Malaria Flashcards
Plasmodium parasite
- lives in RBCs
- anopheles mosquito
Lifecycles
- asexual in human host
- sexual in moquito
- cell replication of merozoites by schizogony
Signs and Symptoms
-incubation period of 7-30 days following bite
-fever, headache, chillls, vomiting
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Geographical distribution
Half the worlds pop. at risk of malaria
-most malarial deaths occur in sub-saharan Africa (1 in 5 child deaths due to malaria)
Treatment for malaria
- no vaccine
- artemisinin-based combat therapy (ACT) is best treatment at present
- vector control -bed nets/insecticide
Cerebral malaria
- plasmodium falciparum (tertian peaks 48h)
- not persistent in liver
- sequestration of infected RBCs in brain
- coma
- death
ILO = the life-cycle of the malaria parasite (Plasmodium species), its vectors, the disease and its characteristic symptoms, the various approaches to control of the infection and its transmission, problems with vaccine development;
the life-cycle of the malaria parasite (Plasmodium species), its vectors, the disease and its characteristic symptoms, the various approaches to control of the infection and its transmission, problems with vaccine development;
Stages of growth
- ring stage - early stage of infection
- trophozoite (growing stage)
- merozoite (multiplication)
- gametocytes
Lifecycle- human
- Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . -parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). -Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites
- Some parasites differentiate into sexual erythrocytic stages (gametocytes)
Life-cycle mosquito
- The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal
- parasites’ multiplication in the mosquito is known as the sporogonic cycle
- While in the mosquito’s stomach, the microgametes penetrate the macrogametes generating zygotes
- zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts
- oocysts grow, rupture, and release sporozoites , which make their way to the mosquito’s salivary glands. -Inoculation of the sporozoites into a new human host
Antigenic variation in P.falciparum
-rate of change -1-2% per division
VAR genes - red cell surface - double function - variant antigen for immune evasion and adhesion to endothelial cells of capillaries
-VAR genes –> Pfemp 1 family of proteins inserted into surface of RBCs
-brain and placenta - most Pfemp1 proteins are specific for adhesion to brain endotheliea, one or two specific for placenta
-The Pfemp1 antigens that bind to placenta are immunologically cross-reactive hence only first pregnancy is threatened
Genetic resistance to malaria
- mutation in haemoglobin genes
- sickle cell anaemia (single nucleotide polymorphism (A to T) of the B-globin gene, –> glutamic acid (E/Glu) being substituted by valine (V/Val) at position 6)
- heterozygote advantage
- blood groups - duffy antigen
- HLA class I alleles (the MHC)
- interleukin-4
Duffy blood group
-duffy negative and resistance to vivax malaria
Malaria and the placenta
- infected RBCs can sequester in the venules of the placenta and brain resulting in stillbirth
- reduced diameter of foetus head
Anti malarial drugs
- quinine (tree bark cinchona)
- chloroquine
- proguanil
- mefloquine
- artemesinin (kills ring stage - before merozoites sequester in the brain)