory tract from infected birds or animals, million cases occur worldwide and approximately 4 million cases occur in the United States, C. pecorum, a recently described species, is annually.3, 4 Chlamydia infections are associated a pathogen of ruminants, but has never been with many clinical syndromes ranging from cervicitis, salpingitis, acute urethral syndrome,endometritis, ectopic pregnancy, infertility, and pelvic inflammatory disease (PID) in the female; Chlamydiae have an unusual intracellular life conjunctivitis and pneumonia in infants born to cycle compromised of two unique forms, the infected mothers; and urethritis, proctitis, and elementary body (EB), which is infectious but not epididymitis in the male.5-7 Because of the metabolically active, and the reticulate body (RB), seriousness of the sequelae of infections, women which is noninfectious but is metabolically active.
bear the most morbidity of chlamydia infections.
After the intracellular EB becomes an RB, the Untreated chlamydia infections lead to PID and multiple episodes of PID can lead to tubal factor RECOMMENDED REGIMENS
infertility.8-11 Unfortunately, symptoms of genitalinfection are often completely absent or very Azithromycin 1 gram orally in a single dose
mild among infected patients, especially women, creating a large reservoir of infected persons who Doxycycline 100 mg orally twice a day for 7 days
continue transmission to new sexual partners.12 s
Chlamydial infections occur primarily among young sexually active persons. Prevalence rates Erythromycin base 500 mg orally 4 times a day
geographical areas, and may range from 5-20% Erythromycin ethylsuccinate 800 mg orally 4 times
in various groups of young adults.7, 13 Because symptoms are absent in most infected individuals, these prevalences may be severely underesti- Ofloxacin 300 mg orally twice a day for 7 days
mated. Thus, widespread screening of individualsat greatest risk (e.g., those individuals who areyoung, sexually active, and have new or multiple Impact on Society
In many societies, especially in the developing world, infertility, which may result from untreatedchlamydia infections, poses a severe psychological For uncomplicated genital infections, such as burden upon women who may be stigmatized by mucopurulent cervicitis in women and urethritis their community or shunned by their husbands.
or nongonococcal urethritis in men, caused by Untreated or undiagnosed ectopic pregnancies C. trachomatis, doxycycline has been the most widely used antichlamydial therapy in previous The serious complications and sequelae of years. However, single dose azithromycin is now untreated chlamydia infections also pose a highly recommended because of its excellent significant economic burden on health care costs.
tissue penetration, its long half life of 5-7 days, Approximately one million cases of symptomatic and lack of concern of compliance.14 Treatment PID are diagnosed annually in the United States, should begin as soon as possible after diagnosis.
leading to 100,000 surgeries and over 275,000 For more persistent infections and complications hospitalizations a year.15, 16 The annual estimated such as pelvic inflammatory infection, the reader cost associated with the sequelae of ectopic is referred to the new Centers for Disease Control pregnancy and infertility may exceed five billion and Prevention’s 1998 Guidelines for the Treatment of Sexually Transmitted Diseases publication.14 Cost-effectiveness studies, utilizing computer Patients should be encouraged to refer their sex modeling and decision tree analyses, have partners for evaluation, testing, and treatment.14 recently been reported, which indicate that it is DNA amplified technology that culture may have more cost-effective to screen and treat infected a sensitivity ranging from 50-85%, depending women than for society to bear the financial burden imposed later due to the medical costs associated with the sequelae diseases such as Because older non-culture tests, such as DFA pelvic inflammatory disease, ectopic pregnancy, and EIA, were traditionally compared to culture as a gold standard, the sensitivities reported inthe older literature can no longer be viewed asaccurate. A recent meta-analysis which adjusted Diagnostic Tools for Detection
the sensitivities of such assays based on a of Chlamydia Infections
sensitivity of culture of 85% has been reported.48 Previously, detection of chlamydia has been Table 2 shows a comparison of the sensitivities accomplished either by 1) staining of chlamydial
and specificities of diagnostic assays available inclusions grown in tissue culture cells,20 2) direct
for the detection of C. trachomatis in clinical examination of patient clinical specimens for the detection of elementary bodies using monoclonalantibodies or direct fluorescent antibody (DFA) staining,21-23 3) antigen detection in enzyme
immunoassay (EIA)24-27 or 4) nucleic acid probe
Sensitivity and specificity of diagnostic tests for the detection of C. trachomatis* hybridization.28-30 Now, new molecular technologies are available that amplify the DNA Diagnostic Method
of chlamydia in clinical specimens,31-47 which offer greatly expanded sensitivities of detection, while maintaining high specificity. Although serological tests for diagnosis of chlamydia infections, such as complement fixation or microimmunofluorescence, are still used for diagnosis of C. psittaci and C. pneumoniae, they are not useful for the diagnosis of C. trachomatis.
epidemiological surveys to associate previous C. trachomatis infection with infertility or Whereas culture was previously thought to be the gold standard for the detection of chlamydia *Sensitivities and specificities adapted from a modified meta-analysis in clinical specimens, it can now be shown of published papers, reference #48 (Howell, M.R. et al. Sex. because of the expanded sensitivity capability of New Specimen Types Available
these include: schools, prisons, military reception for the Detection of C. trachomatis
stations, health vans, shopping malls, and even New nucleic acid (DNA or RNA) amplification technology is so powerful that fewer than 10 elementary bodies can be detected in clinical Screening Strategies
specimens and theoretically even one can serve There is recent evidence that screening and as a target for amplification. Because of this treatment can prevent the sequelae of pelvic improved sensitivity of detection, alternative inflammatory disease (PID) often associated specimen types have been found to be useful with undiagnosed chlamydia infections. In a for chlamydia diagnosis. First-void urine from prospective clinical trial conducted within a large health maintenance organization, the group of amplification tests with great accuracy. Because urines are easily obtained, non-invasive treatment for chlamydia infections developed specimens, they offer a great advantage for 60% fewer cases of PID within a one year large public health screening programs, where follow-up period than did those women who there is no opportunity to obtain a cervical or were control subjects and were not offered urethral specimen. Additionally, urine specimens are highly acceptable to individuals who may be asymptomatic and who are unwilling to submit to chlamydia screening programs have been in a medical examination. Because a clinician is not effect for a number of years, such as the Pacific required for urine collection, cost savings are also Northwest and Wisconsin, for example, the rates generated when screening large numbers of for chlamydia prevalence in the Centers for Disease Control and Prevention supported clinics have steadily declined from prevalences of about shown to be both sensitive and specific for the 13% to less than 5%. In Scandanavian countries, detection of chlamydia when amplified tests are which have had chlamydia control programs in used and which has high acceptability by the place for many years, rates are below 3%.
female patient is a self-administered vaginal or In choosing target populations for chlamydia screening programs, public health clinicians will Although sexually transmitted disease clinics want to concentrate on populations which have and family planning clinics have been the source the most disease and are at most risk for the of specimens for chlamydia screening programs, development of sequelae. These populations usefulness of alternative specimen types has are mostly the young, sexually active females.
made alternative sites for screening programs Adolescents in schools and those young women attractive to public health officials. Some of who attend prenatal and family planning clinics are especially important to include in addition to screening program or because an examination is the more traditional sexually transmitted disease not indicated, clinicians should take advantage of clinics. Underserved populations such as youth the ease of obtaining a urine specimen or even a in detention centers, prostitutes, and homeless self-administered vaginal swab for amplification persons in shelters are important populations for testing. For male patients, the urine specimen is screening also. Treatment of partners to prevent usually always the choice of specimen for testing reinfection of patients is an important issue and for chlamydia with an amplification assay. DNA can be easily addressed with the use of urine amplification tests should not be used for test of cure assays until 3 weeks after therapy because residual DNA from cells rendered non-infective amplification-based screening technology is the by antibiotics may give a positive test when the ability to use the same specimen for the same type of diagnostic assay for other sexually One study which examined incidence rates in transmitted diseases such as gonorrhea. Many adolescents has shown that the young may get studies have shown that coinfection with both reinfected with chlamydia as frequently as every chlamydia and N. gonorrhoeae are common in 6 months on average.55 Studies have also shown sexually active individuals and more evidence is that individuals who practice high risk sexual behaviors, such as new or multiple sex partners infections are more common than previously or who do not use condoms, are at greater risk for chlamydia infections.19, 56-58 Therefore, asymptomatic patients who meet any of these Choice of Diagnostic Test and
criteria should be screened every time they are incontact with a health care facility or screening Specimen for Screening
situation with the use of a non-invasive Even though molecular amplification assays are generally more expensive than older non-culturetests such as DFA, EIA, and probe assays, cost effectiveness assays, which are done from a societal perspective, have been shown to be Clinicians now have a new type of test for thedetection of chlamydial infections which is a new more cost-effective.48 If a female patient has gold standard that is more sensitive for the urogenital symptoms or if a pelvic examination is detection of chlamydia than culture and other being performed on a patient, clinicians should non-culture tests. The nucleic acid amplification obtain a cervical swab for a nucleic acid amplified tests, which amplify chlamydial DNA or RNA in a test, because cervical swabs have the highest clinical specimen, are so powerful that they can sensitivity. If a patient or individual is not be also used with urine specimens and even receiving a pelvic examination, such as in a self-administered vaginal swabs. The use of such tests offers clinicians and public health officials a 8. Westrom LV. Sexually transmitted diseases cost-effective way to control a highly prevalent disease which causes serious morbidity and a 9. Westrom L. Effect of pelvic inflammatory References
Peeling RW, Brunham RC. Chlamydiae as 10. Hillis SD, Joesoef R, Marchbanks PA, Delayed care of pelvic inflammatory disease as a risk factor impaired fertility. Am J Obstet Gaydos CA, Quinn TC, et al. Isolation of Chlamydia pneumoniae from the coronary 11. Hillis SD, Wasserheit JN. Screening for Chlamydia a key to the prevention of pelvic inflammatory disease. N Engl J Med 1996; 3. Centers for Disease Control and Prevention. 12. Quinn TC, Gaydos C, Shepherd M, Bobo L, Hook III EW, Viscidi R, et al. Epidemiologic management of Chlamydia trachomatis and microbiologic correlates of Chlamydia trachomatis infection in sexual partnerships. JAMA 1996; 276:1737-1742.
4. Quinn TC, Cates W. Epidemiology of sexually transmitted diseases in the 1990’s. In: Quinn 13. Stamm WE. Diagnosis of Chlamydia trachomatis genitourinary infections. Ann 14. Centers for Disease Control and Prevention.
1998 guidelines for treatment of sexually transmitted diseases, pelvic inflammatory disease, and infertility: an epidemiologic update. Epidemiol Rev 1990; 12:199-220.
15. Centers for Disease Control. Policy guidelines 6. Gaydos CA. Chlamydia trachomatis infections. Resid Staff Phys 1993; 17-22.
pelvic inflammatory disease (PID). MMWR 1991; 40 (RR-5):1-25.
7. Stamm WE, Holmes KK. Chlamydia trachomatis infections of the adult. In: 16. Cates JW, Rolfs RT, Aral SO. Sexually Holmes KK, Mardh PA, Sparling PF, Wiesner transmitted diseases, pelvic inflammatory PJ, editors. Sexually Transmitted Diseases. disease, and infertility: an epidemiologic New York, NY: McGraw-Hill Co, 1990:181-193.
update. Epidemiol Rev 1990; 12:199-220.
17. Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE. Pelvic inflammatory disease and fertility: a cohort study of 1,844 women 24. Clark A, Stamm WE, Gaydos C, Welsh L, with laparoscopically verified disease and Quinn TC, Schachter J, et al. Multicenter 657 control women with normal laparoscopic evaluation of the antigEnz chlamydia enzyme results. Sex Transmit Dis 1992; 19:185-192.
immunoassay for diagnosis of Chlamydia 18. Howell MR, Quinn TC, Gaydos CA. Screening trachomatis genital infection. J Clin for Chlamydia trachomatis in asymptomatic women attending family planning clinics: 25. Gaydos C, Reichart C, Long J, Welsh L, Neumann T, Hook EW, et al. Evaluation of preventive strategies. Ann Intern Med 1998; Chlamydia trachomatis in genital specimens.
19. Marrazzo JM, Celum CL, Hillis SD, Fine D, J Clin Microbiol 1990; 28:1541-1544.
DeLisle S, Handsfield HH. Performance and 26. Sanders JW, Hook EW, Welsh LE, Shepherd cost-effectiveness of selective screening criteria for Chlamydia trachomatis infection immunoassay for detection of Chlamydia trachomatis in urine of asymptomatic men. chlamydia control strategy. Sex Transmit Dis 27. Chan EL, Brandt K, Horsman GG. A 1-year 20. Centers for Disease Control. Laboratory evaluation of Syva MicroTrak Chlamydia Update: Isolation of Chlamydia trachomatis confirmation by direct fluorescent-antibody assay in a high-volume laboratory. J Clin 21. Taylor HR, Agarwala N, Johnson SL.
Detection of experimental Chlamydia 28. Clarke LM, Sierra MF, Daidone BJ, Lopez N, trachomatis eye infections in conjunctival fluorescein-conjugated monoclonal antibody. and Gen-Probe PACE 2 with cell culture for diagnosis of cervical Chlamydia trachomatis 22. Uyeda CT, Welborn P, Ellison-Birang N, Shunk K, Tsaouse B. Rapid diagnosis of chlamydial infections with the MicroTrak direct test. 29. Warren R, Dwyer B, Plackett M, Pettit K, Rizvi 23. Lidner LE, Geerling S, Nettum JA, Miller SL, Altman KH, Wechter SR. Identification of detection assays for Chlamydia trachomatis. J Clin Microbiol 1993; 31:1663-1666.
immunofluorescence: technique, sensitivity, 30. Stary A, Teodorowicz L, Horting-Muller I, Chlamydia trachomatis in urogenital samples. Sex Transmit Dis 1994; 21:26-30.
31. Jaschek G, Gaydos C, Welsh L, Quinn TC. reaction assays for detecting Chlamydia Direct detection of Chlamydia trachomatis trachomatis nucleic acids. J Clin Microbiol 38. Bass CA, Jungkind Dl, Silverman NS, Bondi JM. Clinical evaluation of a new polymerase J Clin Microbiol 1993; 31:1209-1212.
32. Bobo L, Coutlee F, Yolken RH, Quinn T, Chlamydia trachomatis in endocervical Viscidi RP. Diagnosis of Chlamydia trachomatis cervical infection by detection of amplified DNA with an enzyme immunoassay. 39. Quinn TC, Welsh L, Lentz A, Crotchfelt K, J Clin Microbiol 1990; 28:1968-1973.
Zenilman J, Newhall J, et al. Diagnosis by Amplicor PCR for Chlamydia trachomatis Detection and differentiation of Chlamydia infection in urine samples from women and trachomatis, C. psittaci, and C. pneumoniae men attending sexually transmitted disease by DNA amplification. J Infect Dis 1990; clinics. J Clin Microbiol 1996; 34:1401-1406.
40. Dille BJ, Butzen CC, Birkenmeyer LG. 34. Loeffelholz MD, Lewinski CA, Silver SR, Amplification of Chlamydia trachomatis DNA Purohit AP, Herman SA, Buonagurio DA, et by ligase chain reaction. J Clin Microbiol al. Detection of Chlamydia trachomatis in endocervical specimens by polymerase chain 41. Gaydos CA, Jang D, Welsh LE, Pare B, Chernesky MA, Sellors J, et al. Ligase chain reaction (LCR): a novel DNA amplification 35. Bauwens JE, Clark AM, Loeffelholz MJ, technique for Chlamydia trachomatis (CT) in Chlamydia trachomatis urethritis in men by 42. Schachter J, Stamm WE, Quinn TC, Andrews first-catch urine. J Clin Microbiol 1993; reaction to detect Chlamydia trachomatis infection of the cervix. J Clin Microbiol 1994; Diagnosis of Chlamydia trachomatis 43. Chernesky MA, Lee H, Schachter J, Burczak genitourinary Chlamydia trachomatis infections by using the ligase chain reaction diagnosis of Chlamydia trachomatis urethral on patient-obtained vaginal swabs. J Clin infection in symptomatic and asymptomatic men by testing first void urine in a ligase 50. Stary A, Chouieri B, Lee H. Implications of sensitive molecular diagnosis of Chlamydia trachomatis in non-invasive sample types. 44. Chernesky MA, Jang D, Lee H, Burczak JD, Eleventh Meet. Internat. Soc.STD Research Chlamydia trachomatis infections in men 51. Scholes D, Stergachis A, Heidrich FE, Andrilla and women by testing first-void urine by ligase chain reaction. J Clin Microbiol 1994; pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med 45. Bassiri M, Hu HY, Domeika MA, Burczak J, Svensson LO, Lee HH, et al. Detection of 52. Burstein G, Waterfield G, Joffe A, Zenilman J, Chlamydia trachomatis in urine specimens from women by ligase chain reaction. J Clin amplification in adolescents attending middle Burczak JD, Andrews WW, Muldoon S, et al. Diagnosis of Chlamydia trachomatis 53. Gaydos CA, Crotchfelt KA, Howell MR, genitourinary infection in women by ligase Kralian S, Hauptman P, Quinn TC. Molecular chain reaction assay of urine. Lancet 1995; amplification assays to detect chlamydial 47. Gaydos CA, Ngeow YF, Lee HH, Canavaggio school female students and to monitor the M, Welsh L, Johanson J, et al. Urine as a persistence of chlamydial DNA after therapy. diagnostic specimen for the detection of Chlamydia trachomatis in Malaysia by ligase 54. Workowski KA, Lampe MF, Wong KG, Watts Chlamydia trachomatis genital infection after 48. Howell MR, Quinn TC, Brathwaite W, Gaydos CA. Screening women for Chlamydia trachomatis in family planning clinics: the 55. Burstein G, Gaydos CA, Diener-West M, Howell MR, Zenilman J, Quinn TC. Incident assays. Sex Transmit Dis 1998; 25:108-117.
Chlamydia trachomatis infections among 49. Hook III EW, Smith K, Mullen C, Stephens J, inner-city adolescent females. JAMA 1998; Rinehart L, Pate M, Lee HH. Diagnosis of 56. Marrazzo JM, White CL, Krekeler B, Celum CL, Lafferty WE, Stamm WE, et al. Community-based urine screening for Chlamydia trachomatis with a ligase chain reaction assay. Ann Intern Med 1997; 127:796-803.
Halloran EM. Predictors of Chlamydia trachomatis infection among female adolescents: A longitudinal analysis. Am J Epidemiol 1996; 144:997-1003.
58. Mosure DJ, Berman S, Fine D, DeLisle S, Cates W, Boring III JR. Genital Chlamydia infections in sexually active female adolescents: Do we really need to screen everyone? J Adol Health Care 1997; 20:6-13.
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