Drivers of Resistance in Uganda and Malawi (DRUM): a protocol for the evaluation of One-Health drivers of Extended Spectrum Beta Lactamase (ESBL) resistance in Low-Middle Income Countries (LMICs)

Abstract

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.

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

“…The reason for the regional variation is uncertain. Chikwawa being the rural area of the study [14], participants may have encountered more often organisations such as non-governmental organisations that might have been able to offer them treatment or antibiotics, or participants might have had increased access to antibiotics due to the greater presence of animal farming [26]. This emphasizes the importance of antimicrobial exposure in driving ESBL colonisation, thus highlighting the need for a more responsible antibiotic consumption.…”

“…DRUM was a repeated-measures study in which individuals, clustered into households, were sampled at four timepoints over 6 months. The detailed protocol is available at [14].…”

“…Stool samples from participants were cultured for growth of ESBL-producing bacteria on ESBL CHROMagar™ chromogenic agar (CHROMagar™, France). Bacterial colonies were classified by colour into categories, and speciation of blue colonies took place to identify ESBL-producing K. pneumoniae using polymerase chain reaction (PCR) as previously described in [14]. Throughout this paper, colonisation refers to asymptomatic carriage of either of these pathogens.…”

Investigating risks for human colonisation with extended spectrum beta-lactamase producing E. coli and K. pneumoniae in Malawian households: a one health longitudinal cohort study

“…Between May 2018 and October 2020 we aimed to recruit 300 households, 100 in each of Ndirande (urban), Chileka (peri-urban) and Chikwawa (rural) in the Southern region of Malawi using GPS coordinates derived via an inhibitory with close pair spatial design to avoid systematic biases (see (10) for detailed protocol). These study sites were included to enable variations in environmental health practices, animal practices, antibiotic usage (ABU), and contamination with ESBL-producing bacteria to be contrasted.…”

“…In parallel, observational checklists were completed, documenting key environmental health and household sanitation practices. Lastly, at each visit, up to 20 microbiological samples were taken, inclusive of human stool, animal stool and a broad range of environmental sites (See (10) for details).…”