Sexually Transmitted Infections: Neisseria gonorrhoeae and Chlamydia trachomatis

MID Sexually Transmitted Infections

Overview

  • Definition of STIs vs. STDs: Traditionally described as sexually transmitted diseases (STDs), the term ‘disease’ can be misleading and stigmatizing.
    • Most infections caused by Neisseria gonorrhoeae and Chlamydia trachomatis are asymptomatic.
    • Untreated STIs can result in long-term damage such as infertility, miscarriage, newborn death, cancers, and chronic pain.
    • The term “STI” can reduce stigma/shame associated with “STD” and improve testing rates.
  • Importance of Testing: Widespread, point-of-care testing is essential to reduce transmission due to the high prevalence of asymptomatic infections.

Prevalence

  • Bacterial STIs are extremely common with Chlamydia and gonococcal infections being the most prevalent reportable infectious diseases in the 18-24 age group in the US.
  • Neisseria gonorrhoeae (N. gonorrhoeae):
    • Causative agent of gonorrhea, estimated 3 million cases per year in the U.S., with ~700,000 cases reported.
    • Globally, approximately 83 million cases annually.
    • Can cause Pelvic Inflammatory Disease (PID) in women and epididymitis in men.
    • Symptoms include purulent discharge due to the inflammatory response; asymptomatic carriage is prevalent.

Pathogenesis of Neisseria gonorrhoeae

  1. Entry, Encounter, & Multiplication

    • Human-only pathogen, typically spread by sexual contact.
    • Colonizes mucous membranes: urogenital tract, rectum, pharynx, conjunctiva.
    • Historically can cause blindness in newborns without antibacterial drops.
    • Symptoms often localized, but disseminated disease can occur such as arthritis.
    • Adhesion Mechanisms:
      • Binds to epithelial cells using Opa adhesins and pili.
      • Pili assist in forming microcolonies that are harder to remove and phagocytose; some epithelial cells may internalize bacteria, creating a reservoir for recurrent infections.

  2. Damage: Immune Evasion and Inflammation

    • Immune Evasion mechanisms:
      • IgA protease inactivates secretory IgA, a major defense on mucosal surfaces.
      • Antigenic variation of pili to evade antibody-mediated immunity.
      • Phase variation: Toggles expression of pili and Opa adhesins.
      • LOS modification to survive in the bloodstream.
    • Lack of protective immunity means re-infection is possible even with the same strains.
    • Inflammation:
      • LOS stimulates PMN influx; inflammatory damage can lead to scars in the epithelium, contributing to PID.

  3. Dissemination

    • Local spread to uterus and Fallopian tubes in females; prostate gland and epididymis in males.
    • Chronic/recurrent infections can cause PID in >15% of untreated cases, leading to infertility and ectopic pregnancy.
    • Disseminated gonococcal infections (DGI) occur in 0.5-3% of untreated cases, resulting in arthritis, skin lesions, fever, and malaise.

  4. Transmission

    • N. gonorrhoeae is shed in genital secretions, allowing efficient transmission. Asymptomatic individuals frequently transmit the disease.
    • Capable of binding to sperm, enhancing transmission risk, with maternal transmission during birth potentially leading to neonatal conjunctivitis and blindness.
    • Gonorrheal infections increase the likelihood of HIV and other STDs transmission.

  5. Risk Factors

    • More likely to be symptomatic in males.
    • Multiple sex partners (e.g., sex workers) or co-infections with Chlamydia or HIV increase risk.

Diagnosis

  • Clinical syndrome determined by history and physical examination, followed by microbiological diagnosis.
  • Nucleic Acid Amplification Testing (NAAT) is highly sensitive and specific, recommended for most high-income countries.
  • Gram stain shows Gram-negative diplococci.
  • Culture: Plate cervical or urethral exudates on chocolate agar supplemented with VCN antibiotics (Vancomycin, Colistin, Nystatin).
  • Screening recommendations: Annual screening for all sexually active females under 25, older females at higher risk (e.g., sex workers), and young males who have sex with men.

Treatment and Prevention

  • Antibiotic treatment is essential. Symptoms may resolve without treatment, but repeated infections can cause scarring. Asymptomatic infections may lead to PID and infertility in females.
  • Antibiotics prevent DGI and transmission. Antibiotic resistance is a significant concern.
  • Recommended dual antimicrobial therapy includes:
    • Ceftriaxone (for N. gonorrhoeae).
    • Doxycycline (for Chlamydia co-infections).
  • Prophylactic erythromycin recommended for newborns at birth.
  • Prevention: Use of condoms, rapid diagnosis, and effective contact tracing are critical.
  • The stigma associated with STIs can hinder partner notification and disease burden reduction.

Comparison with Neisseria meningitidis

  • Both N. gonorrhoeae and N. meningitidis are pathogenic Gram-negative diplococci, producing inflammatory LOS.
  • N. gonorrhoeae typically causes localized infections; some systemic disease can occur, unlike N. meningitidis which can survive better in the bloodstream due to capsulation.
  • Both cultured on chocolate agar, but N. gonorrhoeae requires VCN antibiotics, while they differ in pathogenic mechanisms (strict pathogen vs. pathobiont).

Chlamydia trachomatis (Chlamydia)

Overview

  • Parallels with N. gonorrhoeae:
    • Humans are the only host, spread via mucous membranes including sexual contact and maternal transmission.
    • Asymptomatic infections promote further transmission.
  • Key Differentiation: Chlamydia is an obligate intracellular pathogen that cannot be cultured on standard plates.

Clinical Syndromes

  • Trachoma: Infection of the eyes, often transmitted during childbirth; leading cause of preventable blindness globally.
  • Chlamydia: Frequently asymptomatic, but can cause vaginal discharge (cervicitis), urethral discharge (urethritis), pain during urination, and during sex.
  • Pelvic Inflammatory Disease (PID): Common in females under 25, leading to increased risk of infertility and ectopic pregnancy.
  • Neonate pneumonia: Infants may exhibit a “staccato” cough if infected during birth.

Pathogenesis of Chlamydia trachomatis

  1. Obligate Intracellular Lifecycle

    • Cannot grow outside host cells due to limited biosynthetic capability (e.g., inability to synthesize ATP).
    • Inside host cells, it grows within a replicative vacuole known as the inclusion vacuole.
    • Two forms of Chlamydia:
      • Elementary Body (EB): The transmissive form, similar to spores, little metabolic activity, resistant to harsh conditions.
      • Reticulate Body (RB): The replicative form, fragile but capable of replication.

  2. Encounter, Entry, and Transmission

    • Transmitted person-to-person through close contact (sexual and birthing processes).
    • Infects any epithelial tissue, utilizing the Type III secretion system to induce endocytosis of EBs by epithelial cells.
    • Once inside, Chlamydia remodels the phagosomal compartment to prevent lysosomal fusion, allowing for the creation of a replicative inclusion body.
    • EBs convert to RBs, which replicate before transforming back to EBs to infect other epithelial cells once the inclusion body lyses.

Damage Caused by Chlamydia trachomatis

  • Persistent infections elicit a strong cell-mediated immune response, leading to tissue damage.
  • In females, PID due to scarring raises the risk of infertility and ectopic pregnancy.
  • Certain serogroups cause Lymphogranuloma Venereum (LGV), characterized by acute lymphadenitis.
  • Chlamydia urethritis may lead to reactive arthritis, often targeting the knees.

Diagnosis and Treatment

  • Screening is critical; annual screening recommended for sexually active females 25 years or younger, pregnant females, and high-risk individuals.
  • Diagnosis methods include:
    • NAAT: Most sensitive, cannot Gram stain or culture due to obligate intracellular nature.

Treatment and Prevention

  • Treatment focuses on RBs, necessitating antibiotics that can penetrate inclusion vacuoles.
  • Common antibiotics include:
    • Doxycycline: Taken for 7-10 days, often used with ceftriaxone for N. gonorrhoeae co-infections.
    • Azithromycin: Single 1 g dose, enhancing compliance.
  • Treatment recommended for sexual partners.
  • New prophylactic therapy doxy PEP proposed for high-risk groups to prevent chlamydia and potential STI spread, demonstrating reduction rates of 50-80% for chlamydia and syphilis, with potential reductions in gonorrhea.