Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India.
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.


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.


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.


CONCLUSIONS
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.
Valecha
Neena
N
National Institute of Malaria Research, Delhi, India. neenavalecha@gmail.com
Srivastava
Prakriti
P
Mohanty
Suman S
SS
Mittra
Pooja
P
Sharma
Surya K
SK
Tyagi
Prajesh K
PK
Pradhan
Khageswar
K
Dev
Vas
V
Singh
Ruchi
R
Dash
Aditya P
AP
Sharma
Yagya D
YD
D000293:Adolescent; D000328:Adult; D054458:Amplified Fragment Length Polymorphism Analysis; D000818:Animals; D000953:Antigens, Protozoan / Q000187:drug effects / Q000235:genetics; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000187:drug effects* / Q000235:genetics; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
D000953:Antigens, Protozoan; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium