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The Pathogenesis of Severe Malaria

Research Project

Project/Area Number 08044323
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field 寄生虫学(含医用動物学)
Research InstitutionTokai University

Principal Investigator

AIKAWA Masamichi  Tokai Uni., Inst.of Medical Science, Professor, 総合医学研究所, 教授 (90271593)

Co-Investigator(Kenkyū-buntansha) LOOARESSUWAN ソンチャイ  マヒドール大学, 熱帯医学部, 教授
NUSSENZWEIK Ruth  New York State Univ., Tropical Med., Professor, 医学部, 教授
MATSUMOTO Yoshitsugu  Uni.of Tokyo, Agri., Assoc.Professor, 農学部, 助教授 (00173922)
NAGATAKE Tsuyoshi  Nagasaki Uni., Inst.of Trop.Med., Professor, 熱帯医学研究所, 教授 (30164445)
SUZUKI Mamoru  Gunnma Uni., Med.School, Professor, 医学部, 教授 (60056033)
LOOAREESUWAN Sorchai  Mahidol Univ., Tropical Med., Professor
LOOAREESUWAN ソンチャイ  Mahidol University, Tropical Medicine, Professor
PONGPONRATN イー  マヒドン大学, 医学部・病理, 教授
LOOARESUWAN エス  マヒドン大学, 医学部・熱帯医学, 教授
CHEONGSUPHA ティー  マヒドル大学, 医学部・熱帯医学, 教授
NUSSENZWEIG アール  ニューヨーク大学, 医・分子寄生虫, 教授
翠川 裕  鈴鹿医療科学技術大学, 助教授 (10209819)
堤 寛  東海大学, 医・病理, 助教授 (80138643)
本庄 祐  京都大学, 医・医化学, 教授 (80090504)
金田 良雅  東海大学, 医・寄生虫, 教授 (60051471)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1997: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1996: ¥6,600,000 (Direct Cost: ¥6,600,000)
Keywordscerebral malaria / sequestration / subcutaneous tissues / intra mucosa gastric pH / qinghaosue / deferoxamine / artesnate / Deferoxamine Antagonism / Cerebral malaria / Deferoxamine / Antagonism / 胃粘膜 / 毛細血管
Research Abstract

1. We examined 95 cerebral malaria patients in the ICU of Bangkok Hospital for Tropical Diseases.
(1) Sequestration of blood capillary with P.falciparum-infected red blood cells in the brain is a characteristic future of cerebral malaria. We found similar capillary sequestration in subcutaneous tissues in severe malaria patients. In a rhesus monkey model of cerebral malaria, cor relation between sequestration rates in the brain and subcutaneous tissues was observed.
(2) According to a gastric intramucosal pH value, patients were divided into two groups (normal or low). The mortality rate was greater in low (less than 7.3) group. All patients with persistently low gastric intramucosal pH died.
2. We organized an international meeting, "MALARIA WORKSHOP" on June 15,16,1997 at kasumigaseki in Tokyo, Japan. About 50 malaria specialists participated to the meeting and discussed the latest results and information on malaria studies. Understanding of today's crisis of malaria recrudescence, the … More participants convinced the necesity of international cooperative trials in malaria endemic regions.
3. While qinghaosue is a specific anti-cerebral malarial, recrudence sometimes occurs during the treatment with this drug. Then, we tried to enhance the usage of qinghaosue in cerebral malaria treatment with this drug. Then, we tried to enhance the usage of qinghaosue in cerebral malaria treatments by a combination of artesnate (qinghaosue derivative) and other anti-malarial (deferoxamine). Since deferoxamine is an iron chelator and qinghaosue's activity depends on iron, antagonism between the two drugs must be examined at first. Therfore, we (Japan, Tailand, and USA cooperative team) conducted a preliminary trial to detect any antagonism between the two drugs in the Bangkok Hospital for Tropical Diseases. We obsrved 101 adults with severe P.falciparum Malaria admitted with artesnate and placebo or the combination of artesnate and deferoxamine, and conducted randomized, double-blind, prospective study. Statisical analysis showed no evidence for antagonism between the two anti-malarials. We conclude that the combination of artesnate and deferoxamine is safe and effective for treatment of severe malaria and may hasten recovery from hepatocellular dysfunction. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report

Research Products

(47 results)

All Other

All Publications (47 results)

  • [Publications] Aikawa,M. et al.: "A mouse model for cerebral babesiosis." Parasitol.Today.12. 203-205 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "Multi-organ erythrocyte sequestration and ligand expression-blocking vaccine candidate." Am.J,Trop.Med.Hyg.,. 55. 379-383 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "Cross-reactive epitope among proteins in Plasmodivm falciparum Mauer's cleft and primate leucocytes and plates." Am.J.Trop.Med.Hyg.,. 55. 655-659 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "A developmental defec t in Plasmodium falciparum male gametogenesis." J.Cell Biol.,. 135. 269-278 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "A novel Plasmodium falciparum sporozaite and liver stage antigen(SALSA)defines major B,Thelper and CTL epitopes" J.Immunol.,. 156. 2874-2884

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "Membrane knobs of unfixed Plasmodium falciparum-infected erythrocytes:new findings as revealed by atomic force microscopy and surface potential sectroscopy." Exptl.Parasitol.,. 84. 339-343 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakano,Y. et al.: "A correlation of the sequestration rate of Plasmodium coatney-infected erythrocytes in cerebral and subcutaneous tissues of rhesus monkey." Am.J.Med.Hyg.55. 311-314 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M. et al.: "Molecular basis of pathogenesis of cerebral malaria." Microbial Pathogenesis,. 20. 63-72 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Looareesuwan,S. et al.: "Ranndamized double-blind prospective study of Deferoxamine and artesnate in the treatment of severe malaria." NIH/ICDR Report.(1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M.: "Studies of falciparum malaria with atomic force and surface potential microscopes." Anals of Tropical Medicine and Parasitology.91(6). 689-692 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nagakura,K.et al.: "Severe Malaria from a new beach resort." Kansen-shou Gakaishi. 72(2). 63-68 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M.et al.: "The pivotal role of carbonic anhydrase in malaria infection." Medical Hyposesis. 50(1). 19-23 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 相川 正道,永倉 貢一: "「現代の感染症」" 岩波書店, 222 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M.et al.: "“Parasitology of Infectious Diseases"(Vol.11)." Appleton & Lange., 1849 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M.et al.: "Topley and Wilson's Microbiology (Vol.5)." Arnold., 701 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa,M.et al.: "“Malaria:Parasite Biology,Pathogenesis,Protection".ed.by Irwin&Sharman." American Society of Microbiology Press (in Press).,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa M.et al.: "A mouse model for cerebral babesia." Parasitol.Today. 12. 203-205 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa M.et al.: "Multi-organ erythrocyte sequestration and ligand expression-blocking vaccine candidate." Am.J.Med.Hyg.55. 379-383 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa M.et al.: "Cross-reactive epitope among proteins in Plasmodium falciparum Mauer's cleft and primate Leucocytes and plates." Am.J.Med.Hyg.55. 655-659 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "A development defect in Plasmodium falciparum male gametogenesis." J.Cell Biol.135. 269-278 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa M.et al.: "A novel Plasmodium falciparum sporozaite and liver stage antigen (SALSA) defines major B,T helper and CTL epitopes." J.Immunol.156. 2874-2884 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "Membrane knobs of unifixed Plasmodium falciparum-infected erythrocytes : New findings as revealed by atomic force microscopy and surface potential spectroscopy." Exptl.Parasitol.84. 339-343 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakano, Y.et al.: "A correlation of the sequestration rate of Plasmodium coatney-infected erythrocytes in cerebral and subcutaneous tissues of a rhesus monkey." Am.J.Med.Hyg.55. 311-314 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "Molecular basis of pathogenesis of cerebral malaria." Microbial pathogenesis. 20. 63-72 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Looaressuwan, S.et al.: "Randamized double-blind prospective study of deferoxamine and artesnate in the treatment of severe malaria." NIH/ICDR Report. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.: "Studies of falciparum malaria with atomic-force and surface-potential microscopes." Annal.Trop.Med.Parasitol.91 (6). 689-692 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nagakura, K.et al.: "Severe Malaria from a new beach resort." Kansen-shou Gakaishi. 72 (2). 63-68 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "The Pivotal role of carbonic anhydrase in malaria infection." Medical Hyposesis. 50 (1). 19-23 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.and Nagakura, K.: "Genndai no Kansensho". Iwanami-shoten, 222 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et.al.: "Parasitology of Infectious Diseases" (Vol.II). ed.by D.H.Connor, F.W.Chandler, D.A.Schwartz, H.J.Manz and E.E.Lack, Appleton & Lange, 1849 (1205-1221)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "Topley and Wilson's Microbiology and MicrobiologicalmInfections" (Vol.5). Ed.by F.E.G.Cox J.O.Kreier and D.Wakelin, Arnold, 701 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "Malaria : Parasite Biology, Pathogenesis, Protection". (in press), American Society of Microbiology Press.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Aikawa, M.et al.: "Ranndamized double-blind prospective study of Deferoxamine and artesnate in the treatment of severe malaria." NIH/ICDR Report. (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa, M.et al.: "Studies of falciparum malaria with atomic force and surface potential microscopes." Anals of Tropical Medicine and Parasitology. 91.6. 692-689 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa, M.et al.: "Membrane knobs of unfixed Babesia bovis-infected erythrocytes." Prasitology International. 46.4. 241-246 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagakura, K.et al.: "Severe Malaria from a new beach resort." Kansen-shou Gakaishi. 72.2. 63-68 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 相川 正道: "現在のマラリア研究の動向" 今月の治療. 97.7. 85-90 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa, M.et al.: "The pivotal role of carbonic anhydrase in malaria infection." Medical Hyposesis. 50. 19-23 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa, M.et al.: "Parasitology of Infectious Diseases Vol.II" Appleton & Lange, 1205-1221 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa, M.et al.: "Topley and Wilson's Microbiology(Vol.5)" Arnold, 431-444 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 相川 正道, 永倉 貢一: "現代の感染症" 岩波書店, 222 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Aikawa,M.et al.: "Membrane knobs of unfixed P.falciparum-infected erythrocytes : new findings as revealed by atomic force microscopy and surface potential spectroscopy" Exptl. Parasitol.42. 626-636 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Aikawa,M.et al.: "Seroprevelance and specificity of human responses to P.falciparum 110 kDa rhoptry proteins using a C-terminal recombinant protein" Infection and Immunity. (in press). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Aikawa,M.et al.: "The molecular basis of pathogenesis of cerebral malaria" Microbial Pathogenesis. 20. 63-72 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Aikawa,M.et al.: "A novel P.falciparum sporozoite and liver stage antigens" J.Immunol. 156. 2874-84 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 相川正道: "マラリア" 臨床医. 22. 33-35 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 相川正道: "マラリア" 化学療法の領域. 12. 4-7 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-03-31   Modified: 2018-02-02  

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