The epidemiology of paediatric diarrhoeal disease and Shigella infections in Ho Chi Minh City, Vietnam.

Shigella is an enteric pathogen that is the most common bacterial cause of dysentery globally, most frequently infecting children in developing countries. Resistance to common antimicrobials is now widespread and is beginning to make the management of this often-severe infection very challenging. Vaccination offers a realistic option for preventing and controlling shigellosis, yet several critical questions need to be answered before a successfully licensed vaccine can be introduced. Ho Chi Minh City (HCMC), in Vietnam, is a rapidly industrialising urban setting with a high burden of paediatric diarrhoeal disease and is representative of many similar regions globally. Through the structure of a community cohort, the incidence of diarrhoeal disease in children under the age of five in HCMC was found to be 70/100 child years, indicating that diarrhoea remains a significant cause of paediatric morbidity in this location. Furthermore, children living at low elevation in the centre of the city were found to be at increased risk of reported diarrhoeal disease during periods of higher temperature and flooding, highlighting a particular community at risk. This work also documents Shigella as a common cause of dysentery in both hospital and the community in HCMC, with community-based incidence estimated to be 1.5/100 child years in 2-5 year olds. Resistance against a variety of antimicrobials in Shigella was detected, and organisms harbouring mutations against fluoroquinolone activity were found to survive for longer periods in the presence of ciprofloxacin in vitro, suggesting a potential epidemiological advantage against sensitive strains. Finally, the half-life of maternal immunity against the O-antigen of S. sonnei was found to 43 days and by five months of age less than half of children in HCMC have any circulating maternal protection. Work from this thesis will help inform future vaccine rollout efforts and fills important gaps in the current literature surrounding this increasingly challenging infection.