Key environmental exposure pathways to antimicrobial resistant bacteria in southern Malawi: A SaniPath approach.

Antimicrobial resistance (AMR) poses a severe global health threat, yet the transmission pathways of AMR within communal public environments, where humans and animals interact, remain poorly explored. This study investigated AMR risk pathways, prevalence, and seasonality of extended-spectrum ß-lactamase (ESBL) producing E. coli and K. pneumoniae, and observed practices contributing to environmental contamination within urban, peri-urban, and rural Malawi. Using the SaniPath tool, in August 2020, transect walks across three Malawian study sites identified potential AMR exposure pathways, including drains, standing water, soil, and areas of communal hand contact. Subsequently, from September-2020 to August-2021, 1440 environmental samples were collected at critical points along exposure routes (n = 40/month from each site). These underwent microbiological analysis using chromogenic agar techniques to detect the presence of ESBL E. coli and ESBL K. pneumoniae. Results showed the highest ESBL prevalence in urban environments (68.1 %, 95%CI = 0.64-0.72, p < 0.001) with a higher ESBL presence seen in drains (58.8 %, 95%CI = 055-0.62, p < 0.001) and soil (54.1 %, 95%CI = 0.46-0.62, p < 0.001) compared to other pathways. Environmental contamination was attributed to unavailability and poor condition of sanitation and hygiene infrastructure based on key informant interviews with community leaders (n = 9) and confirmed by independent observation. ESBL prevalence varied between seasons (χ2 (2,N = 1440) = 10.89, p = 0.004), with the highest in the hot-dry period (55.8 % (n = 201)). Prevalence also increased with increased rainfall (for ESBL E.coli). We highlight that community environments are likely to be a crucial component in AMR transmission, evident in the abundance of ESBL bacteria in identified exposure pathways. Additionally, poor sanitation infrastructure and practices coupled with seasonal dynamics further affect the presence of ESBLs in communal environments. Therefore, a context appropriate whole system approach that tackles infrastructure and behavioural factors, supported by effective surveillance is required to impact AMR and a range of aligned development challenges in these settings.

Investigating One Health risks for human colonisation with extended spectrum ß-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 ß-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 (41·8%) of 2845 samples of human stool, 290 (29·8%) of 973 samples of animal stool, 339 (66·2%) of 512 samples of river water, and 138 (46·0%) 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 1·66, 95% credible interval 1·38-2·00), living in urban areas (2·01, 1·26-3·24), advanced age (1·14, 1·05-1·25), and living in households where animals were observed interacting with food (1·62, 1·17-2·28) or kept inside (1·58, 1·00-2·43). Human ESBL-producing K pneumoniae colonisation was associated with the wet season (2·12, 1·63-2·76). 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. FUNDING: Medical Research Council, National Institute for Health and Care Research, and Wellcome Trust. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.