University of St Andrews

Infection and Global Health Research Division

HATUA

Holistic Approach to Unravel Antibacterial Resistance in East Africa

The potential harm that increasing levels of antibacterial resistance (ABR) will have on human health is vast.

It is predicted that by 2050, 10 million lives per year and a cumulative 100 trillion US Dollars of economic output may be lost worldwide. In order to address this looming problem a co-ordinated global response is required to try and halt the rise of ABR. HATUA is an interdisciplinary study which is exploring the burden and drivers of antibacterial resistance (ABR) associated with urinary tract infections (UTIs) across East Africa.

Whilst the biological drivers of ABR in pathogens are well explored, the extent to which these are modulated by human behaviour in and around antibiotics is less understood; cultural, social, economic and clinical factors potentially play a part in shaping the way people source, consume, use and distribute antibiotics. The interdisciplinary consortium brings together clinical microbiological, pathogen genomic, social science and modelling data to create a unique combined ABR data set, with which to investigate the drivers of resistance.

The project is establishing a surveillance network across Uganda, Kenya and Tanzania and will recruit 1800 UTI positive patients from nine study areas.

We are conducting quantitative interviews in the clinic, and then the homestead, and recording the treatment seeking behaviour of individuals and influencing factors. Whole genome sequencing will be used to characterize the pathogens we isolate from the patients, investigating their evolution and the genetic basis of resistance in UTI causing bacteria. Combining this social science data with the microbiology and genomic pathogen data, we will construct patient pathways that capture the treatment-seeking and antibiotic-use behaviour for our cohort. Using this construct, we aim to identify ways in which people can be influenced to follow more antibiotic friendly pathways, and disrupt the prevailing spread of ABR across the region.

St Andrews team

Principle Investigator

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Prof Matthew Holden

Professor

School of Geography & Sustainable Development

School of Biology

HATUA consortium team members and institutions

Gallery

HATUA publications and impact

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Publications

Nayiga, S., MacPherson, E. E., Mankhomwa, J., Nasuwa, F., Pongolani, R., Kabuleta, R., Kesby, M., Dacombe, R., Hilton, S., Grace, D., Feasey, N., Chandler, C. I. R. & the AMIS, DRUM, HATUA and SNAP Consortia, “Arming half-baked people with weapons!” Information enclaving among professionals and the need for a care-centred model for antibiotic use information in Uganda, Tanzania and Malawi. 1 Dec 2024, In: Global Health Action. 17, 1, 15 p., 2322839, https://doi.org/10.1080/16549716.2024.2322839

Sado, Keina;  Keenan, Katherine, Manataki, Areti; Kesby, Mike; Mushi, Martha; Mshana, Stephen; Mwanga, Joseph; Neema, Stella; Asiimwe, Benon; Kansiime, Catherine; Bazira, Joel; Maina, John; Kiiru, John; Aduda, Annette; Green, Dominique L; Maldonado-Barragán, Antonio; Abed Al Ahad, Mary; Fredricks, Kathryn; Gillespie, Stephen H; Sabiiti, Wilber; Mmbaga, Blandina T; Kibiki, Gibson; Smith, V Anne; Sandeman, Alison; Sloan, Derek J; Holden, Matthew TG on behalf of HATUA Consortium. Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda. PLOS Glob Public Health 2024 4(2): e0002709, https://doi.org/10.1371/journal.pgph.0002709

Antonio Maldonado-Barragán, Stephen E. Mshana, Xuejia Ke, Katherine Keenan, Stephen H. Gillespie, John Stelling, John Maina, Joel Bazira, Ivan Muhwezi, Martha F. Mushi, Dominique L. Green, Wilber Sabiiti, Alison Sandeman, John Kiiru, Benon Asiimwe, Matthew T. G. Holden, HATUA consortium. Predominance of multidrug-resistant (MDR) bacteria causing urinary tract infections (UTIs) among symptomatic patients in East Africa: a call for action. JAC-Antimicrobial Resistance 2024; v6, Issue 1. https://doi.org/10.1093/jacamr/dlae019

Emmanuel Olamijuwon, Katherine Keenan, Martha F. Mushi, Catherine Kansiime, Eveline T. Konje, Mike Kesby, Stella Neema, Benon Asiimwe, Stephen E. Mshana, Kathryn Fredricks, Benjamin Sunday, Joel Bazira, Alison Sandeman, Derek J. Sloan, Joseph R. Mwanga, Wilber Sabiiti, Matthew T. G. Holden, and CARE Consortium.Treatment seeking and antibiotic use for urinary tract infection in the time of COVID-19 in Tanzania and Uganda: a complex story. Journal of Global Health 2024; 14:05007. https://jogh.org/2024/jogh-14-05007

Katherine Keenan, Kathryn J. Fredricks, Mary Abed Al Ahad et al. HATUA Consortium, Unravelling patient pathways in the context of antibacterial resistance in East Africa.  BMC Infectious Diseases, 23, 414, 2023.  https://doi.org/10.1186/s12879-023-08392-9

Emmanuel Olamijuwon, Eveline Konje, Catherine Kansiime et al. HATUA Consortium. Antibiotic dispensing practices during COVID-19 and implications for Antimicrobial Resistance (AMR): Parallel mystery client studies in Uganda and Tanzania. Antimicrobial Resistance & Infection Control, 2023, 12, 10. https://doi.org/10.1186/s13756-022-01199-4

 John Maina, John Mwaniki, Franklin Mwiti, Susan Kiiru, Japhet Katana, Fredrick Wanja, Joel Mukaya, Osborn Khasabuli, Benon Asiimwe, Stephen Mshana, Matthew Holden, Wilber Sabiiti, John Kiiru and HATUA consortium. Evaluation of the diagnostic performance of the urine dipstick test for the detection of urinary tract infections in patients treated in Kenyan hospitals. Access Microbiology, 2023, 5, 6. https://doi.org/10.1099/acmi.0.000483.v3  

 Susan Kiiru, John Maina, Japhet Katana, John Mwaniki, Benon B Asiimwe, Stephen E Mshana, Matthew T G Holden, HATUA Consortium, John Kiiru, HATUA Consortium. Bacterial etiology of urinary tract infections at Kenyan health facilities and their resistance towards commonly used antibiotics. PLoS One 2023, 26; 18(5) https://doi.org/10.1371/journal.pone.0277279

Adam A. Mwakyoma, Benson R. Kidenya, Caroline A. Minja, Martha F. Mushi, Alison Sandeman, Wilber Sabiti, Mathew TG. Holden and Stephen E. Mshana. Allele Distribution and Phenotypic Resistance to Ciprofloxacin and Gentamicin among Extended Spectrum β-Lactamases Producing Escherichia coli from Urine, Stool, Animals and Environments of Patients with Presumptive Urinary Tract Infection in Tanzania. Frontiers in Antibiotics, 2023, section Antibiotic Resistance, Volume 2. https://doi.org/10.3389/frabi.2023.1164016 

Green, Dominique L.; Keenan, Katherine; Huque, Sarah I.; Kesby, Mike; Mushi, Martha F.; Kansiime, Catherine; Asiimwe, Benon; Kiiru, John; Mshana, Stephen E.; Neema, Stella; Mwanga, Joseph R.; Fredricks, Kathryn J.; Lynch, Andy G.; Worthington, Hannah; Olamijuwon, Emmanuel; Ahad, Mary Abed Al; Aduda, Annette; Mmbaga, Blandina T.; Bazira, Joel; Sandeman, Alison; Stelling, John; Gillespie, Stephen Henry; Kibiki, Gibson; Sabiiti, Wilber; Sloan, Derek J.; Holden, Matthew T. G.; Consortium, HATUA. The Role of Multidimensional Poverty in Antibiotic Misuse: A Study of Self-Medication and Non-Adherence in Kenya, Tanzania, and Uganda. Lancet Global Health, 2023, v11, issue 1. https://doi.org/10.1016/S2214-109X(22)00423-5

Pendo M. Ndaki; Joseph R. Mwanga; Martha F. Mushi; Kathryn Jean Fredricks; Mike Kesby; Eveline T. Konje; Alison Sandeman; Stella Mugassa; Msilikale W. Manyiri; Olga Loza; Katherine Keenan; Stanley M. Mwita; Matthew T. G. Holden; Stephen E. Mshana. Practices and motives behind antibiotics provision in drug outlets in Tanzania: A qualitative study. PLoS One, 2023, 18(8). https://doi.org/10.1371/journal.pone.0290638

Shukrani Philip, Martha F Mushi, Arun Decano, Jeremiah Seni,  Blandina T Mbaga, Happiness Kumburu, Evelyne T Konje, Joseph R Mwanga, Benson  R Kidenya, Betrand Msemwa, Stephen Gillespie, Antonio Maldonado-Barragan, Alison Sandeman, Wilber Sabiiti, Mathew T. G Holden, Stephen E. Mshana. Molecular characterizations of the coagulase-negative staphylococci species causing urinary tract infection in Tanzania: A laboratory based cross-sectional study. Pathogens 2023, 12(2), 180. https://doi.org/10.3390/pathogens12020180

Betrand Msemwa, Martha F. Mushi, Benson Kidenya, Bernard Okamo, Katherine Keenan, Wilber Sabiiti, Donald N. Miyaye, Eveline T. Konje, Vitus Silago, Mariam M.Mirambo, Joseph R. Mwanga, Stephen Gillespie, Antonio Maldonado-Barragan, Alison Sandeman, Mathew Holden, Stephen E.Mshana. Urogenital pathogens in urine samples of clinically diagnosed urinary tract infected patients in Tanzania: A laboratory based cross- sectional study. IJID Regions, v7, 2022, https://doi.org/10.1016/j.ijregi.2022.12.007

Ndaki, P. M., Mushi, M. F., Mwanga, J. R., Konje, E. T., Mugassa, S., Manyiri, M. W., Mwita, S. M., Ntinginya, N. E., Mmbaga, B. T., Keenan, K., Sabiiti, W., Kesby, M., Benitez-Paez, F., Sandeman, A., Holden, M. T. G. & Mshana, S. E.. Non-prescribed antibiotic dispensing practices for symptoms of urinary tract infection in community pharmacies and accredited drug dispensing outlets in Tanzania: a simulated clients approach. BMC Primary Care, 2022. 23, 1, 9 p., 287. https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-022-01905-6

 Ivan Muhwezi, Joel Bazira, Henry Zamarano, Frederick Byarugaba, Wilber Sabiiti, Mathew Holden and Benon B Asiimwe. Quantification and Molecular Characterization of Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae from Agropastoral Communities of Mbarara District, South Western Uganda. Systematic Reviews in Pharmacy, 2022, v13, issue 11. 10.31858/0975-8453.13.11.727-732

Decano, A.G.; Pettigrew, K.; Sabiiti, W.; Sloan, D.J.; Neema, S.; Bazira, J.; Kiiru, J.; Onyango, H.; Asiimwe, B.; Holden, M.T.G. Pan-Resistome Characterization of Uropathogenic Escherichia coli and Klebsiella pneumoniae Strains Circulating in Uganda and Kenya, Isolated from 2017–2018. Antibiotics, 2021, 10, 1547. https://doi.org/10.3390/antibiotics10121547

Ndaki, P.M.; Mushi, M.F.; Mwanga, J.R.; Konje, E.T.; Ntinginya, N.E.; Mmbaga, B.T.; Keenan, K.; Sabiiti, W.; Kesby, M.; Benitez-Paez, F.; Sandeman, A.; Holden, M.T.G.; Mshana, S.E.; HATUA Consortium. Dispensing Antibiotics without Prescription at Community Pharmacies and Accredited Drug Dispensing Outlets in Tanzania: A Cross-Sectional Study. Antibiotics, 2021, 10, 1025. https://doi.org/10.3390/antibiotics10081025

Asiimwe BB, Kiiru J, Mshana SE HATUA Consortium, et al.. 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): BMJ Open 2021, 11: e041418. doi:10.1136/bmjopen-2020-041418

Videos

Fredricks, Kathryn J, Kesby, Mike, Ndaki, Pendo, Mwanga, Joseph R, & Neema, Stella. (2023, March 30). Save your money, save your health: Antibiotics cannot cure a virus. (Jiwekee akiba, kwaajili ya afya yako. Antibayotiki haitibu virusi). Zenodo. https://doi.org/10.5281/zenodo.7634751

Fredricks, Kathryn J, Kesby, Mike, Ndaki, Pendo, Mwanga, Joseph R, & Neema, Stella. (2023, March 30). I’m not a doctor, but I know the basics: Share information, not medication. (Mimi sio daktari, lakini nafahamu mambo ya msingi. Sambaza taarifa, sio dawa.). Zenodo. https://doi.org/10.5281/zenodo.7786571

Kesby, M. & Fredricks, K. (2022) ‘Participatory design of public health messages on Antibiotic use and AMR’, School of Geography & Sustainable Development, University of St Andrews.   https://zenodo.org/record/7319094

Kesby, M. & Fredricks, K. (2023) PAR for AMR – You Tube. On this channel we share public health information materials co-produced with our participants and partner organisations. Participatory Action Research (PAR) seeks to change (not only describe) the phenomena investigated by working WITH rather than ON those studied, enabling them to engage in some/all stages of research (e.g., formulation/design, data collection/analysis, dissemination/impact) (Kindon et al 2007, 2024). Antimicrobial Resistance (AMR) “…arises when the organisms that cause infection evolve ways to survive treatments.

Conference Abstracts and Events

Keenan, K., Holden M., HATUA Consortium. Behavioural, demographic, socioeconomic and environmental factors are jointly associated with risk of antibiotic resistant urinary tract infections in Kenya, Tanzania and Uganda, 2024, 34th European Congress of Clinical Microbiology and Infectious Diseases.

Ke, Xuejia and Keenan, Katherine and Smith, V. Anne, Modelling the Effects of Interventions in Bayesian Networks, the Case of Antibacterial Resistance in East Africa. 9th International Conference On Infectious Disease Dynamics 2023: P2.033, Available at SSRN: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4654924

Clarkson, Madeleine C. and Smith, V. Anne and Keenan, Katherine, Modelling the Interplay between Patients’ Socioeconomic Characteristics, Health Insurance, Contextual Factors and Antibiotic Misuse Behaviour in Tanzania: A Bayesian Belief Network Approach. 9th International Conference On Infectious Disease Dynamics 2023: P2.059, Available at SSRN: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4654935

 March 2022: the HATUA and CARE consortia held a very successful dissemination event in Arusha, Tanzania. After two years of COVID-19 enforced Zoom and Team connectivity, it was a pleasure to meet in person and discuss the tremendous work undertaken by the research teams in Tanzania, Uganda and Kenya. Excellent presentations across the full breadth of HATUA’s holistic vision included talks on the genomic analysis of the pathogens responsible for causing disease in UTI patients, improvements in antimicrobial resistance (AMR) surveillance and capacity building, limitations of current drug dispensing practices, and unravelling the relationship between socioeconomic and behavioural factors and AMR. Great insights also from stakeholders and policymakers on how to translate research findings into impact on AMR policy.

November 2021: The HATUA Consortium was awarded a dedicated scientific session to share findings at the 8th East African Health and Scientific Conference held on 18th November 2021. Nine members of the consortium presented research and together provided a very positive overview of the holistic approach taken by HATUA. The talks were followed by a lively panel session with a large and engaged audience of over 60 attendees.

October 2021: The HATUA consortium, in partnership with Makerere University/UVRI Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) in Uganda, organised a one-day symposium on Friday 22nd October 2021 to showcase success stories and highlights of Infection and Immunity research in Uganda. The symposium was organised by Prof Alison Elliott, one of the HATUA Co-Is, based at UVRI and LSHTM. HATUA partners from St Andrews, Uganda, Tanzania and Kenya attended and presented findings from HATUA.

The role of multidimensional poverty in antibiotic misuse in East Africa: A mixed-methods study. ASTMH Annual Meeting, 2021.Dominique L. Green, Sarah Huque, Mary Abed Al Ahad, Mike Kesby, Stephen E. Mshana, Benon B.Asiimwe, John Kiiru, Stella Neema, Joseph R. Mwanga, Annette Aduda, Wilber Sabiiti, Derek J. Sloan, Katherine Keenan, Matthew T. Holden.

Complex treatment-seeking for symptoms of urinary tract infection in East Africa and links to antibiotic misuse: A mixed-methods study. ASTMH Annual Meeting, 2021. Mary Abed Al Ahad, Sarah Huque, Dominique L. Green, Mike Kesby, Stephen E. Mshana, Benon B. Asiimwe, John Kiiru, Stella Neema, Joseph R. Mwanga, Annette Aduda, Wilber Sabiiti, Derek J. Sloan, Katherine Keenan, Matthew T. Holden.

Kesby M, Neema S, Asiimwe B, HATUA Consortium. (2020). Talking back to the WHO: How grassroots communities in Uganda used Participatory Action Research (PAR) to produce ‘glocally’ meaningful health information on AMR. World One Health Congress, 2020.

Influence on Policy and Practice

HATUA citation in national clinical guidelines. Standard Treatment Guidelines and National Essential Medicines List (STG/NEMLIT), 5th edition 2021

HATUA has been used and cited in the National Action Plan for Antimicrobial Resistance Tanzania 2023-2027 and evidence of poor prescribing from the mystery client studies has been presented to Tanzanian and Ugandan policy makers.

2022 Policy Paper for Ministry of Health, Tanzania: Urgent Need to Address Antimicrobial Dispensing Practices by Drug Outlets in Tanzania. Evidence from HATUA led to the Chief Pharmacist deciding that the current 5-week training course for Accredited Drug Dispensing Outlets (ADDOs) is inadequate, and that new regulations for ADDOs are being considered by Parliament and no new ADDOs can be registered until the training program is extended to include a section on AMR stewardship.

2023 Policy Paper: Urgent Need to Improve Antimicrobial Dispensing Practices by Drug Outlets in Uganda. In Uganda, we have worked with the Pharmaceutical Society of Uganda to develop training materials on antimicrobial stewardship which will be rolled out to pharmacies to help promote antibiotic stewardship.

2021 Policy Paper for Ministry of Health, Tanzania: Towards Improvement of Diagnosis and Patient Management of Urinary Tract Infection in Lower Health Facilities in Tanzania

2023 Dr Katherine Keenan, HATUA Co-I, was invited to speak to a UK Parliamentary Committee on AMR and Poverty.

HATUA Funders

HATUA is a £2.8M, three-year Global Context Consortia Award, funded by the National Institute for Health Research (NIHR), Medical Research Council (MRC) and the Department of Health and Social Care (DHSC). The award is also part of the EDCTP2 programme supported by the European Union.