17. Protozoa (Plasmodium) Flashcards
what is one of the oldest diseases known to man?
Malaria
where does the name “malaria” come from?
the italian words mal’aria meaning bad air
was malaria in canada? where?
yes, in upper and lower canada and out into the prairies
where does malaria rank in “causes of death” for infectious pathogens?
third after HIV/AIDS and tuberculosis
how is malaria transmitted?
from person to person via the bite of a females Anopheles mosquito
in Plasmodium an intracellular or extracellular parasite?
obligate intracellular
what time of day does the female mosquito bite?
dusk and dawn
are all Anopheles species able to transmit the parasite?
no, only about 60 in 380
the accumulation of what spreads the disease?
water
what are the four parasite species that cause malaria in humans?
Plasmodium falciparum
Plasmodium vivax
Plasmodium malariae
Plasmodium ovale
which are the most common parasite species to cause malaria in humans?`
p. falciparum and p. vivax
what are the major features of P. falciparum?
- the most important species, responsible for ~50 of all malaria cases worldwide and nearly all morbidity and mortality from severe malaria
- found in the propics and sub-tropics
what are the major features of P. vivax?
- widest geographical distribution
- seen in tropical and sub-tropical areas, but rare in Africa
- estimated to cause 43% of all malaria cases in the world
what are the major features of P. ovale?
- relatively rarely encountered
- primarily seen in tropical Africa, especially in the west coast, but has been reported in South America and Asia
what are the major features of P. malariae?
- responsible for only 7% of malaria cases
- occurs mainly in sub-tropical climates
what other vertebrates are also infected by Plasmodium parasites?
- non-human primates
- rodents
- birds
- lizards
- ungulates
who is the DH of Plasmodium?
Anopheles mosquito
who is the IH of Plasmodium?
human
what is special about P. vivax and P. ovale?
they have a dormant liver stage: hypnozoite
what Plasmodium stage does the Anopheles mosquito inoculate the human with?
sporozoites
what happens to the sporozoites in the human, in the liver?
they mature into schizonts
what happens to the schizonts?
they rupture and release merozoites
what does the hypnozoite do?
it can persist in the liver and cause relapses by invading the bloodstream weeks or even years later
what is the liver replication stage called?
exo-erythrocytic schizogony
what happens after exo-erythrocytic schizogony?
the parasites undergo asexual multiplication in the erythrocytes - erythrocytic schizogony
what do merozoites infect?
red blood cells
what do the ring stage trophozoites mature into?
schizonts
what do the schizonts rupture into in the erythrocytic schizogony cycle?
merozoites
what do some immature trophozoites differentiate into?
sexual erythrocytic stages (gametocytes)
what stage is responsible for the clinical manifestations of the disease?
the blood stage parasites - erythrocytic cycle
what stage is the parasite ingested in a blood meal from the human?
in the gametocyte stage
what are the male gametocytes called?
microgametocytes
what are the female gametocytes called?
macrogametocytes
what is sporogonic cycle?
the parasites multiplication in the mosquito’s midgut
what occurs in the mosquito’s midgut?
the microgametes penetrate the macrogametes generating zygotes
what happens to the zygotes?
they become motile and elongated (ookinetes)
what do the ookinetes do?
they invade the midgut wall of the mosquito, where they develop into oocysts
what do the oocysts do?
they grow, rupture, and release sporozoites
what do the sporozoites do?
they make their way to the mosquito’s salavary glands and get inoculated into a new human host
is malaria curable and preventable?
yes
how often does someone die of malaria in Africa?
every minute
what are the problems associated with malaria deaths?
- world-wide drug resistance
- limited acquired immunity requires repeat infections
- no vaccine with operational impact
what does it mean to have aquired immunity?
having low levels of the parasite in blood, because of living in endemic areas, and not acquiring the disease
T/F:
aquired immunity is slow to develop
True
T/F:
aquired immunity is short-lived
True
T/F:
acquired immunity means you will have sterilizing immunity
False, lower parasitemia and less symptoms will occur
what are some clinical features of malaria?
- acute febrile attacks
- splenomegaly
- coma
what occurs as a pathology in Malarial infection?
- destruction of erythrocytes
- when replicating parasites burst from the erythrocyte and the parasitic material as well as the erythrocyte material is liberated into the blood
- fever, shivering, convulsions, vomiting, anemia - caused by hemolysis
what is the classic symptom of malaria?
cyclical occurence of sudden coldness followed by stiffness and the fever and sweating lasting for 4-6 hours, occuring every two says in Pvivax and P. ovale infections and every three days in P. malariae infections
which parasite can have recurrent fever every 36-48 hours or a less pronounced and almost continuous fever?
P. falciparum
which parasites can reoccur? why?
- P. vivax and P. ovale
- the dormant stages, hypnozoites, remain in the liver
why is P. falciparum especially virulent?
it causes the expression of sticky proteins on the RBC surface, causing the RBCs to adhere to the lining of capillaries starving tissues especially the brain of oxygen
where are the knobs found?
only on Plasmodium falciparum-infected RBCs
what makes P. falciparum parasite lethal?
its ability to make RBC’s adhere, because it bypasses splenic clearance
what do knobs do?
they cause RBCs to adhere to the endothelium and to each other
the avoidance of splenic clearance leads to symptoms seen in ______ and _______.
- cerebral malaria
- maternal malaria
what is cerebral malaria?
parasites found deep in the vasculature of the brain
what is maternal malaria?
parasites adhere to the lining of the placenta, but do not cross the placental to infect the fetus
how is malaria diagnosed?
blood smear, looking for RBCs infected with Plasmodium
what are the ways to reduce human mosquito contact?
- impregnate bed nets
- repellants, protective clothing
- screens, house spraying
what are the ways to reduce vector capacity?
- environmental modification
- lavacides/insecticides
what are they ways to reduce the parasite reservoire?
- diagnosis and treatment
- prophylaxis with medications based on knowledge of geographic resistance patterns
what is the best resistance against malaria?
to avoid being bitten by mosquitos
what is DDT?
para-dichloro-diphenyltrichloroethane
what is Quinine?
toxic plant alkaloid from the bark of the cinchona tree in South America
what is special about Quinine?
it is the only drug that has remained effective at treating malaria for a long period of time
how is Quinine make today?
same way, extracted from the bark, the synthetic product is very costly
what are the quinoline based antimalarials?
- chloroquine
- mefloquine
what is Chloroquine?
- it is a synthetically manufactured product
- used as a prophylactic and for treatment
- most malaria strains are now resistant
what is mefloquine?
- quinine’s synthetic analogue
- good prophylactic because long half-life
- widespread resistance
- undesirable side effects
- cannot be used with quinine
what is atovaquone/proguanil?
- effective in otherwise resistant falciparum malaria
- expensive
- some resistance
- proguanil is an antifolate
- atovaquone inhibits electron transport and collapses mitochondrial membrane potential; acts against ubiquinol-cytochrome C oxidoreductase (complex III)
what is sulfadoxine/pyrimethamine?
- acts by interfering with folate metabolism (folate antagonist)
- resistance widespread
- side effects
- mainly in pregnant women
why is interfering with folate metabolism helpful?
because parasites have to synthesize their own folic acid and cannot import it like humans can - this applies to Toxo and Plasmodium
what is the essential cofactor in synthesis of nucleic acid precursors and some amino acids
tetrahydrofolic acid (FAH4)
what is artemisinin?
- a chinese drug that has been used as an antimalarial for over 1000 years
- schizonticide in combination with other agents
what are some parasite drug targets?
- digestive vacuole
- hemozoin
- apicoplast
- mitochondrion
- cytosol
- others
what is the new possible drug target is Plasmodium?
- the apicoplast - novel organelle with 4 membranes
- acquired by secondary endosymbiosis
the apicoplast harbours its own ______.
35kb genome
what are the possible functions of the apicoplast?
- fatty acid synthesis
- isprenoid synthesis
- heme synthesis
why are pre-erythrocyte vaccines desirable?
- they target the liver stages, which are presymptomatic and would help reduce the reservoir
what life cycle stage exists in the pre-erythrocytic stage?
merozoites
what life cycle stage would be targeted in the blood?
gametocytes
why is the blood life cycle stage target less desirable?
because it is where symptoms already occur
what are the mechanisms researched in the sporozoite?
- block hepatocyte invasion
- kill sporozoite
what are the mechanisms researched in the asexual erythrocyte phase?
- agglutinate the merozoites before schizint rupture
- block merozoite invasion of RBCs
- prevent cytoadherence of iRBCs by blocking receptor-ligand interactions (CD-36 is such a receptor)
- neutralize harmful soluble parasite toxins
what are the mechanisms researched in the sexual erythrocytic phase?
- kill gametocytes within iRBC
what is the candidate vaccine?
- RTS,S/A01
- consists of sequences of the circumsporozoite (CS) protein of the parasite and the hepatitis B surface antigen HBsAg
- for young children in malaria-endemic countries
