Human African Trypanosomiasis - 1b Flashcards
1
Q
Human African Trypanosomiasis
is also known as
A
African Sleeping Sickness
2
Q
Human African Trypanosomiasis
prevalence
A
- 36 countries in sub-Saharan Africa
- 60 million people at risk
- common in rural populations
- prevalence in villages in Angola, the Democratic Republic of Congo, and Southern Sudan is between 20% and 50%
- associated wit hpoverty
- zoonotic (domstic and wild animals) and anthropomorphic transmission cycles
3
Q
Human African Trypanosomiasis
epidemics
A
- 1896-1906
- 1920-1940
- late 1970s - 2000
- 3 main epidemics correlate with monitoring for disease
- stop screening → number of reported cases increased
- screening by NGOs
- too dangerous in war/unrest → stop screening and testing
4
Q
Transmission
A
- T. brucei transmitted in saliva of tsetse fly (Glossina spp)
- male and femal flies transmit disease
- very painful bite
- 34 different species and sub-species
5
Q
Tsetse fly split into 3 groups based on
A
- distribution
- behaviour
- molecular
- morphology
- riverine flies - associated with water
- savannah - associated with open land
- forest
- different groups have different abilities to tranmit different HAT forms
6
Q
Female flies are
A
viviparous
- deposits a fully developd larva
- burrows into the soil
- pupates
- emerges as an adult fly (month later)
- newly-hatched flies not infected with trypanosomes
- picks up trypanosome from animal or human host, not born with it
multivoltine
- typically producing 4 generations per year
- up to 31 generations over lifespan
7
Q
Female flies are key to
A
vector control
8
Q
Distribution of HAT and Tsetse fly
A
wherever you have the tsetse fly you have the disease
9
Q
HAT is caused by the protozoan parasite
A
Trypanosoma brucei
10
Q
Major forms of the parasite
(T. brucei)
A
- 2 mastigote forms but one has 4 variants
- trypomastigote
- procyclic trypomastigote
- bloodstream trypomastigote
- metacyclic trypomastigote
- short stumpy trypomastigote
- epimastigote
11
Q
Major form of T. brucei
trypomastigote (general)
A
- common morphology in mammalian and insect hosts
- common morphology of infective forms
- the form of the parasite that lives within our blood stream and our lymphatic system
- also the form of the parasite that lives within the gut of the insect vector
- form of the parasite that’s transmitted from the insect to us and from us back to the insect
(4 forms - one in us, one in insect, 2 transmissable forms)
12
Q
T. brucei
procyclic trypomastigote
A
INSECT
- divide by binary fission
- cell coat - procyclin
- lives in midgut of the tsetse fly
13
Q
T. brucei
bloodstream trypomastigote
A
mammal
- found in humans and ungulate animals
- long, slender, bloostream trypomastigote
- divide by binary fission
- cell coat of variant surface glycoproten (VSG) to evade antibody-mediated immune destruction
- lives in bloodstream (or lymphatic system) - extracellular parasite, kicks RBC out of the way
14
Q
T. brucei
metacyclic trypomastigote
A
insect → humans
- unable to divide
- infectious forms compared to replicative forms is that these infectious forms are pre-adapted for life in the forthcoming host (adapted for life in human)
- spat out in the saliva of the tsetse fly
- the form that infects us
15
Q
T. brucei
short stumpy trypomastigote
A
human → insect
-
unable to divide
- infectious forms compared to replicative forms is that these infectious forms are pre-adapted for life in the forthcoming host (adapted for life in insect)
- form that we infect the tsetse fly
16
Q
T. brucei
epimastigote
A
- common morpholog in insect salivary gland
17
Q
Trypomastigote
(picture)
A
18
Q
Epimastigote
(picture)
A
19
Q
Life cycle of T. brucei
(overall picture)
A
20
Q
A
- as tsetse fly takes a blood meal, parasites (metacyclic trypomastigotes) injected from salivary gland into victims bloodstream (salivarian)
- injects saliva into host containing anti-coagulants etc
- also injects the metacyclic trypomastigote - if the fly is infected - into blood or lymphatic system of host
21
Q
As tsetse fly takes a blood meal, parasites
A
(metacyclic trypomastigotes) injected from salivary gland into victims bloodstream (salivarian)
- injects saliva into host containing anti-coagulants etc
- also injects the metacyclic trypomastigote - if the fly is infected - into blood or lymphatic system of host
22
Q
A
- injected metacyclic trypomastigotes transform into bloostream form (BSF) trypomastigotes
- long-slender bloodstream form
- trigger = temperature? (unknown)
- BSF trypomastigotes multiply by binary fission in various body fluids (blood, lymph, spinal fluid)
- begin dividing and colonizing bodily fluids
- initally in blood and lymphatic system, but if given enough time, will cross the blood-brain barrier to get into the cererbal-spinal fluid
- in the human host the long-slender BSF trypomastigotes appear to be able to sense the number of other parasites around them, and through a core sensing mechanism they can talk to each other, get a rough idea of the numbers of parasites, and if the population gets too high they express stumpy induction factor
23
Q
Injected metacyclic trypomastigotes transform into
A
bloostream form (BSF) trypomastigotes
- long-slender bloodstream form
- trigger = temperature? (unknown)
- BSF trypomastigotes multiply by binary fission in various body fluids (blood, lymph, spinal fluid)
- begin dividing and colonizing bodily fluids
- initally in blood and lymphatic system, but if given enough time, will cross the blood-brain barrier to get into the cererbal-spinal fluid
- in the human host the long-slender BSF trypomastigotes appear to be able to sense the number of other parasites around them, and through a core sensing mechanism they can talk to each other, get a rough idea of the numbers of parasites, and if the population gets too high they express stumpy induction factor
24
Q
A
- BSF trypomastigotes differentiate into short stumpy (SS) trypomastigotes
- trigger unknown - stumpy induction factor
- in the human host the long-slender BSF trypomastigotes appear to be able to sense the number of other parasites around them, and through a core sensing mechanism they can talk to each other, get a rough idea of the numbers of parasites, and if the population gets too high they express stumpy induction factor
- stumpy induction factor causes the long slender BSF parasite to shrink and form the short-stumpy trypomastigote
- stumpy induction factor produced in a density-dependent manner
- SS trypomastigotes can’t divide
- pre-adapted for life in insect
- tsetse fly takes a blood meal and ingests BSF and SS trypomastigotes
- they pass into the gut of the insect
- if the SS form isn’t taken up, human immune system will kick in and wipe it out
- dead-end unless the SS gets into the tsetse form
*
25
BSF trypomastigotes differentiate into
short stumpy (SS) trypomastigotes
* trigger unknown - stumpy induction factor
* in the human host the long-slender BSF trypomastigotes appear to be able to sense the number of other parasites around them, and through a core sensing mechanism they can talk to each other, get a rough idea of the numbers of parasites, and if the population gets too high they express stumpy induction factor
* stumpy induction factor causes the long slender BSF parasite to shrink and form the short-stumpy trypomastigote
* stumpy induction factor produced in a density-dependent manner
* SS trypomastigotes can't divide
* pre-adapted for life in insect
* tsetse fly takes a blood meal and ingests BSF and SS trypomastigotes
* they pass into the gut of the insect
* if the SS form isn't taken up, human immune system will kick in and wipe it out
* dead-end unless the SS gets into the tsetse form
26
* in tsetse fly midgut, BSF trypomastigotes die
* SS trypomastigotes transform into **_procyclic trypomastigotes_**
* SS form survives, go into the midgut of the insect vector where they respond to...
* trigger - temperature/citrate/cis-aconitate (temp and carbs)
* procyclic trypomastigotes multiply by binary fission
* colonize insect gut
27
in tsetse fly midgut, BSF trypomastigotes die
SS trypomastigotes transform into
**_procyclic trypomastigotes_**
* SS form survives, go into the midgut of the insect vector where they respond to...
* trigger - temperature/citrate/cis-aconitate (temp and carbs)
* procyclic trypomastigotes multiply by binary fission
* colonize insect gut
28
* procyclic trypomastigotes leave themidgut
* can either get back up through the digestive system and can get back into the salivary gland
* or the procyclic form somehow can access the hemocyl (insect blood supply) to get into the salivary gland
* migrate to the salivary gland
* procyclic trypomastigotes transform into epimastigotes
* trigger unknown
29
procyclic trypomastigotes leave themidgut and goes to the
salivary gland
* can either get back up through the digestive system and can get back into the salivary gland
* or the procyclic form somehow can access the hemocyl (insect blood supply) to get into the salivary gland
* procyclic trypomastigotes transform into epimastigotes
* trigger unknown
30
epimastigotes in the salivary gland:
1. attach to epithelial cells via flagella
2. divide by binary fission
3. sexual reproduction can occur (genetic exchange is NOT an essential stage in life cycle, doesn't involve meiosis - 2 diploid organisms fuse to form a tetraploid, with time lose genetic information to go back toward a diploid state) to colonize that organ
4. transform into metacyclic trypomastigotes (trigger unknown)
* some epimastigotes undergo a cell division that will result in one epimastigote and one metacyclic trypomastigote
* probably density dependent
* the epithelial cells have changed, and parasite off of epithelial cells into lumen (metacyclic form) that's ready to be spat out into the next mammalian host
31
2 sub species of *T. brucei* cause HAT
* *Trypanosoma brucei gambiense*
* **West African trypanosomiasis
* *Trypanosoma brucei rhodesiense*
* East African trypanosomiasis
* differences between the 2 forms
32
*Trypanosoma brucei gambiense*
West African trypanosomiasis
33
*Trypanosoma brucei rhodesiense*
East African trypanosomiasis
34
Other African trypanosomiasis
* found predominantly in ungulate mammals
* sub of brucei
* *Trypanosoma brucei brucei*
* **not infectious to humans
* restricted to cattle
* *Trypanosoma vivax*
* *Trypanosoma congolense*
* above 2 can resist human complement but this form is susceptible to our human complement
35
East African trypanosomiasis
tsetse fly
savannah
36
West African trypanosomiasis
tsetse fly
riverine
37
East African trypanosomiasis
ecology
dry bush/woodland
38
West African trypanosomiasis
ecology
rainforest
rivers
lakes
39
East African trypanosomiasis
geographical range
East/Southern Africa
40
West African trypanosomiasis
geographical range
West/Central Africa
41
Meeting of East and West forms
* East and West forms meet in Uganda
* because of cattle movement worry that the forms will be brougth into contact
* worry that in salivary gland of the insect vector epimastigotes can have sex
* what if the 2 forms get on?
* may get genetic mixing, what will it produce?
* over time, as a result of cattle migration the 2 parasite forms are getting closer
42
East African trypanosomiasis
transmission cycle
zootic
ungulate → human
involving animals
(animal - human - animal)
43
West African trypanosomiasis
transmission cycle
anthropomorphic
human → human
44
East African trypanosomiasis
non-human reservoirs
wild and domestic animals
45
West African trypanosomiasis
non-human reservoirs
rare
46
East African trypanosomiasis
epidemiology
sporadic, safaris
47
West African trypanosomiasis
endemic, some epidemics
48
East African trypanosomiasis
disease progression
rapid progression to death
49
West African trypanosomiasis
disease progression
slow progression (~1 year) leading to death
50
East African trypanosomiasis
parasitaemia
high
51
West African trypanosomiasis
parasitaemia
low
52
East African trypanosomiasis
asymptomatic carriers
rare
53
West African trypanosomiasis
asymptomatic carriers
common
(always there at a very low level)
(difficult to detect in the first place by looking at a blood smear)
54
In the west
* low level constantly going on
* number of asymptomatic cases
* undersestimate number of cases because it's there in a lot of people but at a very low level
* not getting treated because not ill, even though it's there
* asymptomatic to life-threatening can take a long time (long-lasting chronic infection)
55
In the east
* nothing - nothing - spikes
* sporadic outbreaks
* like wildfire - affect a lot of people then die back very quickly
* parasite burden is very high
* humans find it very difficult to suppress parasite numbers
* low number of asymptomatic cases
* because if you get this form of the disease you transfer from asymptomatic to symptomatic very quickly (acute infection)
* infection to death as little as 3-4 weeks
56
Pathology
early stage
blood1
blood
* chancre arises at site of bite in 50%
* moreso with *T. b. rhodesiense* infections
* probably more due to the tsetse fly than the infection
* can heal leaving altered pigmentation
* diagnostic, particularly of *rhodesiense* form
57
Pathology
early stage
blood2
* long slender form begins to divide and colonizes the blood
* intermittent fever, headache
* fibrile episodes of feeling hot then cooled down, again by the week
* because immune system trying to wipe the parasite out
* body responding to antigen insults being thrown at immune system
58
Pathology
early stage
lymphatics
* spreads to body and starts to invade other fluids - including lymphatic system
* continued fibrile episodes
* lymphadenopathy
* localized edemas - water collection
* swelling of the lymph glands
* eg Winterbottom's sign - enlarged neck gland
* deteriorating health
59
Pathology
late stage
CNS
* severe sleep disturbance
can still get treated and recover, but if not:
* severe neurological symptoms
* convulsions
* coma
* personality change
* death
arsenic treatment in East form, but arsenic is lethal also
60
Comparing pathology
61
Diagnosis
* must be cheap, can't rely on power supply
* direct methods
* blood smear
* enrichment
* DEAE anion exchange
* microhaematocrit
* cerebrospinal fluid
62
Diagnosis
direct
blood smear
* ok for East form where parasitaemia can get very high
* not good for West form where parasite density doesn't get very high
63
Diagnosis
direct
enrichment
enrichment
* DEAE anion exchange column
* RBC stay in column, parasites pass through
* can use concentration methods - use ion exhchange column to bind out red blood cells and allow parasites to come through
* microhaematocrit (buffy coat)
* capillary tubes sealed at one end, suck blood up and put into specialized centrifuge, spin to package out all components of blood
* RBC at bottom - WBC with buffy coat - plasma on top
* look at buffy coat for presence or parasite
64
Diagnosis
direct
cerebrospinal fluid
lumbar punctures to diagnose people with late stage symptoms
65
Diagnosis
indirect (seriology)
CATT
Card Agglutination Test for Trypanosomiasis
drop of blood
+ fixed (dead) parasites on a plastic card
⇒ blue granular deposits = infection
* looking for antibodies against the parasite in the person's blood
* if you have antibodies against the parasite it will agglutinate the parasites together to form a granular deposit
* not infected = no blue granulation
* only works for *T. b. gambiense* BUT is cheap (25cents/test)
* need diagnostic tests for East form that kills you faster
66
5 licensed drugs
1. Suramin
2. Pentamidine
3. Melarsoprol
4. Eflornithine
5. NECT (nifurtimox-eflornithine combinational therapy)
67
Prevention and control
1. pre-20th century
2. land clearing
3. slaughter of wild animals
4. pesticide campaigns
5. trapping
6. irradiated males
* control efforts undertaken throughout the African continent long-term sustainable control rarely achieved
* tsetse control efforts tied to poverty, health, politics
68
Prevention and control
pre-20th century
humans didn't settle or cultivate crops in areas where fly prevalent
69
Prevention and control
land clearing
* removal of brush and woody vegetation from area
* Tsetse tend to rest on trunks of trees
* hop around rather than flying
if remove the threat, humans will move into the savannah
70
Prevention and control
slaughter of
wild animals
71
Prevention and control
pesticide campaigns
* aerosol sprays (DDT)
* ecosystems rebelled against
* pour on formulations (cattle)
72
Prevention and control
trapping
* can trap the flies
* attracted to dark objects
* put insecticide in dark object
73
Prevention and control
irradiated males
* try to breed out the disease
74
