MULTIMORBIDITY

Principal Investigator: Celia Gregson Funder(s): NIHR-Wellcome Partnership for Global Health Research, UKaid, Wellcome Trust Life expectancy is rising more rapidly in Africa than any other continent globally. As countries in sub-Saharan Africa (SSA) transition due to rapid urbanisation, their changing demographics are giving rise to an increasing burden of non-communicable diseases (NCDs) of ageing, this includes fractures, often as a consequence of skeletal fragility. Fractures can be devastating, causing pain, disability, loss of productivity and sometimes death. Such fractures may occur in the context of multimorbidity (e.g. obesity and osteoarthritis). At the same time in SSA, communicable diseases (e.g. HIV), with both short- and longer-term sequelae, continue to affect millions of people every year. In high-income countries fractures place significant strain on healthcare services and budgets. For countries in Africa to plan future healthcare services we need to understand the epidemiology of key fracture types, their costs both monetarily and for the patient themselves, and what healthcare resources are currently in place to provide for those who fracture, and that might be amenable to future development. Aims In South Africa, Zimbabwe, and The Gambia we will establish how frequently 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. We will assess recovery, disability and death rates following hip fracture, and identify factors that improve outcomes for patients. We will calculate how much fractures cost health services now and in the future. By talking with patients and healthcare workers we will learn of their experiences and gain insights into how fracture care can be improved in the future. Full study website: http://www.fractures-e3.com

Lead researcher: Prof Katharina Kranzer Funder:University of Bristol (Elizabeth Blackwell Institute Global Public Health Research Strand) Host institute: Biomedical Research & Training Institute (BRTI) Collaborators: Dr Justen Manasa (BRTI), Prof Chiratidzo Ndhlovu (University of Zimbabwe), Dr Hilda Mujuru (University of Zimbabwe), Prof Simbarashe Rusakaniko (University of Zimbabwe) We hypothesise that frontline health care workers are pivotal to SARS-CoV-2 response and establishing rapid SARS-CoV-2 testing and communication of results for healthcare workers will help to prevent nosocomial transmission, reduce transmission in the community and lay the foundation for an effective and robust surveillance system. The aim of this study is to implement comprehensive occupational health services including SAR-CoV-2 testing integrated with screening for major causes of morbidity and mortality in frontline health care workers, with rapid feedback of results to reduce nosocomial spread and trace household contacts. MaCoCo Lead researcher: Rudo Chingono Study coordinator: Tinotenda Taruvinga Funding: UKRI GCRF/Newton Fund Queen Mary University of London (QMUL) Partner(s): Organisation for Public Health and International Development (OPHID) Maximising benefit and minimising the harm of COVID-19 control measures on child and women’s health in four sub-Saharan African countries The MaCOCO study is an MNCH-related project whose aim is to understand the negative impact of COVID-19 disease control measures including lockdown, on child and women’s health. The study will conduct a rapid and urgent impact assessment of COVID-19 and COVID-19 control measures on health systems functioning, child health and women’s health in Ghana, Tanzania, Uganda and Zimbabwe. This will be done with the aim to describe the design and evolution of COVID-19 control measures across these countries and identify interventions, including further research, which will minimise harm to children and women, and avoid worsening gender inequalities. The main deliverables of the study include setting country report incorporating new knowledge about how COVID-19 control measures impact on health of children and girls/women, with recommendations for how children and women may be better protected. The study will also report on the different approaches and strategies taken to control COVID-19 across the four countries, with recommendations on how research and evidence ca be produced and harnessed to strengthen future policy making and implementation. The study will also deliver a series of in-country stakeholder discussions and meetings and establish opportunities for cross country dialogue and a collaborative research network that will set the foundations for future research studies.

Principal Investigator: Claire Calderwood Funder: Wellcome Trust Partners: MOHCC, Harare City Health, Council for the Blind Zimbabwe, Counselling Services Unit Zimbabwe, Peek Vision. TB is a disease of social, biological and economic vulnerability. The same conditions which put people at risk of TB increase the risk of chronic disease and multimorbidity, whilst presenting financial barriers to accessing healthcare. These underlying causes rarely affect an individual in isolation, they cluster in households and communities. Implementing screening for high-risk contacts of people with TB is a core component of the global ‘End TB’ strategy. The IMBA Hutano study (Integrated Multi-disease health checks for TB-affected Households) is nested within ERASE-TB and hypothesises that TB household contacts are a key risk group for TB and other chronic diseases, but that these households have poor healthcare access. We propose that integrating other chronic disease screening with that for TB is an effective way to address the large unmet burden of non-communicable disease morbidity and mortality in high TB-burden communities. In the study we are exploring patterns of disease clustering in individuals and households affected by TB in three African countries (Zimbabwe, Tanzania and Mozambique) and the social context of health screening through qualitative research with members of TB-affected households, healthcare workers and policy makers in Zimbabwe. These data will be used to develop and pilot an integrated health screening package for TB-affected households in Zimbabwe. IMBA Hutano translates from Shona as ‘health of the home’.

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).

Lead researcher: Edith Majonga Funders: Wellcome Trust, Nina Ireland Program for Lung Health Partners: University of Oxford, UCL Institute of Cardiovascular Science 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 explores chronic lung and cardiac disease among older children and adolescents with perinatally HIV with the following aims: Understand the prevalence, clinical features, risk factors and progression of lung and cardiac disease in older children and adolescents (aged 6-16 years) living with perinatally-acquired HIV. Explore the possible pathogenic mechanisms that may be associated with chronic lung disease in this population. Determine normal ranges for cardiac structures and lung capacity among older children and adolescents in Zimbabwe who do not have HIV, using echocardiography and spirometry. 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: Justin Dixon Partner: Organisation for Public Health Interventions and Development (OPHID). The KnowM study brings together a wide range of researchers, policymakers, healthcare professionals and patient groups to develop an interdisciplinary conceptual framework and research strengthening agenda for responding to multimorbidity in the global south. The KnowM study combines ethnographic fieldwork in research and care settings in Zimbabwe with a series of collaborative and participatory research activities. This includes audio-visual diaries, participatory workshops and virtual multi-country symposia – all of which will progressively work towards co-producing research outputs. These methods are designed to cut across disciplinary and disease siloes and move beyond entrenched binaries such as ‘communicable’ and ‘noncommunicable’, ‘acute’ and ‘chronic’ and biological and social that persistently work against more effective and equitable health work. 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. Background OptiMuL (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. The project involves novel approaches to evaluation including a learning assessment framework, embedded ethnographic research, and ‘collective sense-making’. Anticipated outcomes Outcomes include new collaborations and confidence to experiment across historically ‘siloed’ disease programmes; new knowledge and ways of thinking about multimorbidity; capacity and infrastructure for continuous learning about multimorbidity; and new approaches for collaborative evaluation of learning. While outcomes are multimorbidity specific, OptiMuL will contribute to the broader conceptualization and realization of learning health systems in practice. It also furthers some of the most pressing challenges in global health including universal health coverage, healthy ageing, and decolonizing global health. Publications https://journals.plos.org/globalpublichealth/article/authors?id=10.1371/journal.pgph.0003434

Lead researcher: Prof. Celia Gregson, NIHR Global Health Professor of Healthy Ageing Funder: The National Institute for Health Research, UK. KOSHESAI: Keeping Older people healthy: deSigning and evaluating effective HEalth Services to maintain functional AbIlity (KOSHESAI) Life expectancy is rising more rapidly in Africa than any other continent. Whilst welcome, longevity alone is insufficient, and maintenance of functional ability is crucial, that is Healthy Ageing. WHO defines healthy ageing as the process of developing and maintaining the functional ability which consists of a person’s intrinsic capacity within their environment, drawing on physical capacity to walk, see and hear, as well as their cognitive capacity. We aim is to develop and implement an evidence-based clinical framework for non-specialist assessment and management of chronic disorders of ageing which impact functional ability, to improve health and wellbeing of older people living in Zimbabwe. The programme comprises 5 work packages, (1) Characterisation of ‘healthy ageing’ in Zimbabwe; (2) Formative work to develop an integrated multi-component health check for community-dwelling older adults; (3) a Effectiveness-intervention hybrid study and mixed-methods process evaluation of the healthy ageing check; (4) Co-design and implementation of community-based healthy ageing peer-to-peer support groups; and (5) Co-development of a ‘Healthy Ageing Intervention Toolkit’ for wider use. Older people, carers and stakeholders will participate in formative study development and evaluation processes. We will then screen 824 older people living in Harare for conditions impacting functional ability, spanning mobility, malnutrition, cognition, depression, vision, and hearing. If screening positive, initial on-the-spot care will be provided, care will be supported by community-based healthy ageing peer-to-peer support groups, promoting functional ability by facilitating self-management. When we identify a problem we will offer advice, practical solutions and if needed facilitate specialist referral, using an integrated personalised care plan model. The primary outcome will be the proportion who screen positive for ≥1 condition, receive on-the-spot care or complete appropriate referral to support within 4 months. Our findings will enable us to develop a ‘Healthy Ageing Intervention Toolkit’ to guide the structured, comprehensive, person-centred assessment and management of older people, ready for scale-up across sub-Saharan Africa.

Lead researchers: Rashida Ferrand (Zimbabwe), Celia Gregson (UK), Lisa Micklesfield (South Africa) Funders:University of Bristol Global Challenges Research Fund (GCRF) Investment Grant Scheme (UK) Partners:BRTI, University of Bristol, University of the Witwatersrand, MRC Lifecourse Epidemiology Unit University of Southampton Summary: Understanding the impact of HIV infection and its treatment on the musculoskeletal health of African women as they transition through menopause 2019-2021 The scale-up of antiretroviral treatment has dramatically improved survival, such that across Africa, increasing numbers of women with chronic HIV are now reaching the menopause and beyond. The menopause is a period of metabolic change with effects on the skeleton associated with increased fracture risk. Research has seldom focused on African woman at this stage of life. This is a mixed-methods study. We are investigating whether HIV infection and its treatments worsen menopausal bone loss, and whether good viral suppression, achieved through antiretroviral treatment (ART), attenuates this HIV effect. We are examining whether certain ARTs, eg. tenofovir, may have more detrimental effects on bone mass and architecture, and if HIV infection is associated with earlier menopause. We further wish to understand women’s opinions about menopause and their experiences of menopause and associated health, and to identify unmet needs, for example in knowledge, understanding and/or health care provision. Understanding both patterns of bone loss and women’s opinions about menopause in the context of HIV infection will help inform future interventions and guidelines. Materials available to download: Women Menopause booklet Ndebele (pdf) Women Menopause booklet English (pdf) Women Menopause booklet Shona (pdf) The study has three work packages: Workpackage 1: Qualitative Study in Harare and Soweto We will interview women at different stages of menopause to understand country-specific contexts and women’s priorities at this stage in life. Workpackage 2: Longitudinal analysis We will analyse data already collected from 450 women followed-up over a 4-year period in Soweto, Johannesburg, to determine changes in bone density through menopausal transition and how this is influenced by the presence of HIV infection. Workpackage 3: Cross-sectional study We will collect new data from 380 pre-, peri- and post-menopausal women living in Harare. Each will complete detailed questionnaires and undergo musculoskeletal evaluation by DXA and pQCT measurement of bone and muscle mass, as well as assessment of muscle function and physical performance. This body of work will involve team training and build musculoskeletal research capability in these areas, and expand the Sub-Saharan African MuSculOskeletal Network (SAMSON). Developed as part of the Menopause study, please find different formats of the leaflet, webpage, and film about the menopause using the link here: https://menopausezim.wixsite.com/zimbabwe The different formats have been created to allow people speaking different languages, with different levels of literacy, and with different availabilities of communication technologies and connectivity to be able to access information resources about what the menopause is, what to expect and how to manage symptoms.

Principal Investigator: Rashida Ferrand Funders:European & Developing Countries Clinical Trials Partnership (EDCTP) Partners:University of Bristol, University Teaching Hospital of Zambia, Research Centre Borstel Leibniz Lung Center, Biomedical Research & Training Institute, University of Oxford, London School of Hygiene & Tropical Medicine, Sub-Saharan African Musculoskeletal Network,Ministry of Health & Child Welfare One of the adverse effects of the HIV infection among children are bone deficiencies (skeletal development). Therefore, the purpose of this trial is to establish whether supplementation with vitamin D3 (weekly) and calcium carbonate (daily) improves musculoskeletal health among peripubertal CWH (children living with HIV) aged 10-19 years in Zambia and Zimbabwe over a period of 48 weeks. In addition to this, the study will also investigate the intervention's effect on muscle mass and strength and to determine the sustainability of the intervention's effects by performing a follow-up at 96 weeks after the supplementation period. For more information about the trial visit the VITALITY website.