Malaria
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Malaria Almost all deaths are cause by falciparum Pathogenesis: Human: asexual reproduction: SPOROZOITES (infective stage) from salivary gland of mosquito carried hematogenously to • LIVER: (hepatic parenchymal cells) o intrahepatic/preerythrocytic schizogony or merogony o 1 sporozoite→10,000-30,000 merozoites o Liver cell bursts • RBC: MEROZOITES o Attachment via receptor related to Duffy bld grp Ag Fya & Fyb o Multiplication: 6-20 fold/48-72 hrs o ~50/µL of blood- symptomatic **P vivax and ovale- remain dormant (hypnozoites), 3 weeks – yrs and may cause relapses o Intraerythrocytic schizogony or merogony: merozoites→trophozoites o After 48h (72h for P malariae): trophozoites→schizonts **After series of asexual reproduction from liver or RBC: gametocytes are formed Mosquito: sexual reproduction: GAMETOCYTES (infective stage) from blood meal • MIDGUT: fertilization o zygote→ookinete (penetrates & encysts gut wall) o ookinete→oocyst expands by asexual division→ bursts and liberates sporozoites • SALIVARY GLAND: SPOROZOITES Erythrocyte changes • Consumes & degrades Hb→ polymerization →hemozoin • Alters RBC membrane P. falciparum: • ICAM-1- impt in brain • Chondroitin SO4 B- placenta • Cytoadherence • Agglutination / rosetting ** both leads to sequestration of RBCs with mature forms Other 3:
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Sequestration does not occur o P. vivax & ovale- young RBC o P. malariae- old RBC Sickle cell disease, thalassemia and G6PD deficiency- confers protection PfEMP1- mediates attachment to endothelium; most important in Ab formation in falciparum malaria
Clinical features o Classic paroxysms- P. vivax & ovale o Generalized seizures, herald devlpt of cerebral disease- P. falciparum Severe falciparum malaria Cerebral malaria o Coma- characteristic, ominous feature o Diffuse symmetric encephalopathy o Mean opening pressure ~160 mm, slightly elevated CHON o Generalized and repeated convulsions in 50% of children o Discrete spots of retinal opacification (30-60%) Hypoglycemia o Associated with poor prognosis o Quinine & quinidine- ↑pancreatic insulin Lactic acidosis o Most impt contributor to mortality o Respiratory distress / acidotic breathing- poor prognosis o Bicarbonate and lactate- best biochem prognosticators Non-cardiogenic pulmo edema o >80% mortality rate o Aggravated by overhydration Renal impairment o Common in adults o Acute tubular necrosis Hema abnormalities Liver Dysfunction o Mild hemolytic jaundice Chronic complications Tropical Splenomegaly / Hyperreactive Malarial Splenomegaly • Uninhibited production of IgM and formation of
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cryoglobulins→reticuloendothelial hyperplasia, ↑clearance activity→splenomegaly • Pancytopenia Quartan Malarial Nephropathy • Soluble immune complex injury to glomeruli • Focal / segmental GN with splitting of capillary basement membrane Diagnosis: (Table 195-5) • Demonstration of asexual forms o Thin smear- determines level of parasitemia (infected rbc/1000rbc or / 200wbc) • < 10,000- asymptomatic o Thick smear- has ↑dx sensitivity • Phagocytosed malarial pigment inside monocytes or PMNs- recent infection • Normocytic normochromic anemia • Normal WBC count • ↑ acute phase reactants • thrombocytopenia
** both have ↑ risk for hypotension if injected rapidly; should also receive 5-10% dextrose and should be tapered if illness >2 days • Artemisinin derivatives (artemether, atesunate)- for MDR malaria Uncomplicated malaria • Oral chloroquine • Sulfadoxine pyrimethamine- if R to above • If still resistant: o Quinine + tetracycline / doxycycline / clindamycin o Mefloquine o Tetracycline and doxy- CI in pregnant, <8y/o • Oral quinine- assoc w/ cinchonismtinnitus, ↑tone deafness, N/V • All antimalarial quinolones exacerbate orthostatic hypotension • Primaquine for 14 days- eradicate persistent liver stages and prevent relapse in ovale and vivax infection
Treatment: o Chloroquine- tx of choice for benign human malarias (vivax, ovale, malariae) Severe malaria • Parenteral antimalaria • Quinine- most widely used; safe • Quinidine gluconate- preferred that quinidine which is associated with dysrrhythmias & hypotension
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• • •
Sequestration does not occur o P. vivax & ovale- young RBC o P. malariae- old RBC Sickle cell disease, thalassemia and G6PD deficiency- confers protection PfEMP1- mediates attachment to endothelium; most important in Ab formation in falciparum malaria
Clinical features o Classic paroxysms- P. vivax & ovale o Generalized seizures, herald devlpt of cerebral disease- P. falciparum Severe falciparum malaria Cerebral malaria o Coma- characteristic, ominous feature o Diffuse symmetric encephalopathy o Mean opening pressure ~160 mm, slightly elevated CHON o Generalized and repeated convulsions in 50% of children o Discrete spots of retinal opacification (30-60%) Hypoglycemia o Associated with poor prognosis o Quinine & quinidine- ↑pancreatic insulin Lactic acidosis o Most impt contributor to mortality o Respiratory distress / acidotic breathing- poor prognosis o Bicarbonate and lactate- best biochem prognosticators Non-cardiogenic pulmo edema o >80% mortality rate o Aggravated by overhydration Renal impairment o Common in adults o Acute tubular necrosis Hema abnormalities Liver Dysfunction o Mild hemolytic jaundice Chronic complications Tropical Splenomegaly / Hyperreactive Malarial Splenomegaly • Uninhibited production of IgM and formation of
1
cryoglobulins→reticuloendothelial hyperplasia, ↑clearance activity→splenomegaly • Pancytopenia Quartan Malarial Nephropathy • Soluble immune complex injury to glomeruli • Focal / segmental GN with splitting of capillary basement membrane Diagnosis: (Table 195-5) • Demonstration of asexual forms o Thin smear- determines level of parasitemia (infected rbc/1000rbc or / 200wbc) • < 10,000- asymptomatic o Thick smear- has ↑dx sensitivity • Phagocytosed malarial pigment inside monocytes or PMNs- recent infection • Normocytic normochromic anemia • Normal WBC count • ↑ acute phase reactants • thrombocytopenia
** both have ↑ risk for hypotension if injected rapidly; should also receive 5-10% dextrose and should be tapered if illness >2 days • Artemisinin derivatives (artemether, atesunate)- for MDR malaria Uncomplicated malaria • Oral chloroquine • Sulfadoxine pyrimethamine- if R to above • If still resistant: o Quinine + tetracycline / doxycycline / clindamycin o Mefloquine o Tetracycline and doxy- CI in pregnant, <8y/o • Oral quinine- assoc w/ cinchonismtinnitus, ↑tone deafness, N/V • All antimalarial quinolones exacerbate orthostatic hypotension • Primaquine for 14 days- eradicate persistent liver stages and prevent relapse in ovale and vivax infection
Treatment: o Chloroquine- tx of choice for benign human malarias (vivax, ovale, malariae) Severe malaria • Parenteral antimalaria • Quinine- most widely used; safe • Quinidine gluconate- preferred that quinidine which is associated with dysrrhythmias & hypotension
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