eMedicine Specialties > Pediatrics: General Medicine > Parasitology
Malaria: Treatment & Medication
Updated: Apr 28, 2009
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Treatment
Medical Care
- Children with malaria who are fully conscious, who have low-to-moderate fever, and who are maintaining their nutrition and hydration orally can be treated on an outpatient basis.
- Oral paracetamol (acetaminophen) is safe and effective for fever and should be used in doses of 10 mg/kg. This dose can be repeated 3-6 times a day, as required. If the child has hyperpyrexia, tepid sponging can rapidly bring the temperature down.
- Many children with malaria develop anemia. Because onset is gradual, the child withstands a low level of hemoglobin quite well, and blood transfusions are rarely needed. Standard hematinic therapy is effective.
- If repeated vomiting has led to dehydration, the child needs appropriate parenteral fluids to correct it. Glucose-containing fluids help counter the hypoglycemia that sometimes accompanies severe malaria. Vomiting is common in malaria. An antiemetic such as domperidone can be used, and antimalarials should be continued. Vomiting stops when the malaria is cured.
- Indications for immediate hospitalization include the following:
- Intractable vomiting
- Dehydration
- Seizures
- Altered consciousness or coma
- Repeated convulsions
- Difficulty in breathing or acidotic breathing
- Severe pallor (indicating severe anemia)
- Hypoglycemia (blood glucose <2.5 mmol/L or 3 mmol/L in malnourished children)
- Oliguria or anuria, signifying renal affliction
- Shock
- Hyperparasitemia
- Bleeding diathesis
- In a child with malaria, impaired consciousness, respiratory distress, hypoglycemia, and jaundice are risk factors for death. Such a child should be treated as an emergency.
Consultations
- Consult an infectious diseases specialist.
Diet
- No restrictions are needed in the diet for patients well enough for outpatient management. Indeed, the appetite and activity level are remarkably well preserved for the degree of fever.
- Advise increased fluid intake.
Activity
- Children should be allowed to decide their own activity levels. If the fever is intermittent, many children feel quite well between paroxysms of fever and come to no harm through activity.
Medication
Blood schizonticides are the first-line drugs for the treatment of malaria and must be started as soon as the diagnosis is made or even suspected. They act on the asexual forms in the erythrocytes and interrupt clinical attacks. Delay in treatment of P falciparum malaria can lead to development of severe malaria, which has a poorer prognosis than uncomplicated malaria. Chloroquine, quinine, quinidine, mefloquine, halofantrine, and artemisinin compounds are the rapidly acting drugs that can terminate an acute malaria attack. While chloroquine acts rapidly, resistance is widespread and an accurate travel history should be obtained before choosing the antimalarial drug.
Malaria imported from Asia or the Americas is mostly P vivax and is chloroquine responsive. Malaria acquired in Africa is mostly P falciparum and is chloroquine resistant; quinine is an effective drug. P falciparum malaria incurred in South East Asia may be quinine and mefloquine resistant as well; a combination of artesunate and mefloquine is recommended. Time wasted in trials of a drug to which the parasite is resistant can result in a poor outcome, including death.
P vivax and P ovale have dormant stages (hypnozoites) in the liver, and the treatment of an episode of malaria requires eradication of these forms also. The classic treatment is a 3-day course of chloroquine, followed by a 14-day course of primaquine. A shorter course of 5 days of primaquine, started with chloroquine, has been described but is associated with higher relapse rates.
Treatment guidelines for malaria in the United States were recently updated by the Centers for Disease Control and Prevention (CDC).2
Antimalarials
Blood schizonticides are the first-line drugs for the treatment of malaria.
Chloroquine (Aralen)
This drug is effective against the erythrocytic forms of the parasite and is the drug of choice for P vivax, P malariae, and P ovale malaria, against which it is gametocidal as well. It is not effective against hypnozoites. It is very effective against sensitive strains of P falciparum. However, P falciparum resistance to chloroquine is now widespread in Africa and Asia, and it should not be depended upon in severe malaria. Recently, resistance to this drug in P vivax has also been reported, but resistance is currently rare.
Chloroquine can be used as a suppressive prophylactic agent, with the advantage of once-weekly dosing. It is recommended for such use only in regions where drug resistance is not common (parts of Central America, the Caribbean, parts of the Middle East). It is available as tabs that contain 300 mg of the base and injections that contain 40 mg base/mL.
Adult
Treatment: 600 mg of base (1000 mg salt) PO; followed by doses of 300 mg of base after 6, 24, and 48 h
200 mg of base (500 mg salt) IV; diluted in 500 mL of IV fluid and infused over 4-6 h; repeat dose q8h until patient can take PO therapy
Pediatric
Treatment: 25 mg/kg (as base) PO over 3 d; 10 mg/kg initial dose (not to exceed 600 mg); followed by 3 doses of 5 mg/kg after 6, 24, and 48 h
IM injections never used in children; may cause sudden death
5 mg/kg IV diluted in IV fluid and infused over 6 h (0.8 mg/kg/h); can be administered q8h to complete course after 5 infusions or until patient can take PO medication to complete course
Possible delayed or reduced absorption with coadministration of antacids containing magnesium; cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones)
Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones; IM injections in children (may cause sudden death)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer IM to children (IM administration can cause cardiovascular collapse and death); PO use after meals because it causes gastritis; possible shock and death in young children with single PO dose of 600 mg; do not administer rapid parenteral infusions; possible cardiovascular toxicity, including hypotension and cardiac arrest; possible irreversible ototoxicity and retinopathy with high doses for a prolonged period; possible severe reactions in patients with psoriasis and porphyria; causes hemolysis in patients with G-6-PD deficiency
Quinine (Quinamm)
A blood schizonticidal drug and still the DOC for severe and complicated malaria in most parts of the world. It is gametocidal for P vivax and P malariae, but not for P falciparum. It is available as tabs containing 260 mg and as injections containing 300 mg/mL.
Spreading resistance among P falciparum strains to this drug make the drug less reliable in certain parts of Asia and Africa.
Adult
Treatment: 542 mg as base (650 mg salt) PO q8h for 7 d
10 mg/kg (as base) IV diluted in IV fluid and infused slowly q8h; not to exceed 600 mg; switch to PO therapy when patient can tolerate it to complete 7-d course
Pediatric
Treatment: 8.3 mg as base/kg PO tid for 7 d (equivalent to 10 mg as salt/kg)
Do not administer IM except as lifesaving measure in severe malaria while awaiting transport to hospital with requisite facilities
15-20 mg/kg IV diluted in IV infusion fluid to 1 mg/mL; infuse over at least 4 h; followed by 10 mg/kg/dose q8-12h if continuation beyond 48 h is needed; reduce dose to 5 mg/kg q8h; switch to PO therapy as soon as possible
Aluminum-containing antacids may delay or decrease quinine bioavailability when administered concurrently; cimetidine increases quinine blood levels and creates the potential for toxicity; rifamycins decrease quinine concentrations by increasing hepatic clearance of quinine (effect can persist for several days after discontinuing rifamycins); concurrent administration of acetazolamide or sodium bicarbonate may increase toxicity by increasing quinine blood levels; quinine may enhance action of warfarin and other PO anticoagulants by decreasing synthesis of vitamin K–dependent clotting factors; digoxin serum concentrations may increase when digoxin is administered concurrently with quinine; important to monitor digoxin levels periodically; quinidine may decrease plasma cholinesterase activity, causing a decrease in the metabolism of succinylcholine
Documented hypersensitivity; myasthenia gravis (possible respiratory distress and dysphagia); G-6-PD deficiency (possible severe hemolysis); tinnitus or optic neuritis
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
PO use after meals to avoid gastritis; hyperinsulinemia and hypoglycemia; monitor blood glucose; ensure adequate PO intake; if administered parenterally, dilute in dextrose-containing solutions; possible urticaria, angioedema, and asthma even with single dose; possibly fatal orally with large dose, ie, 1 g base in children <5 y; monitor carefully if patient has cardiac dysrhythmia
Quinidine (Quinalan, Quinidex, Quinora)
A stereoisomer of quinine and a blood schizonticidal drug, it is as effective as quinine against blood schizonts but has significantly more cardiac toxicity. This agent is used if quinine is not readily available. It is available as tabs of quinidine sulphate containing 200 mg. The injectable preparation is not always available.
Adult
7.5 mg as base/kg/dose IV in IV fluid over 4 h q8h for 7 d (salt equivalent = 12 mg/kg)
Pediatric
25-30 mg as base/kg/d PO in divided doses for 7 d
15 mg/kg diluted in IV infusion fluid over at least 4h followed by 7.5 mg/kg/dose q8-12h; switch to PO therapy as soon as possible, and complete 7-d course
Possible delayed absorption from GIT with coadministration of antacids containing aluminium; possible delayed excretion of digoxin, warfarin, and other anticoagulants; significantly reduced half-life possible with concomitant phenytoin and phenobarbital
Documented hypersensitivity; myasthenia gravis (possible respiratory distress and dysphagia); G-6-PD deficiency (possible severe hemolysis); AV block or bundle branch block
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Possible hyperinsulinemia and hypoglycemia; monitor blood glucose; ensure adequate PO intake; if administered parenterally, quinidine should be diluted in dextrose-containing solutions; monitor cardiac activity
Pyrimethamine-sulfadoxine (Fansidar)
Antifolate drug combination that is a slow-acting blood schizonticide, effective in some cases of chloroquine-resistant P falciparum malaria, especially those acquired in Africa. This drug is not effective against P vivax malaria. Being slow acting, this combination cannot be used in potentially severe cases. It has no activity against hypnozoites and gametocytes. It is available as tablets containing 25 mg of pyrimethamine and 500 mg of sulfadoxine.
Adult
3 tab PO (75 mg pyrimethamine and 1500 mg sulfadoxine) as a single dose
Pediatric
<2 months: Contraindicated
>2 months: 1.5 mg/kg (based on pyrimethamine component) PO pyrimethamine as a single dose
Concurrent use of antifolic acids, such as methotrexate, and pyrimethamine may increase risk of bone marrow suppression; discontinue therapy if signs of folate deficiency develop; mild hepatotoxicity may occur with concomitant administration of lorazepam and pyrimethamine
Documented hypersensitivity; infants <2 mo; nursing mothers (drug passes the placenta, is excreted in milk, and may cause kernicterus); renal impairment; blood dyscrasias; hepatic damage
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Possible severe, even fatal, cutaneous reactions (1 patient in 5000-8000), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, or epidermal necrolysis; reported fatalities with sulfonamide because of fulminant hepatic necrosis, agranulocytosis, and aplastic anemia; hepatitis and megaloblastic anemia can occur, especially with overdosage; not presently used for prophylaxis because of serious adverse effects
Primaquine
The only drug in clinical use that destroys hypnozoites of both P vivax and P ovale, and so is used for the radical cure of the relapsing malarias. It is also gametocidal against all 4 species of human plasmodia and is used to render patients noninfectious. Primaquine has a very weak effect against erythrocytic forms of P vivax and cannot be used to terminate an acute attack. It has no activity against erythrocytic forms of P falciparum. This drug can be administered to patients on chemoprophylaxis after they have left the endemic area. Not to be used until erythrocytic forms have been destroyed by another drug.
Primaquine is also an effective and fairly safe drug for chemoprophylaxis. Since it acts on the liver forms, it need not be taken before entering a malarious area, nor for more than 3 days after leaving it. This is an advantage for people making sudden or short trips.
Adult
For radical cure of P vivax and P ovale malarias: 15 mg as base PO bid for 14 d
To render patient noninfectious: 15 mg/d PO for 5 d for P falciparum infection
As chemoprophylaxis, 0.5 mg as base/kg daily, starting on the day of entry to a malarious area
Pediatric
For radical cure of P vivax and P ovale malarias: 0.3 mg/kg/d PO primaquine base for 14 d
To render patient noninfectious: 0.3 mg/kg/d PO primaquine base for 5 d for P falciparum infection
Coadministration with quinacrine may increase toxicity, usually not of clinical significance
Documented hypersensitivity; G-6-PD deficiency (significant hemolysis in these patients)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Possible severe hemolysis with G-6-PD deficiency, anemia, and renal failure; bone marrow suppression; not to be used with other drugs having a marrow suppressing effect (eg, chloramphenicol); not used parenterally because of severe hypotension
Halofantrine (Halfan)
A rapid-acting drug against erythrocytic forms of malaria. Primarily used for treatment of acute attacks of malaria caused by multidrug-resistant P falciparum. It is not active against hypnozoites and gametocytes. Because it is a slow acting drug and does not have a parenteral preparation available, the drug is not of use for severe and complicated malaria.
Adult
500 mg PO q6h for 3 doses; repeat after 1 wk
Administer on an empty stomach at least 1 h ac or 2 h pc
Pediatric
<40 kg: 8 mg/kg PO q6h for 3 doses; not to exceed 500 mg/dose; repeat after 1 wk
>40 kg: Administer as in adults
Administer on empty stomach at least 1 h ac or 2 h pc
Mefloquine may interact with halofantrine, leading to potentially fatal prolongation of QTc interval
Documented hypersensitivity; heart block; QT prolongation; electrolyte disorders; AV conduction disorders; syncope; thiamine deficiency; ventricular dysrhythmias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
PO absorption unpredictable; possible poor absorption and efficacy with recommended doses; conversely, possible toxicity if absorption (and blood levels) are high; halofantrine prolongs QT interval, with possible ventricular arrhythmias and even death
Mefloquine (Lariam)
It is useful for the treatment of multidrug-resistant P falciparum infections. It is effective against blood schizonts but has no activity against hypnozoites and gametocytes. Its long half-life makes it suitable for use as a prophylactic drug, and it is the recommended drug in areas where drug resistance is common (chiefly Africa and Asia). Not having a parenteral preparation limits its usefulness for severe and complicated malaria. It is available as tabs containing 250 mg.
Adult
15-25 mg as salt/kg PO as single dose; not to exceed 1500 mg
Pediatric
15-25 mg as salt/kg PO as single dose
Mefloquine administered with beta-blockers, quinine, quinidine, antiarrhythmics, tricyclic antidepressants, or astemizole may potentially cause ECG abnormalities or cardiac arrest; mefloquine and chloroquine administered concomitantly may increase risk of convulsions; concomitant administration with halofantrine may cause potentially fatal prolongation of the QTc interval; valproic acid administered with mefloquine can increase risk for seizures by reducing valproic acid blood levels
Documented hypersensitivity; seizure disorders; neuropsychiatric disorders; cardiac conduction disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Possible giddiness and disturbed balance; possibly hazardous to drive or operate machinery; monitor psychiatric symptoms with prolonged use; stop chemoprophylaxis if confusion, depression, anxiety, or restlessness occur; not to be used for >1 y (prophylaxis)
Artemether (Artenam)
Effective against erythrocytic forms of all 4 human plasmodia but is used for multidrug-resistant P falciparum malaria. It has no action on hepatic forms or gametocytes. Very short elimination half-life, requiring follow-up treatment with mefloquine or treatment for at least 7 d.
Adult
200 mg PO on day 1, followed by 100 mg qd for 5 d
3.2 mg/kg IM loading dose, followed by 1.6 mg/kg qd for 5 d, or until patient is able to take PO therapy
Pediatric
4 mg/kg/d PO divided bid
IM: Administer as in adults
Aurothioglucose mat increase the risk of blood dyscrasias
Documented hypersensitivity; heart block; low leukocyte count
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Possible rash and fever
Artesunate (Lotio Artesan)
Effective against blood forms of all 4 types of human malaria parasites. Special usefulness is its action against multidrug-resistant P falciparum. It has no action against hepatic schizonts, hypnozoites, or gametocytes. This drug is available as 50-mg tabs and IV injections containing 10 mg/mL.
It has been found to be the fastest acting drug against blood forms of the malaria parasite, and so the IV form is especially valuable in the management of severe and complicated malaria.
Resistance to this drug is also spreading, particularly in Southeast Asia. Combinations of artesunate with mefloquine, lumefantrine, and other drugs have been found to be effective against multidrug-resistant malaria.
Adult
100 mg PO initial dose, followed by 50 mg q12h for 5 d
Alternatively, 2.4 mg/kg IV loading dose, followed by 1.2 mg/kg after 12 h, then 1.2 mg/kg qd for 5 d, or until patient is able to take PO therapy
Pediatric
4 mg/kg PO on day 1, followed by 2 mg/kg/d for 3-5 d
Alternatively, 3.2 mg/kg IV on day 1; may be divided bid; then 1.6 mg/kg IV qd for 4 d (total 9.6 mg/kg)
None reported
Documented hypersensitivity; heart block; low leukocyte count
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Possible rash and fever; possible mild GI upset with PO use
Tetracycline (Achromycin V, Sumycin)
Antibiotic with action against blood schizonts of all species of malaria. Its action is slow and it is used in combination with another drug, such as quinine, in areas where resistant P falciparum are common. It is available as capsules containing 250 mg and 500 mg.
Adult
250-500 mg PO q6h for 7 d
Pediatric
<8 years: Do not use
>8 years: 25-40 mg/kg/d PO divided qid for 7 d
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction; children <8 y
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (<8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Clindamycin (Cleocin)
An antibiotic that acts against P falciparum. It has been found to be very effective in combination with quinine, even against malaria acquired in areas where drug resistance is common. Used in combination, it shortens duration of fever and improves cure rates. This is an important drug for use in children because tetracyclines are contraindicated. It is available as capsules containing 75 mg, 150 mg, and 300 mg and as granules that, after reconstitution with water, contain 75 mg/5 mL.
Adult
20 mg as base/kg/d PO divided tid for 7 d
Pediatric
5-10 mg/kg PO q12h for 3-7 d
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile
Atovaquone/proguanil (Malarone)
Recently approved in the United States for the treatment and prophylaxis of malaria. Atovaquone has significant parasiticidal activity. Proguanil and atovaquone have high failure rates when used alone but are very successful in combination. Combining them also reduces the selection of resistant mutants.
Malarone is available for PO use only, and so can be used only for uncomplicated malaria, where it is very effective, even against resistant strains. It is also a useful drug for chemoprophylaxis. It is available as adult (250 mg atovaquone and 100 mg proguanil hydrochloride per tab) and pediatric (62.5 mg atovaquone and 25 mg proguanil hydrochloride per tab) formulations.
Adult
Treatment of malaria: 4 adult Malarone tab PO as a single daily dose for 3 consecutive d
Prophylaxis of malaria: 1 adult tab PO qd; start 2 d before traveling to a malarious area and continue for 7 d after leaving it
Pediatric
Treatment of malaria: single daily dose PO for 3 consecutive d using adult strength tab as follows:
5-8 kg: 2 pediatric tab
9-10 kg: 3 pediatric tab
11-20 kg: 1 adult tab
21-30 kg: 2 adult tab
31-40 kg: 3 adult tab
>40 kg: Administer as in adults
Prophylaxis of malaria: start 2 d before traveling to a malarious area and continue for 7 d after leaving it; dosage is as follows:
11-20 kg: 1 pediatric tab qd
21-30 kg: 2 pediatric tab qd
31-40 kg: 3 pediatric tab qd
>40 kg: 1 adult tab qd
Aurothioglucose mat increase the risk of blood dyscrasias
Documented hypersensitivity; severe renal impairment; breastfeeding women
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dose administered at same time every day with food or milk; abdominal pain, anorexia, nausea, vomiting, headache, and coughing; should not be used for treatment of malaria in persons using Malarone prophylaxis
Artemether and lumefantrine (Coartem)
Indicated for treatment of acute, uncomplicated P falciparum malaria, the most dangerous form of malaria. Contains fixed ratio of 20 mg of artemether and 120 mg of lumefantrine (1:6 parts). Both components inhibit nucleic acid and protein synthesis. Artemether is rapidly metabolized into the active metabolite dihydroartenisinin (DHA), producing an endoperoxide moiety. Lumefantrine may form a complex with hemin, which inhibits the formation of beta-hematin. Has been shown effective in geographical regions where resistance to chloroquine has been reported.
Adult
<35 kg bodyweight: Use pediatric dosing
≥35 kg bodyweight: One dose is 4 tab; take 6 doses over 3-d period as described below
Day 1: Take 1 dose, followed 8 h later by 1 dose
Day 2: Take 1 dose bid
Day 3: Take 1 dose bid
Pediatric
Number of tab per dose by body weight
<5 kg: Do not administer
5 to <15 kg: 1 tab
15 to <25 kg: 2 tab
25 to <35 kg: 3 tab
≥35 kg: Administer as in adults
Take 6 doses over 3-d period as described for adults
CYP3A4 inhibitors (including antiretroviral drugs, macrolide antibiotics, antidepressants, and imidazole antifungal agents) or CYP2D6 inhibitors (eg, flecainide, tricyclic antidepressants) may increase toxicity of lumefantrine, increasing QT prolongation; halofantrine may increase toxicity of lumefantrine, increasing QT prolongation (not for concurrent administration; administer 1 mo apart); antimalarials quinine and quinidine may have additive effects on QT interval (use caution); not approved for severe or complicated P falciparum malaria; not approved for prevention of malaria
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
QT prolongation may occur; avoid use in patients with congenital prolongation of QT interval (family history) and known disturbances of electrolyte imbalance (including hypokalemia or hypomagnesemia); common adverse effects include headache, dizziness, loss of appetite, and fever
More on Malaria |
| Overview: Malaria |
| Differential Diagnoses & Workup: Malaria |
 Treatment & Medication: Malaria |
| Follow-up: Malaria |
| Multimedia: Malaria |
| References |
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References
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Warrell DA. Treatment and prevention of malaria. In: Bruce-Chwatt's Essential Malariology. 3rd ed. London, England: Edward Arnold; 1993:164-95.
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Further Reading
Keywords
malaria, ague, mosquito, Plasmodium vivax, P vivax, Plasmodium ovale, P ovale, Plasmodium malariae, P malariae, Plasmodium falciparum, P falciparum, Anopheles mosquito, malarial fever, quartan malaria, tertian malaria, algid malaria
