Micro- Vector Borne Infections

Question 1

What 2 genera are considered to be in the Rickettsiaceae family?

What 4 genera are in the Anaplasmataceae family?

Answer 1

Rickettsia:

1. rickettsia
2. orientia

Anaplasmatacaeae

1. anaplasma
2. ehrlichia
3. neorickettsia
4. wolbachia

Question 2

Rickettsia genera has more than 30 species associated with human disease. The genera is further broken down into what 2 groups?

Answer 2

1. spotted fever group

2. typhus group

Question 3

Orientia only has one species. What is it and what does it cause?

Answer 3

O. tsutsugamushi

It causes scrub typhus

Question 4

What is the size, shape, and gram stain capacity of Rickettsia and Orientia?
What is required to grow the in vitro? Why?

Answer 4

They are small, pleomorphic gram negative coccobacilli
They contain non-toxic LPS and peptidoglycan.

To grow in vitro, they require living cells like yolk sac of embryonated eggs or tissue culture cell lines because they are OBLIGATE INTRACELLULAR parasites

Question 5

Rickettsia species are found worldwide. Each species has a specific arthropod vecor and one or ore animal reservoirs. What are the 4 arthropod vectors?

Answer 5

1. hard tick–RMSF, tick typhus
2. mites– richettsialpox, scrub typhus
3. lice–
4. fleas– endemic typhus

Question 6

What intracellular parasite causes RMSF?
What is the primary reservoir?
Where are endemic areas in the US?
What is the seasonal preference and arthropod vector?

Answer 6

Intracellular parasite: Rickettsia Rickettsii

Primary reservoir: rodents [although other mammals can be hosts as well]

Endemic areas:
1. Mid-Atlantic states
2. Texas, Oklahoma - Lonestar tick
3. Southeastern US - Dog tick 
[in the west, it is the wood tick]

Seasonal preference: spring/summer

Question 7

How does transmission of the infection differ from Lyme disease in the Ixode tick vs. Rickettsia Rickettsii in the wood, lone star and dog ticks?

Answer 7

Rickettsia is maintained by transovarial transmission [Vertical].

Lyme disease is not maintained by vertical transmission

Question 8

What intracellular parasite causes rickettsialpox?
What is the natural reservoir? arthropod vector?
What are the 2 ways the infection is maintained?
What environment does it occur in?

Answer 8

Rickettsia akari

Natural reservoir: wild rodents/mice
Arthropod vector: mite

Maintained by:

1. mice-to-mice transfer via mites
2. maintained in mites via vertical transmission

Environment: worldwide, but prefers drier environment

Question 9

What disease is caused by:
R. conorii
R. australis
R. africae

Where do they occur? What is the arthropod vector?

Answer 9

Tick Typhus in the Mediterranean, Australia and Africa respectively.

Vector: brown dog tick

Question 10

What are the two forms of typhus?
What is the vector for each type?
What intracellular parasite causes each?
What is the main reservoir of each?

Answer 10

1. Epidemic
   - human louse borne
   - R. prowazekii
   - reservoir : humans [crowding, poor hygiene, poverty] or squirrels [southern flying squirrel]
2. Endemic
   - flea-borne [the rat flea]
   - R. typhi
   - reservoir: rats, mice, rodents in Texas, southern border states

Question 11

What is the intracellular parasite and reservoir/vector of scrub typhus?
How is the parasite maintained?

Answer 11

Orientia tsutsugamushi
Reservoir/vector: mite

Maintained by transovarial transmission

Question 12

What is the pathogenesis of Rickettsia?

Answer 12

1. infecting organism is introduced to human host by a bite, but the tick must stay attached for 24-48 hrs to transmit the Rickettsia
2. local replication
3. bacteremic spread
4. enters host cell by stimulating phagocytosis, then degrading the phagosome using bacterial phospholipase to enter cytoplasm

Question 13

Where do the following grow within the host cell?
How are they released?

1. spotted fever group [rickettsii, akari, africa, australis, coronii]
2. orientia
3. typhus group [prowazekii, typhi]

Why does this difference exist?

Answer 13

1. grow in the cytoplasm and released by membrane protrusion
2. grow in the nucleus and released from membrane protrusion
3. grow in cytoplasm and released by lysis of host cell

Spotted fever group has the ability to polymerize actin.

Question 14

How do Rickettsia get energy?

Answer 14

1. make their own ATP via TCA cycle

2. parasitize the host cell ATP by means of bacterial ATP translocase

Question 15

What are the primary sites of replication in Rickettsia infection?

Answer 15

Vascular endothelium leading to:
1. vasculitis due to cell dysfunction and death leading to capillary damage and leaking of blood cells into perivascular tissue –> petechial hemorrhage

2. exposed subendothelium activates clotting cascade leading to thrombosis and necrosis

Question 16

In general ALL rickettsial infections are characterized by what features?
What is the range of incubation period?

Answer 16

1. Fever, headache, malaise, prostration
2. Skin Rash
3. enlargement of spleen and liver

Incubation is 2-15 days with most lingering around 1 wk

Question 17

A patient presents with a high fever, chills, headache and myalgias. He said it was rapid onset, but he didn’t seek help because he thought it was some viral thing. He had been camping in the woods last week in Georgia and wasn’t sure he cooked his food properly. About 3 to 5 days into the fever, he got a maculopapular rash on his wrists, ankles, palms&soles. The rash spread to his trunk and became petechial. He did NOT have eschar or tache noir.
What is the presumptive diagnosis?

Answer 17

RMSF

• endemic area [southeast-dog tick]
• fever, malaise, headache followed 3 days later by rash
• rash involves palms, soles, wrists, ankles with CENTRIPETAL SPREAD
• unlike the other rickettsial diseases, there was no eschar or tache noir marking the site where the tick bit him

Question 18

What is case fatality for RMSF in elderly and children?

What increases the fatality rate?

Answer 18

Elderly =50%
Children= 20%

Fatality is increased by delaying until after the presentation of the rash

Question 19

What characterisitic of the RMSF rash differentiates it from the other rickettsial diseases?

Answer 19

Centripetal nature [starts on wrists, ankles and then works inward]

Question 20

How does tick typhus presentation differ from RMSF?

Answer 20

1. milder, less fatal
2. less prominent rash that usually appears on trunk
3. tache noir at site of tick bite

Question 21

Describe the presentation of Rickettsialpox.

Answer 21

Phase 1:
Papule at the site of the mite bite becomes tache noir in 7-10 days.

Phase 2:
3-7 days after tache noir, the patient gets
- fever, chills, myalgia
-regional lymphadenopathy
- stiff neck [MENINGITIS LIKE PRESENTATION]
- papulovesicular rash –> crusting

It resolves without therapy and has low mortality.

Question 22

A patient presents with fever chills, myalgia, regional lymphadenopathy and a stiff neck. She has a papulovesicular rash with vesicles and crusting. Near the rash is a black spot. She said the black spot started as just a bump about 2 weeks ago.
What is it likely she has?

Answer 22

Rickettsialpox

Question 23

Describe the pathogenesis of epidemic typhus?
When/how does the infection start?
What is incubation period?
What symptoms show up first?
How is the presentation different from RMSF?

Answer 23

1. bite from pediculus humanus corporis which feeds and then defecates
2. Feces are pruritic so the human scratches and grinds feces into the cut
3. 8 day incubation
4. constitutional symptoms with fever, myalgia, headache, arthralgia
5. 4 to 7 days later a rash begins on the trunk and then spreads outward but SPARES palms, soles, face [unlike RMSF]

Question 24

If a patient is to die of epidemic typhus, what is the usual cause?

Answer 24

Myocarditis or CNS complications

Question 25

How does endemic typhus compare to epidemic?

Answer 25

Similar presentation except: 1. milder 2. rash restricted to chest only

Question 26

What is Brill-Zinsser disease?

Answer 26

reactivation of epidemic typhus that occurs decades after the resolution. It is mild and resolves with minimal sequelae

Question 27

How does the incubation period, rash, presence of tache noir and systemic symptoms differ for scrub typhus and RMSF?

Answer 27

Scrub typhus has a longer incubation period [10-12 days compared to a week] Scrub typhus has a rash more similar to epidemic typhus that starts on the trunk and spreads outward WITH a tache noir where RMSF has a rash that starts peripherally and extends centrally WITHOUT tache noir. Scrub typhus has: - hepatosplenomegaly - cardiac failure - CNS effects like stroke

Question 28

How are rickettsial diseases diagnosed?

Answer 28

1. clinical presentation with good travel history 2. indirect immunofluoresence test [sensitive, specific] done 4th to 8th day of disease that is done to confirm clinical 3. biopsy with PCR is diagnostic but only done in reference labs

Question 29

What is treatment for Rickettsia?

Answer 29

DRUG OF CHOICE: 1. Doxycycline for 5-7 days or until patient is afebrile for 2 or more days - started empirically because time =death or RMSF - done even in pregnant/children b/c life >> discolored teeth Chloramphenicol is used OUTSIDE the US

Question 30

Where do ehrlichia and anaplasma live? | What is their size, gram stain?

Answer 30

Within membrane-bound vacuoles of leukocytes. They form clustered microcolonies called morulae. They are small coccobacilli that have dual membranes like G-, but lack LPS and peptidoglycan. They do not stain with Gram stain.

Question 31

What stain can be used to identify ehrlichia and anaplasma?

Answer 31

Blood smear stains like Giemsa Wright | They do not stain with gram stain because despite the fact they have 2 membranes, they lack LPS and peptidoglycan

Question 32

Human monocytic ehrlichiosis is caused by what organism? | What organism causes human granulocytic ehrlichiosis?

Answer 32

Monocytic ehrlichiosis = E. chaffeensis | Granulocytic ehrlichiosis = Anaplasma phagocytophilum

Question 33

How do ehrlichia and anaplasma get their energy?

Answer 33

They synthesize ATP from glutamine

Question 34

How does where rickettsiae and anaplasmataceae replicate inside the cell differ?

Answer 34

Rickettsia = inside the cytoplasm or nucleus after using phospholipase to degrade the phagosome Anaplasma = prevents lysosome fusion, but remains protected in the phagosome where it divides by binary fission to form the morulae

Question 35

For human monocytic ehrlichiosis, what is the: 1. intracellular organism 2. vector 3. reservoir 4. regional preference

Answer 35

1. Ehrlichiosis chaffeensis 2. Lone star tick and dog tick 3. Rodents 4. Midwest, Mid-Atlantic, Southeast, South Central * *Missouri and Arkansas

Question 36

For human granulocytic ehrlichiosis, what is the: 1. intracellular organism 2. vector 3. reservoir 4. regional preference

Answer 36

1. Anaplasma phagocytophilum 2. Ixode tick [same as Lyme] 3. rodents 4. Upper Midwest, Northeast * Wisconsin

Question 37

What is the clinical course of HGE and HME?

Answer 37

1. Tick bite 2. 7 day incubation 3. gradual onset fever, myalgia, headache [rash only occurs in 1/3] 4. later in the course: - anorexia/weight loss - anemia, leukopenia from hemolysis - abnormal LFTS

Question 38

What are the 2 things done for diagnosis of HGE or HME?

Answer 38

1. Routine blood smear to look for morulae - only 10% of HME will have it - only 20-80% of HGE will have it 2. Serology

Question 39

In what 3 ways does diagnosing HGE, HME differ from diagnosing RMSF?

Answer 39

1. HGE, HME you do NOT do culture as with RMSF 2. PCR is standard for HGE, HME in endemic areas and not for RMSF 3. Vasculitis is NOT observed in ehrlichiosis, but is the hallmark of RMSF

Question 40

What is treatment for ehrlichiosis or anaplasma

Answer 40

Doxycycline

Question 41

To what 2 bacteria is Coxiella phylogenetically related? How does it gram stain? What is its structure? What does it require to be cultured?

Answer 41

It is related to legionella and francisella It does not gram stain but is structurally similar to a Gram negative and has LPS It is a small coccobacilliary organism that is obligate intracellular It requires eggs or tissue culture to grow

Question 42

What is the arthropod vector of coxiella? What are the most common reservoirs? How are humans infected? What are the 3 most common people to get infected?

Answer 42

Ticks carry coxiella from animal to animal NOT from animal to human. The reservoir is large animals like cows, sheep, goats, but also domestic animals like dogs cats and sheep. Humans get infected by inhalation of the organism that is released when milk, urine, feces or ESPECIALLY PLACENTA after parturition is left on the ground and dries. This makes the following most likely to be infected: 1. ranchers 2. microbiologists 3. slaughterhouse workers

Question 43

What is pathogenesis of Q fever?

Answer 43

1. Coxiella spore with VIRULENT LPS1 gets inhaled 2. It is phagocytosed and lysosomal fusion occurs 3. it thrives in the acidic pH of the phagolysosome and is able to go through its life cycle 4. In tissue culture it has phase II LPS which is less virulent

Question 44

A rancher presents with a fever that lasts 1-2 weeks with chills, headache, fatigue, sweating and muscle aches. Upon examination you notice that he has walking pneumonia and granulomatous hepatitis. What is it likely that he has? When will he likely experience resolution?

Answer 44

Acute Q fever | Can resolve spontaneously in 4 to 6 weeks

Question 45

What is the incubation period for acute Q fever? | What determines the length?

Answer 45

10-60 days and depends on the number of spores inhaled. 1-2 spores is enough to cause infection in animal models

Question 46

What are some of the key symptoms of acute Q fever?

Answer 46

1. flu-like symptoms 2. walking pneumonia 3. granulomatous hepatitis [in 1/2]

Question 47

What is the most common presentation of chronic Q fever?

Answer 47

subacute endocarditis

Question 48

How is diagnosis of Q fever made?

Answer 48

1. serological [ELISA, IFA.etc] - acute has IgM and IgG to phase II antigens - chronic has IgG to phase II and phase I antigens

Question 49

What is treatment for Q fever?

Answer 49

doxycycline | [for endocarditis add rifampin]

Question 50

What is prevention for Q fever?

Answer 50

Vaccines are given for those at high risk for infection [lab workers, meat plant, dairy workers, ranchers] Whole cell and partially purified The most effective vaccines have phase I LPS because this is the infective form