- Author: Thomas E Herchline, MD; Chief Editor: Michael Stuart Bronze, MD more...
The 4 major drug classes currently used to treat malaria include quinoline-related compounds, antifolates, artemisinin derivatives, and antimicrobials. No single drug that can eradicate all forms of the parasite's life cycle has been discovered or manufactured yet. Therefore, 1 or more classes of drugs often are given at the same time to combat malarial infection synergistically. Treatment regimens are dependent on the geographic location of infection, the likely Plasmodium species, and the severity of disease presentation.
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.
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 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 this is present. Patients with normal QT intervals on electrocardiogram (ECG) may not be at a significantly increased risk for drug-induced dysrhythmia, but caution is advised, particularly if the patient is taking multiple drug regimens or if he or she is on other drugs affecting the QT interval.
Methemoglobinemia is a complication that may be associated with high-dose regimens of quinine or the derivatives chloroquine and primaquine. A patient presenting with cyanosis and a normal PaO2 on room air should be suspected of having methemoglobinemia.
These agents inhibit growth by concentrating within acid vesicles of the parasite, increasing the internal pH of the organism. They also inhibit hemoglobin utilization and parasite metabolism.
Chloroquine phosphate is effective against P vivax, P ovale, P malariae, and drug-sensitive P falciparum. It can be used for prophylaxis or treatment. This is the prophylactic drug of choice for sensitive malaria.
Quinine is used for malaria treatment only; it has no role in prophylaxis. It is used with a second agent in drug-resistant P falciparum. For drug-resistant parasites, the second agent is doxycycline, tetracycline, pyrimethamine sulfadoxine, or clindamycin.
Quinidine gluconate is indicated for severe or complicated malaria and is used in conjunction with doxycycline, tetracycline, or clindamycin. Quinidine gluconate can be administered IV and is the only parenterally available quinine derivative in the United States.
Doxycycline is used for malaria prophylaxis or treatment. When it is administered for treatment of P falciparum malaria, this drug must be used as part of combination therapy (eg, typically with quinine or quinidine).
Tetracycline may specifically impair the progeny of apicoplast genes, resulting in their abnormal cell division. Loss of apicoplast function in progeny of treated parasites leads to slow, but potent, antimalarial effect.
Clindamycin is part of combination therapy for drug-resistant malaria (eg, typically with quinine or quinidine). It is a good second agent in pregnant patients.
Mefloquine acts as a blood schizonticide. It may act by raising intravesicular pH within the parasite's acid vesicles. Mefloquine is structurally similar to quinine. It is used for the prophylaxis or treatment of drug-resistant malaria. It may cause adverse neuropsychiatric reactions and should not be prescribed for prophylaxis in patients with active or recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders.
Atovaquone may inhibit metabolic enzymes, which in turn inhibits the growth of microorganisms.
Used for pediatric patients, this combination should be administered for uncomplicated P falciparum; can also be used in combination with chloroquine.
This agent is approved in the United States for the prophylaxis and treatment of mild chloroquine-resistant malaria. It 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. The dosage for children is based on body weight; in children 40 kg (88 lb) or less, a lower-dose pediatric tablet (62.5 mg of atovaquone and 25 mg of proguanil hydrochloride) is available.
Primaquine is not used to treat the erythrocytic stage of malaria. Administer the drug for the hypnozoite stage of P vivax and P ovale to prevent relapse.
This drug combination is indicated for the treatment of acute, uncomplicated P falciparum malaria. It contains a 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 dihydroartemisinin (DHA), producing an endoperoxide moiety. Lumefantrine may form a complex with hemin, which inhibits the formation of beta hematin.
Artesunate, a form of artemisinin that can be used intravenously, is available from the CDC. It is not licensed for use in the United States but is available as part of an investigational new drug protocol.
Piola P, Nabasumba C, Turyakira E, et al. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2010 Nov. 10(11):762-9. [Medline].
McGready R, Lee SJ, Wiladphaingern J, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis. 2012 May. 12 (5):388-96. [Medline].
Marchand RP, Culleton R, Maeno Y, Quang NT, Nakazawa S. Co-infections of Plasmodium knowlesi, P. falciparum, and P. vivax among Humans and Anopheles dirus Mosquitoes, Southern Vietnam. Emerg Infect Dis. 2011 Jul. 17(7):1232-9. [Medline].
William T, Menon J, Rajahram G, et al. Severe Plasmodium knowlesi malaria in a tertiary care hospital, Sabah, Malaysia. Emerg Infect Dis. 2011 Jul. 17(7):1248-55. [Medline].
Malaria Surveillance — United States, 2010. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6102a1.htm?s_cid=ss6102a1_e. Accessed: March 1, 2012.
Centers for Disease Control and Prevention. Malaria. Available at http://www.cdc.gov/malaria. Accessed: Sep 15, 2011.
Taylor SM, Parobek CM, Fairhurst RM. Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis. 2012 Jun. 12 (6):457-68. [Medline].
[Guideline] Bailey JW, Williams J, Bain BJ, Parker-Williams J, Chiodini P. General Haematology Task Force. Guideline for laboratory diagnosis of malaria. London (UK): British Committee for Standards in Haematology. 2007;19. [Full Text].
Bailey JW, Williams J, Bain BJ, et al. Guideline: the laboratory diagnosis of malaria. General Haematology Task Force of the British Committee for Standards in Haematology. Br J Haematol. 2013 Dec. 163 (5):573-80. [Medline].
Rapid diagnostic tests for malaria ---Haiti, 2010. MMWR Morb Mortal Wkly Rep. 2010 Oct 29. 59(42):1372-3. [Medline].
Wongsrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer WH. A review of malaria diagnostic tools: microscopy and rapid diagnostic test (RDT). Am J Trop Med Hyg. 2007 Dec. 77(6 Suppl):119-27. [Medline].
Centers for Disease Control and Prevention. Notice to Readers: Malaria Rapid Diagnostic Test. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5627a4.htm. Accessed: September 30, 2011.
de Oliveira AM, Skarbinski J, Ouma PO, et al. Performance of malaria rapid diagnostic tests as part of routine malaria case management in Kenya. Am J Trop Med Hyg. 2009 Mar. 80(3):470-4. [Medline].
d'Acremont V, Malila A, Swai N, et al. Withholding antimalarials in febrile children who have a negative result for a rapid diagnostic test. Clin Infect Dis. 2010 Sep 1. 51(5):506-11. [Medline].
Mens P, Spieker N, Omar S, Heijnen M, Schallig H, Kager PA. Is molecular biology the best alternative for diagnosis of malaria to microscopy? A comparison between microscopy, antigen detection and molecular tests in rural Kenya and urban Tanzania. Trop Med Int Health. 2007 Feb. 12(2):238-44. [Medline].
Dondorp AM, Fanello CI, Hendriksen IC, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 13. 376(9753):1647-57. [Medline]. [Full Text].
Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2012 Jun 13. 6:CD005967. [Medline].
US Food and Drug Administration FDA Approves Coartem Tablets to Treat Malaria. FDA. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149559.htm. Accessed: April 8, 2009.
Teuscher F, Gatton ML, Chen N, Peters J, Kyle DE, Cheng Q. Artemisinin-induced dormancy in plasmodium falciparum: duration, recovery rates, and implications in treatment failure. J Infect Dis. 2010 Nov 1. 202(9):1362-8. [Medline]. [Full Text].
Tozan Y, Klein EY, Darley S, Panicker R, Laxminarayan R, Breman JG. Prereferral rectal artesunate for treatment of severe childhood malaria: a cost-effectiveness analysis. Lancet. 2010 Dec 4. 376(9756):1910-5. [Medline].
Amaratunga C, Sreng S, Suon S, et al. Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study. Lancet Infect Dis. 2012 Nov. 12(11):851-8. [Medline].
Othoro C, Johnston D, Lee R, Soverow J, Bystryn JC, Nardin E. Enhanced immunogenicity of Plasmodium falciparum peptide vaccines using a topical adjuvant containing a potent synthetic Toll-like receptor 7 agonist, imiquimod. Infect Immun. 2009 Feb. 77(2):739-48. [Medline]. [Full Text].
Richards JS, Stanisic DI, Fowkes FJ, et al. Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia. Clin Infect Dis. 2010 Oct 15. 51(8):e50-60. [Medline].
Olotu A, Lusingu J, Leach A, et al. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 2011 Feb. 11(2):102-9. [Medline].
First Malaria Vaccine Approved by EU Regulators. Medscape Medical News. Available at http://www.medscape.com/viewarticle/848608. July 24, 2015;
Janeczko LL. Primaquine protects against P. vivax malaria relapse. Medscape Medical News. Jan 3, 2013. Available at http://www.medscape.com/viewarticle/777109. Accessed: Jan 16, 2013.
Sutanto I, Tjahjono B, Basri H, et al. Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia. Antimicrob Agents Chemother. 2013 Mar. 57 (3):1128-35. [Medline].
Lowes R. FDA Strengthens Warning on Mefloquine Risks. Medscape Medical News. Jul 29 2013. [Full Text].
US Food and Drug Administration. FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects. FDA. Available at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM362232.pdf. Accessed: Aug 6 2013.
Briand V, Bottero J, Noel H, et al. Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine. J Infect Dis. 2009 Sep 15. 200(6):991-1001. [Medline].
Briand V, Cottrell G, Massougbodji A, Cot M. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas. Malar J. 2007 Dec 4. 6:160. [Medline]. [Full Text].
Trape JF, Tall A, Diagne N, et al. Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies: a longitudinal study. Lancet Infect Dis. 2011 Dec. 11(12):925-32. [Medline].
Centers for Disease Control and Prevention. Atlanta, GA: DHHS; 2009. Malaria and Travelers. Available at http://www.cdc.gov/malaria/travelers/index.html. Accessed: Sep 15, 2011.
The RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011/Oct. 365:[Full Text].
White NJ. A vaccine for malaria (editorial). N Engl J Med. 2011/Oct. 365:[Full Text].
[Guideline] Centers for Disease Control and Prevention. Malaria Diagnosis and Treatment in the United States. Available at http://www.cdc.gov/malaria/diagnosis_treatment/index.html. Accessed: Sep 15, 2011.
Poespoprodjo JR, Fobia W, Kenangalem E, et al. Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic. Clin Infect Dis. 2008 May 1. 46(9):1374-81. [Medline]. [Full Text].
|Findings||P falciparum||P vivax||P ovale||P malariae|
|Only early forms present in peripheral blood||Yes||No||No||No|
|Age of infected RBCs||RBCs of all ages||Young RBCs||Young RBCs||Old RBCs|
|Other features||Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms.||Late trophozoites develop pleomorphic cytoplasm.||Infected RBCs become oval, with tufted edges.||Bandlike trophozoites are distinctive.|