Adolescent Health Care: A Practical Guide

Chapter 62

Chlamydia Trachomatis

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.

Etiology

The genus Chlamydia is divided into four species: Chlamydia psittaci, C. pecorum, C. pneumoniae, and C. trachomatis.

1. C. psittaciis responsible for zoonosis and psittacosis, an infection contracted by humans from infected birds, and characterized by interstitial pneumonitis.
2. C. pecorumaffects domestic animals.
3. C. pneumoniaecauses pneumonia, pharyngitis, and bronchitis and most recently has been associated with possible etiological factors in coronary artery disease. Epidemiological studies have revealed that C. pneumoniae is a relatively common cause of infection in school-aged children, and it is probably the most common cause of community-acquired pneumonia in this age-group.
4. C. trachomatisis associated with a spectrum of diseases. This species contains 18 serologically distinct variants known as serovars. Chlamydial genital disease and neonatal disease (pneumonia and conjunctivitis) are caused by serovars B, D, E, F, G, H, I, J, and K. Table 62.1 outlines the major serovars of C. trachomatis. This chapter focuses on nonlymphogranuloma venereum (non-LGV), non–trachoma-causing serovars of C. trachomatis.

Developmental Cycle and Pathogenesis

1. Developmental cycle (Fig. 62.1):
2. C. trachomatisexhibits a unique developmental cycle lasting between 48 and 72 hours.
3. The cycle is characterized by transformation between two morphologically distinct infectious and reproductive forms (Schachter, 1999).
4. The extracellular infectious form, the elementary body, attaches to a susceptible epithelial cell and is ingested.
5. Susceptible host cells seem to have a specific receptor that facilitates attachment to C. trachomatisand facilitates its ingestion. The trachoma serovars responsible for human genital infections may have a very specific attachment site, which may help explain its restricted host range.
6. Once within an endocytotic vesicle, the elementary body reorganizes into the replicating form, the reticulate body. As the reticulate body divides, it fills the endosome with its progeny.
7. After 48 hours, multiplication ceases and the reticulate bodies transform to new infectious elementary bodies. The elementary bodies are then released from the cell by cytolysis or by a process of extrusion of the entire inclusion, which often results in the destruction of the host cell.
8. Affinity for columnar epithelium: Of particular importance to the young female adolescent, C. trachomatishas a predilection for columnar epithelium commonly found in the cervix of young women. This tissue involutes into the endocervical canal with age.
9. Immune response: The signs and symptoms associated with infection are mainly secondary to tissue destruction and the body's immunopathogenic response to the infection.
10. Major outer membrane protein (MOMP): A very important component in the immune response is the presence of this C. trachomatismembrane protein that can induce both a neutralizing antibody and a T-cell mediated immune response. Antibody to MOMP neutralizes chlamydial infectivity both in cellular and animal models. However, the MOMP gene appears capable of frequently developing variants and this mechanism may serve as a type of escape from the neutralizing antibodies mounted by the host. The ability of these polymorphisms to actually protect C. trachomatis from inactivation by the host is not known but would have an important impact on the design and development of future potential vaccines.
11. Heat shock protein: Another important protein is the C. trachomatisheat shock protein (cHSP60),

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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.

TABLE 62.1 Serovars of C. trachomatis

Species Serovar Disease C. trachomatis L1, L2, L3 Lymphogranuloma venereum C. trachomatis A, B, Ba, C Hyperendemic blinding trachoma C. trachomatis D, E, F, G, H, I, J, K Inclusion conjunctivitis, nongonococcal urethritis, cervicitis, proctitis, salpingitis, epididymitis, pneumonia of newborns

FIGURE 62.1 Life cycle of C. trachomatis. (Courtesy of California STD/HIV Prevention Training Center.)

Epidemiology

2005. trachomatisis the most common reported bacterial STD in the United States, with more than 900,000 infections reported to the Centers for Disease Control and Prevention (CDC) in 2005. Because many C. trachomatisinfections are asymptomatic and go undiagnosed, it is estimated that the actual infection rate may be approximately 3 times the reported number, which translates into approximately 3 million Americans infected with chlamydia annually (Centers for Disease Control and Prevention, 2004). Adolescent females ages 15 to 19 had the highest rates of reported C. trachomatis infection in 2004. In men, although rates are much lower than in women, the highest rates were among 20- to 24 year-olds (see Fig. 62.2 for age- and sex-specific rates). Increased testing in females may help explain their higher infection rates. Prevalence rates of C. trachomatis among select adolescent populations are reviewed in Table 62.2.

Overall, national rates reported by the CDC in 2005 are as follows:

1. From 50 states and the District of Columbia, 976,445 C. trachomatisinfections were reported to CDC during 2005

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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.)

2. Overall rate in the United States (2005): 332.5 cases per 100,000 population, an increase of 5.1% since 2004.
3. 496.5 per 100,000 women
4. 161.5 per 100,000 men
5. 2,796.6 per 100,000 females aged 15 to 19 years
6. 505.2 per 100,000 males aged 15 to 19 years
7. 1,247 per 100,000 African Americans, more than eight times higher than the rate among whites (152.1 per 100,000)
8. Median chlamydia test positivity was 6.3% (3.2%–16.3%) in women aged 15 to 24 years screened during visits to selected family planning clinics in all states and outlying areas in 2004.
9. National household sample prevalence: A national household sample was reported in 2004 of more than 14,000 young adults aged 18 to 26 (Miller et al., 2004). The overall prevalence was 4.19% with the following rates by gender and race:

Race Males Females African-American 11.1% 13.95% Latino 7.24% 4.42% White 1.38% 2.52% Asian-American 1.14% 3.31%

5. There was only a small difference in rates based on age with the highest percentage in those aged 20 to 21 (4.7%). In addition, the highest prevalence was in the South (5.4%) versus the Midwest (3.95%), West (3.2%), and Northeast (2.4%). In this sample 0.3% had both chlamydia and gonorrhea infections, with 70% of those with gonorrhea also having chlamydia and 8% of those with chlamydia also having gonorrhea.
6. Since 1996, there has been a 57% increase in chlamydia positivity from 4.9% to 7.7% among women aged 15 to 24 years in the family planning clinics screening programs in Health and Human Services Region X.
7. The overall trend in the 15- to 19-year-old age-group has been an increase in the chlamydia infection rates from 1,318.6 per 100,000 in 2000 to 1621.0 per 100,000 in 2005. A contributing factor in this overall 16% increase in positivity may be the expansion of screening programs to populations with higher prevalence of disease in some regions.
8. The Midwest had the overall highest infection rates in 2002 to 2005. The Northeast had the lowest infection rates.

Risk Factors

1. trachomatisinfection is associated with a number of factors including younger age, presence of cervical ectopy, female gender, prior history of STDs, new sexual partner, multiple sexual partners, living in a community with a high background prevalence, oral contraceptive use, douching, nonwhite race/ethnicity (African-American predominance), unmarried, and young age at sexual debut (Burstein et al., 2001; Williams et al., 2003; Berman and Hein, 1999; Boyer et al., 1999; Baeten et al., 2001; Scholes et al., 1998; Marrazzo et al., 1997; Orr et al., 1994; Stamm, 1999a, b).

Transmission

1. C. trachomatiscan be transmitted during vaginal, anal, or oral sex. An infected mother can also pass infection to her baby during vaginal childbirth.
2. Sixty percent to 75% of females with male sex partners who have C. trachomatisurethritis test positive for C. trachomatis infection (Lycke et al., 1980; Quinn et al., 1996).
3. Twenty-five percent to 50% of male sex partners of females with a mucopurulent cervicitis (MPC) or PID test positive for C. trachomatisinfection.
4. Male to female transmission may be more efficient. Reasons may include increased pathogen contact time in females and more efficient infection of the female endocervix compared to the male urethra (Bolan et al., 1999).
5. However, transmission data among partnerships using the newer nucleic acid amplification technology (NAATs) suggest that the male-to-female and

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female-to-male transmission after multiple sexual encounters may actually be equivalent (Quinn et al., 1996).

6. Recent data suggest that correct and consistent condom use is protective against C. trachomatistransmission (Paz-Bailey et al., 2005; Sayegh et al., 2005).

TABLE 62.2 Adolescent C. trachomatis Prevalence Rates by Population and Type of Testing

Population Test CT (+) Rate (%) n/N Author Year CT, Chlamydia trachomatis; LCR, ligase chain reaction; PCR, polymerase chain reaction; STD, sexually transmitted disease; EIA, enzyme immunoassay; SDA, strand displacement amplification. FEMALES a. Teen detention, school, and community clinics LCR urine 8.5 424/4,968 Marrazzo et al. 1997 b. Teen clinic PCR urine 14.9 47/315 Oh et al. 1997 c. Teen clinic PCR cervix 20.7 86/415 Beck-Sague et al. 1998 d. School-based clinic PCR cervix LCR urine 15.7 64/408 Gaydos et al. 1998 e. STD, family planning, school-based clinic PCR urine PCR cervix 24 771/3,202 Burstein et al. 1998 f. Detention clinic LCR urine 28.3 13/46 Oh et al. 1998 g. Army recruits LCR urine 9.2 1,215/13,204 Gaydos et al. 1998 h. Community outreach clinic LCR urine 12.9 8/62 Rietmeijer et al. 1998 i. Teen clinic PCR cervix 27 70/260 Bunnell et al. 1999 j. School-based clinic LCR urine 11.5 286/2,497 Cohen et al. 1999 k. Emergency department LCR urine 9.9 (females and males) 28/282 Embling et al. 2000 l. Marine recruits LCR cervix, urine, vagina 11 193/1,756 Shafer et al. 2000 m. National job training program EIA probe urine 9.2 413/4,488 Lifson et al. 2001 n. High school–based clinic LCR urine 3.9 11/283 Kent et al. 2002 o. Health maintenance organization SDA urine 5.8 23/393 Shafer et al. 2002 p. Sports-related school-based clinic LCR urine 6.5 13/200 Nsuami et al. 2003 q. Marine recruits LCR urine, cervix, vagina 11.6 207/1,786 Shafer et al. 2003 r. Army recruits LCR urine 9.5 2,189/23,010 Gaydos et al. 2003 Population Test CT (+) Rate (%) n/N Author Year MALES a. Teen, detention school and community clinics LCR urine 5.3 275/5,150 Marrazzo et al. 1997 b. Detention clinic LCR urine 8.8 19/217 Oh et al. 1998 c. Community outreach LCR urine 10.7 17/159 Rietmeijer et al. 1998 d. Enlisted military, nonclinic-based screening LCR urine 3.4 21/618 Brodine et al. 1998 e. Health maintenance organization teen clinic LCR urine 2.11 3/118 Boyer et al. 1999 f. School-based clinic LCR urine 6.2 143/2,308 Cohen et al. 1999 g. Emergency department LCR urine 9.9 (males and females) 28/282 Embling et al. 2000 h. Detention clinic LCR urine 14.4 41/284 Pack et al. 2000 i. High school-based clinic LCR urine 0.8 3/381 Kent et al. 2002 j. Correctional facility clinic LCR urine 2.8–8.9 range Not reported Mertz et al. 2002 k. Sports related school-based clinic LCR urine 2.8 12/436 Nsuami et al. 2003 l. Health maintenance organization SDA urine 4.0 27/711 Tebb et al. 2004

Clinical Manifestations

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).

TABLE 62.3 Comparison of Clinical Manifestations of C. trachomatis and N. gonorrhoeae

Resulting Clinical Syndrome Site of Infection Neisseria gonorrhoeae Chlamydia trachomatis Males Urethra Urethritis Nongonococcal urethritis Epididymis Epididymitis Epididymitis Rectum Proctitis Proctitis Conjunctiva Conjunctivitis Conjunctivitis Systemic Disseminated gonococcal infection: Reiter syndrome Arthritis-dermatitis syndrome Females Urethra Acute urethral syndrome Acute urethral syndrome Bartholin gland Bartholinitis Bartholinitis Cervix Cervicitis Cervicitis Fallopian tube Salpingitis Salpingitis Conjunctiva Conjunctivitis Conjunctivitis Liver capsule Perihepatitis Perihepatitis Systemic Disseminated gonococcal infection: Reiter syndrome Arthritis-dermatitis syndrome

Male Infections

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).

Urethritis

1. Urethritis is the most common problem associated with C. trachomatisin males.
2. C. trachomatiscauses approximately 40% to 60% of NGU in males.
3. C. trachomatisurethral infection is more often asymptomatic than gonococcal urethral infection, and when symptoms occur they are milder with chlamydial urethritis. However, most males with asymptomatic chlamydial urethral infection have a persistent inflammatory response shown by urethral leukocytosis.
4. Urethritis caused by C. trachomatisis associated with the finding of more than 4 polymorphonuclear (PMN) leukocytes per high-power field (HPF) on Gram stains of urethral secretions and/or white blood cells (WBCs) on a first-void urine specimen.
5. There is a 7- to 21-day incubation period from infection to development of symptoms.

Epididymitis

1. C. trachomatisand N. gonorrhoeae infections are responsible for most of the epididymitis cases among men younger than 35 years. In particular, C. trachomatis is responsible for 70% of cases in adolescent and young men.
2. The pathogenesis of chlamydial epididymitis is unclear.
3. Chlamydial urethritis often accompanies the epididymitis among sexually active young males.
4. Males with epididymitis usually complain of unilateral testicular pain and tenderness, and a hydrocele or swelling of the epididymis is usually present. Onset is usually gradual but can be sudden (see Chapter 28 for further description of the work-up for scrotal pain).
5. Complaints of dysuria are present in less than half of men with epididymitis.

Prostatitis

Despite continued study, the role of C. trachomatis in causing nonbacterial prostatitis remains

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controversial. Although definitive studies are lacking, C. trachomatis has been isolated from prostatic secretions and prostatic biopsies from some patients with prostatitis.

Proctitis

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.

Female Infections

Cervicitis

1. Approximately 70% of women infected with C. trachomatisare asymptomatic, others have mild symptoms such as vaginal discharge, vaginal spotting, mild abdominal pain, or dysuria. On examination, the cervix may appear normal or exhibit “hypertrophic” ectopy that appears edematous, and may bleed easily when touched by a swab. There may be a mucopurulent discharge from the cervical os.
2. Ectopy is not synonymous with the inflammatory reaction of the cervix to infection or cervicitis. Ectopy, the presence of columnar epithelial cells on the ectocervix, is a common and normal finding of the developing adolescent cervix. It occurs in 60% to 80% of adolescent cervices. Ectopy is also associated with birth control use. It may be that more adolescents use birth control pills than older adults, birth control pills slow the maturation and involution of the columnar epithelia into the endocervical canal, or birth control pills actually do stimulate the formation of ectopy. However, C. trachomatisinfection is greater in young women with ectopy than in those without ectopy.
3. Chlamydial and gonococcal cervicitis are associated with the finding of more than 30 PMN leukocytes/HPF on Gram stains of cervical secretions.
4. Although the presence of MPC has been related to both C. trachomatisand N. gonorrhoeae infections, in most cases of MPC neither organism is identified on testing. The reverse is also true: in most cases of documented chlamydial and gonococcal cervical infection, MPC is not found on examination.

Urethritis

1. Screening studies in STD clinics suggest that more than 50% of women infected with C. trachomatishave coinfections at both the urethra and endocervix (Stamm, 1999a,b). Women with C. trachomatis isolated from both the cervix and the urethra were more likely to complain of dysuria than women with cervical infection alone.
2. The acute urethral syndrome of chlamydial urethritis is characterized by the finding of “sterile” pyuria for urine pathogens in the face of symptoms of dysuria and frequency in sexually active young women.

Pelvic Inflammatory Disease

See Chapter 63 on PID.

1. Infections can ascend through the cervical os causing endometriosis and infection of the fallopian tubes. When the infection extends to the ovaries and peritoneal cavity it can result in abscess formation.
2. The risk for a 15-year-old female to develop PID is ten times the risk for a 24-year-old young woman.
3. C. trachomatishas been associated with 20% to 50% of the PID cases in the United States.
4. It is estimated that 10% to 40% of females with untreated chlamydial infections develop PID (Cates and Wasserheit, 1991).
5. The spectrum of PID associated with C. trachomatisinfection ranges from acute, severe disease to asymptomatic or “silent” disease.
6. Women with a history of PID can experience serious reproductive sequelae, including infertility, ectopic pregnancy, and chronic pelvic pain. Two studies of C. trachomatisand PID in infertile female patients demonstrated PID as the cause of the infertility in half the patients and found that antichlamydial antibody was strongly associated with a tubal problem associated with infertility (Jones et al., 1982a; Kelver and Nagamani, 1989). Many of these females denied a past history of salpingitis. Undetected or “silent” cases of salpingitis may also be a contributor to ectopic pregnancies.

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

1. C. trachomatisinfections during pregnancy have been associated with adverse outcomes such as spontaneous miscarriage and premature delivery. Infected women can develop PID after vaginal delivery or after therapeutic abortion.
2. Two thirds of infants born to infected mothers become colonized during delivery. Conjunctivitis develops in 18% to 50% of colonized infants, and symptoms peak in the first 5 to 14 days of life.
3. Pneumonia develops in 10% to 20% of colonized infants. Approximately 50% of infants with pneumonia will have concurrent conjunctivitis (Darville, 1998).

Other Infections and Complications, Male and Female

Pharyngeal Colonization

3. trachomatisis isolated from the pharynx but causes few problems. It is present in 3.7% of males and 3.2% of females at risk of genital infection (Jones et al., 1985). In a study by Neinstein and Inderlied (1986), the organism was only isolated in 1 of 100 adolescents examined using older, less-accurate tests.

Conjunctivitis

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

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infection. Symptoms usually include unilateral eye discharge, hyperemia, and pain.

Cardiac Complications

Rare cardiac complications include endocarditis (Dimmitt et al., 1985; Jones et al., 1982b) and myocarditis.

Reiter Syndrome

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.

Differential Diagnosis

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.

Females

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:

1. Infections from N. gonorrhoeae, Trichomonas vaginalis,herpes simplex, human papillomavirus, and other organisms such as Escherichia coli
2. Intrauterine device (IUD)
3. Allergic reaction to contraceptive foam, gel, or film
4. Idiopathic disease, such as local irritation due to feminine hygiene products, perfumes, or sexual activity

Males

The most common problem in males is urethritis, which can also be caused by the following:

1. Infections such as N. gonorrhoeae, Ureaplasma urealyticum, T. vaginalis,human papillomavirus and herpes simplex
2. Allergic reaction to contraceptive foam, gel, or film
3. Idiopathic disease (see earlier description)

In males presenting with symptoms of acute epididymitis or orchitis, it is important to consider the following in the differential diagnosis:

1. Most epididymitis infections that affect sexually active adolescents and young adults are associated with urethritis due to C. trachomatis(most frequent), N. gonorrhoeae, and gram-positive cocci.
2. In young postpubertal men, coliform and Pseudomonas aeruginosaare less common.
3. Gram-negative enteric organisms occur more frequently in men older than 35 years.
4. In homosexual males, epididymitis may also be caused by sexually transmitted organisms such as E. coliamong the insertive partners involved in anal intercourse.
5. It must be remembered that another common cause of an acute painful scrotal swelling in the sexually active male adolescent is torsion of the spermatic cord, which is a surgical emergency. Therefore, the work-up for torsion and an infectious etiology must be done in concert and must be done with urgency. The diagnosis is based on a dual diagnostic work-up for infection and torsion.

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.

Clinical Clues

1. trachomatisinfections should be suspected in all sexually active adolescents, particularly those with multiple partners or signs and symptoms of genitourinary infection including urethritis, cervicitis, epididymitis, or PID. This includes female patients with an edematous friable cervix, mucopurulent endocervical discharge, and WBCs on the wet mount or patients with a urethritis with Gram stains or cultures not consistent with gonococcal infection. In asymptomatic male patients, the urinary leukocyte esterase dipstick test (LET) on a first-catch urine sample is a good screening test for further evaluation for C. trachomatisor N. gonorrhoeae. It must be emphasized that approximately 75% of females and 50% of males with chlamydia are asymptomatic. By treating only presumptive symptomatic cases, a large proportion of infected teenagers will be missed.

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.

Collection Sites

Endocervix

If a pelvic examination is performed, the endocervix can be used as the site for specimen collection. Before

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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.

Urethra

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.

Urine

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.

Vagina

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.

Other Sites

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.

Laboratory Diagnosis

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.

TABLE 62.4 Comparison of C. trachomatis Testing Technologies

Test Types Preferred Test Collection Site Sensitivity Specificity From Centers for Disease Control and Prevention: Screening Tests To Detect Chlamydia trachomatis and Neisseria gonorrhoeaeInfections–2002. MMWR 2002:51. California STD/HIV Prevention Training Center: Sexually transmitted chlamydial infections: A primary care clinician's guide to diagnosis, treatment and prevention, http://www.stdhivtraining.org/pdf/chlamydia_screen.pdf, Dec 2003. Nucleic acid amplification technology (NAAT) Ligase chain reaction (LCR) Polymerase chain reaction (PCR) Yes Male and female urine, endocervical and urethral swabs 80%–90% >98% Transcription-mediated amplification (TMA) Vaginal swab (TMA) Strand displacement amplification (SDA) Cell culture No Endocervical, urethral, rectal, conjunctival, nasopharyngeal 60%–80% >99% Direct fluorescent antibody (DFA) No Endocervical, urethral, rectal, conjunctival, nasopharyngeal 65%–75% 97%–99% Enzyme immunoassay (EIA) No Endocervical, urethral, conjunctival 60%–75% 97%–99% Nucleic acid probe DNA probe hybridization Hybrid capture with signal amplification No Endocervical, urethral, conjunctival 65%–75% 98/99%

Chlamydia-Specific Tests

1. Cell culture: Cultures can be taken from endocervical, urethral, rectal, conjunctival, and nasopharyngeal sites.

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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.

2. DFA or EIA: These tests were the first generation of specific nonculture tests. Although the test performances were slightly poorer than culture in the best laboratories, the DFA and EIA tests can be applied to urine.
3. Nucleic acid probes: The first-generation nonamplified nucleic acid probes included the nucleic hybridization tests. The performance of these nonamplified nucleic acid probes is not significantly better than that of DFA, EIA, and culture.
4. NAATs: The amplified nucleic acid tests have revolutionized chlamydial screening because they have increased sensitivity and can be applied to noninvasive specimens such as urine in both male and female patients. Differing in their approach to amplification of nucleic acid, examples of such tests applied to C. trachomatisdetection include ligase chain reaction (LCR), polymerase chain reaction (PCR), transcription-mediated amplification (TMA), and strand displacement amplification (SDA).

Nonspecific Tests

1. Urinary LET: A nonspecific, but inexpensive test that can be used as a first step to screen asymptomatic males. An LET reading of at least 1+ is suggestive of infection (sensitivity 70%, specificity 80%, and positive predictive value (PPV) 23% for C. trachomatisinfection in asymptomatic men (25 years of age) (Marrazzo et al., 2001). Further definitive testing should be done, when possible, if the LET is positive.
2. Cytology: Cytological specimens are unsatisfactory to detect chlamydial infection.
3. Serology: There is no use for the application of serology in acute genital infection with C. trachomatis. Previous chlamydial infection frequently elicits long-lasting antibodies that cannot be easily distinguished from the antibodies produced in a current infection. Epidemiological studies linking the presence of antibody to tubal factor infertility and most recently to possibly cervical cancer have been of some clinical usefulness.

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.

Treatment

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:

• Emergence of resistance to current regimens is not a problem, which is unlike that found with gonococcal infections.
• Most single-dose regimens for treatment of gonorrhea do not eradicate concomitant chlamydial infections.
• Coinfection with C. trachomatisoften occurs among patients who have gonococcal infection, and therefore presumptive treatment of such patients for C. trachomatis infection is appropriate.
• Dispensing medications for chlamydial infection on site and directly observing the first dose can help maximize compliance with treatment.
• Sexual abstinence for 7 days is needed to ensure effective treatment and reduce reinfection between partners.
• Single-dose oral azithromycin, or a 7-day course of amoxicillin, is now the recommended regimen for treatment of pregnant women.
• Urine-based NAATs have rendered much empirical treatment unnecessary, except in select cases in which the risk is very high and likelihood of follow-up is very low.

Empirical Treatment

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:

• Urethritis: Presence of urethritis should be documented if possible. “Documentation” would include the presence of mucopurulent urethral discharge, Gram stain consistent with chlamydial orgonococcal infection, positive LET results on first-catch urine sample, or (10 WBCs/HPF on first-catch urine. If none of these documentation criteria are present, treatment can be deferred and further testing for N. gonorrhoeae and C. trachomatis can be done with close follow-up. Empirical treatment without documentation of urethritis should be limited to symptomatic patients at high risk for infection (new or multiple sex

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partners, and unprotected sex) who are unlikely to return for follow-up evaluation.

• Mucopurulent cervicitis: Empirical treatment should be initiated if there is mucopurulence on examination in adolescents at increased risk for infection (new or multiple sex partners, and unprotected sex), if follow-up is unlikely, or a relatively insensitive diagnostic test (not a NAAT) is used.
• Pelvic inflammatory disease: Empirical treatment should be initiated in sexually active young women and other women at risk for STDs if the following minimum criteria for PID are present and no other cause for the illness can be identified—uterine/adnexal tenderness or cervical motion tenderness.

Uncomplicated Urethral, Cervical, or Rectal Infection

Recommended Regimens

Uncomplicated urethral, endocervical, or rectal infection in adults and adolescents should be treated with one of the following:

1. Azithromycin 1 g orally in a single dose, OR
2. Doxycycline 100 mg orally b.i.d. for 7 days

Alternative Regimens

Alternative regimens are as follows:

1. Erythromycin base 500 mg by mouth q.i.d. for 7 days, OR
2. Erythromycin ethylsuccinate 800 mg by mouth q.i.d. for 7 days, OR
3. Ofloxacin 300 mg orally b.i.d. for 7 days, OR
4. Levofloxacin 500 mg orally once a day for 7 days

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.

Follow-up

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.

Sex Partners

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.

Pregnant Patients

Recommended Regimen During Pregnancy

1. Azithromycin 1 g PO in a single oral dose, OR
2. Amoxicillin 500 mg PO t.i.d. for 7 days

Alternative Regimens

1. Erythromycin base 500 mg orally q.i.d. for 7 days, OR
2. Erythromycin base 250 mg orally q.i.d. for 14 days, OR
3. Erythromycin ethylsuccinate 800 mg q.i.d. for 7 days, OR
4. Erythromycin ethylsuccinate 400 mg q.i.d. for 14 days

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.

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Acute Epididymitis

Regimen of Choice

1. Ceftriaxone 250 mg intramuscularly once AND
2. Doxycycline 100 mg orally b.i.d. for 10 days

Bed rest and elevation of the scrotum are also recommended.

Alternative Regimen

For acute epididymitis most likely caused by enteric organisms or for patients allergic to cephalosporins and/or tetracyclines:

1. Ofloxacin 300 mg orally b.i.d. for 10 days (can be used in nonpregnant adolescents who weigh >45 kg and young adults older than 18 years) OR
2. Levofloxacin 500 mg orally once daily for 10 days

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

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.

Prevention

1. Goals
2. To prevent overt and “silent” chlamydial PID and its sequelae
3. To prevent perinatal and postpartum infections
4. To prevent adverse consequences of chlamydial infections at other anatomical sites
5. To prevent recurrence of infection in young women that is linked to increased upper reproductive tract tissue damage
6. Prevention strategies
7. Primary prevention

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:

• C. trachomatisinfection is the most common reported STD, particularly among adolescents and young adults
• Adverse consequences of chlamydial infection in self, current, and future partners (e.g., PID and infertility, question of link to cervical cancer in women)
• Symptoms and signs of infection in self and partner (and other STDs)
• Asymptomatic or “silent” infection, particularly the link to undetected PID
• Need for discussion with and treatment of sex partners
• Referrals and services available in the community for testing and treatment of partners
• Discussion of the link between substance use (particularly alcohol and marijuana), poor decision making, and acquisition of STDs including C. trachomatisinfections.

1. Secondary prevention

• Screen females to identify and treat asymptomatic chlamydial infections at least once a year and more often if risky behaviors are identified.
• Implementation of system-wide screening programs in large health maintenance organizations has been shown to be feasible and effective in significantly increasing the C. trachomatisscreening rates (Shafer et al., 2002).
• Rescreening: Retest of index-positive cases 3 to 4 months after treatment.

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.

• Track and treat all positive clients and their partners.
• Recognize C. trachomatis-associated syndromes such as MPC and treat as appropriate.

3. Target populations
4. Sexually active adolescents and young adults

• Female patients: It is recommended to screen sexually active adolescents and females younger than 25 years for C. trachomatisat least annually. With the advent of urine-based testing, the goal should be to screen for C. trachomatis first and perform a pelvic examination only when necessary—not just for chlamydial screening purposes.
• Males patients: The urinary LET has been shown to be a useful “first step” among lower risk sexually active male adolescents and young adult males. If positive, it is more efficacious to perform a more definitive C. trachomatisscreening test such as a NAAT.

1. Pregnant women, including those who will have an induced abortion
2. Adolescents, particularly females, in detention facilities or attending an STD clinic

Web Sites

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.

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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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