Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence.
In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda.
We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1–2) vs 3 (2–3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms.
In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed.
The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348).
WHO: World malaria report. 2015.
WHO: Guidelines for the treatment of malaria. Third edition. 2015.
Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010;376(9753):1647–57. CrossRefPubMedPubMedCentral
Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2012;6:CD005967.
Sinclair D, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2011;3:CD005967.
Week EAB: Report says Uganda health workers using abolished drug. 2016.
Marsh K, Snow RW. Malaria transmission and morbidity. Parassitologia. 1999;41(1–3):241–6. PubMed
Muhindo MK, Kakuru A, Jagannathan P, Talisuna A, Osilo E, Orukan F, Arinaitwe E, Tappero JW, Kaharuza F, Kamya MR, et al. Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated plasmodium falciparum malaria. Malar J. 2014;13(32):1475–2875.
Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, Staedke SG, Rosenthal PJ, Wabwire-Mangen F, Bukirwa H. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One. 2008;3(6):0002390. CrossRef
Kamya MR, Arinaitwe E, Wanzira H, Katureebe A, Barusya C, Kigozi SP, Kilama M, Tatem AJ, Rosenthal PJ, Drakeley C, et al. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control. Am J Trop Med Hyg. 2015;92(5):903–12. CrossRefPubMedPubMedCentral
Zwetyenga J, Rogier C, Tall A, Fontenille D, Snounou G, Trape JF, Mercereau-Puijalon O. No influence of age on infection complexity and allelic distribution in plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria. Am J Trop Med Hyg. 1998;59(5):726–35. CrossRefPubMed
Borre MB, Dziegiel M, Hogh B, Petersen E, Rieneck K, Riley E, Meis JF, Aikawa M, Nakamura K, Harada M, et al. Primary structure and localization of a conserved immunogenic plasmodium falciparum glutamate rich protein (GLURP) expressed in both the preerythrocytic and erythrocytic stages of the vertebrate life cycle. Mol Biochem Parasitol. 1991;49(1):119–31. CrossRefPubMed
Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg. 2003;68(2):133–9. PubMed
Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, et al. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS clinical trials. 2006;1(1):19. CrossRef
Akpaloo W, Purssell E. Does the use of Dihydroartemisinin-Piperaquine in treating patients with uncomplicated falciparum malaria reduce the risk for recurrent new falciparum infection more than Artemether-Lumefantrine? Malar Res Treat. 2014;263674(10):19.
Olliaro P, Pinoges L, Checchi F, Vaillant M, Guthmann JP. Risk associated with asymptomatic parasitaemia occurring post-antimalarial treatment. Tropical Med Int Health. 2008;13(1):83–90. CrossRef
WHO: WHO weekly epidemiological record. 2016.
Phiri K, Esan M, van Hensbroek MB, Khairallah C, Faragher B, ter Kuile FO. Intermittent preventive therapy for malaria with monthly artemether-lumefantrine for the post-discharge management of severe anaemia in children aged 4-59 months in southern Malawi: a multicentre, randomised, placebo-controlled trial. Lancet Infect Dis. 2012;12(3):191–200. CrossRefPubMed
Matangila JR, Mitashi P, Inocencio da Luz RA, Lutumba PT, Van Geertruyden JP. Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review. Malar J. 2015;14(450):015–0988.
Idro R, Aloyo J, Mayende L, Bitarakwate E, John CC, Kivumbi GW. Severe malaria in children in areas with low, moderate and high transmission intensity in Uganda. Tropical Med Int Health. 2006;11(1):115–24. CrossRef
- Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
Agnes N. Kiragga
Ambrose O. Talisuna
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II