The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance
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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||The Impact of Artemether-Lumefantrine on Genes Associated With Antimalarial Resistance in an Area of Seasonal Transmission|
- Levels of expression of pfcrt and pfmdr-1 alleles on day 0, 3, 7, 14, 21, 28 detected by real-time PCR. [ Time Frame: 2007 to 2009 ]
- Parasitological failure occurring at day 3, 7, 14, 21, 28 or any other day during this period. [ Time Frame: within 28 days of subject recruitment ]
- Gametocyte development detected by reverse transcriptase PCR on day 0, 3, 14 and 28 [ Time Frame: 2008 to 2009 ]
Biospecimen Retention: Samples With DNA
Blood spots on glass fibre membranes. 0.5ml of whole blood preserved in TRI reagent.
|Study Start Date:||October 2006|
|Study Completion Date:||December 2006|
Cohort of study participants receiving treatment with artemether-lumefantrine
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.
|Tropical Medicine Research Institute|
|Khartoum, Sudan, 11111|
|Principal Investigator:||Colin Sutherland, PhD.||London School of Hygiene and Tropical Medicine|
|Study Chair:||Badria B El-Sayed, PhD||Tropical Medicine Research Institute|