An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana

Opoku-Okrah, C. 2012. An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana. PhD thesis University of Westminster School of Life Sciences

TitleAn investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana
TypePhD thesis
AuthorsOpoku-Okrah, C.
Abstract

Background: The alpha+-thalassaemias are the most common monogenic

disorders of humans, characterised by microcytic and hypochromic anaemia.

Their 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.

YearApr 2012
FileClement_OPOKU-OKRAH.pdf
Publication dates
CompletedApr 2012

Related outputs

An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana
Opoku-Okrah, C., Gordge, M.P., Kweku Nakua, E., Abgenyega, T., Parry, M., Robertson, C.E. and Smith, C.L. 2014. An investigation of the protective effect of alpha+-thalassaemia against severe Plasmodium falciparum amongst children in Kumasi, Ghana. International Journal of Laboratory Haematology. 36 (1), pp. 62-70.

Alpha thalassaemia and the severity of Plasmodium falciparum infection in microcytic children from the Ashanti region of Ghana
Opoku-Okrah, C., Smith, C.L., Gordge, M.P., Parry, M., Robertson, C.E., Abgenyega, T. and Nakua, E. 2012. Alpha thalassaemia and the severity of Plasmodium falciparum infection in microcytic children from the Ashanti region of Ghana. British Society for Haematology 52nd meeting. Glasgow 16-18 April 2012

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