Browsing by Author "Kusi, Stephen"

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    Detecting and quantifying plasmodium falciparum in blood and tonsils: towards an understanding of malaria-related oncogenesis
    (2013-12-18) Kusi, Stephen
    Epidemiological evidence strongly implicates chronic Plasmodium falciparum infection in the aetiology of endemic Burkitt’s lymphoma, although the role of malaria is still not well understood. A characteristic feature of this tumour is a chromosomal translocation in which a pro-cancer gene, MYC, is juxtaposed to the promoter region of the immunoglobulin heavy chain gene, leading to the uncontrolled growth of B-lymphocytes. This study was designed to test whether the malaria parasite actually resides in tonsils and can directly cause DNA damage which could then predispose to the Burkitt’s lymphoma translocation. Three methods of diagnosis, namely microscopy, rapid diagnostic test (RDT) and qPCR, were used to detect and quantify P. falciparum in blood and tonsils obtained from tonsillectomy patients. Interestingly, parasitemia was detected in tonsils by all three methods, even in cases where parasitemia was negative with whole blood. Comet assay was then performed for each sample to estimate DNA damage. DNA damage was assessed in terms of tail DNA, tail length and tail moment. Consistent with the hypothesis, student t-tests revealed significant differences in DNA damage between low- and high-probability parasitemia samples by all three comet parameters assessed (p-values 0.0266, 0.0316 and 0.0389 respectively; alpha =0.05). These data demonstrate that P. falciparum is a potent mutagen and suggest that the parasite might directly cause the characteristic translocation of endemic Burkitt's lymphoma.