Acute Phase Responses Vary Between Children of HbAS and HbAA Genotypes During Plasmodium falciparum Infection

Abstract

Purpose: Haemoglobin genotype S is known to offer protection against Plasmodium falciparum infections but the mechanism underlying this protection is not completely understood. Associated changes in acute phase proteins (APPs) during Plasmodium falciparum infections between Haemoglobin AA (HbAA) and Haemoglobin AS (HbAS) individuals also remain unclear. This study aimed to evaluate changes in three APPs and full blood count (FBC) indices of HbAA and HbAS children during Plasmodium falciparum infection.

Methods: Venous blood was collected from three hundred and twenty children (6 months to 15 years) in Begoro in Fanteakwa District of Ghana during a cross-sectional study. Full blood count (FBC) indices were measured and levels of previously investigated APPs in malaria patients; C-reactive protein (CRP), ferritin and transferrin measured using Enzyme-Linked Immunosorbent Assays.

Results: Among the HbAA and HbAS children, levels of CRP and ferritin were higher in malaria positive children as compared to those who did not have malaria. The mean CRP levels were significantly higher among HbAA children (p=0.2e-08) as compared to the HbAS children (p=0.43). Levels of transferrin reduced in both HbAA and HbAS children with malaria, but the difference was only significant among HbAA children (p=0.0038), as compared to the HbAS children. No significant differences were observed in ferritin levels between HbAA and HbAS children in both malaria negative (p=0.76) and positive (p=0.26) children. Of the full blood count indices measured, red blood cell count (p=0.044) and haemoglobin (Hb) levels (p=0.017) differed between HbAA and HbAS in those without malaria, with higher RBC counts and lower Hb levels found in HbAS children. In contrast, during malaria, lymphocyte and platelet counts were elevated, whilst granulocytes and Mean Cell Haematocrit counts were reduced among children of the HbAS genotypes.

Conclusion: Significant changes in APPs were found in HbAA children during malaria as compared to HbAS children, possibly due to differences in malaria-induced inflammation levels. This suggests that the HbAS genotype is associated with better control of P. falciparum infection-induced inflammatory response than HbAA genotype.

Keywords: APP; APR; C-reactive protein; Plasmodium falciparum; acute phase proteins; acute phase response; ferritin; transferrin.

Figure 1

C-reactive protein levels between HbAA and HbAS individuals during Plasmodium falciparum infection. The left panel (A) compares the C-reactive protein levels between P. falciparum positive and negative HbAA individuals and the right panel (B) shows C-reactive protein levels between P. falciparum positive and negative HbAS individuals. The x-axis shows malaria status and the y-axis is the log C-reactive protein levels (µg/mL). (C and D) compares the levels of C-reactive proteins in children who were malaria negative and those who were diagnosed to be malaria positive in respect to their genotypes respectively.

Figure 2

Ferritin levels in HbAA and HbAS individuals during Plasmodium falciparum infection. The left panel (A) compares the ferritin levels between individuals of HbAA and HbAS phenotype without malaria and the (B) shows those diagnosed with malaria. The lower left panel (C) compares the ferritin levels between P. falciparum positive and negative HbAA individuals and the right panel (D) shows the ferritin levels among HbAS individuals with malaria and those without malaria. In both panels the y-axis is log ferritin levels (µg/L).

Figure 3

Transferrin levels in HbAA and HbAS individuals during Plasmodium falciparum infection. The left panel (A) compares the transferrin levels between P. falciparum positive and negative HbAA individuals and the right panel (B) shows the transferrin levels among HbAS individuals with malaria and those without malaria. The x-axis shows malaria status, and the y-axis shows the Hb genotypes. In both panels (A&B) the y-axis represents log transferrin levels (nmol/mL). (C and D) compares the levels of transferrin in children who were malaria negative and those who were diagnosed to be malaria positive in respect to their genotypes respectively.