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Malaria and Plasmodium

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  • 1. MALARIA & PLASMODIUM
    • Dr. Shahab Riaz
  • 2. Plasmodium
    • > 100 species
    • Both animals and humans
    • P. vivax  Benign Tertian Malaria (humans)
    • P. ovale  Benign Tertian Malaria (humans)
    • P. malariae  Benign Quartan Malaria (humans/chimpanzees)
    • P. falciparum  Malignant Tertian Malaria (humans)
  • 3. Plasmodia
  • 4. Important Terms
    • Cycle:
    • Asexual cycle in man, sexual cycle in mosquito
    • Trophozoites:
    • Growing form in human blood (ring form and all stages onwards except fully grown gametocytes and Schizonts)
    • Schizont:
    • Asexually dividing form
    • i) Immature schizont
    • ii) Mature schizont
    • Schizogony:
    • Asexual reproduction  N/C divides  Merozoites in RBC and liver
    • Sporogony:
    • Sexual reproduction forming sporozoites (mosquitoes)
  • 5. Important Terms
    • Sporozoite:
    • the morphological form which develops in the mosquito salivary gland and is injected when the mosquito feeds, infecting humans.
    • Gametocyte:
    • From some trophozoites or merozoites in RBCs ???
    • It is infective to mosquito
    • Gametes:
    • From micro and macro-gametocytes
    • Macro-gamete/female (nuclear reduction 1:1)
    • Micro-gamete/male (exflagellation 1:4-8)
    • Zygote:
    • Fertilized macro-gamete
    • Ookinete:
    • A motile zygote
    • Oocyst (Spore):
    • Rounded, immotile ookinete, membranous cyst wall, containing many sporozoites
  • 6. EPIDEMIOLOGY
    • P. vivax and P. falciparum  more common
    • P. ovale  rarest of the 4 species
    • > 200 million people worldwide
    • > 1 million deaths per year
    • Most common lethal infectious disease
  • 7. EPIDEMIOLOGY
    • Tropical & subtropical areas
    • esp. Asia, Africa, Central and South America
    • Certain regions in SE Asia, S. America, E. Africa  Chloroquine Resistant strains of P. falciparum
    • I/V drug use & blood transfusions
  • 8. Habitat
  • 9. HABITAT
    • Female Anopheles  sexual cycle
    • Liver & RBCs of man  asexual cycle
    • RBC Age Variable:
    • P. vivax  youngest erythrocytes
    • P. malariae  oldest erythrocytes
    • P. falciparum  RBCs of every age
  • 10. Anopheles, Culex and Aedes aegyptii
  • 11. Morphology
  • 12. MORPHOLOGY
    • Peripheral blood stained with Leishman’s stain
    • Small Trophozoites (Ring forms):
    • Infected RBC  at first ring form
    • Dot/rod shaped nucleus (red)
    • Peripheral rim of cytoplasm (blue)
    • Central clear vacuole like area (not stained)
    • Different species have different rings
  • 13. MORPHOLOGY
    • Large Trophozoite:
    • Ring form  Large trophozoite
    • Fine grains of pigment Hematin
    • Schizont:
    • Large trophozoite  schizont  N/C fragments  merozoites
    • Gametocytes:
    • Male and female distinguishable
    • Fully grown  rounded  occupies most of RBC
    • P. falciparum  sausage shaped  crescent in RBC
  • 14. Plasmodia in RBCs
  • 15. Life Cycle
  • 16. LIFE CYCLE
    • HOST:
    • Definitive Host  Female anopheles (sexual cycle)
    • Intermediate Host  Man (asexual cycle)
    • VECTOR:
    • Female Anopheles
  • 17. LIFE CYCLE
    • Sexual cycle initiated in Humans  Gametocytes (gametogony in RBCs)  mosquitoes  fusion of M/F gametes  oocyst  many sporozoites (sporogony)
    • Sexual cycle  Sporogony (sporozoites)
    • Asexual cycle  Schizogony (schizonts)
  • 18. Simple Life Cycle Of Plasmodium
  • 19. LIFE CYCLE
    • ASEXUAL CYCLE ; SCHIZOGONY (man)
    • Pre-erythrocytic schizogony or Primary Exo-erythrocytic schizogony
    • Para-erythrocytic schizogony or Secondary Exo-erythrocytic schizogony
    • Erythrocytic schizogony
  • 20. LIFE CYCLE
    • Primary Exo-erythrocytic Schizogony
    • Salivary glands  Sporozoites  human circulation  parenchymal liver cells
    • (mosquitoes) (spindle shaped) (30 mins)
    • rounded and mature
    • to schizonts
    • Micro-merozoites
    • (circulation)
    • Nuclear division to
    • Macro-merozoites Cell rupture EEM released exo- erythrocytic merozoites
    • (re-enter liver cells)
  • 21. LIFE CYCLE
    • Secondary Exo-erythrocytic Schizogony
    • P. vivax and P. ovale  latent form (Hypnozoites)  Relapses
    • in liver
    • P. vivax, ovale and malariae  erythrocytic and pre-erythrocytic merozoites  Re-enter liver cells
  • 22. LIFE CYCLE
    • Erythrocytic Schizogony
    • Micro-merozoites  RBCs  differentiation into  amoeboid form  schizonts
    • ring shaped trophozoites filled with
    • merozoites
    • grows by Globin
    • Hematin accumulates
    • (48 hours P.ovale, vivax & falciparum)
    • Infect other merozoites released RBC rupture
    • Erythrocytes
    • (72 hours for P. malariae)
  • 23. LIFE CYCLE
    • SEXUAL CYCLE; SPOROGONY
    • (mosquito 1-3 weeks)
    • RBCs  macro-gametocytes  die in man  RBCs containing MGs  mosquito
    • micro-gametocytes live in mosquitoes or free MGs
    • Injects into humans
    • and sucks MGs macro-gamete
    • Salivary glands 4-8 micro-gametes
    • Release sporozoites in body cavities
    • micro-gametes enter at
    • macro-gamete projection
    • Oocyst ruptures
    • diploid zygote
    • Haploid sporozoites N/C division Oocyst Gut wall of mosq. motile ookinete
  • 24. Detailed Life Cycle
  • 25. Oocysts in Mosquito
  • 26. Pathogenesis
  • 27. PATHOGENESIS
    • Usual Incubation periods:
    • Vivax : 14 days
    • Malariae: 28 days
    • Falciparum: 11 days
    • Transmission:
    • Mosquito bite
    • I/V drug abuse
    • Blood transfusion
    • Transplacental (congenital)
    • FEVER, ANEMIA, SPLENOMEGALY
  • 28. PATHOGENESIS
    • Malignant Tertian Malaria (P. falciparum)
    • aka pernicious malaria
    • Most likely to be fatal / RBC lysis 24-48 hours
    • 3 weeks or more
    • Large no. of parasites in blood  RBCs of all ages
    • Infected red cells  sticky
    • Clogged capillaries  cerebral malaria (coma & death)
  • 29. PATHOGENESIS
    • Malignant Tertian Malaria (P. falciparum)
    • Life threatening hemorrhage and necrosis
    • Extensive hemolysis  hemoglobinuria  renal damage
    • Black water fever (dark urine)
    • Reddish, dark brown or black
    • Oxy-hemoglobin, met-hemoglobin, Hematin, bile
    • RE system activation and Hemolysin adds to hemolysis
    • 50% mortality rate
  • 30. PATHOGENESIS
    • Splenomegaly (all malarias):
    • ed RBC destruction  ed splenic sequestration  sinusoidal congestion
    • ed lymphocytic and macrophages production
  • 31. PATHOGENESIS
    • Malarial Relapses:
    • P. vivax  2 years
    • Para-erythrocytic stage  liver parenchyma  dormant but viable
    • Resistance lowered  released and activated  complete erythrocytic cycle
    • Not in P. falciparum as no para-erythrocytic stage
    • Transmission other than mosquito bites no relapses
  • 32. Natural Protection
    • Sickle cell trait (heterozygous)
    • Duffy blood group antigen –ve (homozygous recessive) (P.vivax)
    • G6PD deficiency
    • Premunition:
    • Partial immunity
    • Humoral antibodies  block merozoites from invading RBCs
    • Low level of parasitemia  low grade symptoms
  • 33. PATHOGENESIS
    • Commonly Involved Organs:
    • Changes in Blood:
    • Anemia (hemolytic)
    • Leucopenia (exception febrile)
    • Monocytosis (pigmented)
  • 34. Commonly Involved Organs:
    • Spleen:
    • Gross:
    • Enlarged
    • Congested
    • Pigmented (black colour)
    • Soft
    • Micro:
    • Congested capillaries
    • Infected RBCs
    • Hyperplasia of RE cells, containing pigments
  • 35. Commonly Involved Organs:
    • Liver:
    • Gross:
    • Enlarged
    • Congested
    • Micro:
    • Congested sinusoidal capillaries
    • Infected RBCs
    • Increased Kupffer cells (pigmented)
    • Fatty degeneration
  • 36. Commonly Involved Organs:
    • Bone Marrow:
    • Gross:
    • Pigmented (black)
    • Micro:
    • Hyperplasia
    • RE cells contain pigments
    • Infected RBCs
  • 37. Organs Involved in P. Falciparum Infection
    • Kidney:
    • Gross:
    • Congested
    • Micro:
    • Nephritis
    • Congested capillaries
    • Infected RBCs
    • Areas of hemorrhage and necrosis
  • 38. Organs Involved in P. Falciparum Infection
    • Brain:
    • Gross:
    • Congested
    • Petechiae
    • Micro:
    • Congested and blocked capillaries
    • Infected RBCs
    • Areas of hemorrhage and necrosis
  • 39. Organs Involved in P. Falciparum Infection
    • Intestine:
    • Dysenteric syndrome
    • 4. Black water fever
  • 40. Signs and Symptoms
    • Abrupt fever, chills and rigors
    • Headache, myalgia, arthralgia
    • Initially may be continuous then periodic
    • Upto 41ºC or 106 ºF
    • Nausea, vomiting, abdominal pain, anorexia, distaste of mouth
    • Drenching sweats afterwards
    • Well between febrile episodes
    • Splenomegaly
    • 1/3 hepatomegaly
    • Anemia
    • Falciparum fatal bcz of brain and kidney damage
  • 41. Lab Diagnosis
  • 42. Laboratory Diagnosis
    • Blood Exam:
    • a. Microscopic Exam:
    • Take blood during pyrexia
    • Not after even single dose of anti-malarials
    • Thick and thin smears made, dried and stained
    • Thick smear  presence of organisms
    • Thin smear  identification of species
  • 43. Laboratory Diagnosis
    • Thin Smear:
    • Single drop of blood
    • Spread to allow single cell layer
    • Leishman’s stain
    • Oil immersion lens
    • Ring shaped trophozoites in RBCs
    • P. falciparum gametocyte banana, sausage or crescent shaped
    • Other species gametocytes are spherical
    • > 5 % RBCs infected  Dx of P. falciparum
  • 44. Laboratory Diagnosis
    • Thick Smear:
    • 3-5 drops on slide allowed to dry
    • Several cell layers thick
    • Field’s stain or Giemsa stain
    • Oil immersion lens
    • Stain removes Hb from RBCs, MP easily viewed
  • 45. Thin and Thick Smear
  • 46. Laboratory Diagnosis
    • Blood Exam:
    • TLC and DLC:
    • TLC low  leucopenia
    • In fever may be high
    • Monocytosis containing pigments
  • 47. Laboratory Diagnosis
    • Biopsy:
    • BM and liver biopsies in difficult cases
    • Therapeutic Test :
    • Anti-malarials given  if fever subsides  Dx made
    • Serological Tests:
    • Fluorescent antibody testing
    • Complement fixation test
    • Flocculation test
    • Hemagglutination test
  • 48. Treatment
    • Falciparum easily treated before complications as no relapses and no para-erythrocytic stage
    • Chloroquine is treatment of choice for sensitive strains of plasmodia (merozoites)
    • Primaquine (Hypnozoites)
    • Mefloquine or quinine and doxycycline (chloroquine resistant strains of falciparum)
    • Atovaquone and proguanil (Malarone) (CR falciparum)
    • Artemether and lumefantrine   (newer)
  • 49. Prevention
    • Chemoprophylaxis
    • Mosquito netting
    • Window screens
    • Mosquito repellants
    • Protective clothing
    • Special care during night time
    • DDT or kerosene oil spray over pools of water
    • Drainage of stagnant water
    • No vaccine presently available

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