Pediatric Malaria Medication
- Author: Parang N Mehta, MD; Chief Editor: Russell W Steele, MD more...
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, in severe disease. They act on the asexual forms in the erythrocytes and interrupt clinical attacks. Delay in treatment of P falciparum malaria can lead to the development or worsening of severe malaria, which has a poorer prognosis than uncomplicated malaria. Chloroquine, quinine, quinidine, 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 Southeast Asia may be quinine and mefloquine resistant as well; a combination of artesunate and mefloquine, or artesunate and lumefantrine, 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 must include eradication of these. 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. However, this is adequate for gametocidal action, which prevents spread of malaria.
A Cochrane Database of Systematic Reviews study concluded that artesunate is superior to quinine in the treatment of severe malaria in children and adults. The report looked at randomized, controlled trials in which intravenous (IV), intramuscular, or rectal artesunate was compared with IV or intramuscular quinine in the treatment of children and adults with severe malaria.
Blood schizonticides are the first-line drugs for the treatment of malaria.
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 on in severe malaria. 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 tablets that contain 300 mg of the base and injections that contain 40 mg base/mL.
Quinine is a blood schizonticidal drug and is still the drug of choice 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 tablets containing 260 mg and as injections containing 300 mg/mL. Spreading resistance among P falciparum strains to this drug make quinine less reliable in certain parts of Asia and Africa.
A stereoisomer of quinine and a blood schizonticidal drug, quinidine 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 tablets of quinidine sulphate containing 200 mg. The injectable preparation is not always available.
Primaquine is the only drug in clinical use that destroys hypnozoites of 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. It is not to be used until erythrocytic forms have been destroyed by another drug.
Primaquine is 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 or for more than 3 days after leaving it. This is an advantage for people making sudden or short trips.
Mefloquine 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 mefloquine's usefulness for severe and complicated malaria. Mefloquine may cause adverse neuropsychiatric reactions, which may be difficult to identify in children; monitor for symptoms, especially in nonverbal children. The drug is available as tablets containing 250 mg.
Artesunate is effective against blood forms of all 4 types of human malaria parasites. Its special usefulness is against multidrug-resistant P falciparum. It has no action against hepatic schizonts, hypnozoites, or gametocytes. This drug is available as 50-mg tablets and IV injections containing 10 mg/mL.
Artesunate has been found to be the fastest-acting drug against blood forms of the malarial parasite, and so the IV form is especially valuable in the management of severe and complicated malaria.
However, resistance to this drug is spreading, particularly in Southeast Asia. Used alone, artesunate is associated with a high recrudescence rate. It is also feared that solo use will hasten the development of parasite resistance. Combinations of artesunate with mefloquine, lumefantrine, and other drugs have been found to be effective against multidrug-resistant malaria.
Tetracycline is an 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 is common. It is available as capsules containing 250 mg and 500 mg.
This is an antibiotic that acts against P falciparum. Clindamycin 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 the 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.
Atovaquone was recently approved in the United States for the treatment and prophylaxis of malaria. It 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 oral use only and so can be used only for uncomplicated malaria, against which it is very effective, even when used to fight resistant strains. It is also a useful drug for chemoprophylaxis. It is available in adult (250 mg atovaquone and 100 mg proguanil hydrochloride per tablet) and pediatric (62.5 mg atovaquone and 25 mg proguanil hydrochloride per tablet) formulations.
This combination is indicated for the treatment of acute, uncomplicated P falciparum malaria, the most dangerous form of malaria. It contains a 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 dihydroartemisinin (DHA), producing an endoperoxide moiety. Lumefantrine may form a complex with hemin, which inhibits the formation of beta hematin. Artemether and lumefantrine have been shown to be effective in geographic regions where resistance to chloroquine has been reported.
World Health Organization. WHO Fact Sheet on Malaria. Fact Sheet No 94. World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs094/en/print.html. Accessed: June 29, 2007.
Bhatt S, Weiss DJ, Cameron E, et al. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature. 2015 Sep 16. [Medline].
Kelland K. Millions of Children's Lives Saved as Malaria Deaths Plunge -UN. Reuters Health Information. Available at http://www.medscape.com/viewarticle/851119. September 18, 2015; Accessed: September 28, 2015.
Ezeamama AE, Spiegelman D, Hertzmark E, Bosch RJ, Manji KP, Duggan C, et al. HIV Infection and the Incidence of Malaria Among HIV-Exposed Children from Tanzania. J Infect Dis. 2012 May. 205(10):1486-94. [Medline].
Idro R, Marsh K, John CC, Newton CR. Cerebral Malaria; Mechanisms Of Brain Injury And Strategies For Improved Neuro-Cognitive Outcome. Pediatr Res. 2010 Jul 2. [Medline].
Scott JA, Berkley JA, Mwangi I, et al. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. Lancet. 2011 Oct 8. 378(9799):1316-23. [Medline].
FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects. Available at http://www.fda.gov/Drugs/DrugSafety/ucm362227.htm#. Accessed: July 30, 2013.
Abdulla S, Oberholzer R, Juma O, et al. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med. 2008 Dec 11. 359(24):2533-44. [Medline].
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].
Sinclair D, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2011 Mar 16. 3:CD005967. [Medline].