| Abstract | Background: Inappropriate antibiotic prescribing and patient use are key antimicrobial resistance (AMR) drivers. Addressing both are critical to reduce AMR and protect healthcare systems. The World Health Organisation (WHO) AMR Global Action Plan highlights the need to increase surveillance in Low and Middle Income Countries (LMIC) to improve antimicrobial stewardship. This study builds on an earlier health systems research in Uganda, Malawi, and Zambia to measurably improve the quality of clinical care (QoC) and ABU, and to model AMR transmission drivers amongst bacteria. Research Question: Can regular surveillance of AMR and antibiotic use (ABU) in local health systems improve health workers’ prescribing practices and patients’ ABU leading to a lower AMR prevalence? Aims: To develop a metric and evidence use process for improving the management of childhood febrile illness in community settings. Objectives 1.Investigate associations of quality of care (QoC) in a sample of Health Care Facilities (HCF) with AMR to key antibiotics used for febrile illnesses in children 2. Assess the risk of AMR development through analysis of genomic traits from samples collected in study sites; determine future risk of resistance development 3. Use mixed methods to investigate community level health system drivers of ABU and AMR at the sub-district level with particular focus on febrile illnesses 4. Develop a rapid and recurrent surveillance system of ABU and AMR prevalence and of community voices in sub-districts for evidence-based improvement of health system strategies and policies. Methods: This study will be conducted in Uganda. The study will be conducted in urban, peri-urban and rural settings in Northern Uganda. The study focuses on febrile illness of children <5-years, the most common clinical presentation in sub-Saharan Africa. They are often empirically treated with antibiotics which risks spreading AMR. Whilst recommended, microbiological surveillance of AMR is unsustainable due to cost and logistical challenges. A more sustainable approach is to identify differences in AMR prevalence in geographical areas to understand and address local AMR drivers and improve ABU. We will develop a rapid assessment metric and evidence use process for AMR, ABU and QoC through 4 research packages (RP): RP1) Investigates ABU as a local AMR driver by adapting Lot Quality Assurance Sampling (LQAS) to rapidly assess maternal and clinician ABU for febrile children in urban, peri-urban, and rural areas per country with a minimum sample in each area of n=44 febrile children. We will assess the clinician-patient dyad for each sampled case for QoC and ABU using a Rapid Health Facility Assessment tool. RP2) Uses LQAS for microbiological surveillance to detect areas with >20% AMR prevalence in a minimum of n=44 nasal and rectal swabs of febrile children (α<0.044, β<0.0675). We will validate results with a minimum sample of n=240 measuring AMR prevalence. Swabs will be cultured on chromogenic agar containing appropriate antibiotics for Methicillin Resistant Staphylococcus Aureus (MRSA) (nasal) and Extended Spectrum Beta-Lactamase (ESBL)-producing enterobacteriacieae. Selected resulting isolates will be whole genome-sequenced, providing contemporary AMR profiles of bacteria enabling informed decisions for ABU based on circulating resistance genes and associated mobile genetic elements. RP3) Assesses drivers of ABU using mixed methods at community. A probability household survey in each area (n>95, max.95%CI ±0.10) measures service coverage, ABU and treatment seeking. Ethnographic approaches in a sequential explanatory design explain 1) RP1 and household survey results, 2) how people make sense of health, illness, and antibiotics, and 3) serves as a resource for community-driven solution development to address ABU. In the area with the worst QoC score in each country, we will conduct 12 In-Depth Interviews (IDIs) (6 clinicians, 6 pharmacists); 1 Community Dialogue (CD) comprising 3 break-out groups (10-12 fathers, 10-12 mothers and health care providers); and 6 Key Informant Interviews (KII) (3 traditional healers/herbalists, 3 community leaders). RP4) We will support intervention development using the CD approach in combination with national and district stakeholder engagement using the RAPID Outcome Mapping Engagement and Policy-Influence approach. Ethnographic non-participant observation of the engagement, result analysis and intervention development process will lead to a deeper understanding of the strategy development process. |
| Where does this project lie in the translational pathway? | T2 - Human /Clinical Research,T3 - Evidence into Practice ,T4 - Practice to Policy/Population |
| Expected Outputs | This study will develop a metric that health systems in LMICs will use recurrently for AMR and ABU surveillance. The study is expected to generate at least three publications by the applicant and several others through collaboration with partners in the consortium. The overall impact of the study is improved use of antibiotics and a reduced prevalence of AMR. |
| Training Opportunities | The study provides opportunity for training MSc. students in ABU and AMR surveillance. In addition, it offers opportunity for placement in gene sequencing. |
| Skills Required | The ideal student should have computer proficiency in Microsoft Office programmes such as Word, Excel and PowerPoint. S/he should be proficient in written and spoken English. |
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Key Publications associated with this project |
Valadez JJ. Assessing child survival programs in developing countries: testing Lot Quality Assurance Sampling. Cambridge: Harvard University Press; 1991. |
| Lamadrid, Angelo, Caroline Jeffery, Robert Anguyo, Baburam Devkota, Richard Lako, and Joseph J. Valadez. ""Assessing Attitudes Towards Violence against Women and Girls, Their Determinants and Health-Seeking Behaviour among Women and Men in South Sudan: A Cross-Sectional National Survey."" BMJ Open 14, no. 6 (2024): e080022. https://dx.doi.org/10.1136/bmjopen-2023-080022. | |
| Feasey N. Variations in prevalence of antimicrobial resistance in Malawi.: Malawi Liverpool Wellcome Trust Centre, Report to the Ministry of Health of Malawi; 2021. | |
| Berendes S, Lako RL, Whitson D, Gould S, Valadez JJ. Assessing the quality of care in a new nation: South Sudan's first national health facility assessment. Trop Med Int Health. 2014;19(10):1237-48. | |
| Rath RS, Solanki HK. Review of Lot Quality Assurance Sampling, Methodology and its Application in Public Health. Nepal J Epidemiol. 2019 Sep 30;9(3):781-787. doi: 10.3126/nje.v9i3.24507. PMID: 31687252; PMCID: PMC6824847. |