The genomic epidemiology of shigellosis in sub-Saharan Africa

Stenhouse, Georgina ORCID: 0000-0002-9681-9242 (2022) The genomic epidemiology of shigellosis in sub-Saharan Africa. PhD thesis, University of Liverpool.

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Abstract

Shigellosis is a leading cause of diarrhoeal death globally, though the highest prevalence is in low- and middle-income countries with the greatest disease burden falling on children under five years of age. Increasing antimicrobial resistance is a growing hindrance to ongoing effective treatment. Whole genome sequence analysis (WGSA) of the aetiological bacterial genus, Shigella, has been effectively used to better understand the pathogen and disease epidemiology, and antimicrobial resistance (AMR). Shigellae from sub-Saharan Africa has been relatively understudied using WGSA. This thesis reports the findings of three studies applying WGSA to sub-Saharan African Shigella at different population levels (hospital, national and sub-continent). This thesis finds, for the first time, a link between the HIV pandemic and Shigella evolution, with endemic strain diversification and successful introductions coinciding with the HIV epidemic in South Africa. While widespread MDR was confirmed across sub-Saharan Africa, an emergent, pan-susceptible S. flexneri 2a lineage was also identified in South Africa. The greater drug susceptibility of this lineage was found to be linked to the absence of the known MDR element the Shigella resistance locus (SRL). I also found new evidence to suggest that retention of the large virulence plasmid (pINV) is a hinderance to strain success in S. sonnei, which was found to vary between the identified South African sub-Clades. The results from the national study also confirm the ability for multiple S. flexneri strains to coexist while supporting the inability of S. sonnei strains to do likewise. Vaccine development is a current strategy to reduce shigellosis cases in the face of increasing AMR. Previously undetected strains from both serotypes were described in this thesis, highlighting the need for the global application of WGSA for Shigella. This work provides key insights for the tracking of AMR emergence and spread, and effective Shigella vaccine development and future deployment, issues critical for ongoing effective treatment of shigellosis both within sub-Saharan Africa and across the globe. The results also highlight the importance of considering disease dynamics in HIV+ populations and serotype transmission pathway preference when developing public healthcare policy aimed at reducing shigellosis.

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	19 Jan 2023 11:41
Last Modified:	19 Jan 2023 11:41
DOI:	10.17638/03167010
Supervisors:	Kate, Baker Miren, Iturriza-Gomára
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3167010