Plasmodium: Difference between revisions
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Plasmodium
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(→: updated definition to match new CATMAT definition) |
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− | * |
+ | *Mosquito-borne protozoon that causes '''malaria''' |
− | == |
+ | ==Background== |
− | === |
+ | ===Microbiology=== |
− | * Intracellular protozoal parasite of red blood cells |
||
− | * Species that cause human disease are: ''P. falciparum'', ''P. vivax'', ''P. ovale'', ''P. malariae'', and ''P. knowlesi'' (from the macaque monkey) |
||
− | ** ''P. knowlesi'' looks like ''P. malariae'' microscopically, but has a higher (>1%) parasitemia with a clinical course more like ''P. falciparum'' |
||
− | * Identified on thick-and-thin Giemsa-stained blood films |
||
+ | *Intracellular protozoal parasite of red blood cells |
||
− | === Life Cycle === |
||
+ | *Species that cause human disease are: ''P. falciparum'', ''P. vivax'', ''P. ovale'', ''P. malariae'', and ''P. knowlesi'' (from the macaque monkey) |
||
− | * Infected mosquito injects sporozoites into human |
||
+ | **''P. knowlesi'' looks like ''P. malariae'' microscopically, but has a higher (>1%) parasitemia with a clinical course more like ''P. falciparum'' |
||
− | * Sporozoites infect the hepatocytes, which develop intracellular schizonts |
||
+ | *Identified on thick-and-thin Giemsa-stained blood films |
||
− | ** ''P. vivax'' and ''P. ovale'' can have prolonged (months to years) liver stages during which the patient is asymptomatic |
||
− | * The hepatocytes rupture and release trophozoites, which infect erythrocytes and mature into trophozoites |
||
− | * Trophozoites develop into schizonts, then rupture the erythrocyte to release more merozoites |
||
− | ** These cycles of merozoite to trophoziote to schizont to merozoite explain the periodic fevers |
||
− | * Trophozoites can also develop into gametocytes (micro- or macro-gametocytes), which are taken up by the mosquito |
||
− | * In the mosquito, the micro- and macro-gametocytes join to form a zygote, which matures into an ookinete then oocyst, which releases infective sporozoites |
||
− | === |
+ | ===Life Cycle=== |
− | * Infected red blood cells adhere to endothelial cells, and clump, causing rosetting |
||
− | * This causes microvascular obstruction and ischemia, which causes cerebral malaria and metabolic acidosis |
||
− | * Can cause marrow suppression |
||
− | * ''P. falciparum'' manages to avoid splenic sequestration |
||
− | * Hypoglycemia |
||
− | ** In children, hypermetabolic and consumes glucose |
||
− | ** In adults, hyperinsulin state and quinine also contributes |
||
+ | *Infected mosquito injects sporozoites into human |
||
− | === Epidemiology === |
||
+ | *Sporozoites infect the hepatocytes, which develop intracellular schizonts |
||
− | * Transmitted by female ''Anopheles'' mosquitoes, but can also be transmitted through blood transfusions |
||
+ | **''P. vivax'' and ''P. ovale'' can have prolonged (months to years) liver stages during which the patient is asymptomatic |
||
− | * Distribution is that of the ''Anopheles'' mosquito: tropical and subtropical regions worldwide with the exception of North America, Europe, and Australia |
||
+ | *The hepatocytes rupture and release trophozoites, which infect erythrocytes and mature into trophozoites |
||
− | * Distribution varies by species |
||
+ | *Trophozoites develop into schizonts, then rupture the erythrocyte to release more merozoites |
||
− | ** ''P. falciparum'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | **These cycles of merozoite to trophoziote to schizont to merozoite explain the periodic fevers |
||
− | ** ''P. vivax'' in the Americas, India, and Southeast Asia |
||
+ | *Trophozoites can also develop into gametocytes (micro- or macro-gametocytes), which are taken up by the mosquito |
||
− | ** ''P. malariae'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | *In the mosquito, the micro- and macro-gametocytes join to form a zygote, which matures into an ookinete then oocyst, which releases infective sporozoites |
||
− | ** ''P. ovale'' in sub-Saharan Africa |
||
− | ** ''P. knowlesi'' in Southeast Asia |
||
− | * Resistance varies geographically |
||
− | ** Chloroquine-resistant ''P. falciparum'' is widespread in sub-Saharan Africa, Asia, and the Americas (except Mexico, regions west of the Panama Canal, Haiti, and the Dominican Republic) |
||
− | ** Chloroquine-resistant ''P. vivax'' is in Papua New Guinea and Indonesia, with case reports in many other countries |
||
− | ** Chloroquine-resistant ''P. malariae'' is found in Sumatra and Indonesia |
||
− | ** Amodiaquine-resistant ''P. falciparum'' can be found in Africa and Asia |
||
− | ** Mefloquine-resistant ''P. falciparum'' is in Thailand, Cambodia, Myanmar, and Vietnam, with case reports in Brazil and Africa |
||
− | ** Sulfadoxine-pyrimethamine resistance is widespread in Southeast Asia, the Amazon Basin, and Africa |
||
− | ** Atovaquone-proguanil resistance is increasing but still rare |
||
− | ** Reduced quinine susceptibility is reported in Southeast Asia, sub-Saharan Africa, and South America |
||
− | ** Reduced artemisinin susceptibility is reported in Cambodia, Thailand, Vietnam, and Myanmar |
||
− | ** Doxycycline has no known resistance |
||
+ | ===Pathophysiology=== |
||
− | == Clinical Manifestations == |
||
− | * History of travel to an endemic country |
||
− | * Non-specific febrile illness with headaches, myalgias, and malaise |
||
− | * Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever) |
||
− | ** q24h: ''P. falciparum'' |
||
− | ** q48h: ''P. vivax'' or ''P. ovale'' |
||
− | ** q72h: ''P. malariae'' |
||
+ | *Infected red blood cells adhere to endothelial cells, and clump, causing rosetting |
||
− | === Severe malaria === |
||
+ | *This causes microvascular obstruction and ischemia, which causes cerebral malaria and metabolic acidosis |
||
− | * Mostly caused by ''P. falciparum'', though can also be caused by ''P. vivax'' |
||
+ | *Can cause marrow suppression |
||
+ | *''P. falciparum'' manages to avoid splenic sequestration |
||
+ | *Hypoglycemia |
||
+ | **In children, hypermetabolic and consumes glucose |
||
+ | **In adults, hyperinsulin state and quinine also contributes |
||
− | === |
+ | ===Epidemiology=== |
− | * Clinical |
||
− | ** Prostration / impaired consciousness |
||
− | ** Respiratory distress |
||
− | ** Multiple convulsions, which can be from cerebral malaria, hypoglycemia, severe metabolic acidosis, etc |
||
− | ** Circulatory collapse |
||
− | ** Pulmonary edema |
||
− | ** Abnormal bleeding |
||
− | ** Jaundice |
||
− | ** Hemoglobinuria |
||
− | * Laboratory |
||
− | ** Severe anemia (Hb ≤ 50) |
||
− | ** Hypoglycemia (< 2.2) |
||
− | ** Acidosis (pH < 7.25 or bicarb < 15) |
||
− | ** Renal impairment (creatinine > 265) |
||
− | ** Hyperlactatemia |
||
− | ** Hyperparasitemia (≥ 2%) |
||
+ | *Transmitted by female ''Anopheles'' mosquitoes, but can also be transmitted through blood transfusions |
||
− | === Cerebral malaria === |
||
+ | *Distribution is that of the ''Anopheles'' mosquito: tropical and subtropical regions worldwide with the exception of North America, Europe, and Australia |
||
− | * Erythrocytes sequester in the cerebral microvessels |
||
+ | *Distribution varies by species |
||
+ | **''P. falciparum'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | **''P. vivax'' in the Americas, India, and Southeast Asia |
||
+ | **''P. malariae'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | **''P. ovale'' in sub-Saharan Africa |
||
+ | **''P. knowlesi'' in Southeast Asia |
||
+ | *Resistance varies geographically |
||
+ | **Chloroquine-resistant ''P. falciparum'' is widespread in sub-Saharan Africa, Asia, and the Americas (except Mexico, regions west of the Panama Canal, Haiti, and the Dominican Republic) |
||
+ | **Chloroquine-resistant ''P. vivax'' is in Papua New Guinea and Indonesia, with case reports in many other countries |
||
+ | **Chloroquine-resistant ''P. malariae'' is found in Sumatra and Indonesia |
||
+ | **Amodiaquine-resistant ''P. falciparum'' can be found in Africa and Asia |
||
+ | **Mefloquine-resistant ''P. falciparum'' is in Thailand, Cambodia, Myanmar, and Vietnam, with case reports in Brazil and Africa |
||
+ | **Sulfadoxine-pyrimethamine resistance is widespread in Southeast Asia, the Amazon Basin, and Africa |
||
+ | **Atovaquone-proguanil resistance is increasing but still rare |
||
+ | **Reduced quinine susceptibility is reported in Southeast Asia, sub-Saharan Africa, and South America |
||
+ | **Reduced artemisinin susceptibility is reported in Cambodia, Thailand, Vietnam, and Myanmar |
||
+ | **Doxycycline has no known resistance |
||
+ | ==Clinical Manifestations== |
||
− | === Malaria in pregnancy === |
||
− | * Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality |
||
+ | *History of travel to an endemic country |
||
− | === Late or relapsing malaria === |
||
+ | *Non-specific febrile illness with headaches, myalgias, and malaise |
||
− | * ''P. vivax'' and ''P. ovale'' can have liver stages that lie latent for months to years before causing relapses |
||
+ | *Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever) |
||
− | * ''P. malariae'' can have a low-level asymptomatic parasitemia lasting for years before presentation |
||
+ | **q24h: ''P. falciparum'' |
||
+ | **q48h: ''P. vivax'' or ''P. ovale'' |
||
+ | **q72h: ''P. malariae'' |
||
− | == |
+ | ===Severe malaria=== |
− | === Thick and thin peripheral blood films === |
||
− | * Thick for detecting parasites, thin for parasitemia and species |
||
− | * ''P. knowlesi'' looks similar to ''P. malariae'' but presents like ''P. falciparum'' |
||
− | * Usually done three times for improved sensitivity |
||
+ | *Mostly caused by ''P. falciparum'', though can also be caused by ''P. vivax'' |
||
− | === Rapid diagnostic antigen test (RDT) === |
||
− | * Good sensitivity and specificity for falciparum malaria, but lower sensitivity (66-88%) for non-falciparum or at low levels of parasitemia |
||
− | * May cross-react with ANA and RF, and with dengue, hepatitis C, leishmaniasis, trypanosomiasis, schistosomiasis, tuberculosis, and toxoplasmosis |
||
− | * May be positive up to 4 weeks after treatment from persistent gamecotyes and slow antigen clearance, so are not used to document treatment success |
||
− | * BinaxNow is the only test in Canada |
||
− | ** T1 band: histidine-rich protein-2 (HRP-2) of ''P. falciparum'' |
||
− | ** T2 band: aldolase, a common antigen of four species of human malaria parasites |
||
− | ** C+ / T1+ / T2+: ''P. falciparum'' or mixed |
||
− | ** C+ / T1+ / T2–: ''P. falciparum'' |
||
− | ** C+ / T1– / T2+: non-falciparum |
||
− | ** C+ / T1– / T2–: no malaria |
||
− | ** Can remain positive for up to 4 weeks due to detection of dead organisms |
||
− | === |
+ | ====CATMAT Criteria (2019)==== |
− | * PCR is available |
||
− | * Done reflexively in Ontario to confirm species and detect a mixed infection |
||
+ | *Clinical |
||
− | == Management == |
||
+ | **Prostration / impaired consciousness |
||
− | * All returned travellers with fever should have thick and thin smears to rule out malaria |
||
+ | **Respiratory distress |
||
− | * Management depends on severity, including the level of parasitemia, and country of acquisition, which predicts susceptibilities |
||
+ | **Multiple convulsions, which can be from cerebral malaria, hypoglycemia, severe metabolic acidosis, etc |
||
− | ** Most of the world is resistant; when in doubt, treat all ''P. falciparum'' malaria as chloroquine-resistant |
||
+ | **Circulatory collapse |
||
− | * All patients with ''P. falciparum'' malaria should be considered for hospital admission |
||
+ | **Pulmonary edema |
||
− | ** If severe, advocate for ICU-level care |
||
+ | **Abnormal bleeding |
||
+ | **Jaundice |
||
+ | **Hemoglobinuria |
||
+ | *Laboratory |
||
+ | **Severe anemia (Hb ≤ 70 or Hct <20%) |
||
+ | **Hypoglycemia (< 2.2) |
||
+ | **Acidosis (pH < 7.25 or bicarb < 15) |
||
+ | **Renal impairment (creatinine > 265) |
||
+ | **Hyperlactatemia |
||
+ | **Hyperparasitemia |
||
+ | ***≥ 2% for children < 5 years |
||
+ | ***≥5% for non-immune adults and children ≥ 5 years |
||
+ | ***≥10% for semi-immune adults and children ≥ 5 years |
||
+ | *Non-immune: born in non-endemic or low-transmission areas (e.g. as travellers), and those who are more than 6 to 12 months away from malaria exposure |
||
+ | *Semi-immune: birth and long-term residence in an endemic country and prior episodes of malaria |
||
− | === |
+ | ===Cerebral malaria=== |
− | * Chloroquine-sensitive ''P. falciparum'' (Mexico, Central America west of the Panama Canal, Haiti, the Dominican Republic, and most of the Middle East), ''P. vivax'', ''P. ovale'', ''P. malariae'', and ''P. knowlesi'' |
||
− | ** Oral [[Is treated by::chloroquine]] 600 mg base po once, followed by 300 mg base po at 6, 24, and 48 hours |
||
− | *** The dose for salt is 1000 mg and 500 mg |
||
− | * Chloroquine-resistant ''P. falciparum'' (most of the world) or chloroquine-resistant ''P. vivax'' (Papua New Guinea and Indonesia) |
||
− | ** [[Is treated by::Atovaquone-proguanil]] 1000/400 mg (4 tablets) po daily for 3 days |
||
− | ** Alternative: [[Is treated by::quinine]] 542 mg base (650 mg salt) po q8h for 3 to 7 days, plus [[Is treated by::doxycycline]] 100 mg po bid for 7 days |
||
− | ** Prevention of relapsing ''P. vivax'' and ''P. ovale'' |
||
− | *** Indicated for patients with prolonged exposure |
||
− | *** [[Is treated by::Primaquine]] 30 mg base daily for 14 days started concurrent with chloroquine |
||
− | **** First rule out G6PD deficiency and pregnancy |
||
− | *** If pregnant, just treat intermittently until after delivery |
||
+ | *Erythrocytes sequester in the cerebral microvessels |
||
− | === Severe malaria === |
||
− | * Usually due to ''P. falciparum'', though can also be caused by ''P. vivax'' or ''P. knowlesi'' |
||
− | * Admit to hospital, ideally ICU |
||
− | ** Frequent vitals and urine output |
||
− | ** Capillary glucose at least q4h |
||
− | * Antimalarials |
||
− | ** [[Is treated by::Artesunate]] 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours |
||
− | *** Four hours after the last dose, add one of the following |
||
− | **** [[Is treated by::Atovaquone-proguanil]] 1000/400 mg po daily for 3 days |
||
− | **** [[Is treated by::Doxycycline]] 100 mg po BID for 7 days |
||
− | **** [[Is treated by::Clindamycin]] 10 mg/kg IV followed by 5 mg/kg IV q8h for 7 days |
||
− | ** [[Is treated by::Quinine]] 5.8 mg/kg IV loading dose over 30 min followed by 8.3 mg/kg IV infused over 4 hours q8h for 7 days |
||
− | *** Dose of quinine dihydrochloride would be 7 mg/kg and 10 mg/kg |
||
− | *** Do not use loading dose if they had quinine within 24 hours or mefloquine within 2 weeks |
||
− | *** Switch to oral tablets as soon as able to swallow |
||
− | *** If no infusion pump, run the loading dose as quinine 16.7 mg/kg IV over 4 hours |
||
− | *** Concurrent to last dose of quinine |
||
− | **** [[Is treated by::Atovaquone-proguanil]] 1000/400 mg po daily for 3 days |
||
− | **** [[Is treated by::Doxycycline]] 100 mg po BID for 7 days |
||
− | **** [[Is treated by::Clindamycin]] 10mg/kg IV load followed by 5 mg/kg q8h for 7 days |
||
− | ***** [[Is treated by::Clindamycin]] is the preferred treatment in pregnant women and children under 8 years |
||
− | * Treat seizures with benzos; No role for seizure prophylaxis |
||
− | * Avoid steroids in cerebral malaria (worse outcomes) |
||
− | * Exchange transfusion has been investigated; it reduces parasitemia but has no clinically-important benefits |
||
− | ** CATMAT still recommends considering it if parasitemia ≥10% |
||
− | ** Usually 5 to 10 units of pRBC |
||
− | === |
+ | ===Malaria in pregnancy=== |
− | * Clindamycin, not doxycycline or atovaquone-proguanil, should be added to artesunate or quinine |
||
− | * Quinine and chloroquine is safe in pregnancy; artesunate safe after first trimester |
||
− | * So for chloroquine-resistant malaria in pregnancy is treated with quinine and clindamycin |
||
+ | *Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality |
||
− | == Prevention and Chemoprophylaxis == |
||
− | === Behavioural interventions === |
||
− | * Mosquito avoidance (''Anopheles'' mosquitoes are evening biters) |
||
− | ** Long sleeves & pants |
||
− | ** Insecticide-treated clothing |
||
− | ** Bed nets, screens on doors & windows |
||
+ | ===Late or relapsing malaria=== |
||
− | === Chemoprophylaxis === |
||
− | * See [[Malaria chemoprophylaxis]] |
||
+ | *''P. vivax'' and ''P. ovale'' can have liver stages that lie latent for months to years before causing relapses |
||
− | == Further Reading == |
||
+ | *''P. malariae'' can have a low-level asymptomatic parasitemia lasting for years before presentation |
||
− | * Boggild A, ''et al''. [https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2014-40/ccdr-volume-40-7-april-3-2014/ccdr-volume-40-7-april-3-2014.html Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT)]. ''CCDR'' 2014;40(7). |
||
+ | |||
+ | ==Diagnosis== |
||
+ | ===Thick and thin peripheral blood films=== |
||
+ | |||
+ | *Thick for detecting parasites, thin for parasitemia and species |
||
+ | *''P. knowlesi'' looks similar to ''P. malariae'' but presents like ''P. falciparum'' |
||
+ | *Usually done three times for improved sensitivity |
||
+ | |||
+ | ===Rapid diagnostic antigen test (RDT)=== |
||
+ | |||
+ | *Good sensitivity and specificity for falciparum malaria, but lower sensitivity (66-88%) for non-falciparum or at low levels of parasitemia |
||
+ | *May cross-react with ANA and RF, and with dengue, hepatitis C, leishmaniasis, trypanosomiasis, schistosomiasis, tuberculosis, and toxoplasmosis |
||
+ | *May be positive up to 4 weeks after treatment from persistent gamecotyes and slow antigen clearance, so are not used to document treatment success |
||
+ | *BinaxNow is the only test in Canada |
||
+ | **T1 band: histidine-rich protein-2 (HRP-2) of ''P. falciparum'' |
||
+ | **T2 band: aldolase, a common antigen of four species of human malaria parasites |
||
+ | **C+ / T1+ / T2+: ''P. falciparum'' or mixed |
||
+ | **C+ / T1+ / T2–: ''P. falciparum'' |
||
+ | **C+ / T1– / T2+: non-falciparum |
||
+ | **C+ / T1– / T2–: no malaria |
||
+ | **Can remain positive for up to 4 weeks due to detection of dead organisms |
||
+ | |||
+ | ===Molecular=== |
||
+ | |||
+ | *PCR is available |
||
+ | *Done reflexively in Ontario to confirm species and detect a mixed infection |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | *All returned travellers with fever should have thick and thin smears to rule out malaria |
||
+ | *Management depends on severity, including the level of parasitemia, and country of acquisition, which predicts susceptibilities |
||
+ | **Most of the world is resistant; when in doubt, treat all ''P. falciparum'' malaria as chloroquine-resistant |
||
+ | *All patients with ''P. falciparum'' malaria should be considered for hospital admission |
||
+ | **If severe, advocate for ICU-level care |
||
+ | |||
+ | ===Uncomplicated malaria=== |
||
+ | |||
+ | *Chloroquine-sensitive ''P. falciparum'' (Mexico, Central America west of the Panama Canal, Haiti, the Dominican Republic, and most of the Middle East), ''P. vivax'', ''P. ovale'', ''P. malariae'', and ''P. knowlesi'' |
||
+ | **Oral [[Is treated by::chloroquine]] 600 mg base po once, followed by 300 mg base po at 6, 24, and 48 hours |
||
+ | ***The dose for salt is 1000 mg and 500 mg |
||
+ | *Chloroquine-resistant ''P. falciparum'' (most of the world) or chloroquine-resistant ''P. vivax'' (Papua New Guinea and Indonesia) |
||
+ | **[[Is treated by::Atovaquone-proguanil]] 1000/400 mg (4 tablets) po daily for 3 days |
||
+ | **Alternative: [[Is treated by::quinine]] 542 mg base (650 mg salt) po q8h for 3 to 7 days, plus [[Is treated by::doxycycline]] 100 mg po bid for 7 days |
||
+ | **Prevention of relapsing ''P. vivax'' and ''P. ovale'' |
||
+ | ***Indicated for patients with prolonged exposure |
||
+ | ***[[Is treated by::Primaquine]] 30 mg base daily for 14 days started concurrent with chloroquine |
||
+ | ****First rule out G6PD deficiency and pregnancy |
||
+ | ***If pregnant, just treat intermittently until after delivery |
||
+ | |||
+ | ===Severe malaria=== |
||
+ | |||
+ | *Usually due to ''P. falciparum'', though can also be caused by ''P. vivax'' or ''P. knowlesi'' |
||
+ | *Admit to hospital, ideally ICU |
||
+ | **Frequent vitals and urine output |
||
+ | **Capillary glucose at least q4h |
||
+ | *Antimalarials |
||
+ | **[[Is treated by::Artesunate]] 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours |
||
+ | ***Four hours after the last dose, add one of the following |
||
+ | ****[[Is treated by::Atovaquone-proguanil]] 1000/400 mg po daily for 3 days |
||
+ | ****[[Is treated by::Doxycycline]] 100 mg po BID for 7 days |
||
+ | ****[[Is treated by::Clindamycin]] 10 mg/kg IV followed by 5 mg/kg IV q8h for 7 days |
||
+ | **[[Is treated by::Quinine]] 5.8 mg/kg IV loading dose over 30 min followed by 8.3 mg/kg IV infused over 4 hours q8h for 7 days |
||
+ | ***Dose of quinine dihydrochloride would be 7 mg/kg and 10 mg/kg |
||
+ | ***Do not use loading dose if they had quinine within 24 hours or mefloquine within 2 weeks |
||
+ | ***Switch to oral tablets as soon as able to swallow |
||
+ | ***If no infusion pump, run the loading dose as quinine 16.7 mg/kg IV over 4 hours |
||
+ | ***Concurrent to last dose of quinine |
||
+ | ****[[Is treated by::Atovaquone-proguanil]] 1000/400 mg po daily for 3 days |
||
+ | ****[[Is treated by::Doxycycline]] 100 mg po BID for 7 days |
||
+ | ****[[Is treated by::Clindamycin]] 10mg/kg IV load followed by 5 mg/kg q8h for 7 days |
||
+ | *****[[Is treated by::Clindamycin]] is the preferred treatment in pregnant women and children under 8 years |
||
+ | *Treat seizures with benzos; No role for seizure prophylaxis |
||
+ | *Avoid steroids in cerebral malaria (worse outcomes) |
||
+ | *Exchange transfusion has been investigated; it reduces parasitemia but has no clinically-important benefits |
||
+ | **CATMAT still recommends considering it if parasitemia ≥10% |
||
+ | **Usually 5 to 10 units of pRBC |
||
+ | |||
+ | ===Pregnancy=== |
||
+ | |||
+ | *Clindamycin, not doxycycline or atovaquone-proguanil, should be added to artesunate or quinine |
||
+ | *Quinine and chloroquine is safe in pregnancy; artesunate safe after first trimester |
||
+ | *So for chloroquine-resistant malaria in pregnancy is treated with quinine and clindamycin |
||
+ | |||
+ | ==Prevention and Chemoprophylaxis== |
||
+ | ===Behavioural interventions=== |
||
+ | |||
+ | *Mosquito avoidance (''Anopheles'' mosquitoes are evening biters) |
||
+ | **Long sleeves & pants |
||
+ | **Insecticide-treated clothing |
||
+ | **Bed nets, screens on doors & windows |
||
+ | |||
+ | ===Chemoprophylaxis=== |
||
+ | |||
+ | *See [[Malaria chemoprophylaxis]] |
||
+ | |||
+ | ==Further Reading== |
||
+ | |||
+ | *Boggild A, ''et al''. [https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2014-40/ccdr-volume-40-7-april-3-2014/ccdr-volume-40-7-april-3-2014.html Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT)]. ''CCDR'' 2014;40(7). |
||
{{DISPLAYTITLE:''Plasmodium'' species}} |
{{DISPLAYTITLE:''Plasmodium'' species}} |
Revision as of 16:34, 15 August 2020
- Mosquito-borne protozoon that causes malaria
Background
Microbiology
- Intracellular protozoal parasite of red blood cells
- Species that cause human disease are: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi (from the macaque monkey)
- P. knowlesi looks like P. malariae microscopically, but has a higher (>1%) parasitemia with a clinical course more like P. falciparum
- Identified on thick-and-thin Giemsa-stained blood films
Life Cycle
- Infected mosquito injects sporozoites into human
- Sporozoites infect the hepatocytes, which develop intracellular schizonts
- P. vivax and P. ovale can have prolonged (months to years) liver stages during which the patient is asymptomatic
- The hepatocytes rupture and release trophozoites, which infect erythrocytes and mature into trophozoites
- Trophozoites develop into schizonts, then rupture the erythrocyte to release more merozoites
- These cycles of merozoite to trophoziote to schizont to merozoite explain the periodic fevers
- Trophozoites can also develop into gametocytes (micro- or macro-gametocytes), which are taken up by the mosquito
- In the mosquito, the micro- and macro-gametocytes join to form a zygote, which matures into an ookinete then oocyst, which releases infective sporozoites
Pathophysiology
- Infected red blood cells adhere to endothelial cells, and clump, causing rosetting
- This causes microvascular obstruction and ischemia, which causes cerebral malaria and metabolic acidosis
- Can cause marrow suppression
- P. falciparum manages to avoid splenic sequestration
- Hypoglycemia
- In children, hypermetabolic and consumes glucose
- In adults, hyperinsulin state and quinine also contributes
Epidemiology
- Transmitted by female Anopheles mosquitoes, but can also be transmitted through blood transfusions
- Distribution is that of the Anopheles mosquito: tropical and subtropical regions worldwide with the exception of North America, Europe, and Australia
- Distribution varies by species
- P. falciparum in tropical and subtropical Americas, Africa, and Southeast Asia
- P. vivax in the Americas, India, and Southeast Asia
- P. malariae in tropical and subtropical Americas, Africa, and Southeast Asia
- P. ovale in sub-Saharan Africa
- P. knowlesi in Southeast Asia
- Resistance varies geographically
- Chloroquine-resistant P. falciparum is widespread in sub-Saharan Africa, Asia, and the Americas (except Mexico, regions west of the Panama Canal, Haiti, and the Dominican Republic)
- Chloroquine-resistant P. vivax is in Papua New Guinea and Indonesia, with case reports in many other countries
- Chloroquine-resistant P. malariae is found in Sumatra and Indonesia
- Amodiaquine-resistant P. falciparum can be found in Africa and Asia
- Mefloquine-resistant P. falciparum is in Thailand, Cambodia, Myanmar, and Vietnam, with case reports in Brazil and Africa
- Sulfadoxine-pyrimethamine resistance is widespread in Southeast Asia, the Amazon Basin, and Africa
- Atovaquone-proguanil resistance is increasing but still rare
- Reduced quinine susceptibility is reported in Southeast Asia, sub-Saharan Africa, and South America
- Reduced artemisinin susceptibility is reported in Cambodia, Thailand, Vietnam, and Myanmar
- Doxycycline has no known resistance
Clinical Manifestations
- History of travel to an endemic country
- Non-specific febrile illness with headaches, myalgias, and malaise
- Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever)
- q24h: P. falciparum
- q48h: P. vivax or P. ovale
- q72h: P. malariae
Severe malaria
- Mostly caused by P. falciparum, though can also be caused by P. vivax
CATMAT Criteria (2019)
- Clinical
- Prostration / impaired consciousness
- Respiratory distress
- Multiple convulsions, which can be from cerebral malaria, hypoglycemia, severe metabolic acidosis, etc
- Circulatory collapse
- Pulmonary edema
- Abnormal bleeding
- Jaundice
- Hemoglobinuria
- Laboratory
- Severe anemia (Hb ≤ 70 or Hct <20%)
- Hypoglycemia (< 2.2)
- Acidosis (pH < 7.25 or bicarb < 15)
- Renal impairment (creatinine > 265)
- Hyperlactatemia
- Hyperparasitemia
- ≥ 2% for children < 5 years
- ≥5% for non-immune adults and children ≥ 5 years
- ≥10% for semi-immune adults and children ≥ 5 years
- Non-immune: born in non-endemic or low-transmission areas (e.g. as travellers), and those who are more than 6 to 12 months away from malaria exposure
- Semi-immune: birth and long-term residence in an endemic country and prior episodes of malaria
Cerebral malaria
- Erythrocytes sequester in the cerebral microvessels
Malaria in pregnancy
- Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality
Late or relapsing malaria
- P. vivax and P. ovale can have liver stages that lie latent for months to years before causing relapses
- P. malariae can have a low-level asymptomatic parasitemia lasting for years before presentation
Diagnosis
Thick and thin peripheral blood films
- Thick for detecting parasites, thin for parasitemia and species
- P. knowlesi looks similar to P. malariae but presents like P. falciparum
- Usually done three times for improved sensitivity
Rapid diagnostic antigen test (RDT)
- Good sensitivity and specificity for falciparum malaria, but lower sensitivity (66-88%) for non-falciparum or at low levels of parasitemia
- May cross-react with ANA and RF, and with dengue, hepatitis C, leishmaniasis, trypanosomiasis, schistosomiasis, tuberculosis, and toxoplasmosis
- May be positive up to 4 weeks after treatment from persistent gamecotyes and slow antigen clearance, so are not used to document treatment success
- BinaxNow is the only test in Canada
- T1 band: histidine-rich protein-2 (HRP-2) of P. falciparum
- T2 band: aldolase, a common antigen of four species of human malaria parasites
- C+ / T1+ / T2+: P. falciparum or mixed
- C+ / T1+ / T2–: P. falciparum
- C+ / T1– / T2+: non-falciparum
- C+ / T1– / T2–: no malaria
- Can remain positive for up to 4 weeks due to detection of dead organisms
Molecular
- PCR is available
- Done reflexively in Ontario to confirm species and detect a mixed infection
Management
- All returned travellers with fever should have thick and thin smears to rule out malaria
- Management depends on severity, including the level of parasitemia, and country of acquisition, which predicts susceptibilities
- Most of the world is resistant; when in doubt, treat all P. falciparum malaria as chloroquine-resistant
- All patients with P. falciparum malaria should be considered for hospital admission
- If severe, advocate for ICU-level care
Uncomplicated malaria
- Chloroquine-sensitive P. falciparum (Mexico, Central America west of the Panama Canal, Haiti, the Dominican Republic, and most of the Middle East), P. vivax, P. ovale, P. malariae, and P. knowlesi
- Oral chloroquine 600 mg base po once, followed by 300 mg base po at 6, 24, and 48 hours
- The dose for salt is 1000 mg and 500 mg
- Oral chloroquine 600 mg base po once, followed by 300 mg base po at 6, 24, and 48 hours
- Chloroquine-resistant P. falciparum (most of the world) or chloroquine-resistant P. vivax (Papua New Guinea and Indonesia)
- Atovaquone-proguanil 1000/400 mg (4 tablets) po daily for 3 days
- Alternative: quinine 542 mg base (650 mg salt) po q8h for 3 to 7 days, plus doxycycline 100 mg po bid for 7 days
- Prevention of relapsing P. vivax and P. ovale
- Indicated for patients with prolonged exposure
- Primaquine 30 mg base daily for 14 days started concurrent with chloroquine
- First rule out G6PD deficiency and pregnancy
- If pregnant, just treat intermittently until after delivery
Severe malaria
- Usually due to P. falciparum, though can also be caused by P. vivax or P. knowlesi
- Admit to hospital, ideally ICU
- Frequent vitals and urine output
- Capillary glucose at least q4h
- Antimalarials
- Artesunate 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours
- Four hours after the last dose, add one of the following
- Atovaquone-proguanil 1000/400 mg po daily for 3 days
- Doxycycline 100 mg po BID for 7 days
- Clindamycin 10 mg/kg IV followed by 5 mg/kg IV q8h for 7 days
- Four hours after the last dose, add one of the following
- Quinine 5.8 mg/kg IV loading dose over 30 min followed by 8.3 mg/kg IV infused over 4 hours q8h for 7 days
- Dose of quinine dihydrochloride would be 7 mg/kg and 10 mg/kg
- Do not use loading dose if they had quinine within 24 hours or mefloquine within 2 weeks
- Switch to oral tablets as soon as able to swallow
- If no infusion pump, run the loading dose as quinine 16.7 mg/kg IV over 4 hours
- Concurrent to last dose of quinine
- Atovaquone-proguanil 1000/400 mg po daily for 3 days
- Doxycycline 100 mg po BID for 7 days
- Clindamycin 10mg/kg IV load followed by 5 mg/kg q8h for 7 days
- Clindamycin is the preferred treatment in pregnant women and children under 8 years
- Artesunate 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours
- Treat seizures with benzos; No role for seizure prophylaxis
- Avoid steroids in cerebral malaria (worse outcomes)
- Exchange transfusion has been investigated; it reduces parasitemia but has no clinically-important benefits
- CATMAT still recommends considering it if parasitemia ≥10%
- Usually 5 to 10 units of pRBC
Pregnancy
- Clindamycin, not doxycycline or atovaquone-proguanil, should be added to artesunate or quinine
- Quinine and chloroquine is safe in pregnancy; artesunate safe after first trimester
- So for chloroquine-resistant malaria in pregnancy is treated with quinine and clindamycin
Prevention and Chemoprophylaxis
Behavioural interventions
- Mosquito avoidance (Anopheles mosquitoes are evening biters)
- Long sleeves & pants
- Insecticide-treated clothing
- Bed nets, screens on doors & windows
Chemoprophylaxis
Further Reading
- Boggild A, et al. Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT). CCDR 2014;40(7).
References
- ^ Severe Malaria. Tropical Medicine & International Health. 2014;19:7-131. doi:10.1111/tmi.12313_2.