Chagas Disease

Question 1

What parasite causes Chagas disease?

Answer 1

Trypanosoma cruzi

Question 2

Outline the life cycle of the parasite

Answer 2

Trypomastigotes transform into epimastigotes in the hind gut of a triatomine bug. They replicate through binary fission and situate themselves in the hind gut. Metacyclic trypomastigotes are deposited on skin by defecation of the bug. They can be rubbed into wounds or mucosal surfaces. They enter cells and become amastigotes which can replicate through binary fission. Bursting of cells releases trypomastigotes which can infect new cells or bugs.

Question 3

How does the trypomastigote propel itself?

Answer 3

By moving its flagella with energy from its kinetoplast.

Question 4

What is the significance of triatomine development and when does it feed?

Answer 4

Feeds at night. All of the moulting stages are heamatophagous.

Question 5

Other than the vector, how else is T. cruzi transmitted?

Answer 5

Vertical transmission
Blood donors
Food/fruit juice containing crushed bugs/faeces.
Sharing IV needles.

Question 6

Why is it unlikely that Chaga’s would be diagnosed in the acute stage of the disease?

Answer 6

Clinical signs aren’t normally very severe so poor people are unlikely to go to a doctor.

Question 7

What sort of things are seen in the acute stage?

Answer 7

Fever, headaches, hepatosplenomegaly, lymphadenopathy. 10% mortality

Question 8

How does the inter determinate stage differ?

Answer 8

Only see antibodies in the blood and no circulating parasites.

Question 9

What are the clinical signs of the chronic phase?

Answer 9

Fever, aching muscles, loss of appetite, irritability,
Nerve degeneration
Cardiomyopathies (arrhythmia, cardiomegally and apical aneurisms)
Megaoesophagous and megacolon.

Question 10

How is the disease diagnosed in the different stages?

Answer 10

Acute - blood smears, culture and xeondiagnosis.

Chronic - ELISA for antibody, PCR and IHC to detect parasite in tissues.

Question 11

Why was this disease originally thought to be autoimmune?

Answer 11

Lack of parasite seen in the blood.

Question 12

How does housing contribute to disease transmission?

Answer 12

Bugs hide in cracks in mud walls, thatched roofs etc. Proximity to domestic animals and wildlife also.
Best thing to do is improve housing quality.

Question 13

How can insecticides be applied to control chagas?

Answer 13

Paint the walls/spray powdered solutions. These are often expensive and need repeat treatments.

Question 14

How else can he vector transmission be prevented?

Answer 14

Bednets, food hygiene.

Question 15

How is the infection treated?

Answer 15

Benznidamole & nidurtimox - these are old and have no paediatric formulations.

Question 16

Why are there so few treatments?

Answer 16

Disease of poverty and the parasite is intracellular in immune privileged sites so it is hard to treat.

Question 17

Are there any other preventative measures?

Answer 17

Screen pregnant women and blood donors

Question 18

How has the disease migrated to Latin America?

Answer 18

Bugs moved due to deforestation and loss of wild food source.
Movement of migrants - baggage, blood donors
Armadillo and oposum

Question 19

What triggers the immune response in the acute phase?

Answer 19

Parasite mucins and DNA

Question 20

Which immune response clears parasites from the immune system, is there any disadvantages to this type of response?

Answer 20

Cellular response, however, this results in immune complex formation so there could be damage from these and excessive inflammation. The TH2 response does not decrease parasite load but there is a reduced damage due to the above.

Question 21

What is chronic pathology associated with?

Answer 21

Increase antibody production, a TH2 response.

Question 22

How might the parasite cause autoimmunity?

Answer 22

Bystander activation - autoreactive immune cells respond to cardiac antigens when cardiac cells are lysed by the parasite.

Cryptic epitope - antigens released are usually in too small a number or are hidden so would not have been negatively selected against during thymic development.

Molecular mimicry - the parasite has antigens similar to host antigens

Polyclonal lymphocyte activation - parasite activates lots of lymphocytes.

Question 23

How does the parasite escape from the lysosome?

Answer 23

TcTox lyses the vacuolar membrane (it is similar to C9)

Question 24

What are the challenges of T. cruzi?

Answer 24

New drugs
Screening (acute)
Vaccination
Vector Resistance to insecticides