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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.

Background: Neonatal sepsis causes morbidity and mortality in sub-Saharan Africa. Antimicrobial resistance exacerbates outcomes. Poor Infection Prevention and Control practices (IPC) by healthcare workers and caregivers drive infection transmission. The Chatinkha Neonatal Unit in Malawi has experienced Klebsiella pneumoniae outbreaks of neonatal sepsis. We aimed to identify barriers to optimal IPC, focusing on hand hygiene. Methods: We used a focused ethnography to meet the study aim. Combining participant observation over a seven-month period with semi structured interviews with health care workers and patient carers (23) to provide an in-depth understanding of activities relating to hygiene and IPC existing on the ward. To analyse the data, we drew on the framework approach. Results: We found that staff and caregivers had a good understanding and recognition of the importance of ideal IPC, but faced substantial structural limitations and scarce resources, which hindered the implementation of best practices. We present two key themes: (1) structural and health systems barriers that shaped IPC. These included scarce material resources and overwhelming numbers of patients meant the workload was often unmanageable. (2) individual barriers related to the knowledge of frontline workers and caregivers, which were shaped by training and communication practices on the ward. We highlight the importance of addressing both structural and individual barriers to improve IPC practices and reduce the burden of neonatal sepsis in resource-limited settings. Conclusion: For IPC to be improved, interventions need to address the chronic shortages of material resources and create an enabling environment for HCWs and patient caregivers.

Background: The Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW) has undertaken sentinel surveillance of bloodstream infection and meningitis at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi for 20 years. Previously, three epidemics of Salmonella bloodstream infection have been identified. Here we provide updated surveillance data on invasive non-typhoidal Salmonella disease from 2011 – 2019. Methods: Surveillance data describing trends in invasive non-typhoidal Salmonella disease and associated antimicrobial susceptibility profiles are presented for the period January 2011 – December 2019. Results: Between January 2011-December 2019, 128,588 blood cultures and 40,769 cerebrospinal fluid cultures were processed at MLW. Overall, 1.00% of these were positive for S. Typhimurium, 0.10% for S. Enteritidis, and 0.05% positive for other Salmonella species. Estimated minimum incidence of invasive non-typhoidal Salmonella (iNTS) disease decreased from 21/100,000 per year in 2011 to 7/100,000 per year in 2019. Over this period, 26 confirmed cases of Salmonella meningitis were recorded (88.5% S. Typhimurium). Between 2011-2019 there was a substantial decrease in proportion of S. Typhimurium (78.5% to 27.7%) and S. Enteritidis (31.8% in 2011 to 0%) that were multidrug-resistant. Resistance to fluoroquinolones and third-generation generation cephalosporins (3GC) remained uncommon, however 3GC increased amongst Salmonella spp. and S. Typhimurium in the latter part of the period. Conclusions: The total number of iNTS bloodstream infections decreased between 2011-2019. Although the number multidrug resistance (MDR) S. Typhimurium and S. Enteritidis isolates has fallen, the number of MDR isolates of other Salmonella spp. has increased, including 3GC isolates.

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.

Background: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. Objectives: Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation. Methods: Studies included were prospective cross-sectional or cohort studies reporting gut mucosal ESBL-E colonisation in any population in sSA. We searched PubMed and Scopus on 18 December 2018. We summarise the range of prevalence across sites and tabulated risk factors for colonisation. The protocol was registered (Prospero ID CRD42019123559). Results: From 2975 abstracts we identified 32 studies including a total of 8619 participants from a range of countries and settings. Six studies were longitudinal; no longitudinal studies followed patients beyond hospital discharge. Prevalence varied between 5 and 84% with a median of 31%, with a relationship to setting: pooled ESBL-E colonisation in community studies was 18% (95% CI 12 to 28, 12 studies); in studies recruiting people at admission to hospital colonisation was 32% (95% CI 24 to 41% 8 studies); and for inpatients, colonisation was 55% (95% CI 49 to 60%, 7 studies). Antimicrobial use was associated with increased risk of ESBL-E colonisation, and protected water sources or water treatment by boiling may reduce risk. Conclusions: ESBL-E colonisation is common in sSA, but how people become carriers and why is not well understood. To inform the design of interventions to interrupt transmission in this setting requires longitudinal, community studies.

Background: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. Objectives: Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation. Methods: Studies included were prospective cross-sectional or cohort studies reporting gut mucosal ESBL-E colonisation in any population in sSA. We searched PubMed and Scopus on 18 December 2018. We summarise the range of prevalence across sites and tabulated risk factors for colonisation. The protocol was registered (Prospero ID CRD42019123559). Results: From 2975 abstracts we identified 32 studies including a total of 8619 participants from a range of countries and settings. Six studies were longitudinal; no longitudinal studies followed patients beyond hospital discharge. Prevalence varied between 5 and 84% with a median of 31%, with a relationship to setting: pooled ESBL-E colonisation in community studies was 18% (95% CI 12 to 28, 12 studies); in studies recruiting people at admission to hospital colonisation was 32% (95% CI 24 to 41% 8 studies); and for inpatients, colonisation was 55% (95% CI 49 to 60%, 7 studies). Antimicrobial use was associated with increased risk of ESBL-E colonisation, and protected water sources or water treatment by boiling may reduce risk. Conclusions: ESBL-E colonisation is common in sSA, but how people become carriers and why is not well understood. To inform the design of interventions to interrupt transmission in this setting requires longitudinal, community studies.

In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and antimicrobial resistance, burden of disease, information on antimicrobial use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC aims to strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC’s first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with finding more effective and creative uses of existing data and proxy measures, and linking such approaches to existing in-country capabilities. SEDRIC will also promote the translation of technological innovations into public health solutions.

In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and drug resistance, burden of disease, information on antibiotic use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC will strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC’s first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with the need for creativity in the use of existing data and proxy measures, and linking to existing in-country networking infrastructure. SEDRIC will also promote the translation of technological innovations into public health solutions.