Chlamydial Infections

Chlamydial infections are a group of infectious diseases caused by bacteria belonging to the Chlamydiaceae family. The 3 species that can infect humans are Chlamydia trachomatis, C. pneumoniae, and C. psittaci. The most common infection is an STI caused by C. trachomatis, which affects the genitourinary tract. Chlamydia is the most common sexually transmitted bacterial infection in the United States. Other species of Chlamydia mainly cause respiratory infections. Diagnosis is based on nucleic acid amplification tests. Management is with antibiotics. Untreated chlamydial infections may have serious consequences, including sterility, ectopic pregnancies, spontaneous abortions, and chronic pelvic inflammatory disease.

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Overview

Definition

Chlamydial infections are infectious diseases caused by bacteria belonging to the Chlamydiaceae family.

Epidemiology

  • Chlamydia trachomatis:
    • Most commonly affects young adults (15–22 years)
    • Chlamydia is the most common bacterial STD in the United States.
    • 30%–50% of all cases of sterility are caused by Chlamydia.
    • 90% of all cases of sterility from fallopian-tube closure result from chlamydial infections.
    • 2%–3% of pregnant women are populated with C. trachomatis (transmission rate to the infant is 50%).
    • Trachoma (ophthalmic chlamydia):
      • Occurs almost exclusively in tropical countries in individuals living in poor-hygiene conditions
      • After cataract, trachoma is the 2nd most common cause of blindness in the world.
  • C. psittaci:
    • Responsible for 1% of community-acquired pneumonia cases
    • Birds are the main reservoir.
    • Risk groups:
      • Bird owners
      • Animal keepers and vets
      • Employees in pet shops, poultry farms, and slaughterhouses
    • Human-to-human transmission is rare.
  • C. pneumoniae:
    • Age distribution is bimodal: 3–6 years and 60–80 years
    • C. pneumoniae is a very common cause of respiratory infections worldwide.
    • Prevalence of seropositivity is 50% by age 20, and 70%–80% by age 60.

Transmission

  • C. trachomatis:
    • Via vaginal, anal, or oral sex, or direct contact with infected tissues, such as conjunctiva
    • From an infected mother to the baby during vaginal childbirth
    • Serovars a–c: infectious eye secretions, contaminated hands, towels (smear infection), flies
    • Serovars d–k: sexually transmitted, perinatal
    • Serovars l1–l3: sexually transmitted, causes lymphogranuloma venereum
    • Incubation period is 1–3 weeks.
  • C. psittaci:
    • The only zoonotic human pathogen from the Chlamydiaceae family
    • Originates mainly from birds (chickens, ducks, pigeons, exotic birds)
    • Infection by direct contact, or inhalation of dust particles or feces
    • Pathogens are partly infectious even after drying out for up to 4 weeks.
    • Incubation period is 1–4 weeks.
  • C. pneumoniae:
    • Transmitted from person to person via respiratory droplets, aerosolized particles, and fomites
    • Incubation period is 1–4 weeks.
    • C. pneumoniae persists for a long time in the upper respiratory tract.
    • Affected individuals can infect others for a long period of time.

Pathophysiology and Clinical Presentation

Pathophysiology

  • Chlamydia are obligate intracellular bacteria.
  • Classified as gram-negative bacteria but exhibit poor Gram staining
  • Exist in 2 forms: elementary bodies (metabolically inactive) and reticulate bodies
  • Elementary bodies invade the host cell through endocytosis.
  • Inside the cell, elementary bodies convert to metabolically active reticulate bodies.
  • Reticulate bodies replicate inside the host cell via fission.
  • After replication, reticulate bodies reorganize into elementary bodies and are released from the cell.
  • Clusters of replicating reticulate bodies are known as inclusion bodies.
  • C. trachomatis has multiple serovars that cause different clinical manifestations.

C. trachomatis infections

Genital disease (serovars d–k):

  • Women:
    • Fever
    • Urethritis:
      • Painful urination
      • Frequent urination
      • Pyuria
    • Vaginitis: abnormal vaginal discharge
    • Cervicitis/salpingitis:
      • Painful sexual intercourse
      • Abdominal pain
    • Pelvic inflammatory disease (PID):
      • Chronic pelvic pain
      • Difficulty becoming pregnant
      • Ectopic (tubal) pregnancy
  • Men:
    • Painful or burning sensation when urinating
    • Unusual discharge from the penis
    • Testicular pain or swelling
    • Fever
    • Epididymitis
    • Proctitis

Infant disease:

  • Maternal infection can cause spontaneous abortion and premature birth.
  • Transmission to infants occurs during passage through the birth canal.
  • Conjunctivitis (50% transmission rate in maternal infection):
    • Typically occurs 1 week after birth
    • Purulent, mucopurulent, hemorrhagic inflammation of the conjunctiva
    • Eyelid edema
    • Follicular infiltration of the inner eyelid
    • Occurs in 1 eye and then in the other
    • Mostly inconsequential healing
  • Pneumonia:
    • Tachypnea
    • ↑ Respiratory effort
    • Snorkeling sounds while breathing
    • Refusal of food
    • Cyanosis in severe cases
  • Post-infection complications:
    • More common in young men
    • Follow an STD
    • Autoimmune in origin
    • Reactive arthritis
    • Reactive arthritis triad (RAT):
      • Urethritis
      • Conjunctivitis
      • Arthritis

Eye disease (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.

Lymphogranuloma venereum (serovars l1–l3):

  • Sexually transmitted C. trachomatis infection of the lymph nodes and lymphatics
  • Presents with genital ulceration and painful swollen lymph nodes in the groin (often unilateral)
  • Can result in rectal inflammation, fever, or swollen lymph nodes in other parts of the body

Respiratory diseases caused by C. pneumoniae and C. psittaci

  • C. pneumoniae infections are frequently asymptomatic, but can present as:
    • Pharyngitis
    • Sinusitis
    • Bronchitis
    • Pneumonia
    • All symptoms of C. psittaci infections can also occur in C. pneumoniae infections.
  • Acute C. psittaci infections are more symptomatic:
    • Atypical and interstitial pneumonia
    • Dry, persistent, nonproductive cough
    • Extrapulmonary manifestations: 
      • Fever/chills
      • Headaches
      • Photophobia
      • Myalgia
      • Hepatosplenomegaly: 70% of patients
      • Myocarditis
      • Encephalitis
      • Exanthema

Diagnosis

History:

  • Genital infections:
    • Young age
    • Sexually active with multiple partners
    • Urogenital symptoms
    • Abdominal/pelvic pain, fever
  • Trachoma: 
    • Contact with affected individuals
    • Individuals residing in endemic areas
  • Respiratory disease:
    • Exposure to birds
    • Exposure to affected individuals

Physical exam:

  • Genital infections:
    • Tenderness in the lower abdomen
    • Cervical-motion tenderness on pelvic exam
    • Vaginal or penile discharge
    • Inguinal lymphadenopathy, genital lesions (lymphogranuloma venereum)
  • Trachoma: eye exam
  • Respiratory disease:
    • Pharyngitis/sinusitis
    • Wheezing, crackles, decreased breath sounds

Laboratory studies:

  • Nucleic acid amplification test (gold standard):
    • Can be used for different specimens:
      • Cervical or vaginal swabs (women), urethral swabs (men)
      • Clean-catch urine samples
      • Nasopharyngeal swabs, sputum, or bronchoalveolar lavage
    • Amplification of bacterial DNA or RNA sequences using:
      • PCR
      • Transcription-mediated amplification (TMA)
      • DNA strand displacement amplification (SDA)
      • Ligase chain reaction (LCR)
    • Very specific in differentiating chlamydial infections from gonococcal infections
  • Serology testing:
    • More useful in chronic infections
    • Not frequently performed
  • Antigen testing: 
    • Enzyme immunoassay
    • Requires invasive (cervical or urethral) swabs
  • Culture: 
    • Chlamydia require tissue culture to grow
    • Difficult: requires expertise, reserved mostly for research purposes
  • Genetic probe:
    • Requires invasive (cervical or urethral) swabs
    • Lower sensitivity than nucleic acid amplification test
    • Less expensive than nucleic acid amplification test

Management and Complications

Genital infections

General approach:

  • Treatment is with antibiotics.
  • All exposed individuals should be treated to prevent complications, regardless of symptoms.
  • Tests for other STDs should be performed.
  • Therapy for concomitant gonococcal infection, if appropriate
  • HIV test, if status is unknown
  • Sexual partners should be treated.
  • Abstinence for 1 week following treatment completion
  • Retesting for recurrent infection 3 months after treatment
  • Re-evaluation if persistent or recurrent symptoms

Antibiotics:

  • Uncomplicated genital infections (cervicitis/urethritis):
    • 1st line: doxycycline (7 days) or azithromycin (single dose)
    • 2nd line: quinolones for 7 days
  • Proctitis: doxycycline + single dose of ceftriaxone
  • Epididymitis: ceftriaxone + doxycycline for 10 days
  • PID: broad coverage with doxycycline
  • Pregnant women: 
    • Azithromycin: single dose
    • Alternatives: erythromycin or amoxicillin
  • Infants:
    • Oral erythromycin preferred for conjunctivitis and pneumonia
    • Alternative: azithromycin
    • Routine neonatal prophylaxis for gonococcal conjunctivitis is not effective against Chlamydia.

Other infections

Trachoma:

  • Community-based therapy rather than individual treatment due to high transmission rates
  • 1st-line therapy: single dose of oral azithromycin
  • Topical tetracycline can be used if oral azithromycin is not available.

Pneumonia:

  • Empiric therapy:
    • Before pathogen is definitively established
    • Includes macrolides, quinolones, and doxycycline
  • Directed therapy:
    • Doxycycline (7–10 days): 1st-line therapy for C. psittaci infections
  • Azithromycin (5 days): 1st-line therapy for C. pneumoniae infections
Summary of possible complications of Chlamydia infections
C. trachomatisC. psittaciC. pneumoniae
  • Reactive arthritis
  • Sterility
  • PID
  • Ectopic pregnancy
  • Epididymitis
  • Prostatitis
  • Myocarditis
  • Pericarditis
  • Endocarditis
  • Thrombophlebitis
  • CNS involvement
  • Carditis
  • Meningoradiculitis
  • Erythema nodosum
  • Reactive arthritis
Pelvic inflammatory disease (PID), central nervous system (CNS)

Differential Diagnosis

  • Gonorrhea: an STD caused by Neisseria gonorrhoeae that presents with cervicitis, urethritis, and proctitis, and frequently coexists with a chlamydial infection. Gonorrhea can be diagnosed based on nucleic acid amplification test or culture. Treatment is with antibiotics.
  • Herpes: Genital herpes infections are common STIs caused by herpes simplex virus-1 and -2. Primary infection often starts with prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base. Dysuria and painful lymphadenopathy are other manifestations. Herpes infections remain dormant in the neuronal ganglia, which allows for recurrent infections. Treatment is with antiviral therapy.
  • Syphilis: a bacterial infection that usually spreads by sexual contact. Syphilis begins as a painless sore on the genitals, rectum, or mouth. The mode of transmission is via the skin or contact of the mucous membranes with sores. The causative organism can remain dormant in the body before reactivating at certain times. Treatment is with penicillin injection. If untreated, syphilis can damage internal organs and lead to fatality.
  • Genital warts: a manifestation of human papillomavirus (HPV) infection, which is common in adolescents and presents with warts in the genital area. Diagnosis can be made clinically. Warts can be treated by surgical excision or local ablation. HPV has been linked to cervical cancer; therefore, prevention is very important.
  • Community-acquired pneumonia: a bacterial or viral infection of the lung parenchyma. Community-acquired pneumonia can be caused by several organisms and presents with constitutional and respiratory symptoms similar to chlamydial pneumonia. Diagnosis is usually established using sputum cultures. Antibiotics are the mainstay of therapy.

References

  1. Hammerschlag, M. R. (2019). Pneumonia caused by Chlamydia pneumoniae in adults. Retrieved February 1, 2021, from https://www.uptodate.com/contents/pneumonia-caused-by-chlamydia-pneumoniae-in-adults
  2. Hsu, K. (2020). Clinical manifestations and diagnosis of Chlamydia trachomatis infections. Retrieved January 20, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chlamydia-trachomatis-infections
  3. Hsu, K. (2020). Treatment of Chlamydia trachomatis infection. Retrieved January 20, 2021, from https://www.uptodate.com/contents/treatment-of-chlamydia-trachomatis-infection
  4. Richards, M.J. (2020). Psittacosis. Retrieved February 1, 2021, from https://www.uptodate.com/contents/psittacosis
  5. Stamm, W.E. Chlamydia trachomatis infections of the adult. In: Sexually Transmitted Diseases, 4th Edition, Holmes K.K., Sparling P.F., Mardh P.A., et al. (Eds), McGraw-Hill, New York 2008. P.575.
  6. Quinn, T.C., Gaydos C.A. (2015). Treatment for Chlamydia infection–doxycycline versus azithromycin. N Engl J Med; 373:2573.

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