Lecture Notes on Spirochetes, Lyme Disease, and Syphilis

Spirochetes Overview

  • Definition: Spirochetes are a unique group of bacteria distinguished by several specific properties and associated diseases.

Properties of Spirochetes

  • Shape and Size:
    • Thin, spiral/corkscrew shape.
    • So thin that they cannot be visualized by conventional microscopy; visualization requires darkfield microscopy.
  • Membrane Structure:
    • Double-membrane structure, characteristic of Gram-negative bacteria.
    • Outer membrane differs from most Gram-negatives as it does not contain lipopolysaccharides (LPS), specifically in Borrelia burgdorferi and Treponema pallidum.
  • Staining:
    • Do not Gram stain.
  • Motility:
    • Possess unique endoflagella located between the inner and outer membranes, critical for dissemination through tissues.
    • Highly motile, leading to systemic infections.
  • Culture Difficulties:
    • Very difficult to culture in vitro; cannot grow under standard clinical lab conditions.
  • Toxins:
    • Do not produce canonical toxins; damage is associated with growth and inflammation caused by the organism itself.

Diseases Caused by Spirochetes

  1. Syphilis:
    • Causative agent: Treponema pallidum.
    • Transmission: Sexually transmitted and congenital.
  2. Lyme Disease:
    • Causative agent: Borrelia burgdorferi.
    • Transmission: Vector-borne (ticks).
  3. Relapsing Fever:
    • Several species of Borrelia.
    • Transmission: Vector-borne (lice or ticks).
    • Significant in Africa, Asia, Europe, and the Americas; prevalent in the western United States at higher elevations.
  4. Leptospirosis:
    • Causative agent: Leptospira interrogans.
    • Transmission: Zoonotic via urine.
    • Most widespread zoonotic infection, often worsened by flooding, leading to systemic infections such as meningitis, liver, or kidney failure.
  • Significance in U.S.:
    • Syphilis and Lyme disease are the most clinically significant spirochetal diseases in the United States.
    • Relapsing fever and leptospirosis are more prevalent in developing countries.

Lyme Disease - Borrelia burgdorferi

Infection Dynamics

  • Chronic Nature:
    • Can cause chronic multi-system infections; disease manifestations may occur years after initial infection.
    • Linked to immune sequelae, complicating diagnosis.
  • Diagnosis Challenges:
    • Difficult to culture and poor early diagnostics.
    • Diagnosis frequently relies on clinical manifestations and travel history.
  • Risk Factors:
    • Highly prevalent in Northeastern and Great Lakes regions of the U.S.

History and Epidemiology of Lyme Disease

  • Discovered in the late 1970s by Allen Steere, following a cluster of cases of juvenile rheumatoid arthritis in Old Lyme, Connecticut.
  • Considered the most common arthropod-borne illness in the U.S.
  • Cases have increased due to rising deer populations and increased human contact with these animals.

Transmission Cycle

  • Enzoonotic Cycle:
    • Transmitted via tick bites, specifically Ixodes (deer tick) after feeding on infected vertebrates (e.g., mice).
    • Feeding for more than 36 hours facilitates transmission.

Infection Stages

  1. Skin Infection & Local Spread (Days to Weeks):
    • Spirochete attaches to host cells in the skin.
    • Causes characteristic “bull's eye” rash (erythema migrans); this rash appears in only ~50% of cases.
  2. Early Disseminated Infection (Weeks to Months):
    • Utilizes endoflagella for movement through tissues.
    • Can penetrate blood vessel walls leading to multiple tissue colonization; symptoms may include:
      • Skin: Secondary erythema migrans.
      • Heart: Carditis, heart block.
      • Joints: Arthralgia.
      • Nervous System: Shooting pain, paresthesia, Bell’s palsy.
  3. Chronic Infection (Months to Years):
    • Few neutralizing antigens and reduction of surface antigens in certain tissues enable evasion from the immune system.
    • Symptoms may wax and wane; termed the 'second great imitator.' Common manifestations include:
      • Skin: Reddened, atrophic skin.
      • Joints: Chronic arthritis.
      • Nervous System: Cognitive difficulties, Multiple sclerosis-like presentations.

Damage Mechanisms

  • B. burgdorferi does not multiply in high numbers but triggers an inflammatory response due to immunoreactive lipoproteins.
  • Does NOT produce LPS or canonical toxins.

Diagnosis of Lyme Disease

  • Low bacterial presence in tissues complicates diagnosis.
  • Critical clues include:
    • Erythema migrans rash, which is less visible on darker skin types, leading to disparities in diagnosis and treatment (noted that Black Americans are 30% more likely to suffer from arthritis).
    • Clinical diagnostics heavily rely on serology:
    • Two-Step Procedure:
      1. ELISA for anti-B. burgdorferi response (less specific).
      2. Positive ELISA followed by Western Blot to detect antibodies against specific B. burgdorferi proteins.

Treatment and Prevention

  • Behavioral Prevention:
    • Protective clothing and insect repellant in endemic areas.
    • Early tick removal is crucial since infection risk increases after 36 hours of attachment.
  • Antibiotic Treatment:
    • Early treatment with oral doxycycline prevents severe disseminated disease.
    • Doxycycline is also effective against co-infections such as Anaplasma phagocytophilum.
    • Prolonged treatment for chronic Lyme is debated; some patient advocacy groups challenge this perspective.

Syphilis - Treponema pallidum

Overview and Epidemiology

  • Background: Once nearly eradicated in the U.S. in the 1990s, syphilis rates are currently rising.
  • Transmission: Commonly a sexually transmitted infection; however, congenital syphilis poses significant risks, including fetal loss and stillbirth due to the pathogen crossing the placenta.
  • Epidemiological Trends:
    • 200,000 reported cases in the U.S. in 2022.
    • Rising rates particularly among men who have sex with men (MSM).
    • Historically, there has been a stark racial disparity in incidence, with higher rates in African-American populations.
    • The infamous Tuskegee Syphilis Study (1932-1972) highlights historical injustices impacting awareness and treatment.

Entry, Encounter, Transmission, Spread & Multiplication

  • Hosts: Humans are the only known hosts. Infections occur through mucous membranes or skin abrasions.
  • Fetal Infection Risks: Bacteremia in pregnant women increases the risk of fetal infection; the chance of fetal mortality is higher with early infection.
  • Moisture and HIV Connection: Syphilis promotes HIV transmission and vice versa.

Infection Stages

  1. Primary Syphilis (Days-Weeks):
    • Development of a painless ulcer (chancre) that heals spontaneously in 2-6 weeks; includes regional lymphadenopathy.
  2. Secondary Syphilis (Weeks-Months):
    • Sale of infectious skin lesions appears on palms and soles; flu-like symptoms accompany this stage with generalized lymphadenopathy.
  3. Tertiary Syphilis (Years):
    • Over 25% of untreated individuals may develop late manifestations that include gummas, vasculitis, and neurological effects such as sensory loss and personality changes.

Damage Mechanisms

  • No toxins produced by T. pallidum, yet few antigenic targets pose challenges for immune detection.
  • Antigenic variation helps evade immune response; inflammatory responses contribute significantly to tissue damage.
  • Tertiary lesions often contain minimal bacterial presence, suggesting possible autoimmune components.

Diagnosis of Syphilis

  • Screening is advised based on local prevalence and risk factors such as:
    • Newly diagnosed HIV patients.
    • High-risk populations, such as MSM and pregnant women.
  • Testing Methods:
    • Nontreponemal tests: VDRL or RPR, which detect cardiolipin antibodies.
    • Treponemal tests: FTA-ABS for specific T. pallidum antibodies.

Treatment and Prevention

  • Antibiotic Efficacy: Penicillin is effective but challenges exist in reaching high-risk populations.
  • Screening Importance: Regular screenings are crucial, especially for vulnerable populations.
  • Prevention Strategies:
    • Increasing access to healthcare and health education is essential for reducing incidence rates.

Recent Developments

  • The CDC now recommends a new prophylactic therapy, doxycycline Post-Exposure Prophylaxis (doxy PEP), for high-risk groups to reduce rates of chlamydia, syphilis, and potentially gonorrhea by 50-80%.

Similarities between Lyme Disease and Syphilis

  • Both diseases are caused by highly motile spirochetes leading to systemic infections.
  • Much damage is attributed to inflammatory responses rather than direct bacterial effects.
  • Both conditions do not produce toxins; instead, lipoproteins that cause inflammation are present.
  • Chronic infections arise due to immune evasion techniques such as antigenic variation.
  • Disease presents in three stages: localized infection, early disseminated infection, and late disseminated infection.
  • Both diseases exhibit a wide variety of clinical manifestations and face challenges in accurate diagnosis, especially regarding re-infection.