L10 MHD: Rickettsia Flashcards

1
Q

Name the Disease associated with the organism

  1. Rickettsia Rickettsii
  2. R. Akari
  3. R. Prowazekii
  4. R. Typhi
  5. E. Chaffeensis
  6. A. Phagocytophilum, E. Ewingii
  7. Coxiella Burnetii
A
  1. Rocky Mountain Spotted Fever**
  2. Rickettsialpox
  3. Epidemic Typhus (spread by human body louse)**
  4. Murine Typhus (spread by fleas)
  5. Ehrlichiosis (HME human monocyte)**
  6. Ehrlichiosis (HA Human aniplasmosis)**
  7. Q Fever

** denotes organisms marked as important on the slide

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2
Q

General Characteristics of Rickettsia

  1. Gram test?
  2. Motility?
  3. What type of parasite?
  4. All require an arthropod vector except which?
  5. Most Rickettsia cause what symptoms?
  6. You can treat all forms of Rickettsia with what abx?
  7. How does division occur? Is growth slow or fast?
A
  1. Small, gram negative rods
    * *Don’t really use the gram stain to see them- use Giemsa stain where Rickettsia stains bluish/purple**
  2. Non-motile (no flagella)
  3. Obligate intracellular parasite (steal host ATP)
  4. All require arthropod except Q Fever (Coxiella Burnetti)
  5. Most cause severe headache, rashes, and high fever
  6. Doxycycline
  7. Binary fission, slow growth (8-10 hours)
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3
Q

Pathogenesis
1. Bacteria enter by ______________, which requires _______

  1. Once inside host, bacteria can replicate in what two locations?
    - Where do the following replicate: Orienta, Rickettsia, Ehrlichia, Anaplasma, Coxiella?
A
  1. Bacteria enter by endocytosis (requires energy)
  2. Replicate in
    - The cytoplasm: Rickettsia, Orientia
    - Membrane bound cytoplasmic vesicle:
    - -Phagosome: Ehrlichia, Anaplasma
    - -Phagolysosome-like vesicle: Coxiella
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4
Q

Pathogenesis of Ehrlichia & Anaplasma:

  1. Where do they replicate?
  2. How do they prevent their own degradation?
A
  1. Replicate in phagosome
  2. Prevent their own degradation by preventing phagosome/lysosome fusion
    * *If they two fuse, the organisms are killed**
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5
Q

Pathogenesis of Coxiella

  1. Where does it replicate?
  2. What is required for growth?
A
  1. replicates in CCV- Coxiella containing vesicle -phagosome fuses with endosome! (phagolysosome-like)
  2. low pH is required for growth
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6
Q
  1. Where do R. Rickettsii, R. Typhi and Orienta replicate?

2. How do R. Rickettsia and R. Typhi migrate?

A
  1. Replicate/multiply freely in the cytoplasm
  2. R. Rickettsii and R. Typhi (fleas) migrate intracellularly using actin polymerization- polymerize actin at pole, pushes bacteria across cytoplasm- organisms can encounter host cell membrane.
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7
Q
  1. What strain of R. Typhus is transmitted by a human body louse (epidemic)?
  2. Does it use actin polymerization to migrate intracellularly?
  3. How does it exit the host?
A
  1. R. Prowazekii
  2. Does not use actin polymerization! (R. Typhi- flea- endemic strain does!)
  3. Exits host via lysis- keeps growing until they lyse the host cell
    * *R. Rickettsia & R. Typhi exit by budding**
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8
Q

How do R. Rickettsii, R. Typhi and Orientia escape the phagosome?

A

Use phospholipase A

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9
Q
  1. How do Rickettsia, Orientia, Ehrlichia, and Anaplasma fair outside of the cell?
  2. How is Coxiella different?
A
  1. They are unstable and die rapidly- they require CoA & NAD+
  2. Coxiella remains viable for years- it’s resistant to dying
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10
Q

What diseases are spread by the following insect vectors:

  1. Ticks
  2. Mites
  3. Lice
  4. Fleas

What diseases have the following animal reservoirs?

  1. Rodents
  2. Dogs
  3. Flying Squirrels
  4. Deer
A

VECTORS:

  1. Ticks
    - RMSF
    - Ehrlichiosis
  2. Mites
    - Rickettsialpox
    - Scrub Typhus
  3. Lice
    - Epidemic Typhus (R. Prowazekki)
  4. Fleas
    - Murine Typhus (R. Typhi)

RESERVIORS:

  1. Rodents
    - RMSF
    - Rickettsialpox
    - Murine Typhus
    - Ehrlichiosis- HA
  2. Dogs:
    - RMSF
  3. Flying Squirrels:
    - Epidemic Typhis (R. Prowazekki)
  4. Deer
    - Ehrlichiosis- HME
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11
Q
  1. How do R. Ricksettii & R. Typhus cause rash?

2. Where do the rashes form?

A
  1. Bacteria multiply in endothelial cells lining small blood vessels- rupture results in rash
    - Primary lesion: vasculitis in many organs (prominent in the skin)
  2. R. Rickettsii causes a rash that typically starts at wrists and ankles and then spreads to the trunks, palms, and soles
    - R. Typhus produces a rash that starts out centrally and spreads out, sparing the palms and soles

“Rickettsii on wRists, Typhus on the Trunk “

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12
Q

Diagnosis is based on which two of the following:

a) clinical findings
b) epidemiological findings
c) serological findings
d) PCR

A

Based on clinical findings and epidemiologic information

because culturing is difficult, hazardous (obligate intracellular pathogens)

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13
Q

What serological tests can be used and why do we use them?

A

Serologic tests: used to confirm the diagnosis

  • Immunofluorescence assay (IFA) : Relatively sensitive, Requires little antigen, detects IgM and IgG
  • Microfluorescence assay (MIF): tests for antibodies against multiple antigens

PCR is another test that can also be used for diagnosis (uncommon)

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14
Q
  1. Do you treat patient before or after you get the results of a serology test?
  2. What type of therapy is this?
  3. What is the best antibiotic to give patients?
  4. Which are contraindicated?
  5. Is a vaccine available?
A
  1. Therapy before seroconversion because the more therapy is delayed, the less effective it is
  2. Empiric therapy
  3. Tetracyclines (Doxycycline) & Chloramphenicol
  4. Sulfonamides are contraindicated! TEST
    * *R. Rickettsii is resistant to sulfa drugs
  5. Limited vaccines available
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15
Q

RMSF- Rocky Mountain Spotted Fever

  1. Causative agent? How long is the incubation period?
  2. Symptoms? Which is most important?
  3. Most common vector?
  4. Two common reservoirs?
  5. Where in the US is it most common?
A
  1. R. Rickettsii (intracellular, replicates freely in the cytoplasm, spreads via actin polymerization, most common Rickettsial pathogen in the US)
    - Usual incubation period is 2-7 days but could be upwards to 2 weeks
  2. RASH ON EXTREMITIES TEST is the most important symptom; patients also present with severe headache and high fever
    - “Macular rash, initially involving the extremities” TEST
  3. Hard Tick Vectors most common
    - Associated with exposure to wooded areas where ticks exist
  4. Common reservoirs: rodents and dogs
  5. Southeast Atlantic and South Central States
    - More common in the summer
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16
Q
  1. How is RMSF diagnosed?
  2. Best treatment?
  3. How long after a tick bite does it take for transmission of the disease?
  4. What are preventative measure someone could take?
A
  1. Diagnosed by clinical symptoms (rash being the best indicator) and epidemiology
    - Can be confirmed with PCR (gene targets= ompA & ompB)
    - Can be confirmed with (+) MIF test
  2. Tetracyclines (Doxycycline) and Fluoroquinolones are the best to treat RMSF
    - Chloramphenicol not recommended- causes a higher relapse of disease
    - Delayed treatment increases the likelihood of death by 10-25%
  3. Transmission requires 24-48 hours
    - The sooner you get the tick off, the better your odds are of not developing RMSF
  4. Control is impossible, no vaccine available- Avoid wooded areas in the summer, inspect body for ticks if you’ve been in a wooded area
17
Q

Rickettsialpox

  1. Causative agent?
  2. A mild disease with what type of rash?
  3. Phase 1 rash description
  4. Phase 2 rash description
  5. How is the disease treated?
  6. What is the most common vector of disease?
A
  1. R. Akari
  2. Vesicular Rash
  3. Phase 1: Firm Red Papule TEST at the site of the bite, develops into a vesicle, then a black eschar. The bacteria spreads.
  4. Phase 2: 9-14 days, high fever, severe headache, chills/sweats, myalgia, photophobia, vesicular rash TEST
  5. Self-limiting after 1 week, no treatment, no deaths have been reported
  6. Bloodsucking mites found on mice are the most common vectors/reservoirs
18
Q
  1. Brill-Zinsser (Recrudescent Typhus or Brill’s disease) is caused by a relapse of what kind of Typhus?
  2. Who is the reservoir in this case?
A
  1. Relapse of louse borne typhus (R. Prowazekki)
    - Appears 10-40 years after primary attack
    - Milder and often less fatal
  2. Humans are the reservoir for this disease- Rickettsia persists for many years in the lymph nodes
19
Q

Murine Typhus (Endemic Typhus)

  1. Causative agent?
  2. Incubation period?
  3. Symptoms?
  4. What % of cases present with rash?
  5. Vector/Reservoir?
  6. Where is the disease found?
  7. Treatment?
A
  1. R. Typhi (intracellular, replicates freely in the cytoplasm, spreads via actin polymerization)
  2. 1-2 weeks incubation period
  3. Abrupt fever, severe headache, chills, myalgia, nausea
  4. Rash in 50% of cases- late- maculopapular on trunk! TEST*
  5. Vector= rat flea, cat flea
    Reservoir= Rodents
  6. Found in temperate and subtropical coastal areas- 50-100 cases annually in the US
  7. Tetracycline, Doxycycline, Chloramphenicol
20
Q

E. Scrub Typhus

  1. Causative agent?
  2. 50-80% of patients develop what at the site of the bite?
  3. Other symptoms?
  4. What is the vector AND reservoir?
  5. Where is the disease found?
  6. Treatment?
A
  1. Orientia Tsutsugamushi
  2. Necrotic eschar at site of bite in 50-80%
  3. Fever, headache, maculopapular rash after 5 days, lymphandenopathy
  4. Mites are vectors AND reservoir TEST
    - Passage to progeny via infected ova
  5. Disease found in Far East (Southwest Pacific, Southeast Asia, Japan- hence the name that sounds like fancy Japanese restaurant)
  6. Tx: Tetracycline, Doxycycline, or Chloramphenicol
    - Fever disappears within 2-3 weeks without treatment
21
Q

Ehrlichiosis:

  1. Human Anaplasmosis (HA) caused by what?
  2. Human Monocyte Ehrlichiosis (HME) caused by what?
A
  1. HA: granulocytes infected
    - Anaplasma Phagocytophilum
    - Ehrlichia Ewingii
  2. HME: monocytes, mononuclear phagocytes infected
    - Ehrlichia Chaffeensis
22
Q

What two strains cause an eschar to develop?

A
  1. Rickettsialpox

2. Scrub Typhus

23
Q

What diseases are associated with the following rashes?
1. >90% of patients present with this macular rash, that has a centripetal spread (from extremities to center)
2. 20-80% of patients present with rash, macular, that has a centrifugal spread (trunk to extremities)
3. 50% present with a maculopapular rash on the trunk
4. 100% present with a vesicular rash
5.

A
  1. RMSF
  2. Epidemic Typhus
  3. Murine Endemic Typhus
  4. Rickettsialpox
  5. Scrub Typhus
24
Q

Q Fever
1. Causative agent?

  1. Clinical features? Onset? What is a symptom of chronic Q fever?
  2. Epidemiology?
A
  1. Coxiella Burnetii
  2. NO RASH TEST
    - Most human infections are NOT apparent
    - Mild, dry hacking cough and pneumonia sometimes present
    - Onset 9-20 days- abrupt onset of fever, chills & headache
    - Chronic Q Fever: subacute endocarditis
  3. Worldwide distribution, carried by mammals (cattle, goats, sheep) and transmission occurs from animals to human by inhalation of dust
25
Q

Q Fever

  1. Pathology… what is needed for growth?
  2. Physiology and disease progression:
    - Phase 1: intact _______
    - Phase 2: missing _____________ antigen of ______
  3. Dx: how do serum tests differ between acute & chronic infection?
  4. Treatment?
A
  1. Bacteria multiply in acidified phagosome- adapted to growth at a low pH
    - Resistant to drying
  2. phase 1: intact LPS
    - phase 2: missing outermost O antigen of LPS
  3. Serology tests:
    -Acute: look for phase II antigens
    Chronic: look for both phase I & phase II antigens
    Could also use PCR to diagnose
  4. Tetracycline (doxycycline) or combination for chronic infections
    - Vaccines have been developed- only effective if patient has never been exposed
26
Q

G. Ehrlichiosis (HA and HME)

  1. What are the vector and animal reservoirs for disease?
  2. How long until you start experiencing symptoms?
  3. Mortality of disease?
  4. Where is Ehrlichiosis commonly found? During what season is it most common?
A
  1. Vector for both= TICK Test
    - Deer Reservoir: Ehrlichiosis-HME
    - Rodent Reservoir: Ehrlichiosis HA
  2. Onset= 1-2 wks after tick bite
    - Symptoms: flu-like with high fever, headache myalgia (generally no rash)
    - Leukopenia, thrombocytopenia, elevated transaminases
  3. Mortality low but >50% of cases require hospitalization
  4. Commonly found in Midwest & southern states
    - HME: midwest, coastal Atlantic
    - HA: upper midwest, northeast Atlantic
    - Most common in the summer
27
Q

G. Ehrlichiosis (HA and HME)

  1. How long does it take after tick bite to get the disease?
  2. What is the pathology?
  3. How is it diagnosed?
  4. What is the treatment of choice?
A
  1. Transmission of disease within 6 hours after bite
  2. Ehrlichiae infect circulating leukocytes (lack peptidoglycan and LPS)–>Multiply within inclusions–>prevent lysosomal fusion–>Grow until cell lysis
    - Two morphological forms: small elementary bodies (resemble morulae- diagnostic of disease) and larger reticulate bodies
  3. Dx:
    - Morulae- detected in less than 10%, but diagnostic if found
    - PCR
    - IFA
  4. Doxycycline to treat
    - If pregnant use Rifampin
    - Chloramphenicol, penicillins, and macrolides are not effective
    - Vaccines not available
28
Q

Epidemic Typhus

  1. Causative agent?
  2. Responsible for deaths during what war?
  3. What type of rash forms? Where does it start/spread to?
  4. Prominent symptoms?
  5. How fatal is the disease if untreated?
A
  1. R. Prowazekii (Intracellular, replicates in cytoplasm, no actin polymerization)
  2. WW1
  3. Maculopapular rash first on the trunk and then spreads to the extremities- spares palms and soles! TEST*
  4. Other symptoms: headache, malaise, myalgia
  5. More fatal in pts > 40 years old; 20-30% of patients die if disease goes untreated
29
Q

Epidemic Typhus

  1. Disease is associated with what type of conditions? What season does it peak in?
  2. Common vector/reservior?
  3. How is it diagnosed?
  4. How is it treated?
A

Epidemic Typhus

  1. Associated with unsanitary conditions- peaks in winter
  2. Common vector: body louse, common reservoir: humans & flying squirrels
  3. Dx= MIF
  4. Tetracycline (Doxycycline) or chloramphenicol
    - Prevent by louse control.
    - Vaccine available for high risk population