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Malaria: Epidemiology Four species: P. falciparum - PowerPoint PPT Presentation

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Malaria: Epidemiology Four species: P. falciparum, P. vivax, P. ovale, P. malariae Majority of cases are P. falciparum or P. vivax Most deaths caused by falciparum; predominates in tropical Africa, SE Asia, Haiti, Amazon basin, Dominican Republic

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Malaria epidemiology l.jpg
Malaria: Epidemiology

  • Four species: P. falciparum, P. vivax, P. ovale, P. malariae

  • Majority of cases are P. falciparum or P. vivax

  • Most deaths caused by falciparum; predominates in tropical Africa, SE Asia, Haiti, Amazon basin, Dominican Republic

  • Vivax most prevalent in Central America, Middle East, India

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Life Cycle

  • Bite of the Female Anopheles mosquito

  • Sporozoites enter the bloodstream and travel to liver

  • Divide into mature tissue schizonts, containing thousands of daughter merozoites. (exoerythrocytic stage)

  • These rupture after 6-16 days and release merozoites into the bloodstream, where they invade RBC’s (erythrocytic stage)

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Life Cycle

  • Within RBC matures from ring form to trophozoites to mature red cell schizonts (vivax, ovale, falciparum = 48 hours, falciparum = 72 hours); this is the asexual form.

  • Mature schizonts released from RBCs and can infect new red cells.

  • A few merozoites will differentiate into male or female gametocytes (the sexual form.)

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Life cycle

  • Gametocytes do nothing but circulate in the bloodstream until they are ingested again by a mosquito to complete their life cycle in the gut of the Anopheles.

  • Vivax and ovale can remain dormant in the liver as hypnozoites and cause late relapse; falciparum and malariae have no dormant phase.

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  • All malaria spp. digest red cell proteins and hemoglobin. They derive energy by anaerobic glycolysis; therefore patients are prone to hypoglycemia and lactic acidosis.

  • Parasites also deform the RBC membrane, causing hemolysis and accelerated splenic clearance.

  • Thrombocytopenia can occur due to increased splenic sequestration.

  • Release of proinflammatory cytokines during RBC lysis causes fever, chills, malaise.

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  • P. falciparum causes additional pathology by forming sticky knobs on the surface of RBCs via an interaction with actin and spectrin.

  • Knobs bind to receptors on endothelial cells causing microvascular pathology and occlusion

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Clinical manifestations

  • Fevers/chills that are cyclical

  • Sweats, headache, myalgias, fatigue, nausea, vomiting, abd pain, diarrhea, cough

  • Hepatosplenomegaly, jaundice, anemia

  • Vivax, ovale = invade young RBC’s, low level parasitemia, can have late relapse

  • Malariae = preferentially invades mature RBCs resulting in low grade parasitemia, mild symptoms

  • Falciparum = invades all ages RBCs

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  • Renal failure: due to hypovolemia, microvascular occlusion, hemolysis

  • Pulmonary: sequestration of infected RBCs in the lung can cause pulmonary edema/ARDS

  • Hypoglycemia

  • Anemia, DIC

  • Splenic rupture

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  • Travel history

  • Thick and thin smears: every 6 to 12 hours for 48 hours

  • Fluorescent microscopy

  • PCR

  • Antigen detection

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  • Outpatient vs. inpatient

  • Supportive: antipyretics, glucose containing IVF

  • No drug acts on all stages of the life cycle

  • Quinoline derivatives: inhibit heme polymerase activity resulting in accumulation of free heme which is toxic to parasites. Chlorouqine, quinine, quinidine, mefloquine (intra-RBC); primaquine (intra-erythrocytic, intrahepatic, and gametocytes)

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  • Antifolates (pyrimethamine, sulfonadmies, dapsone): kill intrahepatic forms (except hypnozoites) , gametocytes

  • Artemisinin derivatives: not available in the U.S. Bind iron, produce free radicals that damage parasites.

  • Antimicrobials: clinda, atovaquone, tetracycline—act synergistically to kill blood schizonts

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  • Chloroquine: ovale, malariae = not observed. Falciparum = widespread with exception of Haiti, Mexico, Dominican Republic. Vivax = mainly Papua New Guinea

  • Primaquine: vivax from Thailand

  • Quinoline: falciparum from SE Asia

  • Antifolate resistance: prevalent in falciparum throughout the Amazone basin, SE Asia

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  • Chloroquine (primaquine if vivax or ovale) or quinine plus antimicrobial for synergy

  • Parasitemia >5% = iv quinine

  • Exchange transfusion

  • Desferrioxamine