para>Perinatal acquisition may result in neonatal pneumonia and/or conjunctivitis. �
EPIDEMIOLOGY
Incidence
- Mandatory reporting started in 1985; there has generally been a steady increase in incidence since
- 1.4 million reported cases in 2013. Increasing incidence reflects broader screening, improved testing, and better reporting (as opposed to a large increase in disease burden). 2012 to 2013 is the first time since national reporting began that the rate of reported cases decreased.
- Swedish new variant chlamydia (nvCT) first reported in 2006; often produces false-negative tests; largely confined to Nordic countries.
Prevalence
- 446/100,000 people in the United States in 2012
- Populations most affected: young females, ethnic minorities
- Peak incidence: age 18 to 20 years
- Predominant sex: females > males. Females have >2.5 times higher reported incidence and prevalence than males. This likely reflects increased testing in females. Increasing use of urine screening may increase identification in males.
- Infection rates >7 times higher in blacks than whites. Rates are higher in larger urban areas.
- Highest male prevalence in heterosexual adolescents
- Estimated to affect ~2% of young sexually active individuals in the United States
ETIOLOGY AND PATHOPHYSIOLOGY
C. trachomatis serotypes D-K associated with genital tract infections. Chlamydia is an obligate intracellular organism. Chlamydia has biphasic life cycle. Exists extracellularly as elementary body (EB) that is metabolically inactive and infectious. Once taken up by host cell (typically columnar epithelium of the genital tract), the EB prevents lysosomal phagocytosis and transforms to reticulate body (RB) which requires energy from host cell to synthesize RNA, DNA, and proteins. After taking up host cell residence, EB are released and are capable of infecting neighboring cells or spreading the infection through sexual contact. �
RISK FACTORS
Risk correlates with: �
- Number of lifetime sexual partners and number of concurrent sexual partners
- No use of barrier contraception during intercourse
- Younger age (highest in females 15 to 19 years, males 20 to 24 years)
- Black/Hispanic/Native American and Alaskan Native ethnicity
GENERAL PREVENTION
- Screen populations with prevalence >5% at least annually (1)[A].
- Screening recommended if new or >1 sex partner in past 6 months; attending an adolescent clinic, family-planning clinic, STD or abortion clinic, or attending a jail or other detention center clinic. Screen if rectal pain, discharge or tenesmus, testicular pain; test all individuals with urethral or cervical discharge.
- All sexually active women ≤25 years of age should be screened at least yearly. Repeat testing in ~3 months is recommended for those who screen positive because reinfection rate is high regardless of whether the sexual partner is treated (2)[A].
- Consider screening sexually active men ≤25 years of age particularly in high-risk populations.
- Screen men who have sex with men annually.
- Nucleic acid amplification test (NAAT) is the preferred screening test in all circumstances except child sexual abuse involving boys or rectal/oropharyngeal testing in prepubescent girls. For these situations, culture and susceptibility testing is preferred (3)[A].
- Acceptable to screen women for chlamydia on same day as intrauterine device insertion-treat if positive (no need to remove IUD in this circumstance) (4)[B]
COMMONLY ASSOCIATED CONDITIONS
- Females
- PID: ~10% develop PID within 12 months if untreated.
- Infertility, ectopic pregnancy
- Chronic pelvic pain
- Urethral syndrome (dysuria, frequency, and pyuria in the absence of infection)
- Arthritis (less common)
- Spontaneous abortion
- Males
- Epididymitis and nongonococcal urethritis
- Reiter syndrome (HLA-B27)
- Proctitis
- Neonates
- Inclusion conjunctivitis (occurs in ~40% of exposed neonates)
- Otitis media
- Pneumonia
- Pharyngitis
- Diseases caused by other chlamydial species
- Lymphogranuloma venereum (LGV): C. trachomatis serotypes L1 to L3
- Trachoma: C. trachomatis serotypes A-C
DIAGNOSIS
Many patients are asymptomatic. �
Pregnancy Considerations
Test all patients at first prenatal visit.
Test of cure 3 months after treatment for all pregnant patients
Repeat test in 3rd trimester (2)[A].
�
HISTORY
- Complete sexual history, including number of sex partners (lifetime and past year), prior history of STIs, use of barrier protection, commercial sex work, oral or anal receptive intercourse, and partner fidelity
- In females, the most common symptoms are:
- Mucopurulent vaginal discharge, dysuria (urethral syndrome), bartholinitis, abdominopelvic pain (endometritis, salpingitis/PID), right upper quadrant pain (Fitz-Hugh-Curtis syndrome)
- In males, the most common symptoms are:
- Dysuria, urethral discharge (urethritis), scrotal pain (epididymitis), rectal pain or discharge (proctitis), acute arthritis (Reiter syndrome)
PHYSICAL EXAM
- Men and women: external genitalia (rash, lesions), urethral discharge, inguinal lymphadenopathy, pharyngeal exudate, and perianal lesions
- In addition, for women: cervix (discharge, motion tenderness), bimanual examination for cervical motion tenderness, uterine tenderness, ovarian or adnexal tenderness or mass.
- LGV (C. trachomatis serovars L1, L2, or L3): Primary lesion is a small papule that may ulcerate at the site of transmission after an incubation period of 3 to 30 days. Unilateral tender lymphadenopathy. With rectal transmission, LGV causes an invasive proctocolitis.
DIFFERENTIAL DIAGNOSIS
- Neisseria gonorrhoeae: urethritis, proctitis, epididymitis, cervicitis, PID, Bartholin abscess
- Mycoplasma or Ureaplasma urealyticum: urethritis, epididymitis, Reiter disease, PID
- C. trachomatis (serotypes L1 to L3): LGV, proctitis
- Trichomoniasis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Test of choice is NAAT: sensitivity >95%; specificity >99%
- Urine is as sensitive as cervical swab.
- Patient self-collected vaginal swabs is also effective.
- Lab tests may remain positive for 3 weeks after successful treatment.
- Test for concurrent STIs, including gonorrhea, HIV, syphilis; perform cervical cancer (PAP) screening if clinically appropriate.
Follow-Up Tests & Special Considerations
See "Patient Monitoring."� �
TREATMENT
GENERAL MEASURES
- Offer patients concurrent testing for gonorrhea, HIV (after counseling and consent), and possibly syphilis. Also, ensure females are up to date with cervical cancer screening.
- Consider treating gonorrhea empirically.
- All partners (most recent partner and all partners within the past 60 days) should be tested and treated.
MEDICATION
First Line
- http://www.cdc.gov/std/treatment/2010/chlamydial-infections.htm
- Treatment of chlamydial urethritis, cervicitis (including sexual partners of infected persons)
- Azithromycin 1 g PO single dose or
- Doxycycline 100 mg PO BID for 7 days
- First-line PID treatment (outpatient)
- Ceftriaxone 250 mg IM � 1 PLUS doxycycline 100 mg PO for 14 days with or without metronidazole 500 mg PO BID for 14 days or
- Cefoxitin 2 g IM � 1 with probenecid 1 g PO � 1 PLUS doxycycline 100 mg PO for 14 days with or without metronidazole 500 mg PO BID for 14 days
- Azithromycin and ceftriaxone may be given simultaneously in the office to treat both chlamydia and gonorrhea. This reduces nonadherence (2)[A].
- Asymptomatic rectal chlamydia can be treated with doxycycline 100 mg BID � 7 days. Azithromycin 1 g for 1 day is slightly less effective but can also be used, especially if compliance or medication availability is an issue (5,6)[A].
ALERT
Use azithromycin with caution in patients with known QT prolongation, hypokalemia, hypomagnesemia, bradycardia, or who are currently treated with antiarrythmics.
�
Pregnancy Considerations
�
ALERT
Tetracyclines and quinolones are contraindicated in young children:
<45 kg: erythromycin base or ethinyl succinate 500 mg/kg/day PO QID for 14 days
>45 kg but <8 years: azithromycin 1 g PO for 1 day
>8 years: adult regimen
Rule out sexual abuse in children with chlamydial infections.
�
Second Line
For chlamydial urethritis/cervicitis �
- Erythromycin base 500 mg PO QID for 7 days OR erythromycin ethylsuccinate 800 mg PO QID for 7 days
- Levofloxacin 500 mg PO daily for 7 days or orofloxacin 300 mg PO BID for 7 days
ADDITIONAL THERAPIES
Patient delivered partner therapy (PDPT) or expedited partner therapy (EPT): Provide medications or prescriptions to take to sexual partners of persons infected with STIs without clinical assessment. �
- EPT reduces recurrence more effectively than traditional partner referral.
- http://www.cdc.gov/std/ept/legal/
INPATIENT CONSIDERATIONS
The following patients are recommended for inpatient treatment of PID: pregnancy, lack of response or intolerance to oral medicines, suspicion of poor compliance, severe clinical illness, pelvic abscess, and possible need for surgical intervention �
Admission Criteria/Initial Stabilization
Outpatient treatment, unless moderately or severely ill �
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient and all partners should abstain from sexual contact until at least 7 days after completing treatment. �
Patient Monitoring
- Test of cure: not routinely recommended, except in pregnancy
- Sexual partners should be treated.
PATIENT EDUCATION
- Counseling regarding safe sexual practices, use of barrier protection, and abstinence
- Patient and partner should complete antibiotic course.
PROGNOSIS
Prognosis is good following therapy. �
COMPLICATIONS
- Both sexes: Chlamydial infection enhances transmission of and susceptibility to HIV.
- Females: tubal infertility (most common cause of acquired infertility), tubal (ectopic) pregnancy, chronic pelvic pain
- Annual screening of sexually active women would prevent 61% of chlamydia-related PID.
- Males: transient oligospermia and postepididymitis urethral stricture (rare)
REFERENCES
11 Centers for Disease Control and Prevention. 2012 Sexually transmitted disease surveillance. http://www.cdc.gov/std/stats12/chlamydia.htm.22 Workowski �KA, Berman �S, Bauer �H, et al. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1-110.33 Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhea-2014. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6302a1.htm.44 Sufrin �CB, Postlethwaite �D, Armstrong �MA, et al. Neisseria gonorrhea and Chlamydia trachomatis screening at intrauterine device insertion and pelvic inflammatory disease. Obstet Gynecol. 2012;120(6):1314-1321.55 Elgalib �A, Alexander �S, Tong �CY, et al. Seven days of doxycycline is an effective treatment for asymptomatic rectal Chlamydia trachomatis infection. Int J STD AIDS. 2011;22(8):474-477.66 Drummond �F, Ryder �N, Wand �H, et al. Is azithromycin adequate treatment for asymptomatic rectal chlamydia? Int J STD AIDS. 2011;22(8):478-480.
ADDITIONAL READING
- Baud �D, Goy �G, Jaton �K, et al. Role of Chlamydia trachomatis in miscarriage. Emerg Infect Dis. 2011;17(9):1630-1635.
- Price �MJ, Ades �AE, De Angelis �D, et al. Risk of pelvic inflammatory disease following Chlamydia trachomatis infection: analysis of prospective studies with a multistate model. Am J Epidemiol. 2013;178(3):484-492.
- Ray �WA, Murray �KT, Hall �K, et al. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881-1890.
- Unemo �M, Clarke �IN. The Swedish new variant of Chlamydia trachomatis. Curr Opin Infect Dis. 2011;24(1):62-69.
- Won �H, Ramachandran �P, Steece �R, et al. Is there evidence of the new variant Chlamydia trachomatis in the United States? Sex Transm Dis. 2013;40(5):352-353.
SEE ALSO
Cervicitis, Ectropion, and True Erosion; Epididymitis; Gonococcal Infections; HIV/AIDS; Pelvic Inflammatory Disease (PID); Syphilis; Urethritis �
CODES
ICD10
- A56.8 Sexually transmitted chlamydial infection of other sites
- A56.01 Chlamydial cystitis and urethritis
- A56.02 Chlamydial vulvovaginitis
- A71.9 Trachoma, unspecified
- A56.09 Other chlamydial infection of lower genitourinary tract
- A74.0 Chlamydial conjunctivitis
- A56.00 Chlamydial infection of lower genitourinary tract, unsp
- A56.11 Chlamydial female pelvic inflammatory disease
- A56.3 Chlamydial infection of anus and rectum
- A56.19 Other chlamydial genitourinary infection
- A56.2 Chlamydial infection of genitourinary tract, unspecified
ICD9
- 099.50 Other venereal diseases due to chlamydia trachomatis, unspecified site
- 099.41 Other nongonococcal urethritis, chlamydia trachomatis
- 099.53 Other venereal diseases due to chlamydia trachomatis, lower genitourinary sites
- 076.9 Trachoma, unspecified
- 771.6 Neonatal conjunctivitis and dacryocystitis
- 099.52 Other venereal diseases due to chlamydia trachomatis, anus and rectum
- 099.55 Other venereal diseases due to chlamydia trachomatis, unspecified genitourinary site
- 099.59 Other venereal diseases due to chlamydia trachomatis, other specified site
- 099.54 Other venereal diseases due to chlamydia trachomatis, other genitourinary sites
SNOMED
- 240589008 Chlamydia trachomatis infection (disorder)
- 179101003 Urethritis due to Chlamydia trachomatis (disorder)
- 237097008 chlamydial vulvovaginitis (disorder)
- 2576002 Trachoma (disorder)
- 240591000 Neonatal chlamydial conjunctivitis
- 1084821000119103 Cystitis due to Chlamydia (disorder)
- 186731007 Chlamydial infection of anus and rectum (disorder)
- 233610007 Neonatal chlamydial pneumonia (disorder)
CLINICAL PEARLS
- C. trachomatis is common in young sexually active individuals. Annual screening is recommended in sexually active women 25 years of age and younger.
- To prevent recurrence, treat patients and their partners concurrently.
- Test of cure is recommended for pregnant patients at 3 weeks. Pregnant women diagnosed in the 1st trimester should have a second test of cure 3 months after treatment.