resistance

There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malarianext term after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride.

Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity.

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum has been widespread across continents, causing the major hurdle of controlling malaria. Resistance is encoded mainly by point mutations in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) target genes.

 Pyrethroid insecticide resistance in Anopheles gambiae sensu stricto is a major concern to malaria vector control programmes. Resistance is mainly due to target-site insensitivity arising from a single point mutation, often referred to as knockdown resistance (kdr). Metabolic-based resistance mechanisms have also been implicated in pyrethroid resistance in East Africa and are currently being investigated in West Africa. Here we report the co-occurrence of both resistance mechanisms in a population of An. gambiae s.s. from Nigeria.

Insecticides are a key component of vector-based malaria control programmes in Cameroon. As part of ongoing resistance surveillance efforts, Anopheles gambiae s.l. female mosquitoes were exposed to organochlorine (DDT), a carbamate (bendiocarb), an organophosphate (malathion), and three pyrethroids (deltamethrin, lambda-cyhalothrin and permethrin) in WHO bioassay test kits.

Carbamate and organophosphorous compounds could thus be used as alternatives in locations in Cameroon where pyrethroid-resistant populations are found.

Insecticide resistance in Anopheles gambiae threatens the success of malaria vector control programmes in sub-Saharan Africa. In order to manage insecticide resistance successfully, it is essential to assess continuously the target mosquito population. Here, we collected baseline information on the distribution and prevalence of insecticide resistance and its association with target-site mutations in eastern Uganda.

This study reports on the distribution of pyrethroid and DDT resistance and the L1014F knockdown resistance (kdr) mutation in Anopheles gambiae s.l. populations from 21 localities in three different climatic zones of Burkina Faso from August to October 2006. These results have practical significance for malaria vector control programs.