Efficacy of Chloroquine (CQ) Alone Compared to Concomitant CQ and Primaquine for Plasmodium Vivax Infection

Summary

This is a randomized open-label trial to evaluate the efficacy of chloroquine (CQ) alone compared to chloroquine+primaquine (CQ+PQ) in the treatment of uncomplicated malaria caused by Plasmodium vivax infection in a endemic area in the westernmost part of the Amazon Basin of Brazil. The duration of follow up for evaluating CQ efficacy as a schizonticidal drug was 28 days. The duration of complete follow up to detect recurrent P. vivax infections by passive surveillance was six months. All patients in the CQ alone arm received 7 days of PQ treatment (3.5mg/kg total dose) starting on day 28 of the study follow-up.

Timeline

Start

2014-08

Primary completion

2015-08

Completion

2015-09

Publications

• Background Alvarez G, Pineros JG, Tobon A, Rios A, Maestre A, Blair S, Carmona-Fonseca J. Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia. Am J Trop Med Hyg. 2006 Oct;75(4):605-9.
• Background Anez A, Navarro-Costa D, Yucra O, Garnica C, Melgar V, Moscoso M, Arteaga R, Nakao G. [Therapeutic response of Plasmodium vivax to chloroquine in Bolivia]. Biomedica. 2012 Oct-Dec;32(4):527-35. doi: 10.1590/S0120-41572012000400008. Spanish.
• Background Arias AE, Corredor A. Low response of Colombian strains of Plasmodium vivax to classical antimalarial therapy. Trop Med Parasitol. 1989 Mar;40(1):21-3.
• Background Baird JK. Resistance to therapies for infection by Plasmodium vivax. Clin Microbiol Rev. 2009 Jul;22(3):508-34. doi: 10.1128/CMR.00008-09.
• Background Baird JK, Leksana B, Masbar S, Fryauff DJ, Sutanihardja MA, Suradi, Wignall FS, Hoffman SL. Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels. Am J Trop Med Hyg. 1997 Jun;56(6):621-6. doi: 10.4269/ajtmh.1997.56.621.
• Background Baird KJ, Maguire JD, Price RN. Diagnosis and treatment of Plasmodium vivax malaria. Adv Parasitol. 2012;80:203-70. doi: 10.1016/B978-0-12-397900-1.00004-9.
• Background Baird JK, Tiwari T, Martin GJ, Tamminga CL, Prout TM, Tjaden J, Bravet PP, Rawlins S, Ferrel M, Carucci D, Hoffman SL. Chloroquine for the treatment of uncomplicated malaria in Guyana. Ann Trop Med Parasitol. 2002 Jun;96(4):339-48. doi: 10.1179/000349802125001023.
• Background Bray PG, Deed S, Fox E, Kalkanidis M, Mungthin M, Deady LW, Tilley L. Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum. Biochem Pharmacol. 2005 Oct 15;70(8):1158-66. doi: 10.1016/j.bcp.2005.07.021.
• Background Carmona-Fonseca J, Maestre A. Prevention of Plasmodium vivax malaria recurrence: efficacy of the standard total dose of primaquine administered over 3 days. Acta Trop. 2009 Nov;112(2):188-92. doi: 10.1016/j.actatropica.2009.07.024. Epub 2009 Aug 3.
• Background Castillo CM, Osorio LE, Palma GI. Assessment of therapeutic response of Plasmodium vivax and Plasmodium falciparum to chloroquine in a Malaria transmission free area in Colombia. Mem Inst Oswaldo Cruz. 2002 Jun;97(4):559-62. doi: 10.1590/s0074-02762002000400020.
• Background de Santana Filho FS, Arcanjo AR, Chehuan YM, Costa MR, Martinez-Espinosa FE, Vieira JL, Barbosa Md, Alecrim WD, Alecrim Md. Chloroquine-resistant Plasmodium vivax, Brazilian Amazon. Emerg Infect Dis. 2007 Jul;13(7):1125-6. doi: 10.3201/eid1307.061386. No abstract available.
• Background Egan TJ. Chloroquine and primaquine: combining old drugs as a new weapon against falciparum malaria? Trends Parasitol. 2006 Jun;22(6):235-7. doi: 10.1016/j.pt.2006.03.006. Epub 2006 Apr 3.
• Background Garavelli PL, Corti E. Chloroquine resistance in Plasmodium vivax: the first case in Brazil. Trans R Soc Trop Med Hyg. 1992 Mar-Apr;86(2):128. doi: 10.1016/0035-9203(92)90535-k. No abstract available.
• Background Marques MM, Costa MR, Santana Filho FS, Vieira JL, Nascimento MT, Brasil LW, Nogueira F, Silveira H, Reyes-Lecca RC, Monteiro WM, Lacerda MV, Alecrim MG. Plasmodium vivax chloroquine resistance and anemia in the western Brazilian Amazon. Antimicrob Agents Chemother. 2014;58(1):342-7. doi: 10.1128/AAC.02279-12. Epub 2013 Oct 28.
• Background Naing C, Aung K, Win DK, Wah MJ. Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries. Trans R Soc Trop Med Hyg. 2010 Nov;104(11):695-705. doi: 10.1016/j.trstmh.2010.08.009. Epub 2010 Sep 20.
• Background Osorio L, Perez Ldel P, Gonzalez IJ. [Assessment of the efficacy of antimalarial drugs in Tarapaca, in the Colombian Amazon basin]. Biomedica. 2007 Mar;27(1):133-40. Epub 2007 May 31. Spanish.
• Background Phillips EJ, Keystone JS, Kain KC. Failure of combined chloroquine and high-dose primaquine therapy for Plasmodium vivax malaria acquired in Guyana, South America. Clin Infect Dis. 1996 Nov;23(5):1171-3. doi: 10.1093/clinids/23.5.1171.
• Background Rieckmann KH, Davis DR, Hutton DC. Plasmodium vivax resistance to chloroquine? Lancet. 1989 Nov 18;2(8673):1183-4. doi: 10.1016/s0140-6736(89)91792-3.
• Background Ruebush TK 2nd, Zegarra J, Cairo J, Andersen EM, Green M, Pillai DR, Marquino W, Huilca M, Arevalo E, Garcia C, Solary L, Kain KC. Chloroquine-resistant Plasmodium vivax malaria in Peru. Am J Trop Med Hyg. 2003 Nov;69(5):548-52.
• Background Russell B, Chalfein F, Prasetyorini B, Kenangalem E, Piera K, Suwanarusk R, Brockman A, Prayoga P, Sugiarto P, Cheng Q, Tjitra E, Anstey NM, Price RN. Determinants of in vitro drug susceptibility testing of Plasmodium vivax. Antimicrob Agents Chemother. 2008 Mar;52(3):1040-5. doi: 10.1128/AAC.01334-07. Epub 2008 Jan 7.
• Background Russell BM, Udomsangpetch R, Rieckmann KH, Kotecka BM, Coleman RE, Sattabongkot J. Simple in vitro assay for determining the sensitivity of Plasmodium vivax isolates from fresh human blood to antimalarials in areas where P. vivax is endemic. Antimicrob Agents Chemother. 2003 Jan;47(1):170-3. doi: 10.1128/AAC.47.1.170-173.2003.
• Background Soto J, Toledo J, Gutierrez P, Luzz M, Llinas N, Cedeno N, Dunne M, Berman J. Plasmodium vivax clinically resistant to chloroquine in Colombia. Am J Trop Med Hyg. 2001 Aug;65(2):90-3. doi: 10.4269/ajtmh.2001.65.90.
• Background Villalobos-Salcedo JM, Tada MS, Kimura E, Menezes MJ, Pereira da Silva LH. In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine. Ann Trop Med Parasitol. 2000 Dec;94(8):749-58. doi: 10.1080/00034980020027960.
• Ladeia-Andrade S, Menezes MJ, de Sousa TN, Silvino ACR, de Carvalho JF Jr, Salla LC, Nery OA, de Melo GNP, Corder RM, Rodrigues PT, Ferreira MU. Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e01965-18. doi: 10.1128/AAC.01965-18. Print 2019 May.

Drugs

Indications