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., vaginitis, 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. All ocular manifestations are discussed in more detail in the “Conjunctivitis” article.

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; (drug of choice), 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.

Chlamydial genitourinary infections

• Pathogen: : Chlamydia trachomatis serotypes D–K (see “Sexually transmitted infections”)
• Epidemiology
  • One of the most common STIs in the US (∼ 1.5 million reported infections per year) ^[14]
  • One of the most common causes of pelvic inflammatory disease
• Types of infections
  • Men: epididymitis, prostatitis
  • Women: salpingitis, cervicitis
  • Both men and women: urethritis, proctitis ^[15]
• Clinical features
  • The majority of infected individuals are asymptomatic, which leads to a delay in seeking treatment, and thus increases the risk of disease transmission.
  • (Muco)purulent vaginal discharge; and/or intermenstrual/postcoital bleeding
  • Possible dysuria; , pollakiuria, polyuria, dyspareunia
  • See “Pelvic inflammatory disease” for more information.
• Diagnostics
  • NAAT: gold standard
    • PCR detects Chlamydia trachomatis RNA or DNA from vaginal swabs (women) or first-catch urine (men).
    • Helps differentiate between C. trachomatis and N. gonorrhea
  • Antigen detection
    • Uses an enzyme immunoassay
    • The specimen is collected with a swab from the cervix or urethra.
    • The sensitivity is 80–95%. ^[15]
  • Other diagnostic tests ^[16]
    • Culture: rarely used nowadays
    • Serology: may be helpful in the diagnosis of chronic and invasive infections; not performed routinely
• Treatment ^[17]
  • Doxycycline or azithromycin or levofloxacin ^[18]
    • If gonococcal infection is suspected, combine azithromycin with ceftriaxone. ^[19]
    • Pregnant women: azithromycin
  • Expedited partner therapy is recommended in most cases of STIs, particularly chlamydia and gonorrhea.
  • Asymptomatic patients should also be treated to prevent serious complications (e.g., PID and infertility) and further spreading. ^[20]
  • Children
    • Erythromycin for children weighing < 45 kg
    • Azithromycin for children weighing > 45 kg
    • Doxycycline may also be used in children > 8 years of age.
    • Fluoroquinolones are contraindicated.
• Complications
  • PID
  • Fitz-Hugh-Curtis syndrome
  • Ectopic pregnancy
  • Infertility
  • Reactive arthritis
  • Perinatal transmission of infection to the newborn is possible and may result in conjunctivitis, otitis media, and/or pneumonia .
• Screening for chlamydia (USPSTF recommendations)
  • Annual NAAT screening of chlamydia (typically also gonorrhea) for: ^[21]
    • Sexually active women ≤ 24 years
    • Women > 24 years with risk factors (e.g., new or multiple sex partners, sex partner with an STI)
  • If positive for chlamydia, screen for HIV and other STIs. ^[17]

Lymphogranuloma venereum ^[22]

• Pathogen: Chlamydia trachomatis serotypes L1–L3 (see “Sexually transmitted infections”)
• Epidemiology
  • Most common in tropical and subtropical countries
  • Increasing incidence among men who have sex with men
• Clinical features
  • Primary infection; (after approx. one week): small, painless genital ulcers (herpetiform) that heal spontaneously within a few days
  • Secondary infection; (after approx. 3 weeks): painful swelling of the lymph nodes in the inguinal region (buboes) with abscess formation (pus discharge) and systemic symptoms
• Diagnostics: NAAT using swabs of the anogenital lesions, rectal mucosa, and/or lymph node specimens ^[23]
• Treatment: doxycycline or erythromycin
• Complications
  • Fibrotic changes; strictures in the anogenital tract
  • Genital elephantiasis; chronic lymphedema
  • Infertility

C. trachomatis serotypes L1-L3 cause Lymphogranuloma venerum.

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