World Health Organization, 2010. Guidelines for the Treatment of Malaria, 2nd edition. Geneva, Switzerland: World Health Organization.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
World Health Organization, 2012. WHO Evidence Review Group: The Safety and Effectiveness of Single Dose Primaquine as a P. falciparum gametocytocide. Meeting Report. Pullman Hotel, Bangkok, Thailand, August 13–15, 2012, World Health Organization.
World Health Organization, 2015. Policy Brief on Single-Dose Primaquine as Gametocytocide in Plasmodium falciparum Malaria. Geneva, Switzerland: World Health Organization, 8.
Padilla J, Montoya R, 2011. Guía de atención clínica de malaria. Infectio 15: 302–323.
Bunnag D, Harinasuta T, Pinichpongse S, Suntharasami P, 1980. Effect of primaquine on gametocytes of Plasmodium falciparum in Thailand. Lancet 2: 91.
Kaneko A, Kamei K, Suzuki T, Ishii A, Siagian R, Panjaitan W, 1989. Gametocytocidal effect of primaquine in a chemotherapeutic malaria control trial in North Sumatra, Indonesia. Southeast Asian J Trop Med Public Health 20: 351–359.
Singhasivanon V, Chongsuphajaisiddhi T, Sabchareon A, Attanath P, Webster HK, Edstein MD, Lika ID, 1994. Pharmacokinetic study of mefloquine in Thai children aged 5–12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine. Eur J Drug Metab Pharmacokinet 19: 27–32.
Kamtekar KD, Gogtay NJ, Dalvi SS, Karnad DR, Chogle AR, Aigal U, Kshirsagar NA, 2004. A prospective study evaluating the efficacy of a single, 45-mg dose of primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum malaria in Mumbai, India. Ann Trop Med Parasitol 98: 453–458.
Gogtay NJ, Kamtekar KD, Dalvi SS, Mehta SS, Chogle AR, Aigal U, Kshirsagar NA, 2006. A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587]. BMC Infect Dis 6: 16.
El-Sayed B, El-Zaki SE, Babiker H, Gadalla N, Ageep T, Mansour F, Baraka O, Milligan P, Babiker A, 2007. A randomized open-label trial of artesunate-sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan. PLoS One 2: e1311.
Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwein R, Bousema T, 2007. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS One 2: e1023.
Smithuis F et al., 2010. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis 10: 673–681.
Graves PM, Gelband H, Garner P, 2014. Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission. Cochrane Database Syst Rev 6: CD008152.
Graves PM, Gelband H, Garner P, 2015. Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission. Cochrane Database Syst Rev 6: CD008152.
Pukrittayakamee S, Chotivanich K, Chantra A, Clemens R, Looareesuwan S, White NJ, 2004. Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria. Antimicrob Agents Chemother 48: 1329–1334.
Kolaczinski K, Leslie T, Ali I, Durrani N, Lee S, Barends M, Beshir K, Ord R, Hallett R, Rowland M, 2012. Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP. PLoS One 7: e28957.
White NJ, 2013. Primaquine to prevent transmission of falciparum malaria. Lancet Infect Dis 13: 175–181.
Eziefula AC et al., 2014. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect Dis 14: 130–139.
White NJ et al., 2014. Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria. Malar J 13: 483.
Rieckmann KH, McNamara JV, Frischer H, Stockert TA, Carson PE, Powell RD, 1968. Gametocytocidal and sporontocidal effects of primaquine and of sulfadiazine with pyrimethamine in a chloroquine-resistant strain of Plasmodium falciparum. Bull World Health Organ 38: 625–632.
Baird JK, 2012. Reinventing primaquine for endemic malaria. Expert Opin Emerg Drugs 17: 439–444.
Burgess RW, Bray RS, 1961. The effect of a single dose of primaquine on the gametocytes, gametogony and sporogony of Laverania falciparum. Bull World Health Organ 24: 451–456.
Gonçalves BP et al., 2016. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med 14: 40.
Lederman ER, Maguire JD, Sumawinata IW, Chand K, Elyazar I, Estiana L, Sismadi P, Bangs MJ, Baird JK, 2006. Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia. Malar J 5: 108.
Arango EM, Upegui YA, Carmona-Fonseca J, 2012. Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia. Acta Trop 122: 177–182.
Vásquez AM, Sanín F, Alvarez LG, Tobón A, Ríos A, Blair S, 2009. Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development [in Spanish]. Biomedica 29: 307–319.
Sutanto I, Endawati D, Ling LH, Laihad F, Setiabudy R, Baird JK, 2010. Evaluation of chloroquine therapy for vivax and falciparum malaria in southern Sumatra, western Indonesia. Malar J 9: 52.
Shah NK, Schapira A, Juliano JJ, Srivastava B, MacDonald PD, Poole C, Anvikar A, Meshnick SR, Valecha N, Mishra N, 2013. Nonrandomized controlled trial of artesunate plus sulfadoxine-pyrimethamine with or without primaquine for preventing posttreatment circulation of Plasmodium falciparum gametocytes. Antimicrob Agents Chemother 57: 2948–2954.
Daza Camelo L, 2015. Informe Final del Evento Malaria, Colombia, 2015. Bogotá, Columbi: Instituto Nacional de Salud. Subdirección Prevención, Vigilancia y Control en Salud Pública. Dirección de Vigilancia y Análisis del Riesgo en Salud Pública.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565–568.
Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK, 2009. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol 47: 975–980.
Schneider P, Schoone G, Schallig H, Verhage D, Telgt D, Eling W, Sauerwein R, 2004. Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification. Mol Biochem Parasitol 137: 35–41.
Carmona-Fonseca J, Arango E, Blair S, 2008. Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato. Biomedica 28: 195–212.
Osorio L, Pérez Le P, González IJ, 2007. Assessment of the efficacy of antimalarial drugs in Tarapacá, in the Colombian Amazon basin [in Spanish]. Biomedica 27: 133–140.
Blair S, Carmona-Fonseca J, Piñeros J, Ríos A, Alvarez T, Alvarez G, Tobón A, 2006. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malar J 5: 14.
Arango E, Alvarez T, Carmona J, Blair S, 2004. Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia. Biomedica 24: 79–88.
Osorio L, Ferro B, Castillo C, 2002. Effects of chloroquine and sulfadoxine/pyrimethamine on gametocytes in patients with uncomplicated Plasmodium falciparum malaria in Colombia. Mem Inst Oswaldo Cruz 97: 1221–1223.
Méndez F, Muñoz A, Carrasquilla G, Jurado D, Arévalo-Herrera M, Cortese J, Plowe C, 2002. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol 156: 230–238.
Bousema T, Drakeley C, 2011. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev 24: 377–410.
Kast K, Berens-Riha N, Zeynudin A, Abduselam N, Eshetu T, Löscher T, Wieser A, Shock J, Pritsch M, 2013. Evaluation of Plasmodium falciparum gametocyte detection in different patient material. Malar J 12: 438.
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Treatment against Plasmodium falciparum malaria includes blood schizonticides to clear asexual parasites responsible for disease. The addition of gametocytocidal drugs can eliminate infectious sexual stages with potential for transmission and the World Health Organization recommends a single dose (SD) of primaquine (PQ) to this end. The efficacy of PQ at 0.75 mg/kg to suppress gametocytemia when administered in single or fractionated doses was evaluated. A clinical controlled study with an open-label design was executed; three groups of 20 subjects were studied sequentially. All subjects were treated with the standard dose of artemether–lumefantrine plus the total dose of 0.75 mg/kg of PQ administered (without previous G6PD testing) in three different ways: Group “0.75d-3” received 0.75 mg/kg on day 3; Group “0.50d-1 + 0.25d-3” received 0.50 mg/kg on day 1 and 0.25 mg/kg on day 3; Group “0.25d-1,2,3” received 0.25 mg/kg on days 1, 2, and 3. Subjects were evaluated on days 1, 4, and 7 by thick smear microscopy and quantitative polymerase chain reaction to determine the carriage of immature and mature gametocytes. There were no adverse events. The three schemes caused a marked reduction (75–85%) in prevalence of gametocytes on day 4 compared with day 1, but only the group that received 0.75 mg/kg on day 3 maintained the reduced gametocyte burden until day 7. None of the three treatments were able to clear gametocyte carriage on days 4 or 7, but the group that received the SD had the lowest prevalence of gametocytes (15%). Further studies are needed to establish a PQ regimen with complete efficacy against gametocytes.
Financial support: This work was funded by Colciencias (project codes 111556933361, 111571149686); Comité para el Desarrollo de la Investigación (CODI)-Universidad de Antioquia (project codes 2014-969, 2014-1008); Estrategia Sostenibilidad 2014-2015-Universidad de Antioquia; Universidad de Antioquia. MIAA was funded by an scholarship from the Emerging Leaders of the Americas program from Global Affairs Canada.
Authors’ addresses: Maria Arroyo-Arroyo, Eliana Arango, Jaime Carmona-Fonseca, and Amanda Maestre, Grupo Salud y Comunidad, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia, E-mails: maisarroyo@gmail.com, emarango@gmail.com, jaimecarmonaf@hotmail.com, and aemaestre@gmail.com. Beatriz Aristizabal, Laboratorio de Biología Molecular, Hospital Pablo Tobon Uribe, Medellin, Colombia, E-mail: baristizabal@hptu.org.co. Stephanie Yanow, School of Public Health, University of Alberta, Edmonton, AB, Canada, E-mail: yanow@ualberta.ca.
World Health Organization, 2010. Guidelines for the Treatment of Malaria, 2nd edition. Geneva, Switzerland: World Health Organization.
World Health Organization, 2015. Guidelines for the Treatment of Malaria, 3rd edition. Geneva, Switzerland: World Health Organization.
World Health Organization, 2012. WHO Evidence Review Group: The Safety and Effectiveness of Single Dose Primaquine as a P. falciparum gametocytocide. Meeting Report. Pullman Hotel, Bangkok, Thailand, August 13–15, 2012, World Health Organization.
World Health Organization, 2015. Policy Brief on Single-Dose Primaquine as Gametocytocide in Plasmodium falciparum Malaria. Geneva, Switzerland: World Health Organization, 8.
Padilla J, Montoya R, 2011. Guía de atención clínica de malaria. Infectio 15: 302–323.
Bunnag D, Harinasuta T, Pinichpongse S, Suntharasami P, 1980. Effect of primaquine on gametocytes of Plasmodium falciparum in Thailand. Lancet 2: 91.
Kaneko A, Kamei K, Suzuki T, Ishii A, Siagian R, Panjaitan W, 1989. Gametocytocidal effect of primaquine in a chemotherapeutic malaria control trial in North Sumatra, Indonesia. Southeast Asian J Trop Med Public Health 20: 351–359.
Singhasivanon V, Chongsuphajaisiddhi T, Sabchareon A, Attanath P, Webster HK, Edstein MD, Lika ID, 1994. Pharmacokinetic study of mefloquine in Thai children aged 5–12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine. Eur J Drug Metab Pharmacokinet 19: 27–32.
Kamtekar KD, Gogtay NJ, Dalvi SS, Karnad DR, Chogle AR, Aigal U, Kshirsagar NA, 2004. A prospective study evaluating the efficacy of a single, 45-mg dose of primaquine, as a gametocytocidal agent, in patients with Plasmodium falciparum malaria in Mumbai, India. Ann Trop Med Parasitol 98: 453–458.
Gogtay NJ, Kamtekar KD, Dalvi SS, Mehta SS, Chogle AR, Aigal U, Kshirsagar NA, 2006. A randomized, parallel study of the safety and efficacy of 45 mg primaquine versus 75 mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria [ISCRTN50134587]. BMC Infect Dis 6: 16.
El-Sayed B, El-Zaki SE, Babiker H, Gadalla N, Ageep T, Mansour F, Baraka O, Milligan P, Babiker A, 2007. A randomized open-label trial of artesunate-sulfadoxine-pyrimethamine with or without primaquine for elimination of sub-microscopic P. falciparum parasitaemia and gametocyte carriage in eastern Sudan. PLoS One 2: e1311.
Shekalaghe S, Drakeley C, Gosling R, Ndaro A, van Meegeren M, Enevold A, Alifrangis M, Mosha F, Sauerwein R, Bousema T, 2007. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS One 2: e1023.
Smithuis F et al., 2010. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis 10: 673–681.
Graves PM, Gelband H, Garner P, 2014. Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission. Cochrane Database Syst Rev 6: CD008152.
Graves PM, Gelband H, Garner P, 2015. Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission. Cochrane Database Syst Rev 6: CD008152.
Pukrittayakamee S, Chotivanich K, Chantra A, Clemens R, Looareesuwan S, White NJ, 2004. Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria. Antimicrob Agents Chemother 48: 1329–1334.
Kolaczinski K, Leslie T, Ali I, Durrani N, Lee S, Barends M, Beshir K, Ord R, Hallett R, Rowland M, 2012. Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP. PLoS One 7: e28957.
White NJ, 2013. Primaquine to prevent transmission of falciparum malaria. Lancet Infect Dis 13: 175–181.
Eziefula AC et al., 2014. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect Dis 14: 130–139.
White NJ et al., 2014. Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria. Malar J 13: 483.
Rieckmann KH, McNamara JV, Frischer H, Stockert TA, Carson PE, Powell RD, 1968. Gametocytocidal and sporontocidal effects of primaquine and of sulfadiazine with pyrimethamine in a chloroquine-resistant strain of Plasmodium falciparum. Bull World Health Organ 38: 625–632.
Baird JK, 2012. Reinventing primaquine for endemic malaria. Expert Opin Emerg Drugs 17: 439–444.
Burgess RW, Bray RS, 1961. The effect of a single dose of primaquine on the gametocytes, gametogony and sporogony of Laverania falciparum. Bull World Health Organ 24: 451–456.
Gonçalves BP et al., 2016. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med 14: 40.
Lederman ER, Maguire JD, Sumawinata IW, Chand K, Elyazar I, Estiana L, Sismadi P, Bangs MJ, Baird JK, 2006. Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia. Malar J 5: 108.
Arango EM, Upegui YA, Carmona-Fonseca J, 2012. Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia. Acta Trop 122: 177–182.
Vásquez AM, Sanín F, Alvarez LG, Tobón A, Ríos A, Blair S, 2009. Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development [in Spanish]. Biomedica 29: 307–319.
Sutanto I, Endawati D, Ling LH, Laihad F, Setiabudy R, Baird JK, 2010. Evaluation of chloroquine therapy for vivax and falciparum malaria in southern Sumatra, western Indonesia. Malar J 9: 52.
Shah NK, Schapira A, Juliano JJ, Srivastava B, MacDonald PD, Poole C, Anvikar A, Meshnick SR, Valecha N, Mishra N, 2013. Nonrandomized controlled trial of artesunate plus sulfadoxine-pyrimethamine with or without primaquine for preventing posttreatment circulation of Plasmodium falciparum gametocytes. Antimicrob Agents Chemother 57: 2948–2954.
Daza Camelo L, 2015. Informe Final del Evento Malaria, Colombia, 2015. Bogotá, Columbi: Instituto Nacional de Salud. Subdirección Prevención, Vigilancia y Control en Salud Pública. Dirección de Vigilancia y Análisis del Riesgo en Salud Pública.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565–568.
Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK, 2009. Multiplexed real-time PCR assay for discrimination of Plasmodium species with improved sensitivity for mixed infections. J Clin Microbiol 47: 975–980.
Schneider P, Schoone G, Schallig H, Verhage D, Telgt D, Eling W, Sauerwein R, 2004. Quantification of Plasmodium falciparum gametocytes in differential stages of development by quantitative nucleic acid sequence-based amplification. Mol Biochem Parasitol 137: 35–41.
Carmona-Fonseca J, Arango E, Blair S, 2008. Gametocitemia en malaria por Plasmodium falciparum tratada con amodiaquina o artesunato. Biomedica 28: 195–212.
Osorio L, Pérez Le P, González IJ, 2007. Assessment of the efficacy of antimalarial drugs in Tarapacá, in the Colombian Amazon basin [in Spanish]. Biomedica 27: 133–140.
Blair S, Carmona-Fonseca J, Piñeros J, Ríos A, Alvarez T, Alvarez G, Tobón A, 2006. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malar J 5: 14.
Arango E, Alvarez T, Carmona J, Blair S, 2004. Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia. Biomedica 24: 79–88.
Osorio L, Ferro B, Castillo C, 2002. Effects of chloroquine and sulfadoxine/pyrimethamine on gametocytes in patients with uncomplicated Plasmodium falciparum malaria in Colombia. Mem Inst Oswaldo Cruz 97: 1221–1223.
Méndez F, Muñoz A, Carrasquilla G, Jurado D, Arévalo-Herrera M, Cortese J, Plowe C, 2002. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol 156: 230–238.
Bousema T, Drakeley C, 2011. Epidemiology and infectivity of Plasmodium falciparum and Plasmodium vivax gametocytes in relation to malaria control and elimination. Clin Microbiol Rev 24: 377–410.
Kast K, Berens-Riha N, Zeynudin A, Abduselam N, Eshetu T, Löscher T, Wieser A, Shock J, Pritsch M, 2013. Evaluation of Plasmodium falciparum gametocyte detection in different patient material. Malar J 12: 438.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
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