African typanosomiasis

Question 1

Vector of African tryps

Answer 1

Tsetse flies - Glossina spp

Question 2

What diseases do African tryps cause

Answer 2

Human African trypanosomiasis or sleeping sickness

Animal African trypanosomiasis or nagana

Question 3

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

Answer 3

No vaccines and current drugs are too toxic

Question 4

What are the important AT species for HAT

Answer 4

T brucei rhodesiense

T. brucei gambiense

Question 5

What are the important AT species for AAT

Answer 5

T brucei brucei

T viva

T congolense

T evansi (non tsetse transmitted outside of Africa

Question 6

Integrated approach for sleeping sickness elimination

Answer 6

better surveillance
new drugs
effective tsetse control

Question 7

how many species of tsetse flies

Answer 7

over 30

Question 8

What are the stages of HAT

Answer 8

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

Question 9

What happens in stage 1 HAT

Answer 9

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

Question 10

what happens in stage 2 HAT

Answer 10

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

Question 11

T. b rhodesiense sleeping sickness

Answer 11

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

Question 12

What is the main habitat for T.b rhodesiense

Answer 12

Savannah

Question 13

How is T. b gambiense transmitted

Answer 13

human to human only

Question 14

T.b gambiense sleeping sickness

Answer 14

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

Question 15

What is the main habitat for T.b gambiense

Answer 15

Riverine sites

Question 16

Where is T. vivax found

Answer 16

South America (northern - middle countries)
Sub Saharan Africa

Question 17

Where is T.b evansi found

Answer 17

Northern Africa

Latin America and asia

Question 18

Where is T. congolese found

Answer 18

mid Africa and small parts of Latin America

Question 19

Animal trypanosomiasis

Answer 19

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

Question 20

Resistance and susceptible cattle species

Answer 20

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

Question 21

Life cycle of Trypanosoma brucei

Answer 21

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

Question 22

What are the two forms of trypanosomes in the blood

Answer 22

Stumpy

long slender

Question 23

What blood form is able to reinfect tsetse flies

Answer 23

stumpy

Question 24

what blood form is able to divide in the blood

Answer 24

slender

Question 25

how do slender trypanosomes divide in the blood

Answer 25

binary fission

Question 26

what molecule covers the surface of African tryps in the blood

Answer 26

VSG - variant surface glycoprotein

Question 27

How do tryps survive in the bloodstream of the mammal

Answer 27

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

Question 28

which tryp form undergoes antigenic variation

Answer 28

slender

Question 29

when are stumpy forms produced

Answer 29

at the peak of parasitaemia

Question 30

what does the trypanosome VSG coat do

Answer 30

helps to clear antibodies bound on the parasite surface

Question 31

How does VSG help trypanosomes escape the host immune system

Answer 31

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

Question 32

Where can African tryps hide

Answer 32

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

Question 33

what does the flagellar pocket do

Answer 33

incorporates nutrients from the host blood

Question 34

why is T.b brucei not pathogenic to humans

Answer 34

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

Question 35

Life cycle of t brucei in the fly

Answer 35

``` 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 ```

Question 36

how many tsetse carry transmissible trypanosomes

Answer 36

less than 1 percent

Question 37

life cycle of t brucei in the tsetse

Answer 37

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

Question 38

factors influencing trypanosome infection in the tsetse

Answer 38

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

Question 39

summary of African tryps

Answer 39

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