Phylodynamic analysis of re-emergent G3 rotavirus strains in Blantyre, Malawi

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Date
2022-08-17
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Kamuzu University of Health Sciences
Abstract
Study type: Retrospective study Problem: Malawi has experienced the re-emergence of genotype G3 rotavirus strains 6 years after the introduction of Rotarix rotavirus vaccine into the national immunization program in October 2012. Genotype G3 strains were previously detected in 1999, approximately 17 years before the current re-emergence in November 2017. By 2019, genotype G3 had become the predominant genotype causing acute gastroenteritis among under five children in Blantyre, Malawi. It is however, not known how these genotype G3 strains re-emerged in Malawi as wel as how effective the currently used vaccine would be against the genotype G3 strains. Main objective: To investigate the phylodynamic of re-emerging “G3” rotavirus strains in Malawi through whole genome analysis. Specific objectives 1 To describe the complete genotype constellations of G3 rotavirus strains circulating in Malawi. 2 To identify lineages among G3 rotavirus strains circulating in Malawi. 3 To determine the relationship between global and Malawian G3 rotaviruses. 4 To estimate time to most recent common ancestor for G3 rotaviruses in Malawi. 5 To compare the structural conformation of neutralizing epitopes of G3 rotaviruses to RV1’s G1P[8] strain. Methodology The study will utilise already generated sequences of genotype G3 positive rotavirus specimens that were isolated from under-five children recruited for the diarrhea surveillance project. Convenient sampling was used to sample at least one representative genotype G3 strain per calendar month from November 2017 to August 2019 for whole genome sequencing. 27 representative whole genomes of genotype G3 strains passed the final quality control after the whole genome sequencing and will be utilized in this study. In addition, whole genomes of 3 representative genotype G3 strains that circulated from 1997 to 1999 will also be included in the analysis. To understand how these strains emerged, maximum likelihood analysis will be used to generate phylogenetic trees with globally circulating G3 strains to determine the origins. In addition to that, protein modelling will be used to assess vaccine effectiveness against the emerging January G3 strains. Expected Findings and Dissemination of Results The study will uncover the precise origins of the G3 rotavirus strains as well as assess predict whether the current vaccine will be effective against the emerging strains. The findings of this study will be disseminated through national and international conferences as well as peer reviewed journals. A detailed report of the project will be submitted to COMREC while a detailed thesis compiling everything that will be done as well as the results and implication of this work will be submitted to the College of Medicine library for future references.
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Phylodynamic analysis of re-emergent G3 rotavirus strains
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