Borrelia

Question 1

Zoonoses

Answer 1

Infectious diseases of other animal species that are accidentally transmitted to humans.

May be viral, bacterial or parasitic.

Question 2

Vector

Answer 2

Arthropod that transmits infection from animal to human.

Not all zoonoses are transmitted by vectors.

Question 3

Reservoir

Answer 3

The animal species in which the microbe is maintained in nature.

Question 4

Lyme Disease

Answer 4

• Caused by Borrelia burgdorferi
• Spirochete transmitted by deer ticks (Ixodes dammini) to man during a blood meal
• Serious public health problem in the USA (300k cases per year)
  
  • Esp. in regions w/ a large deer population
  • ↑ # of deer and deer ticks ⇒ ↑ incidence of Lyme

Question 5

B. burgdorferi

Morphology and Cultivation

Answer 5

• Loosely-coiled spirochete
• Contains several outer surface proteins ⇒ OspA and OspB
  
  • May undergo antigenic variation
• Fastidious
• Grows best at 33°C in a complex liquid medium

Question 6

B. burgdorferi

Reservoirs

Answer 6

Zoonotic disease w/ animal and tick reservoir.

White footed mouse ⇒ larval and nymph forms (spring)

White tailed deer ⇒ adult ticks (late summer)

Infection of humans (accidental)

Question 7

B. burgdorferi

Transmission

Answer 7

Spirochetes transmitted by ticks that normally feed on deer and white footed mouse:

• Lives in tick midgut until it takes a blood meal
• Contact with mammalian blood ⇒ ∆ expression of Osps ⇒ replication ⇒ gut wall invasion ⇒ dissemination throughout the tick including salivary glands ⇒ injected into mammalian host
  
  • Process takes 24 to 36 hrs
• Tick must feed for 18-24 hrs before mature spirochetes will be injected into the host
  
  • If ticks are removed on a daily basis, risk of transmission is low

Question 8

B. burgdorferi

Epidemiology

Answer 8

Transmission occurs in areas with a large deer population.

Three distinct geographic regions in the US:

• Northeast corridor ⇒ Massachusetts to Maryland
  
  • Highest transmission
• Upper Midwest ⇒ Wisconsin and Minnesota
• Northern California

Question 9

B. burgdorferi

Clinical Infection

Answer 9

3 stages of Lyme disease:

• Stage 1 - Early localized
  
  • Local spread of B. burgdorferi in the skin
  • Characteristic annular lesion @ site of tick bite (bullseye) ⇒ erythema migrans
    
    • Usually occurs within 2 weeks of bite
  • Fever, malaise and headache may accompany the rash
• Stage 2 - Early disseminated
  
  • Local dissemination
  • Multiple smaller annular rashes
  • Other common manifestations:
    
    • Cranial nerve palsies
    • Meningitis
    • Conjunctivitis
    • Systemic sx such as fever, malaise, fatigue and arthralgia
• Stage 3 - Late disseminated
  
  • Period of latency (months to several years)
  • ± Attacks of arthritis affecting large joints, esp. knees
    
    • Episodes become progressively longer
    • Small % of individuals may become chronic and progressive
  • Chronic neurologic involvement may also occur

Question 10

B. burgdorferi

Pathogenesis

Answer 10

Pathology not due to the organism ⇒ no toxins or direct tissue damage

• Early stages ⇒ viable bacteria/inflammation
• Late stage ⇒ immune-mediated injury
  
  • Microbial persistence ⇒ immune response ⇒ bystander injury to the host
  • Affected tissues w/ inflammatory infiltrate of lymphocytes and monocytes
  • Potent inducer of IL-1 and TNF-α
  • HLA-DR4 and IgG to OspA (chronic patients)

Question 11

B. burgdorferi

Diagnosis

Answer 11

• Lesion > 5 cm is pathognomonic
• Difficult to cultivate and visualize
• Pts with Stage 1 disease frequently seronegative ⇒ dx based on clinical manifestations
• More advanced pts ⇒ dx by two-step serological process
  
  • EIA or ELISA
    
    • Done with whole cell antigens
    • Numerous false positives with other spirochete antigens, viral infections and autoimmune diseases
    • Positive or equivocal EIA must be corroborated with an immunoblot
  • Immunoblot or Western
    
    • Uses proteins specific to B. burgdorferi

Question 12

B. burgdorferi

Treatment

Answer 12

• Doxycycline or Amoxicillin PO vs IV
  
  • Duration of therapy is guided by clinical course
  • Usually 2-4 weeks
• Treating stage 1 or 2 prevents stage 3
• Re-infection is possible

Question 13

Post-Treatment

Lyme Disease Syndrome

Answer 13

• 10-20% of treated pts have prolonged sx
  
  • Fatigue
  • Muscle and joint pain
  • Cognitive issues
• May be d/t tissue damage not continued presence of organism
• No e/o to support long term abx tx

Question 14

Chronic Lyme Disease

Answer 14

Persistent pain, fatigue, cognitive sx in the absence of clinical and serological e/o infection w/ B. bergdorferi

Not recognized by the IDSA

Question 15

B. burgdorferi

Prevention

Answer 15

Cover all exposed skin areas and/or use repellent when in tick infected areas

Check for ticks and remove daily

Question 16

Relapsing Fever

Overview

Answer 16

• Periodic episodes of pyrexia with septicemia and apyrexia
  
  • Two forms: epidemic vs endemic
• Caused by several species of Borrelia ⇒ B. recurrentis, B. hermsii, B. turicatae
• Transmitted to man by:
  
  • Soft bodied ticks (Ornithodoros) ⇒ Tick Borne
  • Human louse (Pediculus humanus corporis or Pediculus humanus capitis) ⇒ Louse Borne

Question 17

Epidemic

Relapsing Fever

Answer 17

Louse Borne Relapsing Fever

• Caused by Borrelia recurrentis
• Reservoir host is unknown
• Transmitted to man and spread from man to man by the body or head louse
• Usu. occurs during times of breakdown of public health infrastructure, war, natural disasters etc.
  
  • Common in Sudan, Somalia, and Ethiopia
  • Virtually non-existent in the USA

Question 18

Endemic

Relapsing Fever

Answer 18

Tick Borne Relapsing Fever

• Caused by B. hermsii and B. turicatae
• Transmitted from infected animals ⇒ tick ⇒ man
  
  • Animal reservoirs are wild rodents and other forest animals
  • Vector is the Ornithodorus species (soft tick)
  • Borrelia may be passed trans-ovarily to subsequent generations in the tick
• Occurs primarily in the Western US, Grand Canyon, state and national parks
• Occurs most often in summer

Question 19

Relapsing Fever

Virulence Factors

Answer 19

• Antigenic variation of the infecting strain
• New variants are responsible for relapses
• Ab is not protective for new strains

Question 20

Relapsing Fever

Pathogenesis and Clinical Disease

Answer 20

• Infection is initiated by entry of organisms by bite or crushing of the insect vector
• Spirochetemia develops ⇒ febrile period (~ 7 days)
  
  • Various organs of the reticuloendothelial system may become infected
    
    • Heptatosplenomegaly
    • Hepatic necrosis
    • Cardiac failure
    • Cerebral hemorrhage
• Disappearance of Borrelia from the blood stream ⇒ fever remission (3-10 days)
• Reappearance of fever and Borrelia with new antigenic types ⇒ relapse
  
  • Antigenic variation critical to pathogenesis of the organism
  • Relapses are usually limited to 3 or 4

Question 21

Relapsing Fever

Diagnosis

Answer 21

• Visualize the organism in blood during febrile period
  
  • Direct staining of blood smears by Giemsa or Wright procedures
  • Darkfield microscopy (uncommon)
• Serology by EIA or immunoblot
  
  • Methods are not standardized
  • Serum samples should be sent to the CDC

Question 22

Relapsing Fever

Treatment and Prevention

Answer 22

• Tx w/ Tetracycline or Erythromycin
  
  • Endemic form - 5% mortality
  • Epidemic form - 40% mortality
• Preventative measures include delousing, de-ticking and control