INFECTIONS
AND AMR

Fractures in Sub-Saharan Africa: epidemiology, economic impact and ethnography (Fractures-E3) Principal Investigator(s): Prof Celia Gregson Funder(s): NIHR-Wellcome Partnership for Global Health Research Partner(s): University of KwaZulu-Natal, MRC The Gambia, University of Bristol, London School of Hygiene and Tropical Medicine, University of Oxford, University of Southampton, University of Sheffield, Harare City Health, Sally Mugabe Central Hospital, Parirenyatwa Group of Hospitals, Chitungwiza Hospital, Ministry of Health and Child Care. Background As populations in Africa age, the risk of fragility fractures is predicted to increase. Fractures can have devastating consequences, including pain, disability, and sometimes death, and they also impose significant strain on healthcare services. Therefore, there is a need for a better understanding of fractures to effectively plan future healthcare services. Study Aim In South Africa, Zimbabwe, and The Gambia the study has established how frequently the two key age-related fractures occur: vertebral fractures (the commonest) and hip fractures (the most life-challenging), and the associated risk factors for these fracture types. The study has assessed recovery, disability, pain, quality of life and deaths following hip fracture, and identified factors that improve outcomes for patients. The study has calculated how much fractures cost health services now, so that we can model future health costs. By talking with patients and healthcare workers we have learned their experiences and gained insights into how fracture care can be improved in the future. Study Design This study is an international mixed-methods study using cross-sectional and longitudinal study designs together with ethnographic study to investigate the epidemiology, economic impact and ethnography of fractures in The Gambia and Zimbabwe. Duration The Fractures-E3 study will run from 2020 to 2026, with the last data collection finishing in 2025 Publications Fractures-E3 study protocol paper Study film Fractures-E3 Film (2023) - YouTube

ICAROZ: Impact of Covid-19 in healthcare workers and health care systems in Zimbabwe Principal Investigator: Prof Katharina Kranzer Funders: Elizabeth Blackwell Institute, Welcome Trust, Canadian Embassy, ELMA, UK research and Innovation, UKAID, ZINCAT Partners: MOHCC, Harare City Health, Counselling Services Unit (CSU), Background Frontline healthcare workers are essential for a functioning healthcare system, and their own health is often not addressed. During COVID-19 pandemic healthcare workers were at disproportionately high risk of SARS-CoV-2 infection globally while equally at risk of other communicable and non-communicable diseases just like the general population. This motivated the development, implementation, and adaptation of an integrated health check combining SARS-CoV-2 testing with screening for other communicable and non-communicable diseases. Project aims To establish a model for screening and referral for common communicable and non-communicable diseases for front-line healthcare workers Study design The ICAROZ study is a cross-sectional, mixed method study through which an integrated health check for frontline healthcare workers was implemented in health facilities including tertiary-level hospitals, provincial and district hospitals, primary health clinics (in Harare), private and mission hospitals, in Zimbabwe. The health check included screening for SARS-CoV-2, tuberculosis, HIV, obesity, anemia, common mental health disorder, diabetes, hypertension, chronic kidney disease and vision impairment. A total of 6598 health workers across 48 health facilities accessed the service. Duration July 2020 and July 2022. Publications Comprehensive occupational health services for healthcare workers in Zimbabwe during the SARS-CoV-2 pandemic. Kavenga K, Hannah M Rickman HM, et al. Psychological distress among healthcare workers accessing occupational health services during the COVID-19 pandemic in Zimbabwe. Chingono RMS, Nzvere FP, et al. Evaluation of a comprehensive health check offered to frontline health workers in Zimbabwe. Marambire E, Chingono RMS, et al. Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study. Taruvinga T, Chingono RMS, et al. Prevalence of chronic conditions and multimorbidity among healthcare workers in Zimbabwe: Results from a screening intervention. Calderwood CJ, Marambire E, et al.

Principal Investigator(s): Dr Claire Calderwood Funder(s): The Wellcome Trust Partners: Ministry of Health and Child Care, Harare City Health, Council for the Blind, Zimbabwe, Counselling Services Unit Zimbabwe, Peek Vision. Background TB is a disease associated with social, biological, and economic vulnerability. The conditions that increase the risk of TB also raise the likelihood of other diseases, while creating financial obstacles to healthcare access. Traditional TB screening approaches fail to address pre- existing risks like undernutrition and other chronic conditions, as well as the indirect effects of TB such as loss of livelihood. These risks and consequences contribute to the global TB epidemic and result in poor health and deepened poverty for those affected. Study Aims The IMBA Hutano (Integrated Multi-component health checks for TB-Affected Households) which means “household health” in Shona, aimed to examine the prevalence of chronic conditions among members of TB-affected households and understand the context and experiences of health screening and treatment in this community. The study is developed relevant package of services to meet the needs of TB-affected households, with the goal of improving TB screening uptake, reducing TB incidence, and enhancing overall health. Study design The study is a mixed-methods early-stage implementation research study, with cross-sectional screening for health conditions and 12 month follow up to assess outcomes. Duration The study has completed follow up in March 2024

Lead researcher: Ruramayi Rukuni Funder: Wellcome Trust UK, 2018-2020 Impaired linear growth (stunting) is one of the most common manifestations of perinatally-acquired HIV and can adversely impact bone and muscle development and function, particularly during adolescence – a critical period of growth. We hypothesise that children with HIV may have reduced bone mass accrual during adolescence, which will put them at increased risk of adverse musculoskeletal outcomes such as osteoporosis and fracture. In the IMVASK study (the IMpact of Vertical HIV infection on child and Adolescent SKeletal development), we aim to determine the impact of HIV infection on bone mineral density (BMD) in peri-pubertal children aged 8–16 years who are established on antiretroviral therapy (ART).

INHALE- INvestigation of Heart and Lung disEase among older children in Harare, Zimbabwe Principal Investigator(s): Rashida Ferrand, Edith Majonga Funder: Nina-Ireland Program for Lung Health and Wellcome Trust Partners: University of Oxford, LSHTM, UCL Institute of Cardiovascular Science Background Long-standing HIV infection in children and adolescents is associated with chronic comorbidities, particularly in sub-Saharan Africa where there is often delayed diagnosis of HIV and/or initiation to antiretroviral therapy. Chronic lung and cardiac disease are common comorbidities in children and adolescents with perinatal HIV. The INHALE (Investigation of Heart and Lung Diseases in HIV among older children) study explored chronic lung and cardiac disease among older children and adolescents with perinatally HIV with the following aims: Study Aims The aim of this study was to understand the clinical and functional features of chronic lung and cardiac disease among vertically HIV-infected older children and adolescents. It also aims to explore the possible pathogenic mechanisms that may be associated with chronic lung disease. Study Design Duration Publications Key papers from INHALE 1. Majonga ED, Rehman AM, McHugh G, Mujuru HA, Nathoo K, Odland JO, Ferrand RA, Kaski JP. Incidence and Progression of Echocardiographic Abnormalities in Older Children with Human Immunodeficiency Virus and Adolescents Taking Antiretroviral Therapy: A Prospective Cohort Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020;70(7):1372-8. 2. Majonga ED, Chiesa ST, McHugh G, Mujuru H, Nathoo K, Odland JO, Kaski JP, Ferrand RA. Carotid intima media thickness in older children and adolescents with HIV taking antiretroviral therapy. Medicine. 2020;99(17):e19554. 3. Bhadriraju S, Fadrosh DW, Shenoy MK, Lin DL, Lynch KV, McCauley K, Ferrand RA, Majonga ED, McHugh G, Huang L, Lynch SV, Metcalfe JZ. Distinct lung microbiota associate with HIV-associated chronic lung disease in children. Scientific reports. 2020;10(1):16186-. 4. Yindom LM, Simms V, Majonga ED, McHugh G, Dauya E, Bandason T, Vincon H, Rylance J, Munyati S, Ferrand RA, Rowland-Jones SL. Unexpectedly High Prevalence of Cytomegalovirus DNAemia in Older Children and Adolescents With Perinatally Acquired Human Immunodeficiency Virus Infection. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019;69(4):580-7. 6. Rylance S, Rylance J, McHugh G, Majonga E, Bandason T, Mujuru H, Nathoo K, Rowland-Jones S, Henrion MYR, Simms V, Ferrand RA. Effect of antiretroviral therapy on longitudinal lung function trends in older children and adolescents with HIV-infection. PloS one. 2019;14(3):e0213556. 7. Majonga ED, Rehman AM, Simms V, Mchugh G, Mujuru HA, Nathoo K, Odland JO, Patel MS, Kaski JP, Ferrand RA. High prevalence of echocardiographic abnormalities in older HIV-infected children taking antiretroviral therapy. AIDS (London, England). 2018;32(18):2739. 8. Desai SR, Nair A, Rylance J, Mujuru H, Nathoo K, McHugh G, Majonga E, Metcalfe J, Kranzer K, Ferrand RA. Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed Tomographic Findings. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018;66(2):274-81. 9. Majonga ED, Rehman AM, McHugh G, Mujuru HA, Nathoo K, Patel MS, Munyati S, Odland JO, Kranzer K, Kaski JP, Ferrand RA. Echocardiographic reference ranges in older children and adolescents in sub-Saharan Africa. International Journal of Cardiology. 2017;248(Supplement C):409-13. 10. Rylance J, McHugh G, Metcalfe J, Mujuru H, Nathoo K, Wilmore S, Rowland-Jones S, Majonga E, Kranzer K, Ferrand RA. Chronic lung disease in HIV-infected children established on antiretroviral therapy. Aids. 2016;30(18):2795-803

Principal Investigator(s): Dr Justin Dixon Funder(s): The Wellcome Trust Partner(s): London School of Hygiene and Tropical Medicine and the Organization for Public Health Interventions and Development (OPHID) Ministry of Health and Child Care Background The KnowM study was an interdisciplinary global health collaboration that focused on multimorbidity, which refers to the coexistence of multiple chronic conditions in one individual. While multimorbidity has long been recognized as a health challenge in the global north, it is increasingly acknowledged as an important issue in the global south. The current scientific, healthcare, and disease classification systems are primarily organized around single-disease and single-organ perspectives, which may not adequately address the complexities of multimorbidity. Study Aim The KnowM study aimed to develop an interdisciplinary conceptual framework and research agenda to effectively respond to multimorbidity in sub-Saharan Africa. Study Design The study, brought together researchers, policymakers, healthcare professionals, and patient groups to address the challenges posed by multimorbidity and advance understanding and interventions in sub-Saharan Africa. It combined ethnographic fieldwork, audio-visual diaries, participatory workshops, and multi-country symposia to progressively co-produce research outputs. These methods are designed to overcome disciplinary and disease silos and move beyond entrenched binaries, such as 'communicable' and 'noncommunicable', 'acute' and 'chronic', and 'biological' and 'social', that hinder effective and equitable health work. Duration 2021 -2024 OptiMuL Principal Investigator(s): Dr Justin Dixon Funder(s): The Wellcome Trust Partner(s): Ministry of Health and Child Care, the Organisation for Public Health Interventions and Development (OPHID), and the London School of Hygiene and Tropical Medicine. Study designOptiMuL (Multimorbidity and Learning Health Systems: Optimising Data-to-Action), is a follow-on to the KnowM study that involves the co-development and implementation of a national multimorbidity learning hub to strengthen capacity for domestic learning around multimorbidity in Zimbabwe. Advancing the WHO’s flagship Learning Health Systems framework, the emphasis of the hub is in elevating bottom-up perspectives and practical learning as a central pillar of the development of self-reliant, person-centred health systems able to respond to complex health challenges like multimorbidity. Running from 2024 to 2030, methods include health system and care pathway mapping; a hub co-development phase; and active programme implementation including embedded pilot studies in chosen priority areas. The hub’s priority areas will be determined with hub collaborators during the co-development phase and may include policy and strategy, health information systems / electronic health records, training curricula, clinical guidelines / algorithms development, and integrated care models. Core to ensuring join-up across academic and applied spheres is a programme of policy and professional fellowships. Drawing from successful models including the Fleming Fund Fellowships and EMPOWA programme, these will provide opportunities for practicing decision-makers and professionals to undertake training and development and to lead on ‘change’ projects to kickstart sustained improvements in knowledge-making, policy, and practice in real-time. Publications https://journals.plos.org/globalpublichealth/article/authors?id=10.1371/journal.pgph.0003434

Keeping Older people healthy: deSigning and evaluating effective HEalth Services to maintain functional AbIlity (KOSHESAI) Principal Investigator(s): Prof Celia Gregson Funder(s): The National Institute for Health and Care Research and the Medical Research Council, UK Partner(s): University of Bristol, The Health Research Unit Zimbabwe, Ministry of Health and Child Care Zimbabwe, City of Harare City Health Department, Biomedical Research and Training Institute Background Thanks to advances in health and sanitation, around the world people are living longer than ever before. In these added years of life, older people understandably want health and wellbeing, that is ‘healthy ageing’. However, healthcare services are not currently configured to provide for a rapidly ageing population, meaning older people are more likely to be living with disability and dependence. The World Health Organization (WHO) defines healthy ageing as ‘the process of developing and maintaining a person's functional ability, encompassing their intrinsic capacity to walk, see, hear and remember within their environment, so they can do what they value’. Study Aims The KOSHESAI (Keeping Older people healthy: deSigning and evaluating effective HEalth Services to maintain functional AbIlity, which means ‘to value’ in Shona) study aims to develop and implement an evidence-based clinical framework for non-specialist assessment and management of chronic disorders associated with ageing that impact functional ability. The goal is to improve the health and wellbeing of older individuals living in Zimbabwe. Study Design The programme consists of five work packages: To characterize "healthy ageing" in Zimbabwe. Formative work will develop an integrated multi-component health check for community-dwelling older adults. To co-design and implement community-based healthy ageing peer-to-peer support groups. Conduct a hybrid effectiveness-intervention study with a mixed-methods process evaluation of the healthy ageing check. Leading to the co-development of a "Healthy Ageing Intervention Toolkit" for broader use. Older people, carers and stakeholders will participate in formative study development and evaluation processes. The study is screening 824 older people living in Mufakose and Highfield in Harare, before then moving to rural communities in Murehwa, for conditions impacting intrinsic capacity, spanning mobility, malnutrition, cognition, depression, vision, and hearing. If screening positive, initial on-the-spot care is provided, care is supported by community-based healthy ageing peer-to-peer support groups, promoting functional ability by facilitating self-management. Duration The KOSHESAI study is a five (5) year program running from 2023 to 2025 as follows: 2023 – Secure all ethics & governance permissions 2024 - Formative/ development phase (work packages 1, 2 and 3) 2025 - Urban Recruitment in Harare (work package 3 & 4) 2026 - Rural Recruitment in Murehwa (work package 3 & 4) 2027 - Healthy Ageing Toolkit Production (work package 5) Publications No publications yet available Study Film No film available yet available Website The KOSHESAI study does not have a website yet. However, all documents are stored online on SharePoint. Access to the SharePoint is strictly by permission. More resources No other resources are yet available You could link to this: https://www.bristol.ac.uk/news/2023/may/globalresearch-award.html

Understanding the impact of menopause on the health of African women, particularly those living with HIV (The MENOPAUSE Study) Principal investigator: Prof Celia Gregson Co-investigators: Prof Rashida Ferrand Study team members: Ms Nyasha Buwu, Mr Tafadzwa Madanhire Funder(s): University of Bristol through the Global Challenges Research Fund Partner(s): Biomedical Research & Training Institute, Ministry of Health and Child Care Zimbabwe, University of Bristol (UK), University of The Witwatersrand Background The scale-up of antiretroviral treatment has dramatically improved survival, such that increasing numbers of women with chronic HIV are now reaching the menopause across Africa. However, little is known of the menopausal experiences of African women, including those living with HIV. Research has seldom focussed on African woman at this stage of life. The menopause is a period of change, including rapid skeletal changes which increase fracture risk. Understanding mechanisms of bone loss in the context of HIV infection is intended to help inform interventions and guidelines. Study objectives: To understand the views of women living in Southern Africa, concerning menopause and ageing, particularly of muscles and bones, and the barriers and facilitators to accessing medical treatments. To co-produce contextually relevant resources—booklets and poster—about menopause with women in Zimbabwe and South Africa To quantify declines in bone strength, bone architecture and muscle strength associated with menopausal transition in Southern African women and determine how these differ between those with and without HIV infection. To identify risk factors for menopause-related losses in bone strength and architecture in women living in Southern Africa, including antiretroviral regimes amongst those who are living with HIV. Main activities The activities of this study were carried out via 3 workpackage: WP1: Qualitative Study of menopausal women in South Africa and Zimbabwe WP2: Analyses of pre-collected DXA data in South Africa WP3: New data collection into a cross-sectional study of menopause and musculoskeletal health in Zimbabwe Duration 2019 - 2023 Students attached to the study: Ms Nyasha Buwu (Masters UZ) Publications produced: Social Sciences | Free Full-Text | Improving Experiences of the Menopause for Women in Zimbabwe and South Africa: Co-Producing an Information Resource (mdpi.com) Osteoporosis, Rather Than Sarcopenia, Is the Predominant Musculoskeletal Disease in a Rural South African Community Where Human Immunodeficiency Virus Prevalence Is High: A Cross‐Sectional Study - Gregson - 2022 - Journal of Bone and Mineral Research - Wiley Online Library Menopause is associated with bone loss, particularly at the distal radius, in black South African women: Findings from the Study of Women Entering and in Endocrine Transition (SWEET) - ScienceDirect https://academic.oup.com/jbmr/article/38/5/619/7500029?login=false https://academic.oup.com/jbmr/advance-article/doi/10.1093/jbmr/zjae138/7740686 https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02466-1 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00073-1/abstract Public resources: SA leaflets available here: https://www.menopause.co.za/menopause-facts/ Zim leaflets available here: https://www.thruzim.org/resources Videos: Shona: https://www.youtube.com/watch?v=TO7tfxoE500 Ndebele: https://www.youtube.com/watch?v=HzsYRek-RTg

Principal Investigator(s): Prof Rashida Ferrand Funder(s): European & Developing Countries Clinical Trials Partnership (EDCTP) Partner(s): University of Bristol, University Teaching Hospital of Zambia, Research Centre Borstel Leibniz Lung Center, University of Oxford, London School of Hygiene and Tropical Medicine, Sub-Saharan African Musculoskeletal Network, Ministry of Health and Child Care Background The VITALITY (VITamin D for AdoLescents with HIV to reduce musculoskeletal morbidity and ImmunopaThologY) study aims to address the bone deficits and pubertal delay associated with long-standing HIV in adolescents. Study aims To establish whether supplementation with vitamin D and calcium optimizes musculoskeletal health among peripubertal children with HIV (cwh) Study Design The VITALITY trial is a double-blind, placebo-controlled study conducted in Harare, Zimbabwe and Lusaka, Zambia. The objective is to determine the effect of a high dose of weekly vitamin D3 (20,000 IU) in combination with daily calcium carbonate (500 mg) or placebo over a period of 48 weeks. The primary outcome measure is bone density, assessed using dual-energy X-ray absorptiometry. The study enrolled 842 adolescents between the ages of 11 and 19 years who acquired HIV perinatally and have been on antiretroviral therapy (ART) for at least 6 months. The participants were randomly assigned to receive either the vitamin D and calcium supplementation or a placebo. The findings of this study will contribute to understanding the impact of vitamin D and calcium supplementation on bone health in adolescents with HIV and may inform interventions to reduce musculoskeletal morbidity and immunopathology in this population. Duration: February 2020 to June 2025 Website Vitality Clinical Trial Zimbabwe | Vitality Trial (vitality-trial.co.uk) VITALITY MIND VITALITY Mind is a cross-sectional sub-study conducted in Zimbabwe as part of the VITALITY Clinical Trial. Study Aim It aims to characterize and determine the prevalence of neurocognitive impairment in children and adolescents living with HIV. Neurocognitive impairment is assessed in two ways; with the Kaufman Assessment Battery for Children (KABC-II) and the NIH Toolbox Cognition Battery. Study Design Both of them consist of a set of games and tests which measure different aspects of cognition. The KABC-II uses physical props and the NIH Toolbox is run on a tablet. The study enrolled 253 adolescents living with HIV from the VITALITY trial and 254 age-matched HIV-negative individuals through snowball sampling. The findings will enhance understanding of neurocognitive challenges in adolescents growing up with HIV and inform interventions to improve their well-being. Duration: The project ran from August 2022 to June 2023

CZI -Co-developing information resources towards informed biobanking and sample collection Principal Investigator Funders : Chan Zuckerberg initiative Partners Dr Sarah Snelling, University of Oxford,Prof Collen Masimirembwa, AiBST Background Understanding local community perspectives on genetic and scientific research is essential. We are working with local communities to understand perspectives and co-develop patient information concerning taking blood, genetic testing, collecting tissue samples, and biobanking, in Zimbabwe. This work forms part of a wider international project led by the University of Oxford ‘An Ancestrally Diverse Atlas of the Human Musculoskeletal System’ Study Aims To understand perspectives and attitudes of the local community on tissue and genetic testing in Zimbabwe. To co-produce information resources to help inform the Zimbabwean community about tissue and genetic testing. Study Design TThe project will conduct in-depth interviews (IDIs) with 40 community members and 10 key informants involved in biobanking, using maximum variation sampling. Additionally, it will facilitate participatory workshops with 20 participants Duration 2020-2025 University of Southampton Funder: Chan Zuckerberg initiative Background Understanding local community perspectives on genetic and scientific research is essential. For this study, the team are working with local communities to understand perspectives and co-develop patient information concerning taking blood, genetic testing, collecting tissue samples, and bio banking in Zimbabwe. This work forms part of a wider international project led by the University of Oxford ‘An Ancestrally Diverse Atlas of the Human Musculoskeletal System’ Main objectives of CZIto explore: Investigate Kknowledge of blood collection and biobanking studies in Zimbabwe among XXX Explore Aattitudes and views towards blood collection and biobanking for research Explore Aattitudes and views towards tissue biobanking for research Survey Kknowledge of tissue biobanking and transcriptomic studies in Zimbabwe Duration 2020-2025 Publications No publications yet available Study Film no Website No

Community Blood Pressure Group (Com- BP) Study Principal Investigators: Dr Kalpana Sabapathy, Dr Rudo Chingono Co-Investigators: Professor Chiratidzo Ndhlovu, Dr. Justin Dixon, Prof. Janet Seeley Study Co-ordinator: Ms Fadzaishe Minho Funder(s): UK Medical Research Council Partner(s): London School of Hygiene and Tropical Medicine , Organisation for Public Health Interventions and Development (OPHID), Solidar Med , Ministry of Health and Child Care Background Hypertension is highly prevalent in Southern Africa but most people living with hypertension have not yet been diagnosed and a high proportion have poorly controlled blood pressure. Hypertension is highly preventable by reducing salt intake and other lifestyle measures and treatable with relatively low-cost medications. Improved blood pressure control will reduce the burden of end-stage disease including ischaemic heart disease and stroke which cause significant disability and death. Leveraging communities and peers to increase awareness about hypertension is an innovative and potentially sustainable approach to improve hypertension diagnosis, treatment and prevention. Study Aims The Community Blood Pressure (Com-BP) study has explored the role of community groups to improve the detection and monitoring of blood pressure in the community. Study Design Through interviews and theory of change workshops, key stakeholders informed the design of piloting community based Com-BP groups. Fourteen Com-BP groups consisting of 10-15 community members affected by hypertension in Chitungwiza and Bindura were provided with digital blood pressure machines for shared use. Groups have met regularly led by two facilitators – a community health worker and an additional member nominated collectively by the group. A process evaluation has been conducted to explore lessons learned from the pilot intervention. Potential implications of research: The research will provide evidence on the acceptability and feasibility of Com-BP groups and make recommendations on how similar interventions should be implemented in future. Duration Study dates: October 2023 – April 2025