Lecture 14. Flagellated Protozoa: American Trypanosomes 1

Question 1

What does Trypanosoma cruzi cause?

Answer 1

Chagas disease

Question 2

How many people are infected with Chagas disease in Latin America?

Answer 2

8-10 million people
Most important parasitic disease in Latin America

Question 3

How many new cases and deaths are caused by Chagas disease per year?

Answer 3

500,000 new cases
>10,000 deaths

Question 4

Of the neglected tropical diseases (NTDs), what does Chagas disease have the highest statistic in?

Answer 4

Highest burden of disability-adjusted life years (DALYs) lost among the NTDs

Question 5

What are the vectors for Chagas disease transmission?

Answer 5

Reduviid or Triatominae bugs (not tsetse flies)
All stages (nymphs and adults all take blood meals)
Order Hemiptera, Family Reduviidae, Subfamily Triatominae

Question 6

How can Chagas disease transmission be prevented?

Answer 6

Preventing malting of the reduviid/triatominae bugs can prevent development (malting is essential for survival)

Question 7

How much blood can reduviid/triatomine bugs take up in one blood meal?

Answer 7

8-10x their original body weight (number of parasite that can be taken up in a blood meal is large)

Question 8

What are the main routes of transmission of Chagas disease?

Answer 8

Vector-borne by “kissing bugs” (80%)
Transfusion of infected blood (<4% -20%)
Congenital: mother to foetus (regionally high - predominant transmission in Europe and the USA)
Accidental ingestion of infected sources

Question 9

What happens in the human stages of T. cruzi infection?

Answer 9

1. Triatomine bug takes a blood meal (passes metacyclic trypomastigotes in faeces, trypomastigotes enter bite wound or mucosal membranes, such as the conjunctiva)
2. Metacyclic trypomastigotes penetrate various cells at bite wound site. Inside cells they transform into amastigotes
3. Amastigotes multiply by binary fission in cells of infected tissues
   4a. Intracellular amastigotes transform into trypomastigotes, then burst out of the cell and enter the bloodstream
   4b. Trypomastigotes can infect other cells and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle

Question 10

What happens in the triatomine bug stages of T. cruzi infection?

Answer 10

1. Triatomine bug takes a blood meal (trypomastigotes ingested)
2. Epimastigote stage in midgut
3. Epimastigotes multiply in midgut
4. Metacyclic trypomastigotes in hind gut

Question 11

What is one of the main differences between how triatomine bugs pass on T. cruza when compared to other vectors?

Answer 11

The bug does not transmit the parasite through the salivary glands or by taking the blood meal
Parasite transmitted through bug faeces entering wound (via scratching or rubbing)
Stercorarian transmission, not salivarian transmission (not efficient)

Question 12

How long does it take for the T. cruzi parasite to develop within the triatomine bug?

Answer 12

10-14 days

Question 13

How many triatomine species are responsible for T. cruzi transmission in humans?

Answer 13

~20

Question 14

What are the key vector species for T. cruzi transmission?

Answer 14

Rhodnius prolixus
Triatoma brasiliensis
Panstrongylus megistus
Triatoma infestans
Triatoma dimidiata

Question 15

Where are Triatoma infestans bugs highly domesticated?

Answer 15

Southern Cone countries (South America)

Question 16

How many people are infected globally with Chagas disease?

Answer 16

~8 million

Question 17

How many people infected with Chagas disease live in the US?

Answer 17

300,000, but most are immigrants from Latin America

Question 18

Why is the report that enzootic T. cruzi transmission across the southern half of the US not concerning?

Answer 18

Because locally acquired cases in humans are very rare

Question 19

How has Chagas been able to spread globally?

Answer 19

Chagas is long-lived infection with asymptomatic chronic carriers
Leads to unusual global distribution linked not only to transmission but migration
Subsequent (autochthonous) transmission is not vector-borne. Rather mainly congenital, also blood transfusions and infected organ transplants

Question 20

Why does Spain have a high number of people infected with Chagas?

Answer 20

Bolivians make up 80% of immigrants in Spain

Question 21

How did T. cruzi spread into humans?

Answer 21

Existed among wild animals but later spread to domestic animals and human beings

Question 22

How did T. cruzi get into the urban/pre-urban populations?

Answer 22

Socio-economic changes, rural exodus, deforestation and urbanisation transformed the epidemiological profile of the disease, endemic regions expanded at the start of the 20th century

Question 23

Where do triatomine bugs typically live?

Answer 23

In the wall or roof cracks of poorly constructed homes in rural or suburban areas, becoming active at night, biting exposed areas of skin, then defecating close to the bite

Question 24

What are the risk factors of T. cruzi infection?

Answer 24

Poverty/house construction
Favourable triatomine bug habitats in poorly constructed houses
Deforestation and human colonisation of Triatomine habitats, provides abundant/stationary blood sources
Rural to urban migration
Blood transfusions e.g blood bank prevalence of 1.7% (Sao Paulo, Brazil) to 53.0% (Santa Cruz, Bolivia)
Congenital transmission: e.g. 2-15% urban and 23-81% rural Bolivia

Question 25

How long does it take for a T. cruzi infection to become the acute stage of Chagas disease?

Answer 25

1-2 weeks

Question 26

How long does the acute (symptomatic) form of Chagas disease take to clear?

Answer 26

4-8 weeks

Question 27

In what group of people is the acute form of Chagas disease most often seen?

Answer 27

In children

Question 28

What are the symptoms of Chagas disease in the acute phase?

Answer 28

Fever, swelling lymph glands, liver and spleen enlargement, local inflammation of inoculation site (“Romaña’s sign”)
Mostly mild, self-limited symptoms e.g. fever that do not come to medical attention

Question 29

What can severe acute infections of Chagas disease result in?

Answer 29

Myocarditis, meningoencephalitis, both life-threatening
Case fatality rate is estimated to be 0.25 to 0.50%

Question 30

How long does the chronic phase of Chagas disease last?

Answer 30

Lifelong (without treatment)

Question 31

What are the symptoms of chronic phase Chagas disease?

Answer 31

Cardiomyopathy (caridac disease) in 20–30% of chronically infected individuals
Develop digestive damage (megaviscera)
Peripheral nervous involvement

Question 32

What is chronic T. cruzi infection called when there are no symptoms of disease?

Answer 32

“Indeterminate” forms of infection

Question 33

When does the indeterminate form of chronic T. cruzi infection progress to clinical conditions and in how mny people does this progression occur?

Answer 33

20-30% of people who initially have the indeterminate form progress to clinical conditions developed over decades

Question 34

How can T. cruzi infection be detected?

Answer 34

By looking at parasitaemia levels (quantitive amount of parasites within the blood)

Question 35

How can the acute and early congenital phases of T. cruzi infection be recognised?

Answer 35

High parasitaemia
Microscopy of stained blood smear; PCR, or hemoculture

Question 36

How can the chronic phase of T. cruzi infection be recognised?

Answer 36

Amastigotes remain in cardiac/skeletal muscle/macrophages - Scarce trypomastigotes in blood
Two serological IgG antibody tests due to low sensitivity
No satisfactory test to define parasitological cure (low PCR sensitivity)
No gold standard

Question 37

What two effective drugs are there to treat T. cruzi infections?

Answer 37

Nifurtimox, Benznidazole
Effective against the acute and early chronic phase

Question 38

What are the downsides of using the nifurtimox and benznidazole?

Answer 38

Serious / frequent side-effects (40%), more common with increasing age

Question 39

What effect does treatment have on acute infections?

Answer 39

In acute infection, treatment reduces and shortens clinical severity and duration of detectable parasitemia
Parasitological cure in 60-85% of patients treated in the acute phase

Question 40

The WHO reccomends treatment for which types of T. cruzi infection?

Answer 40

WHO recommends treatment for acute, congenital, and reactivated T. cruzi infection, and for children (up to 18 years of age) with chronic infection

Question 41

Are there any drugs that are effective against chronic phase T. cruzi infections?

Answer 41

No

Question 42

What problems arise when trying to treat chronic T. cruzi infections?

Answer 42

Debate over usefulness in adults with long-standing infection (a randomised trial of benznidazole did not significantly reduce levels of cardiac clinical deterioration over 5 years follow-up)
Clinical trials in progress but hindered by no accepted reference assay to detect chronic T. cruzi infection (3 x serological tests used). PCR insensitive; antibody decay post cure is very slow
Drugs cannot be administered during pregnancy
Specific treatment to alleviate symptoms needed for cardiac, or digestive or neurological symptoms – but will not give parasitological cure

Question 43

Why does treating T. cruzi infections remain problematic?

Answer 43

Serious side effects
Access: less than 1% of patients have access to Benznidazole, (only recommended in areas with vector control or non-endemic due to re-infection and risks associated with treatment.)
Disease is poorly understood by health professionals in non-endemic areas, making detection (esp. in acute phase) difficult
Desperately need new drugs and to improve parasitological detection (some are now in development)

Question 44

When are animals considered reservoirs?

Answer 44

Only if they carry the disease onwards

Question 45

What are the approaches to control T. cruzi in endemic regions?

Answer 45

Sustained vector control of intra-domiciliary vectors in Latin America, prevent vector borne transmission (contact)
Promote engagement with vector control activities

Question 46

What are the approaches to control T. cruzi in endemic and non-endemic regions?

Answer 46

Screen blood transfusions and organ donation worldwide
Screen pregnant women and children to control congenital transmission worldwide
Promote health seeking behaviour and awareness amongst health professionals

Question 47

Does T cruzi have a vaccine?

Answer 47

No