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Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India.
- Source :
-
Malaria journal [Malar J] 2009 May 19; Vol. 8, pp. 107. Date of Electronic Publication: 2009 May 19. - Publication Year :
- 2009
-
Abstract
- Background: Artemisinin-based combination therapy (ACT) is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL), a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 x 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h) was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required.<br />Methods: One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa) were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers msp-1 and msp-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in pfmdr1 was also carried out in the samples obtained from patients before and after the treatment.<br />Results: The PCR corrected cure rates were high at both the sites viz. 100% (n = 53) in Assam and 98.6% (n = 71) in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91) and 184 (91.3%, n = 91) of pfmdr1 gene.<br />Conclusion: AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria in India. The polymorphism in pfmdr1 gene is not co-related with clinical outcome. However, treatment failure can also occur due to incomplete absorption of the drug as is suspected in one case of failure at D7 in the study. AL can be a viable alternative of artesunate plus sulphadoxine/pyrimethamine (AS + SP), however, the drug should be used rationally and efficacy needs to be monitored periodically.
- Subjects :
- Adolescent
Adult
Amplified Fragment Length Polymorphism Analysis
Animals
Antigens, Protozoan drug effects
Antigens, Protozoan genetics
Antimalarials adverse effects
Antimalarials therapeutic use
Artemether, Lumefantrine Drug Combination
Artemisinins adverse effects
Artemisinins therapeutic use
Child
Child, Preschool
Drug Administration Schedule
Drug Combinations
Ethanolamines adverse effects
Ethanolamines therapeutic use
Female
Fluorenes adverse effects
Fluorenes therapeutic use
Follow-Up Studies
Humans
India
Malaria, Falciparum epidemiology
Malaria, Falciparum parasitology
Male
Merozoite Surface Protein 1 drug effects
Merozoite Surface Protein 1 genetics
Middle Aged
Plasmodium falciparum genetics
Plasmodium falciparum isolation & purification
Polymerase Chain Reaction
Prospective Studies
Protozoan Proteins genetics
Recurrence
Treatment Outcome
Young Adult
Antimalarials administration & dosage
Artemisinins administration & dosage
Ethanolamines administration & dosage
Fluorenes administration & dosage
Malaria, Falciparum drug therapy
Plasmodium falciparum drug effects
Protozoan Proteins drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2875
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Malaria journal
- Publication Type :
- Academic Journal
- Accession number :
- 19454000
- Full Text :
- https://doi.org/10.1186/1475-2875-8-107