Malaria Flashcards
Where does the name malaria come from?
italian for bad air - mal’aria. used to think that it was bad air that caused the disease
Where has malaria been eliminated from?
Europe, North America, and the Caribbean
Which genus of parasites causes malaria?
Plasmodium
How prevalent is malaria?
fifth cause of death from infectious diseases worldwide and second in Africa
Why does malaria affect a lot of children under the age of 5?
They have a weaker immune system than older children and adults
What type of parasite is malaria?
obligate intracellular parasite
How is the parasite transmitted?
through the bite of a female Anopheles mosquito
How many species of Anopheles can transmit malaria?
60 species out of 380 known species
Why does water accumulation affect the spread of this disease?
because the mosquitoes breed in water
Why is the Anopheles gambiae species so potent in Africa?
this mosquito chooses to bite humans over any other species of animal, allowing the disease to rapidly spread between people
Is there a vector species in Canada?
yes, so malaria traveled here, it would spread
Which four malaria species cause malaria in humans?
P. falciparum, P. vivax, P. malariae, P. ovale
Why are there so many mosquito species that can transmit the parasite?
because mosquitoes are very species specific
Which malaria species are the most common?
P. falciparum and P. vivax
Which malaria species is the most deadly?
P. falciparum
Which is the only species known to infect two species, both monkeys and humans?
P. knowlesi
How have RBC adapted to reduce Plasmodium infection?
- change the surface antigen on RBC membrane
- have a mutated hemoglobin (ex. sickle-cell)
- deficient in certain enzymes to stop invasion
If there are cures for malaria, why do people still suffer from it today?
- drug resistance
- immunity requires repeated infections
- no effective vaccine
What is required to maintain acquired immunity against malaria?
continual pressure by parasite (constant infection)
What are the clinical symptoms of malaria?
acute febrile attacks (fever), splenomegaly, coma
What is the pathogenesis of malaria?
it cycles in erythrocytes and lyses them at the end of the cycle
What is the classic symptom of malaria?
sudden coldness - rigor - fever & sweating lasting 4-6 hours - repeat every 2-3 depending on species
Which malaria species has a more pronounced, almost continuous fever?
Plasmodium falciparum
Which species has a longer blood stage life cycle?
Plasmodium malariae
Which species have dormant stages in the liver?
Plasmodium vivax & ovale
How is Plasmodium falciparum more virulent than the other species?
it causes RBC to expression adhesion molecules on their surface (called knobs), making the cells stick to blood vessels and not circulate through the spleen- where abnormal RBC would be detected and removed
Which types of malaria are caused by P. falciparum due to splenectic clearance?
cerebral malaria- parasites found deep in the vasculature of the brain
maternal malaria- parasites adhere to the placental lining (can restrict blood flow to fetus)
What is the best protection against malaria?
insect repellant and bed nets
What are some ways to prevent infection?
insecticide-covered nets, repellants, protective clothing, screens, house spraying, larvacides/insecticides, biological control, environmental modification
How did they use to treat the still waters where mosquitoes breed?
used to flood the waters with oil to prevent the larvae from breathing
Which anti-malarial medication targets the dormant cells in the liver?
Primaquine
Which anti-malaria has been used for the past 350 years and how is it obtained?
Quinine is a toxic alkaloid from the bark of the Cinchona tree in South America. extracted from the bark because synthetic product is very expensive
Which two drugs are quinoline-based?
Chloroquine and mefloquine
What is chloroquine?
- synthetic 4-aminoquinoline drug
- used as prophylactin & anti-malarial drug
- most malaria strains are now resistant
What is mefloquine?
- synthetic quinine analog
- good proohylactic
- now widespread resistance
- undesirable side effects
- cannot be used with quinine
Which drugs are used with 95% efficacy against P. falciparum?
Atovaquone/Proguanil (Malarone)
- few side effects
- very expensive
- some resistant strains
- Proguanil is an antifolate
- Atovaquone inhibits ETC chain in mitochondria (targets complex III)
Which drug combination interferes with folate metabolism?
Sulfadoxine/Pyrimethamine (Fansidar)
- folate antagonist
- widespread resistance
- serious side effects
- no longer recommended
Why is folate metabolism so important in some parasites?
they cannot import folic acid and need to synthesise their own
requires tetrahydrofolic acid and some amino acids
Which two genus do we know that cannot import folic acid?
Toxoplasma and Plasmodium
What is Artemisinin?
anti-malarial used in China for over 1000 years, derived from Artemesia annua plant
- now used as parental schizonticide
- most used are artesunate & artemether
How does Artemisinin work?
iron-catalysed decomposition into free radicals that damage the parasite by forming covalent adducts.
now being used with -mefloquine and other anti-malarials because of treatment failures
Which drugs can be used to target the malarial cytosol in its erythrocyte form?
antifolates, pyrimethamine-sulfadoxine, chloproguanil-dapsone, new DHFR inhibitors
Which drugs can be used to target the malarial mitocondria in its erythrocyte form?
atavaquone, tafenoquine, pyridines, new DHODH inhibitors
Which drugs can be used to target the malarial apicoplast in its erythrocyte form?
antibiotics: azithromycin, doxycycline, clindamycine, fosmidomycin
Which drugs can be used to target the malarial hemozoin in its erythrocyte form?
4-aminoquinolines: chloroquine, amodiaquine
& quinolinemethanols: quinine, mefloquine
Which drugs can be used to target the malarial vacuole in its erythrocyte form?
falcipain inhibitors
Why is it difficult to make effective vaccines against malaria?
vaccines right now target the liver stage, the 1h window right before the parasite enters the liver cell. inside the liver cells, vaccines are not effective
the erythrocyte stage window is 1min when the parasites are not within the RBCs
What vaccines against malaria do we have now?
RTS,S/AS01
-contains circumsporozoite protein of malaria + hep B surface antigen
