Chlamydia Genital Infections

Deanna L. Benner A.P.R.N., C.R.N.P.
Anthony Sciscione, D.O.

Basic Information

Definition

Genital infection with Chlamydia trachomatis (CT) is the most prevalent sexually transmitted disease in the U.S. Chlamydia infection can result in cervicitis, acute urethral syndrome, endometritis, pelvic inflammatory disease, ectopic pregnancy, infertility, and chronic pelvic pain in women (see “Pelvic Inflammatory Disease”). In men, CT infection may cause mucopurulent discharge, urethritis, epididymitis, and prostatitis. Newborns born via an infected birth canal are at risk for conjunctivitis and pneumonia. A majority of the men and women affected with CT are asymptomatic. Thus, screening tests play a very important role in detection of this infection to initiate treatment, impede disease sequelae, and prevent further transmissions.

ICD-10CM CODES
A56.2	Chlamydial infection of genitourinary tract, unspecified
A56	Other sexually transmitted chlamydial diseases
A56.0	Chlamydial infection of lower genitourinary tract
A56.00	Chlamydial infection of lower genitourinary tract, unspecified
A56.01	Chlamydial cystitis and urethritis
A56.02	Chlamydia vulvovaginitis
A56.09	Other chlamydial infection of lower genitourinary tract
A56.1	Chlamydial infection of pelviperitoneum and other genitourinary organs
A56.19	Other chlamydial genitourinary infection
A56.2	Chlamydial infection of genitourinary tract, unspecified
A56.3	Chlamydial infection of anus and rectum
A56.4	Chlamydial infection of pharynx
A56.8	Sexually transmitted chlamydial infection of other sites

Epidemiology & Demographics

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C. trachomatis is the most common sexually transmitted disease in the U.S., with more than 1.4 million cases reported annually to the Centers for Disease Control and Prevention. However, it is thought that this number is an underestimate, since many cases of CT infection are asymptomatic and potentially can remain undiagnosed.
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Age is a strong predictor for risk of CT infection. Individuals less than 25 years old are the largest age group affected by C. trachomatis. Chlamydia infections are 10 times more prevalent than gonococcal infections in young women between the ages of 18 and 26 years.
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Chlamydia conjunctivitis occurs in 18% to 44% of infants, and chlamydial pneumonia occurs in 3% to 16% of infants who are delivered by mothers with untreated CT infection at the time of delivery.
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Pelvic inflammatory disease develops in 10% to 15% of women with untreated CT infections.
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Untreated CT increases a person’s risk of acquiring HIV.
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In men, 15% to 55% of nongonococcal urethritis cases are caused by C. trachomatis.

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Table 1 summarizes clinical characteristics of common C. trachomatis infections.

TABLE1 Clinical Characteristics of Common Chlamydia trachomatis InfectionsFrom Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, ed 8, Philadelphia, 2015, Saunders.

	Infection	Symptoms and Signs	Presumptive Diagnosis	Definitive Diagnosis	Treatment
Men	Nongonococcal urethritis	Urethral discharge, dysuria	Urethral leukocytosis; no gonococci seen	Urine or urethral NAAT	Azithromycin, 1 g PO (single dose) or
					Doxycycline, 100 mg PO bid, for 7 days
	Epididymitis	Unilateral epididymal tenderness, swelling; pain; fever, presence of NGU	Urine or urethral NAAT	Urethral leukocytosis; pyuria on urinalysis	STI likely: Ceftriaxone 250 mg IM plus doxycycline, 100 mg PO bid, for 10 days
					History of insertive anal intercourse:
					Ceftriaxone, 250 mg IM, plus levofloxacin, 500 mg bid for 10 days
	Proctitis (non-LGV)	Rectal pain, discharge and bleeding; history of receptive anal intercourse	≥1 PMN/OIF on rectal Gram stain; no gonococci seen	Urine or urethral NAAT; rectal culture or NAAT	Doxycycline, 100 mg PO bid, for 7 days
	LGV	Painful, tender inguinal lymphadenopathy, fever	“Groove sign”	Urine, urethral, lymph node or rectal NAAT; rectal or lymph node culture; LGV-specific testing if available	Doxycycline, 100 mg PO bid, for 21 days
	LGV proctitis	Rectal pain, discharge, and bleeding in MSM; absence of inguinal lymphadenopathy	≥1 PMN/OIF on rectal Gram stain; no gonococci seen	Urine, urethral, or rectal NAAT; rectal culture; LGV-specific testing if available	Doxycycline, 100 mg PO bid, for 21 days
	Conjunctivitis	Ocular pain, redness, discharge; simultaneous genital infection	Gram stain of conjunctival swab negative for bacterial pathogens; PMNs on smear	Rectal culture or NAAT; NAAT of conjunctivae	Azithromycin, 1 g PO (single dose) or Doxycycline, 100 mg PO bid, for 7 days
Women	Cervicitis	Mucopurulent cervical discharge; ectopy, easily induced bleeding	≥20 PMN/OIF on cervical Gram stain	Urine or cervical NAAT	Azithromycin, 1 g PO (single dose) or Doxycycline, 100 mg PO bid, for 7 days
	Urethritis	Dysuria, frequency; no hematuria	Pyuria on UA; negative urine Gram stain and culture	Urine, cervical, or urethral NAAT	Azithromycin, 1 g PO (single dose) or Doxycycline, 100 mg PO bid for 7 days
	Pelvic inflammatory disease	Lower abdominal pain, adnexal pain, cervical motion tenderness	Evidence of mucopurulent cervicitis	Urine or cervical NAAT	Outpatient: Ceftriaxone 250 mg IM as a single dose, plus doxycycline 100 mg PO bid for 14 days, with or without metronidazole, 500 mg PO bid for 14 days
Adults	Conjunctivitis	Ocular pain, redness, discharge; simultaneous genital infection	Gram stain of conjunctival swab negative for bacterial pathogens; PMNs on smear	DFA or NAAT on conjunctival swab	Azithromycin, 1 g PO (single dose) or Doxycycline, 100 mg PO bid for 7 days
Newborns	Conjunctivitis	Ocular pain, redness, discharge; simultaneous genital infection	Gram stain of conjunctival swab negative for bacterial pathogens; PMNs on smear	DFA or NAAT on conjunctival swab; vagina, rectum, pharynx also often positive	Erythromycin base 50 mg/kg/day, orally divided into four doses daily for 14 days; evaluate and treat parents as well
	Pneumonia	Staccato cough, tachypnea, hyperinflation	Diffuse interstitial infiltrate, eosinophilia	Nasopharyngeal NAATs or culture; MIF serology (IgM)	Erythromycin base 50 mg/kg/day, orally divided into four doses daily for 14 days; evaluate and treat parents as well
DFA, Direct fluorescent antibody; IgM, immunoglobulin M; LGV, lymphogranuloma venereum; MIF, microimmunofluorescence; MSM, men who have sex with men; NAAT, nucleic acid amplification test; NGU, nongonococcal urethritis; OIF, oil immersion field; PMN, polymorphonuclear neutrophil; STI, sexually transmitted infection; UA, urinalysis.

Physical Findings & Clinical Presentation

Clinical manifestations in symptomatic women affected with C. trachomatis are vaginal discharge or irregular vaginal bleeding. Purulent discharge or cervicitis may be visualized on speculum exam. Easily induced endocervical bleeding can be noted on exam and is caused by inflammation of endocervical columnar epithelium. Untreated infection can ascend the reproductive tract, causing pelvic inflammatory disease. Clinical signs of pelvic inflammatory disease are cervical, uterine, or adnexal tenderness on exam. Complications of pelvic disease are ectopic pregnancy, infertility, and chronic pelvic pain.

Most men are asymptomatic, but when they do experience symptoms, it is usually dysuria or a mucopurulent penile discharge. A complication that can arise from CT infection in men is epididymitis, which manifests as unilateral testicular pain, hydrocele, or swelling of the epididymis. An untreated CT infection can also cause prostatitis in men. Prostatitis may present as urinary dysfunction, pain with ejaculation, and pelvic pain.

Chlamydial conjunctivitis can be experienced by both men and women and is the result of conjunctiva exposed to infected genital secretions. CT infection can also cause proctitis or infection of the rectum in men and women. This usually presents with rectal pain, discharge, or bleeding. CT infection of the throat is usually asymptomatic in both men and women and not a usual cause of pharyngitis. Less frequent manifestations of CT infection may include perihepatitis (Fitz-Hugh–Curtis syndrome) or reactive arthritis (Reiter’s syndrome).

Etiology

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C. trachomatis consists of 15 serotypes
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Obligate, intracellular bacteria

Diagnosis

Differential Diagnosis

Differential diagnosis depends on presenting symptoms. Some of the common differentials are listed in the following:

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Candidiasis
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Conjunctivitis
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Ectopic pregnancy
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Endometriosis
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Gonorrhea
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Mycoplasma infection
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Pelvic inflammatory disease
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Trichomonas
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Urethritis
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Urinary tract infection

Workup

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Individuals with signs and symptoms mentioned previously should be screened for CT infection. Since the majority of CT infections are asymptomatic, routine screening should be offered to individuals at risk for CT infection. Annual screening of all sexually active women less than 25 years and women at any age at risk for sexually transmitted diseases is recommended. Risk factors include a new sexual partner, more than one sexual partner, individuals not in a mutually monogamous relationship, a previous or concurrent sexually transmitted disease, or working in the sex industry for profit. Screening interval is determined by any new risk for exposure since the last negative screening. The CDC recommends CT screening for all pregnant women under the age of 25 and for any pregnant woman over the age of 25 who is at increased risk for acquiring CT. These same pregnant women should be screened again during the third trimester.

Laboratory Tests

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Nucleic acid amplification tests (NAATs) are the gold standard for diagnosis because of their high sensitivity and specificity for the detection of CT infection. The FDA has approved these tests for male and female urine collection and for provider-collected endocervical, vaginal, and male urethral specimens.
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Rectal and pharyngeal collection site specimens may be taken from individuals who engage in receptive anal and oral intercourse, but these collection sites are not FDA approved.
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For best results, urine collection should be completed with a first-void urine sample.
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Self-collected vaginal swab samples for women have the same sensitivity and specificity as provider-collected samples.
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The same specimen can be used to test for chlamydia and gonorrhea.
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Sexual partners of a person testing positive for CT infection should be treated if they had sexual contact with that individual within 60 days prior to onset of symptoms or CT diagnosis.
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Microscopy should not be used for chlamydia diagnosis; however, greater than 10 white blood cells per high-power field with a mucopurulent discharge can be a presumptive diagnosis.

Treatment

Acute General Rx

Nongonococcal urethritis, urethritis, cervicitis, conjunctivitis (except for lymphogranuloma venereum):

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Azithromycin 1 g PO ×single dose therapy or
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Doxycycline 100 mg PO bid for 7 days

Infection in pregnancy:

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Azithromycin 1 gm PO single-dose therapy

Alternatives:

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Erythromycin 500 mg PO qid for 7 days or
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Erythromycin ethylsuccinate 800 mg PO qid for 7 days

NOTE: Azithromycin (Pregnancy Risk Category B) is generally considered safe and effective during pregnancy and with lactation. Erythromycin base (Pregnancy Risk Category B) is an acceptable alternate agent for treatment of CT infection in pregnancy. Doxycycline is contraindicated in pregnancy. Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity.

Follow-Up

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Observed single-dose therapy should be offered to individuals for whom compliance is a concern.
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To minimize disease transmission to partners, affected persons should be advised to refrain from sexual intercourse for 7 days after single-dose therapy, until completion of 7-day therapy, or until resolution of symptoms.
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To prevent reinfection, affected individuals should refrain from sexual intercourse until all of their partners have been treated.
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Test of cure to detect treatment failure is not needed.
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Re-collection by NAAT method in less than 3 weeks from treatment can yield a false-positive result due to the sensitivity of this testing method.
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Both men and women treated for chlamydia should be retested at approximately 3 months after treatment to screen for reinfection. If patients do not return to clinical settings within 3 months, rescreen the patient at the next presentation for clinical care.
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Pregnant women with chlamydia trachomatis infection should have a test of cure 3 to 4 weeks after treatment and should then be retested within 3 months.

Refer partners for evaluation and treatment.

Recurrent and Persistent Urethritis

Retreat noncompliant patients with the above regimens. If patient was initially compliant, recommended regimens: metronidazole 2 g PO in single dose plus erythromycin base 500 mg PO qid for 7 days or erythromycin ethylsuccinate 800 mg PO qid for 7 days.

Referral

Refer to infectious disease specialist if persistent infection or gynecologist if salpingitis is suspected.

Ferri – Chlamydia Genital Infections