Aspects of pathogenesis of nontyphoidal Salmonella Bacteraemia in Malawian children : a study of pathogen virulence, antibiotic resistance and carriage

Lawrence Msefula, Chisomo
(2009) Aspects of pathogenesis of nontyphoidal Salmonella Bacteraemia in Malawian children : a study of pathogen virulence, antibiotic resistance and carriage. PhD thesis, University of Liverpool.

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Introduction: Multi-drug resistant (MDR) nontyphoid Salmonellae (NTS) enterica serovars Typhimurium (STM) and Enteritidis (SEN) are a major cause of bacteraemia in children and HIV-infected adults in Malawi. The aims of the investigations were to determine the relatedness and virulence of invasive NTS strains, and the mode of antibiotic resistance, and to assess the level of NTS carriage in healthy asymptomatic adults and children in the community and children admitted to hospital with NTS bacteraemia Methods: Pulse field gel electrophoresis (PFGE), plasmid purification, multilocus sequence typing, whole-genome sequencing, polymerase chain reaction and disk diffusion antibiotic-sensitivity testing were used to characterise NTS isolates. Standard microbiological techniques were used to isolate Salmonellae from stool and the oropharynx. Fitness of pre-2002 and post-2002 STM strains was measured using the serum-bactericidal assay, HEp 2 cell-invasion assay and competitive growth in mice and L8 broth. Results: 90% of STM isolates have one PFGE type and plasmid profile. There is no dominant PFGE and plasmid type among SEN strains. 90% (38/42) of STM strains tested belong to a novel sequence type, ST313. SEN strains belong to the worldwide-reported sequence type, ST11. MDR genes in STM strains are encoded on a large self-transferable virulence plasmid pSL T-8T. Chromosomal deletions and prophage insertions distinguish pre-2002 and post-2002 STM strains. There was no significant difference between pre-2002 and post-2002 STM strains in their capacity to invade HEp-2 cells, in their growth in mice and in their sensitivity to serum killing. An NTS carriage rate of 1.6% (13/824) was found in healthy individuals in the community. Stool and oropharyngeal NTS carriage rates in bacteraemic children were 52% and 36% during admission, 13.2% and 13.7% six weeks later in convalescence. Conclusion: The findings suggest that emergence of MDR among STM in 2002 in Blantyre was a result of the appearance of a new dominant 8TM strain and not acquisition of mobile genetic elements. The results further suggest reductive evolution in the dominant STM strain. There is possibly co-selection of virulence and antibiotic resistance in STM strains. The results also suggest that postbacteraemic children are the reservoir of invasive NTS in the community. A longitudinal study of NTS carriage in post-bacteraemic children in the community needs to be conducted.

Item Type: Thesis (PhD)
Depositing User: Symplectic Admin
Date Deposited: 20 Oct 2023 09:25
Last Modified: 20 Oct 2023 09:28
DOI: 10.17638/03174596
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