Browsing by Author "Oduma, Colins Okinyi"

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    Molecular analysis of p53 gene exon 7 codon 249 mutation in hepatocellular carcinoma patients presenting at Moi teaching and referral hospital, Kenya
    (Egerton University, 2019-04) Oduma, Colins Okinyi
    Hepatocellular carcinoma (HCC), a common type of liver cancer arising from progressive transformation of pre-cancerous dysplasia macronodules and hepatocytes is ranked as the fourth leading cause of death globally and a fifth cause of death in Africa. Several risk factors for HCC have been identified that include dietary and life style risks, significant genetic family history and predisposition to genetic mutation. It has been hypothesized that codon 249 of p53 gene is more susceptible to mutation induced by mutagenic and carcinogenic agents, increasing risk and/or progression of HCC. This study sought to identify mutation in codon 249 among HCC patients presenting with stage one cancer at Moi Teaching and Referral Hospital (MTRH), and to further determine the association of the mutation with the development of HCC. A total of forty six (46) archived blood samples for HCC patients and ten (10) controls were used in the study. DNA was extracted and purified from 200 uL aliquots of plasma and PCR amplified then sequenced using p53 exon 7 forward and reverse primers. Mutation detection and analysis were done using Molecular Evolutionary Genetics Analysis v.6.0 and ESPript v.3.0 softwares. The male to female ratio for both patients and controls was 1:1. The age range for HCC patients was from 25 to 67 years with a median of 42 years, and from 24 to 64 years with a median of 41 years for the controls. Guanine (G) - to - thymine (T) transversion in the third base of codon 249 of p53 gene was detected in plasma DNA from 8 of the 46 HCC patients and 1 of the 10 controls. There was no significant difference across gender among HCC subjects with and without mutation (p=0.4549) at 5% level of significance, however, there was a striking picture of significant existence of such mutation in a much older population in the HCC patients (p=<.0001) at 5% level of significance, suggesting that being in the old age is more susceptible to such mutation. There was no significant statistical association of codon 249 mutation between HCC patients and control (p=0.6821) at 5% level of significance. However, there was exaggerated increase in risk of acquiring codon 249 mutation among HCC patients (OR=0.5278: 95% CI 0.0584-4.7736). Consequently, although p53 gene codon 249 mutations has been found very minimal, its existence communicates a probable role in hepatocellular carcinogenesis. Nevertheless, the present study cannot exclude the possibility that mutation in codon 249 may act at later stages of hepatocellular carcinogenesis. This study warrants supplemental cross sectional and longitudinal studies, using larger sample sizes with higher number of HCC patients presenting with different stages to observe pattern across stages.
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    Spatiotemporal Variation in Plasmodium Falciparum Transmission in Selected Sites in Western Kenya
    (Egerton University, 2023) Oduma, Colins Okinyi
    Asymptomatic malaria infections are a threat to elimination of this vector-borne infectious disease. In many endemic regions, malaria transmission is seasonal. However, the impact of seasonality on Plasmodium falciparum (P. falciparum) gametocyte levels in peripheral blood and their transmission to local mosquito vectors are not well understood. Data describing these parasitological indices across regions of varying transmission intensity is scanty. In addition, malaria transmission can vary significantly over small geographic scales, but the drivers of this heterogeneity are not well understood. This study evaluated the impact of seasonality on P. falciparum transmission potential, trends in parasitological indices across areas of differential malaria transmission, and factors that might correlate small scale variation in transmission. Blood samples were collected from individuals living in Homa Bay County (low transmission) and Kisumu County (moderate transmission) in the dry season (n=1116) and rainy season (n=1743). In addition, blood samples were collected from approximately 150 individuals in each of 20 clusters in Busia County (high transmission) in rainy season. Blood samples were screened for P. falciparum parasites using quantitative polymerase reaction (qPCR) and microscopy. In Homa Bay and Kisumu the presence and density of blood gametocytes was measured by reverse transcription PCR (RT-qPCR). Differences in parasite and gametocyte densities across seasons were determined by unpaired t-test. Differences in the prevalence, proportion of submicroscopic and gametocyte positive infections across study sites were determined by χ2 test. A generalized linear mixed effect model was used to determine predictors of infections. Potential mosquito larval habitats and their number within 250 m of a household were determined by ArcMap. In Homa Bay and Kisumu, mean parasite densities did not differ in dry versus rainy season (P=0.562). Gametocyte densities were 3-fold higher in the rainy than dry season (rainy: 3.46 transcripts/uL blood, dry: 1.05 transcripts/uL, P<0.001). Parasite prevalence and densities, and gametocyte prevalence and densities were highest in the high transmission region. In contrast, the proportion of asymptomatic submicroscopic infections was highest in the low transmission region. Proportion of gametocyte positive infections did not differ across transmission intensities. In Busia County, across the 20 clusters, 3-folds and 4-folds variation in parasites prevalence by qPCR and microscopy respectively was observed. Three to 34 larval habitats per cluster, and 0-15 habitats within a 250m radius around households were observed. Low altitude, kitchen located indoors, open eaves, a lower level of education of the household head, younger age, and being male were significant predictors of higher prevalence. The number of habitats and their proximity to households was not a predictor for prevalence. In conclusion, parasites increase their investment in transmission in the rainy season, reflected by higher gametocyte densities. Seasonal changes of gametocytemia among infections need to be considered when designing malaria control measures. Pronounced variation in prevalence at small scales and the determinants need to be considered for malaria surveillance and control.