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  1. Phylum Apicomplexa- (genera and diseases, common physical traits)
    • Plasmodium (malaria)
    • Toxoplasma (toxoplasmosis)
    • Babesia (babesiosis)
    • Pneumocystis (pneumonia)
    • Apical complex: ring-like tubular organelles at the apical end (seen via EM)
    • found in sporozoite and merozoite stages (NEVER gametocytic)
    • *NOTE- f(x) unknown, may help to enter host cell
    • Polar rings are found below the cell membrane anteriorly
  2. Describe the physical characteristics of a Plasmodium merozoite
    • Rhoptries: elongated electron-dense bodies located within the ploar rings (extend posteriorly form membrane)
    • Subpellicular microtubules: radiate from the polar rings parallel to the cell membrane (provide support)
    • Micronemes: small structures that lay parallele to rhoptries (function unknown)
    • Cytostomes: located LATERALLY (cell mouth - pinocytosis)
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  3. Is malaria an important disease? Why or why not?  Give a brief history w/ important facts
    • Malria has killed billions overtime and led to the rise and fall of nations
    • Remains the most important disease of today in terms of death and economic burden
    • Lower rates now (>350mil deaths in 1948, <100mil deaths in 1965, <2mil in modern time) and eradicated in some areas (US)
    • Current estimate of malarial incidence is 800 million
    • 2 billion+ still live in malaria prone areas
    • Spanish conquerors/slaves brought malaria to new world, historically US troops have been heavily diseased
    • severely affected allies AND Japanese in Pacific Islands/ SE Asia during WWII
    • #2 cause of casualty for American soldiers in Vietnam war
  4. Plasmodium- discovery
    • Discovered in India by Ronald Ross (1897)
    • Awarded nobel Prize in 1902 (VERY fast)
  5. How many spp of Plasmodium? How many affect humans? Are they similar or different?
    • >50 spp (wide variety of animals)
    • 4 spp infect humans (P. vivax, P. falciparum, P. malariae, and P. ovale)
    • Biology/life cycle is VERY similar, but there are diagnostic differences
  6. Info about plasmodium vector (name, gender differences w/ reason)
    • Anopheles mosquito
    • Females are bloodsuckers (need cholesterol to brood)
    • Males drank plant jewz, mouthpart cannot penetrate human skin
  7. Malaria Parasite life cycle - invertebrate phase (detail)
    • female Anopheles mosquito takes blood meal that contains both macrogametocytes and microgametocytes
    • gametocytes escape from RBCs and are released into stomach lumen (unaffected by gastric juices)
    • Macrogametocytes develop into macrogametes (nucleus moves from center to periphery of cell)
    • exflagellation: (microgametocyte maturation) nucleus undergoes 3 mitotic divisions producing 6-8 daughter nuclei that rapidy giv rise to microgrametes
    • *NOTE- flagella develops, equal to # nuclei
    • Microgamete swims about (flagella) until it penetrates/fertilizes macrogamete
    • ookinate: delongated, motile, wormlike diploid zygote formed after fertilization
    • oocyst: rounded stage formed after ookinete penetrates the gut wall of mosquito
    • Sporogeny occurs within oocyst to produce many sporozoites, ruptures, and sporozoites migrate to salivary gland for host injection
  8. Describe the sexual phases of Plasmodium life cycle (do not describe entire life cycle).  Who is definitive host? intermediate?
    • schizogony: asexual phase
    • occurs in humans
    • Gamogony: sexual phase
    • occurs in mosquito
    • Sprogony: asexual phase
    • occurs in mosquito
    • Mosquito is definitive host (sexual rep occurs)
    • *NOTE- alt. argument- gametocytes form in human blood and fertilization occurs "in human blood" within mosquito so human is definitive
  9. Malaria Parasite life cycle - vertebrate phase (detail)
    • Infected Anopheles injects saliva contaminated with sporozoites (tiny, elongated) when taking blood meal
    • Within 1 hour sporozoites disappear from circulating blood, and reappear 24-48 hours later in parenchymal cells of liver
    • primary exoerythrocytic schozogonic cycle: inside liver cells
    • sporozoites develop into trophozoites by feeding on host cytoplasm via cytostome (pinocytosis)
    • Apical complex organelles disappear and pseudopodia develop
    • After 1 week trophozoite's nucleus divides rapidly, followed by cytokinesis producing 100s of merozoites
    • *NOTE- merozoites are ~2.5um x 1.5um
    • Merozites rupture from host's liver cells, reenter circulation, and invade RBCs
    • erythrocytic schizogonic cycle: inside RBCs
    • Merozoite transforms into trophozoite on entry to RBC
    • *****parasitophorous vacuole?
    • Trophozoite ingests host cytoplasm and gives appearance of a ring of cytoplasm with a dotlike nucleus (signet ring stage)
    • Trophozoites feed on host hemoglobin, grow, then undergo multipe fission as schizonts producing merozoites (specific number based on spp)
    • *NOTE- each of these merozoites is capable of infecting a new erythrocyte
    • Merozoites may repeat cycle OR may differentiate to male microgametocyte (AKA microgamont) or female macrogametocyte (AKA macrogamont)
    • *NOTE- gametocytes are quickly destroyed by the immune system unless ingested by a mosquito
    • Ingestion of gametocytes by mosquito causes infection of mosquito and continuation of life cycle
  10. (Plasmodium) How long does development of sporozites take? How long do mosquitos remain infective? What alternate means of Plasmodium infection are there?
    • 10-14 days depending on spp
    • Mosquitos remain infective for life
    • Can be transmitted by blood transfusion or syringe
  11. P. vivax and P. ovale- disease, RBC age, RBC size, unique clinical appearances (physical, reproductive, disease-related, developmental stages)
    • Benign tertian malaria
    • Attracted to reticulocytes (immature RBC)
    • Large erythrocytes is diagnostic feature
    • *NOTE- size in P. vivax is much more pronounced than in P. ovale
    • Schuffner's dots
    • 12-24 merozoites produced during schizogony (~1.5um each)
    • Ruptures from RBCs occur at 48 hour intervals with accompanying fever
    • Gametocytes begin to appear ~4 days
    • Macrogametocytes:microgametocytes::2:1
    • Gametocytes ~10um completely fill infected RBC
  12. Types of granules found in Plasmodium infected RBCs (name, spp found, description, cause)
    • Schuffner's dots: products of degenerative changes in cytoplasm? (unknown)
    • Found in P. vivax and P. ovale
    • Distrubuted throughout RBC cytoplasm, stains pink or red
    • Hemozoin granules: byproducts of hemoglobin degradation
    • Found in all Plasmodium infections
    • Found in <1% of RBC population after infection
    • Maurer's dots/clefts: cytoplasmic ppts in the cytoplasm of RBCs
    • Found in P. falciparum infections
    • Ziemann's dots: hemozoin accumulation in trophozoites
    • Found in P. malariae (much more pronounced)
    • Appears during the "banded" trophozoite stage of P. malariae
  13. P. malariae- disease, RBC age, RBC size, unique clinical appearances (physical, reproductive, disease-related, developmental stages)
    • Quartan malaria
    • Likes older cells (affects ~.2% of total RBC population)
    • Infected RBC size does not change
    • Band-like appearance of trophozoites in RBCs
    • Mature trophozoites are difficult to distinguish from macrogametocytes
    • Hemozoin accumulates as a dense mass in center of schizont
    • # merozoites varies from 6-12
    • Merozoites rupture from cell every 72 hours w/ fever or seizure
    • Relapse may occur >50 years after initial infection
  14. P. malariae- disease, prevalence, RBC age, RBC size, unique clinical appearances
    (physical, reproductive, disease-related, developmental stages)
    • Malignant tertian malaria
    • Responsible for >80% of cases
    • RBCs are not enlarged and represent ~10% of total population! (WOW)
    • Multiple infection of 1 cell is common (>1 ring trophozoite and/or 2 nuclei in ring stage)
    • Schizonts produce 8-32 merozoites
    • Rupture is erratic (36-48 hour intervals) w/ fever or seizure
    • Gametocytes are elongated and remain within RBC (macrogametocytes are slightly longer and kidney shaped)
    • Maurer's dots tend to aggregate around nucear region of gametocytes
    • Only ring trophozites and gametocytes in peripheral circulation, larger trophozoites and schizonts are trapped in muscle capillaries and visceral organs
  15. Plasmodium epidemiology (geographical distribution, critical density, breeding conditions,
    • Worldwide, but particularly in tropical regions
    • determined by presence of Anopheles mosquito
    • Critical density: average # of bites/person/night
    • CD influenced by env factors that affect mosquito breeding
    • A decline in CD shows that malaria is on the decline (may disappear if treated/controlled)
    • low CD areas show stable malaria patterns with low-grade infection and little symptoms
    • population immunity is unaffected by env. and climate changes in these areas
    • high CD areas show unstable malaria patterns which are affected by env. and climate changes, leading to periods of high mortality during optimal conditions
    • 16-34C and >60% humidity are favorable Anopheles breeding conditions
  16. Describe the two different sprozoite populations of Plasmodium.  2 types of possible reinfection
    • Short prepatent sporozoites (SPP): undergo usual exoerythrocytic and erythrocytic phases of development, cause malaria
    • Long prepatent sporozoites (LPP): (AKA hypnozoites) remain dormant in hepatocytes
    • relapse may result from small # which have survived developed immunity by remaining isolated from blood (P. vivax, P. ovale)
    • recrudescence: sudden increase in what was a persistant, low-level parasite population in blood
    • relapse: exoerythrocytic stages (hyypnozoites) reactivating
  17. P. falciparum- pathogenicity, 2 basic forms of pathology w/ description
    • P. faclciparum is the most dangerous and causes the highest fatality
    • Host inflammatory reacitons: initiated by rupture of RBCs which release hemozoin, debris, and wastes causing a fever spike
    • *NOTE- this cycle is specific based on spp
    • Anemia: because RBCs are destroyed
    • only P. falciparum produces fatal disease (# parasites is so high that anemia is too severe)
    • Parasitized erythrocytes adhere to capillary walls and to each other causing vessel blockage, leading to anoxia of surrounding tissues
    • cerebral malria: blockage/anoxia in the brain
  18. define ischemia
    blocked blood supply to an organ
  19. List general symptoms of malaira
    • headache
    • fever**
    • fatigue
    • pain (muscular, back)
    • chills
    • sweating
    • dry cough
    • splenomegaly
    • nausea
    • vomiting
  20. P. falciparum- major symptoms, what can cause similar symptoms?
    • Black-water fever: massive hemolysis results in high levels of hemoglobin in urine (VERY DARK urine), high fever, vomiting with blood, and jaundice
    • Black-water fever is also associated with quinine treatment
    • abortion may occur in preggos if placental blood sinuses become blocked
  21. Describe the discovery of quinine treatment.  Why does this treatment give symptoms of P. falciparum?
    • Child w/ malaria-like symptoms visting grandparents had to swim across pond
    • Symptoms were alleviated
    • Physician visited pond and noted that leaves had leached into water
    • Free fatty acids in plasmids are prevented from binding to plasma proteins due to quinine, this leaves the fatty acids free to attack RBCs and black-water fever symptoms can occur
  22. Plasmodium- diagnosis, treatmentl
    • Microscopic demonstration of Plasmodium in blood smears
    • *NOTE- smears should be made at regular intervals of a period of days
    • treated with 4-aminoquinolines, chloroquine, and quinine
    • *NOTE- quinine's use is nearly discontinued due to black-water fever symptoms, but resistance by P. falciparum to other treatments has caused its return
    • quinghaosu (herbal product) used for 2,000 years
  23. Plasmodium- prevention, control
    • Avoidance of infected mosquito bites: screening windows, spraying house interiors with insecticides, use of mosquito nets at night
    • Use of drugs: if taken quickly treatment/prophylactics can prevent malaria infection
    • *NOTE- it is currently very difficult to find reliable, non-toxic drugs due to resistance
    • Control of malaria requires anti-mosquito measures
Card Set:
2014-10-13 05:20:00
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