eMedicine Specialties > Infectious Diseases > Parasitic Infections
Malaria: Treatment & Medication
Updated: Apr 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Speciating the parasite is critical in patients with malaria. Infection with P falciparum may be more severe than infection with other Plasmodium species. In addition, P falciparum is resistant to chloroquine treatment except in Haiti, the Dominican Republic, parts of Central America, and parts of the Middle East. In the United States, patients with P falciparum infection are often treated on an inpatient basis in order to observe for complications attributable to either the illness or its treatment.
Consultations
Consider consulting an infectious disease specialist for assistance with malaria diagnosis, speciation, patient treatment, and disease management. The CDC is an excellent resource if no local resources are available. The CDC Malaria hotline is 770-488-7788; 770-488-7100 is the telephone number to speak with an on-call malaria specialist.
Diet
Patients with malaria should continue intake as tolerated.
Activity
Patients with malaria should continue activity as tolerated.
Medication
Malaria prevention
DEET may be used to prevent transmission of the parasite through mosquitoes. Apply 95% DEET, which lasts up to 10-12 h, or 35% DEET, which lasts 4-6 h. In children, use a concentration of DEET less than 35%; apply sparingly only on exposed skin and remove when no longer exposed. Toxicity that manifests as encephalopathy and seizures has been reported in children exposed to higher concentrations of DEET.
Malaria prophylaxis
Whether a traveler needs malaria prophylaxis is an important question. This decision should be based on the traveler's detailed itinerary and should be based on whether travel is planned to areas where malaria is endemic and possibly drug resistant. Travel to an urban area may not require malaria prophylaxis, while travel to more remote or underdeveloped cities does. Determine the patient's accommodations and time of exposure. Travel during the transmission season, camping, and long-term trips are high-risk activities. Transmission typically does not occur at elevations higher than 2000 m.
Recommendations regarding prophylaxis should be made after reviewing guidelines published by the CDC as they apply to the planned itinerary. An excellent reference for malaria prophylaxis can be found at the CDC's Malaria and Travelers Web site.
Malaria treatment
P falciparum exhibits widespread resistance to chloroquine. Resistance is rare in P vivax infection, and P ovale and P malariae remain sensitive to chloroquine. Primaquine is required in the treatment of P ovale and P vivax infection in order to eliminate the hypnozoites (liver phase).
Artesunate is unavailable in the United States but may be used at 4 mg/kg/d PO for 3 days. Intravenous quinine is also unavailable in the United States. Intravenous quinidine gluconate is used to treat complicated P falciparum malaria.
P falciparum drug resistance is common in endemic areas such as Africa. Standard antimalarials such as chloroquine and antifolates (sulfadoxine-pyrimethamine) are ineffective in many areas. Because of this increasing prevalence of drug resistance and a high likelihood of resistance development to new agents, combination therapy is now becoming the standard of care for treatment of P falciparum infection worldwide. Artemisinins, a new class of antimalarial agent, are often part of these newly recommended regimens. They are not yet available in the United States; however, other combination drugs such as atovaquone and proguanil HCL (Malarone) or quinine in combination remain highly efficacious.
The following is a summary of general recommendations for the treatment of malaria:- P falciparum malaria
- Quinine-based therapy - Quinine (or quinidine) sulfate plus doxycycline or clindamycin or pyrimethamine-sulfadoxine
- Alternative therapy - Atovaquone-proguanil or mefloquine
- P falciparum malaria with known chloroquine susceptibility (only a few areas in Central America and the Middle East) - Chloroquine
- P vivax, P ovale malaria - Chloroquine plus primaquine
- P malariae malaria - Chloroquine
- P knowlesi malaria – Recommendations same as those for P falciparum malaria
Antimalarials
These agents inhibit growth by concentrating within acid vesicles of parasite, increasing the internal pH of the organism. They also inhibit hemoglobin utilization and parasite metabolism.
Chloroquine phosphate (Aralen)
Effective for P vivax, P ovale, P malariae, and drug-sensitive P falciparum. Can be used for prophylaxis or treatment. This is the prophylactic DOC for sensitive malaria. The doses listed below are appropriate for chloroquine phosphate, chloroquine sulfate, and hydroxychloroquine sulfate; chloroquine dihydrochloride has a slightly different dose and schedule.
Adult
Prophylaxis: 300 mg base PO qwk (starting 1-2 wk prior to travel, once qwk in the endemic area, and continuing weekly for 4 wk after returning from endemic area)
Treatment: 600 mg base PO, then 300 mg base PO at 6 h, then repeat 300 mg base PO at 24 h and 48 h
Severe malaria: 10 mg/kg base IV at constant rate over 8 h, followed by 15 mg/kg base over 24 h
Pediatric
Prophylaxis: 5 mg/kg base PO, up to 300 mg weekly (plus 2 wk prior and 4 wk after travel to endemic area)
Treatment: 10 mg/kg base PO (not to exceed 600 mg), then 5 mg/kg base at 6 h, 24 h, and 48 h
Cimetidine may increase serum levels of chloroquine (possibly other 4-aminoquinolones); magnesium trisilicate may decrease absorption of 4-aminoquinolones
Documented hypersensitivity; psoriasis; retinal changes; visual field changes attributable to 4-aminoquinolones
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
Nausea, headache, blood dyscrasias, and retinopathy (rare) may occur with daily use; risk of retinopathy may increase with prophylactic cumulative doses >100 g (ie, 5 y), perform regular ophthalmologic examinations after taking drug for prolonged period or after any visual disturbance
Quinine sulfate (Formula Q)
Used for malaria treatment only, has no role in prophylaxis. Use with second agent in drug-resistant P falciparum. For drug-resistant parasites, second agent is doxycycline, tetracycline, pyrimethamine sulfadoxine, or clindamycin. Quinidine gluconate is an IV alternative. Can also be administered by deep IM injection.
Adult
Prophylaxis: Not indicated
Treatment: 650 mg PO q8h for 3-7 d with second agent if drug-resistant P falciparum
Severe malaria: Quinine dihydrochloride 20 mg/kg IV over 4 h, followed by 10 mg/kg IV q8-12h; switch to PO antimalarial when patient has improved and can take PO medications, reduce dose by one third if used parenterally for more than 72 h
Maintenance: 10 mg/kg salt infused over 2-8 h at 8- to 12-h intervals
Pediatric
25 mg/kg/d PO divided tid, for 3-7 d with second agent
Prophylaxis: Not indicated
Treatment with quinine sulfate: 10 mg/kg/d PO tid for 3-7 d
Treatment with quinine dihydrochloride: 20 mg/kg IV over 4 h, followed by 10 mg/kg IV q8-12h; switch to PO antimalarial when patient has improved and can take PO medications, reduce dose by one third if used parenterally for more than 72 h
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; optic neuritis; tinnitus; G-6-PD deficiency; 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 arrhythmias; monitor blood pressure and glucose levels
Doxycycline (Vibramycin, Vibra-Tabs, Doryx)
Used for prophylaxis or treatment of malaria. When used for treatment of P falciparum malaria, this drug must be used as part of combination therapy (eg, typically with quinine).
Adult
Prophylaxis: 100 mg/d PO (start 1 d prior to travel; use qd in endemic area and qd for 4 wk after travel to endemic area)
Treatment: 100 mg PO bid for 7 d with second agent
Pediatric
<8 years: Do not administer
>8 years:
Prophylaxis: 2 mg/kg/d PO, up to 100 mg/d (start 1-2 d prior to entering endemic area, continue qd while in endemic area and continue qd for 4 wk after travel to endemic area)
Treatment: 2 mg/kg/d PO divided bid for 7 d with second agent
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO 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 (ie, last one-half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines
Pyrimethamine-sulfadoxine (Fansidar)
Can be used for treatment of malaria. No longer considered a first-line agent for prophylaxis because of the adverse effect profile.
Adult
Prophylaxis: Not indicated
Treatment: 3 tab of 25 mg pyrimethamine and 500 mg sulfadoxine PO once
Pediatric
Prophylaxis: Not indicated
Treatment:
<1 year: 0.25 tab PO once
1-3 years: 0.5 tab PO once
4-8 years: 1 tab PO once
9-14 years: 2 tab PO once
>14 years: Administer as in adults
Do not use antifolic drugs (eg, sulfonamides, trimethoprim-sulfamethoxazole combinations) while patient is receiving sulfadoxine and pyrimethamine tab for antimalarial prophylaxis
Documented hypersensitivity; severe renal insufficiency; marked liver parenchymal damage; blood dyscrasias; documented megaloblastic anemia due to folate deficiency; age <2 mo; pregnancy at term and during nursing period
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
Fatalities associated with administration of sulfonamides, although rare, have occurred because of severe reactions, including fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; caution in impaired renal or hepatic function, possible folate deficiency, severe allergy, or bronchial asthma; hemolysis may occur in G-6-PD–deficient individuals; perform a urinalysis with microscopic examination and renal function tests during therapy for patients who have impaired renal function; discontinue if signs of folic acid deficiency develop; folinic acid (leucovorin) may be administered in doses of 5-15 mg IM daily, for >3 d, for depressed platelet or WBC counts in patients with drug-induced folic acid deficiency (when recovery is too slow)
Clindamycin (Cleocin HCl, Cleocin T)
Part of combination therapy for drug-resistant malaria (eg, typically with quinine). Good second agent in pregnant patients.
Adult
900 mg PO tid for 5 d with second agent (typically quinine)
Pediatric
20-40 mg/kg/d PO divided tid for 5 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
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
Mefloquine (Lariam)
Acts as a blood schizonticide. May act by raising intravesicular pH within parasite acid vesicles. Structurally similar to quinine. For prophylaxis or treatment of drug-resistant malaria.
Adult
Prophylaxis: 250 mg PO qd for 3 d prior to entering endemic area, continue qwk in endemic area, and continue qwk for 4 wk after returning from endemic area
Treatment: 750-1250 mg PO once (second-line method because of adverse effects at this higher dose)
Pediatric
Prophylaxis: Administer PO qd for 3 d prior to entering endemic area, continue qwk in endemic area, and continue qwk for 4 wk after returning from endemic area
Prophylaxis:
<15 kg: 5 mg/kg PO
15-19 kg: 0.25 tab PO
20-30 kg: 0.5 tab PO
31-45 kg: 0.75 tab PO
>45 kg: 1 tab PO
Treatment: 15 mg/kg PO as single dose (second-line method because of adverse effects at this higher dose)
Mefloquine administered with beta-blockers, quinine, quinidine, antiarrhythmics, TCAs, 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; epilepsy or seizure disorder; severe psychiatric disorder; diagnosis or treatment for irregular heartbeat
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; may result in marked GI or CNS adverse effects and, therefore, not first-line treatment recommendation; nausea, strange dreams, seizures (rare), and psychosis may occur
Halofantrine (Halfan)
Blood schizonticidal antimalarial agent with no apparent effects on hepatic stages of infection. Exact mechanism of action is unknown. Use for highly resistant malaria. Do not use if patient is using mefloquine for prophylaxis. No role for prophylaxis.
Adult
Prophylaxis: Not indicated
Treatment: 500 mg PO q8h for 3 doses, repeat in 1 wk
Pediatric
Prophylaxis: Not indicated
Treatment: 8 mg/kg PO q8h for 3 doses, repeat in 1 wk
Mefloquine may interact with halofantrine, leading to potentially fatal prolongation of QTc interval
Documented hypersensitivity; coadministration with drugs or clinical conditions known to prolong QTc interval (eg, mefloquine); known or suspected AV conduction disorders; ventricular dysrhythmias; unexplained syncopal attacks
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Prolongs QTc interval at recommended therapeutic dose; serious ventricular dysrhythmias, sometimes associated with sudden death, have been reported; do not administer concomitantly or subsequent to mefloquine; cough, pruritus, and rash (rare) may occur
Atovaquone (Mepron)
May inhibit metabolic enzymes, which in turn inhibit growth of microorganisms. Must use in combination with proguanil.
Adult
Prophylaxis: 250 mg with 100 mg proguanil PO qd; start 1-2 d before entering endemic area, continue qd while in endemic area, and continue for 7 d after exposure has ended (this shortened dosing schedule following travel makes it a good option for patients who are poorly compliant
Treatment: 500 mg PO bid for 3 d
Pediatric
Prophylaxis: Start 1-2 d before entering endemic area, continue qd while in endemic area, and continue for 7 d after exposure has ended
Treatment:
<11 kg: Not established
11-20 kg: 62.5 mg/25 mg PO qd
21-30 kg: 125 mg/50 mg PO qd
31-40 kg: 187.5 mg/75 mg PO qd
May increase zidovudine serum levels; coadministration with rifampin or rifabutin may decrease atovaquone levels; atovaquone may decrease levels of TMP-SMZ
Documented hypersensitivity; severe renal impairment; weight <11 kg (24 lb)
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 elderly patients and in hepatic and renal impairment; must use in combination with proguanil; adverse effects are rare and include abdominal pain, nausea, vomiting, and headache
Proguanil (Paludrine)
This is marketed in combination with atovaquone in the United States (Malarone). For pediatric patients, this combination should be used for uncomplicated P falciparum; can also be used in combination with chloroquine.
Adult
Prophylaxis: 200 mg PO in combination with weekly chloroquine
Prophylaxis with atovaquone/proguanil: 250 mg/100 mg PO qd
Treatment: 200 mg PO bid for 3 d
Pediatric
Prophylaxis:
<8 months: 1/4 tab PO
8 months-3 years: 1/2 tab PO
4-7 years: 3/4 tab PO
8-10 years: 1 tab PO
11-13 years: 1 1/2 tab PO
>14 years: 2 tab PO
Prophylaxis with atovaquone/proguanil:
11-20 kg: 62.5 mg/25 mg PO qd
21-30 kg: 125 mg/50 mg PO qd
31-40 kg: 187.5 mg/75 mg PO qd
11-20 kg: 50 mg PO bid for 3 d
21-30 kg: 100 mg PO bid for 3 d
31-40 kg: 150 mg PO bid for 3 d
None reported
Documented hypersensitivity
Pregnancy
Precautions
Anorexia, nausea, mouth ulcers, and hematuria (rare) may occur
Atovaquone/proguanil (Malarone)
This drug has been approved in the United States for both prophylaxis and treatment of mild chloroquine-resistant malaria. May be a good prophylactic option for patients who are visiting areas with chloroquine-resistant malaria and who cannot tolerate mefloquine. Each tab combines 250 mg of atovaquone and 100 mg of proguanil hydrochloride. Dosage for children is based on body weight; in children 40 kg (88 lb) or less, a lower-dose pediatric tab (62.5 mg of atovaquone and 25 mg of proguanil hydrochloride) is available.
Adult
Prophylaxis: 1 tab PO qd, taken at the same time qd with food or a milky drink; begin 1-2 d before entering a malaria-endemic area, and continue qd during the stay and for 7 d after return
Treatment (P falciparum malaria): 4 tab PO qd as a single dose for 3 consecutive d
Patients with severe malaria are not candidates for PO therapy, and Malarone has not been evaluated for the treatment of severe malaria, including cerebral malaria
Pediatric
Prophylaxis:
11-20 kg (24-45 lb): 1 pediatric tab PO qd
21-30 kg (46-67 lb): 2 pediatric tab qd as single dose
21-30 kg (46-67 lb): 3 pediatric tab qd as single dose
31-40 kg (68-88 lb): 4 pediatric tab qd as single dose
Treatment:
11-20 kg (24-45 lb): 1 adult tab PO qd as single dose for 3 consecutive d
21-30 kg (46-67 lb): 2 adult tab PO qd as single dose for 3 consecutive d
31-40 kg (68-88 lb): 3 adult tab PO qd as single dose for 3 consecutive d
>40 kg (88 lb): 4 adult tab PO qd as single dose for 3 consecutive d
Patients with severe malaria are not candidates for PO therapy, and Malarone has not been evaluated for treatment of severe malaria, including cerebral malaria
Administration of rifampin, rifabutin, tetracycline, and metoclopramide are associated with reduced plasma concentrations of atovaquone; therefore, concomitant administration of Malarone and rifampin or rifabutin is not recommended; parasitemia should be closely monitored in patients receiving tetracycline, and metoclopramide should be used only if other antiemetics are not available
Severe renal impairment (CrCl <30 mL/min), do not use for malaria prophylaxis
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
The most common adverse events in subjects taking Malarone for prophylaxis of malaria include headache and abdominal pain and occur at rates comparable to placebo; in adults, the most commonly reported adverse events possibly attributable to Malarone prophylaxis versus placebo are headache (5% vs 7%) and abdominal pain (3% vs 5%); in pediatric patients, adverse effects include headache (14% vs 14%), abdominal pain (31% vs 29%), and vomiting (7% vs 6%); the most common adverse events reported in >10% of patients taking Malarone for treatment of malaria are abdominal pain, nausea, vomiting, and headache in adults and vomiting in children
Primaquine phosphate
Not used to treat erythrocytic stage of malaria. Administer for hypnozoite stage of P vivax and P ovale to prevent relapse.
Adult
Prophylaxis: 15 mg base (26.3 mg salt) PO qd for 14 d after departure from malaria-risk area
Treatment: Administer as in prophylaxis
Pediatric
Prophylaxis: 0.3 mg/kg base (0.5 mg/kg salt) PO qd for 14 d after departure from malaria-risk area
Treatment: Administer as in prophylaxis
Coadministration with quinacrine may increase toxicity
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
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 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 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 |
| References |
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Further Reading
Keywords
malaria, blackwater fever, tertian fever, quartan fever, jungle fever, airport malaria, Anopheles mosquito, Plasmodium falciparum, P falciparum, Plasmodium vivax, P vivax, Plasmodium ovale, P ovale, Plasmodium malariae, P malariae, Plasmodium knowlesi, P knowlesi, paludismo
