Investigating One Health risks for human colonisation with extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Malawian households: a longitudinal cohort study

Background Low-income countries have high morbidity and mortality from drug-resistant infections, especially from enteric bacteria such as Escherichia coli. In these settings, sanitation infrastructure is of variable and often inadequate quality, creating risks of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales transmission. We aimed to describe the prevalence, distribution, and risks of ESBL-producing Enterobacterales colonisation in sub-Saharan Africa using a One Health approach. Methods Between April 29, 2019, and Dec 3, 2020, we recruited 300 households in Malawi for this longitudinal cohort study: 100 each in urban, peri-urban, and rural settings. All households underwent a baseline visit and 195 were selected for longitudinal follow-up, comprising up to three additional visits over a 6 month period. Data on human health, antibiotic usage, health-seeking behaviours, structural and behavioural environmental health practices, and animal husbandry were captured alongside human, animal, and environmental samples. Microbiological processing determined the presence of ESBL-producing E coli and Klebsiella pneumoniae, and hierarchical logistic regression was performed to evaluate the risks of human ESBL-producing Enterobacterales colonisation. Findings A paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites. A total of 11 975 samples were cultured, and ESBL-producing Enterobacterales were isolated from 1190 (41 center dot 8%) of 2845 samples of human stool, 290 (29 center dot 8%) of 973 samples of animal stool, 339 (66 center dot 2%) of 512 samples of river water, and 138 (46 center dot 0%) of 300 samples of drain water. Multivariable models illustrated that human ESBL-producing E coli colonisation was associated with the wet season (adjusted odds ratio 1 center dot 66, 95% credible interval 1 center dot 38-2 center dot 00), living in urban areas (2 center dot 01, 1 center dot 26-3 center dot 24), advanced age (1 center dot 14, 1 center dot 05-1 center dot 25), and living in households where animals were observed interacting with food (1 center dot 62, 1 center dot 17-2 center dot 28) or kept inside (1 center dot 58, 1 center dot 00-2 center dot 43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2 center dot 12, 1 center dot 63-2 center dot 76). Interpretation There are extremely high levels of ESBL-producing Enterobacterales colonisation in humans and animals and extensive contamination of the wider environment in southern Malawi. Urbanisation and seasonality are key risks for ESBL-producing Enterobacterales colonisation, probably reflecting environmental drivers. Without adequate efforts to improve environmental health, ESBL-producing Enterobacterales transmission is likely to persist in this setting.