Impact case study database

LSHTM’s response to the 2013-2016 West African Ebola epidemic translated expertise into immediate practical and life-saving action. Researchers not only went into the field to help patients, communities and organisations, but also helped contain the spread of Ebola through disease mapping and outbreak analysis. The research benefited international organisations such as WHO, in-country health ministries, UK Aid, and communities affected by Ebola including frontline health workers, by informing resource provision, vaccination strategy and preparation for future outbreaks. This huge mobilisation effort also contributed to sustainable action in the longer term through pioneering education and training programmes and the creation of a new rapid support team.

Shaping the resources needed for Sierra Leone (5.1-5.2)

By demonstrating the effectiveness of Community Care Centres (CCCs) to take the pressure off Ebola treatment centres and reduce the virus transmission, LSHTM research directly underpinned the response in Sierra Leone from 2014 onwards. Modelling the country’s transmission rate of Ebola helped to predict what facilities the country needed and informed the UK Department for International Development (DFID, now FCDO) funding strategy for CCCs. At the request of the government of Sierra Leone and endorsed by the WHO, the UK government committed a GBP427 million package of direct support to help contain, control and treat Ebola. This strategy was informed by LSHTM research on how and where the outbreak was progressing. It included supporting more than 1,470 treatment and isolation beds in Sierra Leone, including the UK’s 6 purpose-built Ebola treatment centres.

Safe and effective vaccination strategy

The pioneering ring vaccine trial in Guinea demonstrated that the rVSV-ZEBOV vaccine was safe and effective, strengthening global capacity to fight future outbreaks of Ebola. Following the publication of the trial results in December 2016, Edmunds, Camacho and Kucharski presented evidence to the WHO Strategic Advisory Group of Experts on Immunisation (SAGE) in early 2017. This highlighted ring vaccination as the optimal vaccine delivery strategy for Ebola (5.3). The WHO then recommended use of rVSV-ZEBOV via ring vaccination under an expanded access/ compassionate use protocol:

‘Ring vaccination, as used in the Phase 3 study in Guinea, is the recommended delivery strategy. This should be adapted to the social and geographic conditions of the outbreak areas and include people at risk including but not limited to: (i) contacts and contacts of contacts; (ii) local and international health-care and front-line workers in the affected areas and (iii) health-care and front-line workers in areas at risk of expansion of the outbreak.’ (5.4)

Based on this recommendation, the ring vaccination strategy was used against Ebola virus in the 2018-2020 outbreak in the Democratic Republic of the Congo (DRC). Over 290,000 people in the DRC received the Merck-manufactured rVSV-ZEBOV vaccine under the ‘compassionate use’ protocol, as well as health and frontline workers in Uganda, South Sudan, Rwanda and Burundi. Preliminary WHO results indicated that the vaccine administered via the ring strategy was 97.5% effective and reduced the chances of death in those who developed Ebola (5.5). In November 2019, the Merck vaccine was licensed by the European Medicines Agency and prequalified by the WHO, making it possible for countries to start their own regulatory processes. It then became available for procurement by UN agencies and The Global Alliance for Vaccines (GAVI). The vaccine was also approved by the US Food & Drug Administration (FDA) in December 2019, citing the Guinea trial as key evidence and commending the study design (5.6). In February 2020, four African countries (the DRC, Burundi, Ghana, and Zambia) became the first to license rVSV-ZEBOV (5.7). This meant it could be administered without prior clinical trials or research protocols.

Preparing for future outbreaks: the UK Public Health Rapid Support Team (UK-PHRST)

The Ebola crisis highlighted the need for the international community to strengthen its response to and control of disease outbreaks before they develop into a global threat. In 2016, LSHTM was chosen because of its instrumental role in the Ebola response to jointly run the newly established GBP20 million initiative, the UK-PHRST, in partnership with Public Health England. The PHRST was headed by LSHTM Professor Dan Bausch and in academic partnership with the University of Oxford and King’s College London. UK-PHRST was developed as part of the UK contribution to global health security and to complement the WHO’s work on the Global Health Emergency Workforce. As well as coordinating and hosting the UK-PHRST as it responded to outbreaks, LSHTM members worked to expand the range of scientific expertise used for outbreak control. The UK-PHRST has since been deployed to 11 outbreaks, where the team supported the response by organisations on the ground via technical advice and expertise on outbreak control measures, tracking the progress of diseases, and delivering training. Outbreaks included: Sierra Leone (2017, disease risk reduction following Freetown landslides), Nigeria (2017, meningitis and 2018, Lassa fever), the DRC (2018-19, Ebola virus), Madagascar (2017, pneumonic plague), Bangladesh (2017-18, diphtheria in displaced Rohingya populations), and COVID-19 (2020).

Making an impact through open-access training

LSHTM staff pooled their expertise to create a unique three-week online course to provide a better understanding of the Ebola virus for health professionals, field workers and students. The course, ‘Ebola in Context’, was delivered via the FutureLearn online platform in 2015 and featured LSHTM and other frontline responders in West Africa. More than 24,000 participants from 185 countries joined the course. The course materials are available online for free, open to re-use by educators.

Recognition, awards and press coverage

LSHTM’s extensive Ebola response, including the work of the modelling team, was widely commended. LSHTM was awarded the prestigious Times Higher Education (THE) ‘University of the Year’ award for 2016. The judges were unanimous in their decision, recognising LSHTM’s wide-ranging and life-saving response to the 2014 epidemic (5.8). The Guinea vaccine trial was runner-up in Science’s ‘Breakthrough of the Year’ in 2015 (5.9). Edmunds received an OBE in the 2016 Queen’s New Year Honours list for his services to infectious disease control, particularly the Ebola crisis response in West Africa (5.10).

LSHTM’s researchers, in partnership with scientists in Senegal, Mali, The Gambia, Burkina Faso and Ghana, were at the forefront of research to find new ways to combat malaria in sub-Saharan Africa. Their findings led to SMC being introduced and rolled out on a wide scale as a new malaria prevention strategy. This dramatically reduced the disease in under 5s, the age group associated with the highest malaria death rate.

Having demonstrated that SMC was safe and effective, LSHTM staff facilitated a project to support national malaria control programmes and in-country health policy officials with high-quality evidence on delivery mechanisms, outcomes, and treatment efficacy and effectiveness. Before the Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project, there were several critical barriers to expanding the rainy season antimalarial treatment approach. These included lack of infrastructure and human resources, insufficient production of drugs, lack of evidence on cost-effectiveness at scale, limited evidence of safety outside a trial setting, and insufficient funding. ACCESS-SMC supported national malaria control programmes to scale up their SMC coverage, providing technical, logistical, and financial support and operational evaluation.

Evidence that seasonal malaria chemoprevention works

In 2012, the WHO Technical Expert Group reviewed the research findings as part of the WHO Global Malaria Programme consultation on SMC (5.1). As a result, the WHO recommended in the same year that children aged 3 to 59 months living in areas of the Sahel and sub-Sahel with highly seasonal malaria transmission should receive SMC for up to four months of the year (5.2). The major impact of this recommendation, underpinned by LSHTM-led research, has been realised during this REF period. In August 2013, the WHO published a guide to help countries adopt and implement the new intervention (5.3).

Regional meetings were then held with malaria control programme managers to explain the new strategy and develop implementation plans; these were initially led by the scientists, and subsequently organised by the West Africa regional Roll-Back Malaria network. SMC was rapidly implemented. In 2014, 8 countries began SMC programmes: Mali, Niger, Chad, Senegal, Nigeria, Togo, The Gambia and Burkina Faso, reaching about 2.5 million children. Also in 2014, UNITAID approved funding for SMC via the ACCESS-SMC project, which further supported SMC programmes in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger and Nigeria. ACCESS-SMC was led by the Malaria Consortium and LSHTM, and other in-country implementation partners (Centre de Support en Santé Internationale, Management Sciences for Health, Medicines for Malaria Venture, the Malaria Modelling Consortium, and Speak Up Africa.) The project rolled out SMC in a phased manner in 2015 and 2016 to a total of around 7 million children.

In Burkina Faso and The Gambia, implementation of SMC was associated with a 42.4% and 56.6% reduction respectively in the number of malaria deaths in hospital during the high transmission period following the introduction of seasonal antimalarial treatment (5.4). The number of confirmed malaria cases at outpatient clinics in the ACCESS-SMC-supported countries reduced by between 25.5 and 55.2% (5.4). Treatment with SMC was associated with 88.2% protective effectiveness in reducing incidence of clinical malaria over 28 days in case-control studies, with low frequency of drug resistance (5.4). Through modelling, it was estimated that over the course of ACCESS-SMC, the project averted over 10 million malaria cases and 60,000 deaths in children in the seven study countries (5.5). Potential overall cost savings of USD66 million were estimated through averting costs of malaria treatment, care and death across Africa, and the net economic cost savings (after deducting the cost of administering SMC) were USD43.2 million across the 7 ACCESS-SMC countries (5.4).

Assisting expansion of SMC

Roll-out beyond ACCESS-SMC was financed by the Global Fund, UNICEF and the President’s Malaria Initiative (PMI), and implemented by the Malaria Consortium and other NGOs. The 2020 World Malaria Report stated that in 2019, the mean total of children treated each month was 21.5 million in 13 countries, in increase from approximately 1.4 million children in 6 countries treated in 2013 (5.6).

LSHTM, as ACCESS-SMC’s academic partner, and collaborators generated evidence on a large scale to demonstrate the long-term safety and effectiveness of SMC. Continued evaluation carried out alongside implementation demonstrated the value of SMC and so allowed implementation to continue during and beyond the ACCESS-SMC project. LSHTM also co-hosted a workshop with WHO providing pharmacovigilance training in 2015 in Morocco, to build and strengthen pharmacovigilance systems in SMC countries. Participants included representatives from national malaria control programmes and national pharmacovigilance centres (5.7).

LSHTM led evaluations which enabled and underpinned implementation by showing SMC to be highly effective even though it was complex to deliver. An independent safety review of the data by the WHO Advisory Committee on Safety of Medicinal Products corroborated SMC’s effectiveness in 2017, endorsing the activities which supported the safe implementation of SMC and concluding that the benefit-risk profile of SMC was positive (5.8).

ACCESS-SMC created demand which led to increased manufacturing capacity for seasonal antimalarial drugs and the development of dispersible formulations. ACCESS-SMC guaranteed funded demand of up to 30 million treatments, which provided an incentive for medical suppliers to increase production. Dispersible tablets produced by Guilin were available for use from 2016 and those from a second supplier, S Kant Healthcare Ltd, developed in partnership with ACCESS-SMC, was submitted for review by the WHO prequalification programme in late 2020.

This programme of research provided high-quality, multi-country data which was crucial for accountability, programme implementation and allocation of resources to prevent newborn deaths and stillbirths. Developing and analysing databases on births and deaths around the time of birth resulted in high-quality evidence to inform what should be prioritised. Systematic review of evidence on interventions enabled actions to be recommended for policy guidelines and programme implementation. This meant that mothers and babies had improved access to services, and led to better health outcomes for newborns.

Informing international targets for newborn mortality and stillbirths

The Lancet Every Newborn Series was published in 2014 and led directly to the development of the United Nations Every Newborn Action Plan (ENAP). Led by UNICEF and the World Health Organization (WHO), ENAP presented evidence-based solutions to prevent newborn deaths and stillbirths, and set out a path to 2020 with global milestones (5.1). The ENAP strategic objectives for ending preventable maternal and neonatal mortality and stillbirths included strengthening and investing in care around the time of birth, strengthening health systems to optimise organisation and delivery of care, minimising inequities to reach every woman and newborn, harnessing the power of communities and societal input, and improving data for decision making and accountability. The plan, based on evidence presented by LSHTM and co-authors in the Every Newborn Series, was endorsed by all 194 member states of the WHO at the 67^th World Health Assembly (WHA) in May 2014. It led to a WHA resolution requesting that the WHO Director-General monitor progress and report periodically to the WHA until 2030 (5.2).

The Lancet series and linked action plan was supported by more than 80 partners and donors and proposed national targets as follows:

• 12 or fewer neonatal deaths per 1000 live births in every country by 2030.

• 12 or fewer stillbirths per 1000 total births in every country by 2030.

The WHA resolution resulted in the Sustainable Development Goal framework including the first global target for neonatal mortality reduction (specifically target 3.2, for all countries to aim to reduce neonatal mortality to at least as low as 12 deaths per 1,000 live births). Targets for both newborn deaths and stillbirths were also included in the United Nations Secretary-General’s Every Women Every Child Strategy and monitoring framework.

Progress towards reducing stillbirth and newborn deaths

In 2014, a global ENAP partnership was established, focused on country implementation, advocacy and metrics to help achieve the targets and milestones in the plan. The country implementation group developed the Every Newborn Tracking Tool in 2014, which was piloted in 10 countries between October and December 2014. It was revised in 2015 and shared with 28 focus countries for their input, chosen on the basis of their high burden of neonatal mortality. The tool was designed to track ENAP implementation and progress towards national milestones, as a standard tracking tool for use in all countries. The essential care elements embedded in the tool, which drew on evidence produced by LSHTM, are now mainstream in many national newborn programmes in LMICs.

90 countries completed the Every Newborn Tracking Tool in 2018. As of 2019, 87% of those countries (78 countries) have completed a newborn action plan and defined newborn mortality reduction targets. 10 countries had a reduction of between 3.7 and 4.8 newborn deaths per 1000 live births since 2013. These countries, termed ‘fast-progressors’, demonstrated how sustainable progress can be realised by leadership for newborn health at the national level, undertaking essential planning and investment, and through focused implementation of inputs which improve quality of care. Improvements based on the ENAP guidance included policies supporting free maternal and newborn care, audits of stillbirth and neonatal deaths, strengthening midwifery education, inpatient care for sick newborns, and inclusion of lifesaving medical products and technology in national essential medicines lists (such as antenatal corticosteroids, chlorhexidine for cord care, and newborn resuscitation devices) (5.3). The tracking tool specifically mapped the ability of countries to monitor the implementation of four high-impact interventions of neonatal resuscitation, treatment of infection, kangaroo mother care, and antenatal corticosteroid use, which were being used in 75 countries as of 2018 (5.4).

As a result of LSHTM and partners’ research demonstrating the effectiveness of kangaroo mother care (KMC) for survival of low-birth-weight infants, WHO published their first guidelines in 2015 on care of preterm labour and of preterm infants to include KMC as an intervention (5.5). As part of the Healthy Newborn Network, a KMC Acceleration Partnership addressed barriers to effective implementation of KMC globally, funded by the Bill & Melinda Gates Foundation. The partnership included approximately 70 KMC stakeholders including researchers, clinicians, government officials, programme managers, international organisations and non-governmental organisations (5.6).

Innovation to give babies a better chance of survival wherever they are born

The Every Newborn Plan and Tracking Tool also crucially shone a light on gaps and areas where national governments were doing too little to reduce newborn deaths and low birth weight. LSHTM-led analyses demonstrated that at current rates of progress, it will be more than a century before African newborns have the same chance of survival as a baby born in the UK, yet most newborn deaths could be prevented by effective use of medical technology. In October 2019, a new GBP50 million partnership to reduce preventable newborn deaths in Africa was announced. The NEST360 partnership, co-founded by Lawn, includes LSHTM, Rice University's Institute for Global Health in the US, and 16 other institutions (12 based in Africa), as well as the governments of Malawi, Kenya, Tanzania and Nigeria. NEST (Newborn Essential Solutions and Technologies) is a bundle of affordable and innovative medical devices and diagnostics selected to address the major causes of death for small and sick newborns. The partnership aims to roll out, test and implement NEST in a sustainable, evidence-based way, with LSHTM leading on implementation research and evaluation, supporting the UN target of halving newborn deaths by 2030 (5.7).

**Open access education

Lawn and others developed two Massive Open Online Courses (MOOCs). ‘The Lancet Maternal Health Series’ course ran 11 times from 2017 to 2020, with over 9,000 participants, hosted on the online platform FutureLearn. The course presented material from a range of maternal health experts and evidence across disciplines and was designed for those considering or undertaking postgraduate study in maternal or neonatal health. A second online course, ‘Improving the Health of Women, Children and Adolescents’, presented the latest data, priorities and debates about the health of adolescents, mothers, newborns and children worldwide. The course has run 9 times to between 2015 and 2020, with over 33,000 learners consisting of healthcare professionals or those working in a health organisation, and those interested in the health of women, children and adolescents (5.8)

LSHTM was one of the leading UK academic groups working throughout 2020 on the COVID-19 pandemic to inform government action, continually presenting evidence to the Scientific Advisory Group for Emergencies (SAGE) and its subgroups. Its multidisciplinary analyses combining mathematical modelling with social and behavioural science were used by SAGE, the Chief Medical Officer (CMO) for England and the UK government Chief Scientific Advisor (CSA) to help formulate policy advice for the government to make evidence-based strategy decisions on virus control measures, including lockdowns, school closures and reopening, and NHS capacity.

LSHTM staff provided their expertise as members of SAGE (Edmunds, Medley, Bonell) and related sub-groups, including as of December 2020:

• the Scientific Pandemic Influenza Group on Modelling (SPI-M) (Kucharski, Davies, Eggo, Funk, Jit, Jombart, Medley (Academic Chair), Edmunds, Mathur, Rosello, Quilty, Clifford, Fearon, Knight)

• the New and Emerging Respiratory Threats Advisory Group (NERVTAG) (Edmunds)

• the Joint Biosecurity Centre Data Science Advisory Board (Medley)

• the Scientific Pandemic Influenza Group on Behaviour (SPI-B) (Bonell, Curtis)

• the Children’s Task and Finish Working Group (TFC) (Eggo, Edmunds, Klepac, Medley) (5.1)

The UK Prime Minister, in thanking SAGE members ahead of the 50^th SAGE meeting on COVID-19, recognised the ‘ extraordinary efforts of scientists… who have been instrumental to Her Majesty’s Government response… SAGE has provided world-leading and rigorous scientific advice which has been invaluable to decision-makers’ (5.2). The CSA, in a letter of thanks to LSHTM’s Director, highlighted the continuing contribution of LSHTM individuals to SAGE by name, recognising ‘ the decisive impact on the valuable scientific advice we have been providing to government through SAGE’ (5.3). Medley, Academic Chair of SPI-M, was made an OBE in October 2020 for services to the COVID-19 response (5.4).

Informing lifesaving restrictions

In parallel with Imperial College London models, CMMID models of a reasonable worst case scenario, exploring national-level impact of shorter duration interventions, curtailing sporting events and leisure activities, and repeated lockdown measures, were presented to SPI-M and SAGE in March 2020 (5.5). This cumulative body of evidence, combined with LSHTM’s tracking of the rising R number, contributed substantially to the SAGE recommendation and UK government decision to instigate national lockdown on 23 March 2020, as well as to earlier decisions on interventions including school closures, case isolation, and curtailment of mass gatherings (5.6). This evidence was weighed by the government alongside competing political priorities influencing the timing of the decision. The evidence informed the decisions which led to quantifiable reductions in COVID-19 infections and deaths, and prevented the NHS from exceeding its capacity to cope. LSHTM CoMix data presented to SPI-M and SAGE demonstrated that the R number fell dramatically over the course of the UK lockdown from 24 March to 13 April (from 2.6 to 0.62) (3.5, 5.7), ensuring critical care capacity in NHS hospitals was not completely overwhelmed. The modelling suggests that the interventions imposed on the UK public prevented the 16-30 million symptomatic COVID-19 cases and 250,00-470,000 deaths which were predicted in an unmitigated epidemic (3.2).

LSHTM staff also presented evidence on the impact of relaxing lockdown measures in April and May 2020, such as reopening schools and the optimal strategy for doing so (5.8). Together with Eggo et al’s evidence demonstrating that susceptibility to COVID-19 was lower in younger age groups, R number tracking by LSHTM informed when it was safe to reopen schools, supporting the decision to partially reopen on 1 June in England.

Public behaviour and awareness

The principles co-developed with LSHTM social scientists were presented from SPI-B to SAGE in October 2020 (5.9) and underpinned communications from the government to the public on restrictions. SAGE endorsed the strategies for sustaining adherence to infection control behaviours emphasising collective identity and mutual care, and the messages were incorporated into communications to the public during the second UK national lockdown in November 2020.

Public engagement and sharing of expert knowledge were critical to increasing public knowledge of the virus and transmission, to improve compliance with restrictions and reduce case numbers. CMMID members made near-daily television appearances across the UK’s major news channels from March 2020 onwards including the Today Programme, BBC News at Ten, Newsnight, Channel 4 News and Sky News, and provided regular expert comment to online and print news outlets. Medley served as a consultant to an e-book to educate children about coronavirus and control measures, working with illustrator Axel Scheffler (The Gruffalo). Published by Nosy Crow, Coronavirus: a book for children was a winner of the FutureBook Awards: Best of Lockdown in November 2020. The book was published under a creative commons licence, which allowed free sharing, and was viewed 1.5 million times on the Nosy Crow website and translated into 63 languages. The print edition raised GBP30,000 for NHS Charities Together (5.10).

LSHTM researchers also mobilised quickly to create a Massive Open Online Course, ‘COVID-19: Tackling the novel coronavirus’ hosted by FutureLearn, to help those interested in the outbreak response and its implications around the world. The free online course ran during March and April 2020 with 236,104 enrolments from 189 countries. The course was a recommended resource by the UK Government and NHS Health England (5.11).

LSHTM handwashing and hygiene experts including Curtis established the multi-partner COVID-19 ‘Hygiene Hub’ in 2020 – a global initiative promoting sharing and learning among researchers and organisations. Between April and December 2020, the Hygiene Hub produced over 180 technical resources incorporating the latest evidence for the COVID-19 response. They were read online more than 64,000 times and LSHTM staff also provided tailored support to more than 140 organisations and governments in 60 countries (5.12).

This programme of research by LSHTM researchers and country partners underpinned the increased introduction of innovative interventions to address common mental health problems in resource-poor settings in India, Zimbabwe and elsewhere. The researchers addressed the shortage in psychiatrists in these settings by training lay health workers to deliver counselling and therapy to thousands of people who would otherwise have missed out on any care.

The ultimate lay worker intervention for mental health: the Friendship Bench

The Friendship Bench trial demonstrated the effectiveness of lay health workers delivering talking therapy at primary care level to help people in their communities suffering from anxiety and depression. Since its pilot in Harare, Zimbabwe, the Friendship Bench has become a national and international tool to improve mental health. The training material was adjusted to suit a wider audience, and the intervention rolled out in 2016 in Harare, in cooperation with the City Health Department, by training groups of 30 lay health workers in three different locations. A randomised design for the roll-out enabled it to be scientifically evaluated. Beneficiaries of the programme experienced an 80% reduction in depression and suicidal thoughts, and a 60% improvement in quality of life (5.1). The Friendship Bench team then trained over 400 ‘grandmothers’ who provided talking therapy in 70 communities in Zimbabwe, helping over 30,000 people in 2017 alone (5.2).

The Friendship Bench became a national programme in Zimbabwe in March 2019, and by then was available in more than 100 communities in Harare, Chitungwiza, and Gweru. By 2020, over 50,000 people across the country had accessed the programme via 700 trained grandmothers (5.3). During the COVID-19 pandemic, when social distancing measures had to be implemented, the Friendship Bench Zimbabwe adapted to provide a free talking therapy service through the ‘Friendship Bench open line’, offering one-to-one support with a trained counsellor over the phone.

A follow-on initiative called ‘Circle Kubatana Tose’ (meaning ‘holding hands together’) enables Friendship Bench clients to join community support groups after they have had individual sessions. These have been running for 6 years in 34 communities, reporting improvement in quality of life, income generation, and school attendance of participants. The groups share personal experiences to support each other, and have set up community gardens and business initiatives.

Spreading globally and sharing learning with high-income countries

From Zimbabwe, the Friendship Bench has been implemented in Malawi, Zanzibar, and Kenya, and also integrated into HIV care. Although the Friendship Bench was developed in the global South, it has been adapted for countries in the global North, a valuable example of South-North learning. In New York, Friendship Benches were piloted in 2016 in the Bronx area of the city and launched in mid-2017, attracting approximately 30,000 visitors in their first year (5.2). A total of 60,000 people visited a New York Friendship Bench between 2017 and 2018, demonstrating the programme’s relevance for high-income settings (5.2, 5.4). The New York programme supplied free downloadable PDF resources for lay health worker training, including training manuals, patient questionnaires, and information on culturally appropriate terminology. Several Canadian organisations have also implemented the approach with support from the original Zimbabwe team and funding from Grand Challenges Canada.

Dixon Chibanda, the founder of Friendship Bench, joined LSHTM in 2018. Prior to this, he gave a TED Talk on the Friendship Bench trial in 2017, which has had 2.9 million views (5.5). Since joining LSHTM, Chibanda has participated in a mental health awareness panel with HRH Prince William The Duke of Cambridge and New Zealand Prime Minster Jacinda Ardern at the 2019 World Economic Forum in Davos. At the Global Mental Health Summit in 2018, The Duke and Duchess of Cambridge pledged their support to the Friendship Bench (5.6).

Training manuals and education programmes

The MANAS and PREMIUM trial outputs were adapted into psychological treatment manuals in 2013, co-authored by Nadkarni, Patel and others, on Counselling for Alcohol Problems and the Healthy Activity Programme. 4 free, competency-based open access digital courses were subsequently developed by the authors in partnership with the Annenberg Physician Training Programme in Addictive Disease and the PREMIUM programme, funded by the Wellcome Trust, and in association with Sangath Organisation and the Government of Goa’s Directorate of Health Services. The courses (Alcohol Counselling; Depression Counselling; Psychological Counselling; and Screening for Alcohol, Tobacco, and Other Substance Abuse Disorders in Primary Care) were hosted by NextGenU.org and aimed at community health workers and lay people providing peer counselling (5.7).

The trials in India also underpinned the specific recommendations of the Disease Control Priorities (DCP) 3 on Mental, Neurological and Substance Use Disorders, which was co-edited by Patel in 2015 (5.8). The DCP is a periodic review of the most up-to-date evidence on cost-effective interventions to address the burden of disease in low-resource settings. It is targeted at governments, universities and physicians, and aims to strengthen capacity for evidence-based decision making.

Based on the outputs of the PREMIUM trials, since re-joining LSHTM in 2018, Nadkarni also delivered training on depression, alcohol and tobacco de-addiction, and on counselling programmes, to several groups of participants in Africa and Asia including nurses, dentists, doctors, and counsellors in Goa in 2020, Buddhist nuns at the Ladakh Nuns Association in 2019, and counsellors and staff at the Sex Workers’ Outreach Programme in Nairobi, Kenya.

Recognising the need for degree-based mental health training for professionals in the field and the importance of strengthening mental health systems worldwide, LSHTM and King’s College London (KCL) launched a Master’s in Global Mental Health in 2012. Nadkarni, Chibanda and others wrote course material based on research findings, and taught students about policy, leadership and research to address the resource shortage of trained psychiatrists and evidence-base for action in global mental health. The MSc has accepted 50 students per year since its inception, with around half from LMICs. Graduates have gone on to careers in national mental health policy and planning, epidemiological and mental health services research, and advisory and advocacy roles in governments, international agencies and non-governmental organisations.

Evidence from the above projects directly enabled millions of people to know their HIV status via international guidelines and test distribution; a crucial first step towards treatment and prevention, and a healthy life. The LSHTM-led research informed programmes and policies implemented by international organisations and national governments. It also created the right environment and global market for development and procurement of innovative HIV testing products. Through STAR’s supporting evidence, HIV self-testing increased dramatically, from negligible volumes in 2015, when there was no supportive policy or quality-assured kits for use in low and middle income countries (LMICs). There are now 4 WHO pre-qualified products, with 5.5 million HIV self-testing kits used in 2018 (5.1).

Securing funding to fill the evidence gap and make an impact

The LSHTM team presented their Wellcome-funded HIV self-testing data to the 20^th Conference on Retroviruses and Opportunistic Infections in 2013. Later that year, a UNAIDS technical update on HIV self-testing was released for resource-limited settings, encouraging development of frameworks to support HIV self-testing in national guidelines but stressing that the evidence base was not yet sufficient to support full guidance (5.2). This technical update was prominently influenced by the research done by LSHTM, LSTM and the MLW, showing HIV self-testing led to increased uptake of HIV treatment. The Malawi data was the only data on HIV self-testing from general LMIC populations.

In September 2013, the STAR Consortium was awarded USD72 million for 2015 to 2020 (lead organisation Population Services International, including USD13.7 million for the LSHTM-led research consortium) to catalyse the market for HIV self-testing, with specific aims of i) providing multi-country evidence to inform WHO guidelines to address this evidence gap, ii) supporting full integration of self-testing into national HIV policy and practice, iii) supporting manufacturers to develop and seek WHO pre-qualification for products for LMICs, and iv) negotiating price reductions for LMICs.

Kit development and distribution to increase access to tests

STAR created an enabling environment for HIV self-testing by generating diverse demand and financing, and accelerating entry to market for self-testing kits. This rapid progress was underpinned by LSHTM-led research, with 650,000 tests distributed prior to WHO prequalification under the research protocols approved by the LSHTM Ethics Committee. In July 2017, the WHO prequalified the first LMIC HIV self-testing kit (OraSure HIV Self-test) which was offered to LMICs for USD2 per kit following investment from the Bill and Melinda Gates Foundation (5.3). By the end of 2020, several quality-assured HIV self-testing products were registered, and the WHO had prequalified 4 tests. 4 STAR Initiative countries (Malawi, South Africa, Zambia and Zimbabwe) drafted regulations governing in vitro diagnostics, including HIV self-test kits. With enabling policies and regulations in place, the number of kits bought by donors increased rapidly, and market forecasting estimated 16 million kits were procured by 2020 (5.4, 5.5). 10 million kits were bought for 2018-19 in the 6 STAR countries alone (Malawi, South Africa, Zambia, Zimbabwe, Lesotho and Eswatini).

Recognising the need to fund and scale-up HIV self-testing beyond the STAR Initiative countries, Unitaid, together with PSI and their partners, engaged ministries of health, the Global Fund and the US President’s Emergency Fund for AIDS Relief (PEPFAR). They encouraged integration of self-testing into plans and budgets. In 2018, PEPFAR included HIV self-testing in its own right in its country guidance as a dedicated testing strategy, and increased funding for HIVST. By 2019, 99 countries had included self-testing in national procurement plans, funded by PEPFAR and the Global Fund (5.6).

Guidelines shaped by STAR evidence

In parallel to scaling up access to self-testing kits, the evidence and experience produced by the STAR Initiative directly led to the development of policy and regulations that made HIV self-testing more widely available. In their capacity as experts on HIV testing and treatment, Corbett was a member of the Guideline Development Group for the 2015 WHO-consolidated guidelines on HIV testing services, and Ayles and Hensen served as external peer reviewers (5.7).

Phase 1 of STAR produced public evidence to inform WHO guidelines on HIV self-testing and partner notification in 2016, which strongly recommended HIV self-testing as an additional testing approach (5.8). This was followed by the WHO prequalification of the first HIV self-test, OraSure, in 2017 (5.3). STAR also provided evidence underpinning the WHO 2019 Consolidated Guidelines on HIV Testing Services revision, notably regarding delivery models and the link to HIV prevention, with Corbett and others listed as external contributors to the supporting evidence, and as part of the external review group (5.9). The results of the trial on community-led delivery of HIV self-testing (3.5), currently in press, were shared at the 10^th International AIDS Society Conference on HIV Science in July 2019 (5.10) in advance of the published paper, and also underpinned the 2019 Consolidated Guidelines.

STAR was decentralised to allow each country to submit protocols around common research questions and to progress at their own pace. WHO reported as of 2019 that 59 countries had policies which allowed HIV self-testing, and 28 countries, across high and low income settings, were actively implementing HIV self-testing (5.4, 5.6). This was in contrast to 2015, when only 3 countries (all of which were high-income) were actively implementing self-testing services as part of their public health HIV response.

This long-term programme of research by LSHTM and overseas partners into LLINs and IRS contributed substantially to the approximately 800 million malaria cases and 300,000 malaria-related deaths which have been prevented since 2013 according to the World Malaria Report 2020 (5.1). LSHTM evaluated LLINs for licensing for malaria control, providing epidemiological evidence via community trials of effectiveness for both controlling malaria and combatting insecticide resistance. This led to WHO prequalification of new vector control products and their widespread procurement and distribution.

Approval and distribution of standard LLINs for malaria protection

WHO’s Pesticide Evaluation Scheme (WHOPES) evaluates LLINs and recommends whether a product meets the criteria for WHO prequalification. Rowland served as a working group expert to this group, advising on safety and efficacy of nets (5.2). WHO transitioned WHOPES to a prequalification team for vector control (PQT-VC) from 2015 to 2017. The methods of LLIN field evaluation, co-developed by LSHTM and WHO, were included in the 2013 WHO Guidelines for Laboratory and Field Testing of LLINs (5.3), and in 2017 influenced WHO advice on trial design for vector control products (5.4).

Pyrethroid-only LLINs are recommended by the WHO as a core intervention in all malaria-endemic areas. Between 2017 and 2020, 20 brands of LLIN entered the global market, of which 15 were standard pyrethroid LLINs (5.2). Each of these was evaluated by LSHTM at PAMVERC trial sites in experimental huts (all 15 brands) or in household 3-year cluster randomised trials (6 brands) before the WHO approved them.

Influenced by LSHTM’s pre-2014 research and subsequent testing of new products, over 2 billion LLINs were distributed in sub-Saharan Africa (as recorded by the Alliance for Malaria Prevention (AMP)) from 2004 to 2020. A total of 65% (1.3 billion) were distributed in the current reporting period of 2014 to 2020, an average of 162 million per year (5.5). 86% of nets were distributed to sub-Saharan Africa; the World Malaria Report 2020 estimates that in 2019, 68% of households in this region had at least one LLIN, and 46% of all those at risk of malaria in Africa were protected by a LLIN (5.1).

Key market stakeholders UNICEF, the President’s Malaria Initiative (PMI), and the Global Fund all invested in and scaled-up their LLIN distribution programmes. For example, UNICEF procurement grew from 29 million LLINs in 2013, to 47.4 million LLINs for 30 countries in 2019. The PMI bought more than 100 million nets in the financial year 2018-19 for the 19 PMI-supported countries (5.6).

Indoor residual spraying

In 2014, the WHO Malaria Policy Advisory Committee Meeting reviewed the evidence – including studies from LSHTM – on combining indoor residual spraying and LLINs. This evidence supported the Operational Manual for Indoor Residual Spraying (IRS) for Malaria Transmission Control and Elimination, published by WHO in 2015 (5.7).

5 new classes of IRS were prequalified by WHO and entered the market following LSHTM evaluation at PAMVERC sites, and LSHTM evidence has been used to determine the optimal strategy depending on insecticide resistance in different settings (5.2). For example, PMI switched IRS strategy in many countries from a formulation requiring bi-annual application to a different, LSHTM-evaluated IRS (Actellic) after it was shown to be effective after only one application per year and to have long residual activity, saving on costs and logistics (5.8).

New tools to fight insecticide resistance

WHO convened a meeting of the Evidence Review Group on PBO-pyrethroid LLINs in October 2017 to review evidence from the LSHTM-led Tanzania trial that PBO-pyrethroid LLINs reduced malaria by 44% compared to the standard pyrethroid LLIN, which was facing increasing mosquito resistance. This led to the WHO making an interim policy recommendation in favour of the PBO-pyrethroid LLIN as a new product class to control malaria in all areas of pyrethroid resistance, which is the majority of endemic Africa (5.9).

The market changed dramatically following this decision. 5 brands of PBO-pyrethroid LLINs were subsequently prequalified by WHO (joining the 15 standard pyrethroid LLIN prequalified products) following LSHTM evaluation (5.4). From less than 1% of international procurements in 2017, PBO-pyrethroid LLINs rose year on year to 21% (43 million) of nets purchased in 2020 (5.4).

Surveillance of insecticide resistance

WHO’s Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM), was published in 2012 as a call to action and implemented over subsequent years. Rowland, Lines and Kleinschmidt were all credited for their roles in developing the plan, which represented a radical shift in WHO policy to include resistance surveillance (5.10). Monitoring resistance is crucial to inform malaria control methods for particular settings and to keep the threat of resistance at bay.

The GPIRM spawned the development in 2017 of the WHO ‘Framework for a national plan for monitoring and management of insecticide resistance in malaria vectors’, to ensure adherence to its recommendations. By the end of 2019, the World Malaria Report 2020 stated that 82 countries reported data on insecticide resistance to the WHO. 2019 reporting was disrupted by COVID-19, but in 2018 alone, 45 countries completed insecticide resistance monitoring and management plans in line with the GPIRM’s 5-pillar strategy, and 36 countries had plans under development (5.1).

Pioneering LSHTM research identified the true scale of avoidable deaths in hospitals in England, and provided the evidence and methodology for a new national approach to preventable deaths, leading to better and safer patient care across NHS trusts.

Shedding light on the true scale of the problem

After the PRISM studies were published, the then Health Secretary Jeremy Hunt adopted the LSHTM estimate that there were 10-12,000 preventable deaths in hospitals in England per year, about a quarter of the previously-held belief of 40,000. In a Commons debate on building a safer NHS, he said:

‘The pioneering work of Helen Hogan, Nick Black and Ara Darzi … estimated that 3.6% of hospital deaths had a 50% or more chance of being avoidable, equating to over 150 deaths every week.’ Hansard 9 March 2016 (5.1).

Hogan and Black’s estimate appeared in the National Patient Safety Strategy for England, the first of its kind, which set out how the NHS would continuously work towards improving patient safety. It was launched in July 2019 with the observation from PRISM findings showing that older people were particularly vulnerable to gaps in care leading to preventable deaths.

‘The opportunity is huge. Hogan et al’s research from 2015 suggests we may fail to save around 11,000 lives a year due to safety concerns, with older patients the most affected.’ National Patient Safety Strategy, July 2019 (5.2).

Press coverage of the research findings in the Guardian, the BBC and other media outlets emphasised the scale of the problem, increasing public awareness and government accountability for taking action to avoid preventable deaths (5.3).

Casting doubt on the use of hospital-wide SMRs

Epidemiologists, statisticians and clinicians were already criticising the use of hospital-wide SMRs as indicators of quality of care. The PRISM study showed that these measures did not reflect the actual preventable death rates for each hospital found on review of case records. This was recognised by the Medical Director of NHS England, Bruce Keogh, and the Director of Patient Safety, NHS England and NHS Improvement, Mike Durkin. In a letter to the medical directors of all NHS trusts in England in December 2015, they said they intended to establish standardised methodology for reviewing deaths in hospitals, and wrote:

‘Prof Nick Black from the LSHTM and Prof Lord Ara Darzi ... determined that about 4% of deaths in our hospitals were potentially avoidable and that there was no obvious relationship with excess deaths over and above the average.’ (5.4)

A new national approach to measuring preventable deaths in hospitals

The LSHTM research raised concerns about the safety of hospital care and provided the basis for a new direct approach to tackle it. Initially, the plan was to use PRISM methodology to review 2,000 deaths per year from hospitals across the NHS, using PRISM estimates of preventable deaths as the national baseline. However, the research had also highlighted the limitations of RCRR as a measure to compare hospital quality, and identified that structured, skilled case note review was best used locally to identify failings in care and determine whether a death was preventable. These findings influenced the Health Secretary to modify policy to focus on a standardised approach of trust-specific quality improvement (Hansard December 2016) (5.5).

The 2017 NHS-wide National Guidance on Learning From Deaths states: ‘ acute trusts should use an evidence-based methodology for reviewing the quality of care provided to those patients who die… such as those based on the PRISM methodology.’ (5.6) Trust Boards were required to regularly collect and annually publish a range of specified information on potentially avoidable deaths and consider what lessons should be learned. This included estimates of preventable deaths within individual organisations, and an assessment of why this might vary from the national average, using methods adapted from Hogan and Black’s work. The guidance has since been expanded to ambulance trusts, paediatric services, and those with learning disabilities. The 2019 National Patient Safety Strategy has acknowledged that examining the care patients received at the end of their lives has provided crucial safety insights and highlighted problems including failure to identify and respond to deterioration.

Nationwide impact and further tools for hospital improvements

To support the work on deaths in hospitals at a national level, NHS England commissioned the National Mortality Case Record Review Programme (NMCRR) to develop mortality reviews in each trust (led by the Royal College of Physicians with Yorkshire and Humber Improvement Academy, in conjunction with software company Datix). The 3 year programme from 2016 to 2019 introduced a proven method of retrospectively reviewing deaths in acute hospital settings (5.7), referencing Hogan and Black’s work, and was a successful vehicle for development of trust-wide quality improvement frameworks (5.8). The Structured Judgement Review (SJR) form, applied to case notes of patients to review the care they received and developed in Yorkshire and Humber, was modified based on PRISM findings to create the final RCRR tool utilised within the programme.

The NMCRR was adopted as a mechanism for implementing the Learning from Deaths policy in England. It was implemented in over 120 of England’s 217 NHS Trusts, and also in a number of Scottish hospitals. According to the 2019 NMCRR statement for stakeholders (5.9), the programme trained around 600 healthcare professionals who cascaded their training to thousands of clinicians throughout NHS Scotland and England. One of the examples of success is Buckinghamshire Healthcare NHS Trust. Within 6 months of implementing the NMCRR, it screened 97% of deaths and made notable improvements in end-of-life care, including increased use of personalised care plans, improved sepsis recognition and treatment, and increased awareness of timely Do Not Attempt CPR decisions. Other successes include the collaborative regional implementation of the SJR by the West of England Academic Health Science Network. The Mid Yorkshire Hospitals NHS Trust incorporated the SJR alongside demographic analyses which identified areas for improvement in care for patients with cerebrovascular disease, and Barking, Having and Redbridge NHS Trust has been developing a faculty of junior doctor mortality reviewers (5.7).

The research, advocacy and expert advice of LSHTM researchers prompted a shift in focus in UK and overseas policy and practice to prioritise the health of trafficking victims, and more survivor-sensitive law enforcement responses. Findings influenced changes in how trafficked people, especially female survivors, are treated by government departments, immigration and law enforcement agencies. Training and resources for healthcare providers, for policing and justice representatives and national referral processes were underpinned by the work led by Zimmerman, which allowed victims of trafficking to receive appropriate medical and psychological treatment and support.

Health and care provisions for victims of trafficking and modern slavery

The National Referral Mechanism (NRM) was introduced in 2009 to meet the UK’s obligations under the Council of Europe Convention on Action against Trafficking in Human Beings. The NRM is a framework for identifying victims of human trafficking and ensuring they receive sufficient protection and support. Before this REF period, the findings from the Stolen Smiles survey provided evidence for Amnesty International and other charities to successfully lobby the Home Office to extend the victim ‘recovery and reflection’ period from 14 days to 45 days. During this reflection period while the relevant authority seeks to make a conclusive decision whether the person is a victim of trafficking and modern slavery, presumed survivors cannot be removed from the UK. The continued benefit of the NRM and of Zimmerman’s contribution are demonstrated in the cumulative number of victims who have been referred to services. According to Home Office statistics, over 39,700 people were referred through the NRM between 2014 and 2020, increasing year on year (5.1).

In 2014, then Home Secretary Theresa May commissioned a review of the NRM. Zimmerman was acknowledged for her contributions to this review in relation to the health of trafficking victims (5.2). The review made a range of recommendations which the government announced as reforms to the NRM in October 2017, including extending the minimum period of ‘move-on’ support for victims from 14 days to 45 days. This period is in addition to the ‘recovery and reflection’ period, and offers ongoing accommodation, counselling and advice, bringing the total period to 90 days, as originally recommended based on Zimmerman’s findings. Other reforms included the establishment of ‘places of safety’ for immediate support, and 6 months of drop-in services, developed in partnership with the Salvation Army, for those transitioning out of the NRM.

Evidence from the Stolen Smiles survey was used to inform the 2014 Annual Report of the Chief Medical Officer, Dame Sally Davies, which focused on women’s health needs (5.3). The section on modern slavery detailed the health risks of trafficked women based on the Stolen Smiles survey. Zimmerman was specifically acknowledged for informing the recommendations, and recommendation 4 of the report advises that Clinical Commissioning Groups and local authorities should ensure that integrated specialist health and social care services are in place to meet referrals safely for modern slavery and trafficking.

Healthcare provider resources – UK

From 2017 onwards, the Gender Violence and Health Centre at LSHTM contributed to Public Health England’s advice and guidance for healthcare practitioners on the health needs of migrant patients (5.4). According to Public Health England, 1 in 8 NHS professionals report previous contact with a person they knew or suspected to have been trafficked, demonstrating the relevance and potential usage of the guidelines. These guidelines were also informed by the findings from the PROTECT study, and the team presented the findings of their report to the All Party Parliamentary Group for Human Trafficking in 2017.

Healthcare provider resources – international

Zimmerman and colleagues at LSHTM’s Gender Violence and Health Centre authored the WHO’s information sheet on human trafficking ‘Understanding and addressing violence against women’, which was downloaded 126,128 times between 2016 and 2020 (5.5).

Zimmerman translated her findings into an International Organization for Migration (IOM) handbook to guide health providers treating trafficked people (5.6). While this was produced in 2009, it was made into an online resource in 2015. Since then, it has been translated into 5 other languages and downloaded over 48,000 times. Since 2013, training has been delivered by the IOM based on this guidance in Belize, Guatemala, Kenya, St Lucia, Chile and Peru.

In 2014, the UN established the UN Action for Cooperation Against Trafficking in Persons (UN-ACT), a United Nations Development Programme collaborative project ensuring a coordinated approach to more strategically and effectively combating trafficking in the Greater Mekong sub-region and beyond. The results of the STEAM study and the IOM guidance for healthcare providers have underpinned various UN-ACT tools and guidelines, including the Supporting the Reintroduction of Trafficked Persons Guidebook for the Greater Mekong sub-region, available in Khmer, Lao, Vietnamese and Thai (5.7).

The United Nations Office of Drugs and Crime Global Report on Trafficking in Persons in the context of armed conflict (2018) drew directly from Zimmerman’s research in the Mekong sub-region (5.8). Furthermore, Zimmerman contributed to the following tools and guidelines produced by the United Nations (UN) Inter-agency Coordination Group against Trafficking in Persons (ICAT), a policy forum of the UN General Assembly which provides a platform for information and good practice on anti-trafficking activities:

• ‘A Toolkit for guidance in designing and evaluating counter-trafficking programmes: Harnessing accumulated knowledge to respond to trafficking in persons’ (2016), which suggested practical responses for counter-trafficking responders based on expert input from Zimmerman (5.9).

• The issue paper ‘Pivoting towards the evidence – building effective counter-trafficking responses using accumulated knowledge and a shared approach to monitoring, evaluation and learning’ (2016), which was underpinned by Zimmerman’s evidence and suggested a road map for capturing and using knowledge accumulated in the sector for effective interventions (5.10).

Extensive, multidisciplinary LSHTM research on male circumcision underpinned international policy recommendations which led to increased use of VMMC to prevent HIV, especially in sub-Saharan Africa. The researchers’ systematic reviews, meta-analyses and economic modelling studies drew from a wide body of research to directly inform WHO HIV prevention guidance. The impact of these policies, guidance and programmes has been further realised since 2013 by the vast scale-up of VMMC services, and the number of HIV infections avoided.

Pre-REF 2021 background impact

WHO/UNAIDS Operational Guidance (2008) for countries on scaling up VMMC services for HIV prevention was directly informed by LSHTM’s evidence of a strong link between male circumcision and reduced HIV prevalence, as well as evidence that the procedure protected against ulcerative STIs (5.1). In 2011, WHO/UNAIDS with The President’s Emergency Plan for AIDS Relief (PEPFAR), the Bill and Melinda Gates Foundation and the World Bank, published a joint strategic 5-year action framework to accelerate the scale-up of VMMC for HIV prevention in Africa (5.2). This was underpinned by the modelling done by the UNAIDS/ WHO/ SACEMA expert group (including Weiss and White), which highlighted the cost-effectiveness of VMMC and outlined male circumcision as an important HIV prevention strategy, alongside other methods such as condom promotion (5.3). This laid the foundations for subsequent guidelines and policy statements.

Economic and health impacts since 2014 - developing guidelines and setting targets

The 2011 WHO/ UNAIDS strategic framework, based on LSHTM evidence, set a goal of circumcising 80% of males in priority countries by 2016 (approximating 20 million circumcisions), and undertaking an additional 8.4 million circumcisions between 2016 and 2025 (5.2). Achieving this 80% coverage among men aged 15 to 49 in the priority countries was estimated to cost USD1.5 billion, but would result in savings of USD16.5 billion by 2025 due to HIV treatment and care costs which would be avoided. As coverage began to gain pace, in 2015 UNAIDS identified VMMC as a crucial intervention and ‘HIV prevention pillar’ to achieving the global fast-track target of fewer than 500,000 new HIV infections annually by 2020, in line with Sustainable Development Goal (SDG) target 3.3: to end AIDS as a public health threat by 2030, and other SDGs relevant to the HIV response. The 2015 UNAIDS Fast Track Strategy also called for renewed commitment to, sustained funding for, and scaled-up implementation of HIV prevention programmes, including VMMC, in the priority countries in eastern and southern Africa (5.4). The 2016 United Nations political declaration on ending AIDS set a target for an additional 25 million men in the 14 priority countries to be circumcised by 2020 (5.5).

The systematic review of the trial evidence underpinned the updated WHO Guidelines for Preventing HIV through Safe Voluntary Medical Male Circumcision for Adolescent Boys and Men in Generalised HIV Epidemics, published in August 2020 (5.6). Additionally, Weiss was a member of the Guideline Development Group. These guidelines strongly recommended that VMMC continue to be promoted as an additional effective HIV prevention option within combination prevention for adolescents 15 years and older and adult men in settings with generalised epidemics, to reduce the risk of heterosexually acquired HIV infection. The guidelines stated ‘evidence that medical male circumcision reduces a man’s risk of heterosexual acquisition of HIV by 59% from three “gold standard” efficacy trials is supported by strong and consistent evidence of an overall 50% reduction in risk from 17 observational studies in diverse settings, including when implemented alongside ART, with its secondary prevention effect.’ Several LSHTM publications are referenced in the guidelines, contributing to this evidence.

Economic and health impacts since 2014 - saving lives and money

The most recent WHO report in stated that, since the implementation of the 2008 guidance until 2020, nearly 27 million men have been circumcised for HIV prevention in the 15 priority countries in East and Southern Africa: Botswana, Eswatini, Ethiopia, Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, South Sudan, Uganda, Tanzania, Zambia and Zimbabwe (5.7). This met the United Nations 2016 commitment of 25 million voluntary male circumcisions by 2020. The majority of the impact of this intervention has been realised since 2014; the latest WHO/ UNAIDS progress report showed that approximately 21 million men were circumcised since then (5.7). This report also demonstrated the long-term impact of VMMC, estimating that if men and boys stopped accessing VMMC today, the number of HIV infections averted would rise to 1.8 million by 2030 and to 5.7 million by 2050; in practice, the benefits are likely to exceed this as programmes continue to provide access to VMMC (5.7). VMMC was found to be highly cost-effective, saving USD1,759 to USD3,300 (depending on targeted age group) per HIV infection in patient treatment and care costs, relative to no VMMC (5.3).

Expanding VMMC for HIV prevention has had direct benefits for female partners of circumcised men, reducing secondary transmission. It also reduces male and female oncogenic STIs such as human papillomavirus (HPV), as well as bacterial vaginosis, and ulcerative STIs (syphilis, herpes simplex virus-2, and chlamydia). These benefits have been evidenced by a comprehensive meta-analysis in 2014 published in the Lancet Global Health which found that VMMC had decreased the incidence of syphilis by 42% in circumcised men compared with uncircumcised men (5.8a). This protective effect was greater for men with HIV, with a reduction of 62%, and female partner syphilis incidence was reduced by 59% overall. There is high-consistency evidence that male circumcision also protects against cervical cancer and cervical dysplasia (5.8b).

Economic and health impacts since 2014 - a focus on safety

To address concerns about the safety of circumcision, efforts were put into developing improved methods and quality standards. As a direct result of her research expertise in this field, Weiss served on the WHO Technical Advisory Group (TAG) on Innovations in Male Circumcision (2010-present) and the WHO VMMC Guidelines development group (2017-2020) which was formed to review more broadly the evidence and policy guidance for scale-up of VMMC (5.9).

In 2013, the TAG, including Weiss, concluded that two specific male circumcision devices were clinically efficacious for male circumcision and safe for healthy adult men when performed by trained providers in public health programmes (provided that surgical backup facilities and skills were available). A subsequent meeting in 2014 confirmed this, and recommended that the devices could be safely used among adolescents aged 13 years and above (5.9). The previously mentioned updated 2020 guidelines recommended the use of WHO-prequalified male circumcision devices as additional methods of male circumcision in the context of HIV prevention for males aged 15 years and older (5.6).

The work of LSHTM on trust and attitudes towards vaccination has helped change the way in which the world thinks about vaccines, and influenced immunisation strategies around the world, bringing crucial evidence and insights to fast-moving and challenging situations affecting public health. The need for locally adapted approaches has been repeatedly championed by the VCP, Larson, and her team.

Informing international vaccination strategy

In 2014, the World Health Organization (WHO) endorsed the definition of vaccine hesitancy proposed by the WHO Strategic Advisory Group of Experts (SAGE) Working Group on Vaccine Hesitancy, of which Larson was a member (5.1). This raised the issue as a major global health threat. The discussions were informed by Larson’s global systematic review of vaccine hesitancy literature between 2007-2012. As a result, WHO SAGE recommended each country should develop a strategy to increase acceptance and demand for vaccination, including ongoing community engagement and trust-building, active hesitancy prevention, regular national assessments of concerns, and crisis response planning (5.2).

Larson was also a key participant, speaker and contributor in the 2019 Global Vaccination Summit in Brussels, co-hosted by the European Commission and the WHO (5.3), which brought together around 400 participants from around the world including political leaders, representatives from international organisations, and health ministries. The event was structured around 3 round table sessions, the first of which was ‘In Vaccines We Trust: stepping up action to increase vaccine confidence’ with Larson as a panel member. As a result of the summit, the European Commission and WHO published ‘10 Actions Towards Vaccination for All.’ Number 4 pledged to ‘tackle the root-causes of vaccine hesitancy, increasing confidence in vaccination, as well as designing and implementing evidence-based interventions.’

Many countries used VCP data and expertise to adapt their immunisation programmes to respond to this evolving threat. Larson and Paterson held workshops in 2019 with 41 participants from the network of countries transitioning from Global Vaccine Alliance (Gavi) support to full domestic financing of their national immunisation programmes: Armenia, Georgia, Ghana, Indonesia, Lao PDR, Moldova, Nigeria, Sao Tome and Príncipe, Sudan, Timor-Leste, Uzbekistan and Vietnam. LSHTM staff, in collaboration with Results for Development, Curatio, Gavi, UNICEF EURO and WHO EURO, then hosted a two-day vaccine hesitancy workshop in Geneva in November 2019, where countries developed action plans to address vaccine hesitancy challenges (5.4).

The VCP’s ‘State of Vaccine Confidence in the EU 2018’ report was requested by the EU Commission to inform their decision making. In the same year, the EU Council adopted a recommendation to strengthen EU cooperation on vaccine-preventable diseases. A roadmap committed to a range of initiatives between 2018 and 2022 to counter online vaccine misinformation and develop evidence-based information tools and guidance to support member states (5.5). These included development of e-learning modules for primary healthcare providers to improve their skills to manage hesitant populations and promote behaviour change. An EU ‘Coalition on Vaccination’ in 2019 brought together European associations of healthcare workers to support delivering accurate information to the public, combating myths around vaccines and vaccination. This followed the VCP’s production of a catalogue of interventions, commissioned by the European Centre for Disease Prevention and Control in 2017 to create a practical tool for organisations in the EU to address vaccine hesitancy (5.6).

Drawing on expertise to promote new Ebola vaccines

The VCP team coordinated the consortium that developed the communication strategy, tools and mobile technology to promote acceptance and uptake of new Ebola vaccines. The Ebola Vaccine Deployment, Acceptance and Compliance (EBODAC) project, led by Larson, started in 2014. It supported vaccine trials in Sierra Leone and preparation for the future deployment of a licensed vaccine, with partners including Janssen, the College of Medicine and Allied Health Sciences, University of Sierra Leone, the Grameen Foundation and World Vision.

The EBODAC project drew on its research-based knowledge on drivers of vaccine hesitancy, and community engagement and social science expertise, to organise effective participant-driven meetings to address rumours circulating among vaccine clinical trial participants. Participant advisory groups set up in clinics administering the vaccine raised important issues. For example, the project team tackled fears around giving blood by following the local tradition of offering condensed milk to make participants feel better after giving blood. Another challenge was ensuring adherence to the two-part vaccine schedule. The team used automatic text reminders and fingerprinting/ iris scanning to make sure the same person received the second vaccination. The EBODAC project contributed to the successful vaccination of all participants in the Ebola vaccine trials (over 700), and is now used as an exemplar of how a good community engagement strategy can ensure the smooth running of clinical trials (5.7).

In 2017, this practice was shared with over 100 experts from across Africa at a symposium in Senegal organised by the EBODAC team: ‘Community engagement, communications and enabling technology in Ebola clinical trials’. The symposium featuring lessons learned in the EBODAC project led to the development of an open access training tool for stakeholders in community engagement, communications and enabling technologies such as mobile training platforms and mobile biometrics for outbreak settings, which are now being adapted for COVID-19 in collaboration with WHO (5.8).

Influencing public discourse

A key component of the VCP’s work has been to counter false information leading to vaccine hesitancy and provide factual, evidence-based information. In 2019 alone, Larson made over 1,000 media appearances, in print, television and online. Examples with the widest reach included comments in the Guardian, Daily Mail, the Telegraph, Fox News, CNN, Associated Press, Science and BBC World (5.9). The vast reach of these media appearances is a critical element of improving vaccine confidence, when levels of trust in vaccines rely strongly on public sentiment, which can be influenced by media coverage.

During the COVID-19 pandemic from April 2020 onwards, the VCP provided social media monitoring reports in partnership with Public Health England with a focus on five preventive behaviours (hand washing, social distancing, self-isolation, wearing masks, and the COVID-19 vaccine) (5.10). This informed the UK government on public sentiment, areas of criticism, and where to reinforce campaign messages to improve public safety. Larson continually contributed to high-profile media discussion during the pandemic, including a feature in the New York Times, and comment in The Times on ways to reassure high-risk groups on the safety of a potential COVID-19 vaccine.

Spread by Aedes aegypti mosquitoes, and sexual transmission, the Zika outbreak caused several countries to issue travel warnings, and heightened concern about the safety of athletes and tourists visiting the 2016 Summer Olympic Games in Rio de Janeiro. Research and impact occurred almost simultaneously; as the outbreak progressed and symptoms emerged, researchers continually provided new data and insights that underpinned interventions, and informed the national and international response and surveillance of the outbreak.

Defining congenital Zika virus

The initial description of the full clinical definition of congenital Zika syndrome, provided by Rodrigues’ work, underpinned the August 2016 WHO rapid advice guidelines for screening and management of affected children (5.1). These guidelines formalised recommendations for families of babies with congenital Zika virus syndrome and provided advice to women of reproductive age and pregnant women about the risks. The work of MERG informed the Zika-related guidance of WHO and the Brazilian Ministry of Health in formulating additional interim guidance for surveillance, care and support for those affected by Zika and the associated conditions (5.2). In part due to efforts by individuals in MERG, the cluster of microcephaly and other neurological disorders was recognised as a National Health Emergency in Brazil and a PHEIC by the WHO (5.3).

By formally establishing the link between Zika virus and microcephaly, LSHTM provided the evidence base for increased risk communication to reduce the chance of being exposed to the virus. For example, WHO advised that pregnant women should not travel to areas of ongoing Zika outbreaks, and that women whose sexual partners lived in or travelled to Zika areas should ensure safe sexual practices or abstain from sex while they were pregnant.

LSHTM staff rapidly acted on research results to improve outcomes for communities affected by microcephaly. In monitoring the cohort of infants with CZS, then aged 3-5 years old, they collected valuable information, including long-term health outcomes and how to support affected families while preparing for future outbreaks. MERG collaborated with the advocacy group, Movimento Zika, to produce and disseminate guides on Zika for mothers of children with CZS. Weekly support groups were held in the local community to allow parents to share knowledge and tips.

In addition, the patient support programme ‘Juntos’ (‘together’), piloted from 2017 to 2018, allowed parent groups in the community to meet regularly to share stories, provide emotional support, and learn about different aspects of Zika, and how they could fight for their rights. Juntos, a programme co-developed by Kuper in the non-profit research and educational hub based in the International Centre for Disability at LSHTM, included training, supervision and mentoring of facilitators, with materials available in English and Portuguese. A short film featuring Juntos, with a focus on setting up parent groups, was completed in collaboration with Medical Aid Films and screened in medical centres across Brazil and Colombia. The researchers have written a facilitator manual and developed a range of resources, available in English, Portuguese and Spanish (5.4).

Evaluating diagnostics

An international virtual biobanking system of Zika-positive clinical samples was developed through the ZikaPLAN diagnostic package in collaboration with UNICEF and WHO, and used as positive controls for evaluation of new diagnostic tests. UNICEF contracted LSHTM in 2017 to assess Zika and other arbovirus tests via lab-based validation, which led to the approval of 2 Zika tests, made by Chembio Diagnostic Systems and SD Biosensor, for UNICEF procurement in 2019 (5.5). UNICEF committed to buying USD1.5million worth of tests and possible further purchases for a total amount of up to USD3.5million for the Chembio product (5.5).

Advising governments, international organisations and the public on risk

The WHO Emergency Committee was chaired by LSHTM’s Heymann (5.3). Its PHEIC declaration mobilised global responses in risk communication, awareness and increased efforts to control the spread of Aedes mosquitoes . LSHTM’s infectious disease experts (including via the inter-disciplinary Centres) addressed this new epidemic from multiple perspectives. Briefed by their colleagues, Logan and Whitworth provided expert input on Aedes control and Zika infection respectively to the Parliamentary and Scientific Committee meeting in 2016, and clinical and travel guidance to the UK government (5.6). Logan, Rodrigues, Watts and Rowland served as members of the Department of Health’s Scientific Advisory Group for Emergencies (SAGE) during the Zika outbreak, which was chaired by Whitty (LSHTM 2001-2019, now Chief Medical Officer for England) (5.7).

LSHTM experts were at the forefront of providing information to the media and general public, with more than 9,000 articles on Zika mentioning LSHTM in 2016 including The Telegraph, Washington Post, Globo and New Scientist. Staff also provided televised expert comment for BBC News, Channel 4 News, ITV News, CNN and many more (5.8). The annual Bug Off campaign, launched by LSHTM in 2016, provides advice to travellers for avoiding vector-borne diseases, including Zika and other infections transmitted by Aedes. Backed by Dame Kelly Holmes, the campaign has reached a global audience of 25 million since its inception, capturing and reflecting sustained interest in minimising risk of overseas travel (5.9).

LSHTM developed the Massive Online Open Course (MOOC): ‘Preventing the Zika virus: understanding and controlling the Aedes mosquito,’ and ran it quarterly from 2016 to 2018, attracting 18,396 students in total. The MOOC was used internationally within academic institutions, governments, control programmes and companies. The course materials remain accessible via the LSHTM Open Educational Resources platform. The International Centre for Disability at LSHTM also launched a MOOC for healthcare professionals, ‘Integrated healthcare for children with developmental disabilities’, with course material drawing on Zika examples from Brazil. The course ran twice in 2019, attracting approximately 7,318 learners (5.10).

Before LSHTM research, HIV programmes tended to leave adolescents out of the picture for testing and treatment because there was little awareness that children infected by their mothers could survive untreated for so long. The studies by LSHTM stimulated a change of focus to include increased testing and coverage of ART in these age groups. Researchers from LSHTM brought international attention to this issue by actively engaging with national and global policy makers to influence policy. As a result, their findings on effective HIV testing and care strategies for adolescents have been widely implemented.

Changing guidelines for HIV testing and care

Ferrand was part of the group informing the guidelines for HIV testing and care of adolescents developed by the World Health Organization (WHO) in 2013 and 2014 (5.1, 5.2). The WHO then convened a technical consultation to inform the updating of HIV treatment guidelines for adolescents. This involved commissioning two systematic reviews (conducted by Ferrand and colleagues) to review evidence on service delivery and clinical outcomes for adolescents, for inclusion in the 2015 Consolidated ARV Guidelines revisions (5.2). These revised guidelines included new recommendations on ART in adolescents.

Findings by Ferrand and colleagues that lack of guardian consent was a key barrier to HIV testing in older children and adolescents led to the Zimbabwe national HIV testing guidelines changing in 2014 to enable healthcare workers to give consent for children to be tested when parental/guardian consent was not available. They also strengthened recommendations for universal testing of children and adolescents (5.3).

Ferrand was a member of two WHO global consultations on addressing illness associated with HIV in 2014 and 2019 (5.4), and presented reviews of evidence on HIV-related comorbidities in children and adolescents. The results of the 2019 review were used to revise the 2020 WHO HIV treatment guidelines including recommending disaggregated indicators for adolescent HIV care and treatment.

Using evidence from the clinical studies, The Center for Disease Control and Prevention (CDC) USA launched an Epidemiologic Assistance (Epi-Aid) investigation in Malawi and Zimbabwe in 2013 in collaboration with LSHTM researchers. An Epi-Aid is a rapid and short-term investigation of an urgent public health problem by the US CDC. The focus of an Epi-Aid investigation is to assist partners in making rapid, practical decisions for actions to prevent and control the public health problem. It reinforced the findings of high prevalence of chronic respiratory morbidity among children with HIV taking ART, feeding into the WHO recommendation on the need to focus on HIV-related comorbidities, specifically lung disease.

New tools for HIV risk screening

The HIV screening tool algorithm which came out of the ZENITH study used a set of questions to identify adolescents at risk of being HIV positive. It was adapted and implemented widely in a number of PEPFAR (The President’s Emergency Plan for AIDS Relief) supported countries for at-risk groups of adults, children (age 0 to 10) and adolescents (age 10 to 19). Ferrand chaired a symposium at the 2018 International AIDS Society meeting which showcased how the HIV screening tool could be used in primary care settings, as well as other strategies to encourage increased HIV testing (such as the economic incentives developed by Ferrand and colleagues) (5.5). The HIV screening tool was recognised as a best practice tool as part of the UNICEF ‘Field Lessons’ initiative to strengthen health services and outcomes among adolescents living with HIV (5.6).

According to a WHO scoping review, as of 2018, tools and questionnaires (either Ferrand’s or as adapted by Bandason et al) were implemented in Zimbabwe, Zambia, Malawi, Uganda and Nigeria to screen adolescents for HIV, and regularly demonstrated high performance (5.7). In Zimbabwe, the algorithm was adapted and implemented among orphans and vulnerable children. In particular, Ferrand provided technical expertise to the Zimbabwe Ministry of Health/ CDC and the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) to adapt the screening tool for use in primary care services.

Raising awareness and creative influence

To help address stigma and other issues faced by adolescents with HIV, Ferrand developed a film, ‘Chiedza’s Song’, and open access educational materials which facilitated discussions in communities and schools (5.8). The film, which premiered at the International AIDS Conference in Durban in 2016, was adapted in partnership with the Ministry of Education and shown in schools in Zimbabwe. Ferrand was also involved in a ‘Let Youth Lead’ roundtable held at LSHTM in 2017, convened by Sentebale (a charity focused on providing psychosocial support to children and adolescents with HIV) and chaired by Prince Harry, the Duke of Sussex (Sentebale’s co-founding patron). This led to a policy brief in 2017 (co-drafted by Ferrand) to support organisations working with adolescents with HIV in Africa to implement evidence-based programmes. The brief provided a snapshot of promising interventions in sub-Saharan Africa to improve outcomes among such groups (5.9).

The Joint Committee on Vaccination and Immunisation (JCVI) advises UK health departments about vaccines that should be introduced. Under the Health Protection (Vaccination) Regulations 2009, the Health Secretary is obliged to adopt these recommendations if certain conditions are met, the most important of which is that they are based on an assessment that demonstrates cost-effectiveness. LSHTM has been the main provider of the first opinion for the health and economic modelling evidence required to assess this, in collaboration with PHE. LSHTM researchers regularly attended JCVI meetings to present evidence before publication, and advised JCVI members prior to their final recommendation. Economic evaluations from LSHTM were also used in the tendering process by the Department of Health and Social Care when selecting manufacturers to supply vaccines to the UK.

As a result of JCVI recommendations underpinned by LSHTM research, changes to vaccine schedules have directly benefited thousands of vaccine recipients since 2013. They have also provided indirect protection to the UK public by reducing the spread of infection and averting cases in other individuals, reduced the burden of several diseases, and saved on NHS resources. There are also the wider benefits of averting costs to society and the individual, and of the quality of life improved by disease prevention.

Evidence of impact on specific vaccines:

Influenza

In 2012, Edmunds and Baguelin presented work to the JCVI on the cost-effectiveness of changes to flu vaccination; the JCVI recommended extending the flu campaign to include school-aged children (age 5 to 17) and children aged 2 to 5 (5.1). This supported the gradual roll-out of seasonal influenza vaccination to children, beginning with a pilot in 2013 where all 2- to 3-year-olds were offered vaccination through GPs in England, and a pilot in English schools. This pilot was extended every year to include all children up to school year 6 (age 10 to 11) in 2019 and 2020 (5.2). It eventually became the largest change ever made to the UK’s vaccination programmes in terms of numbers of people vaccinated. Projections suggested that around 5 million extra people would be vaccinated every year, and around 2.5 million fewer would get influenza, when the programme covered all primary school children, compared to before the programme was implemented. The flu vaccine is now offered to all children aged 2 to 10 years old, meaning all primary school age children are now eligible for vaccination and direct protection from flu, and those aged up to 18 years old in clinical risk groups. Data from the 2019/2020 winter season provided by all local authorities showed that over 2.8 million children from reception to school year 6 were vaccinated, representing 60.4% of the eligible pool of primary school age children (5.3).

With the risk of COVID-19 and flu both circulating at the same time over the winter of 2020, the Scientific Advisory Group for Emergencies (SAGE) (of which Edmunds was a member) advised the UK government that seasonal flu vaccination should be more widely deployed to protect vulnerable individuals (5.4). In autumn 2020, flu vaccination was additionally offered to household contacts of those on the NHS Shielded Patient List, children in year 7 (age 11 to 12) in secondary schools, and health and social care workers employed through Direct Payment and/or Personal Health Budgets (5.4).

HPV

Since 2013, Jit has presented several pieces of work to the JCVI which underpinned successive changes to the HPV vaccination programme, offering direct protection to the public and reducing the burden of HPV-related cancers. These included:

1. Changing the schedule from 3 to 2 doses in 2014 (5.5), saving up to 800,000 doses annually (reflecting the size of the 12-13 age cohort) of a quadrivalent vaccine that costs the NHS up to GBP86.50 per dose to procure and distribute (3.1, 3.2), with the added benefit of reduced logistical complexity. This work also informed international stakeholders, for example, the World Health Organization’s recommendation of a 2-dose HPV vaccination in 2014 (5.6).

2. Rolling out, in 2017, the world’s first programme to vaccinate men who have sex with men (MSM), who are at exceptionally high risk of acquiring HPV-related cancers (5.7).

3. Vaccinating all boys in England aged 12 to 13 from 2019 onwards (5.8).

Meningococcal B

In 2013 and 2014, Edmunds presented impact and cost-effectiveness analyses to the JCVI which led to babies being given the infant meningococcal B vaccination, making the UK the first country in the world to do so (5.9). This was a complex decision, involving a vaccine with an innovative but relatively untried mechanism of action, a rare but devastating disease, and interest from a large number of civil society groups (such as meningitis charities). The vaccine was introduced in 2015 to children at 2, 4 and 12 months, preventing hundreds of meningitis cases per year. Public Health England data in 2020 showed that since the vaccine’s introduction, cases of meningitis B disease in England fell by 62% in children who received at least two doses (5.10).

Conjugate pneumococcal

In 2015, van Hoek presented work to the JCVI showing that vaccinating older adults with a conjugate pneumococcal vaccine would have little impact and not be cost-effective (5.11). Based on this research, the JCVI did not introduce this vaccination. An independent report by RAND Europe stated that this decision saved the NHS up to GBP25 million pounds per year, and the NIHR recognised this work as 1 of 100 examples of positive change arising from its support of research in its first 10 years (5.12).