Chapter 25 -Circulatory System 

Lyme Disease

 

History of the Disease

Lyme disease was first recognized in 1975 in the town of Old Lyme, Connecticut, which gave the disease its name. The discovery came after a cluster of cases of what appeared to be juvenile rheumatoid arthritis was reported among children living near Old Lyme. Dr. Allen Steere, a rheumatologist, investigated these cases and realized that this was a previously unrecognized disease.

 

The causative agent, the spirochete bacterium Borrelia burgdorferi, was identified by Dr. Willy Burgdorfer in 1982. He discovered the connection between the disease and ticks while studying Rocky Mountain spotted fever. Dr. Burgdorfer found the spirochetes in the midguts of Ixodes ticks collected from an area with a high incidence of Lyme disease. The bacterium was subsequently named in his honor.Interestingly, evidence suggests that Lyme disease has been present for thousands of years. The bacterium was found in the 5,300-year-old mummy of Ötzi the Iceman discovered in the Alps.

 

 

Who is Affected by This Disease?

Lyme disease can affect individuals of all ages, genders, and cultural backgrounds, but certain demographic groups face higher risks due to various factors:

 

Age Groups: While anyone can contract Lyme disease, two age groups show higher incidence rates:

• Children aged 5-15 years are particularly at risk due to increased outdoor activities in wooded or grassy areas.

• Adults aged 45-65 years also show higher rates, possibly due to outdoor recreational activities.

 

Gender: Males have historically shown slightly higher rates of Lyme disease, which may be attributed to occupational and recreational exposures in tick-infested environments. However, the gender gap has narrowed in recent years.

 

Geographic and Cultural Factors: People living in or visiting endemic areas face the highest risk. In the United States, this includes residents of the Northeast (from Maine to Virginia), Upper Midwest (Wisconsin and Minnesota), and parts of the Pacific Northwest. In Europe, Lyme disease is prevalent across many countries, especially in Central and Eastern Europe.

 

Occupational Risks: Certain occupations carry elevated risk, including:

• Forestry workers

• Park rangers

• Landscapers

• Farmers

• Outdoor recreation guides

 

 

Symptoms

Lyme disease manifests in several stages with distinct symptom patterns:

 

Early Localized Stage (3-30 days post-tick bite):

• Erythema migrans (EM): The hallmark "bull's-eye" rash appears in about 70-80% of infected persons. It begins at the site of the tick bite and gradually expands over days to weeks, often clearing in the center.

• Flu-like symptoms: Fever, chills, fatigue, body aches, headache, neck stiffness, and swollen lymph nodes.

 

These initial symptoms occur because the bacteria begin multiplying at the bite site, triggering a local inflammatory response. The expanding rash reflects the migration of spirochetes through the skin tissue.

 

Early Disseminated Stage (days to weeks post-infection):

• Facial or Bell's palsy (loss of muscle tone on one or both sides of the face)

• Severe headaches and neck stiffness due to meningitis

• Pain and swelling in large joints

• Heart palpitations or irregular heartbeat (Lyme carditis)

   

These symptoms develop as the bacteria spread through the bloodstream to various tissues and organs, triggering systemic inflammatory responses.

 

Late Disseminated Stage (months to years post-infection):

• Arthritis with severe joint pain and swelling, particularly in the knees

• Neurological problems such as numbness, tingling, shooting pains

• Cognitive defects, sleep disturbances, personality changes

• Inflammation of the brain and spinal cord

 

These late-stage symptoms result from persistent infection and ongoing immune responses that can damage tissues and organs.

 

 

Pathology

Lyme disease affects multiple body systems through complex mechanisms:

 

Cellular Level:

The spirochete Borrelia burgdorferi enters the skin at the tick bite, attaching to host cells using specific surface proteins. It evades the immune system by altering these proteins and suppressing immune responses.

 

Immune System Involvement:

The body responds with innate and adaptive immunity. Neutrophils and macrophages try to eliminate the bacteria, while B cells produce antibodies and T cells attack infected cells. Persistent infection can trigger excessive immune responses that damage tissues.

 

Affected Organs and Systems:

• Integumentary System: The characteristic EM rash arises from inflammation due to spirochete proliferation.

• Musculoskeletal System: Lyme arthritis affects about 60% of untreated patients and causes joint inflammation, mainly in the knee.

•  Cardiovascular System: Lyme carditis occurs in 4-10% of untreated patients, leading to myocarditis, pericarditis, and heart block due to cardiac tissue invasion.

 

Molecular Mechanisms:

 Pathogenesis involves direct bacterial damage and immune-mediated inflammation. Spirochetes produce adhesins (OspA, OspC, DbpA), proteases that degrade host tissues, and immunomodulatory proteins that disrupt immune function.

 

 

 

Cure/Treatments for the Disease?

 

No permanent cure guarantees the complete elimination of the bacterium in all cases, but Lyme disease is treatable with appropriate antibiotics, especially when caught early.

 

 

Antibiotic Treatments:

1. Early Stage Treatment:

   • Doxycycline: First-line treatment for adults and children over 8 years old (100mg twice daily for 10-21 days)

   • Amoxicillin or Cefuroxime: Alternative for younger children and pregnant women

   • The success rate of early treatment is very high, approximately 90-95%

2. Disseminated Stage Treatment:

   • Longer courses of oral antibiotics (14-28 days)

   • For neurological or cardiac involvement, intravenous antibiotics like ceftriaxone may be used

   • Treatment duration: 14-28 days depending on clinical presentation

3. Late Stage Treatment:

   • Intravenous antibiotics (ceftriaxone, penicillin G, or cefotaxime)

   • Treatment duration: Usually 28 days

   • Multiple courses may be necessary for persistent symptoms

Symptomatic Relief:

• NSAIDs for pain and inflammation

• Corticosteroids (used cautiously) for severe arthritis or neurological symptoms

• Temporary cardiac pacing for severe heart block

   

Post-Treatment Lyme Disease Syndrome (PTLDS): Some patients (approximately 10-20%) experience persistent symptoms after standard antibiotic treatment. These may include:

• Fatigue

• Musculoskeletal pain

• Cognitive difficulties

• Sleep disturbance

Management of PTLDS focuses on symptom relief rather than additional antibiotics, as extended antibiotic therapy has not shown consistent benefits in controlled studies.

 

 

What Causes the Disease?

Lyme disease is caused by infection with the spirochete bacterium Borrelia burgdorferi and occasionally by other related Borrelia species (B. mayonii, B. afzelii, and B. garinii). These are gram-negative, microaerophilic bacteria with a distinctive spiral shape and flagella that give them mobility.

 

Transmission Cycle:

1. Vector: The primary vectors are black-legged ticks (Ixodes scapularis in the eastern and midwestern US, Ixodes pacificus in the western US, and Ixodes ricinus in Europe).

2. Reservoir Hosts: The bacteria persist in animal reservoirs, primarily:

   • White-footed mice

   • Chipmunks

   • Shrews

   • Other small mammals

      

3. Transmission Process:

   • Tick eggs hatch into larvae, which feed on small animals (often mice) that may carry B. burgdorferi

   • Larvae become infected when feeding on infected animals

   • Larvae molt into nymphs, which may feed on various animals or humans

   • Nymphs molt into adult ticks that primarily feed on larger animals like deer (which help maintain tick populations but are not competent reservoirs for the bacteria)

   • Infected ticks transmit bacteria during feeding

      

4. Human Infection Mechanism:

   • When an infected tick attaches to human skin, it typically takes 36-48 hours of attachment for efficient bacteria transmission

   • During feeding, the tick's saliva facilitates bacterial entry:

     • Contains anticoagulants and immunomodulatory compounds

     • Creates a favorable microenvironment for bacterial transmission

   • Bacteria multiply at the bite site and can disseminate through the bloodstream and lymphatics

 

 

How is a Person's Daily Life Affected by the Disease?

Living with Lyme disease presents various challenges that impact daily life, varying significantly based on the stage of disease and individual response:

 

Acute Phase Impact:

• Physical limitations due to fatigue, fever, and pain requiring bed rest

• Need for regular medication adherence (typically antibiotics 1-2 times daily)

• Medical appointments for diagnosis, treatment, and monitoring

• Temporary work or school absence during acute illness

• Restriction from certain physical activities

 

Chronic/Persistent Symptoms Impact:

1. Physical Functioning:

   • Reduced mobility and physical capacity due to joint pain and inflammation

   • Exercise intolerance and post-exertional malaise

   • Sleep disruption from pain, causing daytime fatigue

   • Need for mobility aids during severe arthritis flares

   • Requirement for pain management strategies (medications, physical therapy)

      

2. Cognitive Functioning:

   • "Brain fog" affecting concentration and memory

   • Difficulty with complex tasks and multitasking

   • Reading comprehension challenges

   • Potential need for cognitive rehabilitation therapy

      

3. Daily Activities and Self-Care:

   • Medication management (antibiotics, pain relievers, sleep aids)

   • Diet modifications (some patients follow anti-inflammatory diets)

   • Regular exercise within tolerance limits

   • Tick prevention measures when outdoors

 

 

 

Number of People Affected by This Disease

Lyme disease represents a significant global health burden, with varying incidence rates across regions:

 

Global Distribution and Statistics:

• Europe: Approximately 85,000 cases are reported annually, with estimated actual cases exceeding 200,000

  • Highest incidence in Central and Eastern Europe, particularly in:

    • Slovenia

    • Austria

    • Czech Republic

    • Estonia

    • Lithuania​​​​​

    • ​

• Asia: Lyme disease occurs in numerous countries, including:

  • China (particularly in the northeastern provinces)

  • Japan

  • Russia

  • South Korea

 

Treatment Centers/Medical Research

Research and specialized treatment for Lyme disease occur at various institutions worldwide:

 

International Research Centers:

1. University of Wurzburg (Germany)

   • Leading European center for Lyme neuroborreliosis research

   • Studies on diagnostic biomarkers and treatment optimization

2. National Institute for Public Health and the Environment (Netherlands)

   • Conducts epidemiological studies and surveillance

   • Research on tick ecology and prevention strategies

3. Lyme Borreliosis Center at Radboud University (Netherlands)

   • Studies immunological mechanisms in Lyme disease

   • Investigates pathogenesis of persistent symptoms

 

Current Major Research Directions:

1. Improved Diagnostics:

   • Next-generation serological tests with higher sensitivity

   • Direct detection methods for Borrelia proteins

   • Biomarker identification for disease activity

2. Treatment Innovations:

   • Antibiotic combination therapies

   • Novel antimicrobial compounds

   • Immunomodulatory approaches for persistent symptoms

3. Vaccine Development:

   • VLA15 (Valneva/Pfizer) – currently in Phase 3 clinical trials

   • Novel approaches targeting tick saliva proteins

   • Prevention of tick attachment

4. Prevention Strategies:

   • Tick control methods

   • Ecological interventions

   • Enhanced surveillance systems

5. Pathogenesis Research:

   • Mechanisms of immune evasion by Borrelia

   • Genetic factors affecting disease susceptibility

   • Role of co-infections in disease severity

 

Recent Breakthroughs:

• Identification of potential biomarkers for persistent Lyme disease

• Development of more sensitive multiplex serological assays

• Advances in understanding the genetic basis of symptom variability

• Progress in tick microbiome research and its impact on disease transmission

​

 

 

Video

​

​

​

 

 

 

 

 

References

1. OpenStax. (2023). Anatomy and Physiology. OpenStax CNX. Retrieved from https://openstax.org/details/books/anatomy-and-physiology

2. Centers for Disease Control and Prevention. (2023). Lyme Disease. Retrieved from https://www.cdc.gov/lyme/index.html

3. Steere, A. C., Strle, F., Wormser, G. P., Hu, L. T., Branda, J. A., Hovius, J. W., Li, X., & Mead, P. S. (2016). Lyme borreliosis. Nature Reviews Disease Primers, 2, 16090. https://doi.org/10.1038/nrdp.2016.90

4. Shapiro, E. D. (2014). Lyme disease. New England Journal of Medicine, 370(18), 1724-1731. https://doi.org/10.1056/NEJMcp1314325

5. Hatchette, T. F., Davis, I., & Johnston, B. L. (2014). Lyme disease: clinical diagnosis and treatment. Canadian Journal of Infectious Diseases and Medical Microbiology, 25(6), 313-315. https://doi.org/10.1155/2014/526083

6. Fallon, B. A., & Nields, J. A. (1994). Lyme disease: a neuropsychiatric illness. The American Journal of Psychiatry, 151(11), 1571–1583. https://doi.org/10.1176/ajp.151.11.1571

7. Stanek, G., Wormser, G. P., Gray, J., & Strle, F. (2012). Lyme borreliosis. The Lancet, 379(9814), 461-473. https://doi.org/10.1016/S0140-6736(11)60103-7

8. Lantos, P. M. (2015). Chronic Lyme disease. Infectious Disease Clinics of North America, 29(2), 325-340. https://doi.org/10.1016/j.idc.2015.02.006