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Some complications of Plasmodium falciparum infection such as cerebral malaria and pregnancy-associated malaria may be partially due to cytoadherence of erythrocytes infected by mature parasites on microvascular endothelial cells or placental syncytiotrophoblasts. Recently a new cytoadherence receptor, chondroitin-4-sulphate (CSA), was identified first on endothelial cells in primates and then on CHO cells and purified receptors. Further study has implicated CSA in cytoadherence of infected red blood cells to syncytiotrophoblasts in human placenta and Saimiri sciureus monkeys. In solution the minimal size for full inhibitory effect is approximately 9 kDa. Injection of CSA in Plasmodium falciparum-infected Saimiri monkeys resulted in specific release of sequestered erythrocytes infected by mature parasites. An added interest of these findings is that CSA, a glycosaminoglycan, is already in clinical use for treatment of degenerative joint disease. Current data on the parasite ligand for CSA indicates that it is not co-expressed with other cytoadherence ligands and that its binding activity decreases as the parasite matures from the 20th to 40th hour of the cycle. Since one or more var genes encoding the CSA ligand have been identified, it is likely that peptides will be obtained quickly and used either for direct inhibition of cytoadherence on CSA or for development of an anti-sequestration vaccine.

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

Recent advances in cultivation methods and knowledge of in vitro response of Plasmodium falciparum to antimalarials have led to improved chemosensitivity tests. The semimicrotest is a useful tool for screening presumptive antimalarials, and also for the testing sensitivity of strains recovered from patients in hospital and field studies to currently used drugs. Microscopic parasite counts on thin blood films can be replaced by measurement of 3H-hypoxanthine by the uptake parasite. Conditions which ensure optimal parasite growth and high radioisotope incorporation are described. Wells containing less than 3. 10(4) asexual parasites can be studied with this method. Results of the semi-microtest are closely correlated with those of microscopic parasite count. Advantages of both methods are discussed.