Invasion and development of Plasmodium falciparum in erythroblasts of humans carrying G6PD viangchan

• The orthochromatic erythroblast stage is the most susceptible to P. falciparum infection. • P. falciparum parasites were able to invade and develop into mature trophozoites in erythroblasts from G6PD-deficient subjects. • P. falciparum-infected erythroid cells had abnormal morphology and progressive differentiation in a manner independent of G6PD. Emerging evidence suggests the development of malaria parasites in the human bone marrow. Whether glucose-6-phosphate dehydrogenase (G6PD) deficiency affects parasite growth in erythroblast has yet to be determined. Here, we examine the invasion and development of Plasmodium falciparum in human erythroblasts of subjects carrying the most common variant of G6PD Viangchan (871G>A) in Southeast Asia. Erythroblasts were generated by differentiation of erythroids of human CD34-positive hematopoietic stem and progenitor cells isolated from peripheral blood. The results showed that P. falciparum parasites invade polychromatic erythroblasts and develop into mature trophozoites. The percentages and stages of parasitized erythroblasts were not different between the subjects with G6PD normal, heterozygous, or hemizygous G6PD Viangchan. While the sample size (n = 6) limited statistical analysis, these preliminary findings suggest that protection against malaria is not observed in this i n vitro erythroblast model, supporting further validation in expanded cohorts.