P. Knowlesi Trial of Artesunate-mefloquine Versus Chloroquine

Summary

Preliminary studies have supported the background efficacy of local standard anti-malarial medications in the treatment of uncomplicated knowlesi malaria, however this has not been tested systematically and there are no current WHO treatment guidelines for this infection. There are both health cost benefits to a more rapidly acting agent, and due to difficulties with microscopic identification there may be more effective treatment for all malaria species if an aligned treatment guideline could be supported. In addition, no therapeutic efficacy monitoring of current first line anti-malarials used for the treatment of P. vivax malaria have been conducted in Malaysia. The investigators aim to test whether the fixed combination of artesunate-mefloquine is superior to chloroquine in order to define the optimal treatment for both uncomplicated P. knowlesi and P. vivax infection in both adults and children in this region.

Timeline

Start

2012-10

Primary completion

2014-12

Completion

2014-12

Publications

• Background Putaporntip C, Hongsrimuang T, Seethamchai S, Kobasa T, Limkittikul K, Cui L, Jongwutiwes S. Differential prevalence of Plasmodium infections and cryptic Plasmodium knowlesi malaria in humans in Thailand. J Infect Dis. 2009 Apr 15;199(8):1143-50. doi: 10.1086/597414.
• Background 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. doi: 10.3201/eid1707.101551.
• Background Ng OT, Ooi EE, Lee CC, Lee PJ, Ng LC, Pei SW, Tu TM, Loh JP, Leo YS. Naturally acquired human Plasmodium knowlesi infection, Singapore. Emerg Infect Dis. 2008 May;14(5):814-6. doi: 10.3201/eid1405.070863.
• Background Jiang N, Chang Q, Sun X, Lu H, Yin J, Zhang Z, Wahlgren M, Chen Q. Co-infections with Plasmodium knowlesi and other malaria parasites, Myanmar. Emerg Infect Dis. 2010 Sep;16(9):1476-8. doi: 10.3201/eid1609.100339.
• Background Vythilingam I. Plasmodium knowlesi in humans: a review on the role of its vectors in Malaysia. Trop Biomed. 2010 Apr;27(1):1-12.
• Background Figtree M, Lee R, Bain L, Kennedy T, Mackertich S, Urban M, Cheng Q, Hudson BJ. Plasmodium knowlesi in human, Indonesian Borneo. Emerg Infect Dis. 2010 Apr;16(4):672-4. doi: 10.3201/eid1604.091624.
• Background Luchavez J, Espino F, Curameng P, Espina R, Bell D, Chiodini P, Nolder D, Sutherland C, Lee KS, Singh B. Human Infections with Plasmodium knowlesi, the Philippines. Emerg Infect Dis. 2008 May;14(5):811-3. doi: 10.3201/eid1405.071407.
• Background Baird JK. Malaria zoonoses. Travel Med Infect Dis. 2009 Sep;7(5):269-77. doi: 10.1016/j.tmaid.2009.06.004. Epub 2009 Jul 14.
• Background Singh B, Daneshvar C. Plasmodium knowlesi malaria in Malaysia. Med J Malaysia. 2010 Sep;65(3):166-72.
• Results Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, Rahman HA, Conway DJ, Singh B. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis. 2008 Jan 15;46(2):165-71. doi: 10.1086/524888.
• Longley RJ, Grigg MJ, Schoffer K, Obadia T, Hyslop S, Piera KA, Nekkab N, Mazhari R, Takashima E, Tsuboi T, Harbers M, Tetteh K, Drakeley C, Chitnis CE, Healer J, Tham WH, Sattabongkot J, White MT, Cooper DJ, Rajahram GS, Barber BE, William T, Anstey NM, Mueller I. Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi. Cell Rep Med. 2022 Jun 21;3(6):100662. doi: 10.1016/j.xcrm.2022.100662.
• Grigg MJ, William T, Menon J, Barber BE, Wilkes CS, Rajahram GS, Edstein MD, Auburn S, Price RN, Yeo TW, Anstey NM. Efficacy of Artesunate-mefloquine for Chloroquine-resistant Plasmodium vivax Malaria in Malaysia: An Open-label, Randomized, Controlled Trial. Clin Infect Dis. 2016 Jun 1;62(11):1403-1411. doi: 10.1093/cid/ciw121. Epub 2016 Apr 22.
• Grigg MJ, William T, Menon J, Dhanaraj P, Barber BE, Wilkes CS, von Seidlein L, Rajahram GS, Pasay C, McCarthy JS, Price RN, Anstey NM, Yeo TW. Artesunate-mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial. Lancet Infect Dis. 2016 Feb;16(2):180-188. doi: 10.1016/S1473-3099(15)00415-6. Epub 2015 Nov 19.
• Grigg MJ, William T, Dhanaraj P, Menon J, Barber BE, von Seidlein L, Rajahram G, Price RN, Anstey NM, Yeo TW. A study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi malaria in Sabah, Malaysia (ACT KNOW trial). BMJ Open. 2014 Aug 19;4(8):e006005. doi: 10.1136/bmjopen-2014-006005.

Drugs

Indications

No indication recorded.