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Plasmodium falciparum gametocytes: with a view to a kill

Published online by Cambridge University Press:  19 August 2013

ALICE S. BUTTERWORTH ,
TINA S. SKINNER-ADAMS ,
DON L. GARDINER  and
KATHARINE R. TRENHOLME
ALICE S. BUTTERWORTH
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia
TINA S. SKINNER-ADAMS
Affiliation:
Eskitis Institute, Griffith University, Brisbane, Australia
DON L. GARDINER
Affiliation:
School of Medicine, University of Queensland, Brisbane, Australia Australian Institute of Tropical Medicine, James Cook University, Cairns, Australia
KATHARINE R. TRENHOLME*
Affiliation:
Queensland Institute of Medical Research, Brisbane, Australia School of Medicine, University of Queensland, Brisbane, Australia
*
*Corresponding author: QIMR Central Building, 300 Herston Road, Herston, Brisbane, Australia. E-mail: [email protected]
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Summary

Drugs that kill or inhibit the sexual stages of Plasmodium in order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control of Plasmodium falciparum transmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.

Keywords

malariaPlasmodium falciparumgametocytesantimalarialstransmission blockingdrugs
Type
Review Article
Information
Parasitology , Volume 140 , Issue 14 , December 2013 , pp. 1718 - 1734
Copyright
Copyright © Cambridge University Press 2013 

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References

REFERENCES

Adjalley, S. H., Johnston, G. L., Li, T., Eastman, R. T., Ekland, E. H., Eappen, A. G., Richman, A., Sim, B. K., Lee, M. C., Hoffman, S. L. and Fidock, D. A. (2011). Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. Proceedings of the National Academy of Sciences USA 108, E1214–E1223. doi: 10.1073/pnas.1112037108.CrossRefGoogle ScholarPubMed
Aikawa, M. and Beaudoin, R. L. (1970). Plasmodium fallax: high-resolution autoradiography of exoerythrocytic stages treated with Primaquine in vitro. Experimental Parasitology 27, 454–463.CrossRefGoogle ScholarPubMed
Akompong, T., Eksi, S., Williamson, K. and Haldar, K. (2000 a). Gametocytocidal activity and synergistic interactions of riboflavin with standard antimalarial drugs against growth of Plasmodium falciparum in vitro. Antimicrobial Agents and Chemotherapy 44, 3107–3111.CrossRefGoogle ScholarPubMed
Akompong, T., Ghori, N. and Haldar, K. (2000 b). In vitro activity of riboflavin against the human malaria parasite Plasmodium falciparum. Antimicrobial Agents and Chemotherapy 44, 88–96.CrossRefGoogle ScholarPubMed
Alano, P. and Carter, R. (1990). Sexual differentiation in malaria parasites. Annual Review of Microbiology 44, 429–449. doi: 10.1146/annurev.mi.44.100190.002241.CrossRefGoogle ScholarPubMed
Alving, A. S., Arnold, J. and Robinson, D. H. (1952). Mass therapy of subclinical vivax malaria with primaquine. Journal of the American Medical Association 149, 1558–1562.CrossRefGoogle ScholarPubMed
Alving, A. S., Carson, P. E., Flanagan, C. L. and Ickes, C. E. (1956). Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124, 484–485.Google ScholarPubMed
Aminake, M. N., Schoof, S., Sologub, L., Leubner, M., Kirschner, M., Arndt, H. D. and Pradel, G. (2011). Thiostrepton and derivatives exhibit antimalarial and gametocytocidal activity by dually targeting parasite proteasome and apicoplast. Antimicrobial Agents and Chemotherapy 55, 1338–1348. doi: 10.1128/AAC.01096-10.CrossRefGoogle ScholarPubMed
Anders, J. C., Chung, H. and Theoharides, A. D. (1988). Methemoglobin formation resulting from administration of candidate 8-aminoquinoline antiparasitic drugs in the dog. Fundamental and Applied Toxicology 10, 270–275.CrossRefGoogle ScholarPubMed
Andrews, K. T., Fairlie, D. P., Madala, P. K., Ray, J., Wyatt, D. M., Hilton, P. M., Melville, L. A., Beattie, L., Gardiner, D. L., Reid, R. C., Stoermer, M. J., Skinner-Adams, T., Berry, C. and McCarthy, J. S. (2006). Potencies of human immunodeficiency virus protease inhibitors in vitro against Plasmodium falciparum and in vivo against murine malaria. Antimicrobial Agents and Chemotherapy 50, 639–648. doi: 10.1128/AAC.50.2.639-648.2006.CrossRefGoogle ScholarPubMed
Arango, E. M., Upegui, Y. A. and Carmona-Fonseca, J. (2012). Efficacy of different primaquine-based antimalarial regimens against Plasmodium falciparum gametocytemia. Acta Tropica 122, 177–182. doi: 10.1016/j.actatropica.2012.01.005.CrossRefGoogle ScholarPubMed
Arora, K. and Srivastava, A. K. (2005). Antimalarial efficacy of methylene blue and menadione and their effect on glutathione metabolism of Plasmodium yoelii-infected albino mice. Parasitology Research 97, 521–526. doi: 10.1007/s00436-005-1478-4.CrossRefGoogle ScholarPubMed
Atamna, H., Krugliak, M., Shalmiev, G., Deharo, E., Pescarmona, G. and Ginsburg, H. (1996). Mode of antimalarial effect of methylene blue and some of its analogues on Plasmodium falciparum in culture and their inhibition of P. vinckei petteri and P. yoelii nigeriensis in vivo. Biochemical Pharmacology 51, 693–700.CrossRefGoogle ScholarPubMed
Auparakkitanon, S., Chapoomram, S., Kuaha, K., Chirachariyavej, T. and Wilairat, P. (2006). Targeting of hematin by the antimalarial pyronaridine. Antimicrobial Agents and Chemotherapy 50, 2197–2200. doi: 10.1128/AAC.00119-06.CrossRefGoogle ScholarPubMed
Avula, B., Tekwani, B. L., Chaurasiya, N. D., Nanayakkara, N. D., Wang, Y. H., Khan, S. I., Adelli, V. R., Sahu, R., Elsohly, M. A., McChesney, J. D., Khan, I. A. and Walker, L. A. (2013). Profiling primaquine metabolites in primary human hepatocytes using UHPLC-QTOF-MS with (13) C stable isotope labeling. Journal of Mass Spectrometry 48, 276–285. doi: 10.1002/jms.3122.CrossRefGoogle Scholar
Baird, J. K. and Hoffman, S. L. (2004). Primaquine therapy for malaria. Clinical Infectious Diseases 39, 1336–1345. doi: 10.1086/424663.CrossRefGoogle ScholarPubMed
Baird, J. K., McCormick, G. J. and Canfield, C. J. (1986). Effects of nine synthetic putative metabolites of primaquine on activity of the hexose monophosphate shunt in intact human red blood cells in vitro. Biochemical Pharmacology 35, 1099–1106. 0006-2952(86)90145-0 [pii]CrossRefGoogle ScholarPubMed
Baker, D. A. (2010). Malaria gametocytogenesis. Molecular and Biochemical Parasitology 172, 57–65. doi: 10.1016/j.molbiopara.2010.03.019.CrossRefGoogle ScholarPubMed
Baker, J. K., Yarber, R. H., Nanayakkara, N. P., McChesney, J. D., Homo, F. and Landau, I. (1990). Effect of aliphatic side-chain substituents on the antimalarial activity and on the metabolism of primaquine studied using mitochondria and microsome preparations. Pharmaceutical Research 7, 91–95.CrossRefGoogle Scholar
Baldwin, J., Michnoff, C. H., Malmquist, N. A., White, J., Roth, M. G., Rathod, P. K. and Phillips, M. A. (2005). High-throughput screening for potent and selective inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. Journal of Biological Chemistry 280, 21847–21853. doi: 10.1074/jbc.M501100200.CrossRefGoogle ScholarPubMed
Barnes, K. I., Little, F., Mabuza, A., Mngomezulu, N., Govere, J., Durrheim, D., Roper, C., Watkins, B. and White, N. J. (2008). Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. Journal of Infectious Diseases 197, 1605–1613. doi: 10.1086/587645.CrossRefGoogle ScholarPubMed
Basco, L. K. and Le Bras, J. (1993). In vitro activity of monodesethylamodiaquine and amopyroquine against African isolates and clones of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 48, 120–125.CrossRefGoogle ScholarPubMed
Bates, M. D., Meshnick, S. R., Sigler, C. I., Leland, P. and Hollingdale, M. R. (1990). In vitro effects of primaquine and primaquine metabolites on exoerythrocytic stages of Plasmodium berghei. American Journal of Tropical Medicine and Hygiene 42, 532–537.CrossRefGoogle ScholarPubMed
Baty, J. D., Price Evans, D. A. and Robinson, P. A. (1975). The identification of 6-Methoxy 8-aminoquinoline as a metabolite in man. Biomedical Mass Spectronomy 2, 304–306.CrossRefGoogle Scholar
Beaudoin, R. L. and Aikawa, M. (1968). Primaquine-induced changes in morphology of exoerythrocytic stages of malaria. Science 160, 1233–1234.CrossRefGoogle ScholarPubMed
Benoit-Vical, F., Lelievre, J., Berry, A., Deymier, C., Dechy-Cabaret, O., Cazelles, J., Loup, C., Robert, A., Magnaval, J. F. and Meunier, B. (2007). Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Antimicrobial Agents and Chemotherapy 51, 1463–1472. doi: 10.1128/AAC.00967–06.CrossRefGoogle ScholarPubMed
Billker, O., Shaw, M. K., Jones, I. W., Ley, S. V., Mordue, A. J. and Sinden, R. E. (2002). Azadirachtin disrupts formation of organised microtubule arrays during microgametogenesis of Plasmodium berghei. Journal of Eukaryotic Microbiology 49, 489–497.CrossRefGoogle ScholarPubMed
Blank, O., Davioud-Charvet, E. and Elhabiri, M. (2012). Interactions of the antimalarial drug methylene blue with methemoglobin and heme targets in Plasmodium falciparum: a physico-biochemical study. Antioxidants and Redox Signaling 17, 544–554. doi: 10.1089/ars.2011.4239.CrossRefGoogle ScholarPubMed
Bolchoz, L. J., Budinsky, R. A., McMillan, D. C. and Jollow, D. J. (2001). Primaquine-induced hemolytic anemia: formation and hemotoxicity of the arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline. Journal of Pharmacology and Experimental Therapeutics 297, 509–515.Google ScholarPubMed
Boulard, Y., Landau, I., Miltgen, F., Ellis, D. S. and Peters, W. (1983). The chemotherapy of rodent malaria, XXXIV. Causal prophylaxis Part III: Ultrastructural changes induced in exo-erythrocytic schizonts of Plasmodium yoelii yoelii by primaquine. Annals of Tropical Medicine and Parasitology 77, 555–568.CrossRefGoogle ScholarPubMed
Bountogo, M., Zoungrana, A., Coulibaly, B., Klose, C., Mansmann, U., Mockenhaupt, F. P., Burhenne, J., Mikus, G., Walter-Sack, I., Schirmer, R. H., Sie, A., Meissner, P. and Muller, O. (2009). Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso. Tropical Medicine and International Health 15, 713–717. doi: 10.1111/j.1365–3156.2010.02526.x.CrossRefGoogle Scholar
Bousema, T., Okell, L., Shekalaghe, S., Griffin, J. T., Omar, S., Sawa, P., Sutherland, C., Sauerwein, R., Ghani, A. C. and Drakeley, C. (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. Malaria Journal 9, 136. doi: 10.1186/1475-2875-9-136.CrossRefGoogle ScholarPubMed
Brueckner, R. P., Coster, T., Wesche, D. L., Shmuklarsky, M. and Schuster, B. G. (1998 a). Prophylaxis of Plasmodium falciparum infection in a human challenge model with WR 238605, a new 8-aminoquinoline antimalarial. Antimicrobial Agents and Chemotherapy 42, 1293–1294.CrossRefGoogle Scholar
Brueckner, R. P., Lasseter, K. C., Lin, E. T. and Schuster, B. G. (1998 b). First-time-in-humans safety and pharmacokinetics of WR 238605, a new antimalarial. American Journal of Tropical Medicine and Hygiene 58, 645–649.CrossRefGoogle ScholarPubMed
Buchholz, K., Schirmer, R. H., Eubel, J. K., Akoachere, M. B., Dandekar, T., Becker, K. and Gromer, S. (2008). Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum. Antimicrobial Agents and Chemotherapy 52, 183–191. doi: 10.1128/AAC.00773-07.CrossRefGoogle ScholarPubMed
Buchholz, K., Burke, T. A., Williamson, K. C., Wiegand, R. C., Wirth, D. F. and Marti, M. (2011). A high-throughput screen targeting malaria transmission stages opens new avenues for drug development. Journal of Infectious Diseases 203, 1445–1453. doi: 10.1093/infdis/jir037.CrossRefGoogle ScholarPubMed
Buckling, A. G., Taylor, L. H., Carlton, J. M. and Read, A. F. (1997). Adaptive changes in Plasmodium transmission strategies following chloroquine chemotherapy. Proceedings of the Royal Society B, Biological Science 264, 553–559. doi: 10.1098/rspb.1997.0079.CrossRefGoogle ScholarPubMed
Buckling, A., Ranford-Cartwright, L. C., Miles, A. and Read, A. F. (1999). Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitology 118(Pt 4), 339–346.CrossRefGoogle ScholarPubMed
Buffet, P. A., Safeukui, I., Deplaine, G., Brousse, V., Prendki, V., Thellier, M., Turner, G. D. and Mercereau-Puijalon, O. (2011). The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology. Blood 117, 381–392. doi: 10.1182/blood-2010-04202911.CrossRefGoogle ScholarPubMed
Burgess, R. W. and Bray, R. S. (1961). The effect of a single dose of primaquine on the gametocytes, gametogony and sporogony of Laverania falciparum. Bulletin of the World Health Organization 24, 451–456.Google ScholarPubMed
Butcher, G. A. and Sinden, R. E. (2003). Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. American Journal of Tropical Medicine and Hygiene 68, 111–114.CrossRefGoogle ScholarPubMed
Butler, A. R., Gilbert, B. C., Hulme, P., Irvine, L. R., Renton, L. and Whitwood, A. C. (1998). EPR evidence for the involvement of free radicals in the iron-catalysed decomposition of qinghaosu (artemisinin) and some derivatives; antimalarial action of some polycyclic endoperoxides. Free Radical Research 28, 471–476.CrossRefGoogle ScholarPubMed
Campbell, C. C., Chin, W., Collins, W. E. and Moss, D. M. (1980). Infection of Anopheles freeborni by gametocytes of cultured Plasmodium falciparum. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 668–669.CrossRefGoogle ScholarPubMed
Canning, E. U. and Sinden, R. E. (1975). Nuclear organisation in gametocytes of Plasmodium and hepatocystis: a cytochemical study. Zeitschrift fur Parasitenkunde 46, 297–299.CrossRefGoogle ScholarPubMed
Carter, R. and Miller, L. H. (1979). Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bulletin of the World Health Organization 57(Suppl. 1), 37–52.Google ScholarPubMed
Carvalho, L., Luque-Ortega, J. R., Manzano, J. I., Castanys, S., Rivas, L. and Gamarro, F. (2010). Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis. Antimicrobial Agents and Chemotherapy 54, 5344–5351. doi: 10.1128/AAC.00790-10.CrossRefGoogle ScholarPubMed
Cervantes, S., Stout, P. E., Prudhomme, J., Engel, S., Bruton, M., Cervantes, M., Carter, D., Tae-Chang, Y., Hay, M. E., Aalbersberg, W., Kubanek, J. and Le Roch, K. G. (2012). High content live cell imaging for the discovery of new antimalarial marine natural products. BMC Infectious Diseases 12, 1. doi: 10.1186/1471-2334-12-1.CrossRefGoogle ScholarPubMed
Charles, B. G., Miller, A. K., Nasveld, P. E., Reid, M. G., Harris, I. E. and Edstein, M. D. (2007). Population pharmacokinetics of tafenoquine during malaria prophylaxis in healthy subjects. Antimicrobial Agents and Chemotherapy 51, 2709–2715. doi: 10.1128/AAC.01183-06.CrossRefGoogle ScholarPubMed
Chavalitshewinkoon-Petmitr, P., Pongvilairat, G., Auparakkitanon, S. and Wilairat, P. (2000). Gametocytocidal activity of pyronaridine and DNA topoisomerase II inhibitors against multidrug-resistant Plasmodium falciparum in vitro. Parasitology International 48, 275–280. doi: S1383576999000288.CrossRefGoogle ScholarPubMed
Chavalitshewinkoon-Petmitr, P., Pongvilairat, G., Ralph, R. K., Denny, W. A. and Wilairat, P. (2001). Inhibitory effects of 9-anilinoacridines on Plasmodium falciparum gametocytes. Tropical Medicine and International Health 6, 42–45.CrossRefGoogle ScholarPubMed
Chen, P. Q., Li, G. Q., Guo, X. B., He, K. R., Fu, Y. X., Fu, L. C. and Song, Y. Z. (1994). The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin. Chinese Medical Journal 107, 709–711.Google ScholarPubMed
Chevalley, S., Coste, A., Lopez, A., Pipy, B. and Valentin, A. (2010). Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes. Malaria Journal 9, 49. doi: 10.1186/1475-2875-9-49.CrossRefGoogle ScholarPubMed
Childs, G. E., Boudreau, E. F., Milhous, W. K., Wimonwattratee, T., Pooyindee, N., Pang, L. and Davidson, D. E. Jr. (1989). A comparison of the in vitro activities of amodiaquine and desethylamodiaquine against isolates of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 40, 7–11.CrossRefGoogle ScholarPubMed
Chotivanich, K., Sattabongkot, J., Udomsangpetch, R., Looareesuwan, S., Day, N. P., Coleman, R. E. and White, N. J. (2006). Transmission-blocking activities of quinine, primaquine, and artesunate. Antimicrobial Agents and Chemotherapy 50, 1927–1930. doi: 10.1128/AAC.01472-05.CrossRefGoogle ScholarPubMed
Clark, A. M., Baker, J. K. and McChesney, J. D. (1984 a). Excretion, distribution, and metabolism of primaquine in rats. Journal of Pharmaceutical Sciences 73, 502–506.CrossRefGoogle ScholarPubMed
Clark, A. M., Hufford, C. D., Gupta, R. C., Puri, R. K. and McChesney, J. D. (1984 b). Microbial transformation of primaquine by Candida tropicalis. Applied and Environmental Microbiology 47, 537–539.CrossRefGoogle ScholarPubMed
Coleman, R. E. (1990). Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensi. American Journal of Tropical Medicine and Hygiene 42, 196–205.CrossRefGoogle ScholarPubMed
Coleman, R. E., Clavin, A. M. and Milhous, W. K. (1992). Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR mice and Anopheles stephensi mosquitoes. American Journal of Tropical Medicine and Hygiene 46, 169–182.CrossRefGoogle ScholarPubMed
Cosledan, F., Fraisse, L., Pellet, A., Guillou, F., Mordmuller, B., Kremsner, P. G., Moreno, A., Mazier, D., Maffrand, J. P. and Meunier, B. (2008). Selection of a trioxaquine as an antimalarial drug candidate. Proceedings of the National Academy of Sciences USA 105, 17579–17584. doi: 10.1073/pnas.0804338105.CrossRefGoogle ScholarPubMed
Coulibaly, B., Zoungrana, A., Mockenhaupt, F. P., Schirmer, R. H., Klose, C., Mansmann, U., Meissner, P. E. and Muller, O. (2009). Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS ONE 4, e5318. doi: 10.1371/journal.pone.0005318.CrossRefGoogle ScholarPubMed
Croft, S. L., Duparc, S., Arbe-Barnes, S. J., Craft, J. C., Shin, C. S., Fleckenstein, L., Borghini-Fuhrer, I. and Rim, H. J. (2012). Review of pyronaridine anti-malarial properties and product characteristics. Malaria Journal 11, 270. doi: 10.1186/1475-2875-11-270.CrossRefGoogle ScholarPubMed
Cui, L. and Su, X. Z. (2009). Discovery, mechanisms of action and combination therapy of artemisinin. Expert Review of Anti-Infective Therapy 7, 999–1013. doi: 10.1586/eri.09.68.CrossRefGoogle ScholarPubMed
Cumming, J. N., Ploypradith, P. and Posner, G. H. (1997). Antimalarial activity of artemisinin (qinghaosu) and related trioxanes: mechanism(s) of action. Advances in Pharmacology 37, 253–297.CrossRefGoogle ScholarPubMed
Czesny, B., Goshu, S., Cook, J. L. and Williamson, K. C. (2009). The proteasome inhibitor epoxomicin has potent Plasmodium falciparum gametocytocidal activity. Antimicrobial Agents and Chemotherapy 53, 4080–4085. doi: 10.1128/AAC.00088-09.CrossRefGoogle ScholarPubMed
da Cruz, F. P., Martin, C., Buchholz, K., Lafuente-Monasterio, M. J., Rodrigues, T., Sonnichsen, B., Moreira, R., Gamo, F. J., Marti, M., Mota, M. M., Hannus, M. and Prudencio, M. (2012). Drug screen targeted at Plasmodium liver stages identifies a potent multistage antimalarial drug. Journal of Infectious Diseases 205, 1278–1286. doi: 10.1093/infdis/jis184.CrossRefGoogle ScholarPubMed
Darling, S. (1910). Studies in relation to malaria. In Isthmanian Canal Commission 1910 (ed. Laboratory of the Board of Health, I.C.C.), pp. 3–38. Washington Government Printing Office, Washington, DC, USA.Google Scholar
Day, K. P., Karamalis, F., Thompson, J., Barnes, D. A., Peterson, C., Brown, H., Brown, G. V. and Kemp, D. J. (1993). Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0·3-megabase region of chromosome 9. Proceedings of the National Academy of Sciences USA 90, 8292–8296.CrossRefGoogle ScholarPubMed
Dechy-Cabaret, O. and Benoit-Vical, F. (2012). Effects of antimalarial molecules on the gametocyte stage of Plasmodium falciparum: the debate. Journal of Medicinal Chemistry 55, 10328–10344. doi: 10.1021/jm3005898.CrossRefGoogle ScholarPubMed
Dechy-Cabaret, O., Benoit-Vical, F., Robert, A. and Meunier, B. (2000). Preparation and antimalarial activities of “trioxaquines”, new modular molecules with a trioxane skeleton linked to a 4-aminoquinoline. ChemBioChem 1, 281–283.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Dechy-Cabaret, O., Benoit-Vical, F., Loup, C., Robert, A., Gornitzka, H., Bonhoure, A., Vial, H., Magnaval, J. F., Seguela, J. P. and Meunier, B. (2004). Synthesis and antimalarial activity of trioxaquine derivatives. Chemistry 10, 1625–1636. doi: 10.1002/chem.200305576.CrossRefGoogle ScholarPubMed
Deharo, E., Garcia, R. N., Oporto, P., Gimenez, A., Sauvain, M., Jullian, V. and Ginsburg, H. (2002). A non-radiolabelled ferriprotoporphyrin IX biomineralisation inhibition test for the high throughput screening of antimalarial compounds. Experimental Parasitology 100, 252–256. doi: S0014489402000279.CrossRefGoogle ScholarPubMed
Delves, M., Plouffe, D., Scheurer, C., Meister, S., Wittlin, S., Winzeler, E. A., Sinden, R. E. and Leroy, D. (2012). The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLoS Medicine 9, e1001169. doi: 10.1371/journal.pmed.1001169.CrossRefGoogle ScholarPubMed
Dixon, M. W., Peatey, C. L., Gardiner, D. L. and Trenholme, K. R. (2009). A green fluorescent protein-based assay for determining gametocyte production in Plasmodium falciparum. Molecular and Biochemical Parasitology 163, 123–126. doi: 10.1016/j.molbiopara.2008.10.004.CrossRefGoogle Scholar
Duffy, S. and Avery, V. M. (2012). Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening. American Journal of Tropical Medicine and Hygiene 86, 84–92. doi: 10.4269/ajtmh.2012.11-0302.CrossRefGoogle ScholarPubMed
Dunyo, S., Milligan, P., Edwards, T., Sutherland, C., Targett, G. and Pinder, M. (2006). Gametocytaemia after drug treatment of asymptomatic Plasmodium falciparum. PLoS Clinical Trials 1, e20. doi: 10.1371/journal.pctr.0010020.CrossRefGoogle ScholarPubMed
Dyer, M. and Day, K. P. (2000). Commitment to gametocytogenesis in Plasmodium falciparum. Parasitology Today 16, 102–107. doi: S0169-4758(99)01608-7.CrossRefGoogle ScholarPubMed
Edstein, M. D., Kocisko, D. A., Brewer, T. G., Walsh, D. S., Eamsila, C. and Charles, B. G. (2001). Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers. British Journal of Clinical Pharmacology 52, 663–670.CrossRefGoogle ScholarPubMed
Edstein, M. D., Kocisko, D. A., Walsh, D. S., Eamsila, C., Charles, B. G. and Rieckmann, K. H. (2003). Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in Thai soldiers receiving monthly prophylaxis. Clinical Infectious Diseases 37, 1654–1658. doi: 10.1086/379718 CID31533.CrossRefGoogle ScholarPubMed
Elmes, N. J., Nasveld, P. E., Kitchener, S. J., Kocisko, D. A. and Edstein, M. D. (2008). The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific. Transactions of the Royal Society of Tropical Medicine and Hygiene 102, 1095–1101. doi: 10.1016/j.trstmh.2008.04.024.CrossRefGoogle ScholarPubMed
Enosse, S., Butcher, G. A., Margos, G., Mendoza, J., Sinden, R. E. and Hogh, B. (2000). The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone) and chloroquine. Transactions of the Royal Society of Tropical Medicine and Hygiene 94, 77–82.CrossRefGoogle ScholarPubMed
Farber, P. M., Arscott, L. D., Williams, C. H. Jr., Becker, K. and Schirmer, R. H. (1998). Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Letters 422, 311–314.CrossRefGoogle ScholarPubMed
Farfour, E., Charlotte, F., Settegrana, C., Miyara, M. and Buffet, P. (2012). The extravascular compartment of the bone marrow: a niche for Plasmodium falciparum gametocyte maturation? Malaria Journal 11, 285. doi: 10.1186/1475-2875-11-285.CrossRefGoogle ScholarPubMed
Figgitt, D., Denny, W., Chavalitshewinkoon, P., Wilairat, P. and Ralph, R. (1992). In vitro study of anticancer acridines as potential antitrypanosomal and antimalarial agents. Antimicrobial Agents and Chemotherapy 36, 1644–1647.CrossRefGoogle ScholarPubMed
Fisk, T. L., Millet, P., Collins, W. E. and Nguyen-Dinh, P. (1989). In vitro activity of antimalarial compounds on the exoerythrocytic stages of Plasmodium cynomolgi and P. knowlesi. American Journal of Tropical Medicine and Hygiene 40, 235–239.CrossRefGoogle ScholarPubMed
Fivelman, Q. L., McRobert, L., Sharp, S., Taylor, C. J., Saeed, M., Swales, C. A., Sutherland, C. J. and Baker, D. A. (2007). Improved synchronous production of Plasmodium falciparum gametocytes in vitro. Molecular and Biochemical Parasitology 154, 119–123. doi: 10.1016/j.molbiopara.2007.04.008.CrossRefGoogle ScholarPubMed
Fleck, S. L., Pudney, M. and Sinden, R. E. (1996). The effect of atovaquone (566C80) on the maturation and viability of Plasmodium falciparum gametocytes in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 90, 309–312.CrossRefGoogle ScholarPubMed
Fletcher, K. A., Barton, P. F. and Kelly, J. A. (1988). Studies on the mechanisms of oxidation in the erythrocyte by metabolites of primaquine. Biochemical Pharmacology 37, 2683–2690.CrossRefGoogle ScholarPubMed
Foltz, L. M., Dalal, B. I., Wadsworth, L. D., Broady, R., Chi, K., Eisenhauer, E., Kobayashi, K. and Kollmannsburger, C. (2006). Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. American Journal of Hematology 81, 210–211. doi: 10.1002/ajh.20547.CrossRefGoogle Scholar
Fry, M. and Pudney, M. (1992). Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566C80). Biochemical Pharmacology 43, 1545–1553.CrossRefGoogle Scholar
Gamage, S. A., Tepsiri, N., Wilairat, P., Wojcik, S. J., Figgitt, D. P., Ralph, R. K. and Denny, W. A. (1994). Synthesis and in vitro evaluation of 9-anilino-3,6-diaminoacridines active against a multidrug-resistant strain of the malaria parasite Plasmodium falciparum. Journal of Medicinal Chemistry 37, 1486–1494.CrossRefGoogle ScholarPubMed
Gamo, F. J., Sanz, L. M., Vidal, J., de Cozar, C., Alvarez, E., Lavandera, J. L., Vanderwall, D. E., Green, D. V., Kumar, V., Hasan, S., Brown, J. R., Peishoff, C. E., Cardon, L. R. and Garcia-Bustos, J. F. (2010). Thousands of chemical starting points for antimalarial lead identification. Nature 465, 305–310. nature09107 [pii] 10.1038/nature09107.CrossRefGoogle ScholarPubMed
Ganesan, S., Tekwani, B. L., Sahu, R., Tripathi, L. M. and Walker, L. A. (2009). Cytochrome P(450)-dependent toxic effects of primaquine on human erythrocytes. Toxicology and Applied Pharmacology 241, 14–22. doi: 10.1016/j.taap.2009.07.012.CrossRefGoogle ScholarPubMed
Gauthier, T. W. (2000). Methylene blue-induced hyperbilirubinemia in neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency. Journal of Maternal–Fetal Medicine 9, 252–254.Google ScholarPubMed
Ginsburg, H., Famin, O., Zhang, J. and Krugliak, M. (1998). Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochemical Pharmacology 56, 1305–1313.CrossRefGoogle ScholarPubMed
Gogtay, N. J., Kamtekar, K. D., Dalvi, S. S., Mehta, S. S., Chogle, A. R., Aigal, U. and Kshirsagar, N. A. (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 Infectious Diseases 6, 16. doi: 10.1186/1471-2334-6-16.CrossRefGoogle ScholarPubMed
Grande, T., Bernasconi, A., Erhart, A., Gamboa, D., Casapia, M., Delgado, C., Torres, K., Fanello, C., Llanos-Cuentas, A. and D'Alessandro, U. (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. doi: 10.1371/journal.pone.0001101.CrossRefGoogle ScholarPubMed
Graves, P. M., Carter, R. and McNeill, K. M. (1984). Gametocyte production in cloned lines of Plasmodium falciparum. American Journal of Tropical Medicine and Hygiene 33, 1045–1050.CrossRefGoogle ScholarPubMed
Graves, P. M., Gelband, H. and Garner, P. (2012). Primaquine for reducing Plasmodium falciparum transmission. Cochrane Database System Review 9, CD008152. doi: 0.1002/14651858.CD008152.pub2.Google Scholar
Greaves, J., Price-Evans, D. A., Gilles, H. M. and Baty, J. D. (1979). A selected ion monitoring assay for primaquine in plasma and urine. Biomedical Mass Spectrometry 6, 109–112. doi: 10.1002/bms.1200060306.CrossRefGoogle ScholarPubMed
Guiguemde, W. A., Shelat, A. A., Bouck, D., Duffy, S., Crowther, G. J., Davis, P. H., Smithson, D. C., Connelly, M., Clark, J., Zhu, F., Jimenez-Diaz, M. B., Martinez, M. S., Wilson, E. B., Tripathi, A. K., Gut, J., Sharlow, E. R., Bathurst, I., El Mazouni, F., Fowble, J. W., Forquer, I., McGinley, P. L., Castro, S., Angulo-Barturen, I., Ferrer, S., Rosenthal, P. J., Derisi, J. L., Sullivan, D. J., Lazo, J. S., Roos, D. S., Riscoe, M. K., Phillips, M. A., Rathod, P. K., Van Voorhis, W. C., Avery, V. M. and Guy, R. K. (2010). Chemical genetics of Plasmodium falciparum. Nature 465, 311–315. doi: 10.1038/nature09099.CrossRefGoogle ScholarPubMed
Guiguemde, W. A., Shelat, A. A., Garcia-Bustos, J. F., Diagana, T. T., Gamo, F. J. and Guy, R. K. (2012). Global phenotypic screening for antimalarials. Chemistry and Biology 19, 116–129. doi: 10.1016/j.chembiol.2012.01.004.CrossRefGoogle ScholarPubMed
Hale, B. R., Owusu-Agyei, S., Fryauff, D. J., Koram, K. A., Adjuik, M., Oduro, A. R., Prescott, W. R., Baird, J. K., Nkrumah, F., Ritchie, T. L., Franke, E. D., Binka, F. N., Horton, J. and Hoffman, S. L. (2003). A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clinical Infectious Diseases 36, 541–549. doi: 10.1086/367542.CrossRefGoogle ScholarPubMed
Hanada, M., Sugawara, K., Kaneta, K., Toda, S., Nishiyama, Y., Tomita, K., Yamamoto, H., Konishi, M. and Oki, T. (1992). Epoxomicin, a new antitumor agent of microbial origin. Journal of Antibiotics 45, 1746–1752.CrossRefGoogle ScholarPubMed
Hanssen, E., Knoechel, C., Dearnley, M., Dixon, M. W., Le Gros, M., Larabell, C. and Tilley, L. (2011). Soft X-ray microscopy analysis of cell volume and hemoglobin content in erythrocytes infected with asexual and sexual stages of Plasmodium falciparum. Journal of Structural Biology 177, 224–232. doi: 10.1016/j.jsb.2011.09.003.CrossRefGoogle ScholarPubMed
Hatz, C., Abdulla, S., Mull, R., Schellenberg, D., Gathmann, I., Kibatala, P., Beck, H. P., Tanner, M. and Royce, C. (1998). Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years. Tropical Medicine and International Health 3, 498–504.CrossRefGoogle ScholarPubMed
Hawking, F., Wilson, M. E. and Gammage, K. (1971). Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 549–559.CrossRefGoogle ScholarPubMed
Haynes, R. K. and Vonwiller, S. C. (1994). Extraction of artemisinin and artemisinic acid: preparation of artemether and new analogues. Transactions of the Royal Society of Tropical Medicine and Hygiene 88(Suppl. 1), S23–S26.CrossRefGoogle ScholarPubMed
Haynes, R. K., Cheu, K. W., Tang, M. M., Chen, M. J., Guo, Z. F., Guo, Z. H., Coghi, P. and Monti, D. (2011). Reactions of antimalarial peroxides with each of leucomethylene blue and dihydroflavins: flavin reductase and the cofactor model exemplified. ChemMedChem 6, 279–291. doi: 10.1002/cmdc.201000508.CrossRefGoogle ScholarPubMed
Hobbs, C. V., Voza, T., Coppi, A., Kirmse, B., Marsh, K., Borkowsky, W. and Sinnis, P. (2009). HIV protease inhibitors inhibit the development of preerythrocytic-stage plasmodium parasites. Journal of Infectious Diseases 199, 134–141. doi: 10.1086/594369.CrossRefGoogle ScholarPubMed
Hobbs, C. V., Tanaka, T. Q., Muratova, O., Van Vliet, J., Borkowsky, W., Williamson, K. C. and Duffy, P. E. (2013). HIV treatments have malaria gametocyte killing and transmission blocking activity. Journal of Infectious Diseases 208, 139–148. doi: 10.1093/infdis/jit132.CrossRefGoogle ScholarPubMed
Howes, R. E., Piel, F. B., Patil, A. P., Nyangiri, O. A., Gething, P. W., Dewi, M., Hogg, M. M., Battle, K. E., Padilla, C. D., Baird, J. K. and Hay, S. I. (2012). G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Medicine 9, e1001339. doi: 10.1371/journal.pmed.1001339.CrossRefGoogle ScholarPubMed
Hufford, C. D., Clark, A. M., Quinones, I. N., Baker, J. K. and McChesney, J. D. (1983). Microbial metabolism studies on the major microbial and mammalian metabolite of primaquine. Journal of Pharmaceutical Sciences 72, 92–94.CrossRefGoogle ScholarPubMed
Hufford, C. D., Baker, J. K., McChesney, J. D. and Clark, A. M. (1986). Novel sulfur-containing microbial metabolite of primaquine. Antimicrobial Agents and Chemotherapy 30, 234–237.CrossRefGoogle ScholarPubMed
Idowu, O. R., Peggins, J. O., Brewer, T. G. and Kelley, C. (1995). Metabolism of a candidate 8-aminoquinoline antimalarial agent, WR 238605, by rat liver microsomes. Drug Metabolism and Disposition: The Biological Fate of Chemicals 23, 1–17.Google ScholarPubMed
Ifediba, T. and Vanderberg, J. P. (1981). Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature 294, 364–366.CrossRefGoogle ScholarPubMed
Ikilezi, G., Achan, J., Kakuru, A., Ruel, T., Charlebois, E., Clark, T. D., Rosenthal, P. J., Havlir, D., Kamya, M. R. and Dorsey, G. (2013). Prevalence of asymptomatic parasitemia and gametocytemia among HIV-infected Ugandan children randomized to receive different antiretroviral therapies. American Journal of Tropical Medicine and Hygiene 88, 744–746. doi: 10.4269/ajtmh.12-0658.CrossRefGoogle ScholarPubMed
Ittarat, I., Asawamahasakda, W. and Meshnick, S. R. (1994). The effects of antimalarials on the Plasmodium falciparum dihydroorotate dehydrogenase. Experimental Parasitology 79, 50–56. doi: 10.1006/expr.1994.1058.CrossRefGoogle ScholarPubMed
Jeffery, G. M., Young, M. D. and Eyles, D. E. (1956). The treatment of Plasmodium falciparum infection with chloroquine, with a note on infectivity to mosquitoes of primaquine- and pyrimethamine-treated cases. American Journal of Tropical Medicine and Hygiene 64, 1–11.CrossRefGoogle ScholarPubMed
Jiang, J. B., Li, G. Q., Guo, X. B., Kong, Y. C. and Arnold, K. (1982). Antimalarial activity of mefloquine and qinghaosu. Lancet 2, 285–288.CrossRefGoogle ScholarPubMed
Jusko, W. J. and Levy, G. (1967). Absorption, metabolism, and excretion of riboflavin-5′-phosphate in man. Journal of Pharmaceutical Sciences 56, 58–62.CrossRefGoogle ScholarPubMed
Kamtekar, K. D., Gogtay, N. J., Dalvi, S. S., Karnad, D. R., Chogle, A. R., Aigal, U. and Kshirsagar, N. A. (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. Annals of Tropical Medicine and Parasitology 98, 453–458. doi: 10.1179/000349804225003550.CrossRefGoogle ScholarPubMed
Kato, M., Tanabe, K., Miki, A., Ichimori, K. and Waki, S. (1990). Membrane potential of Plasmodium falciparum gametocytes monitored with rhodamine 123. FEMS Microbiology Letters 57, 283–288.CrossRefGoogle ScholarPubMed
Kelner, M. J. and Alexander, N. M. (1985). Methylene blue directly oxidizes glutathione without the intermediate formation of hydrogen peroxide. Journal of Biological Chemistry 260, 15168–15171.CrossRefGoogle ScholarPubMed
Kiszewski, A. (2011). Blocking Plasmodium falciparum malaria transmission with drugs: the gametocytocidal and sporontocidal properties of current and prospective antimalarials. Pharmaceuticals 4, 44–68.CrossRefGoogle Scholar
Kolaczinski, K., Leslie, T., Ali, I., Durrani, N., Lee, S., Barends, M., Beshir, K., Ord, R., Hallett, R. and 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. doi: 10.1371/journal.pone.0028957.CrossRefGoogle ScholarPubMed
Krungkrai, J., Prapunwattana, P. and Krungkrai, S. R. (2000). Ultrastructure and function of mitochondria in gametocytic stage of Plasmodium falciparum. Parasite 7, 19–26.CrossRefGoogle ScholarPubMed
Kumar, N. and Zheng, H. (1990). Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitology Research 76, 214–218.CrossRefGoogle ScholarPubMed
Kurosawa, Y., Dorn, A., Kitsuji-Shirane, M., Shimada, H., Satoh, T., Matile, H., Hofheinz, W., Masciadri, R., Kansy, M. and Ridley, R. G. (2000). Hematin polymerization assay as a high-throughput screen for identification of new antimalarial pharmacophores. Antimicrobial Agents and Chemotherapy 44, 2638–2644.CrossRefGoogle ScholarPubMed
Kurth, F., Pongratz, P., Belard, S., Mordmuller, B., Kremsner, P. G. and Ramharter, M. (2009). In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays. Malaria Journal 8, 79. doi: 10.1186/1475-2875-8-79.CrossRefGoogle ScholarPubMed
Lanners, H. N. (1991). Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. Parasitology Research 77, 478–481.CrossRefGoogle ScholarPubMed
Lederman, E. R., Maguire, J. D., Sumawinata, I. W., Chand, K., Elyazar, I., Estiana, L., Sismadi, P., Bangs, M. J. and Baird, J. K. (2006). Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia. Malaria Journal 5, 108. doi: 10.1186/1475-2875-5-108.CrossRefGoogle ScholarPubMed
Lelievre, J., Almela, M. J., Lozano, S., Miguel, C., Franco, V., Leroy, D. and 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. doi: 10.1371/journal.pone.0035019.CrossRefGoogle Scholar
Lell, B., Faucher, J. F., Missinou, M. A., Borrmann, S., Dangelmaier, O., Horton, J. and Kremsner, P. G. (2000). Malaria chemoprophylaxis with tafenoquine: a randomised study. Lancet 355, 2041–2045. doi: 10.1016/S0140-6736(00)02352-7.CrossRefGoogle ScholarPubMed
Lucantoni, L. and Avery, V. (2012). Whole-cell in vitro screening for gametocytocidal compounds. Future Medicinal Chemistry 4, 2337–2360. doi: 10.4155/fmc.12.188.CrossRefGoogle ScholarPubMed
Mandi, G., Witte, S., Meissner, P., Coulibaly, B., Mansmann, U., Rengelshausen, J., Schiek, W., Jahn, A., Sanon, M., Wust, K., Walter-Sack, I., Mikus, G., Burhenne, J., Riedel, K. D., Schirmer, H., Kouyate, B. and Muller, O. (2005). Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Tropical Medicine and International Health 10, 32–38. doi: 10.1111/j.1365-3156.2004.01356.x.CrossRefGoogle ScholarPubMed
McGowan, S., Porter, C. J., Lowther, J., Stack, C. M., Golding, S. J., Skinner-Adams, T. S., Trenholme, K. R., Teuscher, F., Donnelly, S. M., Grembecka, J., Mucha, A., Kafarski, P., Degori, R., Buckle, A. M., Gardiner, D. L., Whisstock, J. C. and Dalton, J. P. (2009). Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proceedings of the National Academy of Sciences USA 106, 2537–2542. doi: 10.1073/pnas.0807398106.CrossRefGoogle ScholarPubMed
McKenzie, F. E., Jeffery, G. M. and Collins, W. E. (2007). Gametocytemia and fever in human malaria infections. Journal of Parasitology 93, 627–633. doi: 10.1645/GE-1052R.1.CrossRefGoogle ScholarPubMed
Meissner, P. E., Mandi, G., Witte, S., Coulibaly, B., Mansmann, U., Rengelshausen, J., Schiek, W., Jahn, A., Sanon, M., Tapsoba, T., Walter-Sack, I., Mikus, G., Burhenne, J., Riedel, K. D., Schirmer, H., Kouyate, B. and Muller, O. (2005). Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841]. Malaria Journal 4, 45. doi: 10.1186/1475-2875-4-45.CrossRefGoogle ScholarPubMed
Meissner, P. E., Mandi, G., Coulibaly, B., Witte, S., Tapsoba, T., Mansmann, U., Rengelshausen, J., Schiek, W., Jahn, A., Walter-Sack, I., Mikus, G., Burhenne, J., Riedel, K. D., Schirmer, R. H., Kouyate, B. and Muller, O. (2006). Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malaria Journal 5, 84. doi: 10.1186/1475-2875-5-84.CrossRefGoogle ScholarPubMed
Mens, P. F., Sawa, P., van Amsterdam, S. M., Versteeg, I., Omar, S. A., Schallig, H. D. and Kager, P. A. (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. Malaria Journal 7, 237. doi: 10.1186/1475-2875-7-237.CrossRefGoogle ScholarPubMed
Meshnick, S. R. (2002). Artemisinin: mechanisms of action, resistance and toxicity. International Journal for Parasitology 32, 1655–1660. doi: S0020751902001947.CrossRefGoogle ScholarPubMed
Meshnick, S. R., Taylor, T. E. and Kamchonwongpaisan, S. (1996). Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiological Reviews 60, 301–315.CrossRefGoogle ScholarPubMed
Mihaly, G. W., Ward, S. A., Edwards, G., Orme, M. L. and Breckenridge, A. M. (1984). Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. British Journal of Clinical Pharmacology 17, 441–446.CrossRefGoogle ScholarPubMed
Mihaly, G. W., Ward, S. A., Edwards, G., Nicholl, D. D., Orme, M. L. and Breckenridge, A. M. (1985). Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size. British Journal of Clinical Pharmacology 19, 745–750.CrossRefGoogle Scholar
Miller, M. J., Marcus, D. M. and Cameron, D. G. (1965). Latent infections with Plasmodium ovale malaria. Canadian Medical Association Journal 92, 1241–1247.Google ScholarPubMed
Morris, C. A., Duparc, S., Borghini-Fuhrer, I., Jung, D., Shin, C. S. and Fleckenstein, L. (2011). Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration. Malaria Journal 10, 263. doi: 10.1186/1475-2875-10-263.CrossRefGoogle ScholarPubMed
Muller, O., Mockenhaupt, F. P., Marks, B., Meissner, P., Coulibaly, B., Kuhnert, R., Buchner, H., Schirmer, R. H., Walter-Sack, I., Sie, A. and Mansmann, U. (2012). Haemolysis risk in methylene blue treatment of G6PD-sufficient and G6PD-deficient West-African children with uncomplicated falciparum malaria: a synopsis of four RCTs. Pharmacoepidemiology and Drug Safety 22, 376–385. doi: 10.1002/pds.3370.CrossRefGoogle ScholarPubMed
Nasveld, P. E., Edstein, M. D., Reid, M., Brennan, L., Harris, I. E., Kitchener, S. J., Leggat, P. A., Pickford, P., Kerr, C., Ohrt, C. and Prescott, W. (2010). Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrobial Agents and Chemotherapy 54, 792–798. doi: 10.1128/AAC.00354-09.CrossRefGoogle ScholarPubMed
Ndayiragije, A., Niyungeko, D., Karenzo, J., Niyungeko, E., Barutwanayo, M., Ciza, A., Bosman, A., Moyou-Somo, R., Nahimana, A., Nyarushatsi, J. P., Barihuta, T., Mizero, L., Ndaruhutse, J., Delacollette, C., Ringwald, P. and Kamana, J. (2004). Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi. Tropical Medicine and International Health 9, 673–679. doi: 10.1111/j.1365-3156.2004.01255.x.CrossRefGoogle ScholarPubMed
Ni, Y. C., Xu, Y. Q. and Wang, M. J. (1992). Rat liver microsomal and mitochondrial metabolism of primaquine in vitro. Zhongguo Yao Li Xue Bao 13, 431–435.Google ScholarPubMed
Obaldia, N. III, Rossan, R. N., Cooper, R. D., Kyle, D. E., Nuzum, E. O., Rieckmann, K. H. and Shanks, G. D. (1997). WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys. American Journal of Tropical Medicine and Hygiene 56, 508–510.CrossRefGoogle ScholarPubMed
Ochong, E. O., van den Broek, I. V., Keus, K. and Nzila, A. (2003). Short report: association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan. American Journal of Tropical Medicine and Hygiene 69, 184–187.CrossRefGoogle ScholarPubMed
Okamoto, N., Spurck, T. P., Goodman, C. D. and McFadden, G. I. (2009). Apicoplast and mitochondrion in gametocytogenesis of Plasmodium falciparum. Eukaryotic Cell 8, 128–132. doi: 10.1128/EC.00267-08.CrossRefGoogle ScholarPubMed
Okombo, J., Kiara, S. M., Mwai, L., Pole, L., Ohuma, E., Ochola, L. I. and Nzila, A. (2011). Baseline in vitro activities of the antimalarials pyronaridine and methylene blue against Plasmodium falciparum isolates from Kenya. Antimicrobial Agents and Chemotherapy 56, 1105–1107. doi: 10.1128/AAC.05454-11.CrossRefGoogle ScholarPubMed
Pastrana-Mena, R., Dinglasan, R. R., Franke-Fayard, B., Vega-Rodriguez, J., Fuentes-Caraballo, M., Baerga-Ortiz, A., Coppens, I., Jacobs-Lorena, M., Janse, C. J. and Serrano, A. E. (2010). Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. Journal of Biological Chemistry 285, 27045–27056. doi: 10.1074/jbc.M110.122275.CrossRefGoogle ScholarPubMed
Peatey, C. L., Andrews, K. T., Eickel, N., MacDonald, T., Butterworth, A. S., Trenholme, K. R., Gardiner, D. L., McCarthy, J. S. and Skinner-Adams, T. S. (2009 a). Antimalarial asexual stage-specific and gametocytocidal activities of HIV protease inhibitors. Antimicrobial Agents and Chemotherapy 54, 1334–1337. doi: 10.1128/AAC.01512-09.CrossRefGoogle ScholarPubMed
Peatey, C. L., Skinner-Adams, T. S., Dixon, M. W., McCarthy, J. S., Gardiner, D. L. and Trenholme, K. R. (2009 b). Effect of antimalarial drugs on Plasmodium falciparum gametocytes. Journal of Infectious Diseases 200, 1518–1521. doi: 10.1086/644645.CrossRefGoogle ScholarPubMed
Peatey, C. L., Spicer, T. P., Hodder, P. S., Trenholme, K. R. and Gardiner, D. L. (2011). A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes. Molecular and Biochemical Parasitology 180, 127–131. doi: 10.1016/j.molbiopara.2011.09.002.CrossRefGoogle ScholarPubMed
Peatey, C. L., Leroy, D., Gardiner, D. L. and Trenholme, K. R. (2012). Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes? Malaria Journal 11, 34. doi: 10.1186/1475-2875-11-34.CrossRefGoogle ScholarPubMed
Peters, W., Robinson, B. L. and Milhous, W. K. (1993). The chemotherapy of rodent malaria. LI. Studies on a new 8-aminoquinoline, WR 238,605. Annals of Tropical Medicine and Parasitology 87, 547–552.CrossRefGoogle ScholarPubMed
Phillips, M. A. and Rathod, P. K. (2010). Plasmodium dihydroorotate dehydrogenase: a promising target for novel anti-malarial chemotherapy. Infectious Disorders Drug Targets 10, 226–239.CrossRefGoogle ScholarPubMed
Plouffe, D., Brinker, A., McNamara, C., Henson, K., Kato, N., Kuhen, K., Nagle, A., Adrian, F., Matzen, J. T., Anderson, P., Nam, T. G., Gray, N. S., Chatterjee, A., Janes, J., Yan, S. F., Trager, R., Caldwell, J. S., Schultz, P. G., Zhou, Y. and Winzeler, E. A. (2008). In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proceedings of the National Academy of Sciences USA 105, 9059–9064. doi: 10.1073/pnas.0802982105.CrossRefGoogle Scholar
Ponnudurai, T., Meuwissen, J. H., Leeuwenberg, A. D., Verhave, J. P. and Lensen, A. H. (1982). The production of mature gametocytes of Plasmodium falciparum in continuous cultures of different isolates infective to mosquitoes. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 242–250.CrossRefGoogle ScholarPubMed
Portela, M. J., Moreira, R., Valente, E., Constantino, L., Iley, J., Pinto, J., Rosa, R., Cravo, P. and do Rosario, V. E. (1999). Dipeptide derivatives of primaquine as transmission-blocking antimalarials: effect of aliphatic side-chain acylation on the gametocytocidal activity and on the formation of carboxyprimaquine in rat liver homogenates. Pharmaceutical Research 16, 949–955.CrossRefGoogle ScholarPubMed
Posner, G. H., Oh, C. H., Wang, D., Gerena, L., Milhous, W. K., Meshnick, S. R. and Asawamahasadka, W. (1994). Mechanism-based design, synthesis, and in vitro antimalarial testing of new 4-methylated trioxanes structurally related to artemisinin: the importance of a carbon-centered radical for antimalarial activity. Journal of Medicinal Chemistry 37, 1256–1258.CrossRefGoogle ScholarPubMed
Pradines, B., Mabika Mamfoumbi, M., Parzy, D., Owono Medang, M., Lebeau, C., Mourou Mbina, J. R., Doury, J. C. and Kombila, M. (1999). In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine. American Journal of Tropical Medicine and Hygiene 60, 105–108.CrossRefGoogle ScholarPubMed
Pradines, B., Mamfoumbi, M. M., Tall, A., Sokhna, C., Koeck, J. L., Fusai, T., Mosnier, J., Czarnecki, E., Spiegel, A., Trape, J. F., Kombila, M. and Rogier, C. (2006). In vitro activity of tafenoquine against the asexual blood stages of Plasmodium falciparum isolates from Gabon, Senegal, and Djibouti. Antimicrobial Agents and Chemotherapy 50, 3225–3226. doi: 10.1128/AAC.00777-06.CrossRefGoogle ScholarPubMed
Price, R. N. and Douglas, N. M. (2009). Artemisinin combination therapy for malaria: beyond good efficacy. Clinical Infectious Diseases 49, 1638–1640. doi: 10.1086/647947.CrossRefGoogle ScholarPubMed
Price, R. N., Nosten, F., Luxemburger, C., ter Kuile, F. O., Paiphun, L., Chongsuphajaisiddhi, T. and White, N. J. (1996). Effects of artemisinin derivatives on malaria transmissibility. Lancet 347, 1654–1658.CrossRefGoogle ScholarPubMed
Priotto, G., Kabakyenga, J., Pinoges, L., Ruiz, A., Eriksson, T., Coussement, F., Ngambe, T., Taylor, W. R., Perea, W., Guthmann, J. P., Olliaro, P. and Legros, D. (2003). Artesunate and sulfadoxine-pyrimethamine combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Uganda: a randomized, double-blind, placebo-controlled trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 97, 325–330.CrossRefGoogle ScholarPubMed
Pukrittayakamee, S., Chotivanich, K., Chantra, A., Clemens, R., Looareesuwan, S. and White, N. J. (2004). Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria. Antimicrobial Agents and Chemotherapy 48, 1329–1334.CrossRefGoogle ScholarPubMed
Puri, S. K. and Dutta, G. P. (2003). Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys. Acta Tropica 86, 35–40. doi: S0001706X02002899.CrossRefGoogle ScholarPubMed
Puri, S. K. and Dutta, G. P. (2005). Plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound CDRI 80/53 (elubaquine) in rhesus monkeys. Experimental Parasitology 111, 8–13. doi: 10.1016/j.exppara.2005.05.007.CrossRefGoogle ScholarPubMed
Redmond, A. M., Skinner-Adams, T., Andrews, K. T., Gardiner, D. L., Ray, J., Kelly, M. and McCarthy, J. S. (2007). Antimalarial activity of sera from subjects taking HIV protease inhibitors. AIDS 21, 763–765. doi: 10.1097/QAD.0b013e328031f41a.CrossRefGoogle ScholarPubMed
Raabe, A. C., Billker, O., Vial, H. J. and Wengelnik, K. (2009). Quantitative assessment of DNA replication to monitor microgametogenesis in Plasmodium berghei. Molecular and Biochemical Parasitology 168, 172–176. doi: 10.1016/j.molbiopara.2009.08.004.CrossRefGoogle ScholarPubMed
Ribaut, C., Berry, A., Chevalley, S., Reybier, K., Morlais, I., Parzy, D., Nepveu, F., Benoit-Vical, F. and Valentin, A. (2008). Concentration and purification by magnetic separation of the erythrocytic stages of all human Plasmodium species. Malaria Journal 7, 45. doi: 10.1186/1475-2875-7-45.CrossRefGoogle ScholarPubMed
Rieckmann, K. H., McNamara, J. V., Frischer, H., Stockert, T. A., Carson, P. E. and Powell, R. D. (1968). Gametocytocidal and sporontocidal effects of primaquine and of sulfadiazine with pyrimethamine in a chloroquine-resistant strain of Plasmodium falciparum. Bulletin of the World Health Organization 38, 625–632.Google Scholar
Ringwald, P., Meche, F. S. and Basco, L. K. (1999). Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene 61, 446–448.CrossRefGoogle ScholarPubMed
Rohrich, C. R., Ngwa, C. J., Wiesner, J., Schmidtberg, H., Degenkolb, T., Kollewe, C., Fischer, R., Pradel, G. and Vilcinskas, A. (2012). Harmonine, a defence compound from the harlequin ladybird, inhibits mycobacterial growth and demonstrates multi-stage antimalarial activity. Biology Letters 8, 308–311. doi: 10.1098/rsbl.2011.0760.CrossRefGoogle ScholarPubMed
Rosen, P. J., Johnson, C., McGehee, W. G. and Beutler, E. (1971). Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Annals of Internal Medicine 75, 83–86.CrossRefGoogle ScholarPubMed
Rottmann, M., McNamara, C., Yeung, B. K., Lee, M. C., Zou, B., Russell, B., Seitz, P., Plouffe, D. M., Dharia, N. V., Tan, J., Cohen, S. B., Spencer, K. R., Gonzalez-Paez, G. E., Lakshminarayana, S. B., Goh, A., Suwanarusk, R., Jegla, T., Schmitt, E. K., Beck, H. P., Brun, R., Nosten, F., Renia, L., Dartois, V., Keller, T. H., Fidock, D. A., Winzeler, E. A. and Diagana, T. T. (2010). Spiroindolones, a potent compound class for the treatment of malaria. Science 329, 1175–1180. doi: 10.1126/science.1193225.CrossRefGoogle ScholarPubMed
Sachanonta, N., Chotivanich, K., Chaisri, U., Turner, G. D., Ferguson, D. J., Day, N. P. and Pongponratn, E. (2011). Ultrastructural and real-time microscopic changes in P. falciparum-infected red blood cells following treatment with antimalarial drugs. Ultrastructural Pathology 35, 214–225. doi: 10.3109/01913123.2011.601405.CrossRefGoogle Scholar
Sarma, G. N., Savvides, S. N., Becker, K., Schirmer, M., Schirmer, R. H. and Karplus, P. A. (2003). Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development. Journal of Molecular Biology 328, 893–907. doi: S0022283603003474.CrossRefGoogle ScholarPubMed
Saul, A., Graves, P. and Edser, L. (1990). Refractoriness of erythrocytes infected with Plasmodium falciparum gametocytes to lysis by sorbitol. International Journal for Parasitology 20, 1095–1097.CrossRefGoogle ScholarPubMed
Schirmer, R. H., Coulibaly, B., Stich, A., Scheiwein, M., Merkle, H., Eubel, J., Becker, K., Becher, H., Muller, O., Zich, T., Schiek, W. and Kouyate, B. (2003). Methylene blue as an antimalarial agent. Redox Report 8, 272–275. doi: 10.1179/135100003225002899.CrossRefGoogle ScholarPubMed
Schneider, E., Hsiang, Y. H. and Liu, L. F. (1990). DNA topoisomerases as anticancer drug targets. Advances in Pharmacology 21, 149–183.CrossRefGoogle ScholarPubMed
Shekalaghe, S., Drakeley, C., Gosling, R., Ndaro, A., van Meegeren, M., Enevold, A., Alifrangis, M., Mosha, F., Sauerwein, R. and Bousema, T. (2007). Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS ONE 2, e1023. doi: 10.1371/journal.pone.0001023.CrossRefGoogle ScholarPubMed
Sinden, R. E. (1982). Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology 84, 1–11.CrossRefGoogle ScholarPubMed
Sinden, R. E. and Smalley, M. E. (1979). Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle. Parasitology 79, 277–296.CrossRefGoogle ScholarPubMed
Sinden, R. E., Canning, E. U., Bray, R. S. and Smalley, M. E. (1978). Gametocyte and gamete development in Plasmodium falciparum. Proceedings of the Royal Society of London. Series B: Biological Sciences 201, 375–399.Google ScholarPubMed
Skinner-Adams, T. S., McCarthy, J. S., Gardiner, D. L., Hilton, P. M. and Andrews, K. T. (2004). Antiretrovirals as antimalarial agents. Journal of Infectious Diseases 190, 1998–2000. doi: 10.1086/425584.CrossRefGoogle ScholarPubMed
Skinner-Adams, T. S., Stack, C. M., Trenholme, K. R., Brown, C. L., Grembecka, J., Lowther, J., Mucha, A., Drag, M., Kafarski, P., McGowan, S., Whisstock, J. C., Gardiner, D. L. and Dalton, J. P. (2010). Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends in Biochemical Sciences 35, 53–61. doi: 10.1016/j.tibs.2009.08.004.CrossRefGoogle ScholarPubMed
Smalley, M. E. (1977). Plasmodium falciparum gametocytes: the effect of chloroquine on their development. Transactions of the Royal Society of Tropical Medicine and Hygiene 71, 526–529.CrossRefGoogle ScholarPubMed
Smalley, M. E., Abdalla, S. and Brown, J. (1981). The distribution of Plasmodium falciparum in the peripheral blood and bone marrow of Gambian children. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 103–105.CrossRefGoogle ScholarPubMed
Smithuis, F., Kyaw, M. K., Phe, O., Win, T., Aung, P. P., Oo, A. P., Naing, A. L., Nyo, M. Y., Myint, N. Z., Imwong, M., Ashley, E., Lee, S. J. and White, N. J. (2010). Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infectious Diseases 10, 673–681. doi: 10.1016/S1473-3099(10)70187-0.CrossRefGoogle ScholarPubMed
Sowunmi, A. and Fateye, B. A. (2003 a). Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs. Tropical Medicine and International Health 8, 783–792.CrossRefGoogle ScholarPubMed
Sowunmi, A., Fateye, B. A., Happi, T. C., Gbotosho, G. O. and Oduola, A. M. (2003 b). Plasmodium falciparum gametocytaemia in Nigerian children: peripheral immature gametocytaemia as an indicator of a poor response to chloroquine treatment, and its relationship to molecular determinants of chloroquine resistance. Annals of Tropical Medicine and Parasitology 97, 453–468. doi: 10.1179/000349803235002443.CrossRefGoogle ScholarPubMed
Sowunmi, A., Balogun, T., Gbotosho, G. O., Happi, C. T., Adedeji, A. A. and Fehintola, F. A. (2007). Activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual- and sexual-stage parasites in falciparum malaria in children. Antimicrobial Agents and Chemotherapy 51, 1694–1699. doi: 10.1128/AAC.00077-07.CrossRefGoogle ScholarPubMed
Sowunmi, A., Balogun, S. T., Gbotosho, G. O. and Happi, C. T. (2008). Plasmodium falciparum gametocyte sex ratios in children with acute, symptomatic, uncomplicated infections treated with amodiaquine. Malaria Journal 7, 169. doi: 10.1186/1475-2875-7-169.CrossRefGoogle ScholarPubMed
Sowunmi, A., Nkogho, O. O., Okuboyejo, T. M., Gbotosho, G. O., Happi, C. T. and Adewoye, E. O. (2009). Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children. Malaria Journal 8, 297. doi: 10.1186/1475-2875-8-297.CrossRefGoogle ScholarPubMed
Strother, A., Fraser, I. M., Allahyari, R. and Tilton, B. E. (1981). Metabolism of 8-aminoquinoline antimalarial agents. Bulletin of the World Health Organization 59, 413–425.Google ScholarPubMed
Strother, A., Allahyari, R., Buchholz, J., Fraser, I. M. and Tilton, B. E. (1984). In vitro metabolism of the antimalarial agent primaquine by mouse liver enzymes and identification of a methemoglobin-forming metabolite. Drug Metabolism and Disposition: the Biological Fate of Chemicals 12, 35–44.Google ScholarPubMed
Suputtamongkol, Y., Chindarat, S., Silpasakorn, S., Chaikachonpatd, S., Lim, K., Chanthapakajee, K., Kaewkaukul, N. and Thamlikitkul, V. (2003). The efficacy of combined mefloquine-artesunate versus mefloquine-primaquine on subsequent development of Plasmodium falciparum gametocytemia. American Journal of Tropical Medicine and Hygiene 68, 620–623.CrossRefGoogle ScholarPubMed
Tanaka, T. Q. and Williamson, K. C. (2011). A malaria gametocytocidal assay using oxidoreduction indicator, alamar blue. Molecular and Biochemical Parasitology 177, 160–163. doi: 10.1016/j.molbiopara.2011.02.005.CrossRefGoogle Scholar
Tanaka, T. Q., Dehdashti, S. J., Nguyen, D. T., McKew, J. C., Zheng, W. and Williamson, K. C. (2013). A quantitative high throughput assay for identifying gametocytocidal compounds. Molecular and Biochemical Parasitology 188, 20–25. doi: 10.1016/j.molbiopara.2013.02.005.CrossRefGoogle ScholarPubMed
Targett, G., Drakeley, C., Jawara, M., von Seidlein, L., Coleman, R., Deen, J., Pinder, M., Doherty, T., Sutherland, C., Walraven, G. and Milligan, P. (2001). Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. Journal of Infectious Diseases 183, 1254–1259. doi: 10.1086/319689.CrossRefGoogle Scholar
Thurston, J. P. (1953). The chemotherapy of Plasmodium berghei. I. Resistance to drugs. Parasitology 43, 246–252.CrossRefGoogle ScholarPubMed
Trager, W. and Jensen, J. B. (1976). Human malaria parasites in continuous culture. Science 193, 673–675.CrossRefGoogle ScholarPubMed
Tshefu, A. K., Gaye, O., Kayentao, K., Thompson, R., Bhatt, K. M., Sesay, S. S., Bustos, D. G., Tjitra, E., Bedu-Addo, G., Borghini-Fuhrer, I., Duparc, S., Shin, C. S. and Fleckenstein, L. (2010). Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial. Lancet 375, 1457–1467. doi: 10.1016/S0140-6736(10)60322-4.CrossRefGoogle ScholarPubMed
Udeinya, I. J., Brown, N., Shu, E. N., Udeinya, F. I. and Quakeyie, I. (2006). Fractions of an antimalarial neem-leaf extract have activities superior to chloroquine, and are gametocytocidal. Annals of Tropical Medicine and Parasitology 100, 17–22. doi: 10.1179/136485906X78508.CrossRefGoogle ScholarPubMed
Vaidya, A. B., Lashgari, M. S., Pologe, L. G. and Morrisey, J. (1993). Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Molecular and Biochemical Parasitology 58, 33–42.CrossRefGoogle ScholarPubMed
Vale, N., Nogueira, F., do Rosario, V. E., Gomes, P. and Moreira, R. (2009). Primaquine dipeptide derivatives bearing an imidazolidin-4-one moiety at the N-terminus as potential antimalarial prodrugs. European Journal of Medicinal Chemistry 44, 2506–2516. doi: 10.1016/j.ejmech.2009.01.018.CrossRefGoogle ScholarPubMed
Vasquez-Vivar, J. and Augusto, O. (1992). Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling. Journal of Biological Chemistry 267, 6848–6854.CrossRefGoogle ScholarPubMed
von Seidlein, L., Bojang, K., Jones, P., Jaffar, S., Pinder, M., Obaro, S., Doherty, T., Haywood, M., Snounou, G., Gemperli, B., Gathmann, I., Royce, C., McAdam, K. and Greenwood, B. (1998). A randomized controlled trial of artemether/benflumetol, a new antimalarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children. American Journal of Tropical Medicine and Hygiene 58, 638–644.CrossRefGoogle ScholarPubMed
Wainwright, M. and Amaral, L. (2005). The phenothiazinium chromophore and the evolution of antimalarial drugs. Tropical Medicine and International Health 10, 501–511. doi: 10.1111/j.1365-3156.2005.01417.x.CrossRefGoogle ScholarPubMed
Walsh, D. S., Looareesuwan, S., Wilairatana, P., Heppner, D. G. Jr., Tang, D. B., Brewer, T. G., Chokejindachai, W., Viriyavejakul, P., Kyle, D. E., Milhous, W. K., Schuster, B. G., Horton, J., Braitman, D. J. and Brueckner, R. P. (1999). Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand. Journal of Infectious Diseases 180, 1282–1287. doi: 10.1086/315034.CrossRefGoogle ScholarPubMed
Walsh, D. S., Eamsila, C., Sasiprapha, T., Sangkharomya, S., Khaewsathien, P., Supakalin, P., Tang, D. B., Jarasrumgsichol, P., Cherdchu, C., Edstein, M. D., Rieckmann, K. H. and Brewer, T. G. (2004 a). Efficacy of monthly tafenoquine for prophylaxis of Plasmodium vivax and multidrug-resistant P. falciparum malaria. Journal of Infectious Diseases 190, 1456–1463. doi: 10.1086/424468.CrossRefGoogle ScholarPubMed
Walsh, D. S., Wilairatana, P., Tang, D. B., Heppner, D. G. Jr., Brewer, T. G., Krudsood, S., Silachamroon, U., Phumratanaprapin, W., Siriyanonda, D. and Looareesuwan, S. (2004 b). Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse. Clinical Infectious Diseases 39, 1095–1103. doi: 10.1086/424508.CrossRefGoogle ScholarPubMed
Wilkinson, R. N., Noeypatimanondh, S. and Gould, D. J. (1976). Infectivity of falciparum malaria patients for anopheline mosquitoes before and after chloroquine treatment. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 306–307.CrossRefGoogle ScholarPubMed
Williams, J. L. (1999). Stimulation of Plasmodium falciparum gametocytogenesis by conditioned medium from parasite cultures. American Journal of Tropical Medicine and Hygiene 60, 7–13.CrossRefGoogle ScholarPubMed
World Health Organization (2011). World Malaria Report 2011. World Health Organization, Geneva, Switzerland.Google Scholar
Young, J. A., Fivelman, Q. L., Blair, P. L., de la Vega, P., Le Roch, K. G., Zhou, Y., Carucci, D. J., Baker, D. A. and Winzeler, E. A. (2005). The Plasmodium falciparum sexual development transcriptome: a microarray analysis using ontology-based pattern identification. Molecular and Biochemical Parasitology 143, 67–79. doi: 10.1016/j.molbiopara.2005.05.007.CrossRefGoogle ScholarPubMed
Zoungrana, A., Coulibaly, B., Sie, A., Walter-Sack, I., Mockenhaupt, F. P., Kouyate, B., Schirmer, R. H., Klose, C., Mansmann, U., Meissner, P. and Muller, O. (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. doi: 10.1371/journal.pone.0001630.CrossRefGoogle ScholarPubMed