Malaria and Apicomplexa

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sarahmariko
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276571
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Malaria and Apicomplexa
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2014-06-11 14:51:42
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ENT156 MT3
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Malaria and Apicomplexa
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  1. Malaria
    • Disease caused by protozoa in mammals, lizards, and birds.
    • a. P. falciparum
    • b. P. vivax
    • c. P. malariae
    • d. P. ovale
    • e. P. knowlesi (SE Asia)
  2. Transmission of Malaria
    • through mosquitoes and sandflies
    • Mammals: Anopheles
    • Lizards: Culex mosquitoes and Lutziomyia sandflies
    • Birds: Culex or Anopheles
  3. Increasing Problems for Malaria
    • Resurgence in some areas
    • Drug resistance
    • Insecticide resistance in mosquito vectors
    • malaria reporting in some countries is repressed due to tourism
  4. Symptoms of malaria
    • acute malaria paroxysms
    • -periodic episodes of fever alternating with symptom free periods
    • manifesttions and severity depend on plasmodium species and host status
    • 1. immunity, general health
    • 2. nutritional state
    • 3. genetics
    • Sickle cell=immunity.
  5. Relapse of Malaria
    • Relapse:
    • 1)pathogen disappears from blood, goes dormant in some other tissue, disease ceases
    • 2)Pathogen returns to blood, disease renews
    • Recrudescence:
    • pathogen remains in blood at low levels, starts massive reproducing
    • P. falciparum: severe, cerebral malaria
  6. Malaria Paroxysm
    • Paroxysms associated with synchrony of merozoite release.
    • Between paroxysms, temperature is normal and patient feels well.
    • P. falciparum may not exhibit paroxysms
  7. Life Cycle of Plasmodium species
    • A. Four reproductive events in each cycle of
    • Plasmodium life history

    • 1. Two different repetitive asexual cycles
    • (Merogony) in the vertebrate host

    • 2. Gamete production in the vertebrate
    • (Gametogeny) infects the arthropod host

    • 3. Zygote formation leads to one asexual non-
    • repetitive cycle (Sporogony)

    • Human: sexual, definite phase
  8. Development in the Vertebrate Host
    • 1. Exoerythrocytic Merogony (outside red blood
    • cells) phase

    • 2. Asexual reproductive cycle in non circulating
    • tissues
    • a. Hepatocytes in mammals (liver)
    • b. Mononuclear phagocytes in reptiles and birds
    • Sporozites from saliva of insect invade human cell, leading to trophozoite and thus merogony (schizont to merozoite).
  9. Exoerythorocytic Merogony
    • cycle can continue in non circulating tissue. some merozoites form a lasting stage called hypnozoites which can last 20 odd years, hiding in liver. due to some trigger, they will restart cycle and you will get sick. (Recrudescence).
  10. Erythroctic Merogony and Gametogeny
  11. Development of Malaria in the Invertebrate Host
  12. Sporogony in the Anthropod Host
  13. Specific example: Plasmodium falciparum in Humans (Exoerythrocytic)
    • A. Exoerythrocytic
    • Merogony
    • 1. hepatocyte invasion
    • 2. Asexual replication, one cycle only
    • 3. 6-15 days
    • 4. 10,000 merozoites
    • 5. no overt pathology
    • 6. Hypnozoite forms not in P. falciparum
    • a)some EE forms exhibit delayed replication
    • b)Merozoites produced weeks to months after initial infections
    • c) only P. Vivax and P. ovale
    • d) RELAPSE = HYPNOZOITE
  14. Specific example: P. falciparum in humans (Erythrocytic Merogony)
    • Blood invasion
    • 1. Merozoite invasion of cell
    • a) growing parasite places demands on host cell
    • b) ultrastructural modifications of erythrocyte
    • c) collect in deep vascular system
    • 2. Trophozoite development
    • a) intracellular parasite undergoes trophic phase
    • b) young trophozoite called "ring form"
    • c) ingests host hemoglobin
    • -cytosome
    • -food vacuole
    • 2. Meront (Schizont) development
    • a) nuclear division
    • b) many nuclei (6-40)
    • c) Erythrocyte rupture and releases merozoites

    POSITIVE IF CAN ANGLE POLARIZED LIGHT
  15. Specific example: P. falciparum in humans (Gametogony in the human host)
    • 1. Microgametes (♂) & Macrogametes (♀) produced
    • 2. More common as infection progresses
    • 3. Taken up by mosquito during blood meal
  16. Specific example: P. falciparum in human host (sporogony in the mosquito vector)
    • 1. Over 400 species of mosquitoes in the genus
    • Anopheles

    • 2. About 40 are vectors of plasmodium to
    • humans
  17. Specific example: P. falciparum in human host (Zygote formation in the mosquito)
    • 1. Occurs in mosquito gut- gametes exit blood
    • cells- ♂ locates ♀, fuse

    • 2. Male gamete ‘exflagellation’ most obvious
    • a. 3X nuclearreplication
    • b. 8 microgametesformed

    3. Female gamete-no division

    • 4. Zygote formation
    • a. Zygote becomes motileookinete (~24 hr)
    • b. Ookinete transverses gut epithelium
  18. Specific example: P. falciparum in human host (Oocyst formation and sporogony)
    • 1. Ookinete becomes oocyst
    • a. Between epithelium and basal lamina
    • b. Asexual replication sporozoites
    • c. Sporozoites released
    • d. Penetrate salivary glands
  19. Controlling malaria
    • A. Drugs that kill the parasite
    • 1. Example: chloroquine
    • 2. Problems: resistance, price, side effects,
    • logistics

    • B. Insecticides that kill the mosquito vector
    • 1. Example: DDT
    • 2. Problems: resistance, logistics, environmental impacts

    C. Vaccines ????

    D. Genetically Modified Mosquitoes (GMM)

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