Plasmodium: Difference between revisions
From IDWiki
Plasmodium
(Imported from text file) Â |
(→â€) |
||
(32 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
+ | *Mosquito-borne protozoon that causes '''malaria''' |
||
− | = 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) |
||
+ | **Most common cause of disease in humans is ''Plasmodium falciparum'' |
||
+ | **''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 |
||
− | * Intracellular protozoal parasite of red blood cells |
||
+ | *Sporozoites infect the hepatocytes, which develop intracellular schizonts |
||
− | * Species that cause human disease are: ''P. falciparum'', ''P. vivax'', ''P. ovale'', ''P. malariae'', and ''P. knowlesi'' (from the macaque monkey) |
||
+ | **''P. vivax'' and ''P. ovale'' can have prolonged (months to years) liver stages during which the patient is asymptomatic |
||
− | ** ''P. knowlesi'' looks like ''P. malariae'' microscopically, but has a higher (>1%) parasitemia with a clinical course more like ''P. falciparum'' |
||
+ | *The hepatocytes rupture and release trophozoites, which infect erythrocytes and mature into trophozoites |
||
− | * Identified on thick-and-thin Giemsa-stained blood films |
||
+ | *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=== |
||
− | == Life Cycle == |
||
+ | *Infected red blood cells adhere to endothelial cells, and clump, causing rosetting |
||
− | [[File:Malaria_LifeCycle_1-20181031193024771.gif|Malaria lifecycle]] |
||
+ | *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=== |
||
− | * 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 |
||
− | * Schizonts develop in the erythrocytes, then rupture |
||
+ | *Transmitted by female ''Anopheles'' mosquitoes, but can also be transmitted through blood transfusions |
||
− | == Pathogenesis == |
||
+ | *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]] |
||
+ | ***[[Chloroquine]]-resistant ''P. falciparum'' is widespread in sub-Saharan Africa, Asia, and the Americas |
||
+ | ****Chloroquine-susceptible is in Mexico, regions west/north of the Panama Canal, Haiti, and the Dominican Republic, and parts of Middle East |
||
+ | ***[[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== |
||
− | * 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 |
||
+ | *History of travel to an endemic country |
||
− | [[File:image-20181101092857464.png|image-20181101092857464]] |
||
+ | *Non-specific [[Fever in cancer patients|febrile illness]] with [[headache]], [[myalgias]], and [[malaise]] |
||
+ | *Incubation period can vary, but is generally 9 to 14 days for ''P. falciparum'', 12 to 18 days ''P. vivax'' and ''P. ovale'', and longer for others |
||
+ | *Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever) |
||
+ | **q24h: ''P. falciparum'', but wide variation |
||
+ | **q48h: ''P. vivax'' or ''P. ovale'' |
||
+ | **q72h: ''P. malariae'' |
||
+ | **May vary by timepoint in infection, with early infection having daily or more frequent fevers from shedding from the liver stage |
||
+ | *Leukopenia more common |
||
+ | *May have concurrent bacterial or other infections |
||
+ | ===Severe Malaria=== |
||
− | == Epidemiology == |
||
− | * |
+ | *Mostly caused by ''P. falciparum'', though can also be caused by ''P. vivax'' |
− | * Distribution is that of the ''Anopheles'' mosquito: tropical and subtropical regions worldwide with the exception of North America, Europe, and Australia |
||
+ | ====CATMAT Criteria (2019)==== |
||
− | [[File:image-20181031172205815.png|Distribution of Anopheles]] |
||
+ | *Severe disease is defined as the presence of any one of criteria below |
||
− | * Distribution varies by species |
||
+ | *Clinical |
||
− | ** ''P. falciparum'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | **Prostration (unable to walk to sit up without assistance) or impaired consciousness |
||
− | ** ''P. vivax'' in the Americas, India, and Southeast Asia |
||
+ | **Respiratory distress |
||
− | ** ''P. malariae'' in tropical and subtropical Americas, Africa, and Southeast Asia |
||
+ | **Multiple convulsions (>2 in 24 hours), which can be from cerebral malaria, hypoglycemia, severe metabolic acidosis, etc |
||
− | ** ''P. ovale'' in sub-Saharan Africa |
||
+ | **Circulatory collapse (SBP <80 in adults, <50 in children) |
||
− | ** ''P. knowlesi'' in Southeast Asia |
||
+ | **Pulmonary edema |
||
− | * Resistance varies geographically |
||
+ | **Abnormal bleeding |
||
− | ** 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) |
||
+ | **Jaundice (clinical or total bilirubin >25) |
||
− | ** Chloroquine-resistant ''P. vivax'' is in Papua New Guinea and Indonesia, with case reports in many other countries |
||
+ | **Hemoglobinuria (macroscopic) |
||
− | ** Chloroquine-resistant ''P. malariae'' is found in Sumatra and Indonesia |
||
+ | *Laboratory |
||
− | ** Amodiaquine-resistant ''P. falciparum'' can be found in Africa and Asia |
||
+ | **Severe anemia (Hb ≤70 or Hct <20%) |
||
− | ** Mefloquine-resistant ''P. falciparum'' is in Thailand, Cambodia, Myanmar, and Vietnam, with case reports in Brazil and Africa |
||
+ | **Hypoglycemia (<2.2) |
||
− | ** Sulfadoxine-pyrimethamine resistance is widespread in Southeast Asia, the Amazon Basin, and Africa |
||
+ | **Acidosis (pH <7.25 or bicarb <15) |
||
− | ** Atovaquone-proguanil resistance is increasing but still rare |
||
+ | **Renal impairment (creatinine >265) |
||
− | ** Reduced quinine susceptibility is reported in Southeast Asia, sub-Saharan Africa, and South America |
||
+ | **Hyperlactatemia (>5 mmol/L) |
||
− | ** Reduced artemisinin susceptibility is reported in Cambodia, Thailand, Vietnam, and Myanmar |
||
+ | **Hyperparasitemia |
||
− | ** Doxycycline has no known resistance |
||
+ | ***≥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=== |
||
− | == Presentation == |
||
+ | *Classically defined as coma not attributable to other cause such as post-ictal state, hypoglycemia, or another disease altogether[[CiteRef::2014se]] |
||
− | * History of travel to an endemic country |
||
+ | *Seizures are common |
||
− | * Non-specific febrile illness with headaches, myalgias, and malaise |
||
+ | *Most suggestive physical examination finding that helps to rule in malaria and rule out other causes of fever and coma is malarial retinopathy, which can include: |
||
− | * Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever) |
||
+ | **Patchy retinal whitening in the macula (especially peri-foveal) and/or in the peripheral retina |
||
− | ** q24h: ''P. falciparum'' |
||
+ | **White or orange discolouration of retinal vessels |
||
− | ** q48h: ''P. vivax'' or ''P. ovale'' |
||
+ | **White-centred haemorrhages |
||
− | ** q72h: ''P. malariae'' |
||
+ | **Papilloedema |
||
+ | *Pathophysiology is the sequestration of erythrocytes in the cerebral microvessels |
||
− | === |
+ | ===Blackwater Fever=== |
+ | *Caused by massive hemolysis leading to [[hemoglobinuria]], usually in the context of severe malaria but with low or undetectable parasitemia |
||
− | * Mostly caused by ''P. falciparum'', though can also be caused by ''P. vivax'' |
||
+ | *Syndrome of loin pain, [[abdominal pain]], restlessness, [[vomiting]], [[diarrhea]], and [[polyuria]] that is followed by [[oliguria]] and passage of dark red or black urine |
||
+ | *May have [[hepatosplenomegaly]], profound [[anemia]], and [[jaundice]] |
||
+ | *Unclear if it is triggered by exposure to [[quinine]] |
||
− | === |
+ | ===Malaria in Pregnancy=== |
+ | *Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality |
||
− | * Clinical |
||
+ | *''P. falciparum'' has a tropism for the placenta, and can form a reservoir for recurrence even after appropriate treatment |
||
− | ** 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%) |
||
− | === |
+ | ===Late or Relapsing Malaria=== |
+ | *''P. vivax'' and ''P. ovale'' can have liver stages (hypnozoites) that lie latent for months to years before causing relapses |
||
− | * Erythrocytes sequester in the cerebral microvessels |
||
+ | *''P. malariae'' can have a low-level asymptomatic parasitemia lasting for years before presentation |
||
+ | ==Differential Diagnosis== |
||
− | === Malaria in pregnancy === |
||
+ | *Essentially any cause of undifferentiated [[fever]] |
||
− | * Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality |
||
+ | *See also [[fever in the returned traveller]] |
||
+ | ==Diagnosis== |
||
− | === Late or relapsing malaria === |
||
+ | ===Thick and Thin Peripheral Blood Films=== |
||
+ | *Thick for detecting parasites, thin for parasitemia and species |
||
− | * ''P. vivax'' and ''P. ovale'' can have liver stages that lie latent for months to years before causing relapses |
||
+ | *Usually done three times over three days for improved sensitivity |
||
− | * ''P. malariae'' can have a low-level asymptomatic parasitemia lasting for years before presentation |
||
+ | *Clues on microscopy: |
||
+ | **Banana or crescent-shaped gametocytes: ''P. falciparum'' |
||
+ | **Only ring forms, without trophozoites: ''P. falciparum'' more likely |
||
+ | **Amoeboid trophozoite: ''P. vivax'' |
||
+ | **Ring form in an enlarged erythrocyte: ''P. vivax'' |
||
+ | **Band-shaped trophozoite: ''P. malariae'' |
||
+ | **Ring form in an oval-shaped erythrocytes: ''P. ovale'' |
||
+ | **Looks like ''P. malariae'' but clinically severe: ''P. knowlesi'' |
||
+ | ===Rapid Diagnostic Antigen Test (RDT)=== |
||
− | == Diagnosis == |
||
+ | *Detects ''Plasmodium'' antigen in circulating blood |
||
− | * Thick and thin peripheral blood films |
||
+ | *Good sensitivity and specificity for falciparum malaria, but lower sensitivity (66-88%) for non-falciparum or at low levels of parasitemia |
||
− | ** Thick for detecting parasites |
||
+ | **Aldolase less sensitive for ''P. ovale'' and ''P. malariae'' and depends on parasitemia |
||
− | ** Thin for parasitemia and species |
||
+ | **Both may cross-react with ANA and RF, and with [[dengue]], [[hepatitis C]], [[leishmaniasis]], [[trypanosomiasis]], [[schistosomiasis]], [[tuberculosis]], and [[toxoplasmosis]] |
||
− | *** ''P. knowlesi'' looks similar to ''P. malariae'' but presents like ''P. falciparum'' |
||
+ | **Increasing pfhrp2/3 mutations leading to false negatives (higher in South America and Africa)<ref>Jejaw Zeleke, A., Hailu, A., Bayih, A.G. ''et al.'' ''Plasmodium falciparum'' histidine-rich protein 2 and 3 genes deletion in global settings (2010–2021): a systematic review and meta-analysis. ''Malar J'' '''21''', 26 (2022). https://doi.org/10.1186/s12936-022-04051-7</ref> |
||
− | * Rapid diagnostic test (RDT) for antigens |
||
− | * |
+ | *BinaxNOW is the only test in Canada |
+ | **3 bands |
||
− | *** T1 band: histidine-rich protein-2 (HRP-2) of ''P. falciparum'' |
||
+ | ***C band: control |
||
− | *** T2 band: aldolase, a common antigen of four species of human malaria parasites |
||
− | *** |
+ | ***T1 band: histidine-rich protein-2 (HRP-2) of ''P. falciparum'', which is fairly specific and sensitive |
+ | ***T2 band: aldolase, a common antigen of four species of human malaria parasites |
||
− | *** C+ / T1+ / T2–: ''P. falciparum'' |
||
+ | **Interpretation |
||
− | *** C+ / T1– / T2+: non-falciparum |
||
− | *** |
+ | ***C+ / T1+ / T2+: ''P. falciparum'' or mixed |
+ | ***C+ / T1+ / T2–: ''P. falciparum'' |
||
− | *** Can remain positive for up to 4 weeks due to detection of dead organisms |
||
+ | ***C+ / T1– / T2+: non-falciparum |
||
− | * PCR is available |
||
+ | ***C+ / T1– / T2–: no malaria |
||
− | ** Done reflexively in Ontario to confirm species and detect a mixed infection |
||
+ | *Can remain positive for up to 4 weeks due to detection of dead organisms, persistent gamecotyes, and slow antigen clearance, so are not used to document treatment success |
||
+ | *Because of the low specificity, every patient with a positive RDT must have a peripheral blood film |
||
+ | ===Molecular Testing=== |
||
− | == Management == |
||
+ | *PCR and LAMP are available |
||
− | * All returned travellers with fever should have thick and thin smears to rule out malaria |
||
+ | *PCR is done reflexively in Ontario to confirm species and detect a mixed infection |
||
− | * Management depends on severity, including the level of parasitemia, and country of acquisition, which predicts susceptibilities |
||
+ | *LAMP may need to replace RDT due to increasing falciparum false-negatives |
||
− | ** 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 |
||
+ | ==Management== |
||
− | === Uncomplicated malaria === |
||
+ | *All returned travellers with fever should have thick and thin smears to rule out 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'' |
||
+ | *Management depends on species and susceptibility (predicted by country of acquisition), and severity (including the level of parasitemia) |
||
− | ** Oral chloroquine 600 mg base po once, followed by 300 mg base po at 6, 24, and 48 hours |
||
+ | **Most of the world has chloroquine-resistant ''P. falciparum'', so when in doubt, treat all ''P. falciparum'' malaria as resistant |
||
− | *** The dose for salt is 1000 mg and 500 mg |
||
+ | *All patients with ''P. falciparum'' malaria should be considered for hospital admission |
||
− | * Chloroquine-resistant ''P. falciparum'' (most of the world) or chloroquine-resistant ''P. vivax'' (Papua New Guinea and Indonesia) |
||
+ | **If severe, advocate for ICU-level care |
||
− | ** Atovaquone-proguanil 1000/400 mg (4 tablets) po daily for 3 days |
||
+ | **If severe, monitor for [[hypoglycemia]] |
||
− | ** Alternative: quinine 542 mg base (650 mg salt) po q8h for 3 to 7 days, plus doxycycline 100 mg po bid for 7 days |
||
+ | **Monitor with daily peripheral blood films until they are negative |
||
− | ** Prevention of relapsing ''P. vivax'' and ''P. ovale'' |
||
− | *** Indicated for patients with prolonged exposure |
||
− | *** Primaquine 30 mg base daily for 14 days following chloroquine |
||
− | **** First rule out G6PD deficiency and pregnancy |
||
− | *** If pregnant, just treat intermittently until after delivery |
||
− | === |
+ | ===Concurrent Supportive Care=== |
+ | *Fluid resuscitation as needed (too much may be harmful in children) |
||
− | * Usually due to ''P. falciparum'', though can also be caused by ''P. vivax'' or ''P. knowlesi'' |
||
+ | *Rule out [[hypoglycemia]] if sudden change in clinical status (worsened with [[quinine]]) |
||
− | * Admit to hospital, ideally ICU |
||
+ | *Avoid [[steroids]], which are associated with worse outcomes in cerebral malaria |
||
− | ** Frequent vitals & urine output |
||
+ | *Correct coagulopathy and bleeding with blood products and [[vitamin K]] |
||
− | ** Capillary glucose at least q4h |
||
+ | *If [[shock]] develops, treat empirically with antibiotics while getting blood cultures to rule out intercurrent [[bacteremia]] |
||
− | * 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 |
||
− | ** 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 |
||
− | * 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 |
||
− | === |
+ | ===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'' |
||
− | * Clindamycin, not doxycycline or atovaquone-proguanil, should be added to artesunate or quinine |
||
+ | **Oral [[Is treated by::chloroquine]] 600 mg base PO once, followed by 300 mg base PO at 6, 24, and 48 hours |
||
− | * Quinine and chloroquine is safe in pregnancy; artesunate safe after first trimester |
||
+ | ***The dose for salt is 1000 mg and 500 mg |
||
− | * So for chloroquine-resistant malaria in pregnancy is treated with quinine and clindamycin |
||
+ | **If from Papua New Guinea or Indonesia adjacent to Papua New Guinea, treat with [[atovaquone-proguanil]] |
||
+ | *Chloroquine-resistant ''P. falciparum'' (most of the world) or chloroquine-resistant ''P. vivax'' (Papua New Guinea and Indonesia) |
||
+ | **[[Is treated by::Atovaquone-proguanil]] 1000 mg/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'' with radical cure |
||
+ | **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 with once-weekly [[chloroquine]] |
||
+ | ===Severe Malaria=== |
||
− | === Prevention and Chemoprophylaxis === |
||
+ | *Usually due to ''P. falciparum'', though can also be caused by ''P. vivax'' or ''P. knowlesi'' |
||
− | ==== Behavioural interventions ==== |
||
+ | *Admit to hospital, ideally ICU |
||
+ | **Frequent vitals and urine output |
||
+ | **Capillary glucose at least q4h |
||
+ | **Follow peripheral blood films q12-24h until cleared, and longer if pregnant |
||
+ | ***With ''P. falciparum'', can have some fluctuations due to irregular releasing from sequestration |
||
+ | ***Parasitemia and clinical status should both improve by 48 to 72 hours |
||
+ | *Antimalarials |
||
+ | **[[Is treated by::Artesunate]] 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours |
||
+ | ***[[Artesunate]] is held in specific centres in Canada |
||
+ | ***Should be followed by weekly CBC x4 to monitor for post-artesunate delayed hemolysis |
||
+ | ***Four hours after the last dose, add one of the following: |
||
+ | ****[[Is treated by::Atovaquone-proguanil]] 1000 mg/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 |
||
+ | ***Monitor for cardiovascular toxicity ([[hypotension]] and [[QTc prolongation]]), [[ototoxicity]] ([[tinnitus]] and hearing loss), and [[hypoglycemia]] (which is exacerbated by [[quinine]]) |
||
+ | ***Concurrent to last dose of quinine |
||
+ | ****[[Is treated by::Atovaquone-proguanil]] 1000 mg/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 [[benzodiazepines]]; 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=== |
||
− | * Mosquito avoidance (''Anopheles'' mosquitoes are evening biters) |
||
− | ** Long sleeves & pants |
||
− | ** Insecticide-treated clothing |
||
− | ** Bed nets, screens on doors & windows |
||
+ | *Uncomplicated chloroquine-susceptible malaria: |
||
− | ==== Chemoprophylaxis ==== |
||
+ | **[[Chloroquine]], or [[artemether-lumefantrine]] after the first trimester |
||
+ | **Rather than terminal prophylaxis, treat with once weekly [[chloroquine]] until delivery, then reassess for terminal prophylaxis at that point |
||
+ | *Uncomplicated chloroquine-resistant ''P. falciparum'' or ''P. vivax'': |
||
+ | **[[Mefloquine]], [[quinine]], and [[clindamycin]], or [[artemether-lumefantrine]] after the first trimester |
||
+ | *Prevention of relapsing ''P. vivax'' and ''P. ovale'': |
||
+ | **Maintained [[chloroquine]] prophylaxis 300 mg base (500 mg salt) PO weekly for the duration of their pregnancy |
||
+ | **Reassess for terminal with [[primaquine]] or [[tafenoquine]] prophylaxis after delivery |
||
+ | ***[[Primaquine]] preferred if breastfeeding |
||
+ | *Severe malaria: |
||
+ | **Preferred is [[artesunate]] followed by [[clindamycin]] |
||
+ | **Alternative is [[quinine]] followed by [[clindamycin]] |
||
+ | **There are few data on [[artesunate]] in first trimester, but it appears safe, and the overall risk-benefit assessment favours treatment |
||
+ | **Monitor peripheral blood films q12-24h until cleared, and then for a few more days, to confirm clearance and no relapse from parasites sequestered in the placenta |
||
+ | *Other antimalarials |
||
+ | **[[Atovaquone-proguanil]] is likely safe and can be used after the first trimester for any of the above regimens |
||
+ | **[[Doxycycline]], [[primaquine]], and [[tafenoquine]] should be avoided in pregnancy |
||
+ | ==Prevention== |
||
− | * Chemoprophylaxis is recommended for travelers to endemic areas |
||
+ | ===Behavioural Interventions=== |
||
− | * Agent chosen based on the local drug-resistance, patient age, and pregnancy status |
||
+ | *Mosquito avoidance (''[[Anopheles species|Anopheles]]'' mosquitoes are evening biters) |
||
− | ===== Chloroquine-sensitive regions ===== |
||
+ | **Long sleeves & pants |
||
+ | **Insecticide-treated clothing |
||
+ | **Bed nets, screens on doors & windows |
||
+ | ===Chemoprophylaxis=== |
||
− | * Regions include Haiti, the Dominican Republic, Central America north of the Panama Canal, parts of Mexico, parts of South America, north Africa, parts of the Middle East, and west/central China |
||
− | ** See [https://www.canada.ca/en/public-health/services/travel-health/about-catmat/appendix-malaria-risk-recommended-chemoprophylaxis-geographic.html#tbl1 the CATMAT list] for specific countries |
||
− | * Drugs of choice |
||
− | ** Chloroquine (Aralen) preferred, though hydroxychloroquine (Plaquenil) is also acceptable |
||
− | ** Chloroquine or hydroxychloroquine once a week, from 1 week before to 4 weeks after exposure |
||
− | ** Alternatives: atovaquone-proguanil, doxycycline or mefloquine |
||
+ | *See [[Malaria chemoprophylaxis]] |
||
− | ===== Chloroquine-resistant regions ===== |
||
+ | ==Further Reading== |
||
− | * Regions include most of sub-Saharan Africa, South America, Oceania and Asia |
||
− | ** See [https://www.canada.ca/en/public-health/services/travel-health/about-catmat/appendix-malaria-risk-recommended-chemoprophylaxis-geographic.html#tbl1 the CATMAT list] for specific countries |
||
− | ** Some areas of Thailand, Myanmar (Burma), Laos and Cambodia, and southern Vietnam are both chloroquine-resistant and mefloquine-resistant |
||
− | * Drugs of choice |
||
− | ** Atovaquone-proguanil daily, from 1 day before to 1 week after exposure (because it treats the liver phase) |
||
− | ** Doxycycline daily, from 1 day before to 4 weeks after exposure (does not treat the liver phase) |
||
− | ** Mefloquine weekly, from 1 week before to 4 weeks after exposure |
||
− | ** Alternatives: primaquine daily, from 1 day before to 7 days after exposure |
||
− | *** Primaquine contraindicated in G6PD deficiency and pregnancy |
||
+ | *Boggild A, ''et al''. [https://www.canada.ca/en/public-health/services/catmat/canadian-recommendations-prevention-treatment-malaria.html Canadian recommendations for the prevention and treatment of malaria: Statements from the Committee to Advise on Tropical Medicine and Travel (CATMAT)]. |
||
− | ===== Chloroquine-and mefloquine-resistant regions ===== |
||
+ | *[https://www.cdc.gov/malaria/diagnosis_treatment/clinicians1.html CDC Treatment of Malaria: Guidelines For Clinicians (United States)] |
||
+ | {{DISPLAYTITLE:''Plasmodium''}} |
||
− | * Regions include Asia, Africa and the Amazon basin, specifically in rural, wooded regions on the Thai borders with Myanmar, Cambodia, and Laos, as well as in southern Vietnam |
||
+ | [[Category:Haemosporida]] |
||
− | * Drugs of choice |
||
+ | [[Category:Travel medicine]] |
||
− | ** Atovaquone-proguanil daily, from 1 day before to 1 week after exposure |
||
+ | [[Category:Returned travellers]] |
||
− | ** Doxycycline daily, from 1 day before to 4 weeks after exposure |
||
− | ** No approved drugs for pregnancy or children less than 5 kg, though atovaquone-proguanil may be considered after the first trimester |
||
− | |||
− | ===== Pregnancy ===== |
||
− | |||
− | * Mefloquine can be used, if they cannot avoid travelling to malaria-endemic areas |
||
− | ** Can cause neuropsychiatric symptoms |
||
− | |||
− | === Bases and Salts === |
||
− | |||
− | [[File:image-20181031221258061.png|image-20181031221258061]] |
||
− | |||
− | == 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). |
Revision as of 08:41, 19 May 2024
- 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)
- Most common cause of disease in humans is Plasmodium falciparum
- 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
- Chloroquine-resistant P. falciparum is widespread in sub-Saharan Africa, Asia, and the Americas
- Chloroquine-susceptible is in Mexico, regions west/north of the Panama Canal, Haiti, and the Dominican Republic, and parts of Middle East
- 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
- Chloroquine-resistant P. falciparum is widespread in sub-Saharan Africa, Asia, and the Americas
- 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
- Chloroquine
Clinical Manifestations
- History of travel to an endemic country
- Non-specific febrile illness with headache, myalgias, and malaise
- Incubation period can vary, but is generally 9 to 14 days for P. falciparum, 12 to 18 days P. vivax and P. ovale, and longer for others
- Fevers are often periodic, appearing based on rupture of schizonts (tertian and quartan fever)
- q24h: P. falciparum, but wide variation
- q48h: P. vivax or P. ovale
- q72h: P. malariae
- May vary by timepoint in infection, with early infection having daily or more frequent fevers from shedding from the liver stage
- Leukopenia more common
- May have concurrent bacterial or other infections
Severe Malaria
- Mostly caused by P. falciparum, though can also be caused by P. vivax
CATMAT Criteria (2019)
- Severe disease is defined as the presence of any one of criteria below
- Clinical
- Prostration (unable to walk to sit up without assistance) or impaired consciousness
- Respiratory distress
- Multiple convulsions (>2 in 24 hours), which can be from cerebral malaria, hypoglycemia, severe metabolic acidosis, etc
- Circulatory collapse (SBP <80 in adults, <50 in children)
- Pulmonary edema
- Abnormal bleeding
- Jaundice (clinical or total bilirubin >25)
- Hemoglobinuria (macroscopic)
- Laboratory
- Severe anemia (Hb ≤70 or Hct <20%)
- Hypoglycemia (<2.2)
- Acidosis (pH <7.25 or bicarb <15)
- Renal impairment (creatinine >265)
- Hyperlactatemia (>5 mmol/L)
- 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
- Classically defined as coma not attributable to other cause such as post-ictal state, hypoglycemia, or another disease altogether1
- Seizures are common
- Most suggestive physical examination finding that helps to rule in malaria and rule out other causes of fever and coma is malarial retinopathy, which can include:
- Patchy retinal whitening in the macula (especially peri-foveal) and/or in the peripheral retina
- White or orange discolouration of retinal vessels
- White-centred haemorrhages
- Papilloedema
- Pathophysiology is the sequestration of erythrocytes in the cerebral microvessels
Blackwater Fever
- Caused by massive hemolysis leading to hemoglobinuria, usually in the context of severe malaria but with low or undetectable parasitemia
- Syndrome of loin pain, abdominal pain, restlessness, vomiting, diarrhea, and polyuria that is followed by oliguria and passage of dark red or black urine
- May have hepatosplenomegaly, profound anemia, and jaundice
- Unclear if it is triggered by exposure to quinine
Malaria in Pregnancy
- Accumulation of infected erythrocytes in the placenta, causing IUGR, prematurity, and neonatal mortality
- P. falciparum has a tropism for the placenta, and can form a reservoir for recurrence even after appropriate treatment
Late or Relapsing Malaria
- P. vivax and P. ovale can have liver stages (hypnozoites) that lie latent for months to years before causing relapses
- P. malariae can have a low-level asymptomatic parasitemia lasting for years before presentation
Differential Diagnosis
- Essentially any cause of undifferentiated fever
- See also fever in the returned traveller
Diagnosis
Thick and Thin Peripheral Blood Films
- Thick for detecting parasites, thin for parasitemia and species
- Usually done three times over three days for improved sensitivity
- Clues on microscopy:
- Banana or crescent-shaped gametocytes: P. falciparum
- Only ring forms, without trophozoites: P. falciparum more likely
- Amoeboid trophozoite: P. vivax
- Ring form in an enlarged erythrocyte: P. vivax
- Band-shaped trophozoite: P. malariae
- Ring form in an oval-shaped erythrocytes: P. ovale
- Looks like P. malariae but clinically severe: P. knowlesi
Rapid Diagnostic Antigen Test (RDT)
- Detects Plasmodium antigen in circulating blood
- Good sensitivity and specificity for falciparum malaria, but lower sensitivity (66-88%) for non-falciparum or at low levels of parasitemia
- Aldolase less sensitive for P. ovale and P. malariae and depends on parasitemia
- Both may cross-react with ANA and RF, and with dengue, hepatitis C, leishmaniasis, trypanosomiasis, schistosomiasis, tuberculosis, and toxoplasmosis
- Increasing pfhrp2/3 mutations leading to false negatives (higher in South America and Africa)[1]
- BinaxNOW is the only test in Canada
- 3 bands
- C band: control
- T1 band: histidine-rich protein-2 (HRP-2) of P. falciparum, which is fairly specific and sensitive
- T2 band: aldolase, a common antigen of four species of human malaria parasites
- Interpretation
- C+ / T1+ / T2+: P. falciparum or mixed
- C+ / T1+ / T2–: P. falciparum
- C+ / T1– / T2+: non-falciparum
- C+ / T1– / T2–: no malaria
- 3 bands
- Can remain positive for up to 4 weeks due to detection of dead organisms, persistent gamecotyes, and slow antigen clearance, so are not used to document treatment success
- Because of the low specificity, every patient with a positive RDT must have a peripheral blood film
Molecular Testing
- PCR and LAMP are available
- PCR is done reflexively in Ontario to confirm species and detect a mixed infection
- LAMP may need to replace RDT due to increasing falciparum false-negatives
Management
- All returned travellers with fever should have thick and thin smears to rule out malaria
- Management depends on species and susceptibility (predicted by country of acquisition), and severity (including the level of parasitemia)
- Most of the world has chloroquine-resistant P. falciparum, so when in doubt, treat all P. falciparum malaria as resistant
- All patients with P. falciparum malaria should be considered for hospital admission
- If severe, advocate for ICU-level care
- If severe, monitor for hypoglycemia
- Monitor with daily peripheral blood films until they are negative
Concurrent Supportive Care
- Fluid resuscitation as needed (too much may be harmful in children)
- Rule out hypoglycemia if sudden change in clinical status (worsened with quinine)
- Avoid steroids, which are associated with worse outcomes in cerebral malaria
- Correct coagulopathy and bleeding with blood products and vitamin K
- If shock develops, treat empirically with antibiotics while getting blood cultures to rule out intercurrent bacteremia
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
- If from Papua New Guinea or Indonesia adjacent to Papua New Guinea, treat with atovaquone-proguanil
- 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 mg/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 with radical cure
- 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 with once-weekly chloroquine
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
- Follow peripheral blood films q12-24h until cleared, and longer if pregnant
- With P. falciparum, can have some fluctuations due to irregular releasing from sequestration
- Parasitemia and clinical status should both improve by 48 to 72 hours
- Antimalarials
- Artesunate 2.4 mg/kg IV bolus over 1-2 minutes at 0, 12, 24, and 48 hours
- Artesunate is held in specific centres in Canada
- Should be followed by weekly CBC x4 to monitor for post-artesunate delayed hemolysis
- Four hours after the last dose, add one of the following:
- Atovaquone-proguanil 1000 mg/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
- 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
- Monitor for cardiovascular toxicity (hypotension and QTc prolongation), ototoxicity (tinnitus and hearing loss), and hypoglycemia (which is exacerbated by quinine)
- Concurrent to last dose of quinine
- Atovaquone-proguanil 1000 mg/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 benzodiazepines; 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
- Uncomplicated chloroquine-susceptible malaria:
- Chloroquine, or artemether-lumefantrine after the first trimester
- Rather than terminal prophylaxis, treat with once weekly chloroquine until delivery, then reassess for terminal prophylaxis at that point
- Uncomplicated chloroquine-resistant P. falciparum or P. vivax:
- Mefloquine, quinine, and clindamycin, or artemether-lumefantrine after the first trimester
- Prevention of relapsing P. vivax and P. ovale:
- Maintained chloroquine prophylaxis 300 mg base (500 mg salt) PO weekly for the duration of their pregnancy
- Reassess for terminal with primaquine or tafenoquine prophylaxis after delivery
- Primaquine preferred if breastfeeding
- Severe malaria:
- Preferred is artesunate followed by clindamycin
- Alternative is quinine followed by clindamycin
- There are few data on artesunate in first trimester, but it appears safe, and the overall risk-benefit assessment favours treatment
- Monitor peripheral blood films q12-24h until cleared, and then for a few more days, to confirm clearance and no relapse from parasites sequestered in the placenta
- Other antimalarials
- Atovaquone-proguanil is likely safe and can be used after the first trimester for any of the above regimens
- Doxycycline, primaquine, and tafenoquine should be avoided in pregnancy
Prevention
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. Canadian recommendations for the prevention and treatment of malaria: Statements from the Committee to Advise on Tropical Medicine and Travel (CATMAT).
- CDC Treatment of Malaria: Guidelines For Clinicians (United States)
- ↑ Jejaw Zeleke, A., Hailu, A., Bayih, A.G. et al. Plasmodium falciparum histidine-rich protein 2 and 3 genes deletion in global settings (2010–2021): a systematic review and meta-analysis. Malar J 21, 26 (2022). https://doi.org/10.1186/s12936-022-04051-7
References
- ^ Severe Malaria. Tropical Medicine & International Health. 2014;19:7-131. doi:10.1111/tmi.12313_2.