Pathogen Lifecycles Flashcards
what is the difference between a vaccine and a drug?
a vaccine is preventative a drug is for when you already have it
what are the complications with anti-parasite drugs?
- eukaryotic parasites share a lot of the same metabolic machinery as humans
- very narrow therapeutic windows
what transporters or metabolic factors could drugs target?
- quinine transporters
- folic acid metabolism
why is there a very narrow therapeutic window for parasite infection?
- kill it before it kills you
- impacted by parasite specific factors
- needs to go to the appropriate location and be absorbed rapidly
what considerations need to be taken into account when creating a anti-parasitic drug or vaccine?
- parasite diversity
- parasite life cycle
- active host pathogen interactions
- antigen load
- concomitant
- pathology
what are the different forms of Lesimania?
VL (deadliest, least common form)
CL (major impact on morbidity and quality of life)
what is the status of vaccines and drugs to treat Leishmania?
- no vaccines
- limited drugs
what are the common drugs for Leishmania?
- amphotericin B
- pentavalent anitomy
- milefosile
- best to use a mix of these 3 drugs
give an overview of the stages of Leishmania in humans?
- sandfly takes blood meal
- promastigotes are phagocytosed by macrophages
- promastigotes transform into amastigotes within macrophages
- amastigotes multiply in cells of various tissues
give an overview of the stages of Leishmania in the sand-fly?
- uninfected sand fly takes a blood meal
- ingestion of parasitized cell
- amstigotes transform into promastigote stage in the midgut
- divide in the midgut and migrate to the probiscis
what happens when the sandlfy takes a blood meals in stage 1 of the leishmania lifecycle in humans?
- infects promastigote stage into the skin
- metacyclic parasites transmitted to humans
- must be taken up within 24 hours otherwise they are eradicated by our immune system
what is the primary host cell for the Leishmania parasite?
macrophages
how does promastigotes transform into amastigotes inside the macrophages in stage 3 of the human cycle of Leishmania?
- use the lower pH and higher temperature as a trigger for differentiation
- need to transform into amastigotes as these are highly proliferative
what happens when amastigotes multiply in cells of various tissue in stage 4 of the human cycle in Leismania?
- they burst the macrophages
- impact on the immune system
- burst macrophages attract more macrophages
- eradicates your innate immune system
- in VL the Leishmania targets the spleen and liver (engorges)
is it possible for vaccines for Leishmania to be developed?
- mainly children get it but adults are still exposed
- suggests adults have had exposure and that it hasnt manifested
- single lifecycle stage is responsible for the disease
- think there are a lot of carriers
- no antigenic variation detected to date
- targeting of virulence determinants may not be essential for effective cell-mediated immunity
- natural resistance to re-infection
what are the lifecycle stages of T.brucei in the vector (tsetse fly)?
- Tsetse fly takes a blood meal
- Bloodstream trypomastigotes transform into procyclic trypomastigotes in tsetses flys midgut
- procyclic trypomasitgotes leave the midgut and transform into epimastigotes
- epimastigotes multiply in salivary gland
what are the life cycle stages of t.brucei in the human?
- tsetse fly takes a blood meal
- injected metacyclics transform into bloodstream trypomastigotes
- mulitply by binary fission in bodily fluids
- trypomastigotes in blood
what happens when tsetse flies take a blood meal in stage 1 of the vector life cycle in t.brucei?
- bloodstream trypomastigotes are ingested
- stumpy stage
how do procyclic trypomastigotes multiply of stage 2 of the vector life cycle in t.brucei?
multiply by binary fission
what do epimastigotes transform into in stage 4 of the vector life cycle in t.brucei?
metacyclics
what happens when the tsetse fly takes a blood meal in stage 5 of the human lifecycle in t.brucei?
- injects metacyclic trypomastigotes
- non-proliferative, need to differentiate into the slender stage
what stage are the blood stream trypomastigotes (stage 6) in t.brucei?
the slender stage
what bodily fluids do metacyclics multiply in (stage 7) in t.brucei lifecycle?
blood, lymph, spinal fluid
what stage are the trpamstigotes in the blood in stage 8?
stumpy stage - when there’s a certain density of slender they go to the stumpy
when are the stages of t.brucei not profilerative?
during transmission
what are the stages of the t.cruzi lifecycle in humans?
- triatome bug takes a blood meal
- metacyclic penetrate various cells
- amastigotes multiply by binary fission in cells of infected tissues
- intracellular amastigotes transform into trypomastigotes
what are the stages of the t.cruzi lifecyle in the vector (triatome bug)?
- triatome bug takes a blood meal
- epimastigotes in the midgut
- multiply in the midgut
- metacyclic trypomastigotes in the hindgut
in stage 1, what happens when the triatome bug takes a blood meal in t.cruzi?
passes metacyclic in faeces, bite wound or mucosal membranes
in stage 2, what happens when metacyclic penetrate various cells in t.cruzi?
inside cells they transform into amstigotes
in stage 4, what happens when intracellular amstigotes transform into trypamastigotes in t.cruzi?
- burst out of the cell and enter the blood stream
- once they reach a certain density they re-differentiate into the amastigotes
- use the flagellum to rip apart the cells so the trypomastigotes can be released
why is it hard to target amastigotes in t.cruzi?
you would have to target every nucleated cell
what are the obstacles with treatments/vaccines of various parasites?
- 2 lifecycles responsible for disease
- antigenic variation
- t.brucei breaks the BBB
- t.cruzi = genetic diversity
- t.cruzi infects all nucleated cells
- t.cruzi amplification stage is intracellular
- t.cruzi reservoir includes wild animals
what are some examples of gut microbes?
amoebiasis: entamoeba
- giardia lamblia
what is an entamoeba?
- human parasite
- human to human in faeces
- happens in unsanitary situations
- all lifecycle stages in the human gut
what is giardia lamblia?
- contamination of food and water or hands with infective cycsts
- in the gut - multiplies and turns into a cyst
what are helminths?
- tape worms, flukes or round worms
- infection by larvae or eggs
- often migration
- adults do not replicate
what drugs target helminths?
- alendazole
- prazuquantel
- mekendazole
what is the tapeworm life cycle?
- eggs or gravid prologottids in faeces and passed into the environment
- cattle and pigs
- oncospheres hatch
- humans infected by ingesting raw or uncooked meat
- scolex attaches to the intestine
- adults in the small intestine
how are cattle and pigs infected in the tapeworm life cycle?
infected by ingesting vegetation which is contaminated
what happens when oncospheres hatch in the tapeworm lifecycle?
- penetrate intestinal wall and circulate to musculature
- oncospheres develop in cysticerci in muscle
what is the schistosomiasis lifecycle?
- different types from faeces and urine
- eggs latch releasing miracaidia
- miricidia penetrate snail tissue
- sporocysts in snail
- cercariae released by snail into water and becomes free swiming
- penetrates the skin (at legs)
- cercariae lose tail during penetration and become schistosomulae
- circulation
- migrate to portal blood in the liver and mature into adults
- paired adult worms migrate to mesenteric venles of bowel/recti,
what happens when paired adult worms migrate to mesenteric venules of bowel/rectum in the schistomiasis lifecycle?
- lay eggs - circulate to the liver
- shed in stools
- go back into the water
what is a commonly used drug for schistosomiasis?
praiziquantel
what is the ascariasis lifecycle?
- predominantly human
- foregut - round worm
- transmission through faeces
what is the hookworm lifecycle?
- eggs in feaces
- rhabditiform larva hatches
- filariform larva
- penetrates the skin - through feet walking on unsanitased ground
what are the advantages and disadvantages of living vaccines?
- gold standard for levels of protection
- there are ethical and safety issues
what are the advantages and disadvantages of inactivated “dead” vaccines?
- increased safety
- decreased immune genecity versus live vaccines
- less problems with cold storage
what are the consequences of the complex lifecycle of plasmodium?
- distinct life cycle stages
- makes it challenging to eradicate
what are the human stages of the plasmodium lifecycle?
- mosquito takes a blood meal
- exo erythrocytic cycle
- erythrocytic cycle
- gametogenesis
what are the vector stages (mosquito) of the plasmodium lifecycle?
- mosquitoes take up gametocytes during blood meals of infected individuals
- male and female gametocytes fuse within the infected mosquito
in stage 1, what happens when the mosquito takes a blood meal in the plasmodim lifecycle?
injects sporozoites
in stage 2, what happens during the exo erythrocytic cycle in the plasmodium lifecycle?
sporozoites infect liver cells and differentiate into merozoites which are released into the bloodstream
in stage 3, what happens during the erythrocytic cycle in the plasmodium cycle?
mereozoites infect red blood cells and produce either more merozoites or produce gametocytes
in stage 4, what happens during gametogenesis in the plasmodium lifecycle?
mechanisms unknown, gametocytes are produced and released into the bloodstream
in stage 6, what happens when male and female gametocytes fuse within the infected mosquito?
gives rise to sporozoites
what are some compounds used in malaria chemotherapy?
- quinolones
- anti-folates
why cant you use anti-microbials to treat malaria?
there is growing resitance of plasmodium to anti-microbial drugs
- increase in mortality and morbidity
what are the new antimicrobials?
artemisinin compounds
- rapid therapeutic response
- active against multi-resistant plasmodium
- well tolerated by malaria patients
- reduced gametocyte carriage
