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dc.contributor.advisorBulimo, Wallace D.
dc.contributor.advisorOtieno, Micheal Frederick
dc.contributor.authorMaina, George Gachara
dc.date.accessioned2014-02-17T08:44:40Z
dc.date.available2014-02-17T08:44:40Z
dc.date.issued2014-02-17
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/8956
dc.descriptionDepartment of Medical Laboratory Sciences, 174p. 2013, RA 644 .V55M3en_US
dc.description.abstractIn April 2009, a novel influenza A virus was detected in Mexico and California. Thereafter, it spread globally to cause the first influenza pandemic of the 21st century. The virus was found to be antigenically unrelated to human seasonal influenza viruses but genetically related to viruses known to circulate in pigs. In view of its likely swine origin, it was initially referred to as ‘swine-origin influenza virus’ (S-OIV) A/H1N1, or pandemic influenza A (H1N1) 2009 virus but was later renamed by the World Health Organization as influenza A(H1N1)pdm09 virus. In its first year of circulation, the virus is estimated to have caused between 151,700 and 575,400 deaths globally. In Kenya, the virus was first detected in late June 2009 and in the next one year was the dominant virus in circulation. However, no laboratory confirmed deaths occurred in the country. The emergence and subsequent rapid global spread of this influenza virus provided a unique opportunity to observe the evolutionary dynamics of a pandemic influenza virus in Kenya, a tropical region where the virus circulates throughout the year. Understanding the evolution of influenza A(H1N1)pdm09 virus within the country is essential for studying global diversification, the emergence, spread and resistance of the viruses circulating in this region of the world, as well as determining the genetic relationships among the Kenyan strains and vaccine strains. The aim of this study therefore was to reconstruct the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Kenya during its first year of circulation. To accomplish this, the study undertook whole genome Sanger sequencing of 40 influenza A(H1N1)pdm09 virus isolates sampled nationwide during the pandemic period. To understand the evolutionary dynamics of the local A(H1N1)pdm09 viruses, the study employed the Bayesian evolutionary framework to analyze the resulting 320 individual gene sequences and the 40 complete genomes and compared them with sequences from two African countries, UK, USA and China isolated during the same period. The phylogenetic analyses showed that all of the Kenyan sequences sampled in the pandemic period grouped into at least four highly significant clusters and were interspersed with isolates from other countries. Two global clades (2 and 7) were identifiable within the first two weeks of the pandemic in Kenya, with clade 7 undergoing further diversification while clade 2 was not detected beyond the introductory foci. The time of the most recent common ancestor of the strains circulating in Kenya was estimated to be between April and June 2009, two months before the first laboratory confirmed case. High evolutionary rates and fast population growths was also observed. Progressive drift away from the vaccine strain was observed at both the nucleotide and amino acid level, with 2010 strains clustering separate from 2009 strains. A few unique clusters of amino acid changes were identified among all gene segments in the course of the pandemic, but no mutations previously associated with increased virulence were detected. The local strains were shown to be sensitive to neuraminidase inhibitors but resistant to adamantanes. Overall, results from this study indicate that two clades of influenza A(H1N1)pdm09 virus were introduced in Kenya and that the pandemic was sustained by multiple importations. They also indicate that clade 7 viruses dominated local transmission with an efficient community spread that was devoid of any spatial patterns but a progressive genetic drift was evident. In conclusion, adaptive evolution and viral migration seem to play a vital role in shaping the evolutionary dynamics of local A(H1N1)pdm09 viruses.en_US
dc.description.sponsorshipKenyatta Universityen_US
dc.language.isoenen_US
dc.titleMolecular Epidemiology and Evolution of Influenza A(H1N1) pdm09 Virus in Kenyaen_US
dc.typeThesisen_US


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