Malaria

Malaria

1. What is Malaria?

   • mosquito borne infectious disease
     • only females feed on blood
     • larvae require still, stagnant water
   • caused by the parasitic protozoan Plasmodium
   • 300-500 million cases per year in world
   • been around for 10,000yrs

2. Life Cycle

   • shizogony = division of nuclei into thousands
     • no cytoplasm division
     • cell membrane then develops
   • (1) During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host
   • (2) Sporozoites infect liver cells
   • (3) Maturation into Shizonts
     • shizogony
   • (4) Shizonts ruptures to release merozoites
   • Sporozoites > Shizonts > Merozoites > Trophozoites (Ring Stage) > Asexual Replication > Gametocytes > Zygote > Oocyst > Sporozoites
   • (5) Merozoites infect RBC
   • (6) Develop into (ring stage) Trophozoites
     • asexual replication within erythrocytes causes maturation into shizonts again which rupture to release more merozoites
   • (7) Some parasites differentiate into gametocytes
   • (8) Another female mosquito comes along, takes blood meal while ingesting gametocytes
     • sporogonic cycle within mosquito
       • eventually producing sporozoites and infecting new host

3. Malarial Fever

   • caused by haemozoin
     • disposal product formed from digestion of blood
     • known as malarial pigment
     • attractive target for drug development
       • difficult due to antigenic variation
   • parasites digest haemoglobin to release free haem
     • free haem is toxic so it is converted to insoluble crystalline form - haemozoin
   • when RBC's rupture, haemozoin leaks and causes fever of host
   • fever pattern corresponds to erythrocyte rupture and merozoite invasion

4. Different Species

   • Plasmodium Vivax
     • same as ovale
   • Plasmodium Ovale
     • benign tertian - peaks every 48 hours
   • Plasmodium Falciparum
     • malignant tertian - peaks every 48 hours
   • Plasmodium Malariae
     • benign quartan malaira - peaks every 72 hours

5. Antigenic Variation and Sequestration

   • expression of variant antigens on surface of infected RBCs
     • immune evasion strategy
     • no mutation required
     • rate of change around 1-2% per division
       • 40-50 variant genes per clone of parasite
     • e.g. VAR genes
       • responsible for encoding PfEMP-1 family of proteins
         • inserted into surface of RBC
         • also allow for sequestration in brain by adhering to endothelial cells of capillaries
       • in P.falciparum
   • sequestration = adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites) to the endothelium of capillaries and venules

6. Genetic Resistance

   • mutations in haemoglobin genes (haemoglobinopathies)..
     • Thalassaemia a & b
       • 'sea blood'
     • sickle cell anaemia
   • Duffy -ve
     • antigen located on RBC which can function as the receptor for plasm. parasite
       • allows parasite entry to cell
         • if duffy negative, parasite cannot infect RBC
   • certain HLA alleles (MHC)
     • encode proteins involved in antigen presentation
   • Glucose-6-phosphate Dehydrogenase Deficiency
     • G6PD is an enzyme involved with glucose production in RBC

7. Malaria + the Placenta

   • infected RBC can sequester in placenta aswell as in brain
     • causes still birth
   • ultrasound scans show diameter of foetus head is signif. smaller with malaria infection
     • if infection is well treated effect is seen to be resolved by birth

8. Treatments + Prevention

   • Vector Control
     • less mosquitos around to transmit
     • 'flowerpot inspectors'
   • bed nets
     • prevent biting
     • covered in insecticides
   • possible vaccines
   • prophylactic drugs
     • insanity?
   • anti-malarial drugs
     • quinine (cinchona tree bark in peru)
     • chloroquinine
     • artemesin (chinese herb)
       • kills ring stage
       • predates quinine
   • Possible P. falciparum vaccination?
     • this species relies on single basign receptor on surface of RBC to invade cell and does so by attaching a RHS protein to the receptor
       • protein ligand is not polymorphic, vaccine containing RHS protein antibody?

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