Chlamydia infections

Chlamydiaceae is a family of gram-negative, obligate intracellular bacteria that includes 3 organisms pathogenic to humans: Chlamydia trachomatis, Chlamydophila pneumoniae, and Chlamydophila psittaci. C. trachomatis can be differentiated into serotypes A–C, D–K, and L1–L3. Serotypes A–C mainly affect the eyes and cause trachoma. An infection with serotypes D–K can result in genitourinary infections (e.g., cervicitis, PID, urethritis), conjunctivitis, and infant pneumonia. Serotypes L1–L3, in turn, lead to sexually transmitted lymphogranuloma venereum. While both C. pneumoniae and C. psittaci primarily affect the respiratory system, C. psittaci also causes psittacosis. Chlamydial infections are mostly diagnosed based on clinical presentation and are treated with doxycycline or macrolides. In all cases of sexually transmitted chlamydial infection, expedited partner therapy should also be initiated as soon as possible. Ocular manifestations are discussed in more detail in the “Bacterial conjunctivitis” and “Neonatal conjunctivitis” articles.

General characteristics

• Gram-negative organisms that Gram stain poorly
• Obligate intracellular bacteria (unable to produce its own ATP)
• Absent peptidoglycan (muramic acid) in the cell wall, which makes beta-lactam antibiotics ineffective
• Visible as cytoplasmic inclusion bodies on Giemsa stain or fluorescent antibody-stained smear
• Very difficult cultivation

Life cycle

• First phase: elementary bodies (small and dense bodies that characterize the infectious stage of Chlamydiaceae; stable in the extracellular environment and almost inactive metabolically) ^[1]
  1. Attachment of extracellular elementary bodies to target cells (mostly on the respiratory or urogenital epithelium)
  2. Endocytosis
  3. Transformation into reticulate bodies in the endosome
• Second phase: reticulate bodies (represent the obligate intracellular, replicative, and metabolically active form of Chlamydiaceae)
  1. Replication by fission and aggregation of various reticulate bodies in the endosome (at which point they are called inclusion bodies)
  2. Transformation of reticulate bodies into elementary bodies
  3. Lysis of endosomes
  4. Release of newly formed elementary bodies and exit from cell
  5. New start of cycle

Elementary bodies survive in the Environment, Enter the cell via Endocytosis, and Evolve into reticulate bodies.

Reticulate bodies Replicate in the cell and Reorganize to elementary bodies.

Features

Infant pneumonia due to Chlamydia trachomatis (serotypes D–K)

• Transmission: perinatal transmission during delivery via contact with the genital flora of an infected mother ^[4]
• Incubation period: 4–12 weeks after delivery ^[5]
• Clinical features ^[4]
  • Staccato cough, tachypnea, nasal congestion
  • Typically afebrile, although a mild fever is possible
  • Accompanied by neonatal conjunctivitis in up to 50% of all cases
• Diagnostics ^[6]
  • Culture from the nasopharyngeal specimen
  • Nonculture tests, such as direct fluorescence antibody and nucleic acid amplification tests (NAATs), may be performed.
  • CBC may reveal eosinophilia. ^[7]
• Prevention: maternal screening and treatment before birth
• Treatment: oral erythromycin; , azithromycin ^[4]
• Complications: respiratory failure

Chlamydophila pneumoniae

• Transmission: person-to-person transmission of respiratory secretions via aerosols ^[8]
• Incubation period: 3–4 weeks
• Clinical features
  • Sometimes asymptomatic
  • General symptoms of atypical pneumonia
    • Fever
    • Non-productive cough
    • Headache
    • Myalgias
  • Sometimes associated with pharyngitis and hoarseness ^[9]
• Diagnostics ^[6][10]
  • Chlamydia IgG and IgM serology
  • NAAT: performed on the patient's nasopharyngeal swab or sputum
• Treatment
  • First-line treatment: oral azithromycin, clarithromycin
  • Second-line treatment: oral doxycycline
• Complications ^[8]
  • Asthma exacerbation
  • Myocarditis
  • Encephalitis

Chlamydophila psittaci (psittacosis , "parrot fever" , or ornithosis ) ^[11]

• Transmission
  • Airborne; (pathogens from feces and/or dander of infected birds)
  • Mainly affects individuals in contact with free-ranging birds or pets, or occurs as an occupational disease
• Incubation period: 5–14 days ^[11]
• Clinical features: Symptoms can vary greatly.
  • Acute onset of flu-like symptoms; , especially fever
  • Atypical pneumonia with non-productive cough
  • Headaches
  • Arthralgia, myalgia
• Diagnostics ^[12]
  • Culture of respiratory specimens (e.g., sputum, pleural fluid)
  • Polymerase chain reaction (PCR) of respiratory specimens
  • Serology for Chlamydophila psittaci IgG and IgM with the complement-fixation test (CFT) or micro-immunofluorescence (MIF); diagnosis requires either of the following:
    • Four-fold or greater increase in antibody titer between acute and convalescent sera
    • A single IgM antibody titer of 1:16 or higher
• Treatment
  • First-line treatment: doxycycline
  • Second-line treatment: macrolides (e.g., azithromycin, erythromycin)
    • Drugs of choice for children and pregnant women
    • Alternative: fluoroquinolones
• Complications ^[11][13]
  • Respiratory failure
  • Myocarditis, endocarditis
  • Meningoencephalitis
  • Hepatitis

Chlamydophila psittaci accumulates in parrots and other birds and causes atypical pneumonia.

Psittacosis is a notifiable disease and should be reported in most of the states.

Chlamydia trachomatis predominantly affects the genitourinary tract although it can cause pneumonia and neonatal conjunctivitis in infants born vaginally to infected mothers. Disease presentation depends on the serotype involved. Serotypes D–K cause genitourinary chlamydia (nonlymphogranuloma venereum), which presents with urethritis, proctitis, cervicitis, pelvic inflammatory disease, epididymitis, and prostatitis; serotypes L1–L3 cause lymphogranuloma venereum, which presents with either rectal infection (proctitis) or ulceration and inguinal lymphadenopathy.

Etiology

• Chlamydia trachomatis serotypes D–K ^[14]
• May be transmitted through genital-to-genital contact or oropharyngeal-to-genital contact

Epidemiology

• One of the most common STIs in the US ^[15]
• One of the most common causes of pelvic inflammatory disease ^[16]

Clinical features ^[17]

• The majority of infected individuals are asymptomatic. ^[15]
• Patients of any gender may present with urethritis (can cause dysuria; or polyuria) or proctitis
• Patients with female genitalia may additionally present with salpingitis, cervicitis, or symptoms of pelvic inflammatory disease.
  • (Muco)purulent vaginal discharge
  • Abnormal uterine bleeding
  • Postcoital bleeding
  • Dyspareunia
• Patients with male genitalia may additionally present with epididymitis or prostatitis.
• Symptoms of reactive arthritis may also be present. ^[2]

Perinatal transmission can cause neonatal chlamydial conjunctivitis or infant pneumonia due to C. trachomatis.

Diagnostics of genitourinary chlamydia ^[16]

• Preferred test: Nucleic Acid Amplification Test (NAAT)
  • Detects Chlamydia trachomatis RNA or DNA, e.g., by PCR ^[15]
  • Specimen collection: ^[16]
    • Individuals with female genitalia: vaginal swab (preferred), cervical swab, or first-void urine
    • Individuals with male genitalia: first-void urine (preferred) or urethral swab
    • Suspected exposure from rectal intercourse: rectal swab
• Other diagnostic tests: not routinely recommended; a culture may be preferred over NAAT in select circumstances. ^[18]

Management of genitourinary chlamydia ^[16]

Approach

• Start antibiotic therapy (even if asymptomatic), e.g., doxycycline or azithromycin. ^[17]
• Evaluate and treat sexual partners (offer expedited partner therapy where available).
  • All partners in the last 60 days
  • OR, if no partners in the past 60 days, the most recent partner
• Test for common sexually transmitted coinfections.
  • All patients: HIV testing, gonorrhea testing, syphilis testing
  • Men who have sex with men (MSM) diagnosed with chlamydia on a rectal sample: Consider testing for LGV. ^[19]
• Offer patients counseling on safer sex practices including HIV PrEP where appropriate. ^[16]
• Advise patients to abstain from sexual intercourse until all the following criteria are met:
  • Completion of a 7-day regimen or for 7 days after a single-dose regimen
  • Symptom resolution
  • All sexual partners have completed treatment
• Report all cases of genitourinary chlamydia to the local health department. ^[20]

Doxycycline is contraindicated in pregnancy; pregnant patients should be treated with azithromycin. ^[16]

Consider child sexual abuse and human trafficking in adolescents presenting with genitourinary chlamydia.

Antibiotic therapy

• When possible, provide the complete regimen and administer the first dose at the time of visit.
• Recommended regimens
  • Nonpregnant individuals
    • First-line: doxycycline ^[16]
    • Alternative: azithromycin OR levofloxacin (off-label) ^[16]
  • Pregnant individuals
    • Preferred: azithromycin
    • Alternative: amoxicillin ^[16]

Patients with gonorrhea coinfection should be treated with oral doxycycline plus a single dose of intramuscular ceftriaxone. ^[16]

If nonadherence to treatment is a concern, directly observed therapy with azithromycin (given as a single dose) is preferred. ^[16]

Follow-up ^[16]

• Follow-up of pregnant patients with chlamydia
  • Perform a test of cure at 4 weeks.
  • Repeat after 3 months.
  • Individuals with ongoing risk factors for STIs should also be screened for chlamydia in the third trimester. ^[16]
• Follow-up of nonpregnant patients with chlamydia
  • Consider retesting at 4 weeks if any of the following are present:
    • Persistent symptoms
    • Concern for reinfection
    • Concern for poor adherence to treatment regimen
  • Otherwise, retest at 3 months.

Complications ^[16][18]

• PID → Fitz-Hugh-Curtis syndrome
• Ectopic pregnancy
• Infertility
• Reactive arthritis
• Perinatal transmission causing:
  • Neonatal chlamydial conjunctivitis
  • Infant pneumonia due to Chlamydia trachomatis

Screening for chlamydia ^[15][16]

Screen patients using NAAT.

Best practices for screening transgender individuals have not been established; tailor screening to the patient's anatomy. See also “Principles of transgender health care.” ^[16][17]

Screening is typically performed simultaneously with screening for gonorrhea.

Etiology ^[16]

• Caused by Chlamydia trachomatis serotypes L1–L3 ^[16]
• Rectal infection has been associated with mucosal trauma, e.g., from receptive fisting, sex toy use, and group sex. ^[22][23]

C. trachomatis serotypes L1-L3 cause Lymphogranuloma venereum.

Epidemiology

• Globally: more common in tropical and subtropical regions ^[19]
• In high-income countries: increasing incidence among MSM ^[22]

Clinical features ^[16][19]

• Rectal infection (most common): proctitis or proctocolitis
  • ∼ 50% of cases may be asymptomatic or mild. ^[22]
  • Mild symptoms: constipation, mucous streaking of stool ^[23]
  • Severe symptoms: rectal pain, bleeding, and discharge; tenesmus, and systemic symptoms ^[16]
• Genital or anal infection: genital and inguinal disease ^[19]
  • Primary infection (after approx. 1 week)
    • Small, painless genital ulcers (herpetiform) that heal spontaneously within a few days
    • May be accompanied by mucopurulent discharge
  • Secondary infection (2–6 weeks after onset of primary infection)
    • Painful swelling of the lymph nodes in the inguinal region (buboes)
    • If lymph nodes are enlarged above and below the inguinal ligament, the characteristic groove sign may be seen.
    • In one-third of cases, an abscess forms and may rupture, discharging pus.
• Oral infection: oral ulceration, which may be followed by cervical lymphadenopathy ^[16]

Ulcers may have healed by the time patients present with painful lymphadenopathy. ^[16]

Diagnostics ^[16]

• Presumptive diagnosis: recommended, based on the following
  • Clinical presentation
  • Epidemiological information
  • NAAT for C. trachomatis taken from the site of the patient's symptoms, e.g.:
    • Rectal specimen (if symptoms of proctocolitis are present)
    • Swabs of genital or oral lesions
    • Lymph node aspirate ^[19]
  • Exclusion of differential diagnoses of LGV
  • Rectal gram stain in proctitis or proctocolitis: More than 10 WBC per high power field suggests LGV proctitis. ^[16][24]
• Definitive diagnosis: genotyping (e.g., by PCR) of sample taken for NAAT to identify the C. trachomatis serotypes associated with LGV ^[16]

If clinical suspicion for LGV is high, start antibiotic treatment immediately rather than waiting for the results of diagnostic testing. ^[16]

Management ^[16]

Approach

• Start antibiotic therapy; (preferably doxycycline). ^[17]
• Consider bubo drainage.
• Evaluate and treat: ^[16]
  • All partners in the last 60 days ^[16][19]
  • The most recent sexual partner (if no history of sexual contact in the last 60 days).
• Testing for common sexually transmitted coinfections is recommended: HIV testing, gonorrhea testing, syphilis testing.
• Offer patients counseling on safer sex practices, including HIV PrEP where appropriate.
• Advise patients to abstain from sexual intercourse until all the following criteria are met: ^[19]
  • Antibiotic course has been completed
  • Resolution of symptoms
  • All sexual partners have completed treatment
• Report all cases of LGV to the local health department. ^[20]

Antibiotic therapy ^[16]

• Initiate antibiotic treatment without waiting for NAAT results for patients with:
  • Severe proctocolitis symptoms (bloody discharge, tenesmus, or rectal ulcers)
  • Severe inguinal buboes
  • Genital ulcer without an alternative etiology
• Symptomatic patients
  • First-line: doxycycline ^[16]
  • Alternatives: azithromycin (off-label) OR erythromycin ^[16]
  • Pregnant patients: Consider azithromycin (off-label) or erythromycin.
• Asymptomatic partners: short course doxycycline ^[16]

Bubo drainage ^[16][19]

• Consider drainage to prevent formation of ulcers or fistulas.
• Options include needle aspiration or incision and drainage. ^[19]

Follow-up ^[16]

• Regularly reassess the patient until signs and symptoms have resolved.
• Retest for C. trachomatis after completion of treatment.
  • Pregnant women: at 4 weeks
  • Other patients: at 3 months (up to 12 months, if necessary) ^[16]

Differential diagnoses of LGV

• Ulcerations/lymphadenopathy
  • Granuloma inguinale
  • Syphilis
  • Herpes simplex virus
  • Mpox
  • See also “Differential diagnosis of genital lesions” and “Localized lymphadenopathy.”
• Proctitis or proctocolitis ^[23]
  • Gonorrhea
  • Genitourinary chlamydia
  • Syphilis
  • Herpes simplex virus
  • Mpox
  • Gastrointestinal pathogens, e.g., Shigella spp, Escheria coli
  • Inflammatory bowel disease

Lymphogranuloma venereum (pathogen: Chlamydia trachomatis serotypes L1–L3) should not be mistaken for granuloma inguinale (pathogen: Klebsiella granulomatis).

Complications ^[16][19]

Complications represent a tertiary stage of the disease. ^[19]

• Fibrotic changes; strictures in the anogenital tract
• Genital elephantiasis, chronic lymphedema
• Reactive arthritis