Risk factors, temporal dependence, and seasonality of human ESBL-producing E. coli and K. pneumoniae colonisation in Malawi: a longitudinal model-based approach

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