The document discusses Plasmodium, the parasite that causes malaria. It describes the different Plasmodium species that infect humans, including P. falciparum which causes the most severe form of malaria. The life cycle is explained, involving an asexual replication phase in humans and a sexual phase in mosquitos. Symptoms include fever, anemia, and enlarged spleen. Diagnosis involves examining blood smears under a microscope to identify the Plasmodium species and recommend treatment, usually chloroquine for sensitive strains.

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