The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance
The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance in an Area of Seasonal Transmission
調査の概要
詳細な説明
In Sudan the current treatment protocol includes two artemisinin combinations (ACT); artesunate + sulphadoxine/pyrimethamine (AS/SP) as first line and artemether-lumefantrine (AL) as second line. This protocol has been implemented in 2004, since then various studies have reported the high efficacy of both combinations (e.g. Adam et al., 2005; Elamin et al., 2005; Mohamed et al., 2006).
However, there has been no report of the impact of these combinations on drug resistance markers in Sudan. Data from other African countries has shown that AL selects for certain alleles in the pfmdr-1 gene (Sisowath et al., 2005, Dokomajilar et al., 2006; Humphreys et al., 2007), but the impact on the prevalence of different pfcrt and pfmdr-1alleles remains unclear. It is essential to monitor ACT efficacy in addition to identify molecular markers that are associated with response to different drugs to facilitate epidemiological surveys for evidence based decision making. Recent work in The Gambia suggests that transmission-related endpoints, such as emergence of gametocytes after treatment, may be better indicators of emerging drug resistance (Hallett et al., 2006).
The aim of the proposed study is to examine the impact of treatment with artemether-lumefantrine (AL) on alleles of pfcrt and pfmdr-1 in P. falciparum isolates in an area of marked seasonal transmission in eastern Sudan. Most studies of resistance markers measure marker prevalence by DNA amplification, but we will also investigate gene expression using quantitative amplification of mRNA encoding pfcrt and pfmdr-1. The impact of genotype and gene expression levels on treatment outcome, and on the emergence and density of peripheral gametocytes will be examined.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Khartoum、スーダン、11111
- Tropical Medicine Research Institute
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
説明
Inclusion Criteria:
- Mono-infection with P. falciparum by microscopy.
- Initial parasite density of 1000 to 100,000 asexual parasites/µl.
- Absence of general danger signs or other signs of severe and complicated falciparum malaria according to WHO definitions.
- Informed consent provided by patient or parent/guardian.
Exclusion Criteria:
- Pregnancy
- Infection with mixed Plasmodium sp.
- Signs of severe malaria or any danger signs
- Refusal to provide consent
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 観測モデル:コホート
- 時間の展望:見込みのある
コホートと介入
グループ/コホート |
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AL
Cohort of study participants receiving treatment with artemether-lumefantrine
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
時間枠 |
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Levels of expression of pfcrt and pfmdr-1 alleles on day 0, 3, 7, 14, 21, 28 detected by real-time PCR.
時間枠:2007 to 2009
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2007 to 2009
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二次結果の測定
結果測定 |
時間枠 |
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Parasitological failure occurring at day 3, 7, 14, 21, 28 or any other day during this period.
時間枠:within 28 days of subject recruitment
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within 28 days of subject recruitment
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Gametocyte development detected by reverse transcriptase PCR on day 0, 3, 14 and 28
時間枠:2008 to 2009
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2008 to 2009
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協力者と研究者
協力者
捜査官
- 主任研究者:Colin Sutherland, PhD.、London School of Hygiene and Tropical Medicine
- スタディチェア:Badria B El-Sayed, PhD、Tropical Medicine Research Institute
出版物と役立つリンク
一般刊行物
- Dokomajilar C, Nsobya SL, Greenhouse B, Rosenthal PJ, Dorsey G. Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006 May;50(5):1893-5. doi: 10.1128/AAC.50.5.1893-1895.2006.
- Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJ, Mutabingwa TK, Sutherland CJ, Hallett RL. Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria. Antimicrob Agents Chemother. 2007 Mar;51(3):991-7. doi: 10.1128/AAC.00875-06. Epub 2006 Dec 28.
- Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis. 2005 Mar 15;191(6):1014-7. doi: 10.1086/427997. Epub 2005 Feb 8.
研究記録日
主要日程の研究
研究開始
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- AL Oct-Dec/06-07
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