Things I’m learning at med school: Malaria
Protozoan disease of the genus Plasmodium.
Transmitted only by female Anopheles mosquitos.
4 main species: P. falciparum, P. vivax. P. ovale and P. malariae (P. knowlesi may also infect humans but rarely does so, more commonly affecting monkeys).
When inside RBCs the parasite consumes intracellular proteins (particularly haemoglobin). As haem is potentially toxic, plasmodium detoxifies it to a biologically inert form (haemozoin), which can be seen as a coloured pigment.
Plasmodium alters the RBC membrane, making it irregular in shape, more antigenic and less deformable.
Mosquito inoculates plasmodial sporozoites from its salivary glands during a blood meal and motile forms of the parasite are carried rapidly in the bloodstream to the liver where they invade hepatic cells and begin a period of asexual reproduction. An amplification process produces 10,000 – 30,000 daughter merozoites.
Infected liver cells swell and burst, discharging motile merozoites into the bloodstream. RBCs are then invaded and the merozoite takes a ring form known as a trophozoite. The trophozoite multiplies, consumes haemoglobin and fills the RBC; the RBC is now known as a schizont (shown in the image above). When the RBCs rupture, daughter merozoites are released, capable of invading more RBCs and repeating the cycle.
Some parasites may develop into longer-lived gametocytes that can transmit malaria. These may be ingested by another mosquito, which forms a zygote in the insect. It matures and migrates to the salivary glands where it can be transmitted to another human host.
* * *
In P. vivax and P. ovale, a proportion of the intrahepatic forms remain dormant from 3 weeks – 1 year (or more) before reproduction begins (hypnozoites). These are the cause of relapses that characterise infection with these two species.
In P. falciparum, protuberances appear on the surface of RBCs; a specific type of adhesion protein that mediates attachment to receptors on venular and capillary endothelium (cytoadherence). This can lead to blockage and sequestration of RBCs in vital organs. May also adhere to other infected RBCs (agglutination) or non-infected RBCs (rosetting = decreased deformability). Sequestration allows parasites to develop out of reach of splenic processing and filtration, therefore only younger ring forms of asexual parasites are seen circulating in peripheral blood in P. falciparum, so peripheral parasitsaemia is an underestimated value.
Splenic filtration is accelerated (becomes enlarged in later stages).
When schizont ruptures interleukin-1 is released, which causes a fever.
Temperatures exceeding 40◦C damage mature parasites, which synchronise the malarial cycle and if left untreated will present as a tertian fever (except in P. malariae which is quartan).
First symptoms: Fever, malaise, headache, fatigue, abdominal discomfort, muscle aches, nausea, vomiting, orthostatic hypertension. May have: mild anaemia, palpable spleen, slightly enlarged liver, mild jaundice.
Severe P. falciparum: Cerebral malaria due to sequestration and agglutination. May cause coma. ~20% adult mortality.
Acidosis due to accumulation of organic acids (e.g. lactic acid released from RBCs).
Hypoglycaemia as the liver is not maintaining adequate glucose levels due to failure of hepatic gluconeogenesis. There is also increased glucose consumption by host and parasite.
Other symptoms include anaemia, renal failure, pulmonary oedema, hypotension/shock, haemorrhaging, haemoglobinuria and jaundice.
Relies on asexual parasite forms in peripheral blood smears (thick and thin; x1000 oil immersion).
Parasitsaemia expressed as number of parasitised erythocytes per 1000 RBCs.
Antibody stick or card tests can also be used using finger prick blood samples.
Quinidine – Trophozoite stage. Kills gametocytes of P. v, P. o and P. m.
Chloroquine – As above but earlier in the asexual cycle.
Others include amodiaquine, mefloquine, tetra/doxycycline, halofantrine.
Prophylaxis – malarone, chloroquine, doxycycline (these will reduce the incidence of P. f infection but cannot treat it once infected).
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