マラウイ国における熱帯熱マラリア感染に対する抗マラリア薬剤効果 : chloroquineよりsulfadoxine/pyrimethamineへの変更7年後の経過 Antimalarial Drug Efficacy in Plasmodium falciparum Infections in Malawi, Seven Years After Switching From Chloroquine to Sulfadoxine/Pyrimethamine

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Author(s)

    • BWIJO Bwijo BWIJO Bwijo
    • 東京女子医科大学医学部国際環境・熱帯医学 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine
    • 金子 明 KANEKO Akira
    • 東京女子医科大学医学部国際環境・熱帯医学:スウェーデンカロリンスカ病院感染症科 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine:Unit of Infectious Diseases, Karolinska Hospital, Stockholm
    • LUM Jeffrey K [他] LUM Jeffrey K
    • 東京女子医科大学医学部国際環境・熱帯医学 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine
    • ZUNGU Innocent L
    • マラウイ国保健省公衆衛生研究所 Community Health Sciences Unit, Ministry of Health and Population
    • 塚原 高広 TSUKAHARA Takahiro
    • 東京女子医科大学医学部国際環境・熱帯医学 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine
    • 美田 敏宏 MITA Toshihiro
    • 東京女子医科大学医学部国際環境・熱帯医学 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine
    • 小早川 隆敏 KOBAYAKAWA Takatoshi
    • 東京女子医科大学医学部国際環境・熱帯医学 Department of International Affairs and Tropical Medicine Tokyo Women's Medical University, School of Medicine

Abstract

マラウイでは,熱帯熱マラリア患者のchloroquine治療失敗例の増加に伴い,1993年からsulfadoxine/pyrimethamine (SP)がchloroquineに代り導入された.この変更から7年後,我々はサリマ地区の無症候性熱帯熱マラリア感染学童においてin vitroおよびin vivo抗マラリア剤効果,またそれぞれpyrimethamineおよびsulfadoxine耐性と関連する原虫dihydrofolate reductase遺伝子(dhfr)およびdihydropteroate reductase遺伝子(dhps)変異について検討した.対象学童は無作為にchloroquine 3日間の標準投与群(n=50)ないしはSP一回投与群(n=40)に分けられ,治療後28日間にわたり経過が追跡された.In vivoにおけるchloroquineおよびSP感受性率はそれぞれ92%および83%であった.分離熱帯熱マラリア原虫株のin vitro薬剤感受性はSP(n=52),pyrimethamine(52),quinine(36),mefloquine(17)およびamodiaquine(14)に対して検討された.分離株の92%がpyrimethamine耐性を示したにも関わらず,85%はSP感受性であった.Quinineおよびmefloquineに対して検討したすべて,およびamodiaquineに対する93%の分離株はin vitro感受性であった.173例の熱帯熱マラリア感染において,3重変異Asn-108/Ile-51/Arg-59 dhfrおよび2重変異Gly-437/Glu-540 dhpsを持つ原虫が高頻度(78%)で認められた.これらの結果は治療薬剤変更に伴う薬剤圧の減少が原虫chloroquine感受性の回復をもたらしたことを示唆した.高度のpyrimethamineに対するin vitro耐性は高頻度にdhfr3重変異が見られたことと一致した.それにもかかわらず観察された高いSPの効果は,高度pyrimethamine耐性原虫におけるsulfadoxineおよびpyrimethamine間の相乗作用の重要性を示唆した.

In Malawi chloroquine was replaced by sulfadoxine/pyrimethamine (SP) in 1993 because of increasing chloroquine treatment failures in Plasmodium falciparum (P.falciparum) patients. Seven years after this change, we studied in vitro and in vivo efficacies of different antimalarial drugs and mutations of dihydrofolate reductase (dhfr)/dihydropteroate synthase (dhps) genes in P. falciparum infections of asymptomatic school children in Salima. The included children were randomly allocated to either treatment group with a standard dose of 3-days chloroquine (n = 50) or a single dose of SP (40) and followed up for 28 days. The in vivo sensitivity rate of chloroquine and SP were 92% and 83% respectively. P.falciparum isolates were successfully evaluated for in vitro drug sensitivity to SP (n = 52), pyrimethamine (52), amodiaquine (14), quinine (36), and mefloquine (17). Although 92% of the isolates were resistant to pyrimethamine, 85% showed in vitro sensitivity to SP. All isolates assessed for quinine and mefloquine and 93% of the isolates for amodiaquine showed in vitro sensitivity. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/ Glu-540 dhps mutations was found in 173 P. falciparum infections. Our results suggest that the reduced drug pressure accompanying the policy change consequently resulted in recovery of chloroquine sensitivity in parasites. The high in vitro pyrimethamine resistance was consistent with the high prevalence of the dhfr triple mutant. However, the high efficacy of SP confirmed the important role of synergism between pyrimethamine and sulfadoxine in the treatment of highly pyrimethamine-resistant parasites.

Journal

  • Journal of Tokyo Women's Medical College

    Journal of Tokyo Women's Medical College 73(1・2), 1-13, 2003-02

    Tokyo Women's Medical University

Codes

  • NII Article ID (NAID)
    110007525993
  • NII NACSIS-CAT ID (NCID)
    AN00161368
  • Text Lang
    ENG
  • Article Type
    journal article
  • Journal Type
    大学紀要
  • ISSN
    0040-9022
  • NDL Article ID
    025915834
  • NDL Call No.
    Z19-400
  • Data Source
    NDL  NII-ELS  IR 
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