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Tryps and Leish > African typanosomiasis > Flashcards

African typanosomiasis Flashcards

1
Q

Vector of African tryps

A

Tsetse flies - Glossina spp

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2
Q

What diseases do African tryps cause

A

Human African trypanosomiasis or sleeping sickness

Animal African trypanosomiasis or nagana

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3
Q

What are the issues with prevention and treatment of HAT and AAT

A

No vaccines and current drugs are too toxic

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4
Q

What are the important AT species for HAT

A

T brucei rhodesiense

T. brucei gambiense

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5
Q

What are the important AT species for AAT

A

T brucei brucei

T viva

T congolense

T evansi (non tsetse transmitted outside of Africa

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6
Q

Integrated approach for sleeping sickness elimination

A

better surveillance
new drugs
effective tsetse control

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7
Q

how many species of tsetse flies

A

over 30

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8
Q

What are the stages of HAT

A

stage 1 - haemolymphatic phase
tryps multiply in subcutaneous tissues, blood and lymph

stage 2 - neurological phase
parasites cross blood brain barrier to infect the CNS
changes in behaviour, confusion, sensory disturbances and poor coordination
disturbance of the sleep cycle
fatal if untreated

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9
Q

What happens in stage 1 HAT

A

haemolymphatic phase - trypanosomes multiply in the subcutaneous tissues, blood and lymph

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10
Q

what happens in stage 2 HAT

A

neurological phase - cross blood brain barrier and infect the CNS causing changes in behaviour, confusion, sensory disturbances and poor coordination, disturbance of the sleep cycle, fatal if untreated

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11
Q

T. b rhodesiense sleeping sickness

A

Rhodesiense HAT - rapid onset
zoonotic disease
flies feed on game animals
at risk groups include hunters, honey gatherers, fishermen and firewood gatherers

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12
Q

What is the main habitat for T.b rhodesiense

A

Savannah

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13
Q

How is T. b gambiense transmitted

A

human to human only

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14
Q

T.b gambiense sleeping sickness

A

90% of cases
pigs possible reservoir
game animals may be infected with tryps similar to Tbg

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15
Q

What is the main habitat for T.b gambiense

A

Riverine sites

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16
Q

Where is T. vivax found

A 
South America (northern - middle countries)
Sub Saharan Africa
17
Q

Where is T.b evansi found

A

Northern Africa

Latin America and asia

18
Q

Where is T. congolese found

A

mid Africa and small parts of Latin America

19
Q

Animal trypanosomiasis

A

major constraint on animal production with high morbidity and mortality
affects growth, production of milk, meat and dairy products as well as fertility

In sub-saharan Africa it affects 37 million countries with 23 million cattle deaths per year

20
Q

Resistance and susceptible cattle species

A

zebu cattle found throughout east and West Africa susceptible to trypanosomiasis

N’dama breed (West Africa) relatively resistant to the disease - trypanotolerant

transgenic trypanotolerant parasites could be a way to increase meat productivity and boost agriculture in Africa

21
Q

Life cycle of Trypanosoma brucei

A

in the tsetse fly
pro cyclic trypomastigote in the midgut, long/ short epimastigote in the proventriculus, attached epimastigote in epithelium of salivary gland, metacyclic trypomastigote

mammals
long slender form in the bloodstream, enters CNS, short stumpy form in blood stream

22
Q

What are the two forms of trypanosomes in the blood

A

Stumpy

long slender

23
Q

What blood form is able to reinfect tsetse flies

A

stumpy

24
Q

what blood form is able to divide in the blood

A

slender

25
Q

how do slender trypanosomes divide in the blood

A

binary fission

26
Q

what molecule covers the surface of African tryps in the blood

A

VSG - variant surface glycoprotein

27
Q

How do tryps survive in the bloodstream of the mammal

A

antigenic variation
more than 1000 VSG genes
only one VSG at a time from sub-telemetric expression sites on chromosomes
some VSG genes can recombine to form mosaics thus increasing the repertoire of proteins expressed

28
Q

which tryp form undergoes antigenic variation

A

slender

29
Q

when are stumpy forms produced

A

at the peak of parasitaemia

30
Q

what does the trypanosome VSG coat do

A

helps to clear antibodies bound on the parasite surface

31
Q

How does VSG help trypanosomes escape the host immune system

A

switching VSG genes
over-expression on the surface - blocks host antibodies
VSG molecular barrier depends on type f c-terminal domain
fast internalisation of VSG-IgM and recycling of old VSGs
Addition of GLc residues further prevents the immune system recognition

32
Q

Where can African tryps hide

A

in the skin
can survive longer and be infectious to tsetse flies
number of skin tryps remains constant compared to blood parasitaemia

33
Q

what does the flagellar pocket do

A

incorporates nutrients from the host blood

34
Q

why is T.b brucei not pathogenic to humans

A

parasites killed by apoL1 in the bloodstream
rhodesiense express SRA that neutralises apoL1
gambiense uses TLF receptor

Humans deficient in apoL1 are susceptible to animal trypanosomiasis

35
Q

Life cycle of t brucei in the fly

A 
transmission by bite 
infective forms in the salivary glands 
duration - 15-30 days temp dependent 
stages of development in the midgut proventriculus and salivary glands (mouthparts for other species)
low infection rates in flies
36
Q

how many tsetse carry transmissible trypanosomes

A

less than 1 percent

37
Q

life cycle of t brucei in the tsetse

A

midgut - sender and stumpy BSFs
pro cyclic in the midgut - 1 week
mesocyclics in the proventriculus - 2 weeks
promastigote like, epimastigote, metacyclic in the salivary glands - 4 weeks

38
Q

factors influencing trypanosome infection in the tsetse

A 
tsetse immune system 
midgut molecules (hydrolyses)
nutritional starvation (proline and folic acid) 
blood factors 
symbionts
39
Q

summary of African tryps

A

Trypanosomatid parasites develop a flagellum for migration, nutrition and scape host’s immune system

parasites contain a mitochondrial DNA (kDNA)

cause HAT and AAT, are transmitted by the tsetse bite, and survive in the mammalian host thanks to antigenic variation

VSG is central in trypanosome survival in the mammalian host

In the fly, tryps undergo a complex cycle that involves migration to several tsetse organs

Maturation (metacyclogenesis) occurs in the salivary glands (T. bruceispp) or in the mouthparts (T. congolense, T. vivax and T. evansi)

Fly infections cause a feeding phenotype that allows spread of trypanosome transmission

Tryps and Leish (4 decks)

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