Effects of artemisinins on reticulocyte count and relationship to possible embryotoxicity in confirmed and unconfirmed malarial patients

Birth Defects Research Part A - Clinical and Molecular Teratology

Volumn 94, Issue 2, 2012, Pages 61-75

  Clark, Robert L ^a  

^a Artemis Pharmaceutical Research   (United States)

Author keywords

Antimalarial drug; Artemisinin; Artesunate; Embryotoxicity; Malaria; Unconfirmed malaria

Indexed keywords

ARTEMETHER; ARTEMISININ; ARTESUNATE; CHLORPROGUANIL; DAPSONE; DIHYDROARTEMISININ; FERROUS ION; FREE RADICAL; HEMOGLOBIN; MEFLOQUINE; PYRIMETHAMINE PLUS SULFADOXINE;

AREA UNDER THE CURVE; BONE MARROW; CLINICAL TRIAL; DRUG BIOAVAILABILITY; DRUG SENSITIVITY; EMBRYOTOXICITY; ERYTHROBLAST; ERYTHROCYTE; FIRST TRIMESTER PREGNANCY; HUMAN; MALARIA; MALARIA FALCIPARUM; NONHUMAN; PARASITE; PREGNANT WOMAN; PRIORITY JOURNAL; RETICULOCYTE COUNT; RETICULOCYTOPENIA; REVIEW; RISK ASSESSMENT; SINGLE DRUG DOSE; VOLUNTEER;

ADULT; ANIMALS; ANTIMALARIALS; ARTEMISININS; EMBRYO, MAMMALIAN; FEMALE; HUMANS; MALARIA, FALCIPARUM; PREGNANCY; PREGNANCY COMPLICATIONS, PARASITIC; RATS; RETICULOCYTE COUNT; RETICULOCYTES;

EID: 84856776529     PISSN: 15420752     EISSN: 15420760     Source Type: Journal    
DOI: 10.1002/bdra.22868     Document Type: Review

References (132)

1. Adam I, Elwasila E, Mohammed Ali DA, et al. 2004. Artemether in the treatment of falciparum malaria during pregnancy in eastern Sudan. Trans R Soc Trop Med Hyg 98: 509-513.
2. Adam I, Elhassan EM, Omer EM, et al. 2009. Safety of artemisinins during early pregnancy, assessed in 62 Sudanese women. Ann Trop Med Parasitol 103: 205-210.
3. Amexo M, Tolhurst R, Barnish G, Bates I. 2004. Malaria misdiagnosis: effects on the poor and vulnerable. Lancet 364: 1896-1898.
4. Anyasor GN, Ajayi EIO, Saliu JA, et al. 2009. Artesunate opens mitochondrial membrane permeability transition pore. Ann Trop Med Pub Health 2: 37-41.
5. Bialek R, Knobloch J. 1999. Parasitic diseases in pregnancy and congenital parasitosis. Part I: protozoan infections (Review, German). Zeitschrift fur Geburtshilfe und Neonatologie 203: 55-62.
6. Binh TQ, Ilett KF, Batty KT, et al. 2001. Oral bioavailability of dihydroartemisinin in Vietnamese volunteers and in patients with falciparum malaria. Br J Clin Pharmacol 51: 541-546.
7. Bounyasong S. 2001. Randomized trial of artesunate and mefloquine in comparison with quinine sulfate to treat P. falciparum malaria pregnant women. J Med Assoc Thai 84: 1289-1299.
8. Brabin B. 1997. Malaria in pregnancy: current issues. Afr Health 19: 19-20.
9. Brabin B, Piper C. 1997. Anaemia- and malaria-attributable low birthweight in two populations in Papua New Guinea. Ann Hum Biol 24: 547-555.
10. Briand V, Cottrell G, Massougbodji A, Cot M. 2007. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas. Malar J 6: 160.
11. Bunnag D, Viravan C, Looareesuwan S, et al. 1991. Clinical trial of artesunate and artemether on multidrug resistant falciparum malaria in Thailand. A preliminary report. Southeast Asian J Trop Med Public Health 22: 380-385.
12. Cai J, Yang J, Jones DP. 1998. Mitochondrial control of apoptosis: the role of cytochrome c. Biochim Biophys Acta 1366: 139-149.
13. Camacho LH, Gordeuk VR, Wilairatana P, et al. 1998. The course of anaemia after the treatment of acute, falciparum malaria. Ann Trop Med Parasitol 92: 525-537.
14. Cercamondi CI, Egli IM, Ahouandjinou E, et al. 2010. Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women. Am J Clin Nutr 92: 1385-1392.
15. Chance B, Sies H, Boveris A. 1979. Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527-605.
16. Clark RL. 2009. Embryotoxicity of the artemisinin antimalarials and potential consequences for use in women in the first trimester. Reprod Toxicol 28: 285-296.
17. Clark RL, Arima A, Makori N, et al. 2008a. Artesunate: developmental toxicity and toxicokinetics in monkeys. Birth Defects Res B Dev Reprod Toxicol 83: 418-434.
18. Clark RL, Gristwood WE, Lewsley R, et al. 2010. Localization of artesunate and its derivatives in the pregnant rat and fetus following oral administration and relationship to developmental toxicity. Birth Defects Res B Dev Reprod Toxicol 89: 364-365.
19. Clark RL, Lerman SA, Cox EM, et al. 2008b. Developmental toxicity of artesunate in the rat: comparison to other artemisinins, comparison of embryotoxicity and kinetics by oral and intravenous routes, and relationship to maternal reticulocyte count. Birth Defects Res B Dev Reprod Toxicol 83: 397-406.
20. Clark RL, Brannen KC, Sanders JE, Hoberman AM. 2011. Artesunate and artelinic acid: association of embryotoxicity, reticulocytopenia, and delayed stimulation of hematopoiesis in pregnant rats. Birth Defects Res B Dev Reprod Toxicol. 92: 52-68.
21. Crompton M. 1999. The mitochondrial permeability transition pore and its role in cell death. Biochem J 341(Pt 2): 233-249.
22. Coghi P, Basilico N, Taramelli D, Chan WC, Haynes RK, Monti D. 2009. Interaction of artemisinins with oxyhemoglobin Hb-FeII, Hb-FeII, carboxyHb-FeII, heme-FeII, and carboxyheme FeII: significance for mode of action and implications for therapy of cerebral malaria. Chem Med Chem. 4: 2045-53.
23. Cui L, Su XZ. 2009. Discovery, mechanisms of action and combination therapy of artemisinin. Expert Rev Anti Infect Ther. 7: 999-1013.
24. de Mast Q, Syafruddin D, Keijmel S, et al. 2010. Increased serum hepcidin and alterations in blood iron parameters associated with asymptomatic P. falciparum and P. vivax malaria. Haematologica 95: 1068-1074.
25. Deen JL, von Seidlein L. 2002. Antimalarial use during pregnancy and its effect on birthweight. Trans R Soc Trop Med Hyg 96: 573-574.
26. Deen JL, von Seidlein L, Pinder M, et al. 2001. The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg 95: 424-428.
27. Desowitz RS, Shida KK, Pang L, Buchbinder G. 1989. Characterization of a model of malaria in the pregnant host: Plasmodium berghei in the white rat. Am J Trop Med Hyg. 41: 630-634.
28. Dellicour S, Hall S, Chandramohan D, Greenwood B. 2007. The safety of artemisinins during pregnancy: a pressing question. Malar J 6: 15.
29. Dommergues M, Aubény E, Dumez Y, et al. 1992. Hematopoiesis in the human yolk sac: quantitation of erythroid and granulopoietic progenitors between 3.5 and 8 weeks of development. Bone Marrow Transplant 9 Suppl 1: 23-27.
30. Dondorp A, Nosten F, Stepniewska K, et al. 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717-725.
31. Granja AC, Machungo F, Gomes A, et al. 1998. Malaria-related maternal mortality in urban Mozambique. Ann Trop Med Parasitol 92: 257-263.
32. Green DR, Reed JC. 1998. Mitochondria and apoptosis. Science 281: 1309-1312.
33. Gronowicz G, Swift H, Steck TL. 1984. Maturation of the reticulocyte in vitro. J Cell Sci 71: 177-197.
34. Gu HM, Warhurst DC, Peters W. 1984. Uptake of [3H] dihydroartemisinine by erythrocytes infected with Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 78: 265-270.
35. Guerin PJ, Olliaro P, Nosten F, et al. 2002. Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development. Lancet Infect Dis 2: 564-573.
36. Guo X-B, Fu L-C, Yu C-G, et al. 1990. A study on tolerance and toxic side-effects of artesunate intravenous injection on healthy volunteers/clinical trials phase I. Clinical trials on Qinghaosu and its derivatives. In: Li G-Q, Guo XB, Fu Y, editors. Guangzhou College of Traditional Chinese Medicine, Sanya Tropical Medical Institute, Guangzhou. pp 39-43.
37. Haldar K, Mohandas N. 2009. Malaria, erythrocytic infection, and anemia. Hematology Am Soc Hematol Educ Program 87-93.
38. Halliwell B. 2000. The antioxidant paradox. Lancet 355: 1179-1180.
39. Halliwell B, Gutteridge J. 2007. Free Radicals in Biology and Medicine. Oxford: Oxford University Press. pp 111, 189, 199, 206.
40. Haynes RK, Chan WC, Lung CM, Uhlemann AC, Eckstein U, Taramelli D, Parapini S, Monti D, Krishna S. 2007. The Fe2+-mediated decomposition, PfATP6 binding, and antimalarial activities of artemisone and other artemisinins: the unlikelihood of C-centered radicals as bioactive intermediates. ChemMedChem. 2: 1480-1497.
41. He L, LeMasters JJ. 2002. Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? FEBS Lett 512: 1-7.
42. Hollenberg MD, Kaback MM, Kazazian HH Jr. 1971. Adult hemoglobin synthesis by reticulocytes from the human fetus at midtrimester. Science 174: 698-702.
43. Ilett KF, Batty KT. 2005. Artemisinin and its derivatives. Antimicrobial therapy and vaccines - volume II: antimicrobial agents; 2nd edition. In: Yu VL, Edwards G, McKinnon PS, Peloquin C, Morse GD, editors. Pittsburgh: ESun Technologies. pp. 981-1002 (ISBN: 0-9744641-1-2).
44. Jiang JB, Jacobs G, Liang DS, Aikawa M. 1985. Qinghaosu-induced changes in the morphology of Plasmodium inui. Am J Trop Med Hyg 34: 424-428.
45. Kalilani L, Mofolo I, Chaponda M, et al. 2007. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women. PLoS One 2: e1166.
46. Kawamura S, Yoshioka T, Kato T, et al. 1996. Histological changes in rat embryonic blood cells as a possible mechanism for ventricular septal defects produced by an N-phenylimide herbicide. Teratology 54: 237-244.
47. Kelemen E, Calvo W, Fliedner T. 1979. Atlas of Human Hemopoietic Development. Springer-Verlag, Berlin. p. 21.
48. Kietzmann T, Fandrey J, Acker H. 2000. Oxygen radicals as messengers in oxygen-dependent gene expression. News Physiol Sci 15: 202-208.
49. Knights P. 2002a. Artesunate: 14 day preliminary oral (gavage administration) toxicity study in the rat. Covance Report Number 1552/051-D6154.
50. Knights P. 2002b. Artesunate: 4 week oral (gavage administration) toxicity study in the rat. Covance Report Number 1552/059-D6154.
51. Kongpatanakul S, Chatsiricharoenkul S, Khuhapinant A, et al. 2009. Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers. Int J Clin Pharmacol Ther 47: 579-586.
52. Koury MJ, Koury ST, Kopsombut P, Bondurant MC. 2005. In vitro maturation of nascent reticulocytes to erythrocytes. Blood 105: 2168-2174.
53. Kroemer G, Dallaporta B, Resche-Rigon M. 1998. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60: 619-642.
54. Kumar V, Hagler H. 1999. Interactive case study companion to Robbins pathologic basis of disease, sixth edition. Normal reference range table. New York: WB Saunders.
55. Laffan SB, James AC, Maleef BE, et al. 2006. Mitochondrial involvement of artesunate toxicity in rat embryonic erythroblasts. Birth Defects Res A Clin Mol Teratol 76: 329.
56. Lahary A, Labadie G, Duval C, et al. 1995. Normal reticulocyte count and subtype HFR in antenatal blood. Am J Hematol 48: 69-70.
57. Lefèvre G, Looareesuwan S, Treeprasertsuk S, et al. 2001. 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: 247-256.
58. Li GQ, Guo XB, Fu LC, et al. 1994. Clinical trials of artemisinin and its derivatives in the treatment of malaria in China. Trans R Soc Trop Med Hyg 88 Suppl 1: S5-6.
59. Li Q, Cantilena LR, Leary KJ, et al. 2009. Pharmacokinetic profiles of artesunate after single intravenous doses at 0.5, 1, 2, 4, and 8 mg/kg in healthy volunteers: a phase I study. Am J Trop Med Hyg 81: 615-621.
60. Li Q, Xie LH, Johnson TO, et al. 2007. Toxicity evaluation of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats. Trans R Soc Trop Med Hyg 101: 104-112.
61. Li Q, Xie LH, Si Y, et al. 2005. Toxicokinetics and hydrolysis of artelinate and artesunate in malaria-infected rats. Int J Toxicol 24: 241-250.
62. Li QC, Peggins J, Fleckenstein L, et al. 1998. The pharmacokinetics and bioavailability of dihydroartemisinin, arteether, artemether, artesunic acid and artelinic acid in rats. J Pharm Pharmacol 50: 173-182.
63. Longo M, Zanoncelli S, Della Torre P, et al. 2008. Investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Reprod Toxicol 25: 433-441.
64. Longo M, Zanoncelli S, Torre PD, et al. 2006. In vivo and in vitro investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos. Reprod Toxicol 22: 797-810.
65. Maeno Y, Toyoshima T, Fujioka H, et al. 1993. Morphologic effects of artemisinin in Plasmodium falciparum. Am J Trop Med Hyg 49: 485-491.
66. Maleeff BE, James AC, Laffan SB, et al. 2007. In vitro effects of artesunate on rat embryonic and fetal blood cells. Microsc Microanal 13( Suppl 2): 1698-1699.
67. Manyando C, Mkandawire R, Puma L, et al. 2010. Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia. Malar J 9: 249.
68. McGready R, Brockman A, Cho T, et al. 2000a. Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 94: 689-693.
69. McGready R, Cho T, Cho JJ, et al. 1998. Artemisinin derivatives in the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 92: 430-433.
70. McGready R, Cho T, Keo NK, et al. 2001. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 33: 2009-2016.
71. McGready R, Cho T, Samuel V, et al. 2000b. Randomised comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 95: 651-656.
72. McGready R, Nosten F. 1999. The Thai-Burmese border: drug studies of Plasmodium falciparum in pregnancy. Ann Trop Med Parasitol 93 Suppl 1: S19-S23.
73. McGready R, Stepniewska K, Lindegardh N, et al. 2006. The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria. Eur J Clin Pharmacol 62: 1021-1031.
74. McGready R, Tan SO, Ashley EA, et al. 2008. A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated plasmodium falciparum treatment in pregnancy. PLoS Med 5: e253.
75. McIntosh HM, Jones KL. 2005. Chloroquine or amodiaquine combined with sulfadoxine-pyrimethamine for treating uncomplicated malaria. Cochrane Database Syst Rev 4: CD000386.
76. Menendez C. 2006. Malaria during pregnancy. Curr Mol Med 6: 269-273.
77. Mercer AE, Maggs JL, Sun XM, et al. 2007. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J Biol Chem 282: 9372-9382.
78. Mercer AE. 2009. The role of bioactivation in the pharmacology and toxicology of the artemisinin-based antimalarials. Curr Opin Drug Discov Devel. 12: 125-132.
79. Meshnick SR. 2002. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol 32: 1655-1660.
80. Meshnick SR, Taylor TE, Kamchonwongpaisan S. 1996. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev 60: 301-315.
81. Miller RS. 2010. Important clinical trials for licensure of intravenous artesunate in the U.S. Presented at the Annual Meeting of the American Society of Tropical Medicine and Hygiene, 5 Nov 2010.
82. Miyoshi N, Oubrahim H, Chock PB, Stadtman ER. 2006. Age-dependent cell death and the role of ATP in hydrogen peroxide-induced apoptosis and necrosis. Proc Natl Acad Sci U S A 103: 1727-1731.
83. Mutabingwa TK, Muze K, Ord R, et al. 2009. Randomized trial of artesunate+amodiaquine, sulfadoxine-pyrimethamine+amodiaquine, chlorproguanal-dapsone and SP for malaria in pregnancy in Tanzania. PLoS One 4: e5138.
84. Nakata S, Matsumura I, Tanaka H, et al. 2004. NF-kappaB family proteins participate in multiple steps of hematopoiesis through elimination of reactive oxygen species. J Biol Chem 279: 55578-55586.
85. Nosten F, McGready R, d'Alessandro U, et al. 2006. Antimalarial drugs in pregnancy: a review. Curr Drug Saf 1: 1-15.
86. Olliaro PL, Haynes RK, Meunier B, Yuthavong Y. 2001. Possible modes of action of the artemisinin-type compounds. Trends Parasitol 17: 122-126.
87. Onyamboko MA, Meshnick SR, Fleckenstein L, et al. 2011. Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC. Malar J 10: 49.
88. Orten JM, Smith AH. 1934. The proportion of reticulocytes in the blood of albino rats. Am J Physiol 108: 66-73.
89. Palis J, Yoder MC. 2001. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol 29: 927-936.
90. Parapini S, Basilico N, Mondani M, Olliaro P, Taramelli D, Monti D. 2004. Evidence that haem iron in the malaria parasite is not needed for the antimalarial effects of artemisinin. FEBS Lett. 575: 91-94.
91. Piola P, Nabasumba C, Turyakira E, et al. 2010. Efficacy and safety of artemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial. Lancet Infect Dis 10: 762-769.
92. Posobiec LM, Bushdid PB, Laffan SB, et al. 2007. Dihydroartemisinin (DHA) treatment causes decreased proliferation and apoptosis in rat embryonic erythroblasts in whole embryo culture. Birth Defects Res A Clin Mol Teratol 79: 361.
93. Prentice AM, Cox SE, Nweneka CV. 2010. Asymptomatic malaria in the etiology of iron deficiency anemia: a nutritionist's viewpoint. Am J Clin Nutr 92: 1283-1284.
94. Price R, van Vugt M, Phaipun L, Luxemburger C, Simpson J, McGready R, ter Kuile F, Kham A, Chongsuphajaisiddhi T, White NJ, Nosten F. 1999. Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives. Am J Trop Med Hyg. 60: 547-555.
95. Ribeiro I, Olliaro P. 1998. Safety of artemisinin and its derivatives. A review of published and unpublished clinical trials. Med Trop 58: 50-53.
96. Ricci JE, Muñoz-Pinedo C, Fitzgerald P, et al. 2004. Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell 117: 773-786.
97. Sachs J, Malaney P. 2002. The economic and social burden of malaria. Nature 415: 680-685.
98. Sauer H, Wartenberg M, Hescheler J. 2001. Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell Physiol Biochem 11: 173-186.
99. Segel G, Palis J. 2001. Hematology of the Newborn. Williams Hematology. In: Beutler E, Lichtman M, Coller B, Kipps T, Seligsohn U, editors. New York: McGraw-Hill. p. 77.
100. Si Y, Zeng Q, Zhang J, et al. 2004. Evaluation of the embryonic toxicity of artesunate in rats. Am J Trop Med 71: 260.
101. Snow RW, Guerra CA, Noor AM, et al. 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434: 214-217.
102. Steketee RW, Nahlen BL, Parise ME, Menendez C. 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 64: 28-35.
103. Suh KN, Keystone JS. 1996. Malaria prophylaxis in pregnancy and children. Infect Dis Clin Pract 5: 541-546.
104. Tan S, Sagara Y, Liu Y, et al. 1998. The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 141: 1423-1432.
105. Tavassoli M. 1991. Embryonic and fetal hemopoiesis: an overview. Blood Cells 17: 269-281.
106. Tavian M, Hallais MF, Péault B. 1999. Emergence of intraembryonic hematopoietic precursors in the pre-liver human embryo. Development 126: 793-803.
107. Taylor WR, White NJ. 2004. Antimalarial drug toxicity: a review. Drug Saf 27: 25-61.
108. Tegoshi T, Desowitz RS, Pirl KG, Maeno Y, Aikawa M. 1992. Placental pathology in Plasmodium berghei-infected rats. Am J Trop Med Hyg. 47: 643-651.
109. Teja-Isavadharm P, Watt G, Eamsila C, et al. 2001. Comparative pharmacokinetics and effect kinetics of orally administered artesunate in healthy volunteers and patients with uncomplicated falciparum malaria. Am J Trop Med Hyg 65: 717-721.
110. Teramoto S, Tomita T, Matsui H, et al. 1999. Hydrogen peroxide-induced apoptosis and necrosis in human lung fibroblasts: protective roles of glutathione. Jpn J Pharmacol 79: 33-40.
111. ter Kuile FO, van Eijk AM, Filler SJ. 2007. Effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy: a systematic review. JAMA 297: 2603-2616.
112. Tran TH, Day NP, Nguyen HP, et al. 1996. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 335: 76-83.
113. Troyano A, Sancho P, Fernández C, et al. 2003. The selection between apoptosis and necrosis is differentially regulated in hydrogen peroxide-treated and glutathione-depleted human promonocytic cells. Cell Death Differ 10: 889-898.
114. Uppsala University Hospital. 2008. Artnr 40284 Sj74a. Reference range list ("Laborationslista"). Issued on April 22, 2008.
115. Vallely A, Vallely L, Changalucha J, et al. 2007. Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed? Malar J 6: 16.
116. Verhoef H. 2010. Asymptomatic malaria in the etiology of iron deficiency anemia: a malariologist's viewpoint. Am J Clin Nutr 92: 1285-1286.
117. Wang J, Huang L, Long Y, et al. 2009. Effect of mitochondrial permeability transition pore in antimalarial action of artemisinin. Xiandai Shengwuyixue Jinzhan 9: 4006-4009.
118. Ward S, Sevene E, Hastings I, et al. 2007. Antimalarial drugs and pregnancy: safety, pharmacokinetics, and pharmacoviligance. Lancet Infect Dis 7: 136-144.
119. Weina PJ, Haeberle AS, Milhous WK. 2006. Intravenous Artesunate: The New Generation of Lifesaving Treatment for Severe Malaria in the Warfighter. Walter Reed Army Inst of Research, Silver Spring, Maryland.
120. White NJ. 2005. Intermittent presumptive treatment for malaria. PLoS Med 2: e3.
121. White TE, Bushdid PB, Ritter S, et al. 2006. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo. Birth Defects Res B Dev Reprod Toxicol 77: 413-429.
122. White TE, Clark RL. 2008. Sensitive periods for developmental toxicity of orally administered artesunate in the rat. Birth Defects Res B Dev Reprod Toxicol 83: 407-417.
123. White TE, Lordi AW, Bushdid PB, et al. 2007. Autoradiography reveals specific targeting of embryonic and fetal blood cells by the anti-malarial, artesunate. Birth Defects Res A Clin Mol Teratol 79: 362.
124. Wootton DG, Opara H, Biagini GA, et al. 2008. Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap) alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria. PLoS One 3: e1779.
125. World Health Organization. 2006. The role of laboratory diagnosis to support malaria disease management. At WHO website p. 1.
126. World Health Organization. 2007. Assessment of the safety of artemisinins in pregnancy 2007. At WHO website.
127. World Health Organization. 2008. Worldwide prevalence of anaemia 1993-2005. Geneva: World Health Organization. ISBN 9789241596657. .
128. World Health Organization. 2010. Guidelines for the treatment of malaria. At WHO website pp. 9, 13.
129. Wu WM, Wu Y, Wu YL, et al. 1998. Unified mechanistic framework for the Fe(II)-induced cleavage of qinghaosu and derivatives/analogues: The first spin-trapping evidence for the previously postulated secondary C-4 radical. J Am Chem Soc 120: 3316-3325.
130. Zhang H, Wu Y, Wang L, et al. 2009. Study on mitochondria pathway of apoptosis induced by artesunate and thermotherapy in A549 cell line. Zhongguo Gonggong Weisheng 25: 699-701.
131. Zhao YH, Wang JY. 2003. Effect of mitochondrial membrane potential in the neurotoxicity of artemether. Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi 21: 326-329.
132. Zucker RM, Elstein KH, Shuey DL, et al. 1995. Flow cytometric detection of abnormal fetal erythropoiesis: application to 5-fluorouracil-induced anemia. Teratology 51: 37-44.