PARASITOLOGY

Question 1

what is the correlation between parasitological health burden and wealth/development?

Answer 1

as wealth and development increases, parasitological health burden decreases

Question 2

outline the issue of the rise and spread of drug resistant malaria?

Answer 2

only anti-malarial drugs still working are those based on artemisinin plant which has end-peroxide bond causing oxidative bomb inside malaria

however resistance to artemisinin now emerging; evidence of delayed clearance time using drug (important for severe forms of malaria - hours matter)

only drug with no resistance showing is pyronaridine which is best used as combination drug

WHO never declared this an emergency despite their being 241 million malaria cases in 2021

Question 3

outline the importance of parasites still common in developed countries?

Answer 3

trichomonas vaginalis most common pathogenic protozoan infection in developed countries, ST, burden not understood

toxoplasma gondii causes toxoplasmosis (a leading cause of death from food borne illness) and asymptomatic infection in heaps of cunts, thought to have significant effects on host psychology

Question 4

outline the potential for parasites as immunological therapies?

Answer 4

parasitological health burden has decreased with the increase of wealth and development, but autoimmune diseases has also increased

hypothesis that we co-evolved w parasites which wind down our immune system so when they go our immune system naturally higher functioning and less regulated

helminths covered in anti-inflam molecules, have been shown to increase lifespan in mouse models

Question 5

what are nematodes?

Answer 5

nematodes are fucking parasites - roundworms

two examples are enterobius vermicularis and hookworm

Question 6

what are enterobius vermicularis?

Answer 6

common in temperate developed areas like NZ

eggs (ova) very sticky to fomites objects and can remain viable for weeks

male and female ones attach to ascending colon and mate after which female goes to perianal region and lays lots of eggs - person scratches these spreading infection back to you or others

enterobiasis (disease caused) can cause secondary bacterial infection, vulvovaginitis and also there may be possible fertility implications

Question 7

outline the chain of infection for enterobius vermicularis?

Answer 7

causative agent: enterobius vermicularis

reservoir/source: human/fomite/food

means of exit: excretions

mode of transmission: contact/food

portal of entry: GI tract

person of risk: especially infectious for young institutionalised people but generally unpick and no association with gender, social class, race or culture

Question 8

how do you break the chain of infection for enterobius vermicularis?

Answer 8

treat causative agent with 2 doses mebendazole pyrantel pamoate

portal of entry: break this link by hygienic practices e.g. short fingernails, wash hands, wash bed linen

Question 9

what is the association of enterobius vermicularis and dientamoeba fragilis?

Answer 9

D. fragilis commonly found in acute gastro cases and has been associated with E. vermicularis

D. fragilis cysts may attach to surface of nematode eggs and hitch a ride causing co-infection

Question 10

what are hookworms?

Answer 10

hookworm filariform larvae can live for 2 weeks in soil and sense the warmth of your feet so go in your follicle

often accidental infection by dog/cat hookworm causing cutaneous larva migrans

human specific hookworms way worse; filariform live 4 weeks in soil, get into your blood>heart>pulmonary vessels>lungs

larvae stops at alveoli, breaks into airways causing coughing/shortness of breath, coughed up and swallowed in mucus to finally infect intestine

attach to intestinal epithelia and can let their for up to a decade drinking blood - can cause severe anaemia and protein deficiency > can retard growth and mental development in children

leading cause of anaemia in developing world

Question 11

what are the two most common human specific species of hookworm?

Answer 11

ancylostoma duodenale

necator americanus

these are also the two biggest human pathogens we find in soil

Question 12

why can diagnosis of hookworm be difficult?

Answer 12

worms take six weeks to reach maturity and symptoms of infection can therefor appear before eggs found in faeces

Question 13

outline the chain of infection for hook worm?

Answer 13

causative agent: ancylostoma duodenal or nectar americanus

reservoir: soil

means of exit/way out of body: excretions

mode of transmission: contact

portal of entry/way into body: skin

person of risk: anyone in endemic areas

Question 14

how do we break the chain of infection for hookworm?

Answer 14

treatment of causative agent with albendazole and mebendazole

sanitation critical way: breaks reservoir (soil) and means of exit (excretion) cause you stop people shitting everywhere

portal of entry - wear shoes

Question 15

what is hookworm therapy?

Answer 15

hookworms excrete proteins which down regulate parts of your immune response

potential as a medication-free treatment for inflammatory bowel disease

Question 16

what is wucheria bancrofti?

Answer 16

worm causes lymphatic filiaris (LF)

people with LF more at risk of malarial or hookworm infection causing co-morbidities e.g. anaemia

most infections somewhat asymptomatic

Question 17

what are the three causative agents of lymphatic filiaris?

Answer 17

Wucherin bancrofti (most cases), brugia malayi, brugia timori

Question 18

outline the chain of infection for wucheria bancrofti?

Answer 18

causative agent: wucheria bancrofti

reservoir: human (only really found in humans)

means of exit: blood

mode of transmission: vector (mosquito picks up microfilaria which are transmissible form)

portal of entry: skin

persons at risk: people getting bit by mosquito good tasting people, indiscriminate who it infects

Question 19

outline the chain of infection for wucheria bancrofti?

Question 20

how does wucheria bancrofti and other LF causing parasites actually cause LF?

Answer 20

adult larvae cause blockage to lymph nodes causing hydrocele and elephantiasis

Question 21

outline the life cycle of wucheria bancrofti, brugia malayi and brugia timori?

Answer 21

mosquito takes a blood meal - larvae enter skin

adults in lymphatics (causes LF) and produce sheathed microfiliriae that migrate to lymph and blood channels (all over the body)

mosquito takes blood meal - ingests microfiliriae

microfiliriae shed sheaths and infect mosquito and go through some growth stages, eventually migrating to mosquito head/proboscis

cycle repeats!

Question 22

how do you break the chain of infection for wucheria bancrofti?

Answer 22

treatment of causative agent with DEC and ivermectin together - this also deals with reservoir

repellents/nets to break portal of entry

Question 23

what is schistosomiasis?

Answer 23

disease caused by trematodes e.g. S. mansion, S. haematobium, S. japonica

infects hundreds of millions of people world wide, between 4000 and 200,000 deaths annually

emerge from aquatic snails, go through hair follicle>blood stream>liver> mature and start drinking your blood out your vein and fuck and lay eggs

eggs excreted back to environment but are spiky so get caught in different tissues causing problems like granuloma

schistosomiasis is primarily a immunological disease

symptom is pissing blood cause spiky eggs stuck in your kidneys

Question 24

how do trematodes infect snails?

Answer 24

the eggs in environment hatch and shit like miracidia then go seek out the snails

Question 25

outline the chain of infection for Schistosoma haematobium/japonicum/mansoni?

Answer 25

causative agent: S. haematobium, S. japonicum, S. mansoni reservoir/source: aquatic snails means of exit: excretions mode of transmission: contact portal of entry: skin person at risk: anyone in endemic areas

Question 26

how do you break the schistosoma chain of infection?

Answer 26

treatment of causative agent with praziquantel (only kills mature parasite so must give 4-6 weeks after presumed infection) sanitation (e.g. weed removal, stop shitting in water) deals with reservoir and means of exit stop swimming in infected waters (deals with portal of entry)

Question 27

what happened when we switched from microscopy to PCR for examining protists (clue - fragilis)?

Answer 27

showed that some parasites e.g. D fragilis stand out a lot more shows that these parasites are common among New Zealanders

Question 28

what is blastocystis?

Answer 28

most common eukaryotic microbe in human intestinal tract (1 billion infected ww) luminal protist comprising numerous genetically-distinct subtypes (ST) ambiguous clinical significance (present in symptomatic and asymptomatic, possibly ST related different forms e.g. vacuolar, granular, amoeboid blastocystosis - symptoms include abdominal pain, diarrhoea, bloating, nausea

Question 29

outline what we know about the lifecycle of blastocystis spp.?

Answer 29

people eat fecal cysts which are resistant to stomach acid cysts end up in large intestine and here they just absorb nutrients from existing food

Question 30

what is a key thing that needs to be done to better understand blastocystosis?

Answer 30

genetically typing the different serotypes there is evidence that one serotype (ST7) is more associated with pathogenesis well others may be commensal but at the end of the day no-one knows atm as funding limited

Question 31

what is dientamoeba fragilis?

Answer 31

fragile parasite so PCR better than microscopy which can destroy it current surveillance mostly uses microscopy hence inconsistent statistics between countries higher rates in children and 40 year olds (especially in parents and siblings suggesting transmission) high rates in pig farmers

Question 32

what commonalities do dientomoeba fragilis and blastocystis spp. share (in terms of research)?

Answer 32

we don't understand pathogenesis (a big step to fixing this is genotyping them) better diagnosed using PCR than microscopy more research needed on lifecycle both associated with large intestine and free living (not attached) co-infection frequent

Question 33

what is the current evidence for intestinal protozoa significantly affecting human microbiome diversity?

Answer 33

evidence that D. fragilis affects microbiome by increases alpha diversity/species richness some intestinal parasites seem to reduce variation in microbiome between patients (uniform between patients) therefor it is important that we look at full ecology of microbiome not just focus on bacteria

Question 34

what is giardia intestinalis?

Answer 34

intestinal protozoa caught by cyst contaminated food or water low MID (10) so highly virulent outer wall of giardia cyst acid resistant but broken down by proteases in small intestine allowing trophozoites to emerge which attach to small intestine wall via ventral adhesive disc and start divide inhibit absorbance of fats and fat soluble vitamins

Question 35

outline the clinical progression of giardiasis?

Answer 35

diarrhoea gas greasy stools that float(key diagnostic cause inhibited fat absorbance) stomach/abdominal cramps upset stomach or nausea/vomiting dehydration/fluid loss

Question 36

outline the giardia lifecycle?

Answer 36

eat cysts cysts hatch trophozoites which attach to small intestine encystation (cyst forming) occurs under conditions of bile salt conc. changes and alkaline pH, this occurs in large intestine shit out cysts which survive in focal matter well trophozoites die

Question 37

outline the chain of infection for giardia?

Answer 37

causative agent: giardia lamblia/intestinalis reservoir: animals/humans/water means of exit: excretion (100m cysts in one shit) mode of transmission: food/water portal of entry: ingestion (MID 10 cysts) person of risk: anyone can get infected but people in places where giardia common, cunts with aids, people drinking directly from waterways

Question 38

how do you break the chain of infection for giardia?

Answer 38

stop causative agent with treatment with metronidazole, tinidazole or nitazoxanide (combination, resistance emerging) portal of entry: boil drinking water, wash hands, use clean water to wash food encourage breast feeding cause people mix with water and fuck up their babies

Question 39

what is cryptosporidium paarvum?

Answer 39

intestinal protozoa peaks around calving season as common in young animals oocysts target small intestine key difference to giardia is that rather than adhere, it burrows into cell so is intracellular parasite, in cell they multiple and release oocysts

Question 40

outline the clinical progression of cryptosporidium?

Answer 40

watery diarrhoea (unlike giardia) stomach cramps dehydration nausea vomiting fever (unlike giardia) weight loss

Question 41

outline the cryptosporidium chain of infection?

Answer 41

portal of entry - 30 oocysts MID person of risk - anyone but AIDs people, immunosuppressed most at risk break it by treating with nitrazoxanide (can't be used with AIDS cause requires high CD8 cell count), encourage breast feeding, boil drinking water

Question 42

what is Trichomonas vaginalis (Tv)?

Answer 42

most common pathogenic protozoan in developed countries and a highly neglected STD sexually transmitted and full burden not understood causes trichomoniasis - 70% of people no symptoms, men may notice burning after urination or discharge/itching sensation in dick, woman may notice itching, burning of vagina, discomfort w urination, change in colour in vaginal discharge with fishy smell, unpleasant sensation during sex treat trichomonas w metronidazole NZ assessing cost associated with surveillance, best option check people with other STD cause they most likely to have Tv

Question 43

what is toxoplasma gondii?

Answer 43

causative agent of toxoplasmosis, thought to have significant effects on host psychology can only reproduce in cats, mouse is intermediate host cat shits out oocysts, mice eat, oocysts hatch and move from intestine to tissues in mouse, cat eats mouse, cysts burst open in cat and cycle repeats pregnant woman vulnerable to infection cause down regulated immune system, toxoplasma can cross placental barrier (and all barriers) and infect fetus, likes infecting the retina leading to blind/deaf children asymptomatic in a shit load of people, considered to be leading cause of death attributed to food borne illness, chances are you won't know you infected till immunosuppressed use IgG or IgM serology to test for infection, symptoms varied as cysts can be anywhere treat with pyrimethamine and sulfadiazine plus folinic acid, most healthy people recover

Question 44

outline the effects of toxoplasma gondii on host psychology?

Answer 44

makes mice less afraid of/sexually attracted to cats - run towards cat urine/faeces smell we know it effects psychoactive modulators probably somehow regulates hypomethylated arginine vasopressin promoters in medial amygdala (emotion) leading to higher expression of mRNA for AVP potentially linked to depression and schizophrenia in humans

Question 45

what is Naegleria fowleri?

Answer 45

parasite found in still, warm water - its amoeba feed on pond scum causes primary amoebic meningoencephalitis (PAM) which is almost always fatal infection occurs from water going up nasal cavity from water-related activities (e.g. diving) allowing amoeba to penetrate nasal mucosa migrate to brain via olfactory nerves to cause PAM diagnosis from Naegleria fowleri in CSF or tissue specimens potential for miltefosine as treatment (breast cancer and anti leishmania drug)

Question 46

outline the journey from mosquito to the liver for malaria?

Answer 46

mosquito injects saliva during bite along with about 10 sporozoites sporozoites travel to host liver via blood stream and are covered in circumsporozoite proteins (CSP) which they shed to evade immune cells - this makes them very virulent sporozoites reach liver sinusoids, move across endothelium and interact with heparin sulphate proteoglycans (HSPGs), and then cross sinusoidal layer through kupffer cells sporozoite then targets parenchymal liver cells in which they develop into an exoerythrocytic parasite

Question 47

outline malaria development in the liver, how is this different between P. vivax and P. falciparum ?

Answer 47

7-10 days post successful sporozoite infection, they develop into schizonts and then released as merozoites which enter blood stream (one sporozoite can produce as many as 30,000 merozoites) no symptoms prior to RBC infection stage (10-12 days post-bite) Difference in this process between P. falciparum and P. vivax is some P. vivax (about 3 in 10) enter a dormant phase (metabolically dormant hypnozoite - could be 28d to 1 year) before developing into schizont; this can result in relapses of malaria only two drugs which can target it in metabolically dormant phase (primaquine and tafenoquine) which are both 8-aminoquinolines which can cause serious adverse affects (haemolysis) in those with G6PD mutations

Question 48

what are the two kinds of parasites causing malaria?

Answer 48

Plasmodium falciparum (killer) Plasmodium vivax (relapser)

Question 49

what are the differences in RBC tropism between P. falciparum and P. vivax?

Answer 49

falciparum merozoites can invade all RBC types (e.g. normocytes, reticulocytes) (invasion ligand-receptor pair is PfEBA-175/glycophorin A) vivax merozoites can only invade nascent reticulocytes which are early stage RBCs (<2% circulating circulating RBCs) (invasion ligand-receptor pair is (PvDBP/DARC) this means patients infected with vivax show 2% parasitemia at worst

Question 50

how do malarial parasites invade RBCs when they move through blood like cars on a fucking highway?

Answer 50

cause RBCs accumulate in spleen so I think they like slow down here I DONT KNOW IF THIS IS ACTUALLY RIGHT

Question 51

why do people with malaria get a really bad reoccurring fever every 48 hours?

Answer 51

because merizoites develop in RBCs and once this has reached a certain point they burst out to infect other RBCs bursting releases a bunch of contents, particularly hemazoin which is a product of parasite metabolism the release of RBC contents causes the really bad fever

Question 52

what stages do antimalarials treating symptomatic malaria (artesunate, chloroquine, malarone, mefloquine) target?

Answer 52

target the blood stages where parasite replicating in RBC these stages are merozoites invading RBC, develop to trophozoite, then schizont which burst the cell

Question 53

why is malaria caused by P. falciparum more fatal than that caused by P. vivax?

Answer 53

P. falciparum can significantly alter biomechanical properties of host RBC by 18 hours post invasion (trophozoite phase) this occurs as parasite proteins crosslink RBC spectrin causing knob formation on RBC surface (making it stiff). These knobs covered with multi-domain PfEMP-1 proteins capable of sticking to a wide range of endothelial receptors this causes a more severe form of malaria as stiff, sticky RBCs bind capillaries and each other causing blockages which can be fatal if in organs like kidney or brain (cerebral malaria biggest cause of malarial death)

Question 54

why is how soon treatment with artemisinin (key antimalarial) occurs so important with P. falciparum?

Answer 54

stiff/sticky RBC pathology starts occurring 18 hours post invasion so chances get worse artemisin cures by clearing parasite quickly but resistance beginning to emerge which is associated with slower parasite clearance time

Question 55

what is causing artemisinin resistance to emerge?

Answer 55

K13 propellor protein mutations are associated with AS resistance - mutation causes artemisinin to not work somehow this is spreading throughout SE Asia, India, China, Middle East

Question 56

how does artemisinin usually kill parasite?

Answer 56

finds its way into digestive vacuole of parasite where it reacts with Fe2+ break some bonds and form an explosion of ROS within the parasite

Question 57

what is different about P. vivax pathogenesis which means it doesn't form stiff/sticky reticulocytes?

Answer 57

P. vivax remodels reticulocytes and instead of making them sticky makes them deformable somehow that's literally it so its not more deadly or anything just like squishy

Question 58

why do P. falciparum and P. vivax have different pathologies?

Answer 58

falciparum proteins crosslink RBC spectrin making stiff/sticky RBCs which can cause blockages and fatality vivax just makes reticulocytes deformable so less deadly ultimately different pathologies is due to the differing receptor tropism and the changes it makes in those RBCs