Chagas disease Flashcards
Chagas Disease
- Chronic parasitic Infection
- Caused by protozoan: T. Cruzi
- which passes on the enzyme: trypanosome
estimated infection, and locations
15-20 million infected
-more in the southern hemisphere
The vector
Rhodnius prolixus
- 5 nymphal stages that can all harbour T. cruzi
- adults with wings are harder to control
probability of vector and human infection
- 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
How is it transmitted
- contact through feces as the the infected bug defecates as it feeds (sucks blood)
- maybe enter through scratching
- infection first attacks the macrophages
Risk factors (4)
- cogenital (mother to baby), cross placental barrier through blood stream
- blood transfusion
- infected organ donations
- contaminated food/drink such as meat through food chain
very motile, flagellated t. cruzi
tryptomasigote
Triatomine Bug stages
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
Human stages
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
Acute Stage
- 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
Romana sign
- swelling in eye due to trypomastigotes and inflammatory response
- conjuctivitis
Chagoma
Inflammatory nodule at bite site
Indeterminate stage
- no symptoms (controlled by immune system)
- no trypomastigotes in blood stream but may be embedded into tissues
Chronic Stage
- 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
Vector borne transmission in humans (detailed)
- 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
T cruzi Invasion
- 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
Invasion steps
- Trypomastigote attaches to macrophages and anchors it down
- internalization via phagocytosis
- recruitment and fusion of host lysosomes - formation of paristophorous vacuole and parisite is not affected by lysosomal content
- Rather, the change in PH allows trypomastigote to turn into amastigote form
- Vacuole is digested and amastigote released into cytoplasm
- binary fission dividing
- transform back to trypomastigote after many divisions
- host cells bursts and parisites enter blood stream
F- actin
- labels everywhere you have a muscle fibre
blue dots
nuclear labelling, labelling everywhere there is nuclei which includes flagellated trypomastigotes
why is it called kissing bug
- attracted to high CO2 levels
- warm areas for biting such as near lips eyelids
fibronectin
- 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
chagas induced cardiomyopathies distole vs systole
heart fills during dystole creating bulge but cant empty during systole due to compromised muscle cells/ connectivity
benznidazole
- used during acute phase
- heterochromatin unpacking in nucleus
- disrupts epimastigote nuclear envelope and damages double stranded DNA
- forms free radicals in the cell
amiodarone
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
