Article Text

Protocol
Protocol for an interdisciplinary cross-sectional study investigating the social, biological and community-level drivers of antimicrobial resistance (AMR): Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA)
  1. Benon B Asiimwe1,
  2. John Kiiru2,
  3. Stephen E Mshana3,
  4. Stella Neema4,
  5. Katherine Keenan5,
  6. Mike Kesby5,
  7. Joseph R Mwanga6,
  8. Derek J Sloan7,
  9. Blandina T Mmbaga8,
  10. V Anne Smith9,
  11. Stephen H Gillespie7,
  12. Andy G Lynch7,10,
  13. Alison Sandeman7,
  14. John Stelling11,
  15. Alison Elliott12,13,
  16. David M Aanensen14,15,
  17. Gibson E Kibiki16,
  18. Wilber Sabiiti7,
  19. Matthew T G Holden7
  20. HATUA Consortium
    1. 1School of Biomedical Sciences, Makerere University, Kampala, Uganda
    2. 2Centre for Microbiology Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
    3. 3Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
    4. 4College of Humanities and Social Science, Makerere University, Kampala, Uganda
    5. 5Geography and Sustainable Development, University of St Andrews, St Andrews, Fife, UK
    6. 6School of Public Health, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
    7. 7School of Medicine, University of St Andrews, St Andrews, UK
    8. 8Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania
    9. 9School of Biology, University of St Andrews, St Andrews, UK
    10. 10School of Mathematics and Statistics, University of St Andrews, St Andrews, UK
    11. 11Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
    12. 12Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK
    13. 13Immunomodulation and Vaccines Programme, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Institute, Kampala, Uganda
    14. 14Centre for Genomic Pathogen Surveillance, Wellcome Genome Campus, Cambridge, UK
    15. 15Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
    16. 16East African Health Research Commission, Bujumbura, Burundi
    1. Correspondence to Dr Katherine Keenan; katherine.keenan{at}st-andrews.ac.uk

    Abstract

    Introduction Antimicrobial resistance (AMR) is a global health threat that requires urgent research using a multidisciplinary approach. The biological drivers of AMR are well understood, but factors related to treatment seeking and the social contexts of antibiotic (AB) use behaviours are less understood. Here we describe the Holistic Approach to Unravel Antibacterial Resistance in East Africa, a multicentre consortium that investigates the diverse drivers of drug resistance in urinary tract infections (UTIs) in East Africa.

    Methods and analysis This study will take place in Uganda, Kenya and Tanzania. We will conduct geospatial mapping of AB sellers, and conduct mystery client studies and in-depth interviews (IDIs) with drug sellers to investigate AB provision practices. In parallel, we will conduct IDIs with doctors, alongside community focus groups. Clinically diagnosed patients with UTI will be recruited from healthcare centres, provide urine samples and complete a questionnaire capturing retrospective treatment pathways, sociodemographic characteristics, attitudes and knowledge. Bacterial isolates from urine and stool samples will be subject to culture and antibiotic sensitivity testing. Genomic DNA from bacterial isolates will be extracted with a subset being sequenced. A follow-up household interview will be conducted with 1800 UTI-positive patients, where further environmental samples will be collected. A subsample of patients will be interviewed using qualitative tools. Questionnaire data, microbiological analysis and qualitative data will be linked at the individual level. Quantitative data will be analysed using statistical modelling, including Bayesian network analysis, and all forms of qualitative data analysed through iterative thematic content analysis.

    Ethics and dissemination Approvals have been obtained from all national and local ethical review bodies in East Africa and the UK. Results will be disseminated in communities, with local and global policy stakeholders, and in academic circles. They will have great potential to inform policy, improve clinical practice and build regional pathogen surveillance capacity.

    • urinary tract infections
    • microbiology
    • social medicine
    • infection control
    • public health
    https://creativecommons.org/licenses/by/4.0/

    This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

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    Footnotes

    • BBA, JK and SEM contributed equally.

    • Collaborators The Holistic Approach to Unravelling Antibacterial Resistance in East Africa Consortium, which includes all the aforementioned authors, plus: Catherine Kansiime (Makerere University, Uganda), Martha F Mushi (Catholic University of Health and Allied Sciences, Tanzania), Arun Gonzales Decano (University of St. Andrews, UK), Dominique L Green (University of St Andrews, UK), John Mwaniki (Kenya Medical Research Institute, Kenya), Nyanda E Ntinginya (NIMR - Mbeya Medical Research Centre, Tanzania), Joel Bazira (Mbarara University of Science and Technology, Uganda).

    • Contributors BBA contributed to the conceptualisation of the project, helped designed the tools, and led the pilot data collection and main data collection in Uganda. JK contributed to the conceptualisation of the project, helped design the tools, and led the pilot data collection and main data collection in Kenya. SEM contributed to the conceptualisation of the project, helped designed the tools, and led the pilot data collection and main data collection in Tanzania. SN contributed to the conceptualisation of the project, helped design the social science tools, led the pilot data collection and coordinated social science data collection in Uganda, and led WS4. KK contributed to the conceptualisation of the project, helped designed the social science tools, contributed to the analysis plan, led WS5 and wrote the first draft of this protocol. MK contributed to the conceptualisation of the project, helped design the social science tools and contributed to the analysis plan. JRM contributed to the conceptualisation of the project, helped design the social science tools, and coordinated social science data collection in Tanzania. DJS contributed to the conceptualisation of the project, helped design the tools and led WS3. BTM contributed to the conceptualisation of the project and helped coordinate data collection in Kilimanjaro, Tanzania. VAS contributed to the conceptualisation of the project, wrote parts of the data analysis plan and supervised the analyses. SHG contributed to the conceptualisation of the project, led WS2 and oversaw microbiological data quality. AGL advised on the statistical elements for the project and helped draft this protocol. AS coordinated data collection and work stream activities and helped write this draft protocol. JS contributed to the conceptualisation of the project and provided oversight to WS2. AE contributed to the conceptualisation of the project, and helped draft this protocol. DMA contributed to the conceptualisation of the project, and provided the genomic analysis for WS2. GEK contributed to the conceptualisation of the project and facilitated policy dissemination in EAC. WS contributed to the conceptualisation of the project, helped design the tools and led WS1. MTGH led the conceptualisation of the project, helped designed protocols and data collection tools, and was the guarantor of the project. All authors revised the draft and revised versions of the paper.

    • Funding The Holistic Approach to Unravel Antibacterial Resistance in East Africa is a 3-year Global Context Consortia Award (MR/S004785/1) funded by the National Institute for Health Research, Medical Research Council and the Department of Health and Social Care. The award is also part of the EDCTP2 programme supported by the European Union. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This work is supported in part by the Makerere University-Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII). MUII is supported through the DELTAS Africa Initiative (grant number 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences and Alliance for Accelerating Excellence in Science in Africa, and is supported by the New Partnership for Africa’s Development Planning and Coordinating Agency with funding from the Wellcome Trust (grant number 107743) and the UK Government. This paper was funded in part by a grant from the National Institutes of Health (grant number U01CA207167).

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    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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