Novel Insights Into the Protective Role of Hemoglobin S and C Against<i>Plasmodium falciparum</i>Parasitemia

Mangano, Valentina; Kaboré, Youssouf; Bougouma, Edith C.; Verra, Federica; Sepúlveda, Nuno; Bisseyé, Cyrille; Santolamazza, Federica; Avellino, Pamela; Tiono, Alfred B.; Diarra, Amidou; Nébié, Issa; Rockett, Kirk A.; Sirima, Sodiomon B.; Modiano, David

doi:10.1093/infdis/jiv098

Cited by 32 publications

(29 citation statements)

References 47 publications

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“…Studies in murine models have demonstrated that the accelerated breakdown of haem by the increased induction of HO-1 prevents the onset of experimental cerebral malaria in mice [16,17]. Contrary to reports that have implicated the reduction of parasitaemia as a cause of the reduced susceptibility to severe complications of malaria in patients with the HbAS genotype [3,12,32], we found no significant difference in parasite densities between patients with the HbAS genotype and patients with the HbAA genotype during acute malaria infection. Our cohort of children does not have severe forms of malaria; therefore, we cannot rule out the possibility of a difference in parasitaemia between the genotypical groups if they have severe malaria.…”

Section: Discussioncontrasting

confidence: 99%

Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

Ademolue

Amodu

Awandare

2017

Clinical and Experimental Immunology

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SummaryThe controlled induction of haemoxygenase‐1 (HO‐1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. The hemoglobin genotype HbAS confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. Using a longitudinal approach, we investigated the effect of baseline concentrations of HO‐1 on the accumulation of haem during acute Plasmodium falciparum malaria in HbAS and HbAA genotypes. Plasma concentrations of haem, HO‐1 and cytokines were quantified in venous blood obtained from children (9 months–5 years of age) during malaria infection, and at convalescence (baseline levels). Parasitaemia was determined during malaria infection. In patients with the HbAA genotype, there was a significant elevation in the plasma concentration of haem (P = 0.002), and a consequent increased induction of HO‐1 (P < 0.001) during falciparum malaria compared with levels at convalescence. Contrary to HbAA, plasma concentration of haem did not change in the HbAS genotypical group (P = 0·110), and the induction of HO‐1 was reduced during malaria compared with levels at convalescence (P = 0·006). Higher plasma levels of haem were observed in HbAS compared with HbAA at convalescence (P = 0·010), but this difference did not affect the levels of HO‐1 within each genotype (P = 0·450). Relatively milder proinflammatory responses were observed in HbAS children during malaria infection compared to HbAA children. Our findings suggest that a mechanism of reduced susceptibility to severe malaria pathologies by the HbAS genotype may involve the control of haem, leading to controlled levels of HO‐1 and milder proinflammatory responses during acute malaria.

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Section: Discussioncontrasting

confidence: 99%

Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

Ademolue

Amodu

Awandare

2017

Clinical and Experimental Immunology

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“…While protective associations between certain RBC variants and severe malaria have been shown consistently [7,18], associations with uncomplicated malaria have been less straightforward. Multiple studies showed reduced risk of malaria [19][20][21][22][23][24] and lower parasite densities [4,25,26] with HbAS compared to wild-type. For alpha thalassaemia, studies suggested both protection against and enhancement of malaria [5,6,27,28].…”

Section: Introductionmentioning

confidence: 99%

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Kakande

Greenhouse

Bajunirwe

et al. 2020

Malar J

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Background: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. Methods: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. Results: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (− 0.13 ℃, 95% CI − 0.21, − 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α−/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (− 0.19 ℃, 95% CI − 0.31, − 0.06, p = 0.003). Conclusion: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria.

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“…Several studies showed evidence related to the role of hemoglobin S and C in the protection against severe and uncomplicated malaria [21,22]. The role of hemoglobin S and C has already shown in the protection against malaria infection [12].…”

Section: Discussionmentioning

confidence: 99%

“…The study site has been already described elsewhere [12]. Plasma samples were obtained from children and adults belonging to 3 sympatric ethnic groups (Mossi, Fulani, and Rimaïbé).…”

Section: Study Site and Samples Collectionmentioning

confidence: 99%

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Seroreactivity of Populations Living in Endemic Area of Burkina Faso to Plasmodium falciparum Alpha-Helical Coiled Coil Proteins Motifs by Protein Microarray

Ouédraogo¹,

Nunziangeli²,

Bougouma³

et al. 2019

J Trop Dis

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The naturally acquired immunity is one of the models of immunity that is exploited for malaria antigens discovery. We have used multiplex protein microarrays of 92 P. falciparum alpha-helical coiled coil protein motifs to screen plasma samples obtained from 1113 children and adults belonging to three sympatric ethnic groups from malaria endemic area of Burkina Faso. We have investigated the influence of some factors such as age, ethnicity, hemoglobin genotype and sex on the antigens reactivity and the IgG antibody level. We also investigated specifically, the influence of the factors mentioned above on the 36 antigens with the highest antibody prevalence and intensity. As expected, the findings of the study confirmed the positive correlation between age, antigens reactivity and IgG antibody level. Except for three antigens (MSP2_3D7, MR260, and As182.20), the IgG level was higher in adults compared to children. The Fulani ethnic group recognized more antigens with the highest IgG values compared to the sympatric groups of Mossi and Rimaibé, except for six antigens (LR166, LR146, AS182.15, MR214, MR236A, and MSP3). In General, the hemoglobin type and sex did not have any influence on the IgG antibody reactivity and intensity. Except for four antigens (MR232, MR261A, MSP2_3D7, and NANP) 10), there was statistically no IgG intensity difference between people with normal hemoglobin genotype (AA) and the non-(AA) volunteers. Our study has demonstrated that protein microarrays of alpha-helical coiled-coil proteins motifs are suitable to screen the naturally acquired immunity. The findings of the study should be considered in any strategy for new antigen related to alpha-helical coiled coil protein segments discovery for a potential vaccine clinical development.

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Novel Insights Into the Protective Role of Hemoglobin S and C AgainstPlasmodium falciparumParasitemia

Cited by 32 publications

References 47 publications

Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Seroreactivity of Populations Living in Endemic Area of Burkina Faso to Plasmodium falciparum Alpha-Helical Coiled Coil Proteins Motifs by Protein Microarray

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