Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes

Abstract

Studies of the ability of Plasmodium falciparum to grow in vitro in the red blood cells of subjects with certain beta-thalassemia syndromes are often difficult to interpret because of the known inhibitory effect of an elevated cellular content of human fetal hemoglobin (HbF). P falciparum therefore was cultured in vitro in the erythrocytes of subjects with hemoglobin H (HbH) disease and various other alpha- thalassemia genotypes that are unaccompanied by increased levels of HbF. Growth of the malaria parasite was markedly retarded in HbH red blood cells, when compared with growth in blood from normal control subjects. No consistent impairment of growth was seen in the erythrocytes of subjects having deletion of only one or two alpha- globin genes. These results indicate that erythrocytes with a severe thalassemia phenotype provide a less hospitable growth environment for P falciparum than normally hemoglobinized red blood cells, even in the absence of increased levels of HbF.

The membrane characteristics of Plasmodium falciparum‐infected and ‐uninfected heterozygous α0thalassaemic erythrocytes

“…In accordance with the majority of similar studies (Nagel et al, 1981;Ifediba et al, 1985;Kaminsky et al, 1986;Yuthavong et al, 1988;Luzzi et al, 1990;Bunyaratvej et al, 1992), we found no evidence for reduced invasion or growth of P. falciparum parasites in -/aa erythrocytes. Two groups, however, have recently reported evidence for reduced re-invasion of such cells during prolonged culture over two or more schizogonic cycles (Senok et al, 1997;Pattanapanyasat et al, 1999), studies which appear to support the hypothesis that thalassaemia may protect against malaria by reducing invasion and re-invasion efficiency.…”

The role of the red blood cell in host defence against falciparum malaria: an expanding repertoire of evolutionary alterations

“…Minimal changes have been observed in parasite invasion and growth in RBCs from individuals heterozygous for the a-thalassaemia genotype. For RBCs from individuals with homozygote a-thalassaemia, studies show conflicting and thus inconclusive evidence regarding growth and invasion differences (Friedman, 1979;Ifediba et al, 1985;Luzzi et al, 1991a;Bunyaratvej et al, 1992;Williams et al, 2002). RBCs from those with HbH disease show reduced growth and invasion (Ifediba et al, 1985;Brockelman et al, 1987;Chotivanich et al, 2002).…”

“…For RBCs from individuals with homozygote a-thalassaemia, studies show conflicting and thus inconclusive evidence regarding growth and invasion differences (Friedman, 1979;Ifediba et al, 1985;Luzzi et al, 1991a;Bunyaratvej et al, 1992;Williams et al, 2002). RBCs from those with HbH disease show reduced growth and invasion (Ifediba et al, 1985;Brockelman et al, 1987;Chotivanich et al, 2002). Some studies show no differences in invasion or growth in RBCs from individuals with b-thalassaemia (Luzzi et al, 1991a;Bunyaratvej et al, 1992), but one study did find reduced growth (Brockelman et al, 1987).…”

Erythrocyte variants and the nature of their malaria protective effect

“…The nature of the thalassaemia protective effect is not fully understood. Some abnormalities in invasion and growth have been seen in more severe thalassaemias, such as HbH (Ifediba et al, 1985), but results have been conflicting (Pattanapanyasat et al, 1999). For milder forms of thalassaemias, there has been no consistent evidence showing a possible effect on invasion or maturation.…”