Chlamydia

Chlamydiae are obligate intracellular gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview. 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 Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis, and trachoma. C. psittaci causes psittacosis (parrot fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever), whereas C. pneumoniae causes atypical pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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General Characteristics

General characteristics

  • Obligate intracellular bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
    • 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 Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, but exhibit poor Gram staining 
    • Cell wall shows some characteristics of gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, 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. trachomatis C. psittaci C. pneumoniae
Host range Humans primarily
  • Animals primarily
  • Humans occasionally
Humans only
Transmission
  • Sexual contact
  • Autoinoculation
  • Ocular-genital contact
  • Passage through the birth control
Inhalation of contaminated, dried bird feces Aerosolized 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 birds Crowded 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 Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections in the United States
      • Also associated with neonatal conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis and pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. 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 Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease (PID)
      • Symptoms include mucopurulent discharge, dysuria, and pyuria
    • In men: 
      • Urethritis
      • Epididymitis Epididymitis Epididymitis and orchitis are characterized by acute inflammation of the epididymis and the testicle, respectively, due to viral or bacterial infections. Patients typically present with gradually worsening testicular pain and scrotal swelling along with systemic symptoms such as fever, depending on severity. Epididymitis and Orchitis
      • Proctitis
  • Systemic disease:
    • Usually follows a sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Overview: Sexually Transmitted Infections
    • Arthritis
    • Dermatitis
    • Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis; reactive arthritis triad (RAT):
      • Arthritis, urethritis, and uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
      • 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 Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and scarring

Neonatal infections (serovars D–K):

  • Neonatal conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. 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 Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia:
    • Occurs 2–3 weeks after birth
    • Causes diffuse interstitial pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. 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 Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia (psittacosis or “parrot fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. 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 Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis
  • Complications (renal, neurological, hematological) are uncommon, but may occur.

C. pneumoniae

  • Responsible for 1%–20% cases of community-acquired pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Human-to-human transmission through respiratory droplets or contact
  • Presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, cough, shortness of breath
  • Varies in severity from mild to lethal
  • Can cause pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis and upper respiratory symptoms
  • Chronic infection may contribute to the pathogenesis of atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis (nucleic acid of other bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview 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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