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Chlamydial Infections¶

Infectious Diseases | Part 5 – Infectious Diseases: Bacterial · Part 5 – Infectious Diseases: Bacterial · Chapter 194

Key Clinical Points¶

Chlamydiae are obligate intracellular bacteria with a unique biphasic life cycle (Elementary Bodies and Reticulate Bodies).
C. trachomatis is the most prevalent bacterial STI globally, with high asymptomatic rates (83.9% in men, 87.1% in women).
Untreated infections lead to serious complications: PID, infertility, ectopic pregnancy, and chronic pelvic pain.
LGV (serovars L1-L3) causes invasive systemic disease and requires extended treatment (21 days).
Reactive arthritis occurs in 1–2% of NGU cases; associated with HLA-B27 in non-African populations.
NAAT is the gold standard for diagnosis, detecting ~95% of infections compared to ~60% for culture.
CDC recommends annual screening for sexually active women <25 and 3-month post-treatment rescreening.
Neonatal transmission results in inclusion conjunctivitis and pneumonia; requires specific screening/treatment.
Proctitis in MSM may be caused by LGV, presenting as severe ulcerative proctitis resembling HSV disease.
Doxycycline (100 mg BID imes 7 days) or Azithromycin (1 g single dose) are standard first-line treatments.

1. DEFINITION & OVERVIEW¶

• Chlamydiae: Obligate intracellular bacteria causing diverse diseases in humans and nonhuman animals. • Classification of C. trachomatis: Divided into three biovars based on clinical presentation: ◦ Trachoma (serovars A, B, Ba, C) → Ocular trachoma, Urogenital infections ◦ Oculogenital (serovars D–K) → Cervicitis, Salpingitis, Urethritis, Epididymitis, Reactive Arthritis, Proctitis ◦ LGV (serovars L1-L3) → Lymphogranuloma Venereum (Invasive systemic STI) • Biphasic Growth Cycle: ◦ Elementary bodies (EBs): Infectious form; attach to host cells. ◦ Reticulate bodies (RBs): Replicating form; occur within the cell. ◦ Transition: EBs → RBs (replication) → EBs (reorganization for release). ◦ Timing: Cycle takes ~48–72 hours, resulting in a 1–3 week incubation period for STIs.

1.1 Etiologic Agents & Classification¶

• Serovar Significance: Serovars D–K cause urogenital infections; LGV serovars L1-L3 cause invasive systemic disease. Serovars are clinically relevant for LGV due to prolonged treatment requirements.

1.2 Biology & Growth Cycle¶

• Cycle Dynamics: The transition between EBs and RBs explains the 1–3 week incubation period for STIs.

2. EPIDEMIOLOGY¶

• Global Prevalence: ◦ WHO estimates 50 million prevalent cases in men and 77 million in women (2020). • U.S. Statistics: ◦ 1.65 million cases reported in 2022 (495/100,000 population). ◦ Women: 621.2/100,000; Men: 363.7/100,000. ◦ High-risk areas: Louisiana (788.6/100,000) and Black/African American populations (1,113.3/100,000). ◦ Annual healthcare costs exceed $516.7 million. • Asymptomatic Rates: ◦ High prevalence of asymptomatic infection: 83.9% in men, 87.1% in women. ◦ Highest rates among adolescents (57.7% of cases in 15–24 year olds). • Demographic/Setting Variations: ◦ College students: 5.9% (men), 8.8% (women). ◦ Prenatal patients: 3.3–8.3%; Family planning clinics: 7%; STI clinics: >10%.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• Genital Infections: Caused by C. trachomatis serovars D–K (D, E, and F most common). • Pathogenesis: ◦ Driven by immune-mediated mechanisms rather than direct cytopathic effects. ◦ Chlamydial heat-shock protein shares epitopes with human HSP → potential immune cross-reactivity. • Reactive Arthritis: ◦ Occurs in 4–15% of cases linked to C. trachomatis; 1–2% of NGU cases. ◦ Associated with HLA-B27 in non-African populations. ◦ Mechanism: Chlamydiae may spread via macrophages from genital to joint tissues.

4. CLINICAL FEATURES¶

• Genital Infections (NGU): ◦ 30–50% of cases caused by C. trachomatis. ◦ Symptoms: Mucoid discharge, dysuria. ◦ Note: Urethral exudate may require milking to visualize. • Epididymitis: ◦ Follows untreated urethritis; acute epididymitis (6 weeks duration) must be differentiated from tuberculosis. ◦ Symptoms: Unilateral scrotal pain/swelling, fever. • Reactive Arthritis: ◦ Presentation: Conjunctivitis, urethritis, arthritis, and mucocutaneous lesions (keratoderma blenorrhagicum). ◦ Sacroiliitis occurs in 66% of patients. • Pelvic Inflammatory Disease (PID): ◦ C. trachomatis causes up to 50% of PID cases in the U.S. ◦ Symptoms: Lower abdominal pain, fever, adnexal tenderness. • Proctitis: ◦ Occurs in MSM with receptive anal intercourse; symptoms include anorectal pain, bloody discharge. ◦ LGV serovars cause severe ulcerative proctitis resembling HSV disease.

5. DIFFERENTIAL DIAGNOSIS¶

• NGU: ◦ Gonococcal urethritis (purulent discharge). ◦ Mycoplasma genitalium (>40% of cases). ◦ Trichomonas vaginalis (<10% of cases). • PID: ◦ Endometritis, ectopic pregnancy, salpingitis due to N. gonorrhoeae. • Proctitis: ◦ HSV proctitis, Crohn's disease, gonococcal proctitis.

6. INVESTIGATIONS & DIAGNOSIS¶

Initial Assessment: Identify clinical syndrome (NGU, PID, Proctitis, Reactive Arthritis) and risk factors.
Microscopy/Culture (Preliminary): ◦ Men (NGU/PGU): Gram stain with ≥2 WBCs/HPF (high prevalence) or ≥5 WBCs/HPF (low prevalence); no GNID; leukocyte esterase test if microscopy is unavailable. ◦ Women (Cervicitis): Leukorrhea, defined as >10 WBCs/HPF on microscopic examination of vaginal fluid. ◦ Reactive Arthritis: Gram stain with ≥5 WBC/HPF; lack of GNID. ◦ Neonates: Negative culture and Gram's stain for gonococci, Haemophilus spp., pneumococci, staphylococci.
Confirmatory Testing (Gold Standard): ◦ NAAT (PCR or TMA) is the gold standard for detecting C. trachomatis DNA in urine, vaginal/cervical swabs, or rectal swabs. ◦ Culture: Less sensitive but useful for antimicrobial susceptibility testing.
Specific Diagnostic Criteria per Condition: ◦ Men (NGU/PGU): Urine NAAT. ◦ Women (Cervicitis): Vaginal or cervical NAAT. ◦ Women (Urethritis): Sterile pyuria; negative routine urine culture → Urine NAAT. ◦ Rectal: Negative gonococcal NAAT and Gram's stain; at least 1 WBC/HPF in rectal Gram's stain → NAAT. ◦ Reactive Arthritis: Gram stain with ≥5 WBC/HPF; lack of GNID → Urine or vaginal NAAT. ◦ Neonates: Tissue culture, conjunctival NAAT (not FDA cleared), or DFA-stained scraping of conjunctival material.

Table 1 Summary¶

Table 1 outlines the diagnostic pathway based on clinical presentation: ◦ Men (NGU/PGU): Gram stain ≥2-5 WBC/HPF + No GNID → Urine NAAT. ◦ Women (Cervicitis): Leukorrhea (>10 WBC/HPF) or clinical signs → Vaginal/Cervical NAAT. ◦ Women (Urethritis): Sterile pyuria, negative culture → Urine NAAT. ◦ Rectal: ≥1 WBC/HPF in rectal Gram + No Gonococcal infection → NAAT. ◦ Reactive Arthritis: Gram stain ≥5 WBC/HPF; no GNID → Urine or Vaginal NAAT. ◦ Neonates: Negative cultures for common pathogens → Tissue culture, Conjunctival NAAT (not FDA cleared), or DFA-stained scraping.

7. MANAGEMENT & TREATMENT¶

Standard Treatment (NGU/PID): ◦ Doxycycline: 100 mg BID imes 7 days. ◦ Azithromycin: 1 g single dose. ◦ Moxifloxacin: 400 mg BID imes 7 days.
Specialized Treatment (LGV): ◦ Doxycycline: 100 mg BID imes 21 days (required for extended treatment of invasive disease).
Screening Protocols: ◦ Women <25 years: Annual screening for sexually active individuals. ◦ Pregnant Women: Routine screening during first trimester; treat with Azithromycin 1 g single dose to prevent neonatal infection. ◦ MSM: Annual screening at anatomically exposed sites (rectal and pharyngeal).
Follow-up: ◦ Partners must be treated and retested at 3 months post-treatment.

7.1 Screening Guidelines¶

• Women <25: Annual screening. ◦ Pregnancy: First trimester screening; Azithromycin 1 g single dose. ◦ MSM: Annual rectal and pharyngeal screening.

8. PROGNOSIS & COMPLICATIONS¶

• Pelvic Inflammatory Disease (PID): ◦ Tubal factor infertility (30–40%). ◦ Ectopic pregnancy (5–10%). ◦ Chronic pelvic pain. • Lymphogranuloma Venereum (LGV): ◦ Rectal strictures in 10–20% of cases. • Reactive Arthritis: ◦ Resolves in 2–6 months but may recur.

9. SPECIAL CONSIDERATIONS¶

• Pregnancy: ◦ Screening at first prenatal visit; treat with Azithromycin 1 g single dose to prevent neonatal conjunctivitis and pneumonia. • MSM: ◦ Higher prevalence requires targeted annual screening of rectal and pharyngeal sites. • HIV Co-infection: ◦ Increased risk of persistent infection, PID complications, and severe reactive arthritis.

9.1 Pregnancy¶

• Screening during first prenatal visit; treatment with Azithromycin 1 g single dose.

9.2 MSM¶

• Annual screening for rectal and pharyngeal infections.

10. KEY PEARLS & CLINICAL TRAPS¶

• Asymptomatic Rates: 80–90% of women with genital chlamydia are asymptomatic. ◦ High prevalence in adolescents (57.7%). • LGV Treatment: Requires extended duration (21 days) compared to standard 7-day courses. ◦ LGV causes severe ulcerative proctitis in some cases. • Diagnostic Superiority: NAATs detect ~95% of infections, whereas culture only detects ~60%.

Reference Tables¶

TABLE 194-1 Diagnostic Tests for Sexually Transmitted and Perinatal Chlamydia trachomatis Infection INFECTION Men¶

Harrison's 22e, p.1473

INFECTION	SUGGESTIVE SIGNS/SYMPTOMS	PRESUMPTIVE DIAGNOSISa	CONFIRMATORY TEST OF CHOICE
Men
NGU, PGU	Discharge, dysuria	Gram’s stain with ≥2 WBCs/high power field (HPF) in high- prevalence settings (e.g., STI clinics) or ≥5 WBCs/HPF in lower-prevalence settings. No gram-negative intracellular diplococci (GNID). In the absence of microscopy: positive leukocyte esterase test on first catch urine	Urine NAAT for C. trachomatis
	Unilateral intrascrotal swelling, pain, tenderness; fever; NGU	Gram’s stain with ≥2 (or ≥5) WBCs/HPF; no GNID; urinalysis with pyuria
Women
Cervicitis	Mucopurulent cervical discharge, sustained endocervical bleeding easily induced by nontraumatic passage of a swab through the cervical os	Leukorrhea, defined as >10 WBCs/HPF on microscopic examination of vaginal fluid, might be a sensitive indicator of cervical inflammation with a high negative predictive value	Vaginal (or cervical) NAAT for C. trachomatis
	Lower abdominal pain, cervical motion tenderness, adnexal tenderness or masses	C. trachomatis always potentially present in salpingitis
Urethritis	Dysuria and frequency without hematuria	MPC; sterile pyuria; negative routine urine culture	Urine NAAT for C. trachomatis
Adults of Either Sex
	Rectal pain, discharge, tenesmus, bleeding; history of receptive anorectal intercourse	Negative gonococcal NAAT and Gram’s stain; at least 1 WBC/HPF in rectal Gram’s stain
Reactive arthritis	NGU, arthritis, conjunctivitis, typical skin lesions	Gram’s stain with ≥5 WBC/HPF; lack of GNID	Urine or vaginal NAAT for C. trachomatis
	Regional adenopathy, primary lesion, proctitis, systemic symptoms	None
Neonates
Conjunctivitis	Purulent conjunctival discharge 5–12 days after birth	Negative culture and Gram’s stain for gonococci, Haemophilus spp., pneumococci, staphylococci	Tissue culture, conjunctival NAAT for C. trachomatis (not FDA cleared); DFA-stained scraping of conjunctival material
	Subacute, afebrile pneumonia in infants aged 1–3 months	None