Skip to main content

Advertisement

Log in

Strategic use of antimalarial drugs that block falciparum malaria parasite transmission to mosquitoes to achieve local malaria elimination

  • Review
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

The ultimate aim of malaria chemotherapy is not only to treat symptomatic infection but also to reduce transmission potential. With the absence of clinically proven vaccines, drug-mediated blocking of malaria transmission gains growing interest in the research agenda for malaria control and elimination. In addition to the limited arsenal of antimalarials available, the situation is further complicated by the fact that most commonly used antimalarials are being extensively resisted by the parasite and do not assist in blocking its transmission to vectors. Most antimalarials do not exhibit gametocytocidal and/ or sporontocidal activity against the sexual stages of Plasmodium falciparum but may even enhance gametocytogenesis and gametocyte transmissibility. Artemisinin derivatives and 8-aminoquinolines are useful transmission-blocking antimalarials whose optimal actions are on different stages of gametocytes. Transmission control interventions that include gametocytocides covering the spectrum of gametocyte development should be used to reduce and, if possible, stop transmission and infectivity of gametocytes to mosquitoes. Potent gametocytocidal drugs could also help deter the spread of antimalarial drug resistance. Novel proof-of-concept compounds with gametocytocidal activity, such as trioxaquines, synthetic endoperoxides, and spiroindolone, should be further tested for possible clinical utility before investigating the possibility of integrating them in transmission-reducing interventions. Strategic use of potent gametocytocides at appropriate timing with artemisinin-based combination therapies should be given attention, at least, in the short run. This review highlights the role that antimalarials could play in blocking gametocyte transmission and infectivity to mosquitoes and, hence, in reducing the potential of falciparum malaria transmissibility and drug resistance spread.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abay SM (2013) Blocking malaria transmission to Anopheles mosquitoes using artemisinin derivatives and primaquine: a systematic review and meta-analysis. Parasit Vectors 6:278

    PubMed  PubMed Central  Google Scholar 

  • Abdul-Ghani R, Farag H, Allam A, Azazy A (2014a) Measuring resistant-genotype transmission of malaria parasites: challenges and prospects. Parasitol Res 113:1481–1487

    PubMed  Google Scholar 

  • Abdul-Ghani R, Al-Maktari MT, Al-Shibani LA, Allam AF (2014b) A better resolution for integrating methods for monitoring Plasmodium falciparum resistance to antimalarial drugs. Acta Trop 137C:44–57

    Google Scholar 

  • Adjalley SH et al (2011) Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. Proc Natl Acad Sci U S A 108:E1214–E1223

    PubMed  PubMed Central  Google Scholar 

  • Adjuik M et al (2004) Artesunate combinations for treatment of malaria: meta-analysis. Lancet 363:9–17

    PubMed  CAS  Google Scholar 

  • Ali E, Mackinnon MJ, Abdel-Muhsin AM, Ahmed S, Walliker D, Babiker HA (2006) Increased density but not prevalence of gametocytes following drug treatment of Plasmodium falciparum. Trans R Soc Trop Med Hyg 100:176–183

    PubMed  CAS  Google Scholar 

  • Aminake MN et al (2011) Thiostrepton and derivatives exhibit antimalarial and gametocytocidal activity by dually targeting parasite proteasome and apicoplast. Antimicrob Agents Chemother 55:1338–1348

    PubMed  PubMed Central  CAS  Google Scholar 

  • Andagalu B, Mativo J, Kamau E, Ogutu B (2014) Longitudinal study on Plasmodium falciparum gametocyte carriage following artemether-lumefantrine administration in a cohort of children aged 12-47 months living in Western Kenya, a high transmission area. Malar J 13:265

    PubMed  PubMed Central  Google Scholar 

  • Arango EM, Upegui YA, Carmona-Fonseca J (2012) Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia. Acta Trop 122:177–182

  • Barnes KI et al (2005) Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa. PLoS Med 2:e330

    PubMed  PubMed Central  Google Scholar 

  • Beavogui AH et al (2010) Low infectivity of Plasmodium falciparum gametocytes to Anopheles gambiae following treatment with sulfadoxine-pyrimethamine in Mali. Int J Parasitol 40:1213–1220

    PubMed  PubMed Central  CAS  Google Scholar 

  • Benoit-Vical F et al (2007) Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Antimicrob Agents Chemother 51:1463–1472

    PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  Google Scholar 

  • Bousema JT et al (2006) Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis 193:1151–1159

    PubMed  CAS  Google Scholar 

  • Bousema T et al (2010) Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs. Malar J 9:136

    PubMed  PubMed Central  Google Scholar 

  • Bray RS, Burgess RW, Fox RM, Miller MJ (1959) Effect of pyrimethamine upon sporogony and pre-erythrocytic schizogony of Laverania falciparum. Bull World Health Organ 21:233–238

    PubMed  PubMed Central  CAS  Google Scholar 

  • Brueckner RP, Lasseter KC, Lin ET, Schuster BG (1998a) First-time-in-humans safety and pharmacokinetics of WR 238605, a new antimalarial. Am J Trop Med Hyg 58:645–649

    PubMed  CAS  Google Scholar 

  • Brueckner RP, Coster T, Wesche DL, Shmuklarsky M, Schuster BG (1998b) Prophylaxis of Plasmodium falciparum infection in a human challenge model with WR 238605, a new 8-aminoquinoline antimalarial. Antimicrob Agents Chemother 42:1293–1294

    PubMed  PubMed Central  CAS  Google Scholar 

  • Buchholz K, Burke TA, Williamson KC, Wiegand RC, Wirth DF, Marti M (2011) A high-throughput screen targeting malaria transmission stages opens new avenues for drug development. J Infect Dis 203:1445–1453

    PubMed  PubMed Central  Google Scholar 

  • Buckling AG, Taylor LH, Carlton JM, Read AF (1997) Adaptive changes in Plasmodium transmission strategies following chloroquine chemotherapy. Proc Biol Sci 264:553–559

    PubMed  PubMed Central  CAS  Google Scholar 

  • Buckling A, Ranford-Cartwright LC, Miles A, Read AF (1999) Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitol 118:339–346

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Butcher GA (1997) Antimalarial drugs and the mosquito transmission of Plasmodium. Int J Parasitol 27:975–987

    PubMed  CAS  Google Scholar 

  • Butterworth AS, Skinner-Adams TS, Gardiner DL, Trenholme KR (2013) Plasmodium falciparum gametocytes: with a view to a kill. Parasitology 140:1718–1734

    PubMed  CAS  Google Scholar 

  • Chauhan SS, Sharma M, Chauhan PM (2010) Trioxaquines: hybrid molecules for the treatment of malaria. Drug News Perspect 23:632–646

    PubMed  CAS  Google Scholar 

  • Chavalitshewinkoon-Petmitr P, Pongvilairat G, Auparakkitanon S, Wilairat P (2000) Gametocytocidal activity of pyronaridine and DNA topoisomerase II inhibitors against multidrug-resistant Plasmodium falciparum in vitro. Parasitol Int 48:275–280

    PubMed  CAS  Google Scholar 

  • Chen PQ et al (1994) The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin. Chin Med J (Engl) 107:709–711

    CAS  Google Scholar 

  • Chiodini PL et al (1995) Evaluation of atovaquone in the treatment of patients with uncomplicated Plasmodium falciparum malaria. J Antimicrob Chemother 36:1073–1078

    PubMed  CAS  Google Scholar 

  • Chomcharn Y, Surathin K, Bunnag D, Sucharit S, Harinasuta T (1980) Effect of a single dose of primaquine on a Thai strain of Plasmodium falciparum. Southeast Asian J Trop Med Public Health 11:408–412

    PubMed  CAS  Google Scholar 

  • Chotivanich K et al (2006) Transmission-blocking activities of quinine, primaquine, and artesunate. Antimicrob Agents Chemother 50:1927–1930

    PubMed  PubMed Central  CAS  Google Scholar 

  • Chutmongkonkul M, Maier WA, Seitz HM (1992) Plasmodium falciparum: effect of chloroquine, halofantrine and pyrimethamine on the infectivity of gametocytes for Anopheles stephensi mosquitoes. Ann Trop Med Parasitol 86:103–110

    PubMed  CAS  Google Scholar 

  • Coleman RE (1990) Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensi. Am J Trop Med Hyg 42:196–205

    PubMed  CAS  Google Scholar 

  • Coleman RE, Clavin AM, Milhous WK (1992) Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR mice and Anopheles stephensi mosquitoes. Am J Trop Med Hyg 46:169–182

    PubMed  CAS  Google Scholar 

  • Coleman RE, Nath AK, Schneider I, Song GH, Klein TA, Milhous WK (1994) Prevention of sporogony of Plasmodium falciparum and P. berghei in Anopheles stephensi mosquitoes by transmission-blocking antimalarials. Am J Trop Med Hyg 50:646–653

    PubMed  CAS  Google Scholar 

  • Coulibaly B et al (2009) Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS ONE 4:e5318

    PubMed  PubMed Central  Google Scholar 

  • Crockett M, Kain KC (2007) Tafenoquine: a promising new antimalarial agent. Expert Opin Investig Drugs 16:705–715

    PubMed  CAS  Google Scholar 

  • Czesny B, Goshu S, Cook JL, Williamson KC (2009) The proteasome inhibitor epoxomicin has potent Plasmodium falciparum gametocytocidal activity. Antimicrob Agents Chemother 53:4080–4085

    PubMed  PubMed Central  CAS  Google Scholar 

  • Dechy-Cabaret O, Benoit-Vical F, Robert A, Meunier B (2000) Preparation and antimalarial activities of “trioxaquines”, new modular molecules with a trioxane skeleton linked to a 4-aminoquinoline. Chembiochem 1:281–283

    PubMed  CAS  Google Scholar 

  • Dechy-Cabaret O et al (2004) Synthesis and antimalarial activity of trioxaquine derivatives. Chemistry 10:1625–1636

    PubMed  CAS  Google Scholar 

  • Delves MJ, Sinden RE (2010) A semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studies. Malar J 9:35

    PubMed  PubMed Central  Google Scholar 

  • Delves MJ et al (2012) The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLoS Med 9:e1001169

    PubMed  PubMed Central  Google Scholar 

  • Drakeley CJ et al (2004) Addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a significant but short-lived reduction in infectiousness for mosquitoes. Trop Med Int Health 9:53–61

    PubMed  CAS  Google Scholar 

  • Drakeley C, Sutherland C, Bousema JT, Sauerwein RW, Targett GA (2006) The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol 22:424–430

    PubMed  Google Scholar 

  • Eastman RT, Fidock DA (2009) Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol 7:864–874

    PubMed  PubMed Central  CAS  Google Scholar 

  • Enosse S, Butcher GA, Margos G, Mendoza J, Sinden RE, Høgh B (2000) The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone) and chloroquine. Trans R Soc Trop Med Hyg 94:77–82

    PubMed  CAS  Google Scholar 

  • Giha HA (2010) Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope. Parasitol Res 106:549–552

    PubMed  Google Scholar 

  • Giha HA, Elbashir MI, A-Elbasit IE, A-Gadir TM, ElGhazali G (2008) Bimodal transmission of cerebral malaria and severe malarial anemia and reciprocal co-existence of sexual and asexual parasitemia in an area of seasonal malaria transmission. Parasitol Res 103:81–85

    PubMed  Google Scholar 

  • Githeko AK, Brandling-Bennett AD, Beier M, Atieli F, Owaga M, Collins FH (1992) The reservoir of Plasmodium falciparum malaria in a holoendemic area of western Kenya. Trans R Soc Trop Med Hyg 86:355–358

    PubMed  CAS  Google Scholar 

  • Gogtay NJ, Kamtekar KD, Dalvi SS, Chogle AR, Aigal U, Kshirsagar NA (2004) Preliminary report of the evaluation of the gametocytocidal action of bulaquine, in adult patients with acute, Plasmodium falciparum malaria. Ann Trop Med Parasitol 98:525–528

    PubMed  CAS  Google Scholar 

  • Gogtay NJ et al (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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Govere JM, Durrheim DN, Mngomezulu NM, Barnes K, Sharp B (2003) Infectivity of Plasmodium falciparum gametocytes to Anopheles arabiensis after treatment with sulfadoxine-pyrimethamine. Trans R Soc Trop Med Hyg 97:707–708

    PubMed  CAS  Google Scholar 

  • Grande T et al (2007) A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS ONE 2:e1101

    PubMed  PubMed Central  Google Scholar 

  • Graves PM, Gelband H, Garner P (2014) Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission. Cochrane Database Syst Rev (in press) doi: 10.1002/14651858.CD008152.pub3.

  • Hale BR et al (2003) A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clin Infect Dis 36:541–549

    PubMed  CAS  Google Scholar 

  • Hallett RL et al (2004) Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes. Antimicrob Agents Chemother 48:3940–3943

    PubMed  PubMed Central  CAS  Google Scholar 

  • Hallett RL et al (2006) Chloroquine/sulphadoxine-pyrimethamine for Gambian children with malaria: transmission to mosquitoes of multidrug-resistant Plasmodium falciparum. PLoS Clin Trials 1:e15

    PubMed  PubMed Central  Google Scholar 

  • Handunnetti SM, Gunewardena DM, Pathirana PP, Ekanayake K, Weerasinghe S, Mendis KN (1996) Features of recrudescent chloroquine-resistant Plasmodium falciparum infections confer a survival advantage on parasites, and have implications for disease control. Trans R Soc Trop Med Hyg 90:563–567

    PubMed  CAS  Google Scholar 

  • Hawking F, Wilson ME, Gammage K (1971) Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum. Trans R Soc Trop Med Hyg 65:549–559

    PubMed  CAS  Google Scholar 

  • Hogh B et al (1998) The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. Am J Trop Med Hyg 58:176–182

    PubMed  CAS  Google Scholar 

  • Howes RE, Battle KE, Satyagraha AW, Baird JK, Hay SI (2013) G6PD deficiency: global distribution, genetic variants and primaquine therapy. Adv Parasitol 81:133–201

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kiszewski AE (2011) Blocking Plasmodium falciparum malaria transmission with drugs: the gametocytocidal and sporontocidal properties of current and prospective antimalarials. Pharmaceuticals 4:44–68

    PubMed Central  CAS  Google Scholar 

  • Klein TA, Tada MS, Lima JBP (1991) Infection of Anopheles darlingi fed on patients with Plasmodium falciparum before and after treatment with quinine or quinine plus tetracycline. Am J Trop Med Hyg 44:604–608

    PubMed  CAS  Google Scholar 

  • Kone A et al (2010) Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival. Int J Parasitol 40(10):1221–1228

    PubMed  PubMed Central  CAS  Google Scholar 

  • Kremsner PG, Krishna S (2004) Antimalarial combinations. Lancet 364:285–294

    PubMed  CAS  Google Scholar 

  • Kumar N, Zheng H (1990) Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol Res 76:214–218

    PubMed  CAS  Google Scholar 

  • Lanners HN (1991) Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. Parasitol Res 77:478–481

    PubMed  CAS  Google Scholar 

  • Lawpoolsri S et al (2009) Optimally timing primaquine treatment to reduce Plasmodium falciparum transmission in low endemicity Thai-Myanmar border populations. Malar J 8:159

    PubMed  PubMed Central  Google Scholar 

  • Lelièvre J, Almela MJ, Lozano S, Miguel C, Franco V, Leroy D, Herreros E (2012) Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence “transmission blocking” assay. PLoS ONE 7:e35019

    PubMed  PubMed Central  Google Scholar 

  • Lell B et al (2000) Malaria chemoprophylaxis with tafenoquine: a randomised study. Lancet 355:2041–2045

    PubMed  CAS  Google Scholar 

  • López-Antuñano FJ (1999) Is primaquine useful and safe as true exo-erythrocytic merontocidal, hypnozoitocidal and gametocidal antimalarial drug? Salud Publica Mex 41:410–419

    PubMed  Google Scholar 

  • Mehlhorn H (ed) (2008) Encyclopedia of parasitology, 3rd edn. Heidlberg, Springer

    Google Scholar 

  • Mehra N, Bhasin VK (1993) In vitro gametocytocidal activity of artemisinin and its derivatives on Plasmodium falciparum. Jpn J Med Sci Biol 46:37–43

    PubMed  CAS  Google Scholar 

  • Méndez F et al (2002) Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol 156:230–238

    PubMed  Google Scholar 

  • Méndez F et al (2007) Selection of antifolate-resistant Plasmodium falciparum by sulfadoxine-pyrimethamine treatment and infectivity to Anopheles mosquitoes. Am J Trop Med Hyg 77:438–43

    PubMed  Google Scholar 

  • Mens PF et al (2008) A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Malar J 7:237

    PubMed  PubMed Central  Google Scholar 

  • Mita T, Tanabe K, Kita K (2009) Spread and evolution of Plasmodium falciparum drug resistance. Parasitol Int 58:201–209

    PubMed  CAS  Google Scholar 

  • Mockenhaupt FP et al (2005) Plasmodium falciparum dhfr but not dhps mutations associated with sulphadoxine-pyrimethamine treatment failure and gametocyte carriage in northern Ghana. Trop Med Int Health 10:901–908

    PubMed  CAS  Google Scholar 

  • Müller O et al (2013) Haemolysis risk in methylene blue treatment of G6PD-sufficient and G6PD-deficient West-African children with uncomplicated falciparum malaria: a synopsis of four RCTs. Pharmacoepidemiol Drug Saf 22:376–385

    PubMed  Google Scholar 

  • Murambiwa P, Masola B, Govender T, Mukaratirwa S, Musabayane CT (2011) Anti-malarial drug formulations and novel delivery systems: a review. Acta Trop 118:71–79

    PubMed  CAS  Google Scholar 

  • Newton PN et al (2006) Manslaughter by fake artesunate in Asia–will Africa be next? PLoS Med 3:e197

    PubMed  PubMed Central  Google Scholar 

  • Nosten F, Hien TT, White NJ (1998) Use of artemisinin derivatives for the control of malaria. Med Trop (Mars) 58:45–49

    CAS  Google Scholar 

  • Nosten F et al (2000) Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 356:297–302

    PubMed  CAS  Google Scholar 

  • Okell LC, Drakeley CJ, Ghani AC, Bousema T, Sutherland CJ (2008) Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar J 7:125

    PubMed  PubMed Central  Google Scholar 

  • Ouédraogo AL et al (2008) Seasonal patterns of Plasmodium falciparum gametocyte prevalence and density in a rural population of Burkina Faso. Acta Trop 105:28–34

    PubMed  Google Scholar 

  • Peatey CL et al (2010) Antimalarial asexual stage-specific and gametocytocidal activities of HIV protease inhibitors. Antimicrob Agents Chemother 54:1334–1337

    PubMed  PubMed Central  CAS  Google Scholar 

  • Peatey CL, Spicer TP, Hodder PS, Trenholme KR, Gardiner DL (2011) A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes. Mol Biochem Parasitol 180:127–131

    PubMed  CAS  Google Scholar 

  • Peatey CL, Leroy D, Gardiner DL, Trenholme KR (2012) Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes? Malar J 11:34

    PubMed  PubMed Central  Google Scholar 

  • Price RN et al (1996) Effects of artemisinin derivatives on malaria transmissibility. Lancet 347:1654–1658

    PubMed  CAS  Google Scholar 

  • Price R et al (1999) Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am J Trop Med Hyg 60:1019–1023

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Reeve PA, Toaliu H, Kaneko A, Hall JJ, Ganczakowski M (1992) Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency. J Trop Med Hyg 95:349–351

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Ringwald P, Meche FS, Basco LK (1999) Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria. Am J Trop Med Hyg 61:446–448

    PubMed  CAS  Google Scholar 

  • Robert V, Molez JF, Trape JF (1996) Short report: gametocytes, chloroquine pressure, and the relative parasite survival advantage of resistant strains of falciparum malaria in west Africa. Am J Trop Med Hyg 55:350–351

    PubMed  CAS  Google Scholar 

  • Robert V, Awono-Ambene HP, Le Hesran JY, Trape JF (2000) Gametocytemia and infectivity to mosquitoes of patients with uncomplicated Plasmodium falciparum malaria attacks treated with chloroquine or sulfadoxine plus pyrimethamine. Am J Trop Med Hyg 62:210–216

    PubMed  CAS  Google Scholar 

  • Sáenz FE, Mutka T, Udenze K, Oduola AM, Kyle DE (2012) Novel 4-aminoquinoline analogs highly active against the blood and sexual stages of Plasmodium in vivo and in vitro. Antimicrob Agents Chemother 56:4685–4692

    PubMed  PubMed Central  Google Scholar 

  • Sawa P et al (2013) Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J Infect Dis 207:1637–1645

    PubMed  CAS  Google Scholar 

  • Schirmer RH et al (2003) Methylene blue as an antimalarial agent. Redox Rep 8:272–275

    PubMed  CAS  Google Scholar 

  • Schlitzer M (2008) Antimalarial drugs— what is in use and what is in the pipeline. Arch Pharm 341:149–163

    CAS  Google Scholar 

  • Schneweis S, Maier WA, Seitz HM (1991) Haemolysis of infected erythrocytes—a trigger for formation of Plasmodium falciparum gametocytes? Parasitol Res 77:458–460

    PubMed  CAS  Google Scholar 

  • Shekalaghe S et al (2007) Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS ONE 2:e1023

    PubMed  PubMed Central  Google Scholar 

  • Shute PG, Maryon M (1954) The effect of pyrimethamine (daraprim) on the gametocytes and oocysts of Plasmodium falciparum and Plasmodium vivax. Trans R Soc Trop Med Hyg 48:50–63

    PubMed  CAS  Google Scholar 

  • Sinden RE (1982a) Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology 84:1–11

    PubMed  CAS  Google Scholar 

  • Sinden RE (1982b) Gametocytogenesis of Plasmodium falciparum in vitro: ultrastructural observations on the lethal action of chloroquine. Ann Trop Med Parasitol 76:15–23

    PubMed  CAS  Google Scholar 

  • Smalley ME (1977) Plasmodium falciparum gametocytes: the effect of chloroquine on their development. Trans R Soc Trop Med Hyg 71:526–529

    PubMed  CAS  Google Scholar 

  • Smalley ME, Sinden RE (1977) Plasmodium falciparum gametocytes: their longevity and infectivity. Parasitology 74:1–8

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  PubMed Central  CAS  Google Scholar 

  • Sokhna CS, Trape JF, Robert V (2001) Gametocytaemia in Senegalese children with uncomplicated falciparum malaria treated with chloroquine, amodiaquine or sulfadoxine + pyrimethamine. Parasite 8:243–250

    PubMed  CAS  Google Scholar 

  • Sowunmi A, Fateye BA (2003) Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs. Trop Med Int Health 8:783–792

    PubMed  CAS  Google Scholar 

  • Sowunmi A, Balogun ST, Gbotosho GO, Happi CT (2008) Plasmodium falciparum gametocyte sex ratios in children with acute, symptomatic, uncomplicated infections treated with amodiaquine. Malar J 7:169

    PubMed  PubMed Central  Google Scholar 

  • Sowunmi A et al (2009) Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children. Malar J 8:297

    PubMed  PubMed Central  Google Scholar 

  • Suputtamongkol Y et al (2003) The efficacy of combined mefloquine-artesunate versus mefloquine-primaquine on subsequent development of Plasmodium falciparum gametocytemia. Am J Trop Med Hyg 68:620–623

    PubMed  CAS  Google Scholar 

  • Sutanto I et al (2013) The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South Sumatra, Western Indonesia: an open-label, randomized, controlled trial. Clin Infect Dis 56:685–693

    PubMed  CAS  Google Scholar 

  • Sutherland CJ et al (2002) Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. Am J Trop Med Hyg 67:578–585

    PubMed  CAS  Google Scholar 

  • Sutherland CJ et al (2005) Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med 2:e92

    PubMed  PubMed Central  Google Scholar 

  • Talman AM, Domarle O, McKenzie FE, Ariey F, Robert V (2004) Gametocytogenesis: the puberty of Plasmodium falciparum. Malar J 3:24

    PubMed  PubMed Central  Google Scholar 

  • Tanaka TQ, Williamson KC (2011) A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue. Mol Biochem Parasitol 177:160–163

    PubMed  PubMed Central  CAS  Google Scholar 

  • Tangpukdee N et al (2008) Gametocyte clearance in uncomplicated and severe Plasmodium falciparum malaria after artesunate-mefloquine treatment in Thailand. Korean J Parasitol 46:65–70

    PubMed  PubMed Central  Google Scholar 

  • Targett G et al (2001) Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. J Infect Dis 183:1254–1259

    PubMed  CAS  Google Scholar 

  • Taylor WR, White NJ (2004) Antimalarial drug toxicity: a review. Drug Saf 27:25–61

    PubMed  CAS  Google Scholar 

  • Teklehaimanot A, Nguyen-Dinh P, Collins WE, Barber AM, Campbell CC (1985) Evaluation of sporontocidal compounds using Plasmodium falciparum gametocytes produced in vitro. Am J Trop Med Hyg 34:429–434

    PubMed  CAS  Google Scholar 

  • Tjitra E, Suprianto S, Anstey NM (2002) Higher gametocyte prevalence following failure of treatment of Plasmodium falciparum malaria with sulfadoxine-pyrimethamine and the combination of chloroquine plus sulfadoxine-pyrimethamine: implications for progression of anti-folate resistance. Trans R Soc Trop Med Hyg 96:434–437

    PubMed  CAS  Google Scholar 

  • Tripathi R, Puri SK, Dutta GP (1996) Sodium beta-artelinate—a new potential gametocytocide. Exp Parasitol 82:251–254

    PubMed  CAS  Google Scholar 

  • van der Kolk M, Tebo AE, Nimpaye H, Ndombol DN, Sauerwein RW, Eling WM (2003) Transmission of Plasmodium falciparum in urban Yaoundé, Cameroon, is seasonal and age-dependent. Trans R Soc Trop Med Hyg 97:375–379

    PubMed  Google Scholar 

  • van Pelt-Koops JC et al (2012) The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to Anopheles mosquito vector. Antimicrob Agents Chemother 56:3544–3548

    PubMed  PubMed Central  Google Scholar 

  • von Seidlein L, Drakeley C, Greenwood B, Walraven G, Targett G (2001a) Risk factors for gametocyte carriage in Gambian children. Am J Trop Med Hyg 65:523–527

    Google Scholar 

  • von Seidlein L, Jawara M, Coleman R, Doherty T, Walraven G, Targett G (2001b) Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria. Trop Med Int Health 6:92–98

    Google Scholar 

  • Walsh DS et al (2004) Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria. J Infect Dis 190:1456–1463

    PubMed  CAS  Google Scholar 

  • White NJ (2008) The role of anti-malarial drugs in eliminating malaria. Malar J 7:S8

    PubMed  PubMed Central  Google Scholar 

  • White NJ (2013) Primaquine to prevent transmission of falciparum malaria. Lancet Infect Dis 13:175–181

    PubMed  CAS  Google Scholar 

  • White NJ, Olliaro PL (1996) Strategies for the prevention of antimalarial drug resistance: rationale for combination chemotherapy for malaria. Parasitol Today 12:399–401

    PubMed  CAS  Google Scholar 

  • WHO (2010) Guidelines for the treatment of malaria, 2nd edn. World Health Organization, Geneva

    Google Scholar 

  • Wilairatana P, Krudsood S, Tangpukdee N (2010a) Appropriate time for primaquine treatment to reduce Plasmodium falciparum transmission in hypoendemic areas. Korean J Parasitol 48:179–182

    PubMed  PubMed Central  CAS  Google Scholar 

  • Wilairatana P, Tangpukdee N, Krudsood S (2010b) Long term primaquine administration to reduce Plasmodium falciparum gametocyte transmission in hypoendemic areas. Southeast Asian J Trop Med Public Health 41:1306–1311

    PubMed  CAS  Google Scholar 

  • Zoungrana A et al (2008) Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS ONE 3:e1630

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rashad Abdul-Ghani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdul-Ghani, R., Beier, J.C. Strategic use of antimalarial drugs that block falciparum malaria parasite transmission to mosquitoes to achieve local malaria elimination. Parasitol Res 113, 3535–3546 (2014). https://doi.org/10.1007/s00436-014-4091-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-014-4091-6

Keywords

Navigation