New challenges posed by the development of resistance against
artemisinin-based combination
therapies (ACTs) as well as previous first-line
therapies, and the continuing absence of
vaccine, have given impetus to research in all areas of
malaria control. This review portrays the ongoing progress in several directions of
malaria research. The variants of RTS,S and apical membrane
antigen 1 (AMA1) are being developed and test adapted as multicomponent and multistage
malaria control
vaccines, while many other
vaccine candidates and methodologies to produce
antigens are under experimentation. To track and prevent the spread of
artemisinin resistance from Southeast Asia to other parts of the world, rolling circle-enhanced
enzyme activity detection (REEAD), a time- and cost-effective
malaria diagnosis in field conditions, and
a DNA marker associated with
artemisinin resistance have become available. Novel mosquito repellents and mosquito trapping and killing techniques much more effective than the prevalent ones are undergoing field testing. Mosquito lines stably infected with their symbiotic wild-type or genetically engineered bacteria that kill sympatric
malaria parasites are being constructed and field tested for stopping
malaria transmission. A complementary approach being pursued is the addition of
ivermectin-like
drug molecules to ACTs to cure
malaria and kill mosquitoes. Experiments are in progress to eradicate
malaria mosquito by making it genetically male sterile. High-throughput screening procedures are being developed and used to discover molecules that possess long in vivo half life and are active against liver and blood stages for the fast cure of
malaria symptoms caused by simple or relapsing and
drug-sensitive and
drug-resistant types of varied
malaria parasites, can stop gametocytogenesis and sporogony and could be given in one dose. Target-based
antimalarial drug designing has begun. Some of the putative next-generation
antimalarials that possess in their scaffold structure several of the desired properties of
malaria cure and control are exemplified by OZ439,
NITD609, ELQ300 and
tafenoquine that are already undergoing clinical trials, and
decoquinate,
usnic acid, torin-2,
ferroquine,
WEHI-916, MMV396749 and
benzothiophene-type
N-myristoyltransferase (NMT) inhibitors, which are candidates for future clinical usage. Among these,
NITD609, ELQ300,
decoquinate,
usnic acid, torin-2 and NMT inhibitors not only cure simple
malaria and are prophylactic against simple
malaria, but they also cure relapsing
malaria.