Chagas

Question 1

What is another name for Chagas?

Answer 1

Trypanosomes Cruzi (T. Cruzi)

Question 2

Chagas overview

Answer 2

• South American trypanosomiasis
• 16-18M affected
• 50,000 die each year
• Vector transmitted
• Triatomine bug (kissing bug)

Question 3

Where would you find Triatomine bugs?

Answer 3

Live in traditional houses

Question 4

Clasic symptom of Chagas?

Answer 4

Swollen eye (Romana’s sign)

Question 5

Where do you find the infective stages of Chagas?

Answer 5

In faeces of Triatomine bug
It is a stealthy bug

Question 6

Human stages of Chagas life cycle

Answer 6

1. Metacyclic trypomastigotes penetrate cells, transorm into amstigotes
2. Amastigotes multiply by binary fissiom in cells of infected tissue
3. Intracellular amastigotes transform into trypomastigotes then burst out of cell into bloodstream (taken up by bug)

Question 7

Triatomine Stage of Chagas life cycle

Answer 7

1. Triatomine bug takes blood meal (trypomastigotes ingested)
2. Epimastigote in midgut
3. mulitplies in midgut
4. metacyclic trypomastigotes in hindgut
5. Triatomine bug takes blood meal, metacyclic trypomatigotes enter through faece

Question 8

Chronic symptoms of Chagas?

Answer 8

Develop after 10-40 years
cardiac problems (enlarged heart, cardiac arrest)
Enlargement of oesophagus or large bowel

Question 9

What molecules does T.cruzi use to attach to host cells?

Answer 9

2 main types of molecule on surface of host cell - trans-sialidases and membrane mucins

Question 10

How are molecules used to aid T.cruzi

Answer 10

• Gp85/trans-sialidases are a trypomastigote stage-specific glycoprotein
• Lot of variability - avoids immune destruction
• over 100 gene in genome encoding Gp85
• Genes found in sub telomeric regions

Question 11

Chagas cell invasion

Answer 11

• trypanosomes have remarkable capacity to invade every nucleated cell
• lives in parasitophorous vacuole
• triggers intracellular Ca2+ rise
• causes accumulation of lysosomes

Question 12

What is the significance of lysosome accumulation?

Answer 12

• Fools the cell into thinking there is damage
• sets in action a cellular wound repair process
• the lysosomes are hijacked by Chagas

Question 13

How does Chagas cause increase in intracellular Ca2+

Answer 13

• secretes molecules known as oligopeptidase B which binds to GPCR on host and activates PLC. Induces increase in Ca2+
• Secretes cruzipain which cleaves kininogen into kinins, which bind to cell surface ALSO activating PLC

Question 14

What must Chagas do in order to transform into an amastigote?

Answer 14

Go in via lysosomal membrane
Low pH triggers differentiation, and also switches on production of Tc-Tox

Question 15

What does Tc-Tox do?

Answer 15

• disrupts the parasitophrous vacuole and frees the parasite into the cytoplasm where it replicates
• Tc-Tox similar to the molecule that the immune system uses to punch holes in cells - C9, a member of the complement system

Question 16

What are tissue topisms in regards to Chagas?

Answer 16

• Data suggests parasite genetics determines which organs/cells the parasite prefers to invade

Question 17

Why is chagas cell invasion different to other protozoans?

Answer 17

Unlike Leishmania, the major way of engulfment is not an actin mediated phagocytic event. The membrane of the parasitophrous vacuole is not derived from the plasma membrane of the host cell

Question 18

Mammalian forms of T. cruzi

Answer 18

Trypomastigotes and Amastigotes