Drug resistance
One of the greatest problems in the fight against malaria is the speed with which the parasites are able to develop resistance to a succession of drugs. The MRP is actively involved in research into this problem. (See also Molecular Epidemiology )
Drug resistance arises through one or more mutations in the parasite genome which cause changes in the enzyme system or organelle targeted by the drug. This is seldom an all or nothing phenomenon, and it is usually an accumulation of mutations which finally renders the drug unusable. Professor Nick White has suggested that anti-malaria therapy is simply a race against evolution, and it is only a matter of time before any advantage given by a new drug is neutralised by natural selection of resistant mutants. Thus, a mutation which gives the parasite a selective advantage quickly spreads and in this way, for example, resistance to chloroquine which originated in South East Asia became established in East Africa and then rapidly spread throughout Africa.
Paradoxically one of the oldest drugs, quinine, is a fortunate exception to this process. Although resistance has been documented it has not yet spread in this fashion.
Detection of drug resistance?
Volunteer malaria patients are treated with the drug in question and their condition is monitored over the next 28 days. This extended period is necessary because parasites with partial resistance may drop to microscopically undetectable levels in the blood and then stage a comeback as the levels of drug in the bloodstream decrease. However in the worst type of resistance the number of parasites in the blood may barely decrease or even increase when the drug is administered.
This type of study is fairly demanding in that patients must be persuaded to return regularly for checkups. An attractive alternative is a laboratory-based procedure in which parasites isolated from patients are cultured in artificial medium containing red blood cells in the presence of a range of concentrations of the drug, allowing conclusions to be drawn as to whether a higher than normal concentration of drug is needed to inhibit parasite growth, which would indicate resistance.