Impact case study database

LSHTM research into the impact of azithromycin, and the global mapping of trachoma, was life-changing for millions of people in trachoma-affected communities. It also accelerated progress towards global elimination of trachoma. Although the December 2020 target for Global Elimination of Trachoma as a public health problem 2020 (GET2020) was not met and the target has been reset to 2030, considerable steps towards elimination have been achieved, underpinned by LSHTM-generated evidence and data.

The LSHTM team presented annually (both before and after 2013) at the WHO-hosted meeting of partners in the WHO Alliance for GET2020 to ensure research findings were translated into policy and practice, nationally and internationally (5.1). This annual meeting was routinely attended by national trachoma control programme managers from all currently or formerly endemic countries, and by the major NGOs involved in control of trachoma.

Treatment and elimination

Through the vast reach of the Global Trachoma Mapping Project (GTMP) and Tropical Data, and underpinned by LSHTM research demonstrating efficacy, optimal administration, and cost-effectiveness, Pfizer has shipped approximately 397 million azithromycin doses to national trachoma control programmes since 2013 (5.2). Year on year, these programmes scaled up considerably, with LSHTM expertise continuously involved via leadership (Solomon, Bailey, Foster), technical support for resource provision, and advocacy.

According to WHO estimates, 95.2 million people were given antibiotics for treatment of trachoma in 2019 alone (5.3), demonstrating the sustained impact of the research. WHO also estimates that the number of people at risk of trachoma has gone down from 1.5 billion in 2002 to 137 million in 2020, a reduction of 91%, and the number of people requiring surgery for trachomatous trichiasis has been reduced from 7.6 million in 2002 to 2 million in 2020, a drop of 74% (5.4).

Since 2013 and as of July 2020, 12 countries reported achieving the GET2020 elimination goals: Cambodia, China, Ghana, The Gambia, Islamic Republic of Iran, Iraq, Lao People’s Democratic Republic, Mexico, Morocco, Myanmar, Nepal, and Togo. 8 of these (Cambodia, China, Islamic Republic of Iran, Lao People’s Democratic Republic, Ghana, Mexico, Morocco, and Nepal) have been validated by WHO as having eliminated trachoma as a public health problem (5.4).

A guide for programme managers on trachoma control, published jointly in 2006 by WHO, LSHTM and the International Trachoma Initiative and co-authored by Solomon, Kuper, Mabey and Foster, was downloaded over 7,000 times between 2016 and 2020 (5.5), demonstrating the guide is still useful at a local level over a decade later.

After findings demonstrated that twice-yearly treatment of azithromycin could significantly reduce under-5 mortality, the WHO issued recommendations in 2020 suggesting mass treatment of children aged 1 to 11 months with azithromycin should be considered in sub-Saharan African settings where under 5 mortality was more than 80 per 1000. These recommendations were underpinned by LSHTM’s evidence and several LSHTM staff served as experts to the consultation in March 2018 (5.6).

In 2014, Mabey was appointed as a Commander of the British Empire for services to health development in Africa and Asia. In 2019, he received the Prince Mahidol Award in the field of Public Health for his work on trachoma in Africa (5.7).

Allocation of resources

Information produced by the GTMP helped to guide implementation of azithromycin and surgical treatment. The GTMP mapped areas where no data previously existed, due to remoteness, insecurity, or competing public health priorities. As a result, it revealed that interventions would be required to eliminate trachoma for 100 million people living in areas previously categorised as ‘suspected endemic’. Up to 1,100 local surveyors and analysts were trained to carry out disease mapping, and open access disease maps were made available via the online ‘Trachoma Atlas’. These findings doubled the population known to need action against trachoma, resulting in a global at-risk population of 200 million people, and completed the global baseline trachoma map.

For example, on the basis of GTMP data, approximately 38% of the total population at risk were found to live in Ethiopia, which had one of the highest trachoma prevalence rates in the world. Ethiopia’s Federal Minister for Health announced the ‘Fast Track Initiative’ in 2014 to clear the estimated backlog of more than 700,000 who needed trichiasis surgery. The country trained over 1,000 Integrated Eye Care Workers to perform surgery and 17,000 health extension workers to identify and refer trichiasis cases, and set up 50 mobile surgical teams. Ethiopia implemented this initiative nationwide and committed USD1.7million of government money. In 2016 it achieved 84% coverage of endemic districts with surgery and antibiotics (5.8).

Since February 2016, Tropical Data has supported more than 1500 surveys across 41 countries, examining 5 million people. In the Tropical Data consortium of scientific, technological and implementing partners which built on the methodologies developed and implemented by the GTMP, LSHTM provided scientific oversight (Harding-Esch as Chief Scientist), the International Trachoma Initiative provided the core data management service, RTI International managed the system technology, Sightsavers provided project management, documentation, budgeting and training packages, and the WHO set standards and protected country interests. The work of Tropical Data has allowed 109,511,552 treatments to be donated to support mass drug administration (MDA), confirmed that MDA could be stopped in 485 Evaluation Units (EUs), confirmed that MDA was not needed in 220 EUs, and helped countries confirm completion of pre-validation surveillance in 264 EUs (5.9).

LSHTM research underpinned the global strategy for the elimination of congenital syphilis, which saw worldwide rollout and success during this REF period. It brought this previously neglected disease on to the agenda through burden studies, and paved the way for an ambitious and effective programme of research on solutions. Progress in elimination has been accelerated via further pioneering LSHTM research on POCTs and tireless advocacy leading to declining syphilis rates (at a time when rates of other sexually transmitted infections have increased (5.1)) and greater access to and distribution of POCTs.

Input to target-setting, guidance and strategy

Following the dissemination of LSHTM’s 2002 Mwanza research, international momentum to eliminate congenital syphilis gained pace. This was underpinned by Watson-Jones’ rates of adverse outcomes of untreated maternal syphilis, leading the WHO to launch a major new initiative for the global elimination of congenital syphilis in 2007. Her work subsequently informed, and was heavily cited in, the 2010 Centres for Disease Control and Prevention (CDC) and WHO ‘road map’ for the global elimination of syphilis, the 2012 WHO Investment Case for Eliminating Mother-to-child Transmission of Syphilis (5.2) and the WHO Global Health Sector Strategy on Sexually Transmitted Infections, 2016-2021 (5.3). While publication of some of these examples precede the current REF period, the impact of these programmes, guidance and strategies was wide-ranging and extended until 2020. Indeed, the last document called for a reduction of the congenital syphilis rate to less than 50 per 100,000 live births in all countries by 2030.

In 2017, WHO published guidance on the use of dual HIV/syphilis rapid diagnostic tests as interim advice for countries planning to introduce them in antenatal services and other testing sites. This guidance was also informed by Mabey and Peeling’s work (5.4). In 2019, the WHO released a policy brief recommending the rapid dual HIV/ syphilis test for pregnant women, including a checklist of issues to consider when implementing dual testing in order to maximise its benefits.

Increased testing and treatment

Following Mabey and Peeling’s rapid diagnostics evaluation study and their publication of the Lancet comment on ‘Avoiding HIV and dying of syphilis’, the Global Fund for AIDS, TB and Malaria announced it would fund country programmes to buy syphilis point of care tests, starting in 2007 and 2008. This was supported by the Global Congenital Syphilis Partnership, established in 2012 by Peeling at LSHTM. The partnership included global leaders in health and development such as the Bill and Melinda Gates Foundation, Save the Children, WHO and CDC, which provided technical support for the use and evaluation of dual HIV/syphilis POCTs.

In 2015, the SD BIOLINE HIV/syphilis dual test was accepted on the list of prequalified in vitro diagnostics based on laboratory evaluations of rapid tests led by Peeling and WHO. The simple test required only a drop of blood from the patient’s finger and gave results in 15 minutes (5.5a). It was offered to women at their first antenatal check-up. In 2019, a second test was awarded prequalification status after field studies showed optimal sensitivity and specificity for HIV diagnosis and good sensitivity and specificity for syphilis (5.5b).

In collaboration with UNICEF and WHO, Peeling organised the 2018 workshops for maternal and child health programmes in 25 countries. They identified reasons for the gap in testing services and opportunities for increasing syphilis screening, and promoted policies for the use of diagnostics to eliminate mother-to-child transmission of HIV/syphilis. These workshops led to many countries, with donor and partner support, identifying reliable and predictable sources of additional funding. This allowed them to supplement existing HIV prevention of mother-to-child-transmission programmes to include dual HIV/syphilis testing and ensure a reliable supply of benzathine penicillin for treatment of syphilis. Following the workshops, countries including Uganda, Kenya and Nigeria updated their testing algorithm in 2018 to include the dual HIV/ syphilis POCT as the first routine test for pregnant women attending antenatal care services (5.6). The 2019 WHO progress report states that ‘strong progress had been made in reducing vertical transmission of syphilis during pregnancy through antenatal care programmes,’ and treatment coverage for syphilis among pregnant women was estimated to have increased to nearly 90% in 2016 and 2017 in the Americas region, a major success of the Global Health Strategy (5.7).

Major steps towards global elimination

In 2015, Cuba became the first country to be validated by WHO as having achieved the elimination of mother-to-child-transmission of HIV and syphilis, and in 2016, Thailand, Belarus and Moldova joined the list. In 2017, Anguilla, Antigua & Barbuda, Bermuda, Cayman Islands, Montserrat, St Christopher & Nevis were also validated as having achieved elimination, joined by Malaysia in 2018 and the Maldives and Sri Lanka in 2019 (5.8).

A 2019 WHO publication reviewed changes in the global burden of maternal and congenital syphilis associated adverse birth outcomes between 2012 and 2016. The estimated total number of congenital syphilis cases was reduced by 12% over this four-year period, reflecting the progress made in a previously neglected area. The authors concluded that the decrease in congenital syphilis cases was due to increased access to syphilis screening and treatment in antenatal clinics worldwide (5.10). The WHO stated in their Progress report on HIV, viral hepatitis and sexually transmitted diseases that in 2017, 100% of low- and middle-income countries included syphilis screening in their antenatal care package (5.9). This, plus increased attendance at antenatal appointments, increased syphilis testing coverage among pregnant women at their appointments, and increased syphilis treatment coverage to save babies’ lives (5.10), can be significantly attributed to the extensive LSHTM research which evaluated POCTs and demonstrated their low cost and accessibility.

The research carried out by the MenAfriCar consortium in Chad, led by staff from LSHTM and local partners, demonstrated for the first time that MenAfriVac was highly effective in reducing transmission of group A meningococcus by preventing carriage and thus halting an epidemic. It also suggested that if people across the meningitis belt were given the vaccine, group A meningococcal disease could be eliminated. Crucially, the findings gave the international community, including The Global Alliance for Vaccines and Immunization (Gavi), the confidence to invest in and accelerate widespread deployment of the vaccine. It has since been given to over 300 million people in Africa through mass campaigns. On the basis of study results, MenAfriVac has also been incorporated into the routine infant immunisation programme in many African meningitis belt countries to sustain protection against group A outbreaks.

Informing vaccination strategy

The trial results were disseminated through face-to-face meetings with stakeholders in the Ministry of Health and major non-governmental organisations in Chad, as well as with WHO staff. The study findings were also presented in reputable journals, at a meeting of the UK Meningitis Research Foundation in November 2013, and at a symposium during the 2014 annual meeting of the American Society of Tropical Medicine and Hygiene.

LSHTM researchers presented their results at the WHO Strategic Advisory Group of Experts on immunisation meeting of October 2014 in the session ‘Meningococcal A conjugate vaccine impact and routine immunisation schedule in infants and young children’ (5.1). The study results were cited in the WHO 2015 Meningococcal A conjugate vaccine updated guidance on the use of meningococcal conjugate vaccines, and led the WHO to emphasise the importance of completing mass vaccination campaigns in individuals aged 1 to 29 years in all countries in the African meningitis belt. Based on the high level of herd immunity demonstrated by mass campaigns, the updated guidance in 2015 specifically introduced additional recommendations to those in the 2011 position paper:

• That countries of the African meningitis belt complete their campaigns in individuals aged 1-29 years and introduce 1 dose of meningococcal A conjugate vaccine at 9-18 months of age into the routine immunisation programme within 1-5 years following their mass campaign. A one-time catch-up campaign should also be conducted for birth cohorts born since the initial mass vaccination and who will be outside the target age for the routine dose.

• That periodic campaigns should be considered where routine childhood vaccination is less than 60%, to provide sufficient herd protection to protect those not immunised (5.2).

These updated recommendations benefited the rest of the meningitis belt countries still to experience implementation of MenAfriVac via Gavi support; a further 60 million people via catch-up campaigns in the Democratic Republic of Congo, South Sudan, Guinea Bissau, Chad, Kenya (2016) and Burundi, Eritrea, Rwanda, and Tanzania (2017) (5.3).

In 2018, a WHO task force was established to develop a global roadmap for how to control and defeat meningitis by 2030, with LSHTM representation from Greenwood and others in their capacity as experts. The roadmap set out a call to action to improve prevention and epidemic control of meningitis, disease surveillance and treatment, support for patients, and advocacy and engagement, and in 2020 the World Health Assembly approved the roadmap and adopted a new resolution to defeat meningitis within the decade (5.4).

Mass rollout of the vaccine

A review by the WHO of country reports on MenAfriVac and routine WHO immunisation data showed that by the end of 2018, 304.9 million people in 22 of 26 meningitis belt countries had received MenAfriVac through mass campaigns. By the end of 2018, a total of 8 of the 26 countries had introduced MenAfriVac into their routine immunisation programmes including 7 with catch-up vaccinations for birth cohorts born after the initial roll-out: Ghana and Sudan (2016), Burkina Faso, Central African Republic, Chad, Mali and Niger (2017), and Côte d’Ivoire (2018). The Central African Republic introduced MenAfriVac into its routine immunisation programme immediately after the mass 1- to 29-year-old vaccinations in 2017 so no catch-up was needed. The Gambia and Nigeria ran catch-up campaigns in 2019 before introduction into routine immunisation. (5.3)

Targeted approach led to herd immunity

By targeting over 227 million 1 to 29 year olds between 2010 and 2018, the mass vaccination campaigns helped to bring about herd immunity in the 26 countries of the meningitis belt. Serogroup A meningitis virtually disappeared in all areas where the vaccine was given, with the primary cause of epidemic meningitis, the group A meningococcus, practically eliminated from the entire region. In vaccinated populations, confirmed group A diseases incidence was reduced by more than 99% (5.5). It was estimated in 2015 by the Centre for Global Development that 142,000 young lives were saved, around 284,000 permanent disabilities avoided, and more than 1 million meningitis cases prevented (5.6). MenAfriVac was also featured in the ‘Millions Saved’ project in the published book Millions Saved: New Cases of Proven Success in Global Health, as a case study of a remarkable result developed from strategic partnerships, innovative technology, and a drive to end the cycle of disease.

Gavi disbursed USD367 million to meningitis A programmes for campaigns and an emergency stockpile of the vaccine, offering financial support to countries integrating MenAfriVac into childhood immunisation programmes. The mass vaccination campaign cost USD1.40 per person, and it is estimated that MenAfriVac achieved a cost per Disability Adjusted Life Year (DALY) averted of USD96.36, confirming its cost-effectiveness.

While deployment of MenAfriVac may have eventually occurred in the African meningitis belt without the MenAfriCar research, the research of LSHTM and partners significantly contributed to the accelerated rollout and scale up of this vaccine, and continued global elimination efforts, as recognised by the WHO (5.7).

CRASH — changing the way bleeding from trauma is treated

The CRASH-2 trial led to a worldwide change in treatment practices, with treatment using TXA now regarded as the standard of care in severe injury. In 2010, LSHTM successfully applied to include tranexamic acid on the World Health Organization (WHO) List of Essential Medicines, and in 2011 and 2012, the British and US Armies included TXA in their combat care treatment protocols. Since 2013, the sustained impact of these protocol changes recommending worldwide use of TXA following severe injury has led to increased use in armed conflict settings and globally, and to reduced mortality. A 2018 paper in BMJ Military Health showed that 93% of military doctors knew the initial dose of TXA, and 91% knew of the CRASH trial and the optimal time for delivery of the drug (5.1).

In 2019, the then UK Defence Secretary Gavin Williamson granted a GBP5 million transformation fund for the development of the TXA auto-injector, which is expected to benefit up to a third of seriously injured soldiers who would otherwise die from their wounds (5.2).

TXA was the first drug to be fast-tracked for use in the NHS under the government’s medicines innovation scheme, and was used widely across the NHS. The National Institute for Clinical Excellence (NICE) guideline 2016 for ‘Major trauma: assessment and initial management’ recommends use of intravenous TXA as soon as possible in patients with major trauma and active bleeding (5.3).

To facilitate the implementation of these protocols and the use of the medicine, LSHTM led efforts with patients, media (winning the 2013 NIHR media competition), clinicians and policy makers (the National Clinical Director, NHS Trusts, the World Health Organization). From 2012 to 2015, the team worked with RoadPeace, the road traffic victims’ charity, in monitoring NHS Trust use of TXA via annual Freedom of Information requests to NHS Trusts. The team then worked with Professor Chris Moran, the National Clinical Director for Trauma, to revise the best practice tariff for trauma to incentivise treatment with tranexamic acid at the crash scene and within three hours of injury, with an additional per patient payment (of GBP2,800 in 2017). Payments depended on achieving a series of quality standards, which include TXA administration to severely injured patients (5.4). TXA is now administered under patient group directives by paramedics across UK Ambulance Trusts and London’s Air Ambulance (5.5).

Research led by Professor Timothy Coats of the University of Leicester described the use of TXA in trauma care in England and Wales since the publication of the CRASH-2 trial. Their analysis of data from the Trauma Audit and Research Network (TARN) showed that TXA use had increased from near zero in 2010 to 10% in 2016, and 80% of those that received TXA did so within 3 hours of injury. (5.5a)

The administration of TXA in patients with haemorrhage requiring transfusion in Major Trauma Centres increased from near zero in 2010 to 90% in 2016, and in association with wider changes in UK trauma management, the odds of survival have increased by nearly a fifth between 2008 and 2017 (5.5b).

Following Roberts’ criticism of the BBC over a 2011 episode of Holby City promoting a trauma drug for which there was no evidence of saving lives, LSHTM trauma experts successfully lobbied the BBC to include TXA in its other emergency care soap, Casualty (2017), advocating for accurate representation and promotion of drugs to prevent bleeding. The BBC’s 2014 programme ‘An Hour to Save Your Life’ highlighted the current use of TXA in UK trauma care implemented as a direct result of CRASH-2 (5.6).

In 2019, Roberts was awarded the first Faculty of Public Health Bazalgette Professorship Champion of Evidence Award, which recognises major contributions to public health policy and/or practice through research translation for the benefit of UK population health (5.7).

WOMAN — making TXA part of maternity care

The life-saving impact of the WOMAN trial has gone further than the vast scale of the trial itself which demonstrated the innovative potential and alternative application of a well-established drug. Safe, effective and affordable PPH treatments are critical to saving the lives of pregnant women globally, and the findings of this trial had important implications for the delivery of high-quality maternity care.

The WHO was given access to the trial results prior to publication and acted quickly to update its guidance, reflecting the urgency of action to prevent maternal deaths in line with the Sustainable Development Goal (SDG) 3 to reduce maternal and newborn mortality. In March 2017, the WHO convened a panel of international experts to review and prioritise the evidence for updating the recommendations in maternal and perinatal health. Recommendations relating to PPH prevention and treatment (including the recommendation on the use of tranexamic acid for PPH treatment) were listed as highest priority for implementation. In April 2017, new WHO guidance was released following the panel review of evidence, strongly recommending early use of TXA within three hours of birth as part of standard care when PPH is diagnosed (5.8a). This was directly informed by the results of the WOMAN trial and also highlighted the need for all health systems, regardless of their level of resources, to recognise that TXA is a life-saving intervention that should be made readily available for PPH management wherever emergency obstetric care is provided. Professional organisations, including the Royal Society for Obstetricians & Gynaecologists, endorsed the results (5.9).

In 2019, the WHO updated its essential medicines list to include TXA specifically for PPH (5.8b). In most countries, the cost per dose of TXA is only GBP2 and it is already available for treating blood loss.

The Wellcome Trust, who funded the trial, undertook further work following the trial results to understand, identify and address country-specific issues and local barriers around TXA use for PPH. Training of 25 practitioners across 10 provinces in Tanzania in 2019 and 2020 was followed up by mentorship to health care professionals. In Nepal, Wellcome worked closely with the Family Welfare Division of the Ministry of Health and clinicians and public health experts at community and regional levels to develop policy guidelines and protocols for TXA for PPH management in 2020. As a result, Nepal’s PPH treatment and guidance policy was updated to recommend TXA in line with WHO guidelines (5.10).

The WOMAN Trial results were reported by media in more than 60 countries and generated over 800 pieces of coverage across TV, radio, print and online. This included more than 450 online articles, plus at least 350 TV and radio pieces identified by broadcast monitoring, although this figure is likely to be much higher as stories were syndicated to around 2,500 stations globally. There were in excess of 4,200 posts about the results on social media, with a potential reach of 79 million people (5.11).

Peek Vision developed from proof of concept to a fully-fledged social enterprise, with innovative health solutions that have been rolled out in Kenya, Pakistan, Zimbabwe, and Botswana. Peek’s ground-breaking system reduced the need for expensive and bulky eye health equipment, and its national programmes have allowed an entire generation of schoolchildren in these countries to receive low-cost comprehensive eye care services — screening, referral and treatment to reduce poor vision and blindness.

Global partnerships for impact

Peek was developed from LSHTM as an independent social enterprise organisation in 2015, retaining close links to LSHTM through the ICEH. In 2016, Peek became independently owned by the newly established charitable foundation, the Peek Vision Foundation, consisting of the Foundation and its trading arm, Peek Vision Ltd. Profits generated by Peek Vision Ltd belong to the Foundation, which reinvests its funds in building eye care capacity in low- and middle- income countries (5.1).

Peek’s products and services include: the Peek Acuity app, Peek Retina (mobile camera adapter), Peek School Eye Health and Community Eye Health programmes, eye health surveys (RAAB), and real time data reporting and analysis. Since 2016, Peek has been a registered manufacturer of medical devices under the UK Government Medicines and Healthcare Products Regulatory Agency. Peek Acuity Pro and Peek Retina (launched in 2017) are registered class 1 medical devices and CE certified. By the end of May 2019, Peek Acuity had been downloaded over 50,000 times in 137 countries by programme staff including teachers and healthcare workers. It was winner of ‘Tech for Social Impact’ prize in 2016, voted for by Google and McKinsey (5.2), having previously been awarded the 2015 Index Project Award alongside Tesla and Duolingo (5.3). In 2018, the Peek team’s work in Kenya won the All African Public Service Innovation Award from the African Union.

Screening and treatment for poor vision

High quality research, programmes, and collaboration with local and international experts using Peek helped screen almost 300,000 individuals in Botswana, Kenya, India, Pakistan and Zimbabwe. A further 20,000 were assessed and 7,000 requiring treatment were treated as part of programmes to improve poor vision (5.1). The original Kenyan trial was scaled up by the Ministries of Health and Education to a countywide programme beginning in 2015, and this was replicated and further developed in India and Botswana. In 2016, the Botswana government, alongside local and international partners, joined with Peek to implement Peek vision screening in over 120,000 schoolchildren. Over 90% of children attended follow-up appointments. The successful pilot led to the commitment in 2017 by the Ministry of Health and Wellness in Botswana to deliver a government-funded national programme to screen every schoolchild and teacher in the country, and to deliver appropriate eye care services as needed (5.4).

Strengthening health systems

The Peek system gave programme implementers access to live, real-time field data to drive systematic improvements, while support from partners enabled increased growth. The partnership with disability and development non-governmental organisation CBM facilitated rapid progress in Pakistan and Zimbabwe. In Pakistan, the CBM-Peek programme fully integrated Peek into a large-scale community eye health programme in 2019, screening over 30,000 people (5.1). Before Peek was introduced, 40% of eye consultations for eye health services at local hospitals were related to refractive errors. Since adopting Peek, this was reduced to 1%, as these issues could be solved by local optometrists, leaving eye health hospitals better placed to treat more complex eye conditions. Peek also provided data on the number of ‘lost’ individuals, which meant these individuals were followed up, triaged and an applicable intervention was delivered (e.g. surgery or spectacles provision). The Peek data allowed the partners to improve their service provision, increasing compliance with referrals to eye exams from 58% to 82% over 6 months. In Zimbabwe, the CBM-Peek partnership introduced Peek tools to 2 further school eye health programmes and a community eye health programme.

WHO’s Universal eye health: a global action plan 2014-19 cites the RAAB as a standard method for generating epidemiological evidence for the magnitude and causes of visual impairment as well as on eye care services (5.5). RAAB was used in more than 330 surveys in over 70 countries, and has evolved to a recognised standard that informs both district level eye health planning and global data on visual impairment. Delivered on the Peek platform since 2015, this software was used in Cambodia, Pakistan, Palestine, Zimbabwe and Nepal. mRAAB6, developed by Peek as a front-end mobile data collection system for RAABs, and the predecessor to the current version RAAB7, was used 125 times between 2015 and 2019 (representing populations in excess of 100 million people) (5.6).

Advocacy to move eye health up the agenda

Alongside development of the Peek software and associated activities (training and partnerships with local eye health organisations to deliver screening and treatment), Bastawrous and Peek have achieved policy impact by advocating the importance of eye health as part of universal health coverage. On Commonwealth Day in March 2018, Bastawrous addressed Her Majesty The Queen, other senior members of the Royal Family, the then UK Prime Minister, and delegates from the 53 Commonwealth countries at Westminster Abbey on the life-changing work of Peek (5.7). In April 2018, 53 Commonwealth heads of government agreed to take action to ensure all citizens have access to quality eye care. Peek was involved in supporting and calling for this development as a partner of the ‘Vision for the Commonwealth’ consortium (5.8), made up of 6 leading eye health organisations who have joined efforts to end avoidable blindness and poor vision across the Commonwealth.

Bastawrous co-founded and is global ambassador of the ‘Vision Catalyst Fund’ working with major banks, eye health organisations and funders to develop innovative financing modes for eye health, the subject of his 2018 TED talk, which has been viewed over 1.4 million times (5.9).

The body of evidence generated by LSHTM and partners was key in the international rollout of conjugate pneumococcal vaccines to 149 WHO member countries, via WHO recommendations and adoption in the portfolio of Gavi-supported vaccines. The research significantly contributed to the estimation of the burden of morbidity and mortality from pneumococcal disease prevented by PCV, and the role of the vaccination in herd immunity. It informed next steps in decision making for governments considering introducing and continuing this life-saving vaccine programme.

Demonstrating vaccine efficacy and effectiveness

The results of the Gambian trial and a parallel study in South Africa provided crucial information to the WHO Strategic Advisory Group of Experts’ (SAGE) recommendations that PCVs should be introduced into routine infant immunisation programmes of all countries with high child mortality. This was accepted by WHO in 2007 (5.1).

The findings of the 2017 evaluation, led by Mackenzie, showed that the vaccine had reduced the incidence of IPD in children aged 2-59 months by around 55%, and of hospitalised pneumonia by 30%. This demonstrated the considerable and sustained impact of PCV on IPD and pneumonia in Gambian children since the introduction of the vaccines in the routine infant immunisation programme. SAGE reviewed this evidence in 2017, and used it to formulate their 2017 recommendations on PCV. Their recommendations endorsed the efficacy of 2 PCVs (PCV13 and PCV10), and gave further guidance for countries on dose schedule, country-level choice of vaccine depending on prevalence of pneumococcal strains, and product-switching (5.2). Scott, Flasche, Greenwood and Mackenzie contributed to the expert consultation on optimising PCV impact in 2017. The evidence and recommendations presented fed directly into the WHO SAGE working group held immediately afterwards (5.3)

The sustained impact of the original recommendation to introduce a PCV to routine infant immunisation in 2007, plus further PCV recommendations in 2017 underpinned by LSHTM and MRCG evidence, was evident. By the end of 2019, 60 Gavi-eligible countries across 3 continents had introduced a PCV into their routine immunisation programmes, with only 3 of 54 countries in sub-Saharan Africa having not yet introduced PCV. The outcomes of the original Gambian trial still underpinned the WHO position paper in 2019, demonstrating the sustained attributable impact of the research (5.4).

According to Gavi’s 2019 Annual Report, 184 million children were vaccinated by the end of 2018, with this figure projected to have reached more than 225 million children by the end of 2019. The continued scale-up of PCV was expected to prevent over 700,000 future deaths among children in Gavi-supported countries by 2020 (5.5).

Both the trial and surveillance evidence in Africa focused on PCV13 in South Africa and The Gambia. But the success of PCV10 in Kenya demonstrated by Scott and colleagues contributed to several large African countries introducing a PCV vaccine, including Nigeria, Ethiopia, Madagascar, Zambia and Uganda. The preliminary results of the study on the safety of PCV10 were submitted for prequalification to WHO in 2012, and led to the approval of the formulation for use from 2013 onwards in Gavi countries (5.6).

Catch-up campaigns

Flasche’s research demonstrating the effectiveness of catch-up campaigns in Kenya was used as evidence to inform the WHO position and recommendations in both 2017 and 2019: that catch-up vaccination at the time of PCV introduction should be used to accelerate its impact on disease in children aged 1-5 years.

‘Wherever possible, catch-up vaccination at the time of introduction of PCV should be used to accelerate its impact on disease in children aged 1–5 years, particularly in settings with a high disease burden and mortality. If there is limited availability of vaccine or of financial resources for catch-up vaccination, the youngest children (e.g. <2 years of age) should be prioritised to receive catch-up doses of PCV because of their higher risk for pneumococcal disease.’ (5.2, 5.4).

In 2018, the Gavi Board approved support for catch-up vaccination campaigns as part of future introductions. Timor-Leste was the first country to benefit from this change in Gavi’s programmatic support, with the catch-up campaign expected to be introduced in 2021 (5.7).

Cost saving for LMICs

Roca’s research evaluating the immunogenicity of the multi-dose preparation of PCV13 led the WHO SAGE working group on PCV to recommend PCV13 for WHO prequalification in 2016. This enabled the vaccine, Prevenar 13 multi-dose vial (MDV), to be used by United Nations agencies and countries worldwide (5.8). The vaccine offered significant benefits to LMICs. Pfizer stated it resulted in a 75% reduction in the cold-chain requirements for temperature-controlled supply chain, and in UN and UNICEF shipping costs and storage requirements at national, regional and community levels. The pre-qualified multi-dose vial presentation was introduced in 2017 for shipment to countries supported by Gavi, preceded by Pfizer announcing a cost reduction from USD3.30 per dose to USD3.10 per dose in its multi-vial per-dose price, to all Gavi-eligible countries using PCV13 (5.8).

The current licensed versions of the vaccine are PCV13 and PCV10. Both PCV10 and PCV13 have substantial impacts against pneumonia, providing protection against different pneumococcal strains, and nasopharyngeal carriage. One of Gavi’s aims is to encourage competition on vaccine price, and it encouraged different countries to take up PCV10 (GSK) and PCV13 (Pfizer). Following LSHTM trials and surveillance evidence of cost savings in The Gambia and Kenya of both vaccines, Gavi signed further agreements in 2017 with both manufacturers under the Advanced Market Commitment to keep the dose price no more than USD3.50 and allow countries no longer eligible for Gavi support to access the same pricing until 2025. In 2018, UNICEF (as Gavi’s procurement agency) entered a new supply agreement with Pfizer to supply 19 million doses annually from 2018 for a period of 10 years (5.5).

As of 2019, 60 countries across Africa, Asia, the Americas and the Middle East had introduced pneumococcal conjugate vaccination under the Advanced Market Commitment; 10 of these countries are using PCV10 while the remaining 50 are using PCV13. Within the REF period (2014 onwards), 22 countries introduced a PCV (16 using PCV13). In 2019, manufacturer Pfizer further reduced the price of PCV13 available to Gavi-supported countries, from USD2.95 to USD2.90 per dose. This cost reduction benefited the approximately 50 countries using PCV13 (5.5).