Jun 19 – 22, 2024
Squamish, BC, Canada
Canada/Pacific timezone
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UNMASKING THE EVOLUTIONARY DYNAMICS OF G1P[8] ROTAVIRUSES TO ELUCIDATE REASONS FOR THE DISAPPEARANCE OF G1P[8] STRAINS IN BLANTYRE, MALAWI

Not scheduled
20m
Squamish, BC, Canada

Squamish, BC, Canada

Poster Phylodynamics & phylogeography

Speaker

Mr Chimwemwe Mhango (Malawi-Liverpool-Wellcome programme)

Description

Background: G1P[8] rotaviruses consistently circulated in Malawi from 1997 to 2019. They represent genogroup I and normally possess a Wa-like genetic backbone. However, the majority of G1P[8] strains that circulated between 2013 and 2014 in Blantyre, Malawi soon after the introduction of Rotarix® rotavirus vaccine, exhibited a DS-1-like genetic backbone more common of genogroup II rotaviruses. Here we conducted a whole genome sequencing (WGS) study to determine the phylodynamics of G1P[8] post 2014 as well as elucidate reasons behind their disappearance in 2019.

Methods: We recruited under-five children presenting with acute gastroenteritis at Queen Elizabeth Central Hospital. We systematically sampled and generated WGS for G1P[8] strains (n=84) that circulated from 2015 to 2019 in Blantyre. We used time-resolved phylogenetic analysis and Maximum likelihood trees to define clades and explore phylogeographical distribution respectively. Haplotype inference was used to estimate the population genetic diversity.

Results: WGS revealed that the G1P[8] (n=82) strains had the G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 while two strains had the G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1 genotype constellations. Genome segment time-resolved phylogenetic analysis revealed new clusters L4 and L5, genetically distinct from L1, L2 and L3 previously described to circulate in Malawi from 1997 – 2014. Phylogeographic analysis revealed a monophyletic cluster between L4 strains to contemporary G1P[8] strains characterised in Mozambique and India. Phylogenetic networks suggest both inter- and intragenogroup reassortment events contributed to the genetic diversity of G1P[8] strains post 2014. Haplotype inference of the VP7 and VP4 genome segments of G1P[8] strains revealed a wider genetic diversity within these segments before vaccine introduction compared to post-vaccine strains.

Conclusion: Malawian G1P[8] strains reverted from a DS-1-like to a Wa-like genotype constellation after 2014. Our work uncovered addition clusters L4 and L5 from 2015 to 2019. Our findings suggest cross-border introduction and reassortments events as major drivers of diversity. Our data suggest reassortment events and reduced genetic diversity led to the disappearance of G1P[8] in 2019.

Primary author

Mr Chimwemwe Mhango (Malawi-Liverpool-Wellcome programme)

Co-authors

Mr End Chinyama (Malawi-Liverpool-Wellcome Program) Mr Francis Dennis (Department of Electron Microscopy and Histopathology, Noguchi Memorial Institute for Medical Research, University of Ghana.) Prof. Benjamin Kumwenda (Department of Biomedical Sciences, School of Life Sciences and Allied Health Professions, Kamuzu University of Health Sciences, Blantyre, Malawi.) Dr Celeste Donato (Enteric Diseases Group, Murdoch Children’s Research Institute, 50 Flemington Road, Parkville, Melbourne 3052, Australia.) Mr Valantine Ndze (Faculty of Health Sciences, University of Buea, P.O Box 63, Buea, Cameroon.) Prof. A. Duncan Steele (Diarrheal Pathogens Research Unit, Sefako Makgatho Health Sciences University, Medunsa 0204, Pretoria, South Africa.) Prof. Arox Kamng'ona (Department of Biomedical Sciences, School of Life Sciences and Allied Health Professions, Kamuzu University of Health Sciences, Blantyre, Malawi) Prof. Nigel Cunliffe (NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, United Kingdom.) Mr Martin Nyaga (Next Generation Sequencing Unit and Division of Virology, Faculty of Health Sciences, University of Free State, Bloemfontein 9300, South Africa) Dr Chrispin Chaguza (Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA;) Dr Khuzwayo Jere (NIHR Health Protection Research Unit in Gastrointestinal Infections, University of Liverpool, United Kingdom.)

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