Therapeutic efficacy and safety of Artemether/Lumefantrine for the treatment of uncomplicated P. falciparum Malaria and parasite genetic factors associated with parasite clearance or treatment failure

Alex Shayo1, Celine Mandara2, Joram Buza1, Francis Shahada1, Martha Lemnge2 and Deus Ishengoma2

1The Nelson Mandela African Institute of Science and Technology, P.O.BOX 447,
Arusha, Tanzania

2National Institute for Medical Research, Tanga Medical Research Centre, P.O, BOX 5004, Tanga, Tanzania

Background
Drug efficacy testing is recommended by the World health Organisation (WHO) for monitoring the efficacy of artemisinin based combination therapy (ACTs) which has been deployed in most malaria endemic countries as the first line treatment for uncomplicated malaria. The present study aims at assessing the efficacy and safety of Artemether/Lumefantrine (ALu) for the treatment of uncomplicated falciparum malaria and relates the treatment outcome to any detectable variations in the parasite genome.
Method
This study is an open-label, single-arm trial, which is being conducted at Mkuzi Health Centre in Muheza, Tanga; which is one of the eight National Malaria Control Program (NMCP) sentinel sites. The study will recruit 88 children aged 6 months to 10 years with uncomplicated falciparum malaria and meeting other inclusion criteria as per WHO protocol of 2009. Follow-up will be done for 28 days and the primary end point is parasitological cure on day 28. Secondary end points include: parasitological cure on day 14, improvement in haemoglobin levels at day 28 from the day 0 baseline, reduction in gametocyte carriage at day 14 and day 28 from the day 0 baseline, occurrence and severity of adverse events and genomic profile of P. falciparum.
Results
A total of 126 patients were screened and 66 of these have been enrolled during a 30 day recruitment period. Six patients completed day 28 while 60% completed day 14 of follow-up. There was no early treatment failure, two had late clinical failure and 4 had adequate clinical and parasitological response. No serious adverse events have been reported. Enrollment and follow-up are expected to be completed by the end of August 2013 and final results will be presented.
Conclusions
Unlike studies conducted at NMCP sentinel sites in the past few years, there has been an increase in the number of cases leading to increased enrollment rates. Despite the reported cases of late clinical failure, the efficacy of ALu is still high. Thus, PCR analysis will be done to distinguish recrudescent from new infections among patients with treatment failure.