Monday, August 12, 2013

Malaria

ConditionsDiseases List - back

ConDis

Cyclical infection of parasites that start at the liver and invade red blood cells and reinfects future mosquitos
  • 2 mil deaths in Africa

Fundamentals:

Malaria Cycle - Life Cycle of Parasite
  • Bite of infected mosquito (Anopheles sp.)
  • Mosquito injects sporozoites
  • Sporozoites invade the liver
    • Hepatocyte/Parenchymal cells - Liver
  • In the liver sporozoites transform into exoerythocytic parasites
    • Schizogony - asexual reproduction
  • Hepatocyte releases merozoites
    • Further invading liver cells
  • Exoerythrocytic parasites differeciate into gametocytes
    • Blood stream
  • Another mosquito is infected by gametocytes
    • Gametocytes transform into sporozoites
Stages of Infection
  • Liver
  • Blood - Erythrocytic

LOC:

Causes:

1)Genetic:

2)Pathogenic:

  • Infection of parasites
    • Plasmodium sp
      • P. falciparum
        • Only one patent erythrocytic cycle
      • P. vivax - N. Korea - extreme temperate areas
        • Blood stage infections
      • P. ovale
        • Blood stage infections
      • P. berghei
      • P. knowelsi - ? infectivity

3)Biochemical:

  • G6P dehy deficiency "protects against falciparum malaria"
    • Parasites require reduced glutathione and products of 5PP/PPP/3P for optimal growth

4)Anatomical:

Route Of Transmission ROT:

Pathogenesis:

1)Genetic:

2)Pathogenic:

  • Parasite invades liver cells and red blood cells
    • Parasite multiplies in cells
    • Lysis releases more parasites to infect further cells

3)Biochemical:

4)Anatomical:

Specifics:

Invasion Observations in Human Hepatoma cells (HepG2-A16) - innoculated by P. berghei
  • Parasitophorous vacuole membrane - reacts with monoclonal antibody
    • Plasma membrane of liver cell
  • As sporozite enters there is a narrow band (rhoptries) a connection from sporozite to plasma membrane
  • Sporozite is contained in the vacuole inside the cell
  • 24 hr transformation into trophozoites
  • Pellicle and subpellicular microtubules break down
Exoerythrocytic Stage
  • Schizogony occurs bet 24-48 hrs
    • Nuclear division forming many nuclei
    • EE are larger and have mroe nuclei than liver cells
  • 68 hr EE merozoites (infectious to mice)
Differenciation - Large Cells
  • Less reactive to P. vivax monoclonal antibody
  • 24 hr trophozoites transformation
  • EE parasites grow slowly until day 3
  • Day 5 nuclear division and schizonts rapidly grow until Day 9
    • May have 80 micrometer and 1k nuclei
  • Primary schizonts: small nondividing parasites evident after schizogony
    • Resemble hypnozoites - connected with liver infection relapses of malaria
Differenciation - Small Cells
  • Reactive to P. vivax monoclonal antibody
  • Small EE seen at Day 5
  • Grow until Day 9
    • May have 5-6 micrometer
  • Differenciation seems equal numbers of small and large cells


  • Sporozites are immunogenic
    • Elicit antibody response in humans = protection? Nussenzweig Immunization against sporozites
    • Species specific cirumsporozite protein antigens: covers mice/primate/human malarial sporozites
      • Interaction to the monoclonal antibodies a ruins/reduces the infectivity into hosts
        • P. knowelsi - CS protien = 12 AA repeated 12 times
        • P. falciparum - CS protien = 41 tandem repeats of tetrapeptide

Symptoms:

Diagnosis:

Treatment:

Prevention:

Additional Information:

  • Malaria and the Liver - Hollindale. 1985