Week 4 - Leishmaniasis Flashcards
How many countries is Leish distributed over?
88
how many new cases each year?
2 million
how many people are infected each year?
12 million
how many deaths are there per year?
52,000
how many people are at risk each year? what may cause this to rise
350 million
global woarming
what is the parasite transmitted by?
Sand flies
how big are sand flies?
2mm in length
what are adult sand flies characterised by?
hairy body and wings
Generally Phlebotomus sp are found in which ecosystems?
desert / semi arid
Lutzomyia sp are found in which ecosystem?
forest
why is the term sand fly misleading?
they do not fly, rather hop as short bursts of flight only
which gender spread the disease?
only females
when do sandflies most actively feed?
nocturnal and dusk
what sort of feeders are sand flies?
saw feeders. their saw like mouth parts create a wound which allows blood to well up in to a pool
suck the blood and lymph from that pool
where is the parastie located inthe sand fly?
anterior portion of gut and pharynx
how does the sand fly transmit the parasite?
regurgitates it up
transmission of leish can be both ___ and ___
zoonotic
anthroponotic
Zoonotic transmission is common in which 2 places? and which animals are reservoirs?
mediterranean
latin america
canines and rodents
generally whether the transmission cycle is zoonotic or antrhoponotic depends on which factor?
the human density in that area
What are 4 other mechanisms of transmission of leish?
blood transfusion
organ / bone marrow transplant
congenital - mother to foetus
drug usage - needle sharing
how many different species of Leishmania are there and how many can infect humans?
30
21 can infect humans
What has molecular typing demonstrated about some o fthe Leishmania species?
that in the old and new world the species are synonymous
How can you distinguish Leishmania species?
morphologcically indistinguishable
can only distinguish by molecular level
What are the 2 forms of the parasite?
promastigote
amastigote
where do you find the promastigote?
insect vector
key features of the promastigote?
flagellum sticks straight out of the body
kinetoplast in front of nucleus
what are the 2 types of promastigote?
non infectious promastigote
infectious metacyclic promastigote
The non - infectious promastigote is found where? can it divide?
insect gut
binary fission
the infectious metacyclic promastigote is found where? can it divide?
human macrophages and neutrophils
non - dividing
also found in the insect gut - transformed from non-infectious promastigote
what does the term metacyclic generally mean?
go from the insect to human
Key features of the amastigote?
intracellular
infectious
invade macrophages and neutrophils - binary fission
non motile
when the amastigote is inside the macrophage what are they like?
inside a vesicular compartment - essentially have a membrane around them which is derived from the host
which form of the parasite is transmitted back from humans into the insect?
amastigote
Life cycle :
the sand fly takes a meal and starts to regurgitate ___ _____ form parasites into the host
infectious metacyclic promastigote
What causes the regurgitation mechansim in the sand fly?
the parasite
dysfunctional stomedeal valve at foregut/midgut junction
when the insect feeds the blood goes down into the gut and because the valve doesnt close properly it washes back up into the host bringing up metacyclic promastigote
The whole process of regurgitating the parasite is exacerbated by what?
parasite secretes promastigote secretory gel that acts like a bung and promotes the insect to feed for longer
increases the chance of the parasite being transferred into the pool of blood if the feeding time is longer
why do the insect saliva and promastigote secretory gel contain elements that our immune system will respond to?
Our immune system responds to the damage done by the insect feeding and also responds to the secretory gel and insect saliva so this magnifies the attraction of neutrophils to that site.
Want more neutrophils for the metacyclic promastigote to infect
How does the metacyclic promastigote form invade neutrophil cells?
phagocytosed
What does the parasite do to the neutrophil cells?
alters their gene expresssion to promote itself
why doesnt the parasite want to stay in the neutrophil cells?
because they are short lived
what are the 2 hypotheses as to how the parasite gets form the neutrophils into macrophages?
trojan horse
simple one
explain the trojan horse hypothesis
Infects neutrophil
causes the neutrophil to undergo apoptosis
apoptotic marjers are then exposed on the cell surface of the neutrophil
the macrophages recognise the apoptotic markers and consume the dying cell
phagocytose the neutrophil along with the metacyclic promastigote inside the neutrophil
what happens to the metacyclic promastigote once it is inside the macrophage?
undergoes differentiation into an amastigote and then starts dividing
in the trojan horse hypothesis what is the trojan horse?
neutrophil
what is the simple hypothesis as to how the metacyclic promastigotes get into macrophages?
Whilst the metacyclic is inside the neutrophil undergoes differentiation into amastigote
amastigotes start to divide and rupture the neutrophil
the amastigotes are released into the blood stream and then taken up by the macrophages
What is key about the 2 hypothesis as to how the metacyclic promastigotes get out of the neutrophils?
they both lead to amastigotes form in the macrophage where they can divide and rupture the macrophage and then reinfect other cells
how long can leishmania infection last?
6 months
why is it likely we have these 2 different hypotheses?
because we are dealing with 21 different leish species