Chlamydia

Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. Chlamydiae species have a complex replication cycle consisting of 2 morphological forms: elementary bodies and reticulate bodies. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Sometimes, C. psittaci and C. pneumoniae are classified as a separate genus, Chlamydophila. C. trachomatis is the most common bacterium responsible for causing sexually transmitted diseases in the United States and is associated with urogenital infections, lymphogranuloma venereum, neonatal conjunctivitis, and trachoma. C. psittaci causes psittacosis (parrot fever), whereas C. pneumoniae causes atypical pneumonia.

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General Characteristics

General characteristics

  • Obligate intracellular bacteria:
    • Cannot produce their own adenosine triphosphate (ATP)
    • Capable of synthesizing their own macromolecules
  • Staining:
    • Visualized using Giemsa stain: nucleic acid stain
    • Classified as gram-negative bacteria, but exhibit poor Gram staining 
    • Cell wall shows some characteristics of gram-negative bacteria, but lacks peptidoglycans.
    • Lack of peptidoglycans makes them insensitive to β-lactam antibiotics.
    • Iodine stain: to visualize inclusion bodies (replicating intracellular forms)
  • Life cycle:
    • Elementary body (EB): infectious, metabolically inactive, spore-like
    • Reticulate body (RB): non-infectious, metabolically active, replicative form (seen only within host cells)
  • Pathogenic species:
    • C. trachomatis 
    • C. psittaci 
    • C. pneumoniae

Mnemonic

To help recall the characteristics of the life cycle, remember the 3 Es and 2 Rs:

  • Elementary bodies Enter the cells and are the “Enfectious” form.
  • Reticular bodies Replicate.

Reservoirs, transmission, and risk factors

Table: Reservoirs, transmission, and risk factors
C. trachomatisC. psittaciC. pneumoniae
Host rangeHumans primarily
  • Animals primarily
  • Humans occasionally
Humans only
Transmission
  • Sexual contact
  • Autoinoculation
  • Ocular-genital contact
  • Passage through the birth control
Inhalation of contaminated, dried bird fecesAerosolized droplets
Risk factors
  • Age < 25 years
  • Reports of new sexual partners in the last 3 months
  • History of prior C. trachomatis infection
  • Inconsistent use of condoms
Exposure to birdsCrowded settings (schools, nursing homes); the elderly are at higher risk for severe disease.

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Clinical Relevance (C. trachomatis)

Epidemiology

  • Most common bacterial cause of sexually transmitted genital infections in the United States
  • More prevalent in young adults (< 26 years of age)
  • Higher incidence in African Americans, Alaskans, and Native Americans
  • Co-infection with other sexually transmitted pathogens is common.
  • Trachoma (ocular infection) is endemic in some areas of Africa, Asia, Latin America, the Middle East, and the Pacific Rim.
  • Leading infectious cause of blindness worldwide

Transmission

  • 1 in 20 sexually active young women aged 14–24 years has chlamydia.
  • Many infections are asymptomatic, especially in women.
  • Rates of transmission between symptomatic and asymptomatic individuals are unknown.
  • Trachoma:
    • Person-to-person through ocular and nasal secretions
    • Eye-seeking flies

Pathogenesis

  • Elementary bodies invade the host cell through endocytosis.
  • Inside the cell, they convert to the metabolically active reticulate bodies.
  • Reticulate bodies replicate inside the host cell via fission.
  • They then reorganize into elementary bodies that are released from the cell.
  • Clusters of replicating reticulate bodies are known as inclusion bodies and can be visualized using Giemsa, Pap, or iodine staining.
  • There are multiple serovars of C. trachomatis:
    • Serovars A–C: cause trachoma
    • Serovars D–K: 
      • Most common sexually transmitted infection in the United States
      • Also associated with neonatal conjunctivitis and pneumonia (acquired during passage through the birth canal)
    • Serovars L1–L3: 
      • Also sexually transmitted
      • Cause lymphogranuloma venereum (LGV)

Clinical presentation

Sexually transmitted:

  • Urogenital infections (serovars D–K):
    • In women: 
      • Often asymptomatic 
      • Cervicitis
      • Urethritis
      • Salpingitis
      • Pelvic inflammatory disease (PID)
      • Symptoms include mucopurulent discharge, dysuria, and pyuria
    • In men: 
      • Urethritis
      • Epididymitis
      • Proctitis
  • Systemic disease:
    • Usually follows a sexually transmitted infection
    • Arthritis
    • Dermatitis
    • Reactive arthritis; reactive arthritis triad (RAT):
      • Arthritis, urethritis, and uveitis
      • More common in men
  • Lymphogranuloma venereum (serovars L1–L3):
    • Primary infection: genital ulcer, usually small and painless
    • Secondary infection:
      • Involvement of regional lymph nodes (inguinal, perianal)
      • Presents with severe inflammation and scarring

Neonatal infections (serovars D–K):

  • Neonatal conjunctivitis:
    • Occurs 2–30 days following birth
    • Causes eyelid swelling, hyperemia, and purulent discharge
    • Can lead to conjunctival scarring and corneal vascularization
    • Prevention: routine topical erythromycin after birth
  • Infant pneumonia:
    • Occurs 2–3 weeks after birth
    • Causes diffuse interstitial pneumonia if untreated

Trachoma (serovars A–C):

  • Early-stage (active trachoma): 
    • Conjunctivitis
    • Redness, light sensitivity, mucopurulent discharge
  • Late-stage (cicatrical trachoma):
    • Conjunctival scarring
    • Repeated infections lead to eyelid scarring, entropion, and eventually corneal damage and blindness.

Identification

  • Nucleic acid amplification testing (NAAT): gold standard
  • Other tests mostly used for research purposes:
    • Serology
    • Culture (needs to be grown in tissue culture)
    • Antigen detection
    • Genetic probe methods

Clinical Relevance (C. psittaci and C. pneumoniae)

C. psittaci

  • Causes about 1% of community-acquired pneumonia (psittacosis or “parrot fever”)
  • Transmitted from birds, usually by inhalation of dried feces
  • Human-to-human transmission is possible.
  • Incubation period 5–14 days
  • Systemic symptoms (may be more prominent than respiratory):
    • Fever, myalgias, sweats, rigors
    • Headache (may be severe), photophobia
  • Respiratory symptoms: cough, dyspnea, chest pain, hemoptysis
  • Complications (renal, neurological, hematological) are uncommon, but may occur.

C. pneumoniae

  • Responsible for 1%–20% cases of community-acquired pneumonia
  • Human-to-human transmission through respiratory droplets or contact
  • Presents with fever, cough, shortness of breath
  • Varies in severity from mild to lethal
  • Can cause pharyngitis and upper respiratory symptoms
  • Chronic infection may contribute to the pathogenesis of atherosclerosis (nucleic acid of other bacteria and viruses have also been found in atherosclerotic plaques).

References

  1. Hammerschlag M. R. (2019). Pneumonia caused by Chlamydia pneumoniae in adults. Retrieved 05 January 2021, from https://www.uptodate.com/contents/pneumonia-caused-by-chlamydia-pneumoniae-in-adults
  2. Hsu K. (2019). Clinical manifestations and diagnosis of Chlamydia trachomatis infections. Retrieved 05 January 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chlamydia-trachomatis-infections
  3. Hsu K. (2019). Epidemiology of Chlamydia trachomatis infections. Retrieved 05 January 2021, from https://www.uptodate.com/contents/epidemiology-of-chlamydia-trachomatis-infections
  4. Richards M. R. (2020). Psittacosis. Retrieved 05 January 2021, from https://www.uptodate.com/contents/psittacosissearch=chlamydia%20psittaci
  5. Zhao, Xue-Qiao. (2020). Pathogenesis of atherosclerosis. Retrieved January 12, 2021, from https://www.uptodate.com/contents/pathogenesis-of-atherosclerosis

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