In vitro and genetic aspects of treatments for falciparum malaria: studies of conventional and novel drugs with a particular focus on Papua New Guinea

[Truncated abstract] Malaria remains a significant global health problem. Plasmodium falciparum, the predominant and most virulent infecting species, has developed resistance to most antimalarial drugs. Drug sensitivity is monitored by i) in vivo (clinical) outcome, ii) in vitro response of cultured parasites to a range of drug concentrations, and iii) presence of resistance-associated molecular markers. Few studies have integrated these approaches which can all contribute to the development of treatment regimens that improve clinical outcome and delay spread of resistance. Recent clinical studies have shown high rates of treatment failure in Papua New Guinea (PNG), necessitating a proposed change from chloroquine (CQ) or amodiaquine (AQ) plus sulfadoxine-pyrimethamine (SP) to artemisinin combination therapy (ACT). The in vitro sensitivity of 64 P. falciparum isolates from Madang Province to CQ, AQ, monodesethyl-amodiaquine (DAQ), piperaquine (PQ), naphthoquine (NQ), mefloquine (MQ), lumefantrine (LM), dihydroartemisinin (DHA) and azithromycin was assessed by colorimetric lactate dehydrogenase growth inhibition assay. Its non-isotopic, semiautomated, high-throughput nature makes it suitable for field use in developing countries.