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Title: Red blood cell polymorphisms and their associations with malaria and other nonmalaria related diseases in Kilifi, Kenya
Author: Opi, Daniel Herbert
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2013
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The high morbidity and mortality associated with malaria has exerted considerable pressure on the human genome, selecting for polymorphisms thought to confer a survival advantage against severe and fatal malaria. The strongest protection is seen with HbAS and a+thalassaemia, offering up to 90% and 60% protection against severe malaria respectively. However, co-inheritance of these conditions, due to their geographical overlap, results in a negative interaction with their independent protection against malaria being lost. Through a series of in -vitro experiments, I show that this can be explained through the mechanism of cytoadherence. While Plasmodium Jalciparum infected HbAS and a+thalassaemia RBCs bound less well to endothelial receptors independently, this advantage was lost with co-inheritance of both conditions, a fact, however, not explained by changes in rosetting, PfEMPl or knob expression. The Sl2 and MCCb alleles of the Knops blood group system and blood group 0 of the ABO system occur at high frequencies in malaria endemic populations. However, sparse evidence is available on the protection they confer against malaria and biological mechanisms responsible. Using a series of epidemiological and clinical studies from Kilifi, I show that while Sl2 protects ag~inst cerebral and fatal malaria, MCCb increased susceptibility to both. MCCb is therefore under selection from nonmalaria related forces seen with its protection against lower respiratory tract infections and gastroenteritis. These associations with severe malaria could not be explained through the mechanisms of rosetting or cytoadherence. Non-O blood groups were associated with increased susceptibility to severe malarial anaemia and fatal malaria while protecting against several common non-malaria related diseases. While rosetting plays a role in these malaria related outcomes cytoadherence does not seem to be important. Finapy, I found that age, a+thalassaemia and the Knops blood group antigens . influence RBC CRi expression. Additionally, CRi deficiency is common in Kilifi, "associated with reduced rosetting.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available