Lecture 14. Flagellated Protozoa: American Trypanosomes 1 Flashcards
What does Trypanosoma cruzi cause?
Chagas disease
How many people are infected with Chagas disease in Latin America?
8-10 million people
Most important parasitic disease in Latin America
How many new cases and deaths are caused by Chagas disease per year?
500,000 new cases
>10,000 deaths
Of the neglected tropical diseases (NTDs), what does Chagas disease have the highest statistic in?
Highest burden of disability-adjusted life years (DALYs) lost among the NTDs
What are the vectors for Chagas disease transmission?
Reduviid or Triatominae bugs (not tsetse flies)
All stages (nymphs and adults all take blood meals)
Order Hemiptera, Family Reduviidae, Subfamily Triatominae
How can Chagas disease transmission be prevented?
Preventing malting of the reduviid/triatominae bugs can prevent development (malting is essential for survival)
How much blood can reduviid/triatomine bugs take up in one blood meal?
8-10x their original body weight (number of parasite that can be taken up in a blood meal is large)
What are the main routes of transmission of Chagas disease?
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
What happens in the human stages of T. cruzi infection?
- Triatomine bug takes a blood meal (passes metacyclic trypomastigotes in faeces, trypomastigotes enter bite wound or mucosal membranes, such as the conjunctiva)
- Metacyclic trypomastigotes penetrate various cells at bite wound site. Inside cells they transform into amastigotes
- 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
What happens in the triatomine bug stages of T. cruzi infection?
- Triatomine bug takes a blood meal (trypomastigotes ingested)
- Epimastigote stage in midgut
- Epimastigotes multiply in midgut
- Metacyclic trypomastigotes in hind gut
What is one of the main differences between how triatomine bugs pass on T. cruza when compared to other vectors?
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)
How long does it take for the T. cruzi parasite to develop within the triatomine bug?
10-14 days
How many triatomine species are responsible for T. cruzi transmission in humans?
~20
What are the key vector species for T. cruzi transmission?
Rhodnius prolixus
Triatoma brasiliensis
Panstrongylus megistus
Triatoma infestans
Triatoma dimidiata
Where are Triatoma infestans bugs highly domesticated?
Southern Cone countries (South America)
How many people are infected globally with Chagas disease?
~8 million
How many people infected with Chagas disease live in the US?
300,000, but most are immigrants from Latin America
Why is the report that enzootic T. cruzi transmission across the southern half of the US not concerning?
Because locally acquired cases in humans are very rare
How has Chagas been able to spread globally?
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
Why does Spain have a high number of people infected with Chagas?
Bolivians make up 80% of immigrants in Spain
How did T. cruzi spread into humans?
Existed among wild animals but later spread to domestic animals and human beings
How did T. cruzi get into the urban/pre-urban populations?
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
Where do triatomine bugs typically live?
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
What are the risk factors of T. cruzi infection?
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
How long does it take for a T. cruzi infection to become the acute stage of Chagas disease?
1-2 weeks
How long does the acute (symptomatic) form of Chagas disease take to clear?
4-8 weeks
In what group of people is the acute form of Chagas disease most often seen?
In children
What are the symptoms of Chagas disease in the acute phase?
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
What can severe acute infections of Chagas disease result in?
Myocarditis, meningoencephalitis, both life-threatening
Case fatality rate is estimated to be 0.25 to 0.50%
How long does the chronic phase of Chagas disease last?
Lifelong (without treatment)
What are the symptoms of chronic phase Chagas disease?
Cardiomyopathy (caridac disease) in 20–30% of chronically infected individuals
Develop digestive damage (megaviscera)
Peripheral nervous involvement
What is chronic T. cruzi infection called when there are no symptoms of disease?
“Indeterminate” forms of infection
When does the indeterminate form of chronic T. cruzi infection progress to clinical conditions and in how mny people does this progression occur?
20-30% of people who initially have the indeterminate form progress to clinical conditions developed over decades
How can T. cruzi infection be detected?
By looking at parasitaemia levels (quantitive amount of parasites within the blood)
How can the acute and early congenital phases of T. cruzi infection be recognised?
High parasitaemia
Microscopy of stained blood smear; PCR, or hemoculture
How can the chronic phase of T. cruzi infection be recognised?
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
What two effective drugs are there to treat T. cruzi infections?
Nifurtimox, Benznidazole
Effective against the acute and early chronic phase
What are the downsides of using the nifurtimox and benznidazole?
Serious / frequent side-effects (40%), more common with increasing age
What effect does treatment have on acute infections?
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
The WHO reccomends treatment for which types of T. cruzi infection?
WHO recommends treatment for acute, congenital, and reactivated T. cruzi infection, and for children (up to 18 years of age) with chronic infection
Are there any drugs that are effective against chronic phase T. cruzi infections?
No
What problems arise when trying to treat chronic T. cruzi infections?
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
Why does treating T. cruzi infections remain problematic?
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)
When are animals considered reservoirs?
Only if they carry the disease onwards
What are the approaches to control T. cruzi in endemic regions?
Sustained vector control of intra-domiciliary vectors in Latin America, prevent vector borne transmission (contact)
Promote engagement with vector control activities
What are the approaches to control T. cruzi in endemic and non-endemic regions?
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
Does T cruzi have a vaccine?
No
