Inhibitory factors in breastmilk, maternal and infant sera against in vitro growth of Plasmodium falciparum malaria parasite.

Complications from falciparum malaria are responsible for over one million infant deaths annually. There is as yet no clinically protective vaccine that has been developed against human malaria parasites. While several studies have demonstrated the inhibitory properties of human sera against Plasmodium falciparum, there is no reported investigation that has examined the protective effects of human breastmilk against the malaria parasite. This study demonstrates the presence of significant antibody titers to ring, trophozoite, schizont and gametocyte stages of P. falciparum in 144 Nigerian maternal milk samples and also in paired maternal and infant sera. The study also demonstrates significant in vitro growth inhibition of P. falciparum by maternal and infant sera, but most notably by breastmilk samples and breastmilk constituents, such as lactoferrin and sIgA. The results therefore suggest a protective in vivo role for breastmilk in the possible modulation of malaria frequency, severity and complications.

Cultivation of Plasmodium falciparum parasites in a serum-free medium.

The elimination of serum from Plasmodium falciparum culture media could decrease costs, enhance procurement, and improve the feasibility of large-scale production of parasite material. We provide a semi-defined, serum-free formulation, of commercially available constituents that supports P. falciparum parasite growth at rates comparable with those obtained with serum-supplemented media. The medium is composed of RPMI 1640 to which HEPES, extra glucose, bicarbonate, and hypoxanthine have been added. Bovine albumin and serum-derived, lipids-cholesterol-rich mixture are then used in place of serum.

Treatment of chloroquine-resistant malaria in monkeys with a drug combination that reverses resistance in vitro.

Compounds that inhibit the P-glycoprotein-related efflux mechanism of multidrug-resistant cells reverse chloroquine resistance in vitro. Hence, the co-administration of chloroquine and an efflux-blocking drug could potentially treat chloroquine-resistant malaria infections. We administered a drug combination (chloroquine and a tiapamil analogue), that has been shown to reverse chloroquine resistance in vitro, to Aotus monkeys but failed to safely clear experimentally-induced chloroquine-resistant Plasmodium falciparum parasitaemias.

Plasmodium falciparum malaria: band 3 as a possible receptor during invasion of human erythrocytes.

Human erythrocyte band 3, a major membrane-spanning protein, was purified and incorporated into liposomes. These liposomes, at nanomolar concentrations of protein, inhibited invasion of human erythrocytes in vitro by the malaria parasite Plasmodium falciparum. Liposomes containing human band 3 were ten times more effective in inhibiting invasion than those with pig band 3 and six times more effective than liposomes containing human erythrocyte glycophorin. Liposomes alone or liposomes containing erythrocyte glycolipids did not inhibit invasion. These results suggest that band 3 participates in the invasion process in a step involving a specific, high-affinity interaction between band 3 and some component of the parasite.

Severe malaria and glucose-6-phosphate-dehydrogenase deficiency: a reappraisal of the malaria/G-6-P.D. hypothesis.

Nigerian children with convulsions and Plasmodium falciparium parasitaemia above 100,000/microliter did not show a decreased frequency of glucose-6-phosphate-dehydrogenase (G.-6-P.D.) deficiency. A re-evaluation of earlier studies has led to the conclusion that clinical evidence of protection against falciparum malaria in G.-6-P.D.-deficient individuals is lacking. Evidence for the possible role of malaria in selecting for G.-6-P.D.-deficient genes consists solely of the geographical association of high frequencies of G.-6-P.D. deficiency with endemic malaria.

Low erythrocyte pyridoxal-kinase activity in Blacks: Its possible relation to falciparum malaria.

The red-cell glucose-6-phosphate dehydrogenase (G.-6-P.D.) activity and red-cell pyridoxal-kinase (P.L.K.) activity of 27 Nigerian children with severe Plasmodium falciparum parasitaemia were compared with those of 26 healthy Nigerian children and 6 White adults. The mean P.L.K. activity of the malaria patients was similar to that of the Whites but significantly higher than that of the Nigerian controls. Correction for reduced mean red-cell age in patients was made by comparing the P.L.K.: G.-6-P.D. ratio for those subjects with stable G.-6-P.D. phenotypes. The mean P.L.K.:G.-6-P.D. ratio was the same for malaria patients and adult White but significantly higher than that for the Nigerian controls. These results suggest that the relatively high frequency of low red-cell P.L.K. activity among Blacks may have been selected for by falciparum malaria.