Chagas disease

Question 1

Chagas Disease

Answer 1

• Chronic parasitic Infection
• Caused by protozoan: T. Cruzi
• which passes on the enzyme: trypanosome

Question 2

estimated infection, and locations

Answer 2

15-20 million infected

-more in the southern hemisphere

Question 3

The vector

Answer 3

Rhodnius prolixus

• 5 nymphal stages that can all harbour T. cruzi
• adults with wings are harder to control

Question 4

probability of vector and human infection

Answer 4

• rhodnius prolixus infection probability increases with number of bloodmeals
• therefore, humans have a bigger chance at infection if bit by an adult due to increased parasitic load

Question 5

How is it transmitted

Answer 5

• contact through feces as the the infected bug defecates as it feeds (sucks blood)
• maybe enter through scratching
• infection first attacks the macrophages

Question 6

Risk factors (4)

Answer 6

• cogenital (mother to baby), cross placental barrier through blood stream
• blood transfusion
• infected organ donations
• contaminated food/drink such as meat through food chain

Question 7

very motile, flagellated t. cruzi

Answer 7

tryptomasigote

Question 8

Triatomine Bug stages

Answer 8

1) takes blood meal with trypomastigote prozoan
2) epimastigotic stage - must survive the midgut
- the less motile version
- may undergo binary fission and multiply in midgut
3) enters hind gut and transitions/differentiates to metacyclic trypomastigote
4) bites human and transfers metacyclic trypomastigotes through feces

Question 9

Human stages

Answer 9

1) metacyclic trypomastigote penetrate various cells at bite wound site where they transform into amastigotes
2) amastigotes multiply through binary fission inside the tissue
3) intracellular amastigotes transform back into trypomastigotes and burst out of cell to enter the blood stream
4) cycle continues as more trypomastigotes enter cells

Question 10

Acute Stage

Answer 10

• prevalent in children under 10 due to priming immune system
• chagoma and romana sign
• trypanosomes appear in blood in 10 days
• symptoms of inflammation appear after 2-3 weeks after infection

Question 11

Romana sign

Answer 11

• swelling in eye due to trypomastigotes and inflammatory response
• conjuctivitis

Question 12

Chagoma

Answer 12

Inflammatory nodule at bite site

Question 13

Indeterminate stage

Answer 13

• no symptoms (controlled by immune system)

- no trypomastigotes in blood stream but may be embedded into tissues

Question 14

Chronic Stage

Answer 14

• only 40% reach this stage, some die in indeterminate stage due to dorman amastigotes
• some are symptomatic, some are asymptomatic
• low levels of parasites in blood

Question 15

Vector borne transmission in humans (detailed)

Answer 15

• recruitment and fusion with lyosomes required for tryptomastagotes to penetrate cells
• enclose tryptomastagotes within vacuoles where it breaks free and differentiates into amastigotes
• binary fission replication leading to cell lysis and spread of infection into blood stream as it transforms back into tryptomastigotes
• cycle restarts
• after decades of cycle, leads to mega esophagus, megacolon, cardiomyopathy

Question 16

T cruzi Invasion

Answer 16

• infection driven by adhesion and internalization
• TC can develop ability to recognize and bind to receptors
• produce actin finger like projections
• interaction between ligands/receptors
• actin and lysosome dependent mechanisms

Question 17

Invasion steps

Answer 17

1. Trypomastigote attaches to macrophages and anchors it down
2. internalization via phagocytosis
   - recruitment and fusion of host lysosomes
3. formation of paristophorous vacuole and parisite is not affected by lysosomal content
4. Rather, the change in PH allows trypomastigote to turn into amastigote form
5. Vacuole is digested and amastigote released into cytoplasm
6. binary fission dividing
7. transform back to trypomastigote after many divisions
8. host cells bursts and parisites enter blood stream

Question 18

F- actin

Answer 18

• labels everywhere you have a muscle fibre

Question 19

blue dots

Answer 19

nuclear labelling, labelling everywhere there is nuclei which includes flagellated trypomastigotes

Question 20

why is it called kissing bug

Answer 20

• attracted to high CO2 levels

- warm areas for biting such as near lips eyelids

Question 21

fibronectin

Answer 21

• invovled in muscle cell connectivity
• infected cardiac tissue, fibronectin distribution is compromised which compromises muscle cell connectivity, which influences coordinated contraction of atria and ventricles

Question 22

chagas induced cardiomyopathies distole vs systole

Answer 22

heart fills during dystole creating bulge but cant empty during systole due to compromised muscle cells/ connectivity

Question 23

benznidazole

Answer 23

• used during acute phase
• heterochromatin unpacking in nucleus
• disrupts epimastigote nuclear envelope and damages double stranded DNA
• forms free radicals in the cell

Question 24

amiodarone

Answer 24

for chagas due to arrythmias

• slows cardiac action potential propogation
• interrupts calcium homeostasis which is anti parasitic
• parasites have membrane blebs
• loss of intracellular material
• alteration to mitochondrial DNA
• many side effects