The effect of X chromosome inactivation on the inhibition of Plasmodium falciparum malaria growth by glucose-6-phosphate-dehydrogenase- deficient red cells

Abstract Previous data on in vitro culture of Plasmodium falciparum malaria demonstrated that red cell glucose-6-phosphate dehydrogenase deficiency (G6PD-) inhibited parasite growth in deficient hemizygous males. This study investigated the effect of heterozygosity for G6PD- on parasite growth. Blood was obtained from 8 female Sardinian G6PD- heterozygotes with G6PD normal cells ranging from 13% to 60%. For comparison, blood from a G6PD- hemizygous male, containing 100% deficient red cells, was mixed in different proportions with compatible normal blood. In both experiments, parasite growth was inhibited by the presence of deficient cells. In both cases, it was found that the inhibition could be explained by a simple dilution of normal cells by G6PD- cells. Thus, the typical female heterozygote is also protected to a significant extent. When considering the “malaria hypothesis” as it relates to G6PD, protection of the female heterozygote as well as the male hemizygote must be taken into account.

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The effect of X chromosome inactivation on the inhibition of Plasmodium falciparum malaria growth by glucose-6-phosphate-dehydrogenase- deficient red cells

Blood ◽

10.1182/blood.v62.4.866.bloodjournal624866 ◽

1983 ◽

Vol 62 (4) ◽

pp. 866-868

Author(s):

EF Jr Roth ◽

C Raventos Suarez ◽

A Rinaldi ◽

RL Nagel

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Parasite Growth ◽

Red Cells ◽

Normal Cells ◽

Hemizygous Male ◽

Glucose 6 Phosphate Dehydrogenase ◽

Cell Glucose

Previous data on in vitro culture of Plasmodium falciparum malaria demonstrated that red cell glucose-6-phosphate dehydrogenase deficiency (G6PD-) inhibited parasite growth in deficient hemizygous males. This study investigated the effect of heterozygosity for G6PD- on parasite growth. Blood was obtained from 8 female Sardinian G6PD- heterozygotes with G6PD normal cells ranging from 13% to 60%. For comparison, blood from a G6PD- hemizygous male, containing 100% deficient red cells, was mixed in different proportions with compatible normal blood. In both experiments, parasite growth was inhibited by the presence of deficient cells. In both cases, it was found that the inhibition could be explained by a simple dilution of normal cells by G6PD- cells. Thus, the typical female heterozygote is also protected to a significant extent. When considering the “malaria hypothesis” as it relates to G6PD, protection of the female heterozygote as well as the male hemizygote must be taken into account.

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Wild isolates of Plasmodium falciparum malaria show decreased sensitivity to in vitro inhibition of parasite growth mediated by autologous host antibodies

Clinical & Experimental Immunology ◽

10.1111/j.1365-2249.1997.273-ce1163.x ◽

1997 ◽

Vol 107 (2) ◽

pp. 321-327 ◽

Cited By ~ 4

Author(s):

B. WÅHLIN FLYG ◽

H. PERLMANN ◽

P. PERLMANN ◽

F. ESPOSITO ◽

K. BERZINS

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Parasite Growth ◽

In Vitro Inhibition

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Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria

Science ◽

10.1126/science.360396 ◽

1978 ◽

Vol 202 (4368) ◽

pp. 650-652 ◽

Cited By ~ 82

Author(s):

E. Roth ◽

M Friedman ◽

Y Ueda ◽

I Tellez ◽

W Trager ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Red Cells

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Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab281 ◽

2021 ◽

Author(s):

Mélissa Mairet-Khedim ◽

Sandrine Nsango ◽

Christelle Ngou ◽

Sandie Menard ◽

Camille Roesch ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Southeast Asia ◽

Falciparum Malaria ◽

Gene Polymorphisms ◽

Plasmodium Falciparum Malaria ◽

Molecular Profile ◽

Uncomplicated Plasmodium Falciparum Malaria ◽

In Vitro Survival ◽

Phenotypic Susceptibility

Abstract Background Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and methods Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia.

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