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Title: Immunological mechanisms that determine why some African children develop severe malarial anaemia while others develop cerebral malaria in response to infection with Plasmodium falciparum
Author: Mandala, Wilson Lewis
ISNI:       0000 0001 3617 924X
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2007
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Introduction and Objectives: In Sub-Sahara Africa, malaria is an infectious disease caused mainly by Plasmodium falciparum. Most cases occur in children under five years of age. About 98 percent of the children suffer only from uncomplicated malaria (UCM) but a minority develop life-threatening severe malaria. Severe malaria encompasses three clinical syndromes; cerebral malaria (CM), severe malarial. anaemia (SMA) and severe respiratorY distress (SRD). The underlying reasons for this disparity are ·still unknown. The objective of this study was to investigate the immunological mechanisms that determine why some children develop CM while others develop SMA when infected with P. falciparum. Materials and Methods: Leucocyte and lymphocyte subsets were determined in Malawian children aged between 6 months and 5 years presenting with UCM, SMA and CM and in healthy controls. Activation and memory status of different cells were also determined. Sera Th1 and Th2 cytokines and percentages of cytokine-producing cells were measured for all groups. Results: CM patients were characterised by transient pan-lymphopenia, neutrophilia and thrombocytopenia while SMA patients were characterised by lymphocytosis. Interestingly, the percentage of T regulatory cells was lower in acute SMA patients compared to acute CM patients. Lymphocytes from CM patients were more activated and had a higher proportion with a memory phenotype compared with those from SMA patients, but monocytes in both groups showed a lack of activation markers. The sera of CM patients contained higher concentrations of both Th1 and Th2 cytokines. Surprisingly, CM patients had lower percentages of TNF-u, IFN-y and IL-2producing CD4+, CD8+ and yo T cells and NK cells compared to controls, whereas SMA patients had higher percentages of cytokine-producing lymphocyte subsets compared to controls. Both CM and SMA patients had low percentages of TNF-u and IL-6 producing monocytes compared to controls, but recovery of function was quicker in CM patients. Conclusion: Children with CM and SMA have cytokine profiles and lymphocyte activation and memory phenotypes which are consistent with the hypothesis that CM is a result of immunopathological response while SMA is a result of a na'ive response to the malaria infection. However, the panlymphopenia and apparently low proportion of cytokine-producing lymphocytes and monocytes in the CM group do not fit this hypothesis and require further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available