The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance

NCT ID: NCT00440752

Last Updated: 2008-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-10-31

Study Completion Date

2006-12-31

Brief Summary

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The newly introduced antimalarial drug artemether-lumefantrine is currently recommended as second line antimalarial in Sudan. Recurrent infection after treatment with this drug has been associated with selection of certain genes in the malaria parasite. However there is no information on this association in Sudan.This study is going to look into the genetics of resistance to artemether-lumefantrine.

Detailed Description

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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.

Conditions

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Falciparum Malaria Antimalarials

Keywords

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Artemether-lumefantrine Plasmodium falciparum drug resistance genes

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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AL

Cohort of study participants receiving treatment with artemether-lumefantrine

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role collaborator

World Health Organization

OTHER

Sponsor Role collaborator

International Atomic Energy Agency

OTHER_GOV

Sponsor Role collaborator

Tropical Medicine Research Institute

OTHER

Sponsor Role lead

Principal Investigators

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Colin Sutherland, PhD.

Role: PRINCIPAL_INVESTIGATOR

London School of Hygiene and Tropical Medicine

Badria B El-Sayed, PhD

Role: STUDY_CHAIR

Tropical Medicine Research Institute

Locations

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Tropical Medicine Research Institute

Khartoum, Khartoum State, Sudan

Site Status

Countries

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Sudan

References

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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.

Reference Type BACKGROUND
PMID: 16641472 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17194834 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15717281 (View on PubMed)

Other Identifiers

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AL Oct-Dec/06-07

Identifier Type: -

Identifier Source: org_study_id