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Title: Fetal haemoglobin and malaria
Author: Pasvol, Geoffrey
ISNI:       0000 0001 1570 9002
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1978
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The inherited disorders of human haemoglobin are very common in some populations. Relative protection afforded to heterozygous carriers of these conditions against P. falciparum malaria is a likely cause for these high gene frequencies. However, very little is known at the cellular level of how this protective effect works. As an approach to this problem, an in vitro culture technique was developed in order to examine the factors which might modify the interaction of P. falciparum with human red cells. Fetal haemoglobin was of particular interest as a means of protection, since young infants, who are known to have high levels of this haemoglobin, are relatively resistant to P. falciparum. Furthermore, there is increasing evidence that infants heterozygous for thalassaemia and other haemoglobinopathies have higher levels of fetal haemoglobin than expected during the first year of life. A paucity of parasites was observed in the fetal haemoglobin-containing cells in young infants but this was shown to be due to the predilection of the parasite for metabolically young cells. Fetal haemoglobin was shown to have no effect on the rates of invasion of parasites into cells from a variety of conditions. However fetal haemoglobin caused significant retardation of growth once the parasite had entered the cell. This effect was independent of cell age. Further findings indicated that in the sickling disorders and glucose-6-phosphate dehydrogenase deficiency the red cell provided an unfavourable environment for the development of P. falciparum. This was not the case in thalassaemia and haemoglobin C and E traits. It was therefore suggested that these latter disorders have maintained their high frequencies due to the relatively high level of fetal haemoglobin which occurs in heterozygous carriers at an early stage in life, and protects them at an age when mortality from falciparum malaria is at its highest.
Supervisor: Weatherall, D. J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available