Infection and Global Health Research Division

Research at the University of St Andrews School of Medicine

HATUA

Holistic Approach to Unravel Antibacterial Resistance in East Africa

PI: Prof Matthew Holden, School of Medicine

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.

HATUA Consortium Team Members and Institutions:

Dr Benon Asiimwe, Makerere University, Kampala, Uganda.
Dr John Kiiru, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
Prof Stephen Mshana, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
Dr Stella Neema, Makerere University, Kampala, Uganda.
Dr Joseph Mwanga, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
Prof Blandina Mmbaga, Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
Dr John Stelling, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
Prof Alison Elliott, Uganda Virus Research Institute, Kampala, Uganda.
Prof David Aanensen, Sanger Institute, UK.
Prof Gibson Kibiki, East African Health Research Commission, Burundi.

HATUA Publications and Impact

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. Accepted by BMC Infectious Diseases, May 2023. Preprint available at Research Square https://www.researchsquare.com/article/rs-1933132/v1

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, January 2023. DOI: https://doi.org/10.21203/rs.3.rs-1276230/v1

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, January 2023. https://doi.org/10.1016/S2214-109X(22)00423-5

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. Preprint medRxiv doi: https://doi.org/10.1101/2023.03.04.23286801. Accepted by PLOS Global Public Health 2023.

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 (2022), doi: 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. Nov 2022, BMC Primary Care. 23, 1, 9 p., 287. https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-022-01905-6

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

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

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 v.13, issue 11. DOI: 10.31858/0975-8453.13.11.733-743

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

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

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,;y 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; Sabiti, 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. Available at SSRN: https://ssrn.com/abstract=3938836 or http://dx.doi.org/10.2139/ssrn.3938836

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

Arun Gonzales Decano, Kerry Pettigrew, Wilber Sabiiti, Derek Sloan, Stella Neema, Joel Bazira, John Kiiru, Hellen Atieno Onyango, Benon Asiimwe, Matthew T. G. Holden. Pan-resistome characterization of uropathogenic Escherichia coli and Klebsiella pneumoniae strains circulating in Uganda and Kenya isolated from 2017-2018. medRxiv 2020.03.11.20034389; doi:https://doi.org/10.1101/2020.03.11.20034389

Conference Abstracts and Events

March 2022: the HATUA and CARE consortia held a hugely 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.

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.

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. Submitted to 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. Submitted to 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

Dissemination Reports

HATUA Dissemination in Kilimanjaro 15th May 2021

HATUA Community Dialogue in Mbarara, Uganda, November 2020

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.