Multi-system Pathogens

Question 1

1. What are the three characteristics of a multi-system infection?

Answer 1

1. An infection caused by an agent that can:
   * *disseminate** to multiple tissues
   * *replicate** and/or persist in those tissues
   * *cause disease** in multiple tissues

Question 2

What 4 mechanisms allow “professional” multi-system pathogens to evade the immune system?

Answer 2

Antigenic variation, serum resistance, cloaking, cell invasion

Question 3

1. What survival mechanisms are utilized by Borrelia?
2. What survival mechanisms are utilized by Treponema pallidum?
3. What two multi-system bugs utilize phagocytosis prevention?
4. What multi-system bugs utilize cell invasiveness? (intracellular replication, spread)

Answer 3

1. Antigenic variation, Complement inactivation, tissue invasiveness
2. Antigenic variation, few surface proteins, tissue invasiveness (extracellular replication/spread)
3. Bacillus anthracis, Yersinia pestis
4. Anaplasma, Ehrlichia, Rickettsia, Bartonella, Chlamydia, Coxiella

Question 4

1. What are three examples of antigenic variation (recombination) and what bugs do each of these?
2. How do *Borrelia *and Leptospira inactivate complement?
3. How do many bacteria manage to “cloak” themselves?

Answer 4

1. Recombination of Vls & Vmp loci

Recombination of TprK locus
(Treponema pallidum)

2. Borrelia and Leptospira inactivate complement by binding to factor H.
3. They bind to fibronectin and other plasma proteins.

(*Borrelia - *Lyme disease/Relapsing fever)

Question 5

There are three main mechanisms for cell invasion:

1. What organism binds to, enters, replicates in late endosomes, and autophagosomes of NEUTROPHILS ?
2. What organism binds to, enters, replicates in early endosomes of **MONOCYTIC CELLS **?
3. What organism binds to, enters, replicates in cytoplasm of ENDOTHELIAL CELLS ?

Answer 5

1. Anaplasma phagocytophilum
2. Ehrlichia chaffeensis
3. Rickettsia species

Question 6

There are 3 main types of tissue invasion. Which organism:

1. Sequesters and activates host plasminogen and matrix metalloproteinases ?
2. Utilizes endogenous proteases ?
3. Penetrates between cells ?

Answer 6

1. Borrelia, Leptospira
2. Teponema pallidum
3. Borrelia, Leptospira

Question 7

What is the difference between and “opportunist” and a “professional” pathogen from a multi-system infectious stand point?

Answer 7

Opportunists are otherwise typically benign bugs put in places they don’t belong and affect immunocompromised patients

Professional pathogens all can cause disease in immunocompetent hosts and some are transmitted by an arthropod vector.

Question 8

What are some routes of entry/disruptions that allow opportunists to set up shop?

Answer 8

1. Disruptions to physical barriers: CVADs, Injections, Surgery, Dialysis
2. SYSTEMIC disruptions: Chemo, Radiation, Immunosuppression, Immunodeficiency

Question 9

1. What does Biological transmission by a vector mean?
2. What does Vector competence mean?
3. What does transstadial transmission mean?
4. What is transovarial transmission?

Answer 9

1. Specific life stage in a vector
2. Ability of a vector to transmit a pathogen
   Three processes: Acquire-Maintain-Transmit
3. Pathogen is transmitted/maintained in different life stages. (Lyme, Anaplasmosis, Ehrlichiosis)
4. Transmitted from one generation to another.
   (Rocky Mountain Spotted Fever, Rickettsiosis)

Question 10

What are the tick-borne, Gram-negative, intracellular bacilli that replicate in vacuoles?

Answer 10

• Anaplasmosis*
• Ehrlichiosis*

Question 11

What is the tick-borne, gram-negative intracellular bacilli that replicates in cytoplasm?

Answer 11

Rocky Mountain Spotted Fever

Question 12

What tick-borne, Gram-negative extracellular spirochete replicates outside of host cells?

Answer 12

Lyme disease

Question 13

1. What diseases can result from Ixodes scapularis**?
2. What diseases can result from Ixodes pacificus?

Answer 13

1. Anaplasmosis
   Lyme disease
   Ehrlichiosis
2. Anaplasmosis
   Lyme disease

Question 14

1. What is the key difference between tick larvae and nymphs/adults?
2. When is the peak season for transmission of Ixodes scapularis?
3. When is the secondary peak from adult ticks?

Answer 14

1. Larvae have 6 legs and are often not infected

Nymphs/Adults have 8 legs, are potentially infected

2. Spring to early summer.
3. Fall

Question 15

1. What organism causes Human Granulocytic Anaplasmosis?
2. What is its physical characteristics?
3. How does it function?
4. What does it do to its neutrophil host?

Answer 15

1. Anaplasma phagocytophilum
2. TINY Gram negative coccobacillus
3. OBLIGATE intracellular that replicates in vauoles b/c it has no LPS or peptidoglycan. It has type IV secretion.
4. Disrupts whole array of function yet activates chemokine expression and degranulation

Question 16

1. What is the typical organism that causes Ehrlichiosis?
2. What does it look like?
3. What does it invade?

Answer 16

1. E. chaffeensis
2. TINY Gram negative coccobacilli
3. Monocytes and neutrophils

Question 17

1. What is the incubation period for Anaplasmosis and Ehrlichiosis?
2. What are the common symptoms?
3. How are they diagnosed?
4. What is the treatment?

Answer 17

1. 1-2 weeks
2. Headache, Myalgia, Anorexia, Pancytopenia, elevated liver enzymes
3. Intracellular colonies seen on blood smear, PCR, Serology at 30 days
4. Doxycycline (covers Lyme) or Rifampin (DOESNT cover Lyme)

Question 18

1. How is Rickettsia rickettsii transmitted in the tick?
2. How is it similar/different from Anaplasmosis and Ehrlichiosis?
3. What type of cell does it affect?
4. How does it move intracellularly?

Answer 18

1. Transovarial AND Transstadial
2. It is ALSO a TINY gram negative coccobacilli that is OBLIGATE intracellular with type IV secretion. It is DIFFERENT because it replicates in the cytoplasm and DOES HAVE LPS and PDG.
3. Endothelial cells.
4. By polymerizing actin (actin tail)

Question 19

1. What is the incubation period for RMSF?
2. What are the hallmark symptoms for RMSF?
3. How is a diagnosis made?
4. What is the treatment?

Answer 19

1. ~1 week
2. Rash starting on ankles, wrists, forehead - small macules progress to maculopapules then to petechiae
3. Clinical Judgement: tick bite, endemic area, season, symptoms
4. Oral doxycyline (NOT other tetracyclines) or chloramphenicol

Question 20

1. What is the most common vector borne illness in the northern hemisphere?
2. What organism causes it?
3. What are it’s physical characteristics?

Answer 20

1. Lyme disease!
2. Borrelia burgdorferi
3. Gram negative spirochete, extracellular,
   no LPS/toxins/special secretion systems

Question 21

1. How long is required for transmission of Borelia?
2. What is the hallmark sign/symptom of early/localized disease?
3. What is the hallmark of early disseminated disease?
4. What are the hallmarks of late disseminated disease?

Answer 21

1. >36 hours
2. Erythema migrans >5cm
3. facial palsy, polyradiculopathy, pancarditis, AV nodal block
4. Arthritis, encephalopathy, polyradiculopathy

Question 22

1. What is sufficient evidence for diagnosis and start treatment for Borelia (Lyme)?
2. What if this isn’t present?
3. Why can’t serology be used to assess success of treatment?
4. What is the treatment?

Answer 22

1. Clear EM lesion with likely known tick encounter
2. ELISA + western blot
3. Both IgM and IgG may remain positive for years after treatment
4. Oral doxycycline for early, amoxicillin for preggers. Ceftriaxone for CNS involvement

Question 23

1. What is the Geography for Lyme and Anaplasmosis diseases?
2. What is the geography for RMSF?
3. What is the geography for Ehrlichiosis?

Answer 23

1. Southeast, Northeast, Great lakes
2. Whole US
3. Southeast, Midwest