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

Sammarro, Melodie and Rowlingson, Barry and Cocker, Derek and Chidziwisano, Kondwani Regson and Jacob, Shevin T. and Kajumbula, Henry and Mugisha, Lawrence and Musoke, David and Lester, Rebecca and Morse, Tracy and Feasey, Nicholas and Jewell, Christopher P. (2022) Risk factors, temporal dependence, and seasonality of human ESBL-producing E. coli and K. pneumoniae colonisation in Malawi : a longitudinal model-based approach. Other. medRxiv, Cold Spring Harbor. (https://doi.org/10.1101/2022.08.11.22278326)

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Background Antimicrobial resistance (AMR) represents an important threat to achieving the sustainable development goals in Sub-Saharan Africa (sSA). sSA is reported to have the highest estimated death rate attributable to AMR, with Extended-Spectrum Beta-Lactamase-producing Enterobacterales, such as Klebsiella pneumoniae and Escherichia coli, representing the greatest challenge. However, the dynamics of human colonisation with such bacteria in the sSA community setting are not well known. Inadequate water, sanitation and hygiene (WASH) infrastructure and associated behaviours are thought to play an important role in transmission of AMR-bacteria, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of public health policies that interrupt transmission of AMR-bacteria. Methods and Findings In this 18-month study, individuals from households in diverse areas of Southern Malawi were recruited and human stool samples were longitudinally collected. 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 between timepoints. Important risk factors were identified, with men having a lower risk of becoming colonised with ESBL-producing E. coli (OR 0.786 CrI[0.678-0.910]) and the use of a tube well or a borehole as a water drinking source highly increasing the risk of becoming colonised (OR 1.550 CrI[1.003-2.394]). Coming into contact with standing water also appeared to be negatively associated with colonisation status (OR 0.749 CrI[0.574-0.978]). For ESBL-producing K. pneumoniae, having recently taken a course of antibiotics increased the risk of being colonised (OR 1.281 CrI[1.049-1.565]). We also found a negative association between eating from shared plates and colonisation with ESBL-producing K. pneumoniae (OR 0.672 CrI[0.460- 0.980]). Finally, we detected a temporal correlation range of eight to eleven weeks, providing evidence that within-household transmission occurs within this time frame. Conclusions We suggest that interventions aimed at preventing transmission might have the best impact when targeted at the household-level and focused on a combination of improving WASH infrastructure and modifying associated behaviours. Additionally, we showed that antibiotic use is important when looking at colonisation with ESBL-producing K. pneumoniae and therefore infection prevention and control measures and antibiotic use and stewardship training could help in reducing transmission.


Sammarro, Melodie, Rowlingson, Barry, Cocker, Derek, Chidziwisano, Kondwani Regson, Jacob, Shevin T., Kajumbula, Henry, Mugisha, Lawrence, Musoke, David, Lester, Rebecca, Morse, Tracy ORCID logoORCID: https://orcid.org/0000-0003-4185-9471, Feasey, Nicholas and Jewell, Christopher P.;