Recent Advances in Transmission-Blocking Drugs for Malaria Elimination

References

• WHO . World Malaria Report: 2018, WHO. Geneva, Switzerland (2018).
   Google Scholar
• Leoni S , BuonfrateD, AnghebenA, GobbiF, BisoffiZ. The hyper-reactive malarial splenomegaly: a systematic review of the literature. Malaria J.14(1), 185 (2015).
   PubMedGoogle Scholar
• Viriyavejakul P , KhachonsaksumetV, PunsawadC. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression. Malaria J.13(1), 106 (2014).
   PubMedGoogle Scholar
• Thanachartwet V , DesakornV, SahassanandaD, KyawWin KKY, SupapornT. Acute renal failure in patients with severe falciparum malaria: using the WHO 2006 and RIFLE criteria. Int. J. Nephrol.2013, 841518 (2013).
   PubMedGoogle Scholar
• Idro R , MarshK, JohnCC, NewtonCRJ. Cerebral malaria: mechanisms of brain injury and strategies for improved neuro-cognitive outcome. Pediatr Res.68(4), 267–274 (2010).
   PubMed Web of Science ®Google Scholar
• Phillips MA , BurrowsJN, ManyandoC, van HuijsduijnenRH, Van VoorhisWC, WellsTNC. Malaria. Nat. Rev. Dis. Primers3, 17050 (2017).
   PubMed Web of Science ®Google Scholar
• Doerig C , RaynerJC, ScherfA, TobinAB. Post-translational protein modifications in malaria parasites. Nat. Rev. Microbiol.13(3), 160–172 (2015).
   PubMed Web of Science ®Google Scholar
• Sinden RE , CanningEU, BrayRS, SmalleyME. Gametocyte and gamete development in Plasmodium falciparum. Proc. R. Soc. Lond. B. Biol. Sci.201(1145), 375–399 (1978).
   PubMed Web of Science ®Google Scholar
• Smith RC , Vega-RodríguezJ, Jacobs-LorenaM. The Plasmodium bottleneck: malaria parasite losses in the mosquito vector. Mem. Inst. Oswaldo Cruz.109(5), 644–661 (2014).
   PubMed Web of Science ®Google Scholar
• WHO . Policy brief on single-dose primaquine as a gametocytocide in Plasmodium falciparum malaria (2015). www.who.int/malaria/publications/atoz/policy-brief-single-dose-primaquine-pf/en/.
   Google Scholar
• Lucantoni L , LoganathanS, AveryVM. The need to compare: assessing the level of agreement of three high-throughput assays against Plasmodium falciparum mature gametocytes. Sci. Rep.7, 45992 (2017).
   PubMedGoogle Scholar
• Lucantoni L , FidockDA, AveryVM. Luciferase-based, high-throughput assay for screening and profiling transmission-blocking compounds against Plasmodium falciparum gametocytes. Antimicrob. Agents Chemother.60(4), 2097–2107 (2016).
   PubMed Web of Science ®Google Scholar
• Bolscher JM , KoolenKMJ, van GemertGJet al. A combination of new screening assays for prioritization of transmission-blocking antimalarials reveals distinct dynamics of marketed and experimental drugs. J. Antimicrob. Chemother.70(5), 1357–1366 (2015).
   PubMed Web of Science ®Google Scholar
• Miguel-Blanco C , LelièvreJ, DelvesMJet al. Imaging-based high throughput screening assay to identify new molecules with transmission-blocking potential against P. falciparum female gamete formation. Antimicrob. Agents Chemother.59(6), 3298–3305 (2015).
   PubMed Web of Science ®Google Scholar
• Vos MW , StoneWJR, KoolenKMet al. A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes. Sci. Rep.5, 18704 (2015).
   PubMed Web of Science ®Google Scholar
• Sun W , TanakaTQ, MagleCTet al. Chemical signatures and new drug targets for gametocytocidal drug development. Sci. Rep.4, 3743 (2014).
   PubMed Web of Science ®Google Scholar
• Lucantoni L , DuffyS, AdjalleySH, FidockDA, AveryVM. Identification of MMV malaria box inhibitors of Plasmodium falciparum early-stage gametocytes, using a luciferase-based high-throughput assay. Antimicrob. Agents Chemother.57(12), 6050–6062 (2013).
   PubMed Web of Science ®Google Scholar
• Wadi I , AnvikarAR, NathM, PillaiCR, SinhaA, ValechaN. Critical examination of approaches exploited to assess the effectiveness of transmission-blocking drugs for malaria. Future Med. Chem.10(22), 2619–2639 (2018).
   PubMed Web of Science ®Google Scholar
• D'Alessandro S , SilvestriniF, DecheringKet al. A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection. J. Antimicrob. Chemother.68(9), 2048–2058 (2013).
   PubMed Web of Science ®Google Scholar
• Reader J , BothaM, TheronAet al. Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination. Malaria J.14(1), 213 (2015).
   PubMedGoogle Scholar
• Lelièvre J , AlmelaMJ, LozanoSet al. Activity of clinically relevant antimalarial drugs on Plasmodium falciparum mature gametocytes in an ATP bioluminescence “Transmission Blocking” assay. PLoS ONE7(4), e35019 (2012).
   PubMed Web of Science ®Google Scholar
• Peatey CL , SpicerTP, HodderPS, TrenholmeKR, GardinerDL. A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes. Mol. Biochem. Parasitol.180(2), 127–131 (2011).
   PubMed Web of Science ®Google Scholar
• Buchholz K , BurkeTA, WilliamsonKC, WiegandRC, WirthDF, MartiM. A high-throughput screen targeting malaria transmission stages opens new avenues for drug development. J. Infect. Dis.203(10), 1445–1453 (2011).
   PubMed Web of Science ®Google Scholar
• Adjalley SH , JohnstonGL, LiTet al. Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. PNAS.108(47), E1214 (2011).
   PubMed Web of Science ®Google Scholar
• Tanaka TQ , DeuE, Molina-CruzAet al. Plasmodium dipeptidyl aminopeptidases as malaria transmission-blocking drug targets. Antimicrob. Agents Chemother.57(10), 4645–4652 (2013).
   PubMed Web of Science ®Google Scholar
• Tanaka TQ , WilliamsonKC. A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue. Mol. Biochem. Parasitol.177(2), 160–163 (2011).
   PubMed Web of Science ®Google Scholar
• Leba L-J , MussetL, PelleauSet al. Use of Plasmodium falciparum culture-adapted field isolates for in vitro exflagellation-blocking assay. Malaria J.14(1), 234 (2015).
   PubMedGoogle Scholar
• Ruecker A , MathiasDK, StraschilUet al. A male and female gametocyte functional viability assay to identify biologically relevant malaria transmission-blocking drugs. Antimicrob. Agents Chemother.58(12), 7292–7302 (2014).
   PubMed Web of Science ®Google Scholar
• Delves MJ , RueckerA, StraschilUet al. Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs. Antimicrob. Agents Chemother.57(7), 3268–3274 (2013).
   PubMed Web of Science ®Google Scholar
• Azevedo R , MarkovicM, MachadoM, Franke-FayardB, MendesAM, PrudêncioM. A bioluminescence method for in vitro screening of Plasmodium transmission-blocking compounds. Antimicrob. Agents Chemother.61(6), e02699–e02716 (2017).
   PubMed Web of Science ®Google Scholar
• Plouffe DM , WreeM, DuAlan Yet al. High-throughput assay and discovery of small molecules that interrupt malaria transmission. Cell Host Microbe.19(1), 114–126 (2016).
   PubMed Web of Science ®Google Scholar
• Duffy S , AveryVM. Identification of inhibitors of Plasmodium falciparum gametocyte development. Malaria J.12(1), 408 (2013).
   PubMedGoogle Scholar
• Delves M , PlouffeD, ScheurerCet al. The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites. PLOS Med.9(2), e1001169 (2012).
   PubMed Web of Science ®Google Scholar
• Delves MJ , SindenRE. A semi-automated method for counting fluorescent malaria oocysts increases the throughput of transmission blocking studies. Malaria J.9, 35 (2010).
   PubMed Web of Science ®Google Scholar
• Chevalley S , CosteA, LopezA, PipyB, ValentinA. Flow cytometry for the evaluation of anti-plasmodial activity of drugs on Plasmodium falciparum gametocytes. Malaria J.9, 49 (2010).
   PubMed Web of Science ®Google Scholar
• Peatey CL , Skinner-AdamsTS, DixonMWA, McCarthyJS, GardinerDL, TrenholmeKR. Effect of antimalarial drugs on Plasmodium falciparum gametocytes. J. Infect. Dis.200(10), 1518–1521 (2009).
   PubMed Web of Science ®Google Scholar
• Benoit-Vical F , LelièvreJ, BerryAet al. Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Antimicrob. Agents Chemother.51(4), 1463–1472 (2007).
   PubMed Web of Science ®Google Scholar
• Chavalitshewinkoon-Petmitr P , PongvilairatG, AuparakkitanonS, WilairatP. Gametocytocidal activity of pyronaridine and DNA topoisomerase II inhibitors against multidrug-resistant Plasmodium falciparum in vitro. Parasitol. Intl.48(4), 275–280 (2000).
   PubMedGoogle Scholar
• Birkett AJ . Status of vaccine research and development of vaccines for malaria. Vaccine.34(26), 2915–2920 (2016).
   PubMed Web of Science ®Google Scholar
• Sauerwein RW , BousemaT. Transmission blocking malaria vaccines: assays and candidates in clinical development. Vaccine33(52), 7476–7482 (2015).
   PubMed Web of Science ®Google Scholar
• Slater AF . Chloroquine: mechanism of drug action and resistance in Plasmodium falciparum. Pharmacol. Ther.57(2–3), 203–235 (1993).
   PubMed Web of Science ®Google Scholar
• Yeo SJ , LiuDX, KimHS, ParkH. Anti-malarial effect of novel chloroquine derivatives as agents for the treatment of malaria. Malaria J.16(1), 80 (2017).
   PubMedGoogle Scholar
• Kreidenweiss A , KremsnerPG, MordmullerB. Comprehensive study of proteasome inhibitors against Plasmodium falciparum laboratory strains and field isolates from Gabon. Malar J.7(1), 187 (2008).
   PubMedGoogle Scholar
• Combrinck JM , MabothaTE, NcokaziKKet al. Insights into the role of heme in the mechanism of action of antimalarials. ACS Chem. Bio.8(1), 133–137 (2013).
   PubMed Web of Science ®Google Scholar
• Wong W , BaiXC, SleebsBEet al. Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nature Microbio.2(6), 17031 (2017).
   PubMed Web of Science ®Google Scholar
• Rohrbach P , SanchezCP, HaytonKet al. Genetic linkage of Pfmdr1 with food vacuolar solute import in Plasmodium falciparum. EMBO J.25(13), 3000–3011 (2006).
   PubMed Web of Science ®Google Scholar
• de Villiers KA , MarquesHM, EganTJ. The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials. J. Inorgan. Biochem.102(8), 1660–1667 (2008).
   PubMed Web of Science ®Google Scholar
• Mwai L , KiaraSM, AbdirahmanAet al. In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in PFCRT and PFMDR1. Antimicrob. Agents Chemother.53(12), 5069–5073 (2009).
   PubMed Web of Science ®Google Scholar
• Auparakkitanon S , ChapoomramS, KuahaK, ChirachariyavejT, WilairatP. Targeting of hematin by the antimalarial pyronaridine. Antimicrob. Agents Chemother.50(6), 2197–2200 (2006).
   PubMed Web of Science ®Google Scholar
• García-Estrada C , PradaCF, Fernández-RubioC, Rojo-VázquezF, Balaña-FouceR. DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery. Proc. Biol. Sci.277(1689), 1777–1787 (2010).
   PubMed Web of Science ®Google Scholar
• Nixon GL , MossDM, ShoneAEet al. Antimalarial pharmacology and therapeutics of atovaquone. J. Antimicrob. Chemother.68(5), 977–985 (2013).
   PubMed Web of Science ®Google Scholar
• Fidock DA , WellemsTE. Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. PNAS.94(20), 10931–10936 (1997).
   PubMed Web of Science ®Google Scholar
• Khositnithikul R , Tan-AriyaP, MungthinM. In vitro atovaquone/proguanil susceptibility and characterization of the cytochrome b gene of Plasmodium falciparum from different endemic regions of Thailand. Malaria J.7(1), 23 (2008).
   PubMedGoogle Scholar
• Curtis J , MaxwellCA, MsuyaFH, MkongewaS, AllouecheA, WarhurstDC. Mutations in DHFR in Plasmodium falciparum infections selected by chlorproguanil-dapsone treatment. J. Infect Dis.186(12), 1861–1864 (2002).
   PubMed Web of Science ®Google Scholar
• Rathod PK , McErleanT, LeePC. Variations in frequencies of drug resistance in Plasmodium falciparum. PNAS.94(17), 9389–9393 (1997).
   PubMed Web of Science ®Google Scholar
• Bridgford JL , XieSC, CobboldSAet al. Artemisinin kills malaria parasites by damaging proteins and inhibiting the proteasome. Nat. Comm.9(1), 3801 (2018).
   PubMedGoogle Scholar
• Gebru T , MordmüllerB, HeldJ. Effect of fluorescent dyes on in vitro-differentiated, late-stage Plasmodium falciparum gametocytes. Antimicrob. Agents Chemother.58(12), 7398–7404 (2014).
   PubMed Web of Science ®Google Scholar
• Pybus BS , MarcsisinSR, JinXet al. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malaria J.12(1), 212 (2013).
   PubMed Web of Science ®Google Scholar
• Kemirembe K , CabreraM, CuiL. Interactions between tafenoquine and artemisinin-combination therapy partner drug in asexual and sexual stage Plasmodium falciparum. Intl. J. Parasitol. Drugs Drug Res.7(2), 131–137 (2017).
   PubMed Web of Science ®Google Scholar
• Ramsay RR , DunfordC, GillmanPK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. British J. Pharmacol.152(6), 946–951 (2007).
   PubMed Web of Science ®Google Scholar
• Prieto JH . The Binding of methylene blue to Plasmodium falciparum glutathione reductase. Biophys. J.112(3), 351a (2017).
   Web of Science ®Google Scholar
• Uhlemann AC , WittlinS, MatileH, BustamanteLY, KrishnaS. Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277). Antimicrob. Agents Chemother.51(2), 667–672 (2007).
   PubMed Web of Science ®Google Scholar
• Lanteri CA , ChaorattanakaweeS, LonCet al. Ex vivo activity of endoperoxide antimalarials, including artemisone and arterolane, against multidrug-resistant Plasmodium falciparum isolates from Cambodia. Antimicrob. Agents Chemother.58(10), 5831–5840 (2014).
   PubMed Web of Science ®Google Scholar
• Chopra I , RobertsM. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Bio. Rev.65(2), 232–260 (2001).
   PubMed Web of Science ®Google Scholar
• Achieng AO , IngasiaLA, JumaDWet al. Reduced in vitro doxycycline susceptibility in Plasmodium falciparum field isolates from Kenya is associated with PfTetQ KYNNNN sequence polymorphism. Antimicrob. Agents Chemother.58(10), 5894–5899 (2014).
   PubMed Web of Science ®Google Scholar
• White NJ . Antimalarial drug resistance. J. Clin. Invest.113(8), 1084–92 (2004).
   PubMed Web of Science ®Google Scholar
• Coronado LM , NadovichCT, SpadaforaC. Malarial hemozoin: from target to tool. BBA - General Subjects1840(6), 2032–2041 (2014).
   PubMed Web of Science ®Google Scholar
• Ginsburg H , GolenserJ. Glutathione is involved in the antimalarial action of chloroquine and its modulation affects drug sensitivity of human and murine species of Plasmodium. Redox Report.8(5), 276–279 (2003).
   PubMed Web of Science ®Google Scholar
• Smalley ME , SindenRE. Plasmodium falciparum gametocytes: their longevity and infectivity. Parasitology74(1), 1–8 (1977).
   PubMed Web of Science ®Google Scholar
• Buckling A , Ranford-CartwrightLC, MilesA, ReadAF. Chloroquine increases Plasmodium falciparum gametocytogenesis in vitro. Parasitology.118(4), 339–346 (1999).
   PubMedGoogle Scholar
• Butcher GA . Antimalarial drugs and the mosquito transmission of Plasmodium. Intl. J. Parasitol.27(9), 975–987 (1997).
   PubMed Web of Science ®Google Scholar
• Hogh B , ThompsonR, HetzelCet al. Specific and nonspecific responses to Plasmodium falciparum blood-sage parasites and observations on the gametocytemia in school children living in a malaria-endemic area of Mozambique. Am J. Trop. Med. Hyg.52(1), 50–59 (1995).
   PubMed Web of Science ®Google Scholar
• Drakeley CJ , JawaraM, TargettGATet al. 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. Intl. Health.9(1), 53–61 (2004).
   PubMed Web of Science ®Google Scholar
• Targett G , DrakeleyC, JawaraMet al. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. J. Infect. Dis.183(8), 1254–1259 (2001).
   PubMed Web of Science ®Google Scholar
• von Seidlein L , JawaraM, ColemanR, DohertyT, WalravenG, TargettG. Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria. Trop. Med. Intl. Health.6(2), 92–98 (2001).
   PubMed Web of Science ®Google Scholar
• Ringwald P , MecheFS, BascoLK. Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria. Am. J. Trop. Med. Hyg.61(3), 446–448 (1999).
   PubMed Web of Science ®Google Scholar
• Lines JD , WilkesTJ, LyimoEO. Human malaria infectiousness measured by age-specific sporozoite rates in Anopheles gambiae in Tanzania. Parasitology102(Pt 2), 167–177 (1991).
   PubMedGoogle Scholar
• Sowunmi A , FateyeBA. Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs. Trop. Med. Intl. Health.8(9), 783–792 (2003).
   PubMed Web of Science ®Google Scholar
• Robert V , Awono-AmbeneHP, LeHesran JY, TrapeJF. 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(2), 210–216 (2000).
   PubMed Web of Science ®Google Scholar
• Hallett RL , SutherlandCJ, AlexanderNet al. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes. Antimicrob. Agents Chemother.48(10), 3940–3943 (2004).
   PubMed Web of Science ®Google Scholar
• Ecker A , LakshmananV, SinnisP, CoppensI, FidockDA. Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes. J. Infect. Dis.203(2), 228–236 (2011).
   PubMed Web of Science ®Google Scholar
• Sowunmi A , NkoghoOO, OkuboyejoTM, GbotoshoGO, HappiCT, AdewoyeEO. Effects of mefloquine and artesunate mefloquine on the emergence, clearance and sex ratio of Plasmodium falciparum gametocytes in malarious children. Malaria J.8(1), 297 (2009).
   PubMedGoogle Scholar
• Harinasuta T , LasserreR, BunnagD, LeimerR, VinijanontS. Trials of mefloquine in vivax and of mefloquine plus ‘Fansidar’ in falciparum malaria. Lancet.325(8434), 885–888 (1985).
   Google Scholar
• Price RN , NostenF, LuxemburgerCet al. Effects of artemisinin derivatives on malaria transmissibility. Lancet.347(9016), 1654–1658 (1996).
   PubMed Web of Science ®Google Scholar
• Stepniewska K , PriceRN, SutherlandCJet al. Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity. Malaria J.7(1), 249 (2008).
   PubMedGoogle Scholar
• Penna-Coutinho J , AlmelaMJ, Miguel-BlancoCet al. Transmission-blocking potential of MEFAS, a hybrid compound derived from artesunate and mefloquine. Antimicrob. Agents Chemother.60(5), 3145–3147 (2016).
   PubMed Web of Science ®Google Scholar
• Vugt MV , WilairatanaP, GemperliBet al. Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria. Am. J. Trop. Med. Hyg.60(6), 936–942 (1999).
   PubMed Web of Science ®Google Scholar
• Price RN , MarfurtJ, ChalfeinFet al. In vitro activity of pyronaridine against multidrug-resistant Plasmodium falciparum and Plasmodium vivax. Antimicrob. Agents Chemother.54(12), 5146 (2010).
   PubMed Web of Science ®Google Scholar
• Duffy S , LoganathanS, HolleranJP, AveryVM. Large-scale production of Plasmodium falciparum gametocytes for malaria drug discovery. Nat. Protoc.11(5), 976–992 (2016).
   PubMed Web of Science ®Google Scholar
• Peatey CL , LeroyD, GardinerDL, TrenholmeKR. Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes?Malaria J.11(1), 34 (2012).
   PubMedGoogle Scholar
• Duparc S , Borghini-FuhrerI, CraftCJet al. Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials. Malaria J.12(1), 70 (2013).
   PubMedGoogle Scholar
• Srivastava IK , VaidyaAB. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob. Agents Chemother.43(6), 1334–1339 (1999).
   PubMed Web of Science ®Google Scholar
• Butcher GA , SindenRE. Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. Am. J. Trop. Med. Hyg.68(1), 111–114 (2003).
   PubMed Web of Science ®Google Scholar
• Butcher GA , MendozaJ, SindenRE. Inhibition of the mosquito transmission of Plasmodium berghei by Malarone™ (atovaquone-proguanil). Ann. Trop. Med. Parasitol.94(5), 429–436 (2000).
   PubMed Web of Science ®Google Scholar
• Enosse S , ButcherGA, MargosG, MendozaJ, SindenRE, HoghB. The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone™) and chloroquine. Trans. R. Soc. Trop. Med. Hyg.94(1), 77–82 (2000).
   PubMed Web of Science ®Google Scholar
• Blagborough AM , ChurcherTS, UptonLM, GhaniAC, GethingPW, SindenRE. Transmission-blocking interventions eliminate malaria from laboratory populations. Nat. Comm.4, 1812 (2013).
   PubMed Web of Science ®Google Scholar
• van Vugt M , LeonardiE, PhaipunLet al. Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil. Clin. Infect. Dis.35(12), 1498–1504 (2002).
   PubMed Web of Science ®Google Scholar
• Premji Z , UmehRE, Owusu-AgyeiSet al. Chlorproguanil–dapsone–artesunate versus artemether–lumefantrine: a randomized, double-blind Phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria. PLoS ONE.4(8), e6682 (2009).
   PubMed Web of Science ®Google Scholar
• Tiono AB , DickoA, NdububaDAet al. Chlorproguanil-dapsone-artesunate versus chlorproguanil-dapsone: a randomized, double-blind, Phase III Trial in African children, adolescents and adults with uncomplicated Plasmodium falciparum malaria. Am. J. Trop. Med. Hyg.81(6), 969–978 (2009).
   PubMed Web of Science ®Google Scholar
• Beavogui AH , DjimdeAA, GregsonAet al. Low infectivity of Plasmodium falciparum gametocytes to Anopheles gambiae following treatment with sulfadoxine-pyrimethamine in Mali. Intl. J. Parasitol.40(10), 1213–1220 (2010).
   PubMed Web of Science ®Google Scholar
• Barnes KI , LittleF, MabuzaAet al. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J. Infect. Dis.197(11), 1605–1613 (2008).
   PubMed Web of Science ®Google Scholar
• Ndounga M , MayenguePI, TaharRet al. Efficacy of sulfadoxine-pyrimethamine, amodiaquine, and sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated falciparum malaria in the urban and suburban areas of Brazzaville (Congo). Acta Trop.103(3), 163–171 (2007).
   PubMed Web of Science ®Google Scholar
• Sowunmi A , AdedejiAA, GbotoshoGO, FateyeBA, HappiTC. Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children. Mem. Inst. Oswaldo Cruz101(8), 887–893 (2006).
   PubMed Web of Science ®Google Scholar
• Schneider, P, BousemaT, OmarSet al. (Sub)microscopic Plasmodium falciparum gametocytaemia in Kenyan children after treatment with sulphadoxine-pyrimethamine monotherapy or in combination with artesunate. Intl. J. Parasitol.36(4), 403–408 (2006).
   PubMed Web of Science ®Google Scholar
• Bousema JT , GouagnaLC, MeutstegeAMet al. Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in western Kenya. Trop. Med. Intl. Health.8(5), 427–430 (2003).
   PubMed Web of Science ®Google Scholar
• Méndez F , MuñozÁ, CarrasquillaGet al. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am. J. Epidemiol.156(3), 230–238 (2002).
   PubMed Web of Science ®Google Scholar
• von Seidlein L , MilliganP, PinderMet al. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet355(9201), 352–357 (2000).
   PubMed Web of Science ®Google Scholar
• Kone A , vande Vegte-Bolmer M, Siebelink-StoterRet al. Sulfadoxine-pyrimethamine impairs Plasmodium falciparum gametocyte infectivity and Anopheles mosquito survival. Intl. J. Parasitol.40(10), 1221–1228 (2010).
   PubMed Web of Science ®Google Scholar
• Hallett RL , DunyoS, OrdRet al. Chloroquine/sulphadoxine-pyrimethamine for Gambian children with malaria: transmission to mosquitoes of multidrug-resistant Plasmodium falciparum. PLoS Clin Trials.1(3), e15 (2006).
   PubMedGoogle Scholar
• Chutmongkonkul M , MaierWA, SeitzHM. Plasmodium falciparum: effect of chloroquine, halofantrine and pyrimethamine on the infectivity of gametocytes for Anopheles stephensi mosquitoes. Ann. Trop. Med. Parasitol.86(2), 103–110 (1992).
   PubMed Web of Science ®Google Scholar
• Hogh B , Gamage-MendisA, ButcherGAet al. The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. Am. J. Trop. Med. Hyg.58(2), 176–182 (1998).
   PubMed Web of Science ®Google Scholar
• WHO . Guidelines for the Treatment of Malaria. World Health Organization, Geneva, Third edition. www.who.int/malaria/publications/atoz/9789241549127/en/ (2015).
   Google Scholar
• Abay SM . Blocking malaria transmission to Anopheles mosquitoes using artemisinin derivatives and primaquine: a systematic review and meta-analysis. Parasites Vectors.6(1), 278 (2013).
   PubMedGoogle Scholar
• Carmona-Fonseca J , ArangoE, BlairS. Gametocytemia in falciparum malaria treated with amodiaquine or artesunate. Biomedica28(2), 195–212 (2008).
   PubMed Web of Science ®Google Scholar
• WWARN Gametocyte Study Group . Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data. BMC Med.14(1), 79 (2016).
   PubMedGoogle Scholar
• Bousema T , OkellL, ShekalagheSet al. 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 J.9(1), 136 (2010).
   PubMedGoogle Scholar
• Okell LC , DrakeleyCJ, GhaniAC, BousemaT, SutherlandCJ. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malaria J.7(1), 125 (2008).
   PubMedGoogle Scholar
• Barnes KI , DurrheimDN, LittleFet al. Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu–Natal, South Africa. PLoS Med.2(11), e330 (2005).
   PubMed Web of Science ®Google Scholar
• Chen PQ , LiGQ, GuoXBet al. The infectivity of gametocytes of Plasmodium falciparum from patients treated with artemisinin. Chin. Med. J.107(9), 709–711 (1994).
   PubMed Web of Science ®Google Scholar
• Makanga M . A review of the effects of artemether-lumefantrine on gametocyte carriage and disease transmission. Malaria J.13(1), 291 (2014).
   PubMedGoogle Scholar
• Price RN . Potential of artemisinin-based combination therapies to block malaria transmission. J. Infect. Dis.207(11), 1627–1629 (2013).
   PubMed Web of Science ®Google Scholar
• Bousema JT , SchneiderP, GouagnaLCet al. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum . J. Infect. Dis. 193(8), 1151–1159 (2006).
   PubMed Web of Science ®Google Scholar
• Sutherland CJ , OrdR, DunyoSet al. Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med.2(4), e92 (2005).
   PubMed Web of Science ®Google Scholar
• van den Broek I , KitzC, AlAttas S, LibamaF, BalasegaramM, GuthmannJP. Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malaria J.5, 113 (2006).
   PubMed Web of Science ®Google Scholar
• Kern SE , TionoAB, MakangaMet al. Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis. Malaria J.10, 210 (2011).
   PubMedGoogle Scholar
• Kumar N , ZhengH. Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu on Plasmodium falciparum. Parasitol. Res.76(3), 214–218 (1990).
   PubMed Web of Science ®Google Scholar
• Smithuis F , KyawMK, PheOet al. Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect. Dis.10(10), 673–681 (2010).
   PubMed Web of Science ®Google Scholar
• Coulibaly B , PritschM, BountogoMet al. Efficacy and safety of triple combination therapy with artesunate-amodiaquine-methylene blue for falciparum malaria in children: a randomised controlled trial in Burkina Faso. J. Infect. Dis.211(5), 689–697 (2015).
   PubMed Web of Science ®Google Scholar
• Okebe J , BousemaT, AffaraMet al. The gametocytocidal efficacy of different single doses of primaquine with dihydroartemisinin-piperaquine in asymptomatic parasite carriers in the Gambia: a randomized controlled trial. EBioMedicine13, 348–355 (2016).
   PubMed Web of Science ®Google Scholar
• WHO . Overview of malaria treatment (2019). www.who.int/malaria/areas/treatment/overview/en/
   Google Scholar
• Shah NK , TyagiP, SharmaSK. The impact of artemisinin combination therapy and long-lasting insecticidal nets on forest malaria incidence in tribal villages of India, 2006–2011. PLoS ONE8(2), e56740 (2013).
   PubMed Web of Science ®Google Scholar
• Esu E , EffaEE, OpieON, UwaomaA, MeremikwuMM. Artemether for severe malaria. Cochrane database Syst. Rev.6, CD010678 (2014).
   Google Scholar
• Makanga M , KrudsoodS. The clinical efficacy of artemether/lumefantrine (Coartem®). Malaria J.8(Suppl. 1), S5 (2009).
   PubMedGoogle Scholar
• Navaratnam V , MansorSM, SitNW, GraceJ, LiQ, OlliaroP. Pharmacokinetics of artemisinin-type compounds. Clin. Pharmacokinet.39(4), 255–270 (2000).
   PubMed Web of Science ®Google Scholar
• Chotivanich K , SattabongkotJ, UdomsangpetchRet al. Transmission-blocking activities of quinine, primaquine, and artesunate. Antimicrob. Agents Chemother.50(6), 1927–1930 (2006).
   PubMed Web of Science ®Google Scholar
• Djimde AA , MaigaAW, OuologuemDet al. Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children. Parasite23, 3 (2016).
   PubMedGoogle Scholar
• Sowunmi A , BalogunT, GbotoshoGO, HappiCT, AdedejiAA, FehintolaFA. Activities of amodiaquine, artesunate, and artesunate-amodiaquine against asexual- and sexual-stage parasites in falciparum malaria in children. Antimicrob. Agents Chemother.51(5), 1694 (2007).
   PubMed Web of Science ®Google Scholar
• Price RN , NostenF, SimpsonJAet al. Risk factors for gametocyte carriage in uncomplicated falciparum malaria. Am. J. Trop. Med. Hyg.60(6), 1019–1023 (1999).
   PubMed Web of Science ®Google Scholar
• Bousema JT , GouagnaLC, MeutstegeAMet al. Treatment failure of pyrimethamine-sulphadoxine and induction of Plasmodium falciparum gametocytaemia in children in Western Kenya. Trop. Med. Intl. Health.8(5), 427–430 (2003).
   PubMed Web of Science ®Google Scholar
• Sirima SB , OgutuB, LusinguJPAet al. Comparison of artesunate-mefloquine and artemether-lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, Phase 4 trial. Lancet Infect. Dis.16(10), 1123–1133 (2016).
   PubMed Web of Science ®Google Scholar
• Yavo W , KonateA, KassiFKet al. Efficacy and safety of artesunate-amodiaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in sentinel sites across Cote d'Ivoire. Malaria Res. Treat.2015, 878132 (2015).
   PubMedGoogle Scholar
• Yeka A , DorseyG, KamyaMRet al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS ONE3(6), e2390 (2008).
   PubMed Web of Science ®Google Scholar
• Kamya MR , YekaA, BukirwaHet al. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin. Trials.2(5), e20 (2007).
   PubMedGoogle Scholar
• Mweresa CK , SawaP, YussufRUet al. Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J. Infect. Dis.207(11), 1637–1645 (2013).
   PubMed Web of Science ®Google Scholar
• Sawa P , ShekalagheSA, DrakeleyCJet al. Malaria transmission after artemether-lumefantrine and dihydroartemisinin-piperaquine: a randomized trial. J. Infect. Dis.207(11), 1637–1645 (2013).
   PubMed Web of Science ®Google Scholar
• Mens PF , SawaP, van AmsterdamSMet al. 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 J.7, 237 (2008).
   PubMed Web of Science ®Google Scholar
• 4ABC- The Four Artemisinin-Based Combinations (4ABC) Study Group . A head-tohead comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. PLoS Med.8, e1001119 (2011).
   PubMed Web of Science ®Google Scholar
• Lefèvre G , LooareesuwanS, TreeprasertsukSet al. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am. J. Trop. Med. Hyg.64(5–6), 247–256 (2001).
   PubMed Web of Science ®Google Scholar
• Zwang J , AshleyEA, KaremaCet al. Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis. PLoS ONE4(7), e6358 (2009).
   PubMed Web of Science ®Google Scholar
• Sowunmi A , BalogunST, GbotoshoGO, HappiCT. Plasmodium falciparum gametocyte sex ratios in children with acute, symptomatic, uncomplicated infections treated with amodiaquine. Malaria J.7(1), 169 (2008).
   PubMedGoogle Scholar
• Gonçalves D , HunzikerP. Transmission-blocking strategies: the roadmap from laboratory bench to the community. Malaria J.15(1), 95 (2016).
   PubMedGoogle Scholar
• Ouedraogo AL , GonçalvesBP, GnemeAet al. Dynamics of the human infectious reservoir for malaria determined by mosquito feeding assays and ultrasensitive malaria diagnosis in Burkina Faso. J. Infect. Dis.213(1), 90–99 (2015).
   PubMed Web of Science ®Google Scholar
• Sowunmi A , FehintolaFA, AdedejiAAet al. Open randomized study of artesunate-amodiaquine vs. chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children. Trop. Med. Int. Health.10(11), 1161–1670 (2005).
   PubMed Web of Science ®Google Scholar
• Adjuik M , AgnameyP, BabikerAet al. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet359(9315), 1365–1672 (2002).
   PubMed Web of Science ®Google Scholar
• Agomo PU , MeremikwuMM, WatilaIMet al. Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria. Malaria J.7(1), 172 (2008).
   PubMedGoogle Scholar
• Sagara I , DialloA, KoneMet al. A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am. J. Trop. Med. Hyg.79(5), 655–661 (2008).
   PubMed Web of Science ®Google Scholar
• Tangpukdee N , KrudsoodS, SrivilairitSet al. Gametocyte clearance in uncomplicated and severe Plasmodium falciparum malaria after artesunate-mefloquine treatment in Thailand. Korean J. Parasitol.46(2), 65–70 (2008).
   PubMed Web of Science ®Google Scholar
• Shekalaghe S , DrakeleyC, GoslingRet al. Primaquine clears submicroscopic Plasmodium falciparum gametocytes that persist after treatment with sulphadoxine-pyrimethamine and artesunate. PLoS ONE2(10), e1023 (2007).
   PubMed Web of Science ®Google Scholar
• Schneider P , BousemaT, OmarSet al. (Sub)microscopic Plasmodium falciparum gametocytaemia in Kenyan children after treatment with sulphadoxine-pyrimethamine monotherapy or in combination with artesunate. Int. J. Parasitol.36(4), 403–408 (2006).
   PubMed Web of Science ®Google Scholar
• Priotto G , KabakyengaJK, PinogesLet al. Artesunate and sulfadoxine-pyrimethamine combinations for the treatment of uncomplicated Plasmodium falciparum malaria in Uganda: a randomized, double-blind, placebo controlled trial. Trans. R. Soc. Trop. Med. Hyg.97(3), 325–330 (2003).
   PubMed Web of Science ®Google Scholar
• Oesterholt MJAM , AlifrangisM, SutherlandCJet al. Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya. PLoS ONE4(2), e4364 (2009).
   PubMed Web of Science ®Google Scholar
• Mohamed AO , AbdelHamid MM, MohamedOSet al. Efficacies of DHA–PPQ and AS/SP in patients with uncomplicated Plasmodium falciparum malaria in an area of an unstable seasonal transmission in Sudan. Malaria J.16(1), 163 (2017).
   PubMedGoogle Scholar
• The Worldwide Antimalarial Resistance Network DPSG . The effect of dosing regimens on the antimalarial efficacy of dihydroartemisinin-piperaquine: a pooled analysis of individual patient data. PLoS Medicine10(12), e1001564 (2013).
   PubMed Web of Science ®Google Scholar
• Sutanto I , SuprijantoS, KosasihAet al. 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(5), 685–693 (2013).
   PubMed Web of Science ®Google Scholar
• Denis MB , DavisTM, HewittSet al. Efficacy and safety of dihydroartemisinin-piperaquine (Artekin) in Cambodian children and adults with uncomplicated falciparum malaria. Clin. Infect Dis.35(12), 1469–1476 (2002).
   PubMed Web of Science ®Google Scholar
• Dabira E . Gametocyte carriage after a treatment with primaquine combined with dihydroartemisinin-piperaquine in malaria infected asymptomatic individuals. BMJ Global Health2(Suppl. 2), A20 (2017).
   Google Scholar
• Grande T , BernasconiA, ErhartAet al. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru. PLoS ONE2(10), e1101 (2007).
   PubMed Web of Science ®Google Scholar
• Lanners HN . Effect of the 8-aminoquinoline primaquine on culture derived. Parasitol. Res.77(6), 478–481 (1991).
   PubMed Web of Science ®Google Scholar
• Schlesinger PH , KrogstadDJ, HerwaldtBL. Antimalarial agents: mechanisms of action. Antimicrob. Agents Chemother.32(6), 793–798 (1988).
   PubMed Web of Science ®Google Scholar
• Aikawa M , BeaudoinRL. Morphological effects of 8-aminoquinolines on the exoerythrocytic stages of Plasmodium fallax. Mil. Med.134(10), 986–999 (1969).
   PubMed Web of Science ®Google Scholar
• Marcsisin SR , ReichardG, PybusBS. Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: current state of the art. Pharm. Ther.161, 1–10 (2016).
   PubMed Web of Science ®Google Scholar
• Wadi I , PillaiCR, AnvikarAR, SinhaA, NathM, ValechaN. Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking. Malaria J.17(1), 11 (2018).
   PubMedGoogle Scholar
• Lin JT , LonC, SpringMDet al. Single dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission in Cambodia: an open-label randomized trial. PLoS ONE12(6), e0168702 (2017).
   PubMed Web of Science ®Google Scholar
• White NJ . Primaquine to prevent transmission of falciparum malaria. Lancet Infect. Dis.13(2), 175–181 (2013).
   PubMed Web of Science ®Google Scholar
• Shekalaghe SA , ter BraakR, DaouMet al. In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A–) individuals. Antimicrob. Agents Chemother.54(5), 1762 (2010).
   PubMed Web of Science ®Google Scholar
• Karwacki JJ , ShanksGD, KummalueT, WatanasookC. Primaquine induced hemolysis in a Thai soldier. Southeast Asian. J. Trop. Med. Public Health.20(4), 555–556 (1989).
   PubMedGoogle Scholar
• Eziefula AC , BousemaT, YeungSet al. Single dose primaquine for clearance of Plasmodium falciparum gametocytes in children with uncomplicated malaria in Uganda: a randomised, controlled, double-blind, dose-ranging trial. Lancet Infect. Dis.14(2), 130–139 (2014).
   PubMed Web of Science ®Google Scholar
• Tine RC , SyllaK, FayeBTet al. Safety and efficacy of adding a single low dose of primaquine to the treatment of adult patients with Plasmodium falciparum malaria in Senegal, to reduce gametocyte carriage: a randomized controlled trial. Clin. Infect. Dis.65(4), 535–543 (2017).
   PubMed Web of Science ®Google Scholar
• Dicko A , BrownJM, DiawaraHet al. Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised Phase 2 trial. Lancet Infect. Dis.16(6), 674–684 (2016).
   PubMed Web of Science ®Google Scholar
• Mwaiswelo R , NgasalaBE, JovelIet al. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malaria J.15(1), 316 (2016).
   PubMedGoogle Scholar
• Bancone G , ChowwiwatN, SomsakchaicharoenRet al. Single low dose primaquine (0.25 mg/kg) does not cause clinically significant haemolysis in G6PD deficient subjects. PLoS ONE11(3), e0151898 (2016).
   PubMed Web of Science ®Google Scholar
• White NJ , AshleyEA, RechtJet al. Assessment of therapeutic responses to gametocytocidal drugs in Plasmodium falciparum malaria. Malaria J.13(1), 483 (2014).
   PubMedGoogle Scholar
• Batu AT . Primaquine induced haemolysis in G6PD deficient Burmese. Trans. R. Soc. Trop. Med. Hyg.64, 785–786 (1970).
   PubMed Web of Science ®Google Scholar
• Khandelia V , PyarsabadiP, NamaU, ChittoraS, SwamiY, RichariyaH. The potential nephrotoxic effect of single tablet of 15mg primaquine in G6PD deficient Hadoti region population of India. Intl. J. Adv. Med.4(2), 605 (2017).
   Google Scholar
• Salvidio E , PannacciulliI, TizianelloA, AjmarF. Nature of hemolytic crisis and the fate of G6PD deficient, drug-damaged erythrocytes in Sardinians. N. Engl. J. Med.276(24), 1339–1344 (1967).
   PubMed Web of Science ®Google Scholar
• John CC . Primaquine plus artemisinin combination therapy for reduction of malaria transmission: promise and risk. BMC Med.14(1), 65 (2016).
   PubMedGoogle Scholar
• Gonçalves BP , PettH, TionoABet al. Age, weight, and CYP2D6 genotype are major determinants of primaquine pharmacokinetics in African children. Antimicrob. Agents Chemother.61(5), e02590–e02616 (2017).
   PubMed Web of Science ®Google Scholar
• Bennett JW , PybusBS, YadavaAet al. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N. Engl. J. Med.369(14), 1381–1382 (2013).
   PubMed Web of Science ®Google Scholar
• Wright GE , NiehausDJ, DrogemollerBI, KoenL, GaedigkA, WarnichL. Elucidation of CYP2D6 genetic diversity in a unique African population: implications for the future application of pharmacogenetics in the Xhosa population. Ann. Hum. Genet.74(4), 340–350 (2010).
   PubMed Web of Science ®Google Scholar
• Meltzer E , SchwartzE. Low-dose primaquine for falciparum malaria. Lancet Infect. Dis.14, 449 (2014).
   PubMedGoogle Scholar
• Bright AT , AlenaziT, ShokoplesSet al. Genetic analysis of primaquine tolerance in a patient with relapsing vivax malaria. Emerg. Infect. Dis.19(5), 802–805 (2013).
   PubMed Web of Science ®Google Scholar
• Langholz Kristensen K , DragstedUB. Recurrent Plasmodium vivax malaria due to dose-dependent primaquine resistance: a case report. Scand. J. Infect. Dis.46(1), 63–65 (2013).
   PubMedGoogle Scholar
• Stone W , GonçalvesBP, BousemaT, DrakeleyC. Assessing the infectious reservoir of falciparum malaria: past and future. Trends Parasitol.31(7), 287–296 (2015).
   PubMed Web of Science ®Google Scholar
• Lin JT , SaundersDL, MeshnickSR. The role of submicroscopic parasitemia in malaria transmission: what is the evidence?Trends Parasitol.30(4), 183–190 (2014).
   PubMed Web of Science ®Google Scholar
• Chen IT , GoslingRD. Targeting Plasmodium falciparum transmission with primaquine: same efficacy, improved safety with a lower dose?Expert Rev. Clin. Pharmacol.7(6), 681–686 (2014).
   PubMed Web of Science ®Google Scholar
• Lacerda MVG , Llanos-CuentasA, KrudsoodSet al. Single-dose tafenoquine to prevent relapse of Plasmodium vivax malaria. New Eng. J. Med.380(3), 215–228 (2019).
   PubMed Web of Science ®Google Scholar
• Ramharter M , NoedlH, ThimasarnK, WiedermannG, WernsdorferG, WernsdorferWH. In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum. Am. J. Trop. Med. Hyg.67(1), 39–43 (2002).
   PubMed Web of Science ®Google Scholar
• Edstein MD , KociskoDA, BrewerTG, WalshDS, EamsilaC, CharlesBG. Population pharmacokinetics of the new antimalarial agent tafenoquine in Thai soldiers. British J. Clin. Pharmacol.52(6), 663–670 (2001).
   PubMed Web of Science ®Google Scholar
• Lell B , FaucherJF, MissinouMAet al. Malaria chemoprophylaxis with tafenoquine: a randomised study. Lancet355(9220), 2041–2045 (2000).
   PubMed Web of Science ®Google Scholar
• Brueckner RP , CosterT, WescheDL, ShmuklarskyM, SchusterBG. Prophylaxis of Plasmodium falciparum infection in a human challenge model with WR 238605, a new 8-aminoquinoline antimalarial. Antimicrob. Agents Chemother.42(5), 1293–1294 (1998).
   PubMed Web of Science ®Google Scholar
• Crockett M , KainKC. Tafenoquine: a promising new antimalarial agent. Expert. Opin. Investig. Drugs16(5), 705–715 (2007).
   PubMed Web of Science ®Google Scholar
• Obaldia N , RossanRN, CooperRDet al. WR 238605, chloroquine, and their combinations as blood schizonticides against a chloroquine-resistant strain of Plasmodium vivax in Aotus monkeys. Am. J. Trop. Med. Hyg.56(5), 508–510 (1997).
   PubMed Web of Science ®Google Scholar
• Cooper RD , MilhousWK, RieckmannKH. The efficacy of WR 238605 against the blood stages of a chloroquine resistant strain of Plasmodium vivax. Trans. R. Soc. Trop. Med. Hyg.88(6), 691–692 (1994).
   PubMed Web of Science ®Google Scholar
• Peters W , RobinsonBL, MilhousWK. The chemotherapy of rodent malaria. LI. Studies on a new 8-aminoquinoline, WR 238,605. Annals Tropical Med. Parasitol.87(6), 547–552 (1993).
   PubMed Web of Science ®Google Scholar
• Coleman RE , ClavinAM, MilhousWK. Gametocytocidal and sporontocidal activity of antimalarials against Plasmodium berghei ANKA in ICR mice and Anopheles stephensi mosquitoes. Am. J. Trop. Med. Hyg.46(2), 169–182 (1992).
   PubMed Web of Science ®Google Scholar
• Ponsa N , SattabongkotJ, KittayapongP, EikaratN, ColemanRE. Transmission-blocking activity of tafenoquine (WR-238605) and artelinic acid against naturally circulating strains of Plasmodium vivax in Thailand. Am. J. Trop. Med. Hyg.69(5), 542–547 (2003).
   PubMed Web of Science ®Google Scholar
• Green, JA, MohamedK, GoyalNet al. Pharmacokinetic interactions between tafenoquine and dihydroartemisinin-piperaquine or artemether-lumefantrine in healthy adult subjects. Antimicrob. Agents Chemother.60(12), 7321–7332 (2016).
   PubMed Web of Science ®Google Scholar
• St Jean PL , XueZ, CarterNet al. Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial. Malaria J.15, 97 (2016).
   PubMed Web of Science ®Google Scholar
• Marcsisin SR , SousaJC, ReichardGAet al. Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds. Malaria J.13(1), 2 (2014).
   PubMedGoogle Scholar
• GlaxoSmithKline . G6PD (Glucose-6-Phosphate Dehydrogenase) Study to Evaluate Hemolysis Potential of TFQ (Tafenoquine). ClinicalTrials.gov.Bethesda, MDhttps://clinicaltrials.gov/ct2/show/NCT01205178.(2018).
   Google Scholar
• Coulibaly B , ZoungranaA, MockenhauptFPet al. Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS ONE4(5), e5318 (2009).
   PubMed Web of Science ®Google Scholar
• Lu G , NagbanshiM, GoldauNet al. Efficacy and safety of methylene blue in the treatment of malaria: a systematic review. BMC Med.16(1), 59 (2018).
   PubMed Web of Science ®Google Scholar
• Wadi I , PrasadD, BatraNet al. Targeting asexual and sexual blood stages of human malaria parasite P. falciparum with 7-chloroquinoline based [1,2,3]-triazoles. ChemMedChem14(4), 484–493 (2019).
   PubMed Web of Science ®Google Scholar
• Kumar H , WadiI, DevarajiV, PillaiCR, GhoshSK. A novel quinoline-appended chalcone derivative as potential Plasmodium falciparum gametocytocide. J. Vector Borne Dis. [ IN PRESS]
   Web of Science ®Google Scholar
• Bountogo M , ZoungranaA, CoulibalyBet al. Efficacy of methylene blue monotherapy in semi-immune adults with uncomplicated falciparum malaria: a controlled trial in Burkina Faso. Trop. Med. Intl. Health.15(6), 713–717 (2010).
   PubMed Web of Science ®Google Scholar
• Zoungrana A , CoulibalyB, SiéAet al. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS ONE3(2), e1630 (2008).
   PubMed Web of Science ®Google Scholar
• Meissner PE , MandiG, WitteSet al. Safety of the methylene blue plus chloroquine combination in the treatment of uncomplicated falciparum malaria in young children of Burkina Faso [ISRCTN27290841]. Malaria J.4(1), 45 (2005).
   PubMedGoogle Scholar
• Kiszewski AE . Blocking Plasmodium falciparum malaria transmission with drugs: the gametocytocidal and sporontocidal properties of current and prospective antimalarials. Pharmaceuticals4(1), 44–68 (2010).
   Google Scholar
• Walter-Sack I , RengelshausenJ, OberwittlerHet al. High absolute bioavailability of methylene blue given as an aqueous oral formulation. Eur. J. Clin. Pharm.65(2), 179–189 (2009).
   PubMed Web of Science ®Google Scholar
• McDonagh EM , BautistaJM, YoungsterI, AltmanRB, KleinTE. PharmGKB summary: methylene blue pathway. Pharmacogenet. Genomics23(9), 498–508 (2013).
   PubMed Web of Science ®Google Scholar
• Sikka P , BindraVK, KapoorS, JainV, SaxenaKK. Blue cures blue but be cautious. J. Pharm. Bioallied Sci.3(4), 543–545 (2011).
   PubMedGoogle Scholar
• Foltz LM , DalalBI, WadsworthLDet al. Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug Triapine. Amer. J. Hemat.81(3), 210–211 (2006).
   PubMed Web of Science ®Google Scholar
• Liao YP , HungDZ, YangDY. Hemolytic anemia after methylene blue therapy for aniline-induced methemoglobinemia. Vet. Hum. Toxicol.44(1), 19–21 (2002).
   PubMedGoogle Scholar
• Karadsheh NS . Metoclopramide-induced methemoglobinemia in a patient with co-existing deficiency of glucose-6-phosphate dehydrogenase and NADH-cytochrome b5 reductase: failure of methylene blue treatment. Haematologica86(6), 659–660 (2001).
   PubMed Web of Science ®Google Scholar
• Rosen PJ , JohnsonC, McGeheeWG, BeutlerE. Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency. Ann. Intern Med.75(1), 83–86 (1971).
   PubMed Web of Science ®Google Scholar
• Dart CR . Medical Toxicology. 3rd Edition. Lippincott Williams and Wilkins, PA, USA (2004).
   Google Scholar
• Mandi G , WitteS, MeissnerPet al. Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso. Trop. Med. Intl Health.10(1), 32–38 (2005).
   PubMed Web of Science ®Google Scholar
• Middali MM . Postoperative methemoglobinemia with associated G-6-P-D deficiency in infant cardiac surgery – enigmas in diagnosis and management. Paediatr. Anaesth.15(4), 334–337 (2005).
   PubMed Web of Science ®Google Scholar
• Golden PJ , WeinsteinR. Treatment of high-risk, refractory acquired methemoglobinemia with automated red blood cell exchange. J. Clin. Apher.13(1), 28–31 (1998).
   PubMed Web of Science ®Google Scholar
• Müller O , MockenhauptFP, MarksBet al. 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(4), 3768385 (2013).
   PubMed Web of Science ®Google Scholar
• University of Oxford . Pharmacokinetic and in vitro transmission blocking activities study of primaquine compare to methylene blue in healthy volunteer both G6PD normal and G6PD deficiency. In: ClinicalTrials.gov. Bethesda,MD, USA (2016). https://clinicaltrials.gov/ct2/show/NCT01668433
   Google Scholar
• Heidelberg University . Methylene blue against falciparum malaria in Burkina Faso (BlueACTn). In: ClinicalTrials.gov. Bethesda, MD, USA (2016). https://clinicaltrials.gov/ct2/show/NCT02851108
   Google Scholar
• Toure OA , ValechaN, TshefuAKet al. A Phase 3, double-blind, randomized study of arterolane maleate-piperaquine phosphate vs artemether-lumefantrine for falciparum malaria in adolescent and adult patients in Asia and Africa. Clin. Infect. Dis.62(8), 964–971 (2016).
   PubMed Web of Science ®Google Scholar
• Krudsood S , WilairatanaP, TangpukdeeNet al. Safety and tolerability of elubaquine (bulaquine, CDRI 80/53) for treatment of Plasmodium vivax malaria in Thailand. Korean J. Parasitol.44(3), 221–228 (2006).
   PubMedGoogle Scholar
• Noel S , SharmaS, ShankarR, RathSK. Identification of differentially expressed genes after acute exposure to bulaquine (CDRI 80/53) in mice liver. Basic Clin. Pharmacol. Toxicol.103(6), 522–529 (2008).
   PubMed Web of Science ®Google Scholar
• Dutta GP . New antimalarial drug discovery in India and future strategy for malaria control. Proc. Ind. Natl Sci. Acad.82(1), 31–52 (2016).
   Google Scholar
• Puri SK , DuttaGP. Plasmodium cynomolgi: gametocytocidal activity of the anti-malarial compound CDRI 80/53 (elubaquine) in rhesus monkeys. Exp. Parasitol.111(1), 8–13 (2005).
   PubMed Web of Science ®Google Scholar
• von Seidlein L , AuburnS, EspinoFet al. Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malaria J.12(1), 112 (2013).
   PubMedGoogle Scholar
• Gogtay NJ , KamtekarKD, DalviSSet al. A randomized, parallel study of the safety and efficacy of 45mg primaquine versus 75mg bulaquine as gametocytocidal agents in adults with blood schizonticide-responsive uncomplicated falciparum malaria. BMC Infect. Dis.6(1), 16 (2006).
   PubMedGoogle Scholar
• Tan KR , MagillAJ, PariseME, ArguinPM. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am. J. Trop. Med. Hyg.84(4), 517–531 (2011).
   PubMed Web of Science ®Google Scholar
• Batra N , RajendranV, AgarwalDet al. Synthesis and antimalarial evaluation of [1, 2,3]-triazole-tethered sulfonamide-berberine hybrids. ChemistrySelect.3(34), 9790–9793 (2018).
   Web of Science ®Google Scholar
• Baragaña B , HallyburtonI, LeeMCSet al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature522(7556), 315 (2015).
   PubMed Web of Science ®Google Scholar
• Wells TN , Hooftvan Huijsduijnen R, Van VoorhisWC. Malaria medicines: a glass half full?Nat. Rev. Drug Disc.14(6), 424–442 (2015).
   PubMed Web of Science ®Google Scholar
• Ashley EA , PhyoAP. Drugs in development for malaria. Drugs78(9), 861–879 (2018).
   PubMed Web of Science ®Google Scholar
• Goldgof GM , DurrantJD, OttilieSet al. Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor. Sci. Rep.6, 27806 (2016).
   PubMed Web of Science ®Google Scholar
• van Pelt-Koops JC , PettHEet al. The spiroindolone drug candidate NITD609 potently inhibits gametocytogenesis and blocks Plasmodium falciparum transmission to Anopheles mosquito vector. Antimicrob. Agents Chemother.56(7), 3544–3548 (2012).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . Cipargamin (2018). www.mmv.org/node/11219/overlay
   Google Scholar
• Nagle A , WuT, KuhenKet al. Imidazolopiperazines: lead optimization of the second-generation antimalarial agents. J. Med. Chem.55(9), 4244–4273 (2012).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . Developing antimalarials to save lives(2018). www.mmv.org/related-story-type/kaf156
   Google Scholar
• Charman SA , Arbe-BarnesS, BathurstICet al. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. PNAS108(11), 4400–4405 (2011).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . Artefenomel (2018). www.mmv.org/related-story-type/artefenomel
   Google Scholar
• Phillips MA , LothariusJ, MarshKet al. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci. Transl. Med.7(296), 296ra111 (2015).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . DSM265 Phase IIa Investigation treating Plasmodium falciparum or vivax. https://clinicaltrials.gov/ct2/show/NCT02123290. (2018).
   Google Scholar
• Ghidelli-Disse S , Lafuente-MonasterioMJet al. Identification of Plasmodium PI4 kinase as target of MMV390048 by chemoproteomics. Malaria J.13(1), 38 (2014).
   PubMedGoogle Scholar
• Paquet T , LeManach C, CabreraDGet al. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci. Transl. Med.9(387), eaad9735 (2017).
   PubMed Web of Science ®Google Scholar
• Medicines for Malria Venture . MMV390048(2015). www.mmv.org/newsroom/film/mmv390048
   Google Scholar
• Held J , JeyarajS, KreidenweissA. Antimalarial compounds in Phase II clinical development. Exp. Opin. Invest. Drugs.24(3), 363–382 (2015).
   PubMed Web of Science ®Google Scholar
• Umeda T , TanakaN, KusakabeY, NakanishiM, KitadeY, NakamuraKT. Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum. Sci. Rep.1, 9 (2011).
   PubMed Web of Science ®Google Scholar
• Zhang B , WattsKM, HodgeDet al. A second target of the antimalarial and antibacterial agent fosmidomycin revealed by cellular metabolic profiling. Biochem.50(17), 3570–3577 (2011).
   PubMed Web of Science ®Google Scholar
• Sparr C , PurkayasthaN, KolesinskaBet al. Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by combination with the cell-penetrating peptide octaarginine. Antimicrob. Agents Chemother.57(10), 4689–4698 (2013).
   PubMed Web of Science ®Google Scholar
• Mombo-Ngoma G , RemppisJ, SieversMet al. Efficacy and safety of fosmidomycin-piperaquine as nonartemisinin-based combination therapy for uncomplicated falciparum malaria: a single-arm, age de-escalation proof-of-concept study in Gabon. Clin. Infect. Dis.66(12), 1823–1830 (2018).
   PubMed Web of Science ®Google Scholar
• Dubar F , EganTJ, PradinesBet al. The antimalarial ferroquine: role of the metal and intramolecular hydrogen bond in activity and resistance. ACS Chem. Biol.6(3), 275–287 (2011).
   PubMed Web of Science ®Google Scholar
• Biot C , TaramelliD, Forfar-BaresIet al. Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity. Mol. Pharm.2(3), 185–193 (2005).
   PubMed Web of Science ®Google Scholar
• Henry M , BriolantS, FontaineAet al. In vitro activity of ferroquine is independent of polymorphisms in transport protein genes implicated in quinoline resistance in Plasmodium falciparum. Antimicrob. Agents Chemother.52(8), 2755–2759 (2008).
   PubMed Web of Science ®Google Scholar
• Sanofi . To evaluate the efficacy of a single dose regimen of ferroquine and artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria (FALCI). https://clinicaltrials.gov/ct2/show/NCT02497612
   Google Scholar
• Koita OA , SangareL, MillerHDet al. AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, Phase 2, non-inferiority clinical trial. Lancet Infect. Dis.17(12), 1266–1275 (2017).
   PubMed Web of Science ®Google Scholar
• Yuthavong Y , TarnchompooB, VilaivanTet al. Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target. PNAS109(42), 16823–16828 (2012).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . Safety, tolerability and chemoprotective activity of P218 in PfSPZ challenge model. https://clinicaltrials.gov/ct2/show/NCT03707041
   Google Scholar
• Le Bihan A , de KanterR, Angulo-BarturenIet al. Characterization of novel antimalarial compound ACT-451840: Preclinical assessment of activity and dose–efficacy modeling. PLoS Med.13(10), e1002138 (2016).
   PubMed Web of Science ®Google Scholar
• Idorsia Pharmaceuticals Ltd . Effect of ACT-451840 against early Plasmodium falciparum blood stage infection in healthy subjects. https://clinicaltrials.gov/ct2/show/NCT02223871
   Google Scholar
• Idorsia Pharmaceuticals Ltd . Safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT-451840 in healthy subjects (Part A). https://clinicaltrials.gov/ct2/show/NCT02186002
   Google Scholar
• Moore BR , LamanM, SalmanSet al. Naphthoquine: an emerging candidate for artemisinin combination therapy. Drugs76(7), 789–804 (2016).
   PubMed Web of Science ®Google Scholar
• Ifakara Health Institute . Safety, tolerability, pharmacokinetics and efficacy of ARCO. https://clinicaltrials.gov/ct2/show/NCT01930331
   Google Scholar
• Spillman NJ , KirkK. The malaria parasite cation ATPase PfATP4 and its role in the mechanism of action of a new arsenal of antimalarial drugs. Intl. J. Parasitol. Drugs Drug Res.5(3), 149–162 (2015).
   PubMed Web of Science ®Google Scholar
• St. Jude Children's Research Hospital . First-in-human study of an oral Plasmodium falciparum plasma membrane protein inhibitor. https://clinicaltrials.gov/ct2/show/NCT02661373
   Google Scholar
• White NJ , PukrittayakameeS, PhyoAPet al. Spiroindolone KAE609 for falciparum and vivax malaria. New Eng. J. Med.371(5), 403–410 (2014).
   PubMed Web of Science ®Google Scholar
• Phyo AP , SeidleinLv. Challenges to replace ACT as first-line drug. Malaria J.16, 296 (2017).
   PubMed Web of Science ®Google Scholar
• Upton LM , BrockPM, ChurcherTSet al. Lead clinical and preclinical antimalarial drugs can significantly reduce sporozoite transmission to vertebrate populations. Antimicrob. Agents Chemother.59(1), 490–497 (2015).
   PubMed Web of Science ®Google Scholar
• Diagana TT . Supporting malaria elimination with 21st century antimalarial agent drug discovery. Drug Disc. Today.20(10), 1265–1270 (2015).
   PubMed Web of Science ®Google Scholar
• White NJ , DuongTT, UthaisinCet al. Antimalarial activity of KAF156 in falciparum and vivax malaria. New Eng. J. Med.375(12), 115261160 (2016).
   PubMed Web of Science ®Google Scholar
• Kuhen KL , ChatterjeeAK, RottmannMet al. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrob. Agents Chemother.58(9), 5060–5067 (2014).
   PubMed Web of Science ®Google Scholar
• McNamara CW , LeeMC, LimCSet al. Targeting Plasmodium PI(4)K to eliminate malaria. Nature504(7479), 248–253 (2013).
   PubMed Web of Science ®Google Scholar
• Rottmann M , McNamaraC, YeungBKSet al. Spiroindolones, a potent compound class for the treatment of malaria. Science329(5996), 1175–1180 (2010).
   PubMed Web of Science ®Google Scholar
• Magistrado PA , CoreyVC, LukensAKet al. Plasmodium falciparum cyclic amine resistance locus (PfCARL), a resistance mechanism for two distinct compound classes. ACS Infect. Dis.2(11), 816–826 (2016).
   PubMed Web of Science ®Google Scholar
• Sanofi . To evaluate the efficacy of a single dose regimen of ferroquine and artefenomel in adults and children with uncomplicated Plasmodium falciparum Malaria (FALCI). In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT02Sanofi497612
   Google Scholar
• Phyo AP , JittamalaP, NostenFHet al. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label Phase 2 trial. Lancet Infect. Dis.16(1), 61–69 (2016).
   PubMed Web of Science ®Google Scholar
• Collins KA , WangCYT, AdamsMet al. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions. J. Clin. Invest.128(4), 1551–1562 (2018).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . MMV390048 and its antimalarial activity against Plasmodium falciparum in healthy adult subjects, part B. In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT02783833
   Google Scholar
• Medicines for Malaria Venture . MMV390048 against early Plasmodium falciparum blood stage infection in healthy participants. In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT02281344
   Google Scholar
• Vivas L , RattrayL, StewartLBet al. Antimalarial efficacy and drug interactions of the novel semi-synthetic endoperoxide artemisone in vitro and in vivo. J. Antimicrob. Chemother.59(4), 658–65 (2007).
   PubMed Web of Science ®Google Scholar
• Ramharter M , BurkhardtD, NemethJ, AdegnikaAA, KremsnerPG. In vitro activity of artemisone compared with artesunate against Plasmodium falciparum.Am. J. Trop. Med. Hyg.75(4), 637–9 (2006).
   PubMed Web of Science ®Google Scholar
• Coertzen D , ReaderJ, vander Watt Met al. Artemisone and artemiside are potent panreactive antimalarial agents that also synergize redox imbalance in Plasmodium falciparum transmissible gametocyte stages. Antimicrob. Agents Chemother.62(8), e02214–e02217 (2018).
   PubMed Web of Science ®Google Scholar
• University of Oxford . Artemisone for the treatment of uncomplicated falciparum malaria in western Cambodia (AMOS). In: ClinicalTrials.gov. Bethesda (MD). https://clinicaltrials.gov/ct2/show/NCT00936767
   Google Scholar
• Fernandes JF , LellB, AgnandjiSTet al. Fosmidomycin as an antimalarial drug: a meta-analysis of clinical trials. Future Microbiol.10(8), 1375–1390 (2015).
   PubMed Web of Science ®Google Scholar
• Lell B , RuangweerayutR, WiesnerJet al. Fosmidomycin, a novel chemotherapeutic agent for malaria. Antimicrob. Agents Chemother.47(2), 735–738 (2003).
   PubMed Web of Science ®Google Scholar
• Missinou MA , BorrmannS, SchindlerAet al. Fosmidomycin for malaria. Lancet360(9349), 1941–1942 (2002).
   PubMed Web of Science ®Google Scholar
• Borrmann S , AdegnikaAA, MoussavouFet al. Short-course regimens of artesunate fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria. Antimicrob. Agents Chemother.49(9), 3749–3754 (2005).
   PubMed Web of Science ®Google Scholar
• Albert Schweitzer Hospital . Efficacy of fosmidomycin-clindamycin for treating malaria in Gabonese children. In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT00214643
   Google Scholar
• Borrmann S , AdegnikaAA, MatsieguiPBet al. Fosmidomycin-clindamycin for Plasmodium falciparum infections in African children. J. Infect. Dis.189(5), 901–908 (2004).
   PubMed Web of Science ®Google Scholar
• Borrmann S , IssifouS, EsserGet al. Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria. J. Infect. Dis.190(9), 1534–1540 (2004).
   PubMed Web of Science ®Google Scholar
• Lanaspa M , MoraledaC, MachevoSet al. Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria. Antimicrob. Agents Chemother.56(6), 2923–2928 (2012).
   PubMed Web of Science ®Google Scholar
• Borrmann S , LundgrenI, OyakhiromeSet al. Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria. Antimicrob. Agents Chemother.50(8), 2713 (2006).
   PubMed Web of Science ®Google Scholar
• Puta C , ManyandoC. Enhanced gametocyte production in fansidar-treated Plasmodium falciparum malaria patients: implications for malaria transmission control programmes. Trop. Med. Intl. Health.2(3), 227–227 (1997).
   PubMed Web of Science ®Google Scholar
• Sanofi . Dose ranging study of ferroquine with artesunate in African adults and children with uncomplicated Plasmodium falciparum malaria (FARM). In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT00988507
   Google Scholar
• Mustfa K , LandauI, ChabaudAGet al. Effects of the antimalarial drugs ferroquine and artesunate on Plasmodium yoelii gametocytegenesis and vectorial transmission. Sante21(3), 133–142 (2011).
   PubMedGoogle Scholar
• McCarthy JS , RückleT, DjeriouEet al. A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study. Malaria J.15(1), 469 (2016).
   PubMedGoogle Scholar
• Held J , SupanC, SalazarCLet al. Ferroquine and artesunate in African adults and children with Plasmodium falciparum malaria: a Phase 2, multicentre, randomised, double-blind, dose-ranging, non-inferiority study. Lancet Infect. Dis.15(12), 1409–1419 (2015).
   PubMed Web of Science ®Google Scholar
• Krogstad D . Studies of a candidate aminoquinoline antimalarial (AQ-13). In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT01614964
   Google Scholar
• Boss C , AissaouiH, AmaralNet al. Discovery and characterization of ACT-451840: an antimalarial drug with a novel mechanism of action. Chem. Med. Chem.11(18), 1995–2014 (2016).
   Google Scholar
• Bruderer S , HurstN, de KanterRet al. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob. Agents Chemother.59(2), 935–942 (2015).
   PubMed Web of Science ®Google Scholar
• Batty KT , SalmanS, MooreBRet al. Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a pharmacokinetic study. Antimicrob. Agents Chemother.56(5), 2472–2784 (2012).
   PubMed Web of Science ®Google Scholar
• Laman M , MooreBR, BenjaminJMet al. Artemisinin-naphthoquine versus artemether-lumefantrine for uncomplicated malaria in Papua New Guinean children: an open-label randomized trial. PLoS Med.11(12), e1001773 (2014).
   PubMed Web of Science ®Google Scholar
• Karl S , LamanM, MooreBRet al. Gametocyte clearance kinetics determined by quantitative magnetic fractionation in Melanesian children with uncomplicated malaria treated with artemisinin combination therapy. Antimicrob. Agents Chemother.59(8), 4489 (2015).
   PubMed Web of Science ®Google Scholar
• Benjamin J , MooreB, LeeSTet al. Artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a tolerability, safety, and preliminary efficacy study. Antimicrob. Agents Chemother.56(5), 2465 (2012).
   PubMed Web of Science ®Google Scholar
• Tjitra E , HasugianAR, SiswantoroHet al. Efficacy and safety of artemisinin-naphthoquine versus dihydroartemisinin-piperaquine in adult patients with uncomplicated malaria: a multi-centre study in Indonesia. Malaria J.11, 153 (2012).
   PubMed Web of Science ®Google Scholar
• Jimenez-Diaz MB , EbertD, SalinasYet al. (+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium. PNAS111(50), E5455–E5462 (2014).
   PubMed Web of Science ®Google Scholar
• Medicines for Malaria Venture . SJ733 induced blood stage malaria challenge study (SJ733IBSMCS). In: ClinicalTrials.gov. Bethesda, MD. https://clinicaltrials.gov/ct2/show/NCT02867059
   Google Scholar