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Cocker, Derek (2022) An investigation into the role of human, animal and environmental factors on transmission of ESBL E. coli and ESBL K. pneumoniae in southern Malawian communities, Thesis (Doctoral), Liverpool School of Tropical Medicine.
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D Cocker PhD - Thesis Final.pdf - Accepted Version Download (7MB) | Preview |
Abstract
In sub-Saharan Africa (sSA) there is a high prevelance of gut colonisation with antimicrobial resistant (AMR) bacteria and a high morbidity and mortality from drug-resistant infections. Given the reliance on third generation cephalosporins (3GCs) in human health, two of the most important AMR bacteria found in these settings include the extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae, E. coli and K. pneumoniae. These bacteria are present in the guts of humans and animals and also within the wider environment. In LMICs, the key factors that lead to community ESBL colonisation are unclear, and I hypothesise that within low-income settings, ineffectual household water, sanitation and hygiene (WASH) practices and a paucity of WASH infrastructure contribute to ESBL contamination of the household environment and pollution of the riverine and community environment via inadequate management of faecal sludge. Interactions between humans, animals and environmental reservoirs of ESBL bacteria in these settings promotes the acquisition, maintenance and spread of ESBL E. coli and ESBL K. pneumoniae, ultimately resulting in increased levels of gut carriage of these drug resistant organisms. To that end, in this thesis I present the results from two observational studies undertaken in southern Malawi designed to broadly assess key One Health risks for human carriage of ESBL E. coli and ESBL K. pneumoniae in Malawian communities. Firstly , within a large household-centred study I found a paucity of household WASH infrastructure and access to materials to enable safe toileting, adequate sanitation or effectual hand-hygiene and waste management in urban, peri-urban and rural communities, paralleled by behavioural proxies that may increase the risk of bacterial transmission, such as household attitudes to water usage, foodhygiene, open defaecation, and handwashing. Microbiological surveillance of the households illustrated a staggeringly high prevalence of ESBL colonisation in humans and animals, alongside ESBL contamination of the household and broader environment (i.e. rivers and drains). Risk factor analysis highlighted the importance of the wet season alongside differences in WASH and animal factors between urban, peri-urban and rural settings that lead to differing AMR prevelance and regional risk profiles. Lastly, in addition to the high levels of ESBL bacteria found within the river networks, I identified elevated levels of antibiotics and other resistance driving chemicals within urban rivers, suggesting that the riverine system may be a key ecological niche for AMR in this setting. In summary, within this thesis, I highlight the key role that WASH infrastructure and behaviours play in driving human carriage of ESBL bacteria in communities of southern Malawi and identify key differences in risks of ESBL colonisation from urban, peri-urban and rural settings. Therefore, I propose that future interventions and policy designed to interrupt ESBL AMR transmission should adopt a One- Health approach, consider the integration of community-based WASH interventions, and be cognisant of regional differences in AMR-prevalence, making adaptions wherever possible which are tailored to the local population for maximal effect.
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