0603 - Biology of Malaria Flashcards
What is the global distribution of malaria?
Now restricted to tropical and subtropical areas, formerly widespread including europe and USA.
>90% of malaria deaths are in Africa. Serious economic burden.
What is the Cause of malaria?-
Protozoan parasite of plasmodium genus. All vertebrates can be infected by malaria parasites. Transmitted via arthropod vector (40 species of female anopheles mosquito).
What are the 5 Species that can affect humans (in order of importance).
Plasmodium Falciparum - Most lethal (cerebral malara/renal failure). Tertian malara (fevers every 48 hours).
Plasmodium Vivax - Rarely kills, but has dormant stage (hypnozoite in liver) so can relapse.
Plasmodium Ovale - Rare species, long incubation, with regular 3-month relapses (hypnozoites).
Plasmodium malariae - Quartan malaria (fevers every 72 hours), relapse episodes without hypnozoites.
Plasmodium knowlesi - Simian malaria - quotidian malaria (fevers every 24 hours).
Describe the life cycle of malaria (including naming stages)
Complex - 3 asexual stages involving reproduction, one sexual stage without reproduction.
1 - Sporozoites living in salivary glands in mosquito. Transferred in saliva during blood meal.
2 - Sporozoites travel through blood to liver, infect hepatocytes and undergoing asexual reproduction into merozoites - thousands in a single hepatocyte. It ruptures
3 - Intraerythrocytic cycle - Merozoites infect RBCs. Eats haemoglobin, divides up to 32 within 48 hours into schizont. Cell ruptures, each is able to invade another. Some of these become gametocytes.
4 - Gametocytes sucked up by uninfected mosquito. Fuse in gut to form an ookinete and forms oocyst outside gut wall.
5. Asexual multiplication into hundreds of thousands of sporozoites. Rupture Oocytes and move to salivary glands.
Describe the Erythrocyte stage of malaria.
Infects RBC as a merozoite.
In around 12 hours, grows into the ‘ring stage’
In around 36 hours, matures into a trophozoite (consuming 70% of cell Hb, using 15%)
In around 44 hours becomes a schizont
Increasing size causes cell rupture, with merozoites released.
What of parasite factors contributing to malarial morbidity?
Multiplication capacity (deplete host defences)
Red cell selectivity (e.g. for reticulocytes vs erythrocytes - anaemic faster)
Can cytoadhere and rosette - sequester in circulation. (Cytoadherence to uninfected cells, endothelial cells, placenta - allows them to evade spleen and block microvessels).
Induce cytokine release.
Antigenicity - change exposed antigens on parasite or infected RBC.
Resistance.
Why is it difficult to develop a malaria vaccine?
Immunity is poorly understood - slow to develop (multiple courses) and short-lived, and specific for a particular malaria parasite species.
Parasite generally hidden inside host cells, so can’t build effective immunity. Ig’s from immune adults can protect non-immune patients. Attenuated sporozoites can partially immunise patients, so may become basis for a vaccine.
However it will come eventually and animal results have been promising.
What are the symptoms of malaria?
Low level - fever, rigors, headache, nausea, vomiting, diarrhoea, abdo pain, lethargy.
High level - haemolytic anaemia, renal failure, hypoglycaemia, lactic acidosis, hyperpyrexia, cerebral infarctions.
How can malaria be prevented?
Wear protective clothing - particularly covering ankles.
Use a bed net.
Use insect repellent on all exposed skin
Mosquito-proof house (screens, spray, burning coils)
Prophylactic medication.
How does malaria prophylaxis work?
Not technically prophylaxis - only kills in blood AFTER it has come out of liver. Now getting drug resistant. Need to be taken before, during, and after travel. Type of prophylaxis depends on area to be visited and pattern of resistance.
How does malaria treatment work?
Depends whether uncomplicated (no severe symptoms) or complicated.
Uncomplicated - treat with ACT (artemisinin-based combination therapy). Combination to reduce resistance. And 14-day course of primaquine to kill hypnozoites.
Complicated - IV or IM Artesunate plus 3 day course of oral ACT.
