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a complete knowledge of malaria pathophysiology

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  2. 2. Some Imp.Terminologies <ul><li>Incubation Period : From the injection of sporozoite to the point of first manifestation of clinical illness. </li></ul><ul><li>It varies from 8 to 40 days in its four diff. species </li></ul><ul><li>Microscopic threshold: The minimum level of parasitaemia necessary for their detection in the blood </li></ul><ul><li>Fever threshold: Clinical disease develop only after further multiplication . </li></ul><ul><li>Primary Attack: First Clinical illness that marks the end of incubation period. </li></ul>
  3. 3. Pathogenesis <ul><li>Malaria is initiated by the bite of an infected female anopheline mosquito & injects the malaria parasite into blood. </li></ul><ul><li>Sporozoite multiply in the parenchymal cells of liver </li></ul><ul><li>After maturation averg. 1- 2 weeks, merozoites are released and invade the erythrocytes. Microscopic threshold. </li></ul><ul><li>The infected erythrocytes rupture and release gametocytes, merozoites, pyrogens and toxins. Fever threshold </li></ul>
  4. 4. <ul><li>The febrile paroxysm comprises three successive stages. </li></ul><ul><li>Cold stage : the patient experiences intense cold & uncontrollable shivering, lasting 15 to 60 minutes. </li></ul><ul><li>Hot stage : the patient feels intensely hot fever mounts to 41C, lasting 2 to 6 hours. </li></ul><ul><li>Headache, Nausea and vomiting are common during this period. </li></ul><ul><li>Sweating stage : the patient is drenched in profuse sweat, the temp. drops rapidly and patient usually falls into deep sleep. </li></ul><ul><li>The paroxysm usually begins in early afternoon and lasts 8 to 12 hrs </li></ul>
  5. 5. <ul><li>P. malariae have afebrile period of 72hours while it is 48 hours for P. falciparum, vivax and ovale </li></ul>
  6. 6. <ul><li>During the second blood meal , the RBCs infected with gametocyte are taken up by the mosquito from infected human. </li></ul><ul><li>The male & female gametes fertilize, to ultimately form the sporozoite, in the gut. </li></ul><ul><li>From the gut parasite reach the Anophele’s Salivary glands. </li></ul><ul><li>When such a Anopheles mosquito bites a human, these sporozoites repeat the Plasmodium life cycle. </li></ul>
  7. 7. What are the Reasons behind Clinical Manifestations ? <ul><li>All clinical manifestations are due to: </li></ul><ul><li>1 ) The products of Erythrocytic schizogony, following completion of erythrocytic schizogony. </li></ul><ul><li>2) The host’s reaction to them. </li></ul><ul><li>What are these Products? </li></ul><ul><li>Red cell fragments </li></ul><ul><li>Merozoites </li></ul><ul><li>Malarial pigments. </li></ul><ul><li>Parasitic debris. </li></ul><ul><li>Macrophage and polymorph release endogenous pyrogens.. </li></ul><ul><li>Cytokines </li></ul>
  8. 8. MALIGNANT TERTIAN <ul><li>It is because….. </li></ul><ul><li>this is the most highly pathogenic of all plasmodia. P. Falciparum </li></ul><ul><li>The erythrocytic schizogony occurs in deeper capillaries of various organs.. </li></ul><ul><li>In acute falciparum malaria , following heavy infection of RBCs the RBCs becomes Deformed & sticky and adhere to one another & the capillaries of internal organs </li></ul><ul><li>Thus the infected cells are held back in the capillaries and block them leading to blockage, congestion and hypoxia related necrosis of tissues. </li></ul><ul><li>In severe cases the rate of parasitized cells may even be up to 50% </li></ul><ul><li>The cycle completes in 2- 3 weeks.. </li></ul><ul><li>COMPLICATIONS </li></ul><ul><li>CEREBRAL MALARIA  hyperpyrexia, coma, paralysis. </li></ul><ul><li>ALGID MALARIA  circulatory collapse, cold clammy skin. </li></ul><ul><li>SEPTICAEMIC MALARIA  Alveolar, coronary & renal capillaries are congested. </li></ul>
  9. 9. <ul><li>Occurs in all types of malaria. </li></ul><ul><li>Anemia is hemolytic. </li></ul><ul><li>Decreased erythropoiesis. </li></ul><ul><li>SPLENOMEGALY </li></ul><ul><li>Spleen is always enlarged in malaria. </li></ul><ul><li>Cellular hyperplasia, dilated sinusoids & accumulation of macrophages accentuate enlargement. </li></ul>ANAEMIA Some Major Complications
  10. 10. BLACK WATER FEVER <ul><li>Massive intravascular haemolysis caused by antierythrocytic antibodies </li></ul><ul><li>Mostly associated with repeated attacks of Falciparum </li></ul><ul><li>Inadequate treatment with quinine.. </li></ul><ul><li>Manifestation : </li></ul><ul><li>Bilious vomiting, </li></ul><ul><li>prostration, </li></ul><ul><li>dark red or blackish urine.. </li></ul>
  11. 12. <ul><li>TSS ( Tropical Splenomegaly syndrome) </li></ul><ul><li>A Chronic mild condition…. </li></ul><ul><li>Results from abnormal immunological response to malaria. </li></ul><ul><li>Features : </li></ul><ul><li>High titres of circulating antimalarial antibody. </li></ul><ul><li>Absence of malaria parasites, </li></ul><ul><li>Hyper Ig aemia, cryoglobulinemia. </li></ul>
  12. 13. MEROZOITE-INDUCED MALARIA <ul><li>Malaria is sporozoite induced </li></ul><ul><li>Injection of merozoites can directly lead to infection of RBCs. </li></ul><ul><li>Its self limiting. </li></ul><ul><li>This may occur in: </li></ul><ul><li>Transfusion Malaria </li></ul><ul><li>Therapeutic Malaria </li></ul><ul><li>Congenital Malaria </li></ul>
  13. 14. What is the Role of Immune system in MALARIA ? <ul><li>Innate - </li></ul><ul><li>It seems to play a very obscure role ! </li></ul><ul><li>For e.g. – Does not multiply in sickle cell, Individuals lacking Duffy blood group Ag are resistant </li></ul><ul><li>Acquired – </li></ul><ul><li>Immune System induces specific immunity with a clinical cure. </li></ul><ul><li>the parasite is continuously prevalent in blood at subclinical levels, premunition. </li></ul><ul><li>Immunity is strain specific thus infection by diff. strain of the same species is not protective. </li></ul>
  14. 15. IMMUNOPATHOLOGY <ul><li>Malaria is known to produce some depression of the immune system. </li></ul><ul><li>For e.g : Responsible for conditions such as – </li></ul><ul><li>Burkitt’s lymphoma </li></ul><ul><li>a Lymphoma due to EBV </li></ul><ul><li>Autoimmunity – </li></ul><ul><li>Erythrocytes undergo antigenic changes due to infection leading to auto immune phenomena. </li></ul>
  15. 16. <ul><li>WHY IS IT THAT PLASMODIUM </li></ul><ul><li>AFFECTS ONLY HUMANS AND NOT </li></ul><ul><li>MOSQUITOES ? </li></ul>
  16. 17. Manifestations of Severe Malaria <ul><li>Prostration </li></ul><ul><li>Impaired consciousness/coma </li></ul><ul><li>Multiple convulsions </li></ul><ul><li>Circulatory shock </li></ul><ul><li>Jaundice </li></ul><ul><li>Severe anemia </li></ul><ul><li>Acute renal failure </li></ul><ul><li>Disseminated intravascular coagulation </li></ul><ul><li>Hemoglobinuria </li></ul>