Trypanosmiases paper Barret et al 2003

Question 1

What is one of the most prevalent diseases in central and south america?

Answer 1

Chagas disease

Question 2

Why is disease containment an achievable goal with trypanosomiases?

Answer 2

Because of the life strategy of the arthropod vectors

Question 3

What has stimulated research into new drug targets for the trypanosomiases?

Answer 3

THey are some of the earliest diverging members of the eukaryote and share several biochemical peculiarities.

Question 4

What have frustrated efforts to design drugs effective against both speceis?

Answer 4

Differences in ways in which trypanosome species intercact with their hosts

Question 5

What is the protozoan order than trypanosomiases are in?

Answer 5

Kinetoplastida

Question 6

Several trypanosome speceis cause important vector diseases but only 2 cause significant human disease, what are they?

Answer 6

T.brucei an t.cruzi

Question 7

What other genus does the Kinetoplastida contain which also causes disease in the tropics and sub tropics?

Answer 7

Leishmania

Question 8

A substantial amount of similarity exists between t.brucei and t.cruzi, list 2 of them

Answer 8

both are trasnmitted by insect vectors

both share many aspects of their basic biochemical physiology

Question 9

There are profound differences at the level of the host parasite interface and what has this caused?

Answer 9

frustrated most efforts to use information gained about one species to assist in control of the other

Question 10

List 3 of the structural similarities between t.brucei and t.cruzi

Answer 10

Single celled flagellates
Transmitted by insect vectors
Share phases of local multiplication in their human host followed by dissemintation and localisation in target organs in which they cause potentially lethal damage

Question 11

What can account for why clinical manifestations and susceptibility to treatment differ?

Answer 11

ALthough there are many similarities between the 2 diseases, there are key differences between the organisms which account for why clinical manifestations and susceptibility to treatment differ.

Question 12

What did Stevens et al 2001 discover about the evolutionary history of the trypanosomes?

Answer 12

Comparison of 18S rRNA gene sequences from multiple trypanosome species obtained from diverse hosts, combined with other molecular approaches suggest tje genus Trypanosoma is monophyletic.

Question 13

How did Stevens et al 1999 show when t.brucei and t.cruzi shared a common ancestor?

Answer 13

By superimposing estimates with the molecular clock on vicariance biogeography it is suggested that they shared a common ancestor 100 mya

Question 14

What does the prehistoric dating suggest about t.brucei?

Answer 14

Indicates that human beings were exposed to african trypanosomes concomitantly with their evolution

Question 15

What does the prehistoric dating suggest about t.cruzi?

Answer 15

American typanosomes evolved independenly of their host homo sapiens who probably joined the host range of t.cruzi only within the past 12 000 too 40 000 years when man arrived on the american continent

Question 16

T.brucei and t.cruzi are both transmitted by biting insects but a fundamental difference between the means of transmission has been incorporated into the classification of these organisms : ?

Answer 16

T.brucei are known as salivaria because they are transmitted by the Tsetse fyl saliva
T.cruzi belongs to the stercoraria because transmission is via vector faeces

Question 17

Transmission of both organisms can also be via 3 things?

Answer 17

Blood transfusion, contaminated needles, or the congenital route

Question 18

Prata 2001 found a rare case of transmission of t.cruzi how?

Answer 18

breastfeeding

Question 19

In 1985 WHO estimates that how many people are at risk of chagas disease in latin america?

Answer 19

100 million

Question 20

What is the vector of t.cruzi?

Answer 20

bugs in sub family triatominae and family reduviidae

assassin bugs

Question 21

the three most important speceis of assasin bugs that are vectors of t.cruzi are what?

Answer 21

Triatoma infestans
Rhodrius polixus
Panstrongylus megistus

Question 22

How many lineages of t.cruzi are there and which one causes chagas disease?

Answer 22

two linneages: type 1 and type 2

type 2 is the cause of chagas

Question 23

Describe a little about type 1 and type 2 linneages of t.cruzi

Answer 23

Type 1 is widespread in mammalian hosts within a wild cycle.

Type 2 is more restricted in its host range to only a few mammalian species in a peridomestic habitat

Question 24

Chagas disease undergoes ____ stages in its natural course, is potentially ____ and there are no _____.

Answer 24

distinct
fatal
vaccines

Question 25

What happens after entry into the host?

Answer 25

T.cruzi invades host cells.

Question 26

What has an important early role in reacting to infection and in carrying parasites to other sites within the body?

Answer 26

macrophages

Question 27

T.cruzi ____ differentiate into replicative ____ within cells before differentiation back to ____ ____ trypomastigotes that leave one cell type and invade others.

Answer 27

trypomastigotes amastigotes bloodstream form

Question 28

The surface of the parasite is covered by ____ ___ _____.

Answer 28

Mucin type glycoproteins

Question 29

These mucin type glycoproteins attach to the membrane how?

Answer 29

By glycosylphophotidylinositol (GPI) anchors similar to those of the variant surface glycoproteins in african trypanosomes

Question 30

What are the major recipients of the sialic acid transferred by surface trans-sialidase?

Answer 30

Mucins

Question 31

T.cruzi has several ____ mucin genes and the exposed _______ moiety of the molecules belonging to one of the mucin families is ______.

Answer 31

hundred n-terminal hypervariable

Question 32

What can T.cruzi derived GPI anchors activate?

Answer 32

host macrophages

Question 33

What is judged imporatnt in control of infection and outcome of chagas disease?

Answer 33

T.cruzi is a potent stimulator of cell mediated immunity and induction of macrophage proinflammatory cytokines is judged important.

Question 34

How is t.cruzi usually transmitted?

Answer 34

as infected triatomine vectors gorge themselves on blood from sleeping hosts

Question 35

What do the faeces depsotied by the insect during feeding contain?

Answer 35

metacyclic trypomastigotes

Question 36

what allow the trypomastigotes to breech the skin and invade host cells?

Answer 36

itching produced by the vectors bite induces the individual to scratch causing microabrasions in the skin

Question 37

When do clinical manifestations of the acute stage occur? | how long do they last?

Answer 37

6-10 days after infection | last 1-2 months

Question 38

what is a chagoma?

Answer 38

symptom | frequent inflammation at the site of infection leads to an oedematous swelling known as a chagoma

Question 39

what is romanas sign?

Answer 39

symptom swelling of the eyelids after infection at this site and allows easy symptomatic diagnosis in up to half of those cases showing overt manifestations of acute disease

Question 40

when do most acute cases arise? age

Answer 40

before 15 years | mainly between 1 and 5 years

Question 41

Why does the acute phase usually pass unnoticed?

Answer 41

symptoms typical of general malaise in other infections

Question 42

can death occur in the acute phase?

Answer 42

yes usulaly with symptoms similar to that seen in T.b.r infection

Question 43

what are 4 other symptoms of the acute stage that are common?

Answer 43

rash fever heptasplenomegaly oedema of the face and elsewhere

Question 44

what can electrocardiograms show in the acute stage?

Answer 44

abnormalities and primary t-wave changes

Question 45

where can parasties easily be detected in the acute stage?

Answer 45

peripheral blood

Question 46

when does the acute stage of the disease end?

Answer 46

when the immunological balance between the host and the parasite greatly reduces the number of circulating trypomastigotes, rendering direct parasitological diagnosis impossible

Question 47

what happens after the acute stage?

Answer 47

people enter the chronic stage | patients become asymptomatic with typical findings on the electrocardiogrpahy and chest radiography

Question 48

how mnay people contineu in this state known as indeterminate form of chronic chagas disease for hte rest of their lives?

Answer 48

70-85%

Question 49

15-30% will develop in the chronic stage manifestations of organ damage producing what?

Answer 49

the cardiac, digestive, or nervous forms of chronic chagas diesease 10-25 years after initial infection

Question 50

what are symptoms of the chronic stage manifestation of organ damage?

Answer 50

chest pain, palpitations, dizziness, and peripheral oedema | heart failure and sudden death are common

Question 51

what are the 2 drugs for treatment of chagas?

Answer 51

two nitroheterocyclic drugs: nifurtimox benzindazole

Question 52

when was nifurtimox introduced and what is it used to treat?

Answer 52

1960s acute chagas drug is trypanocidal mainly against circulating trypanomastigotes and is better tolerated by young patients

Question 53

When was benzindazole introduced?

Answer 53

1970

Question 54

What is the problem with both drugs?

Answer 54

they occassionally induce serious side effects and neither has high efficacy against chronic chagas disease

Question 55

What did Sasa estanoi et al 1998 and Andrade et al 1996 show in studies on Benznidazole?

Answer 55

showed that benznidazole depleted anti t.cruzi reactivity in specific serological tests and lowered prevalence of heart alterations by 62% in school children

Question 56

What did DaSilva 1999 show about treatment?

Answer 56

that treatment of the symptomatic complications of chagas disease is also effective improvement of quality of life

Question 57

What did Wang 1995 show have long been regarded as potential drug targets?

Answer 57

biochemical pathways general to trypanosomatids but absent from mammalian hosts

Question 58

Croft 1999 Differences between t.brucei and t.cruzi at the level of the host parasite interaction, however, lead to a huge variation in the _____ _____ needed for agents used against the different diseases

Answer 58

pharmacological criteria

Question 59

HAT is seldom diagnosed before the late stage so drugs must cross the ___ ___ ___ to be effective

Answer 59

blood brain barrier

Question 60

to target t.cruzi amastigotes drugs must also enter many mammalian cell types, which causes what?

Answer 60

diminishes the quantity of drug available to interact with the parasites and amplifies risks of host cell toxic effects

Question 61

What has a proportion of research into trypanosomes over the past 20 years been related to?

Answer 61

has been related to target identification and development of lead compounds that interact with these targets

Question 62

What are the 4 approaches to control fo chagas disease?

Answer 62

vector control personal prophylaxis serological control of blood banks treatment of infected individuals

Question 63

What are the 3 approaches to control of HAT?

Answer 63

treatment of infected individuals vector control active case finding with mobile teams

Question 64

what is the main way that tsetse flies and triatominae differ ecologically?

Answer 64

triatominae usually crawl within peridomestic environments, and bitten while asleep indoors where as tsetse flies are active during the day

Question 65

what is the one important ecological factor that tsetse flies and triatominae share? and this makes them vulnerable to interventions aimed at altering their environment and lowering their reproductive rate

Answer 65

k strategists | low reproductive rate, high survival rate, adapted for the efficient exploitation of their habitat

Question 66

triatomine bugs reside where? so what would be a good control prevention?

Answer 66

within the hatched roofs and cracked walls of rural huts. | exchanging these for corrugated iron / wood / stone

Question 67

DDT is not effective against triatomine bugs but what is?

Answer 67

other organochlorides are effective

Question 68

what occurred before the 1970s?

Answer 68

successful insecticide control campaigns in argentina, brazil, chile, and venezuela encouraged other endemic countries to adopt similar methods

Question 69

today acute chagas disease has been eliminated from many __ ____ and the cost benefit initiatives are highly positive

Answer 69

rural areas

Question 70

there is some concern about what with the eradication?

Answer 70

eradication of the domsetic sp will open a niche for sylvatic triatominae to inhabit

Question 71

Barrat et al 2003 showed what were the priorities for research into trypanosomiases? (4 points)

Answer 71

1. development of sustainable, multicomponent approaches to control of insect vectors 2. Identification of drug targets with genome data bases and their validation by genetic approaches 3. Improvement in practical diagnostic techniques capable of detecting infection and staging the disease 4. Improvement in understanding of the parts played by the parasites and of host responses to them in development of pathophysiology