Treatment of uncomplicated falciparum malaria in nonpregnant adults and children
- Johanna Daily, MD, MSc
Johanna Daily, MD, MSc
- Section Editor — Malaria
- Associate Professor, Department of Medicine, Division of Infectious Diseases
- Albert Einstein College of Medicine
- Section Editors
- Karin Leder, MBBS, FRACP, PhD, MPH, DTMH
Karin Leder, MBBS, FRACP, PhD, MPH, DTMH
- Section Editor — Travel Medicine
- Head of Infectious Diseases Unit
- Monash University, Australia
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Uncomplicated falciparum malaria consists of symptomatic Plasmodium falciparum infection with a positive parasitologic test and parasitemia <4 percent, in the absence of symptoms consistent with severe malaria (table 1).
Issues related to treatment of uncomplicated falciparum malaria in nonpregnant adults and children will be reviewed here. Issues related to treatment of severe malaria, treatment of malaria in pregnant women, and treatment of non-falciparum malaria are discussed separately. (See "Treatment of severe malaria" and "Prevention and treatment of malaria in pregnant women" and "Overview of non-falciparum malaria in nonpregnant adults and children".)
Uncomplicated falciparum malaria consists of symptomatic P. falciparum infection with a positive parasitologic test and parasitemia <4 percent, in the absence of symptoms consistent with severe malaria (table 1). (See "Treatment of severe malaria".)
To establish the diagnosis of malaria, microscopy of blood smears or a rapid diagnostic test (RDT) should be performed. RDTs often can provide the speciation to guide therapy. If the initial diagnostic evaluation is negative, follow-up testing should be performed each day for two more days. (See "Diagnosis of malaria".)
PRINCIPLES OF TREATMENT
Issues related to treatment of malaria, including indications for hospitalization, antimalarial selection and parasitemia monitoring are discussed below.
- World Health Organization. Guidelines for the treatment of malaria, 3rd ed, WHO, Geneva 2015. http://www.who.int/malaria/publications/atoz/9789241549127/en/ (Accessed on September 10, 2015).
- Centers for Disease Control and Prevention. Treatment Guidelines: Treatment of Malaria (Guidelines for Clinicians), 2013. http://www.cdc.gov/malaria/resources/pdf/clinicalguidance.pdf (Accessed on September 10, 2015).
- Centers for Disease Control and Prevention. Malaria Information and Prophylaxis, by Country [A]. http://www.cdc.gov/malaria/travelers/country_table/a.html (Accessed on March 21, 2016).
- Laufer MK, Thesing PC, Eddington ND, et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 2006; 355:1959.
- Newton P, White N. Malaria: new developments in treatment and prevention. Annu Rev Med 1999; 50:179.
- Douglas NM, Nosten F, Ashley EA, et al. Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics. Clin Infect Dis 2011; 52:612.
- Smithuis F, Kyaw MK, Phe O, et al. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis 2010; 10:673.
- Deen JL, von Seidlein L, Dondorp A. Therapy of uncomplicated malaria in children: a review of treatment principles, essential drugs and current recommendations. Trop Med Int Health 2008; 13:1111.
- Ashley EA, Dhorda M, Fairhurst RM, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2014; 371:411.
- Mavoko HM, Nabasumba C, da Luz RI, et al. Efficacy and safety of re-treatment with the same artemisinin-based combination treatment (ACT) compared with an alternative ACT and quinine plus clindamycin after failure of first-line recommended ACT (QUINACT): a bicentre, open-label, phase 3, randomised controlled trial. Lancet Glob Health 2017; 5:e60.
- World Health Organization. Updated WHO Policy Recommendation (October 2012): Single dose Primaquine as a gametocytocide in Plasmodium falciparum malaria. WHO, Geneva 2012. http://www.who.int/malaria/pq_updated_policy_recommendation_en_102012.pdf (Accessed on March 05, 2013).
- Sutanto I, Suprijanto S, Kosasih A, et al. The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial. Clin Infect Dis 2013; 56:685.
- Lawpoolsri S, Klein EY, Singhasivanon P, et al. Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations. Malar J 2009; 8:159.
- Graves PM, Gelband H, Garner P. Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission. Cochrane Database Syst Rev 2015; :CD008152.
- White NJ, Qiao LG, Qi G, Luzzatto L. Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common. Malar J 2012; 11:418.
- Amaratunga C, Lim P, Suon S, et al. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 2016; 16:357.
- Lin JT, Ubalee R, Lon C, et al. Microscopic Plasmodium falciparum Gametocytemia and Infectivity to Mosquitoes in Cambodia. J Infect Dis 2016; 213:1491.
- Das D, Tripura R, Phyo AP, et al. Effect of high-dose or split-dose artesunate on parasite clearance in artemisinin-resistant falciparum malaria. Clin Infect Dis 2013; 56:e48.
- Stepniewska K, Ashley E, Lee SJ, et al. In vivo parasitological measures of artemisinin susceptibility. J Infect Dis 2010; 201:570.
- Rueangweerayut R, Phyo AP, Uthaisin C, et al. Pyronaridine-artesunate versus mefloquine plus artesunate for malaria. N Engl J Med 2012; 366:1298.
- Dondorp AM, Nosten F, Yi P, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 2009; 361:455.
- 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; 12:851.
- Phyo AP, Nkhoma S, Stepniewska K, et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. Lancet 2012; 379:1960.
- Spring MD, Lin JT, Manning JE, et al. Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study. Lancet Infect Dis 2015; 15:683.
- Takala-Harrison S, Jacob CG, Arze C, et al. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis 2015; 211:670.
- Tun KM, Imwong M, Lwin KM, et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect Dis 2015; 15:415.
- Nyunt MH, Hlaing T, Oo HW, et al. Molecular assessment of artemisinin resistance markers, polymorphisms in the k13 propeller, and a multidrug-resistance gene in the eastern and western border areas of Myanmar. Clin Infect Dis 2015; 60:1208.
- Huang F, Takala-Harrison S, Jacob CG, et al. A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment. J Infect Dis 2015; 212:1629.
- Chenet SM, Akinyi Okoth S, Huber CS, et al. Independent Emergence of the Plasmodium falciparum Kelch Propeller Domain Mutant Allele C580Y in Guyana. J Infect Dis 2016; 213:1472.
- Taylor SM, Parobek CM, DeConti DK, et al. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in Sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 2015; 211:680.
- Kamau E, Campino S, Amenga-Etego L, et al. K13-propeller polymorphisms in Plasmodium falciparum parasites from sub-Saharan Africa. J Infect Dis 2015; 211:1352.
- Ménard D, Khim N, Beghain J, et al. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N Engl J Med 2016; 374:2453.
- Looareesuwan S, Chulay JD, Canfield CJ, Hutchinson DB. Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. Am J Trop Med Hyg 1999; 60:533.
- de Alencar FE, Cerutti C Jr, Durlacher RR, et al. Atovaquone and proguanil for the treatment of malaria in Brazil. J Infect Dis 1997; 175:1544.
- Bustos DG, Canfield CJ, Canete-Miguel E, Hutchinson DB. Atovaquone-proguanil compared with chloroquine and chloroquine-sulfadoxine-pyrimethamine for treatment of acute Plasmodium falciparum malaria in the Philippines. J Infect Dis 1999; 179:1587.
- Looareesuwan S, Wilairatana P, Chalermarut K, et al. Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 1999; 60:526.
- Pasvol G, Newton CR, Winstanley PA, et al. Quinine treatment of severe falciparum malaria in African children: a randomized comparison of three regimens. Am J Trop Med Hyg 1991; 45:702.
- Stanley J. Malaria. Emerg Med Clin North Am 1997; 15:113.
- Looareesuwan S, Wilairatana P, Vanijanonta S, et al. Efficacy of quinine-tetracycline for acute uncomplicated falciparum malaria in Thailand. Lancet 1992; 339:369.
- Davis TM, Dembo LG, Kaye-Eddie SA, et al. Neurological, cardiovascular and metabolic effects of mefloquine in healthy volunteers: a double-blind, placebo-controlled trial. Br J Clin Pharmacol 1996; 42:415.
- Looareesuwan S, Viravan C, Vanijanonta S, et al. Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria. Lancet 1992; 339:821.
- Luxemburger C, ter Kuile FO, Nosten F, et al. Single day mefloquine-artesunate combination in the treatment of multi-drug resistant falciparum malaria. Trans R Soc Trop Med Hyg 1994; 88:213.
- Maguire JD, Marwoto H, Richie TL, et al. Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia. Clin Infect Dis 2006; 42:1067.
- Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA 2007; 297:2264.
- PRINCIPLES OF TREATMENT
- Indications for hospitalization
- Antimalarial selection
- - Chloroquine-sensitive malaria
- Clinical approach
- Reversion of chloroquine resistance
- - Chloroquine-resistant malaria
- Within endemic areas
- - Clinical approach
- - Recurrent infection
- - Reducing transmissibility
- - Artemisinin resistance
- Outside endemic areas
- - Clinical approach
- - Recrudescence
- Monitoring parasitemia
- INVESTIGATIONAL ANTIMALARIAL DRUGS
- SUMMARY AND RECOMMENDATIONS