| Abstract | Background: The alpha+-thalassaemias are the most common monogenic disorders of humans, characterised by microcytic and hypochromic anaemia. heir high frequency reflects selective advantage against death from Plasmodium falciparum malaria. The most common type of alpha+-thalassaemia amongst people of African descent is the -α3.7 deletional type and affects 26-33% of Ghanaians. Plasmodium falciparum malaria is a major cause of mortality amongst children in sub-Saharan Africa. Unlike HbAS, HbAC and G6PD deficiency there remains debate about whether alpha+-thalassaemia protects against malaria and the mechanism for the protection.
Methods: 1672 children of ≤10 years were recruited and individuals with G6PD deficiency, HbAC and Hb AS reported to protect against malaria were excluded. 732 children with Plasmodium falciparum were tested for Hb, RBC, MCV, MCH and parasite density. The subjects were then categorised into normocytic and microcytic using a cut off MCV value of 76fL and normochromic and hypochromic using a cut off MCH value of 25 pg.
Microcytic hypochromic individuals were genotyped by Polymerase Chain Reaction for the -α3.7 deletional thalassaemia mutation. Results: The frequency of Plasmodium falciparum malaria in the studied population was 54.1%. There was a frequency of 21.0% for the heterozygous (-α/αα) and 8.3% for the homozygous (-α/-α) alpha+-thalassaemia, resulting in a carriage rate (α/αα & -α/-α) of 29.3%. Among the microcytic patients, geometric mean parasite density (GMPD) values were lower in the presence of an alpha+thalassaemia genotype (-α/αα GMPD 9015, n=126 and -α/-α GMPD 6852, n=49) compared to normal genotype (αα/αα GMPD 51794, n=358) (p<0.001).
Severe malaria (GMPD ≥100000/μL) was less prevalent in microcytic patients with an alpha+-thalassaemia genotype (-α/αα 11.9% and -α/-α 16.3%) than either normocytic patients or microcytic patients with a normal genotype (32.9% and 53.6% respectively) (p<0.03). GMPD values were lower in hypochromic alpha+-thalassaemia genotypes (-α/αα GMPD 1728, n=44 and -α/-α GMPD 7160, n=23) compared to normal genotype (αα/αα GMPD 48997, n=141) (p<0.001), and individuals with Hb > 5 g/dL had lower GMPD compared to the severely anaemic (Hb ≤ 5 g/dL) (p<0.001). The differences in severe Plasmodium falciparum parasitaemia as well as the GMPD between children ≤ 60 and > 60 months for both the homozygous and heterozygous alpha+-thalassaemia were not significant at p=0.399 and p=0.207 respectively. Conclusion: The severity of Plasmodium falciparum parasitaemia measured, as either GMPD or prevalence of severe parasitaemia was significantly lower in both the -α/αα and -α/-α- groups compared to microcytic individuals with normal genotype. Even though GMPD differed significantly amongst all alpha+-thalassemia genotypes, it was not driven by hypochromasia. Among the homozygous and heterozygous alpha+-thalassaemias, children with severe anaemia had a significantly high GMPD than their counterparts who were not severely anaemic making them more susceptible to severe malaria anaemia. No loss of protection was seen in children younger or older than 60 months and therefore the protective effect from severe malaria might not wane with age.
The mechanism of protection from severe Plasmodium falciparum malaria is not clear, however the influence of microcytosis and hypochromasia on parasite density requires more research. |
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