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Background Sub-Saharan Africa has the highest estimated death rate attributable to antimicrobial resistance (AMR), especially due to Extended-Spectrum Beta-Lactamase-producing Enterobacterales (ESBL-E). However, the dynamics of human colonisation in the community with ESBL-E are not well described. Inadequate water, sanitation and hygiene (WASH) infrastructure and associated behaviours are thought to play an important role in transmission of ESBL-E, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of future policies. Methods In this 18-month study, using microbiological data and household surveys, we built a multivariable hierarchical harmonic logistic regression model to identify risk factors for colonisation with ESBL-producing E. coli and K. pneumoniae, reflecting household structure and temporal correlation of colonisation status. Results Being male was associated with a lower risk of colonisation with ESBL-producing E. coli (OR 0.786 CrI[0.678-0.910]) whilst the use of a tube well or a borehole was associated with an increased risk (OR 1.550 CrI[1.003-2.394]). For ESBL-producing K. pneumoniae, recent antibiotic exposure increased risk of colonisation (OR 1.281 CrI[1.049-1.565]) while sharing plates decreased that risk (OR 0.672 CrI[0.460-0.980]). Finally, the temporal correlation range of eight to eleven weeks provided evidence that within-household transmission occurs within this time frame. Conclusions We describe different risks for colonisation with different enteric bacterial species. Our findings suggest interventions to reduce transmission targeted at the household-level need to focus on improving WASH infrastructure and associated behaviours, whilst at the community level they should focus on both environmental hygiene and antibiotic stewardship.

In sub-Saharan Africa (sSA), there is high morbidity and mortality from severe bacterial infection and this is compounded by antimicrobial resistance, in particular, resistance to 3rd-generation cephalosporins. This resistance is typically mediated by extended-spectrum beta lactamases (ESBLs). To interrupt ESBL transmission it will be important to investigate how human behaviour, water, sanitation, and hygiene (WASH) practices, environmental contamination, and antibiotic usage in both urban and rural settings interact to contribute to transmission of ESBL E. coli and ESBL K. pneumoniae between humans, animals, and the environment. Here we present the protocol for the Drivers of Resistance in Uganda and Malawi (DRUM) Consortium, in which we will collect demographic, geospatial, clinical, animal husbandry and WASH data from a total of 400 households in Uganda and Malawi. Longitudinal human, animal and environmental sampling at each household will be used to isolate ESBL E. coli and ESBL K. pneumoniae. This will be complimented by a Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) survey and structured observations to understand the contextual and psychosocial drivers of regional WASH practices. Bacterial isolates and plate sweeps will be further characterised using a mixture of short-,long-read and metagenomic whole-genome sequencing. These datasets will be integrated into agent-based models to describe the transmission of EBSL resistance in Uganda and Malawi and allow us to inform the design of interventions for interrupting transmission of ESBL-bacteria.