Although artesunate and mefloquine have been used as monotherapies in the treatment of malaria in Kenya for a long time, there is insufficient data on the clinical outcome when used as combination therapy in this population. The objective of the study was to derive data on the efficacy and safety profile of artesunate-mefloquine combination in the treatment of uncomplicated Plasmodium falciparum malaria in Kenya. The trial was an open label single arm clinical trial, conducted in Bungoma district Hospital. Study area was Bungoma District of Kenya, an endemic area of malaria. The study was conducted between January 2004 and April 2004. A total of 200 males and females with uncomplicated plasmodium falciparum malaria weighing 35kg and above were recruited in the study. In the evaluable patient population the day 28 cure rate was 98.4% while day 14 and 7 cure rates were 98.4% and 99.2% respectively. There was rapid relief of symptoms the median time of fever clearance was one day and the most common drug related adverse events were headache dizziness and asthenia. There was no significant derangement in the haematological, biochemical and ECG parameters in the patients on treatment. Artesunate-mefloquine combination given simultaneously was found to be highly effective and safe in the treatment of uncomplicated malaria

Drug resistant malaria is mostly due to Plasmodium falciparum, the highly prevalent species in tropical Africa, Amazon, and Southeast Asia. P. falciparum is responsible for severe involvement of fever or anemia causing more than a million deaths per year. Rationale for treatment is becoming weak as multiple drug resistance against well-tolerated drugs develops. P. falciparum drug resistant malaria originates from chromosomal mutations. Analyses using molecular, genetic and biochemical approaches showed that: 1) impaired uptake of chloroquine by the parasite vacuole is a common characteristic of resistant strains, this phenotype correlates with pfmdr1 and pfcrt gene mutations; 2) one S108N to four (N51I, C59R, I164L) point mutations of dihydrofolate reductase, the enzyme target of antifolinics (pyrimethamine and proguanil), give moderate to high level of resistance to these drugs; 3) resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase (A437G, K540E), their enzyme target, impairing their capacity to potentiate antifolinic drugs; 4) resistance to atovaquone plus proguanil involves one single mutation on atovaquone target, cytochrome b (Y268S, C or N); 5) resistance to mefloquine is thought to be linked to the over expression of pfmdr1, a pump expelling toxic waste from eukaryotic cells. P. falciparum resistance levels may differ according to places and time, depending on malaria transmission and drug pressure. Coupling in vivo to in vitro tests, and using molecular tests is essential for the surveillance of replacement drugs. Low cost biochemical tools are urgently needed for a prospective monitoring of resistance.