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Malaria - Coggle Diagram
Malaria
Epidemiology
- Malaria still close to #1 infectious cause of child mortality (TB)
- est 2-300 mil clinical cases/year
- 1 bil people are affected
- Seriously hinders social + economic development; $12 bil in direct costs (10% household spending), causes absenteeism
Deaths
Most in Africa/tropical regions, 0.5 million deaths/year, mostly children
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'Viro'logy
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Pathogen
Apicomplexa, Plasmodium [species]
- falciparum (most important)
- vivax
- ovale
- malariae
- knowles
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Life Cycle
- Mosquito, 1-2 wks (sexual)
- Liver, 1-2 wks (asexual)
- Blood (RBCs), 2-3 days (asexual)
- Disease occurs 1 wk- 1 month after infection (only in blood stage)
- Gametocytes are taken up by mosquito
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Cytoadherence/Sequestration
- Infected cell avoids splenic clearance by adhering to vessel wall/tissue (spleen is good at clearing bad RBCs in the blood)
- Depending on species of plasmodium, different areas of vessels (with different structures) will be preferred
Placental Malaria
- In mothers who had malaria when younger
- Can transfer disease to children through placenta bc there’s no clearance happening there
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Preference
- Different Plasmodium species prefer different RBCs
- falciparum likes everything, can affect >= 10% of RBCs
- vivax only affects young RBCs, affects ~1% but can still have bad symptoms
Immune Evasion
- Variation in ligand usage: EBA175 pathway. Affects everyone differently, evades some immune systems
Vector
Anopheles mosquito, only the female ones
Treatment
- Access to available interventions is poor
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Drug Targets
KAHRP
- Knockout protein, remove knobs on parasite, disable it from adhering to vascular endothelium
PTEX
- Genetic knockdown of PTEX (the translocon for PEXEL proteins) will kill parasites
- Can’t completely knock out gene, but can knock it down. More knock down = more death
- Interfere with export pathway to stop 5-10% of genome being exported, which would contain virulence and survival factors (normally, a drug target would remove 1-2 genes)
- Recent 3D atomic structure model of PTEX allows for rational drug design to block PTEX
Immunity
- Actually possible (with repeated exposure)
- Severe disease immunity develops quickly
- Broad/robust immunity takes time
- Pregnant women return to susceptible state
- RBC surfaces are highly polymorphic, changes were most likely caused because of malaria selective pressure
Prevention
Vaccine
None, yet
—> No powerful public health intervention scheme
Anti-Merozoite (Blood Stage)
- Robust immunity
- Short time to act bc this stage only lasts for about 10-20 seconds. Target primary and secondary contacts
- Most likely solution
Transmission Blocking
- Stops development in mosquito; produces Abs to protect mosquito
- Controversial. Person themselves doesn’t get protected, but can help to protect others. Ethics issues here
Pre-erythrocytic: RTSS
- Surface protein of sporozoite, mixed with Hep B
- Reduces infection risk by 30-50%
- Only lasts about 3-6 months, max a year
- Suitable short term, but not for public intervention/eradication
Pre-erythrocitic: Whole parasite
- All 5k proteins, attenuated (irradiated/genetically disabled)
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