Micro- Zoonotic Infections: Borrelia & Leptospira

Question 1

What organism causes Lyme disease?

Answer 1

Spirochete classified as Borrelia burgdorferi

Question 2

What regions of the US are foci for Lyme disease?

What does the distribution correlate with?

Answer 2

1. mid-Atlantic
2. northeast
3. Midwest
4. California/Oregon

This correlates with the distribution of the hard tick vector Ixodes scapularis, Ixodes pacificus

Question 3

What fraction of patients with Lyme disease give history of a tick bite?

Answer 3

1/3

Question 4

What is necessary to maintain endemic foci of Lyme disease?
Where do adult ticks generally mate?
Is there vertical transmission?

Answer 4

Repeated infection of mammalian hosts in the area [usually mice].

Adult ticks mate on deer and there is NOT vertical transmission. Tick eggs are sterile and must be infected with borrelia burgdorferi themselves.

Question 5

Describe the pathogenesis of spirochetes to human hosts.

Answer 5

1. Spirochetes live in Ixode tick gut
2. Blood meal of tick activates the spirochetes to travel to salivary glands
3. Tick spreads spirochete to the host

Whole process takes 55 hours

Question 6

After spirochetes inoculate the host through tick bite, where do they spread?

Answer 6

1. migrate outward in skin causing erythema migrans

2. hematogenous spread

Question 7

What supports the idea that autoimmunity plays a role in severity of spirochete infection?

Answer 7

Chronic disease [arthritis] is associated with certain HLA types

Question 8

What are the 3 stages of Lyme disease?
What percent of patients are affected by each stage?
How long does each stage last?

Answer 8

Stage 1 [65% experience this]

• skin symptoms [erythema migrans]
• constitutional symptoms [regional adenopathy, fever, headache, myalgia]
• lasts from 2 weeks to 2 months

Stage 2: [<25% experience this]

• CNS: numbness, stiff neck, facial muscle paralysis
• Heart: rhythm irregularity/heart block
• lasts from 1 month to 3 months

Stage 3: [50% experience this]

• Joints: swelling, pain, arthritis
• lasts from 1.5 months to 4 years

Question 9

Describe the classic clinical presentation of erythema migrans.

Answer 9

begins at the site of the tick bite as a macule or papule and then develops into a spreading annular lesion.

Question 10

A patient presents with erythema migrans, regional lymphadenopathy, fever, headache and myalgias.
What stage of Lyme disease is this?

Answer 10

Stage 1 : Early

Question 11

What are the 3 signs of early disseminated disease in Lyme disease?

Answer 11

1. musculoskeletal:
   - arthralgia
   - migratory arthritis
   - frank arthritis
2. Neurologic:
   - meningitis
   - facial palsy
   - peripheral neuropathy
3. Cardiac
   - AV block

Question 12

What is characteristic of late Lyme disease?

Answer 12

1. Frank arthritis
   - weeks to years after onset of Lyme disease
   - 2 or more large joints [knees usually].
   - attacks are recurrent over period of years, but then subside
2. peripheral neuropathy and/or encephalopathy

Question 13

How is diagnosis of Lyme disease made?

Answer 13

1. characteristic lesion [EM] in patients living or traveling through endemic areas
   - B. burgdorferi is RARELY recovered in clinical specimen
   - ticks are <2mm and hard to see
   - EM is often seronegative
2. Serological confirmation
   - ELISA PLUS Immunoblot [Western Blot]
3. PCR of joint fluid

Question 14

What is treatment for B. burgdorferi during the EM stage to hasten recovery and prevent late sequelae?

Answer 14

21 days of:

1. doxycycline
2. amoxicillin

Question 15

What treatment is given for severe or refractory Lyme disease?

Answer 15

2-4 weeks of IV:

1. ceftriaxone
2. cefotaxime

Question 16

What is Post Lyme Disease Syndrome?

Answer 16

Even after presumably effective therapy, the patient still experiences:

1. muscle aches
2. fatigue
3. joint pain

Question 17

What is prophylaxis for Lyme disease?

Answer 17

Minimize risk in exposed areas.

• antibiotic prophylaxis after a tick bite is NOT cost effective because only 2% will actually get LD
• no vaccine is available [used to have OspA but too many side effects]

Question 18

What are the 2 types of Relapsing Fevers?
What is the vector for each?
What are the causative organisms for each?
What is the endemic region for each?

Answer 18

1. epidemic
   - vector: human body louse [pediculus humanis]
   - agent: Borrelia recurrentis
   - North Africa
2. Endemic
   - vector: soft body tick
   - agents: B. hermsii, B, turicatae, B. parkeri
   - mountainous areas of north America

Question 19

What percent of cases of Epidemic RF are lethal?

What facilitates the lethality?

Answer 19

40% of epidemic RF are lethal.

This is facilitated by antimicrobial therapy [tetra, erythro] that elicit a severe Jarisch-Herxheimer reaction

Question 20

What causes infection of human hosts by B. recurrentis?

Answer 20

B. recurrentis is in the vector of human body louse.
Infection is NOT caused by bite from the louse, but rather from the scratching and crushing of the infected louse into the bite and/or other superficial wounds

Question 21

What are the wild animal reservoirs of endemic RF?

Answer 21

Squirrels and other rodents

Question 22

Describe the pathogenesis of relapsing fever.

Answer 22

1. high grade spirochetemia with multisystem involvement
2. intermittent waves of relapse due to antigenic variation

antigen 1–> antibody 1
antigen 2–> antibody 2 etc etc etc

Question 23

What are the clinical manifestations of RF?

Answer 23

1. Acute onset “flu-like” symptoms
   - fever
   - headache
   - muscle ache
2. conjunctival suffusion [redness of pink-eye but without inflammatory exudate]
3. Petechiae
4. Hepatosplenomegaly
5. CNS involvement in 1/3

Question 24

What are the 3 main causes of death from relapsing fever?

Answer 24

1. myocarditis
2. shock
3. hepatic failure

Question 25

How is diagnosis of relapsing fever made?

Answer 25

demonstration of organism in peripheral blood smear

Question 26

What is treatment for relapsing fever?

Answer 26

1. tetracycline

2. erythromycin

Question 27

What is Jarisch-Herxheimer rxn?

Answer 27

Occurs hours after treatment in a large portion of patients with RF.
Release of bacterial constituents that provoke TNFa cytokine cascade leading to:
-fever, flushing
-tachycardia
- vasomotor instability

Question 28

What are all pathogenic leptospires serovars of?
What is the regional distribution and what are the reservoirs?
How does infection occur and who is at risk?

Answer 28

Leptospira interrogans
Worldwide zoonosis with reservoirs being wild and domestic mammals.

Infection occurs by indirect contact with URINE of infected animals via food, soil, water

Occupational, military, recreational risk

Question 29

What are the 2 phases of illness for leptospirosis?

How long does each stage tend to last?

Answer 29

1. Leptospiremic phase [2-7 days]
   - flu like illness with fever, myalgia, headache, GI
2. Immune phase [anicteric =0-30days, icteric 10-30days]
   - Anicteric = aseptic meningitis, uveitis, rash, conjunctival suffusion
   - Icteric = hepatic/renal dysfunction [ATN], myocarditis, vascular collapse [ Weil’s]

Question 30

Where are leptospires present during leptospiremic and immune stages?

Answer 30

Leptospiremic:
1. blood, CSF

Immune

1. CSF early
2. Urine the whole time

Question 31

How is diagnosis of Leptospirosis made?

Answer 31

1. cultured from blood in first 7-10 days, after which urinanalysis
2. serological diagnosis = 4x rise in agglutination titer or titer >1:100

Question 32

What is treatment for leptospirosis?

Answer 32

1. oral doxycycline for travellers or military in endemic areas
2. IV ampicillin, penicillin, ceftriaxone, tetracycline for treatment

Question 33

How do you avoid leptospirosis?

Answer 33

1. vaccine for pets/livestock

2. rat control