Parasitology Flashcards
Whip worm (type of roundworm) - Trichuris trichuria
Direct life cycle in humans. Most roundworm helminths oral-faecal transmission (onchocercaisis not). Infection persists for years. Asymptomatic to severe symptoms.
Adult worm lays eggs in LI. 15-30 days to develop. Eggs passed out in faeces. After ingestion, eggs hatch in SI.
Treat with albendazole/mebendazole.
Pin worm (type of roundworm) - Enterobius
Crawl out of rectum and lay egg in peri-anal region. Eggs spread by touching contaminated bed clothes.
Giant round worm - Ascaris lumbricoides
Cause disease by simple mechanical blockage of intestines.
Toxocara canis (type of roundworm)
Dog definitive host, human intermediate host. Cause human toxocariasis when eggs ingested. Larval worms don’t develop but migrate to eye and brain to cause blindness and epilepsy respectively.
Taenia solium/pork tapeworm (type of flatworm)
Human definitive host, pig intermediate host. Humans ingest cysticerci (larvae stage) from infected pig. Develop into a hermaphroditic (produce male and female gametes) adult worm, causing taeniasis. This is asymptomatic usually but can cause anaemia and emaciation.
Adult worm produces gravid proglottids (eggs) and excreted in our faeces. Eggs ingested by pig where they hatch and become cysticerci and develop in pig muscle and brain.
Intermediate host suffer severe disease. Pigs don’t live long enough to suffer. But if humans ingest eggs (and become intermediate host), eggs hatch and become cysticerci which grow and cause cysticercosis. Big cysticerci obstruct organ function, in brain it causes epilepsy, blindness, seizures.
Cystercerci rupture cause massive inflammatory response.
Schistosomiasis/Bilharzia caused by Schistosomes/blood flukes (type of flatworm)
Mainly in sub-Saharan Africa.
Intestinal disease: Hepato-splenomegaly, liver calcification.
Bladder disease: Bladder fibrosis, cancer, calcification, sandy patches on cervix.
Human definitive host, snail intermediate host.
Cercaria (larvae stage) in water penetrates human skin. Goes to liver portal circulation where it matures to adult. Male and female adult worm pair goes to mesenteric venules and lay eggs which are shed in faeces.
Eggs hatch in water, releasing miracidia (pre-larvae stage), and invades snail. Develops into cercaria and released into water.
Morbidity due to eggs refluxing with blood flow back to liver to from granuloma which cause fibrosis, calcification. Eggs can go through intestinal wall to form granulomas in there.
Cercaria infection causes initial TH1 response. Egg deposition starts TH2 response. Then there’s a modified TH2 response with IL-10 and Treg cell production to limit immunopathology.
Leishmania
Helminths are multicellular eukaryotes but protozoa are unicellular eukaryotes.
Leishmania has a tropical and sub-tropical distribution.
No definitive host as meiosis not part of life cycle. Sand fly is the invertebrate vector. Intermediate hosts dependent on what sand fly feeds on (e.g. humans).
Amastigote ingested by sand fly and turn into promastigote. Promastigote’s flagellum attaches to sand fly midgut to prevent loss by defecation. Promastigote develops then migrates to behind mouthparts. Promastigote injected during next sand fly blood meal.
Promastigote taken up by macrophages and dendritic cells. DCs cause TH1 response, activates macrophages which kills promastigote. Inflammatory damage to host. Some promastigote survives and turn into amastigote which is picked up by sand fly.
Promastigote flagellated and amastigote non-flagellated. Both promastigote and amastigote have axoneme, basal body, and kinetoplast which contains DNA. Kinetoplast is held within the single mitochondrion.
Outer surface of parasite+flagellum coated with LPG (carbohydrate). LPG maintains parasite in sand fly midgut by bidning galactin. As promastigote develops, LPG changes lengths and side chains, releasing parasite from midgut which travels to mouthparts.
From promastigote to amastigote in intermediate host, LPG gets longer and more side chains, which prepares it to resist macrophage oxidative busts.
Leishmania evolution
Divided into Old world (Eurasia) + New world (Americas).
All species cause symptoms ranging from a simple cutaneous lesion to severe visceral disease and facial tissue destruction.
L.chagasi was brought to Brazil by Portuguese explorers, with dogs as reservoir hosts. L.chagasi closely related to L.infantum which is from Portugal.
In Brazil: For L.braziliensis, two-toed sloth is the natural intermediate host. But urbanisation made humans its new intermediate host, so will cause severe pathology.
L.major is common in Eurasia. P.papatasi (sandfly species) is its restrictive host, only allowing it to grow inside it. P.arabicusis is its permissive host, also allowing other Leishmania species to grow inside it. Hence L.major can avoid competition and can expand its ecological niche, since P.arabicusis grows at higher elevations.
P.papatasi has lectin galactin on midgut which is specific for L.major LPG.
Toxoplasma gondii
Cat family is definitive host. No invertebrate vector as transmission is via carnivory. All warm-blooded animals are potential intermediate hosts. T.gondii is an obligate intracellular parasite and infects any nucleated cell. T.gondii has global distribution.
Toxoplasma is classified as a coccidian related to Eimeria and Neospora species.
Cat ingest bradyzoite (tissue cyst) from infected meat or sporozoite (oocyst) from faeces. They transform into tachyzoite then transform into micro and macro gametocytes that fuse to form an oocyst that is shed in faeces. Oocyst divide by meiosis in environment to form octet of sporozoites.
Immune pressure can cause tachyzoite to become bradyzoite/tissue cyst, which are quiescent, and re-activate upon immune suppression. Healthy people are immune after 1st infection.
Tachyzoite cause mild flu-like symptoms in healthy people, but fatal encephalitis and blindness in immunosuppressed. Can cross placenta and cause birth detects.
T.gondii evolution
3 clonal lineages, types 1,2,3. 90-95% similarity between the lineages. Most recent common ancestor for NA and Europe parasite strain 6-10000 years ago, after which it went through a population bottleneck (like L.chagasi).
SA strains have more diversity due to more cat species in SA.
T.gondii can pass directly between intermediate hosts via carnivory, skipping direct host. This is unique to toxoplasmas, and is why it has a global distribution.
Apical complex
Micronemes secrete proteins that bind host cell surface and allows parasite to glide along host surface. Find a suitable site and blow a hole through membrane.
Rhoptries secrete parasitic protein and membrane to form a parasitophorous vacuole in the host cell.
Dense granules processes host cell molecules for parasite uptake.
Note that invasion of host cell is done without using any host cell function (unlike bacterial invasion).
Rodents have evolved IRGs (immune related GTPases) which destroy PVs and parasites. Type 1 T.gondii strains have rhoptry protein 18 (ROP18), which phosphorylates and inactivates IRGs. Humans don’t have those IRGs
Protozoa anti-immune system mechanisms
Leishmania uses gp63 to cleave C3b to iC3b. This prevents MAC formation but enhances uptake by macrophages (iC3b is an opsonin).
Trypanosomes expresses gp160, its own version of decay-accelerating factor.
Malaria stats and info
Transmitted by female mosquitoes of the Anopheles species. Mostly in sub-Saharan Africa. Half of deaths in children under 5, this high pre-reproductive mortality has caused our genome to evolve resistance against malaria.
P.ovale, P.vivax, P.malariae, P.falciparum. P.falciparum dominates sub-Saharan Africa, but there’s human resistance in sub-Saharan Africa against P.vivax. P.vivax active in Brazil and Indonesia.
P.falciparum life cycle
Mosquito inject sporozoites into us which travel to hepatocytes. Liver stage merogony (asexual reproduction) turns sporozoite into merozoite and amplifies parasite number. 10000 merozoite in a schizont (all the merozoite that a single schizont makes). So sporozoite vaccines not useful.
Merozoite moves to RBCs and transforms into ring form trophozoite during merogony. Only tens of trophozoites in a single schizont. Trophozoites produce proteins that decorate RBC which allows ‘rosetting’ (see later).
Some merozoites turn instead into micro and macro gametocyte (so there is also sexual reproduction). They’re taken up together by mosquito and fuse within mosquito to form a diploid ookinete. Ookinete becomes oocyst. Oocyst attaches to mosquito stomach and undergoes meiosis to become sporozoites, 20% reach mosquito salivary glands, 10-100 sporozoites injected in a single feeding event.
Plasmodium’s disease mechanism
Liver stage is asymptomatic. RBC phase: muscle ache, fever, nausea. 1-5 year olds gets severe disease (adults have clinical immunity but obvs still have parasites in them, infants protected by maternal antibodies): anaemia, cerebral inflammation, renal failure, respiratory distress. Probably due to imbalance of cytokines, inappropriate activation of cells. Cytokine imbalance also regulates adhesion molecules of vascular endothelium, increasing sequestration.
RBC cycle critical for disease. Parasite enters RBC using apical complex like toxoplasma (malaria is an apicomplexan). But also need irreversible attachment of the apical end of the merozoite to RBC: P.vivax has DBP (duffy binding protein) which bind RBC’s DARC protein. So in sub-Saharan Africa, most people have DARC negative alleles. P.falciparum has many other ways to bind RBCs.
