eMedicine Specialties > Emergency Medicine > Infectious Diseases
Malaria: Treatment & Medication
Updated: May 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Emergency Department Care
- Assess airway, breathing, and circulation; intervene as necessary. Protective airway may be indicated in cases of severe central nervous system complications.
- If evidence of life-threatening hemolytic anemia is determined, establish large-bore intravenous (IV) lines, initiate fluid resuscitation, and administer transfusion of type-specific packed RBCs.
- Hyponatremia likely reflects continued oral hypotonic fluid intake in the setting of hypovolemia and requires no therapy beyond rehydration.6 Overly aggressive treatment of hyponatremia may lead to death.
- Consider exchange transfusion for life-threatening complications.
- Monitor and treat hypoglycemia, as needed.
- Search for any signs of microvascular malarial complications.
- Laboratory analysis is helpful, although it is not always readily available to determine Plasmodium species, level of drug resistance, and degree of parasitemia. Obtain complete history for the laboratory.
- General hospital admission guidelines are as follows:
- Patients with suspected or confirmed P falciparum or P knowlesi infection
- Children
- Pregnant women
- Immunodeficient individuals
- Intensive care unit admission guidelines are as follows:
- Immediate life-threatening complications present, such as coagulopathy or end-organ failure
- Presence of signs and symptoms consistent with cerebral malaria (eg, altered mental status, repeated seizures, coma)
- Patients who are nonimmune with a falciparum parasitemia greater than 2% or who are semi-immune with a P falciparum parasitemia greater than 5%
- Presence of any other severe malarial complications
- A reliable, semi-immune, adult patient with a P vivax, P ovale, or P malariae infection may be treated on an outpatient basis. However, special care must be taken if P malariae is diagnosed solely on the basis of a blood smear, as it may be confused with the sometimes fatal P knowlesi, an infection that would require inpatient treatment. Those treated as outpatients should have adequate follow-up care, including daily blood smears to confirm that the treatment is effective in decreasing parasitemia.
- If the infection is caused by an unidentified species or by mixed species, treat it as if it were caused by P falciparum. In the absence of known drug sensitivities, assume that the Plasmodium species in question is chloroquine resistant. If Southeast Asia is the origin of the infection, then assume mefloquine resistance.
- If a patient is diagnosed with P falciparum malaria with a parasitemia greater than 10% or if the patient is experiencing life-threatening complications (ie, coma, respiratory failure, coagulopathy, fulminant kidney failure), then investigate exchange transfusion as a treatment option. If transfusion is undertaken, it should continue until the parasitemia falls below 5%, although the mortality benefit of this intervention has not been proven.
- Administer parenteral quinidine, quinine, or artemisinin therapy in conjunction with exchange transfusion to eradicate the protozoa from the bloodstream.
- The World Health Organization also has guidelines on treatment of malaria.7
Consultations
It is recommended that the emergency physician contact an infectious disease clinician or the pathologist when confronted with a possible case of malaria based upon history and physical examination to ensure proper identification and diagnosis. It is particularly recommended that the physician contact the CDC directly for any known or suspected case. Consider HIV testing if indicated.
- To aid in identification of the species of Plasmodium, also notify the pathologist of the patient’s information, including the following:
- Determine where the patient has traveled and when the patient returned home.
- Determine if the patient has been diagnosed with malaria ever before. If so, find out which species of Plasmodium caused the previous infection.
- Determine what medication or prophylaxis the patient has taken, and find out when the last dose was administered.
- Determine if the patient has a history of blood transfusion or of nonsterile needle usage.
- Identify the date and time that the patient's blood sample was drawn and determine what condition the patient was in at that time (eg, patient was symptomatic, any periodicity of symptoms). Also provide an indication of the severity of illness.
- The Centers for Disease Control and Prevention has guidelines on the investigations of locally acquired mosquito-transmitted malaria.8
Medication
Antimalarial drugs have a rich history, since malaria was possibly the first human infection to be treated pharmacologically. The Chinese use of an extract from the sweet wormwood tree has led to artesemial drugs that, although expensive, are very effective. South American indigenous people have used the bark and root of the cinchona tree. The active ingredient in these medications turned out to be artemisinin and quinine, respectively, which now comprise 2 of the 4 major drug classes currently used to treat malaria. The 4 classes include quinoline-related compounds, antifolates, artemisinin derivatives, and antimicrobials.
No one drug that can eradicate all forms of the parasite's life cycle has been discovered or manufactured yet. Therefore, one or more classes of drugs often are given at the same time to combat malarial infection synergistically.
Beware of counterfeit antimalarial drugs being taken by patients that may have been purchased overseas or via the Internet. They may not contain any active ingredients at all and may contain dangerous materials.
Malaria treatment is not always straightforward. Contacting the CDC for the latest treatment guidelines and drug regimens is advised.9 Not all recommended treatment regimens or drugs are included below. Treatment in pregnancy and complicated malaria requires specialized drug regimens. Consult the CDC for further guidance. For the most recent CDC recommendations concerning malaria treatment, call the CDC Malaria Hotline at (770) 488-7788 (M-F, 8 am-4:30 pm, Eastern Time). For emergency consultation after hours, call (770) 488-7100 and request to speak with a CDC Malaria Branch clinician. The CDC table of guidelines for treatment of malaria in the United States can be downloaded as a pdf at Guidelines for Treatment of Malaria.
Treatment regimens are dependent on the geographic derivation of infection, the likely Plasmodium species, and the severity of disease presentation.
Antipyretics, such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), are indicated to reduce the level of discomfort caused by the infection and to reduce fever. NSAIDs should be used with caution if bleeding disorder or hemolysis is suspected.
Antimalarials can cause significant prolongation of the electrocardiograph QT interval, which can be associated with an increased risk of potentially lethal ventricular dysrhythmias. Patients receiving these drugs should be assessed for QT prolongation at baseline and carefully monitored if present. Those with normal QT intervals on ECG may not be at significant increased risk for drug-induced dysrhythmia, but caution is advised, particularly if the patient is taking multiple drug regimens, or if the patient is on other drugs affecting the QT interval.
Methemoglobinemia is a complication that may be associated with high-dose regimens of quinine the derivatives chloroquine and primaquine.10 A patient presenting with cyanosis and a normal PaO2 on room air should be suspected of having methemoglobinemia.
Malaria vaccine production and distribution continues to be in the research and development stage.
Antiprotozoal
Chloroquine phosphate remains the DOC if the patient is infected with a nonresistant strain of Plasmodium species. For chloroquine-resistant strains, a form of quinine is the drug next in line.
Chloroquine Phosphate (Aralen)
Inhibits parasite growth by concentrating within acid vesicles of the parasite and increasing its internal pH. In addition, inhibits hemoglobin utilization and metabolism by the parasite.
Adult
600 mg base (=1,000 mg salt) PO immediately, followed by
300 mg base (=500 mg salt) PO at 6, 24, and 48 h
Total dose: 1,500 mg base (=2,500 mg salt) 10 mg base/kg PO immediately, followed by 5 mg base/kg PO at 6-h, 24-h, and 48-h intervals
Species not identified
Pediatric
10 mg base/kg PO, not to exceed 600 mg; then 5 mg base/kg PO; not to exceed 300 mg at 6-h, 24-h, and 48-h intervals (total 25 mg base/kg)
Cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Documented hypersensitivity; psoriasis; retinal and visual field changes attributable to 4-aminoquinolones; hypotension when given IV; impairs intradermal rabies vaccine
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
Sodium channel blocking activity may increase toxicity of type Ia antidysrhythmic drugs or others with quinidinelike effects; ECG should be checked to monitor increased QRS interval effect
Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness; retinopathy, tinnitus, nerve deafness, skin eruption, headache, anorexia, nausea, vomiting, and diarrhea may occur
Clindamycin (Cleocin)
Three major drug metabolites have been shown to have strong inhibitory effects, possibly by targeting apicoplast, a chloroplast-like organelle of uncertain function.
Inhibition causes modest antimalarial effects initially but is much more potent against progeny of treated parasites. Progeny inherits nonfunctional apicoplasts, blocking production of apicoplast proteins causing a "delayed-death effect".
Adult
20 mg base/kg/d PO divided tid for 7 d
Pediatric
Administer as in adults
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
Doxycycline (Vibramycin, Vibra-Tabs, Doryx)
May specifically impair progeny of apicoplast genes resulting in their abnormal cell division. Loss of apicoplast function in progeny treated parasites leads to slow but potent antimalarial effect.
Adult
100 mg PO bid for 7d
Pediatric
<8 years: Not recommended unless treatment benefit outweighs risks (consult CDC)
>8 years: 4 mg/kg/d PO divided bid for 7d
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction
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 (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Primaquine
If uncomplicated infection is caused by P vivax or P ovale, important to treat patient with primaquine to prevent relapse. If species is initially unknown, then identified as P vivax or P ovale, primaquine phosphate treatment should be initiated. Binds to DNA and may disrupt parasite's mitochondria, causing major disruption in metabolic process of the parasite. Exoerythrocytic forms of the parasite are inhibited.
Adult
30 mg base PO qd for 14 d
Pediatric
0.5 mg base/kg PO qd for 14 d or 0.8 mg base/kg PO once/wk for 14 d
Coadministration with quinacrine or other quinidinelike drugs may increase toxicity (see chloroquine)
Documented hypersensitivity; drugs that suppress bone marrow
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
Caution in G-6-PD deficiency and those with tendency to develop granulocytopenia
Quinine sulfate (Formula Q)
Used in chloroquine-resistant or unknown resistant infections. By increasing pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.
Adult
542 mg base (=650 mg salt) PO tid for 3-7 d
Pediatric
8.3 mg base/kg (=10 mg salt/kg) PO tid for 3-7 d
Aluminum-containing antacids may delay or decrease quinine bioavailability when administered concurrently; cimetidine increases quinine blood levels and creates 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 oral anticoagulants by decreasing synthesis of vitamin K-dependent clotting factors; digoxin serum concentrations may increase when digoxin administered concurrently with quinine; important to monitor digoxin levels periodically; quinidine may decrease plasma cholinesterase activity, causing decrease in metabolism of succinylcholine
Documented hypersensitivity; those with optic neuritis, tinnitus, G-6-PD deficiency, or history of blackwater fever
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in G-6-PD deficiency and tendency to develop granulocytopenia; prolonged treatment or overdosing with quinine may cause cinchonism; quinine has quinidinelike activity and thus can cause cardiac dysrhythmias due to sodium channel blocking activity
Quinidine gluconate (Cardioquin, Quinalan, Quinidex, Quinora)
Indicated for severe or complicated malaria and used in conjunction with one of the following: doxycycline, tetracycline, or clindamycin. Increases pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.
Adult
6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 h, then 0.0125 mg base/kg/min (=0.02 mg salt/kg/min) continuous infusion for at least 24 h
Length of treatment varies by geographic origin of infection (consult CDC)
Pediatric
Administer as in adults
Delays absorption of digoxin; antagonizes effects of antimyasthenics; mefloquine increases risk of seizures
Documented hypersensitivity; those with optic neuritis, tinnitus, G-6-PD deficiency, or history of cardiac dysrhythmias
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in G-6-PD deficiency and in patients with a tendency to develop granulocytopenia; prolonged treatment or overdosing with quinine may cause cinchonism; quinine has quinidinelike activity and can cause cardiac dysrhythmias via sodium channel blocking activity
Tetracycline (Achromycin V, Sumycin)
May specifically impair progeny of apicoplast genes resulting in their abnormal cell division. Loss of apicoplast function in progeny treated parasites leads to slow but potent antimalarial effect.
Adult
250 mg PO qid for 7 d
Pediatric
<8 years: Not recommended unless benefits outweigh risks (consult with CDC)
>8 years: 25 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 oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction
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 (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
Antimalarials
These agents inhibit growth of malarial pathogens by interfering with their stages of growth. US Food and Drug Administration has approved Coartem tablets (artemether and lumefantrine) for the treatment of acute, uncomplicated malaria infections.11Artemether 20 mg/lumefantrine 120 mg (Coartem)
Indicated for treatment of acute, uncomplicated Plasmodium falciparum malaria, the most dangerous form of malaria. Contains fixed ratio of 20 mg artemether and 120 mg 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.
Adult
<35 kg body weight: Use pediatric dosing
>35 kg body weight: 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
<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
Mefloquine (Lariam)
Not used in complicated malaria. Acts as a blood schizonticide and may act by raising intravesicular pH within the parasite acid vesicles. Structurally similar to quinine.
Adult
15 mg base/kg PO, then 10 mg base/kg PO 6-8 h later (not to exceed 1250 mg; usually 750 mg PO, then 500 mg PO at 6-8 h)
684 mg base (=750 mg salt) PO as initial dose, followed by 456 mg base (=500 mg salt) PO given 6-12 h after initial dose
Total dose = 1,250 mg salt 13.7 mg base/kg (=15 mg salt/kg) PO as initial dose, followed
by 9.1 mg base/kg (=10 mg salt/kg) PO given 6-12 h after initial dose
Pediatric
13.7 mg base/kg (=15 mg salt/kg) PO as initial dose, followed by 9.1 mg base/kg (=10 mg salt/kg) PO given 6-12 h after initial dose
Mefloquine administered with beta-blockers, quinine, quinidine, antiarrhythmics, TCAs, or astemizole may 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 QTc interval; valproic acid administered with mefloquine can increase risk of seizures by reducing valproic acid blood levels
Documented hypersensitivity; patients with seizure disorder, heart block, or psychiatric 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
Use for >1 y not established; perform periodic evaluations, including LFTs, when using for prolonged periods; mefloquine may have cardiac depressant effects and antifibrillatory activity
Not recommended in infections originating in some Southeast Asian countries due to drug resistance
Artemether (Artenam)
Used only for severe or complicated malaria. Not FDA approved.
Adult
3.2 mg/kg IM (anterior thigh), then 1.6 mg/kg IM q24h until PO therapy is possible (never IV)
Pediatric
Administer as in adults
None reported
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
Brainstem neurotoxicity and death in nonhuman primates have been reported; drug fever may occur
Artesunate
Experimental drug.
Adult
4 mg/kg PO qd for 3 d (total dose 12 mg/kg; 1 tab = 50 mg); for severe or complicated malaria, use 2.4 mg/kg IV load, then 1.2 mg/kg IV at 12 h and 24 h, then 1.2 mg/kg IV q24h until PO therapy is possible
Pediatric
Administer as in adults
None reported
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
Brainstem neurotoxicity and death in nonhuman primates have been reported; drug fever may occur
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 Treatment & Medication: Malaria |
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References
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Further Reading
Keywords
malaria, paludism, paludismo, black water fever, blackwater fever, mosquito vector, plasmodia, species, mosquito, mosquito bite
