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

Tetteh, Mary; Addai‐Mensah, Otchere; Kyei-Baafour, Eric; Lamptey, Helena; Williams, J. Parker; Kupeh, Edward King; Egbi, Godfred; Kwayie, Anna Boadi; Abbam, Gabriel; Afrifah, David Amoah; Debrah, Alexander Yaw; Ofori, Michael F.

doi:10.2147/jir.s301465

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…We also report that coinheritance of homozygous a-thalassaemia with HbAC and heterozygous a-thalassaemia with HbAS increased the risk of P. falciparum asymptomatic parasitaemia about threefold compared to wild-type. Our results agree with previous reports of protection against severe malaria but not asymptomatic infections conferred by HbAS and HbAC phenotypes (1,8,16,39,(49)(50)(51), and protection against severe malaria anaemia but not against parasite carriage in homozygous a-thalassaemia (52,53). Taken together, our findings and previous studies reinforce the hypothesis that reduced cytoadhesion of infected RBCs (54) rather than a parasitaemia reduction in vivo is the most likely explanation for the protection afforded by these haemoglobinopathies.…”

Section: Discussionsupporting

confidence: 93%

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

Lamptey¹,

Seidu²,

Lopez-Perez³

et al. 2023

Front. Hematol.

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BackgroundThe protective effect of certain haemoglobinopathies, such as HbS, HbC, and α-thalassaemia, against severe malaria has long been established; however, there is only limited and equivocal evidence regarding their impact on asymptomatic parasitaemia. Here, we investigated the effect of HbS, HbC, and α-thalassaemia on asymptomatic P. falciparum parasitaemia and acquired immunity among children in Northern Ghana.Materials and methodsA cross-sectional study was conducted among 1,017 healthy children (1-17 years) in 13 malaria-endemic communities in Northern Ghana. The children were screened for structural Hb phenotypes using SickleSCAN, for P. falciparum infection using anti-HRP2 malaria RDT and subsequently confirmed by capillary electrophoresis and PCR, respectively. α-thalassaemia genotyping was done using PCR. Levels of IgG specific for six recombinant malaria antigens (PfCSP, GLURP, MSP3, Pfs230, HB3VAR06, and IT4VAR60) and crude asexual blood-stage antigens were evaluated by ELISA.Results266 out of the 1,017 participants had either HbAC (18%) or HbAS (8.4%), whereas 35% had α‐thalassaemia. Twenty-five percent and 6% HbAC individuals co-inherited heterozygous and homozygous α-thalassaemia respectively. Similarly, 25% and 10.5% of HbAS co-inherited heterozygous and homozygous α-thalassaemia. Asymptomatic parasitaemia rates were 23%, 24%, and 19% in those with HbAA, HbAC and HbAS, respectively. The overall parasite carriage rates in heterozygous (21%) and homozygous α-thalassaemia (25%) individuals were similar to that of individuals without α-thalassaemia (23%). P. falciparum parasite carriage risk was about three times higher among homozygous α-thalassaemia individuals with HbAC (OR = 2.97; 95% CI 0.83-10.62) and heterozygous carriers with HbAS variants (OR = 2.86; 95% CI 0.85-9.60) compared to the wildtype. In HbAS individuals, IgG levels to IT4VAR60 and HB3VAR06 were significantly lower, whereas anti-CSP levels were higher than in HbAA and HbAC.ConclusionsCo-inheritance of HbAS and HbAC with α-thalassaemia increased the risk of asymptomatic parasitaemia, an indication of a negative epistatic effect between these Hb variants. Antibody levels against non-PfEMP1 antigens were slightly higher among HbAS children, but quite similar in all study groups, indicating differences in parasite exposure.

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Section: Discussionsupporting

confidence: 93%

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

Lamptey¹,

Seidu²,

Lopez-Perez³

et al. 2023

Front. Hematol.

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Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1–Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C

Oleinikov,

Seidu,

Oleinikov

et al. 2023

The Journal of Infectious Diseases

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Protective immunity to malaria is mainly antibody-mediated and members of the PfEMP1 family are important targets. Abnormal display of PfEMP1 on the infected erythrocytes (IEs) surface and reduced cytoadhesion have been demonstrated in HbAS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of IgG specific for several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific IgG in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.

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The influence of hemoglobin C on Plasmodium falciparum parasite density

MOUSTAPHA,

YANSAMBOU,

AMADOU

et al. 2024

Preprint

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Malaria and sickle cell disease are public health problem in sub-Saharan Africa. We study the influence of hemoglobin type on parasite density in suspected sickle cell malaria patients in Maradi, Niger. This was a descriptive study with retrospective data collection between 2012 and 2023. Electrophoresis methods were used to determine the hemoglobin type and thick smear for the parasite density. This study involved 875 participants with a sex ratio of 1.06; their mean age was 14.25 years [02 months − 80 years]. Thick smear analysis of all participants revealed 52.91% positive, and the arithmetic mean of 242 p/uL (40 p/uL − 2600 p/uL). The most prevalent hemoglobin types were hemoglobin A (66.17%), following with hemoglobin S (29.14%) and hemoglobin C (3.66%). The geometric mean of the parasite density applied to the hemoglobin type shows that hemoglobin C (289.65 p/uL) and hemoglobin S (291.39 p/uL) stand out as being the highest. These results show that the differences in parasite density between hemoglobin A, hemoglobin S and hemoglobin C are statistically significant (p = 2.28x10− 59). Regression analysis showed that hemoglobin C had a significant positive influence (p = 0.029) on parasite density. The hemoglobin A2, hemoglobin F and hemoglobin S, did not have a statistically significant impact on parasite density. According to this study, person with predominant hemoglobin S and hemoglobin C have highest parasitemia than patients with predominant hemoglobin A type. It’s necessary to conduct others studies to determine the mechanism by how hemoglobin type affects parasite density in malaria.

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

Cited by 3 publications

References 35 publications

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1–Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C

The influence of hemoglobin C on Plasmodium falciparum parasite density

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