1921
Volume 76, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

16α-Bromoepiandrosterone (HE2000) is a synthetic androstane steroid that has immune effects in pre-clinical models of malaria, tuberculosis, and infection with human immunodeficiency virus. In pilot studies, 42 patients with confirmed uncomplicated malaria were treated with a seven-day course of HE2000 by either buccal administration or intramuscular injection. Of the 42 patients, 41 showed a 50% reduction in blood levels of parasites, the primary endpoint of the study. Of these, 32 (76%) cleared malaria parasites below detectable levels. All febrile patients became afebrile by the end of treatment. There was no reduction in gametocyte forms. Adverse events were transient and mild to moderate in intensity. The anti-malarial response was generally similar with either the intramuscular or buccal routes of administration. HE2000 shows a safety profile and pharmacologic activity worthy of further investigation to understand its role in the treatment of malaria, perhaps in combination with anti-malarial agents.

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2007-02-01
2017-09-22
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References

  1. Milhous WK, Kyle DE, 1998. Introduction to the modes of action of and mechanisms of resistance to antimalarials. Sherman IW, ed. Malaria: Parasite Biology, Pathogenesis, and Protection. Washington, DC: American Society for Microbiology Press, 303–316.
  2. Peters W, 1987. Chemotherapy and Drug Resistance in Malaria. New York: Academic Press, 145–273.
  3. Danis M, Bricaire F, 2003. The new drug combinations: their place in the treatment of uncomplicated Plasmodium falciparum malaria. Fundam Clin Pharmacol 17 : 155–160.
  4. Loria RM, Padgett DA, 1992. Androstenediol regulates systemic resistance against lethal infections in mice. Arch Virol 127 : 103–115.
  5. Loria RM, Inge TH, Cook SS, Szakal AK, Regelson W, 1988. Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA). J Med Virol 26 : 301–314.
  6. Padgett DA, Loria RM, Sheridan JF, 1997. Endocrine regulation of the immune response to influenza virus infection with a metabolite of DHEA-androstenediol. J Neuroimmunol 78 : 203–211.
  7. Daigle J, Carr DJ, 1998. Androstenediol antagonizes herpes simplex virus type 1-induced encephalitis through the augmentation of type I IFN production. J Immunol 160 : 3060–3066.
  8. Pedersen NC, North TW, Rigg R, Reading C, Higgins J, Leutenegger C, Henderson GL, 2003. 16alpha-bromoepiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: initial enhancement leading to long-term suppression. Vet Immunol Immunopathol 94 : 133–148.
  9. Hernandez Pando R, Aguilar Leon D, Orozco H, Serrano A, Ahlem C, Trauger R, Schramm B, Reading C, Frincke J, Rook GAW, 2005. 16α-bromoepiandrosterone restores T helper cell Type 1 activity and accelerates chemotherapy-induced bacterial clearance in model of progressive pulmonary tuberculosis. J Infect Dis 191 : 299–306.
  10. Ben-Nathan D, Padgett DA, Loria RM, 1999. Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity. J Med Microbiol 48 : 425–431.
  11. Whitnall MH, Elliott TB, Harding RA, Inal CE, Landauer MR, Wilhelmsen CL, McKinney L, Miner VL, Jackson WE, Loria RM, Ledney GD, Seed TM, 2000. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int J Immunopharmacol 22 : 1–14.
  12. Freilich D, Ferris S, Wallace M, Leach L, Kallen A, Frincke J, Ahlem C, Hacker M, Nelson D, Hebert J, 2000. 16alpha-bromoepiandrosterone, a dehydroepiandrosterone (DHEA) analogue, inhibits Plasmodium falciparum and Plasmodium berghei growth. Am J Trop Med Hyg 63 : 280–283.
  13. Rasmussen KR, Healey MC, 1992. Dehydroepiandrosterone-induced reduction of Cryptosporidium parvum infections in aged Syrian golden hamsters. J Parasitol 78 : 554–557.
  14. Wongsrichanalai C, Sirichaisinthop J, Karwacki JJ, Congpuong K, Miller RS, Pang L, Thimasarn K, 2001. Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders. Southeast Asian J Trop Med Public Health 32 : 41–49.
  15. World Health Organization, 2003. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization.
  16. Agresti A, 2002. Statistical Inference for Binomial Parameters. Categorical Data Analysis. New York: Wiley-Interscience, 14–21.
  17. Reading C, Dowding C, Schramm B, Garsd A, Onizuka-Handa N, Stickney D, Frincke J, 2006. Improvement in immune parameters and HIV-1 viral response in individuals treated wtih 16alpha-bromoepiandrosterone (HE2000). Clin Microbiol Infect 12 : 1082–1088.
  18. Spellberg B, Edwards JE Jr, 2001. Type 1/type 2 immunity in infectious diseases. Clin Infect Dis 32 : 76–102.
  19. Taylor-Robinson AW, 1998. Immunoregulation of malarial infection: balancing the vices and virtues. Int J Parasitol 28 : 135–148.
  20. Malaguarnera L, Imbesi RM, Pignatelli S, Simpore J, Malaguarnera M, Musumeci S, 2002. Increased levels of interleukin-12 in Plasmodium falciparum malaria: correlation with the severity of disease. Parasite Immunol 24 : 387–389.
  21. Torre D, Speranza F, Giola M, Matteelli A, Tambini R, Biondi G, 2002. Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria. Clin Diagn Lab Immunol 9 : 348–351.
  22. Musumeci M, Malaguarnera L, Simpore J, Messina A, Musumeci S, 2003. Modulation of immune response in Plasmodium falciparum malaria: role of IL-12, IL-18 and TGF-beta. Cytokine 21 : 172–178.
  23. Serghides L, Kain KC, 2001. Peroxisome proliferator-activated receptor gamma-retinoid X receptor agonists increase CD36-dependent phagocytosis of Plasmodium falciparum-parasitized erythrocytes and decrease malaria-induced TNF-alpha secretion by monocytes/macrophages. J Immunol 166 : 6742–6748.
  24. White NJ, 2002. The assessment of antimalarial drug efficacy. Trends Parasitol 18 : 458–464.
  25. Djimde AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 : 558–563.
  26. Cravo P, Culleton R, Hunt P, Walliker D, Mackinnon MJ, 2001. Antimalarial drugs clear resistant parasites from partially immune hosts. Antimicrob Agents Chemother 45 : 2897–2901.
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  • Received : 13 Dec 2005
  • Accepted : 20 Oct 2006

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