Rethinking a 70-year-old antimalarial drug
Mathematical modelling suggests how to make an antimalarial treatment safer for more patients.
Malaria is the most important parasitic disease that affects humans. Over half of the malaria cases in Asia and South America are caused by a species of malaria parasite called Plasmodium vivax (known as vivax malaria). This form of malaria results in repeated illness because dormant parasites in the liver wake at intervals to infect the blood. The only available drug that can stop these relapses is a drug called primaquine, which was developed seventy years ago.
Unfortunately, primaquine causes dangerous side effects in certain individuals who are deficient in an enzyme called G6PD, which helps defend red blood cells against stresses. Primaquine damages these cells so that they burst, leading to anaemia. This is a major problem because G6PD deficiency is common in regions where malaria is present: in some areas up to 30% of the population may be G6PD deficient. Since G6PD testing is not widely available, doctors often avoid prescribing primaquine to treat malaria, which results in more cases of disease relapse. Failing to prevent vivax relapses causes extensive illness and hinders efforts to eliminate malaria.
Is there a way to give this drug to patients that would be safer for people with G6PD deficiency? Primaquine destroys older rather than younger red blood cells. James Watson and colleagues used mathematical modelling to see whether it is possible to develop a primaquine treatment strategy that would allow a gradual destruction of older red blood cells in individuals with G6PD deficiency, which would be safer. The mathematical model incorporates data from previous studies in malaria patients and healthy volunteers with G6PD deficiency and combines this with knowledge of how red blood cells are produced and destroyed. Watson and colleagues predicted that giving primaquine over 20 days in a steadily increasing dose was safer than current recommendations.
Mathematical models are simplifications of real world processes. The only way to test these findings properly will be to run a clinical trial that gives healthy volunteers who are G6PD deficient a course of primaquine treatment with a steadily increasing dose.
To find out more
Read the eLife research paper on which this eLife digest is based: “Modelling primaquine-induced haemolysis in G6PD deficiency” (February 3, 2017).
