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Reference Manager
BibTeX
Zotero
EndNote
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Cui L, Mascorro CN, Fan Q, Rzomp KA, Khuntirat B, Zhou G, Chen H, Yan G, Sattabongkot J, 2003. Genetic diversity and multiple infections of Plasmodium vivax malaria in western Thailand. Am J Trop Med Hyg 68: 613–619.
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Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, Guthmann JP, Nosten F, Carlton J, Looareesuwan S, Nair S, Sudimack D, Day NP, Anderson TJ, White NJ, 2007. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis 195: 927–933.
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Van den Eede P, Van der Auwera G, Delgado C, Huyse T, Soto-Calle VE, Gamboa D, Grande T, Rodriguez H, Llanos A, Anne J, Erhart A, D'Alessandro U, 2010. Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon. Malar J 9: 151.
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Alvarez G, Pineros JG, Tobon A, Rios A, Maestre A, Blair S, Carmona-Fonseca J, 2006. Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia. Am J Trop Med Hyg 75: 605–609.
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Efficacy of Three Different Regimens of Primaquine for the Prevention of Relapses of Plasmodium vivax Malaria in the Amazon Basin of Peru
Salomón Durand
Salomón Durand
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Cesar Cabezas
Cesar Cabezas
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Andres G. Lescano
Andres G. Lescano
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Mariela Galvez
Mariela Galvez
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Sonia Gutierrez
Sonia Gutierrez
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Nancy Arrospide
Nancy Arrospide
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Carlos Alvarez
Carlos Alvarez
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Meddly L. Santolalla
Meddly L. Santolalla
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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David J. Bacon
David J. Bacon
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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Paul C. F. Graf
Paul C. F. Graf
US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru; Instituto Nacional de Salud, Lima, Peru; Universidad Nacional Mayor de San Marcos, Lima, Peru; Universidad Peruana Cayetano Heredia, Lima, Peru; Direccion Regional de Salud Loreto, Iquitos, Peru; US Naval Medical Center San Diego, San Diego, California
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We evaluated the efficacy of three primaquine (PQ) regimes to prevent relapses with Plasmodium vivax through an open-label randomized trial in Loreto, Peru. Vivax monoinfections were treated with chloroquine for 3 days and PQ in three different regimes: 0.5 mg/kg per day for 5 days (150 mg total), 0.5 mg/kg per day for 7 days (210 mg total), or 0.25 mg/kg per day for 14 days (210 mg total). Biweekly fever assessments and bimonthly thick smears were taken for 210 days. Recurrences after 35 days were considered relapses. One hundred eighty cases were enrolled in each group; 90% of cases completed follow-up. There were no group-related differences in age, sex, or parasitemia. Relapse rates were similar in the 7- and 14-day regimes (16/156 = 10.3% and 22/162 = 13.6%, P = 0.361) and higher in the 5-day group (48/169 = 28.4%, P < 0.001 and P = 0.001, respectively). The 7-day PQ regimen used in Peru is as efficacious as the recommended 14-day regimen and superior to 5 treatment days.
Author Notes
Financial support: This study was supported by the US Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) Work Unit Number 847705.82000.25GB.B0016, the National Institute of Health of Peru, and the Pan-American Health Organization/US Agency for International Development (PAHO-USAID) Americas Malaria Initiative/Amazonic Network of Antimalarial Drug Resistance, AMI/RAVREDA project. A.G.L. is also sponsored by Training Grant 2D43 TW007393 awarded to the US Naval Medical Research Unit No. 6 by the Fogarty International Center of the US National Institutes of Health.
Authors' addresses: Salomón Durand, Meddly L. Santolalla, and David J. Bacon, US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru, E-mails: salomondurand@gmail.com, med_robles@hotmail.com, and david.bacon@nrl.navy.mil. Cesar Cabezas, Instituto Nacional de Salud, Lima, Peru, and Universidad Nacional Mayor de San Marcos, Lima, Peru, Email: ccabezas@ins.gob.pe. Andres G. Lescano, US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru, and Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: willy.lescano@med.navy.mil and wlescano@hotmail.com. Mariela Galvez and Carlos Alvarez, Direccion Regional de Salud Loreto, Iquitos, Peru, E-mails: mariel_gal@hotmail.com and calvarez@diresaloreto.gob.pe. Sonia Gutierrez and Nancy Arrospide, Instituto Nacional de Salud, Lima, Peru, E-mails: sgutierrez@ins.gob.pe and narrospide@hotmail.com. Paul C. F. Graf, US Naval Medical Research Unit No. 6 (NAMRU-6), Lima and Iquitos, Peru, and US Naval Medical Center San Diego, San Diego, CA, E-mail: Paul.Graf@med.navy.mil.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2012. World Malaria Report. Geneva: World Health Organization.
-
2.
Baird JK, Hoffman SL, 2004. Primaquine therapy for malaria. Clin Infect Dis 39: 1336–1345.
-
3.
Klein TA, Tada MS, Lima JB, Tang AT, 1992. Infection of Anopheles darlingi fed on patients infected with Plasmodium vivax before and during treatment with chloroquine plus primaquine in Costa Marques, Rondonia, Brazil. Mem Inst Oswaldo Cruz 87: 191–195.
-
4.
Bray PG, Deed S, Fox E, Kalkanidis M, Mungthin M, Deady LW, Tilley L, 2005. Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum. Biochem Pharmacol 70: 1158–1166.
-
5.
Baird JK, Basri H, Subianto B, Fryauff DJ, McElroy PD, Leksana B, Richie TL, Masbar S, Wignall FS, Hoffman SL, 1995. Treatment of chloroquine-resistant Plasmodium vivax with chloroquine and primaquine or halofantrine. J Infect Dis 171: 1678–1682.
-
6.
Baird JK, Leksana B, Masbar S, Fryauff DJ, Sutanihardja MA, Suradi, Wignall FS, Hoffman SL, 1997. Diagnosis of resistance to chloroquine by Plasmodium vivax: timing of recurrence and whole blood chloroquine levels. Am J Trop Med Hyg 56: 621–626.
-
7.
Clyde DF, McCarthy VC, 1977. Radical cure of Chesson strain vivax malaria in man by 7, not 14, days of treatment with primaquine. Am J Trop Med Hyg 26: 562–563.
-
8.
Schmidt LH, Fradkin R, Vaughan D, Rasco J, 1977. Radical cure of infections with Plasmodium cynomolgi: a function of total 8-aminoquinoline dose. Am J Trop Med Hyg 26: 1116–1128.
-
9.
Collins WE, Jeffery GM, 1996. Primaquine resistance in Plasmodium vivax. Am J Trop Med Hyg 55: 243–249.
-
10.
John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, Price RN, 2012. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J 11: 280.
-
11.
WHO, 2010. Guideline for the Treatment of Malaria: Global Malaria Programme. Geneva: World Health Organization.
-
12.
MINSA, 2000. Politica de Medicamentos para el control de la malaria en el Peru. Lima, Peru: MINSA.
-
13.
Abdon NP, Pinto AY, das Silva R do S, de Souza JM, 2001. Assessment of the response to reduced treatment schemes for vivax malaria. Rev Soc Bras Med Trop 34: 343–348.
-
14.
Pinto AY, Ventura AM, Calvosa VS, Silva Filho MG, Santos MA, Silva RS, Souza JM, 1998. Clinical efficacy of four schemes for vivax malaria treatment in children. J Pediatr (Rio J) 74: 222–227.
-
15.
Orjuela-Sanchez P, da Silva NS, da Silva-Nunes M, Ferreira MU, 2009. Recurrent parasitemias and population dynamics of Plasmodium vivax polymorphisms in rural Amazonia. Am J Trop Med Hyg 81: 961–968.
-
16.
Schoeler GB, Flores-Mendoza C, Fernandez R, Davila JR, Zyzak M, 2003. Geographical distribution of Anopheles darlingi in the Amazon Basin region of Peru. J Am Mosq Control Assoc 19: 286–296.
-
17.
Pan American Health Organization, 1998. Evaluation of the Therapeutic Efficacy of Drugs for the Treatment of Uncomplicated Plasmodium falciparum Malaria in the Americas. Washington, DC: Pan American Health Organization.
-
18.
Graf PC, Durand S, Alvarez Antonio C, Montalvan C, Galves Montoya M, Green MD, Santolalla ML, Salas C, Lucas C, Bacon DJ, Fryauff DJ, 2012. Failure of supervised chloroquine and primaquine regimen for the treatment of Plasmodium vivax in the Peruvian Amazon. Malar Res Treat 2012: 936067.
-
19.
Cui L, Mascorro CN, Fan Q, Rzomp KA, Khuntirat B, Zhou G, Chen H, Yan G, Sattabongkot J, 2003. Genetic diversity and multiple infections of Plasmodium vivax malaria in western Thailand. Am J Trop Med Hyg 68: 613–619.
-
20.
Imwong M, Snounou G, Pukrittayakamee S, Tanomsing N, Kim JR, Nandy A, Guthmann JP, Nosten F, Carlton J, Looareesuwan S, Nair S, Sudimack D, Day NP, Anderson TJ, White NJ, 2007. Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites. J Infect Dis 195: 927–933.
-
21.
McCollum AM, Soberon V, Salas CJ, Santolalla ML, Udhayakumar V, Escalante AA, Graf PC, Durand S, Cabezas C, Bacon DJ, 2014. Genetic variation and recurrent parasitaemia in Peruvian Plasmodium vivax populations. Malar J 13: 67.
-
22.
Van den Eede P, Van der Auwera G, Delgado C, Huyse T, Soto-Calle VE, Gamboa D, Grande T, Rodriguez H, Llanos A, Anne J, Erhart A, D'Alessandro U, 2010. Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon. Malar J 9: 151.
-
23.
Mendoza IG, 1965. Comparative Study of Two Regimens of Radical Treatment of Vivax Malaria in Mexico. Geneva: World Health Organization.
-
24.
Cedillos RA, Warren M, Jeffery GM, 1978. Field evaluation of primaquine in the control of Plasmodium vivax. Am J Trop Med Hyg 27: 466–472.
-
25.
Carmona-Fonseca J, Maestre A, 2009. Prevention of Plasmodium vivax malaria recurrence: efficacy of the standard total dose of primaquine administered over 3 days. Acta Trop 112: 188–192.
-
26.
Alvarez G, Pineros JG, Tobon A, Rios A, Maestre A, Blair S, Carmona-Fonseca J, 2006. Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia. Am J Trop Med Hyg 75: 605–609.
-
27.
Thaeler AD Jr, Arnold J, Alving AS, 1953. A clinical study of primaquine (S. N. 13,272) in the treatment of malaria among the Miskito Indians of Nicaragua. Am J Trop Med Hyg 2: 989–999.
-
28.
Miller LH, Wyler DJ, Glew RH, Collins WE, Contacos PG, 1974. Sensitivity of four Central American strains of Plasmodium vivax to primaquine. Am J Trop Med Hyg 23: 309–310.
-
29.
Villalobos-Salcedo JM, Tada MS, Kimura E, Menezes MJ, Pereira da Si LH, 2000. In-vivo sensitivity of Plasmodium vivax isolates from Rond nia (western Amazon region, Brazil) to regimens including chloroquine and primaquine. Ann Trop Med Parasitol 94: 749–758.
-
30.
Duarte EC, Pang LW, Ribeiro LC, Fontes CJ, 2001. Association of subtherapeutic dosages of a standard drug regimen with failures in preventing relapses of vivax malaria. Am J Trop Med Hyg 65: 471–476.
-
31.
White NJ, 2011. Determinants of relapse periodicity in Plasmodium vivax malaria. Malar J 10: 297.
-
32.
Pedro RS, Guaraldo L, Campos DP, Costa AP, Daniel-Ribeiro CT, Brasil P, 2012. Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil. Malar J 11: 245.
-
33.
Chen N, Auliff A, Rieckmann K, Gatton M, Cheng Q, 2007. Relapses of Plasmodium vivax infection result from clonal hypnozoites activated at predetermined intervals. J Infect Dis 195: 934–941.
-
34.
Van den Eede P, Soto-Calle VE, Delgado C, Gamboa D, Grande T, Rodriguez H, Llanos-Cuentas A, Anne J, D'Alessandro U, Erhart A, 2011. Plasmodium vivax sub-patent infections after radical treatment are common in Peruvian patients: results of a 1-year prospective cohort study. PLoS ONE 6: e16257.
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