Malaria and Plasmodium

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Malaria and Plasmodium

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

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